Editor’s Choice Articles

Cardiovascular disease (CVD) is the leading cause of death worldwide. In addition to the high mortality rate, people suffering from CVD often endure difficulties with physical activities and productivity that significantly affect their quality of life. The high prevalence of debilitating risk factors such as obesity, type 2 diabetes mellitus, smoking, hypertension, and hyperlipidemia only predicts a bleak future. Current traditional CVD interventions offer temporary respite; however, they compound the severe economic strain of health-related expenditures. Furthermore, these therapeutics can be prescribed indefinitely. Recent advances in the field of epigenetics have generated new treatment options by confronting CVD at an epigenetic level. This involves modulating gene expression by altering the organization of our genome rather than altering the DNA sequence itself. Epigenetic changes are heritable, reversible, and influenced by environmental factors such as medications. As CVD is physiologically and pathologically diverse in nature, epigenetic interventions can offer a ray of hope to replace or be combined with traditional therapeutics to provide the prospect of addressing more than just the symptoms of CVD. This review discusses various risk factors contributing to CVD, perspectives of current traditional medications in practice, and a focus on potential epigenetic therapeutics to be used as alternatives. Full article

As the global human population continues to increase, the use of saline–alkali land for food production is an important consideration for food security. In addition to breeding or cultivating salt-tolerant crop varieties, microorganisms are increasingly being evaluated for their ability to improve plant salt tolerance. Barley is one of the most important and salt-tolerant cereal crops and is a model system for investigating the roles of microorganisms in improving plant salt tolerance. However, a comprehensive review of the mechanisms by which microorganisms improve barley salt tolerance remains lacking. In this review, the mechanisms of barley salt tolerance improvement by microorganisms are summarized, along with a discussion of existing problems in current research and areas of future research directions. In particular, with the development of sequencing technology and the great reduction of prices, the use of omics can not only comprehensively evaluate the role of microorganisms but also evaluate the impact of the microbiome on plants, which will provide us with many opportunities and challenges in this research area. Full article

The aim of this study was to investigate the impact of changes in aquaporin expression on the growth of onion (Allium cepa L.) plants when subjected to dual applications of microorganism-based soil amendments and foliar nanoencapsulated mineral nutrients. Multiple physiological parameters related to water, gas exchange, and nutrient content in leaf, root, and bulb tissues were determined. Additionally, the gene expression of aquaporins, specifically PIP1, PIP2 (aquaporin subfamily plasma membrane intrinsic protein), and TIP2 (aquaporin subfamily tonoplast intrinsic protein), was analyzed. The findings revealed that the foliar application of nutrients in a nanoencapsulated form significantly enhanced nutrient penetration, mobilization, and overall plant growth to a greater extent than free-form fertilizers. Amendments with microorganisms alone did not promote growth but influenced the production of secondary metabolites in the bulbs. The combination of microorganisms and nanoencapsulated mineral nutrients demonstrated synergistic effects, increasing dry matter, mineral content, and aquaporin gene expression. This suggests that aquaporins play a pivotal role in the transport of nutrients from leaves to storage organs, resulting in the overexpression of PIP2 aquaporins in bulbs, improved water uptake, and enhanced cell growth. Therefore, the combined treatment with microorganisms and nanoencapsulated mineral nutrients may be an optimal approach for enhancing onion productivity by regulating aquaporins under field conditions. Full article

The increase in incidence of superficial fungal infections combined with the emergence of antifungal resistance represents both a global health challenge and a considerable economic burden. Recently, dermatophytes, the main culprit causing superficial fungal infections, have started to exhibit antifungal resistance. This can be observed in some of the most common species such as Trichophyton rubrum and Trichophyton mentagrophytes. Importantly, the new subspecies, known as Trichophyton indotineae, has been reported to show high resistance to terbinafine, a first-line treatment for dermatophyte infections. Compounding these issues is the realization that diagnosing the causative infectious agents requires using molecular analysis that goes beyond the conventional macroscopic and microscopic methods. These findings emphasize the importance of conducting antifungal susceptibility testing to select the appropriate antifungal necessary for successful treatment. Implementing these changes may improve clinical practices that combat resistant dermatophyte infections. Full article

Purpose: To measure the ocular motility parameters of the Developmental Eye Movement (DEM) test objectively, with an eye tracker in subjects with intellectual disability (ID). Methods: The DEM test was performed on 45 subjects with ID, while their eye movements were recorded with an eye tracker. Some objective parameters of ocular motility were obtained through each subtest (A, B, and C) of the full DEM test. Results: There was a significant positive correlation between the saccadic speed (cc: 0.537; p = 0.001) and length (cc: 0.368; p = 0.030) of both eyes for the same subject. People with a higher percentage of ID exhibited a greater number of fixations, saccades, and errors, and took longer to perform the DEM test than those with a lower ID percentage, who had greater numbers of these parameters than subjects without ID. Subjects without ID exhibited faster saccades, with a higher amplitude, than subjects with ID. Conclusions: The eye tracker quantifies ocular motility parameters involved in the DEM test in subjects with ID. Both eyes’ movements in subjects with ID were conjugated, exhibiting saccades of the same length and speed. All parameters were different in subjects with ID compared to those in subjects without ID, so normative tables specifically for subjects with ID are necessary. Full article

Understanding and addressing post-radical prostatectomy (RP) erectile dysfunction (ED) is of paramount importance for clinicians. Cavernous nerve (CN) injury rat model studies have provided consistently promising experimental data regarding regaining erectile function (EF) after nerve damage-induced ED. However, these findings have failed to translate efficiently into clinical practice, with post-RP ED therapeutic management remaining cumbersome and enigmatic. This disparity highlights the need for further standardization and optimization of the elaborate surgical preparation protocols and multifaceted reporting parameters involved in reliable CN injury rat model experimentation. Even so, despite its technical complexity, this animal model remains instrumental in exploring the functional implications of RP, i.e., surgical lesions of the neurovascular bundles (NVBs). Herein, besides cavernous nerve (CN) dissection, injury, and electrostimulation, multiple pressure measurements, i.e., mean arterial pressure (MAP) and intra-cavernosal pressure (ICP), must also be achieved. A transverse cervical incision allows for carotid artery cannulation and MAP measurements. Conversely, ICP measurements entail circumcising the penis, exposing the ischiocavernous muscle, and inserting a needle into the corporal body. Finally, using an abdominal incision, the prostate is revealed, and the major pelvic ganglia (MPG) and CNs are dissected bilaterally. Specific surgical techniques are used to induce CN injuries. Herein, we provide a narrative and illustrative overview regarding these complex experimental procedures and their particular requirements, reflecting on current evidence and future research perspectives. Full article

Maintenance of the health of our oceans is critical for the survival of the oceanic food chain upon which humanity is dependent. Zooplanktonic copepods are among the most numerous multicellular organisms on earth. As the base of the primary consumer food web, they constitute a major biomass in oceans, being an important food source for fish and functioning in the carbon cycle. The potential impact of climate change on copepod populations is an area of intense study. Omics technologies offer the potential to detect early metabolic alterations induced by the stresses of climate change. One such omics approach is lipidomics, which can accurately quantify changes in lipid pools serving structural, signal transduction, and energy roles. We utilized high-resolution mass spectrometry (≤2 ppm mass error) to characterize the lipidome of three different species of copepods in an effort to identify lipid-based biomarkers of copepod health and viability which are more sensitive than observational tools. With the establishment of such a lipid database, we will have an analytical platform useful for prospectively monitoring the lipidome of copepods in a planned long-term five-year ecological study of climate change on this oceanic sentinel species. The copepods examined in this pilot study included a North Atlantic species (Calanus finmarchicus) and two species from the Gulf of Mexico, one a filter feeder (Acartia tonsa) and one a hunter (Labidocerca aestiva). Our findings clearly indicate that the lipidomes of copepod species can vary greatly, supporting the need to obtain a broad snapshot of each unique lipidome in a long-term multigeneration prospective study of climate change. This is critical, since there may well be species-specific responses to the stressors of climate change and co-stressors such as pollution. While lipid nomenclature and biochemistry are extremely complex, it is not essential for all readers interested in climate change to understand all of the various lipid classes presented in this study. The clear message from this research is that we can monitor key copepod lipid families with high accuracy, and therefore potentially monitor lipid families that respond to environmental perturbations evoked by climate change. Full article

The aim of this review was to describe the uterine microbiome composition that has been analyzed so far and describe potential pathways in the carcinogenesis of the endometrium. The microbiome in the uterine environment is involved in apoptosis and proliferation during the menstruation cycle, pregnancy maintenance, and immune system support. However, bacteria in the uterus could stimulate inflammation, which when chronic results in malignancy. An altered gut microbiota initiates an inflammatory response through microorganism-associated molecular patterns, which leads to intensified steroidogenesis in the ovaries and cancers. Moreover, intestinal bacteria secreting the enzyme β-glucuronidase may increase the level of circulating estrogen and, as a result, be influential in gynecological cancers. Both the uterine and the gut microbiota play a pivotal role in immune modulation, which is why there is a demand for further investigation from both the diagnostic and the therapeutic perspectives. Full article

Viral hepatitis, caused by hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), or hepatitis E virus (HEV), is a major global public health problem. These viruses cause millions of infections each year, and chronic infections with HBV, HCV, or HDV can lead to severe liver complications; however, they are underdiagnosed. Achieving the World Health Organization’s viral hepatitis elimination goals by 2030 will require access to simpler, faster, and less expensive diagnostics. The development and implementation of point-of-care (POC) testing methods that can be performed outside of a laboratory for the diagnosis of viral hepatitis infections is a promising approach to facilitate and expedite WHO’s elimination targets. While a few markers of viral hepatitis are already available in POC formats, tests for additional markers or using novel technologies need to be developed and validated for clinical use. Potential methods and uses for the POC testing of antibodies, antigens, and nucleic acids that relate to the diagnosis, monitoring, or surveillance of viral hepatitis infections are discussed here. Unmet needs and areas where additional research is needed are also described. Full article

Fetal growth restriction (FGR) is a pathological state that represents a fetus’s inability to achieve adequate growth during pregnancy. Several maternal, placental, and fetal factors are likely associated with FGR etiology. FGR is linked to severe fetal and neonatal complications, as well as adverse health consequences in adulthood. Numerous randomized controlled trials (RCTs) have demonstrated improved growth in FGR fetuses with promising treatment strategies such as maternal micronutrient, amino acid, and nitric oxide supplementation. Elevated inflammation in pregnant women diagnosed with FGR has been associated with an imbalance between pro- and anti-inflammatory cytokines. Gut microbiota dysbiosis may result in increased FGR-related inflammation. Probiotic treatment may relieve FGR-induced inflammation and improve fetal growth. The aim of this review is to provide an overview of the gut microbiota and inflammatory profiles associated with FGR and explore the potential of probiotics in treating FGR. Full article

Febuxostat, initially developed as a xanthine oxidase inhibitor to address hyperuricemia in gout patients, has evolved into a versatile therapeutic agent with multifaceted applications. This review provides a comprehensive overview of febuxostat’s mechanism of action, its effectiveness in gout management, its cardiovascular safety profile, renal and hepatic effects, musculoskeletal applications, safety considerations, and emerging research prospects. Febuxostat’s primary mechanism involves selective inhibition of xanthine oxidase, resulting in reduced uric acid production. Its pharmacokinetics require personalized dosing strategies based on individual characteristics. In gout management, febuxostat offers a compelling alternative, effectively lowering uric acid levels, relieving symptoms, and supporting long-term control, especially for patients intolerant to allopurinol. Recent studies have demonstrated its cardiovascular safety, and it exhibits minimal hepatotoxicity, making it suitable for those with liver comorbidities. Febuxostat’s potential nephroprotective effects and kidney stone prevention properties are noteworthy, particularly for gout patients with renal concerns. Beyond gout, its anti-inflammatory properties hint at applications in musculoskeletal conditions and a broader spectrum of clinical contexts, including metabolic syndrome. Emerging research explores febuxostat’s roles in cardiovascular health, neurological disorders, rheumatoid arthritis, and cancer therapy, driven by its anti-inflammatory and antioxidative properties. Future directions include personalized medicine, combination therapies, mechanistic insights, and ongoing long-term safety monitoring, collectively illuminating the promising landscape of febuxostat’s multifaceted therapeutic potential. Full article

Somatic copy number alterations (SCNAs) are frequently observed in high-grade ovarian serous carcinoma (HGOSC). However, their impact on gene expression levels has not been systematically assessed. In this study, we explored the relationship between recurrent SCNA and gene expression using The Cancer Genome Atlas Pan Cancer dataset (OSC, TCGA, PanCancer Atlas) to identify cancer-related genes in HGOSC. We then investigated any association between highly correlated cancer genes and clinicopathological parameters, including age of diagnosis, disease stage, overall survival (OS), and progression-free survival (PFS). A total of 772 genes with recurrent SCNAs were observed. SCNA and mRNA expression levels were highly correlated for 274 genes; 24 genes were classified as a Tier 1 gene in the Cancer Gene Census in the Catalogue of Somatic Mutations in Cancer (CGC-COSMIC). Of these, 11 Tier 1 genes had highly correlated SCNA and mRNA expression levels: TBL1XR1, PIK3CA, UBR5, EIF3E, RAD21, EXT1, RECQL4, KRAS, PRKACA, BRD4, and TPM4. There was no association between gene amplification and disease stage or PFS. EIF3E, RAD21, and EXT1 were more frequently amplified in younger patients, specifically those under the age of 55 years. Patients with tumors carrying PRKACA, BRD4, or TPM4 amplification were associated with a significantly shorter OS. RECQL4 amplification was more frequent in younger patients, and tumors with this amplification were associated with a significantly better OS. Full article

This review delves into the therapeutic applications of amphetamine-type stimulants such as lisdexamphetamine dimesylate, mixed amphetamine salts, 3,4-methylenedioxymethamphetamine (MDMA), dextroamphetamine, and phentermine. These compounds have been investigated for their potential in treating a range of psychiatric disorders, including attention deficit hyperactivity disorder (ADHD), drug dependence, post-traumatic stress disorder (PTSD), and obesity. Lisdexamphetamine dimesylate has shown promise in effectively treating ADHD symptoms in both children and adults. Additionally, it has been explored as a potential treatment for drug dependency and withdrawal, demonstrating encouraging results. Mixed amphetamine salts have also exhibited efficacy in reducing ADHD symptoms in adults. Future research should explore their potential use in treating bipolar disorder and cocaine dependence, considering the associated risks and benefits. MDMA-assisted psychotherapy has emerged as an innovative approach to treating PTSD, leading to sustained reductions in symptoms and even promoting post-traumatic growth. Furthermore, it has shown promise in managing anxiety related to life-threatening illnesses. Dextroamphetamine and phentermine have demonstrated efficacy in treating cocaine and opioid dependence, ADHD, and obesity. However, careful consideration and monitoring by medical professionals are essential due to the potential risks and benefits associated with them. In conclusion, amphetamine-type stimulants present a promising avenue for therapeutic interventions in various psychiatric conditions. Nevertheless, further research is necessary to comprehensively understand their mechanisms of action, dosage requirements, and long-term effects in different patient populations. Full article

Mitochondrial degeneration in various neurodegenerative diseases, specifically in Alzheimer’s disease, involves excessive mitochondrial fission and reduced fusion, leading to cell damage. P110 is a seven-amino acid peptide that restores mitochondrial dynamics by acting as an inhibitor of mitochondrial fission. However, the role of P110 as a neuroprotective agent in AD remains unclear. Therefore, we performed cell culture studies to evaluate the neuroprotective effect of P110 on amyloid-β accumulation and mitochondrial functioning. Human SH-SY5Y neuronal cells were incubated with 1 µM and 10 µM of P110, and Real-Time PCR and Western blot analysis were done to quantify the expression of genes pertaining to AD and neuronal health. Exposure of SH-SY5Y cells to P110 significantly increased APP mRNA levels at 1 µM, while BACE1 mRNA levels were increased at both 1 µM and 10 µM. However, protein levels of both APP and BACE1 were significantly reduced at 10 µM of P110. Further, P110 treatment significantly increased ADAM10 and Klotho protein levels at 10 µM. In addition, P110 exposure significantly increased active mitochondria and reduced ROS in live SH-SY5Y cells at both 1 µM and 10 µM concentrations. Taken together, our results indicate that P110 might be useful in attenuating amyloid-β generation and improving neuronal health by maintaining mitochondrial function in neurons. Full article

This randomized interventional study aimed to determine the effects of n-3 polyunsaturated fatty acids, selenium, vitamin E, and lutein supplementation in the form of enriched chicken egg consumption on microvascular endothelium-dependent vasodilation, oxidative stress, and microvascular response to an acute strenuous training session (ASTS) in competitive athletes. Thirty-one male athletes were assigned to a control (n = 17) or a Nutri4 group (n = 14) who consumed three regular or enriched chicken eggs per day, respectively, for 3 weeks. Significantly enhanced endothelium-dependent responses to vascular occlusion (PORH) and iontophoresis of acetylcholine (AChID) were observed in the Nutri4 group but not in the control group after egg consumption. Formation of peroxynitrite and hydrogen peroxide in peripheral blood mononuclear cells, as well as serum concentration of 8-iso prostaglandin F2α, decreased in the Nutri4 group while remaining unchanged in controls. PORH and AChID were reduced post-ASTS compared with pre-ASTS, both before and after the diets, in both groups. However, the range of PORH responsiveness to ASTS (ΔPORH) increased after consumption of enriched eggs. These results suggest that consumption of enriched chicken eggs has a beneficial effect on microvascular endothelium-dependent vasodilation and the reduction of oxidative stress levels in competitive athletes. Also, microvascular adaptation to the ASTS was improved after consumption of Nutri4 eggs. Full article

Movile Cave, situated in Romania close to the Black Sea, constitutes a distinct and challenging environment for life. Its partially submerged ecosystem depends on chemolithotrophic processes for its energetics, which are fed by a continuous hypogenic inflow of mesothermal waters rich in reduced chemicals such as hydrogen sulfide and methane. We sampled a variety of cave sublocations over the course of three years. Furthermore, in a microcosm experiment, minerals were incubated in the cave waters for one year. Both endemic cave samples and extracts from the minerals were subjected to 16S rRNA amplicon sequencing. The sequence data show specific community profiles in the different subenvironments, indicating that specialized prokaryotic communities inhabit the different zones in the cave. Already after one year, the different incubated minerals had been colonized by specific microbial communities, indicating that microbes in Movile Cave can adapt in a relatively short timescale to environmental opportunities in terms of energy and nutrients. Life can thrive, diversify and adapt in remote and isolated subterranean environments such as Movile Cave. Full article

This narrative review presents a comprehensive overview of the diagnosis and management of pityriasis versicolor (PV), a common superficial fungal infection caused by the yeast Malassezia. PV is characterised by scaly hypopigmented or hyperpigmented patches, primarily affecting the upper trunk, neck, and upper arms. Regarding commensal interactions, Malassezia utilises nutrient sources without affecting the human host. In cases of pathogenicity, Malassezia can directly harm the host via virulence factors or toxins, or indirectly by triggering damaging host responses. The diagnosis typically relies on recognising characteristic clinical features. Due to the wide variability in its clinical presentation, recognising the differential diagnosis is critical. In this paper, we discuss the clinical differentials, with their dermatoscopic presentation, but also describe a range of helpful diagnostic techniques (microscopy, conventional and ultraviolet-induced fluorescence dermatoscopy, and confocal microscopy). Topical therapies are the primary treatment for PV, encompassing non-specific antifungal agents like sulphur with salicylic acid, selenium sulphide 2.5%, and zinc pyrithione. Additionally, specific topical antifungal medications with either fungicidal or fungistatic properties may also be incorporated into the topical treatment regimen, such as imidazoles, allylamines, and ciclopirox olamine. Systemic therapies might occasionally be used. Patient education and the promotion of good personal hygiene are pivotal to reduce the risk of recurrence. In recurrent cases, particularly during warmer and more humid periods, prolonged prophylaxis with topical agents should be considered. Full article

Liver transplantation (LT) is the only curative treatment for various liver diseases, including acute liver failure, end-stage liver disease, and selected unresectable liver malignancies. Combination antiretroviral therapy has improved outcomes for people living with HIV (PLWH), transforming the status of acquired immune deficiency syndrome from a fatal disease to a chronic and manageable condition. These powerful antiviral therapies have not only increased the number of HIV+ enlisted patients by improving their survival but also made the use of HIV+ organs a viable option. In this review, we summarise current knowledge on the peculiarities of liver transplantation in PLWH. In particular, we focus on the indications, contraindications, specific considerations for treatment, and outcomes of LT in PLWH. Finally, we present available preliminary data on the use of HIV+ liver allografts. Full article

Background: The protection of pregnant workers should be based on evidence regarding the risks to reproductive health from exposure to specific work environments and conditions. The objective of this study was to identify the effects on mothers and newborns resulting from environmental exposure to various occupational risks. Methods: The study cohort was composed of 399 women admitted to the Obstetrics/Postpartum ward at Hospital La Fe in Valencia, Spain. Face-to-face interviews were conducted to establish associations between workplace exposure during pregnancy and its effects on maternal and newborn health. Sex, anthropometric characteristics, and blood gas analysis in arterial and venous umbilical cord blood at delivery were collected. Results: A total of 138 women were exposed to biological and/or chemical risks, 122 to physical risks, and 139 at no risk of exposure. In the group with chemical and/or biological risks, the frequency of women who resorted to in vitro fertilization to achieve the studied pregnancy is less than half of the group exposed to physical risks, with statistically significant differences (p = 0.047). The mean values for the arterial analysis in both exposure groups were within average values, with similar pH values between them, but the mean values of PCO2 and PO2 were lower in the group of neonates of mothers exposed to physical risks, with a significant difference for arterial PO2 (p = 0.027). Conclusion: Our analysis contributes evidence for planning and prioritizing preventive actions to protect women’s reproductive health. The results suggest the continuation of a future project that would consider more factors and potentially increase the sample size. Full article

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, mainly causes respiratory and intestinal symptoms and changes in the microbiota of patients. We performed a systematic search in major databases using “Bifidobacterium” and “COVID-19” or “SARS-CoV-2” as key terms to assess the relationship of the genus to COVID-19. After the selection steps, 25 articles were analyzed. Of these, eighteen were observational, and seven were interventional articles that evaluated the use of Bifidobacterium alone or in mix as probiotics for additional treatment of patients with COVID-19. All stages and severities were contemplated, including post-COVID-19 patients. Overall, Bifidobacterium was associated with both protective effects and reduced abundance in relation to the disease. The genus has been found to be abundant in some cases and linked to disease severity. The studies evaluating the use of Bifidobacterium as probiotics have demonstrated the potential of this genus in reducing symptoms, improving pulmonary function, reducing inflammatory markers, alleviating gastrointestinal symptoms, and even contributing to better control of mortality. In summary, Bifidobacterium may offer protection against COVID-19 through its ability to modulate the immune response, reduce inflammation, compete with pathogenic microbes, and maintain gut barrier function. The findings provide valuable insights into the relationship between the disease and the genus Bifidobacterium, highlighting the potential of microbiota modulation in the treatment of COVID-19. Full article

The small compound [5-(3,4-dichlorophenyl) furan-2-yl]-piperidine-1-ylmethanethione (DFPM) inhibits ABA responses by activating effector-triggered immune signal transduction in Arabidopsis. In addition to the known function of DFPM as an antagonist of ABA signaling, DFPM causes accession-specific root growth arrest in Arabidopsis Columbia-0 via the TIR-NLR protein VICTR (VARIATION IN COMPOUND TRIGGERED ROOT growth response) in an EDS1/PAD4/RAR1/SGT1B-dependent manner. Although DFPM could control the specific steps of various cellular responses, the functional residues for the activity of DFPM or the existence of a stronger version of DFPM modification have not been characterized thoroughly. This study analyzed twenty-two DFPM derivatives during root growth arrest, inhibition of ABA signaling, and induction of biotic signal transduction to determine critical residues that confer the specific activity of DFPM. Furthermore, this study identified two more Arabidopsis accessions that generate significant root growth arrest in response to DFPM derivatives dependent on multiple amino acid polymorphisms in the coding region of VICTR. The isolation of novel compounds, such as DFPM-5, and specific amino acid polymorphisms critical for the compound-induced responses will help determine the detailed regulatory mechanism for how DFPM regulates abiotic and biotic stress signaling interactions. Full article

Drug-metabolizing enzymes (DMEs) and transporters play a major role in drug efficacy and safety. They are regulated at multiple levels and by multiple factors. Estimating their expression and activity could contribute to predicting drug pharmacokinetics and their regulation by drugs or pathophysiological situations. Determining the expression of these proteins in the liver, intestine, and kidney requires the collection of biopsy specimens. Instead, the isolation of extracellular vesicles (EVs), which are nanovesicles released by most cells and present in biological fluids, could deliver this information in a less invasive way. In this article, we review the use of EVs as surrogates for the expression and activity of DMEs, uptake, and efflux transporters. Preliminary evidence has been provided for a correlation between the expression of some enzymes and transporters in EVs and the tissue of origin. In some cases, data obtained in EVs reflect the induction of phase I-DMEs in the tissues. Further studies are required to elucidate to what extent the regulation of other DMEs and transporters in the tissues reflects in the EV cargo. If an association between tissues and their EVs is firmly established, EVs may represent a significant advancement toward precision therapy based on the biotransformation and excretion capacity of each individual. Full article

Although coronavirus disease 2019 (COVID-19) is no longer a Public Health Emergency of International Concern (PHEIC), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has had a vast impact to date. Hence, continuous management is required, given the uncertainty caused by the potential evolution of SARS-CoV-2. Reverse transcription-quantitative PCR (RT-qPCR) diagnosis has been fundamental in overcoming this issue. In this study, the performances of two rapid RT-qPCR assays (Real-Q Direct SARS-CoV-2 Detection Kit and Allplex™ SARS-CoV-2 fast PCR Assay) with short PCR times were comparatively evaluated using a STANDARD M nCoV Real-Time Detection Kit (STANDARD M, conventional RT-qPCR assay). All kits showed a limit of detection values (10²–10³ copies/reaction). The evaluation showed that the two rapid assay tests had ≥97.89% sensitivity and ≥99.51% specificity (κ = 0.98) for individual samples and ≥97.32% sensitivity and ≥97.67% specificity for pooled samples compared to STANDARD M. These results indicate that the two rapid RT-qPCR kits, which showed significant time reduction in performance, are as effective as a conventional RT-qPCR assay. They are likely to increase not only the number of tests that can be performed but also the efficiency of sustainable management of COVID-19 in the long term. Full article

The introduction of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment standards and significantly enhanced patient prognoses. However, the utilization of these groundbreaking therapies has led to the observation and reporting of various types of adverse events, commonly known as immune-related adverse events (irAEs). In the following article, we present four patients who encountered uncommon toxicities induced by ICIs. The first patient was a 59-year-old female diagnosed with stage 4 lung adenocarcinoma. She received immunotherapy (pembrolizumab) together with chemotherapy and subsequently developed autonomic neuropathy (AN). The next two patients also received chemo-immunotherapy (pembrolizumab) and were both 63-year-old males with stage 4 lung adenocarcinoma. One of the two experienced palmoplantar keratoderma, while the other presented with Reiter’s syndrome (urethritis, conjunctivitis and arthritis). The 4th patient, an 80-year-old male with stage 4 squamous cell carcinoma of the lung, received chemo-immunotherapy (pembrolizumab) and developed myasthenia gravis. Full article

Fungi are the most diverse living organisms on planet Earth, where their ubiquitous presence in various ecosystems offers vast potential for the research and discovery of new, naturally occurring medicinal products. Concerning human health, cancer remains one of the leading causes of mortality. While extensive research is being conducted on treatments and their efficacy in various stages of cancer, finding cytotoxic drugs that target tumor cells with no/less toxicity toward normal tissue is a significant challenge. In addition, traditional cancer treatments continue to suffer from chemical resistance. Fortunately, the cytotoxic properties of several natural products derived from various microorganisms, including fungi, are now well-established. The current review aims to extract and consolidate the findings of various scientific studies that identified fungi-derived bioactive metabolites with antitumor (anticancer) properties. The antitumor secondary metabolites identified from extremophilic and extremotolerant fungi are grouped according to their biological activity and type. It became evident that the significance of these compounds, with their medicinal properties and their potential application in cancer treatment, is tremendous. Furthermore, the utilization of omics tools, analysis, and genome mining technology to identify the novel metabolites for targeted treatments is discussed. Through this review, we tried to accentuate the invaluable importance of fungi grown in extreme environments and the necessity of innovative research in discovering naturally occurring bioactive compounds for the development of novel cancer treatments. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily affects the respiratory system but can also lead to neurological complications. Among COVID-19 patients, the endothelium is considered the Achilles heel. A variety of endothelial dysfunctions may result from SARS-CoV-2 infection and subsequent endotheliitis, such as altered vascular tone, oxidative stress, and cytokine storms. The cerebral hemodynamic impairment that is caused is associated with a higher probability of severe disease and poor outcomes in patients with COVID-19. This review summarizes the most relevant literature on the role of vasomotor reactivity (VMR) in COVID-19 patients. An overview of the research articles is presented. Most of the studies have supported the hypothesis that endothelial dysfunction and cerebral VMR impairment occur in COVID-19 patients. Researchers believe these alterations may be due to direct viral invasion of the brain or indirect effects, such as inflammation and cytokines. Recently, researchers have concluded that viruses such as the Human Herpes Virus 8 and the Hantavirus predominantly affect endothelial cells and, therefore, affect cerebral hemodynamics. Especially in COVID-19 patients, impaired VMR is associated with a higher risk of severe disease and poor outcomes. Using VMR, one can gain valuable insight into a patient’s disease progression and make more informed decisions regarding appropriate treatment options. A new pandemic may develop with the COVID-19 virus or other viruses, making it essential that healthcare providers and researchers remain focused on developing new strategies for improving survival in such patients, particularly those with cerebrovascular risk factors. Full article

The green model microalga Chlamydomonas reinhardtii recently emerged as a sustainable production chassis for the efficient biosynthesis of recombinant proteins and high-value metabolites. Its capacity for scalable, rapid and light-driven growth in minimal salt solutions, its simplicity for genetic manipulation and its “Generally Recognized As Safe” (GRAS) status are key features for its application in industrial biotechnology. Although nuclear transformation has typically resulted in limited transgene expression levels, recent developments now allow the design of powerful and innovative bioproduction concepts. In this review, we summarize the main obstacles to genetic engineering in C. reinhardtii and describe all essential aspects in sequence adaption and vector design to enable sufficient transgene expression from the nuclear genome. Several biotechnological examples of successful engineering serve as blueprints for the future establishment of C. reinhardtii as a green cell factory. Full article

This study seeks to offer a contribution to the method of subtyping major depressed patients by exploring the possible relationships between circulating brain-derived neurotrophic factor (BDNF), different peripheral inflammatory/metabolic markers in the blood and clinical characteristics. Thirty-nine patients, thoroughly diagnosed according to the DSM-5 criteria, underwent a comprehensive set of evaluations encompassing structured interviews, rating scales and a panel of blood tests. Correlation and comparison analyses were carried out by means of non-parametric statistical tests. Concurrently, a principal component analysis was performed to explain biochemical variance. The findings of our research unveiled that leukocyte counts, their ratios and other inflammatory parameters are positively correlated with depression scores. Moreover, we found variations within the BDNF pools of depressed patients. Specifically, higher levels of platelet-poor plasma BDNF (PPP-BDNF) were correlated with augmented inflammatory markers in patients showing specific episode characteristics, whereas reduced platelet BDNF (PLT-BDNF) provided a better indication of the changes that were linked to a diagnosis of long-term depression. Our findings suggest that PPP-BDNF and PLT-BDNF might differentiate depression conditions. They also imply usefulness in appraising peripheral biomarker profiles in patients for a deeper characterization of major depressive episodes. At the same time, it is plausible that they might constitute novel avenues for developing more tailored therapeutic strategies for patients with MDs. Full article

(1) Background: Delirious mania is a neuropsychiatric condition characterized by the rapid onset of delirium, psychosis, and mania. Due to the presence of catatonic signs and symptoms, some authors considered this syndrome to be a specific excited catatonia subtype. Usually, delirious mania is responsive to intravenous benzodiazepines (BZDs) or to electroconvulsive therapy (ECT). (2) Methods: In the present study, we describe the case of a 64-year-old woman with a diagnosis of recurrent major depressive disorder. We assessed the severity of the clinical picture and the response to ECT treatment with the Bush–Francis Catatonia Rating Scale (BFCRS). (3) Results: After eleven sessions of ECT, the patient presented a reduced BFCRS total score, with a resolution of the autonomic abnormalities (temperature, respiratory, and heart rate). (4) Conclusions: These data demonstrate how important it is to diagnose this syndrome as soon as possible to set up an effective therapy, avoiding the use of antipsychotic drugs and preventing potentially fatal complications. The initial administration of BZDs IV and the subsequent ECT application, associated with intensive care of life-threatening general medical conditions, guaranteed us a good level of efficacy in obtaining a complete resolution of the clinical picture. Full article

Coronary artery disease and acute coronary syndromes are accountable for significant morbidity and mortality, despite the preventive measures and technological advancements in their management. Thus, it is mandatory to further explore the pathophysiology in order to provide tailored and more effective therapies, since acute coronary syndrome pathogenesis is more varied than previously assumed. It consists of plaque rupture, plaque erosion, and calcified nodules. The advancement of vascular imaging tools has been critical in this regard, redefining the epidemiology of each mechanism. When it comes to acute coronary syndrome management, the presence of ruptured plaques almost always necessitates emergent reperfusion, whereas the presence of plaque erosions may indicate the possibility of conservative management with potent antiplatelet and anti-atherosclerotic medications. Calcified nodules, on the other hand, are an uncommon phenomenon that has largely gone unexplored in terms of the best management plan. Future studies should further establish the importance of detecting the underlying mechanism and the role of various treatment plans in each of these distinct entities. Full article

Chemically modified curcumin, CMC2.24, is a promising therapeutic that has shown efficacy in ameliorating excessive pigmentation in our previous studies. However, its inherent disadvantages of color, stability, solubility, and cytotoxicity to melanocytes and keratinocytes at concentrations > 4 µg/mL posed challenges in its use in cosmetic formulations. To overcome these limitations, chemical reduction by hydrogenation of CMC2.24 (compound 1) was developed to yield products at different time points of hydrogenation (1 h, 2 h, 4 h, and 24 h) referred to as partially (2, 3, 4) or fully hydrogenated (5) products, and the effects of the degree of hydrogenation on melanogenesis in vitro were explored. Compound 1 and products 2–5 were evaluated using mushroom tyrosinase activity assays with two substrates (L-tyrosine and L-DOPA), then cellular assays using B16F10 mouse melanoma cells, MNT-1 human melanoma cells, and physiological normal human melanocytes (HEMn-DP cells). The cytotoxicity, melanin contents, cellular tyrosinase activities, and cellular oxidative stress were evaluated. Moreover, the recovery of melanin contents in HEMn-DP cells was also studied. Our results provide novel insights into the role of the degree of hydrogenation of compound 1 on the biological effects of melanogenesis, which were dependent on cell type. To the best of our knowledge, this is the first study to show that in HEMn-DP cells, the anti-melanogenic efficacy of the yellow-colored CMC2.24 is retained as early as 1 h after its hydrogenation; this efficacy is enhanced with longer durations of hydrogenation, with a robust efficacy achieved for the 24 h hydrogenated product 5 at the lowest concentration of 4 µg/mL. A similar potency could be achieved for product 4 at higher concentrations, although interestingly, both differ only by a minor amount of dihydro-CMC2.24. Our results indicate promise for using products 4 & 5 as a skin-lightener in cosmetic formulations with the advantages of lack of color combined with a potency much greater than that of the parent compound 1 at lower concentrations and reversibility of the effects on melanocytes. This, along with the easy synthesis and scale-up of the hydrogenation method for CMC2.24 and the documented higher solubility, stability, and bioavailability of tetrahydrocurcumin, provides further impetus to incorporating these derivatives in cosmetic formulations. The results of this study can help to extend the therapeutic window of the lead compound CMC2.24 by providing options for selecting partially or fully hydrogenated derivatives for cosmetic applications where a trade-off between color and efficacy is needed. Thus, the degree of hydrogenation can be tuned for desired biological effects. Further studies are warranted to evaluate the efficacy of products 4 & 5 at suppressing pigmentation in 3D skin-tissue equivalents and in vivo models. Full article

Gestation is a crucial life stage for both women and offspring, and outcomes are affected by many environmental factors, including diet. The Mediterranean dietary pattern (MD) is considered a healthy eating pattern that can provide the nutritional requirements of pregnancy. Meanwhile, iron deficiency anemia is one of the most frequent complications related to pregnancy. This study aimed to evaluate how the level of adherence to the MD influences maternal gestational weight gain and specific iron-related maternal biochemical parameters during the pregnancy. Accordingly, an observational, population-based study using data from pregnant women conducted over the entire course of their pregnancy was carried out. Adherence to the MD was assessed once using the MEDAS score questionnaire. Of the 506 women studied, 116 (22.9%) were classified as demonstrating a high adherence, 277 (54.7%) a medium adherence, and 113 (22.3%) a low adherence to the MD. No differences were observed in gestational weight gain among the MD adherence groups but the adequacy of weight gain did vary among the groups, with the proportions of inadequate (insufficient or excessive) weight gain presenting the most notable differences. Total anemia prevalence was 5.3%, 15.6%, and 12.3%, respectively, during the first, second, and third trimesters. For iron-related biochemical parameters, no differences are observed among the adherence groups during pregnancy. With high adherence to the MD as the reference group, the crude odds of iron deficiency diagnosis are significant in the first trimester for both the medium [OR = 2.99 (1.55–5.75)] and low [OR = 4.39 (2.15–8.96)] adherence groups, with deficient adherence to the Mediterranean dietary pattern being responsible for 66.5% (35.5–82.6) and 77.2% (53.5–88.8) of the risk of iron deficiency diagnosis for medium and low adherence, respectively. However, adjusted odds ratios were not significant, possibly due to the small sample size. Our data suggest that MD adherence could be related to gestational weight gain adequacy and that optimal adherence could reduce iron deficiency and/or anemia during pregnancy in the studied population. Full article

This study aimed to research the involvement of enterotoxigenic E. coli (ETEC) and C. difficile or C. perfringens type C in the aetiology of neonatal piglet diarrhoea in Greece and to identify preventive factors for them. A total of 78 pooled faecal samples were collected randomly from 234 suckling piglets (1–4 days of age) with diarrhoea from 26 pig farms (3 piglets × 3 litters × 26 farms = 234 piglets = 78 faecal pool samples). The collected samples were initially screened for the presence of E. coli and C. difficile or C. perfringens via cultivation on MacConkey and anaerobic blood agar, respectively. Subsequently, the samples were pooled on ELUTE cards. From samples tested, 69.23% of those in the farms were ETEC F4-positive, 30.77% were ETEC F5-positive, 61.54% ETEC were F6-positive, 42.31% were ETEC F4- and E. coli enterotoxin LT-positive, 19.23% were ETEC F5- and LT-positive, 42.31% were ETEC F6- and LT-positive, while LT was found in 57.69% of those in the farms. C. difficile was involved in many cases and identified as an emerging neonatal diarrhoea etiological agent. Specifically, Toxin A of C. difficile was found in 84.62% and Toxin B in 88.46% of those in the farms. Antibiotic administration to sows in combination with probiotics or acidifiers was revealed to reduce the detection of antigens of ETEC and the enterotoxin LT of E. coli. Full article

A drug’s aqueous solubility is defined as the ability to dissolve in a particular solvent, and it is currently a major hurdle in bringing new drug molecules to the market. According to some estimates, up to 40% of commercialized products and 70–90% of drug candidates in the development stage are poorly soluble, which results in low bioavailability, diminished therapeutic effects, and dosage escalation. Because of this, solubility must be taken into consideration when developing and fabricating pharmaceutical products. To date, a number of approaches have been investigated to address the problem of poor solubility. This review article attempts to summarize several conventional methods utilized to increase the solubility of poorly soluble drugs. These methods include the principles of physical and chemical approaches such as particle size reduction, solid dispersion, supercritical fluid technology, cryogenic technology, inclusion complex formation techniques, and floating granules. It includes structural modification (i.e., prodrug, salt formation, co-crystallization, use of co-solvents, hydrotrophy, polymorphs, amorphous solid dispersions, and pH variation). Various nanotechnological approaches such as liposomes, nanoparticles, dendrimers, micelles, metal organic frameworks, nanogels, nanoemulsions, nanosuspension, carbon nanotubes, and so forth have also been widely investigated for solubility enhancement. All these approaches have brought forward the enhancement of the bioavailability of orally administered drugs by improving the solubility of poorly water-soluble drugs. However, the solubility issues have not been completely resolved, owing to several challenges associated with current approaches, such as reproducibility in large scale production. Considering that there is no universal approach for solving solubility issues, more research is needed to simplify the existing technologies, which could increase the number of commercially available products employing these techniques. Full article

Natural scaffolds remain an important basis for drug development. Therefore, approaches to natural bioactive compound discovery attract significant attention. In this account, we summarize modern and emerging trends in the screening and identification of natural antibiotics. The methods are divided into three large groups: approaches based on microbiology, chemistry, and molecular biology. The scientific potential of the methods is illustrated with the most prominent and recent results. Full article

Advanced heart failure is a growing problem for which the best treatment is cardiac transplantation. However, the shortage of donors’ hearts made left ventricular assist devices as destination therapy (DT-LVAD) a highly recommended alternative: they improved mid-term prognosis as well as patients’ quality of life. Current intracorporeal pumps with a centrifugal continuous flow evolved in the last few years. Since 2003, when first LVAD was approved for long-term support, smaller device sizes with better survival and hemocompatibility profile were reached. The most important difficulty lies in the moment of the implant. Recent indications range from INTERMACS class 2 to 4, with close monitoring in intermediate cases. Moreover, a large multiparametric study is needed for considering the candidacy: basal situation, with a special interest in frailty, comorbidities, including renal and hepatic dysfunction, and medical background, considering every prior cardiac condition, must be evaluated. In addition, some clinical risk scores can be helpful to measure the possibility of right heart failure or morbi-mortality. With this review, we sought to summarize all the device improvements, with their updated clinical results, as well as to focus on all the patient selection criteria. Full article

We evaluated 13 patients affected by myasthenia gravis (MG) who had coronavirus disease 2019 (COVID-19) before vaccination and 14 myasthenic patients who contracted severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection after vaccination to evaluate factors related to different COVID-19 outcomes. We compared the two groups’ previous stability of MG and the severity of SARS-CoV-2 infection. Vaccinated and non-vaccinated patients were comparable in terms of severity of the previous MG course (mean maximum myasthenia gravis Foundation of America–MGFA–Class III) and during SARS-CoV-2 infection (mean MGFA Class II). In non-vaccinated patients, the hospitalization and severe course percentages were 61.5%, while the mortality reached 30.8%. The hospitalization, severe course, and mortality percentages in vaccinated patients were 7.1%. In deceased, non-vaccinated patients, greater myasthenia severity in the past clinical history, but not at the time of infection, was observed. Similarly, older age at MG onset and at the time of infection correlated with a more severe COVID-19 course in non-vaccinated patients (p = 0.03 and p = 0.04), but not in the group of vaccinated patients. In summary, our data support a protective role of vaccination in myasthenic patients, even if anti-CD20 therapy might be associated with a poor immune response to vaccines. Full article

In animal models, melanocyte-stimulating hormones (MSHs) protect the liver from various injuries. Erythropoietic protoporphyria (EPP), a metabolic disorder, leads to the accumulation of protoporphyrin (PPIX). In addition to the most prominent symptom of incapacitating phototoxic skin reactions, 20% of EPP patients exhibit disturbed liver functioning and 4% experience terminal liver failure caused by the hepatobiliary elimination of excess PPIX. Skin symptoms are mitigated through the application of the controlled-release implant afamelanotide, an α-MSH analog, every sixty days. Recently, we showed that liver function tests (LFTs) improved during afamelanotide treatment when compared to before treatment. The present study investigated whether this effect is dose-dependent, as the evidence of dose dependency would support a beneficial influence of afamelanotide. Methods: In this retrospective observational study, we included 2933 liver-function tests, 1186 PPIX concentrations and 1659 afamelanotide implant applications in 70 EPP patients. We investigated whether the number of days since the preceding afamelanotide dose or the number of doses during the preceding 365 days had an effect on LFTs and PPIX levels. In addition, we assessed the effect of global radiation. Results: Inter-patient differences exerted the most prominent effect on PPIX and LFTs. In addition, PPIX increased significantly with an increase in the number of days since the last afamelanotide implant (p < 0.0001). ALAT and bilirubin decreased significantly with an increasing number of afamelanotide doses in the preceding 365 days (p = 0.012, p = 0.0299, respectively). Global radiation only influenced PPIX (p = 0.0113). Conclusions: These findings suggest that afamelanotide ameliorates both PPIX concentrations and LFTs in EPP in a dose-dependent manner. Full article

Agastache rugosa, otherwise called Korean mint, has a wide range of medicinal benefits. In addition, it is a rich source of several medicinally valuable compounds such as acacetin, tilianin, and some phenolic compounds. The present study aimed to investigate how the Tartary buckwheat transcription factor AtMYB12 increased the primary and secondary metabolites in Korean mint hairy roots cultured under light and dark conditions. A total of 50 metabolites were detected by using high-performance liquid chromatography (HPLC) and gas chromatography–time-of-flight mass spectrometry (GC-TOFMS). The result showed that the AtMYB12 transcription factor upregulated the phenylpropanoid biosynthesis pathway genes, which leads to the highest accumulation of primary and secondary metabolites in the AtMYB12-overexpressing hairy root lines (transgenic) than that of the GUS-overexpressing hairy root line (control) when grown under the light and dark conditions. However, when the transgenic hairy root lines were grown under dark conditions, the phenolic and flavone content was not significantly different from that of the control hairy root lines. Similarly, the heat map and hierarchical clustering analysis (HCA) result showed that most of the metabolites were significantly abundant in the transgenic hairy root cultures grown under light conditions. Principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) showed that the identified metabolites were separated far based on the primary and secondary metabolite contents present in the control and transgenic hairy root lines grown under light and dark conditions. Metabolic pathway analysis of the detected metabolites showed 54 pathways were identified, among these 30 were found to be affected. From these results, the AtMYB12 transcription factor activity might be light-responsive in the transgenic hairy root cultures, triggering the activation of the primary and secondary metabolic pathways in Korean mint. Full article

Aberrant accumulation of the neurotransmitter L-glutamate (L-Glu) has been implicated as a mechanism of neurodegeneration, and the release of L-Glu after stroke onset leads to a toxicity cascade that results in neuronal death. The acai berry (Euterpe oleracea) is a potential dietary nutraceutical. The aim of this research was to investigate the neuroprotective effects of acai berry aqueous and ethanolic extracts to reduce the neurotoxicity to neuronal cells triggered by L-Glu application. L-Glu and acai berry effects on cell viability were quantified using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays, and effects on cellular bioenergetics were assessed via quantitation of the levels of cellular ATP, mitochondrial membrane potential (MMP), and production of reactive oxygen species (ROS) in neuroblastoma cells. Cell viability was also evaluated in human cortical neuronal progenitor cell culture after L-Glu or/and acai berry application. In isolated cells, activated currents using patch-clamping were employed to determine whether L-Glu neurotoxicity was mediated by ionotropic L-Glu-receptors (iGluRs). L-Glu caused a significant reduction in cell viability, ATP, and MMP levels and increased ROS production. The co-application of both acai berry extracts with L-Glu provided neuroprotection against L-Glu with sustained cell viability, decreased LDH production, restored ATP and MMP levels, and reduced ROS levels. Whole-cell patch-clamp recordings showed that L-Glu toxicity is not mediated by the activation of iGluRs in neuroblastoma cells. Fractionation and analysis of acai berry extracts with liquid chromatography-mass spectrometry identified several phytochemical antioxidants that may have provided neuroprotective effects. In summary, the acai berry contains nutraceuticals with antioxidant activity that may be a beneficial dietary component to limit pathological deficits triggered by excessive L-Glu accumulations. Full article

Fungi biofilms have been found growing on spacecraft surfaces such as windows, piping, cables, etc. The contamination of these surfaces with fungi, although undesirable, is highly difficult to avoid. While several biofilm forming species, including Penicillium rubens, have been identified in spacecraft, the effect of microgravity on fungal biofilm formation is unknown. This study sent seven material surfaces (Stainless Steel 316, Aluminum Alloy, Titanium Alloy, Carbon Fiber, Quartz, Silicone, and Nanograss) inoculated with spores of P. rubens to the International Space Station and allowed biofilms to form for 10, 15, and 20 days to understand the effects of microgravity on biofilm morphology and growth. In general, microgravity did not induce changes in the shape of biofilms, nor did it affect growth in terms of biomass, thickness, and surface area coverage. However, microgravity increased or decreased biofilm formation in some cases, and this was incubation-time- and material-dependent. Nanograss was the material with significantly less biofilm formation, both in microgravity and on Earth, and it could potentially be interfering with hyphal adhesion and/or spore germination. Additionally, a decrease in biofilm formation at 20 days, potentially due to nutrient depletion, was seen in some space and Earth samples and was material-dependent. Full article

Despite the improvements in the treatment of coronary artery disease (CAD) and acute myocardial infarction (MI) over the past 20 years, ischemic heart disease (IHD) continues to be the most common cause of heart failure (HF). In clinical trials, over 70% of patients diagnosed with HF had IHD as the underlying cause. Furthermore, IHD predicts a worse outcome for patients with HF, leading to a substantial increase in late morbidity, mortality, and healthcare costs. In recent years, new pharmacological therapies have emerged for the treatment of HF, such as sodium-glucose cotransporter-2 inhibitors, angiotensin receptor-neprilysin inhibitors, selective cardiac myosin activators, and oral soluble guanylate cyclase stimulators, demonstrating clear or potential benefits in patients with HF with reduced ejection fraction. Interventional strategies such as cardiac resynchronization therapy, cardiac contractility modulation, or baroreflex activation therapy might provide additional therapeutic benefits by improving symptoms and promoting reverse remodeling. Furthermore, cardiac regenerative therapies such as stem cell transplantation could become a new therapeutic resource in the management of HF. By analyzing the existing data from the literature, this review aims to evaluate the impact of new HF therapies in patients with IHD in order to gain further insight into the best form of therapeutic management for this large proportion of HF patients. Full article

One of the most important challenges horticultural crops confront is drought, particularly in regions such as the Mediterranean basin, where water supplies are usually limited and will become even scarcer due to global warming. Therefore, the selection and diversification of stress-tolerant cultivars are becoming priorities of contemporary ornamental horticulture. This study explored the impact of water stress on two Tropaeolum species frequently used in landscaping. Young plants obtained by seed germination were exposed to moderate water stress (half the water used in the control treatments) and severe water stress (complete withholding of irrigation) for 30 days. Plant responses to these stress treatments were evaluated by determining several growth parameters and biochemical stress markers. The latter were analysed by spectrophotometric methods and, in some cases, by non-destructive measurements using an optical sensor. The statistical analysis of the results indicated that although the stress responses were similar in these two closely related species, T. minus performed better under control and intermediate water stress conditions but was more susceptible to severe water stress. On the other hand, T. majus had a stronger potential for adaptation to soil water scarcity, which may be associated with its reported expansion and naturalisation in different regions of the world. The variations in proline and malondialdehyde concentrations were the most reliable biochemical indicators of water stress effects. The present study also showed a close relationship between the patterns of variation of flavonoid and chlorophyll contents obtained by sensor-based and spectrophotometric methods. Full article

Wolfiporia extensa (WE) is a medicinal mushroom and an excellent source of naturally occurring anti-inflammatory substances. However, the particular bioactive compound(s) and mechanism(s) of action against inflammation have yet to be determined. Here, we studied anti-inflammatory bioactive compounds and their molecular mechanisms through network pharmacology. Methanol (ME) extract of WE (MEWE) was used for GC-MS analysis to identify the bioactives, which were screened by following Lipinski’s rules. Public databases were used to extract selected bioactives and inflammation-related targets, and Venn diagrams exposed the common targets. Then, STRING and Cytoscape tools were used to construct protein-protein (PPI) network and mushroom-bioactives-target (M-C-T) networks. Gene Ontology and KEGG pathway analysis were performed by accessing the DAVID database and molecular docking was conducted to validate the findings. The chemical reactivity of key compounds and standard drugs was explored by the computational quantum mechanical modelling method (DFT study). Results from GC-MS revealed 27 bioactives, and all obeyed Lipinski’s rules. The public databases uncovered 284 compound-related targets and 7283 inflammation targets. A Venn diagram pointed to 42 common targets which were manifested in the PPI and M-C-T networks. KEGG analysis pointed to the HIF-1 signaling pathway and, hence, the suggested strategy for preventing the onset of inflammatory response was inhibition of downstream NFKB, MAPK, mTOR, and PI3K-Akt signaling cascades. Molecular docking revealed the strongest binding affinity for “N-(3-chlorophenyl) naphthyl carboxamide” on five target proteins associated with the HIF-1 signaling pathway. Compared to the standard drug utilized in the DFT (Density Functional Theory) analysis, the proposed bioactive showed a good electron donor component and a reduced chemical hardness energy. Our research pinpoints the therapeutic efficiency of MEWE and this work suggests a key bioactive compound and its action mechanism against inflammation. Full article

Background: Scientific studies point to a significant global vitamin D deficiency. The recommended dose of vitamin D for the adult population in Central Europe is 800–2000 IU/day. The aim of our study was to determine whether doses of 1000 IU or 2000 IU of vitamin D₃ are adequate to achieve the sufficiency reference values of [25(OH)D]. Methods: Seventy-two healthy volunteers, average age twenty-two, took part in the study. The study was conducted from October to March in order to eliminate intra-dermal vitamin D production. Vitamin D₃ in an oleaginous mixture was used. The participants used either 1000 IU or 2000 IU/daily for two 60-day periods with a 30-day break. Results: The dose of 1000 IU, taken for 60 days, increased vitamin D levels relatively little. Furthermore, serum vitamin D levels decreased in the 30 days following the cessation of supplementation. Taking 2000 IU daily led to a sharp increase in serum levels which plateaued 30 days after the subjects stopped using vitamin D₃ drops. Conclusions: Both doses, taken daily, can help maintain adequate vitamin D levels during the winter months. A daily dose of 2000 IU, however, maintained the desired levels of vitamin D for a longer period. Full article

Plants are constantly faced with biotic or abiotic stress, which affects their growth and development. Yield reduction due to biotic and abiotic stresses on economically important crop species causes substantial economic loss at a global level. Breeding for stress tolerance to create elite and superior genotypes has been a common practice for many decades, and plant tissue culture can be an efficient and cost-effective method. Tissue culture is a valuable tool to develop stress tolerance, screen stress tolerance, and elucidate physiological and biochemical changes during stress. In vitro selection carried out under controlled environment conditions in confined spaces is highly effective and cheaper to maintain. This review emphasizes the relevance of plant tissue culture for screening major abiotic stresses, drought, and salinity, and the development of disease resistance. Further emphasis is given to screening metal hyperaccumulators and transgenic technological applications for stress tolerance. Full article

The endocannabinoid system consists of several phytocannabinoids, cannabinoid receptors, and enzymes that aid in numerous steps necessary to manifest any pharmacological activity. It is well known that the endocannabinoid system inhibits the pathogenesis of the inflammatory and autoimmune disease rheumatoid arthritis (RA). To the best of our knowledge, no research has been done that explains the network-pharmacology-based anti-rheumatic processes by focusing on the endocannabinoid system. Therefore, the purpose of this study is to further our understanding of the signaling pathways, associated proteins, and genes underlying RA based on the abundant natural endocannabinoids. The knowledge on how the phytocannabinoids in Cannabis sativa affect the endocannabinoid system was gathered from the literature. SwissTarget prediction and BindingDB databases were used to anticipate the targets for the phytocannabinoids. The genes related to RA were retrieved from the DisGeNET and GeneCards databases. Protein–protein interactions (high confidence > 0.7) were carried out with the aid of the string web server and displayed using Cytoscape. The Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway analysis was used to perform enrichment analyses on the endocannabinoid–RA common targets. ShinyGO 0.76 was used to predict the biological processes listed in the Gene Ontology (GO) classification system. The binding affinity between the ligand and the receptors was precisely understood using molecular docking, induced-fit docking, and a molecular dynamics simulation. The network pharmacology analyses predicted that processes like response to oxygen-containing compounds and peptodyl-amino acid modification are related to the potential mechanisms of treatment for RA. These biological actions are coordinated by cancer, neuroactive ligand–receptor interaction, lipids and atherosclerosis, the calcium signaling pathway, and the Rap1 signaling pathway. According to the results of molecular docking, in the context of RA, phytocannabinoids may bind to important target proteins such PIK3CA, AKT1, MAPK9, PRKCD, BRAF, IGF1R, and NOS3. This entire study predicted the phytocannabinoids’ systemic biological characteristics. Future experimental research is needed, however, to confirm the results so far. Full article

The involvement of the changed expression/function of neurotrophic factors in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD), has been suggested. AD is one of the age-related dementias, and is characterized by cognitive impairment with decreased memory function. Developing evidence demonstrates that decreased cell survival, synaptic dysfunction, and reduced neurogenesis are involved in the pathogenesis of AD. On the other hand, it is well known that neurotrophic factors, especially brain-derived neurotrophic factor (BDNF) and its high-affinity receptor TrkB, have multiple roles in the central nervous system (CNS), including neuronal maintenance, synaptic plasticity, and neurogenesis, which are closely linked to learning and memory function. Thus, many investigations regarding therapeutic approaches to AD, and/or the screening of novel drug candidates for its treatment, focus on upregulation of the BDNF/TrkB system. Furthermore, current studies also demonstrate that GDNF, IGF1, and bFGF, which play roles in neuroprotection, are associated with AD. In this review, we introduce data demonstrating close relationships between the pathogenesis of AD, neurotrophic factors, and drug candidates, including natural compounds that upregulate the BDNF-mediated neurotrophic system. Full article

The genus Kalanchoe Adans. (Crassulaceae) is native to Madagascar and comprises 145 species, being naturalized in the tropics and cultivated worldwide. In addition to having ornamental value, several Kalanchoe species are commonly used in popular medicine for the treatment of inflammatory conditions, wounds, gastric ulcers, and other diseases. The great importance of the genus is reflected on its acknowledgment by traditional and alternative health systems and organizations, as well as on the growing number of papers reporting pharmacological properties of extracts and isolated compounds from Kalanchoe. Among these properties, we highlight anti-inflammatory, antitumor, wound healing, antiulcer, and muscle relaxing properties. These activities are attributed mostly to flavonoids and bufadienolides, the main secondary metabolites reported in Kalanchoe extracts. While bufadienolides are generally related to cytotoxic and muscle relaxing activities, flavonoids are commonly reported as anti-inflammatory and wound healing agents. This review provides up to date information and perspectives on bioactive compounds from the Kalanchoe genus that are potentially useful for the development of new drugs. It includes not only a discussion on the advantages of the Kalanchoe species as source of bioactive compounds, but also the gaps, opportunities, and challenges to translate the acquired knowledge into innovation for drug development. Full article

There is a wide range of sequelae affecting COVID-19 survivors, including impaired physical capacity. These sequelae can affect the quality of life and return to work of the active population. Therefore, one of the pillars of following-up is the evaluation of physical capacity, which can be assessed with field tests (such as the six-minute walk test, the one-minute standing test, the Chester step test, and the shuttle walking test) or laboratory tests (such as the cardiopulmonary exercise test). These tests can be performed in different contexts and have amply demonstrated their usefulness in the assessment of physical capacity both in post-COVID-19 patients and in other chronic respiratory, metabolic, cardiologic, or neurologic diseases. However, when traditional tests cannot be performed, physical function can be a good substitute, especially for assessing the effects of an intervention. For example, the Short Physical Performance Battery assessment and the Timed Up and Go assessment are widely accepted in older adults. Thus, the test should be chosen according to the characteristics of each subject. Full article