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Medicines, Volume 8, Issue 8 (August 2021) – 6 articles

Cover Story (view full-size image): We isolated a serum calcium-decreasing factor (caldecrin) from pancreas that is also known as chymotrypsin C; however, the blood calcium-lowering activity of caldecrin is not connected to its protease activity. We found that caldecrin, with or without protease activity, suppressed receptor activator of NF-k (kappa) B ligand-induced osteoclast formation from bone marrow macrophages and bone resorption by mature osteoclasts. Caldecrin also inhibited lipopolysaccharide (LPS)-induced osteoclast formation and LPS-mediated M1 macrophage polarization. In addition, protease-deficient caldecrin prevented bone resorption in ovariectomized mice and skeletal muscle destruction in dystrophic mice. These results suggest that caldecrin is a multifunctional protease.View this paper
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Review
Role of Microbial Infection-Induced Inflammation in the Development of Gastrointestinal Cancers
Medicines 2021, 8(8), 45; https://0-doi-org.brum.beds.ac.uk/10.3390/medicines8080045 - 17 Aug 2021
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Abstract
There has been increasing evidence that a local inflammatory response stimulates tumor cells to acquire metastatic potential, and the concept of inflammatory oncotaxis has been spreading in recent years. However, the interaction between microbial inflammation and the development of gastrointestinal cancer is still [...] Read more.
There has been increasing evidence that a local inflammatory response stimulates tumor cells to acquire metastatic potential, and the concept of inflammatory oncotaxis has been spreading in recent years. However, the interaction between microbial inflammation and the development of gastrointestinal cancer is still unclear. This review summarizes the present knowledge on the role of microbial inflammation in the development of gastrointestinal cancers from the perspective of molecular biological findings. Chronic inflammation caused by bacterial infection is known to induce cancers as exemplified by Helicobacter pylori, which is associated with the development of gastric cancer via the activation of the TLR4 pathway by bacterial lipopolysaccharide followed by cancer growth through CagA-MET signaling. In addition, the development of inflammatory bowel diseases has been known to become a risk factor for colorectal cancers, where inflammation caused by certain bacterial infections plays a key role. It is also known that the cancer microenvironment is associated with cancer growth. Moreover, infectious complication after surgery for gastrointestinal cancers may promote tumor progression via the stimulation of pathogen-associated molecular patterns and various inflammatory mediators secreted by immunocytes. Further research on the link between microbial inflammation and cancer progression is needed to drive a paradigm shift in cancer treatment. Full article
(This article belongs to the Special Issue Feature Papers in Cancer Biology and Anticancer Therapeutics)
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Review
Herb–Drug Interactions: Worlds Intersect with the Patient at the Center
Medicines 2021, 8(8), 44; https://0-doi-org.brum.beds.ac.uk/10.3390/medicines8080044 - 05 Aug 2021
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Abstract
This review examines three bodies of literature related to herb–drug interactions: case reports, clinical studies, evaluations found in six drug interaction checking resources. The aim of the study is to examine the congruity of resources and to assess the degree to which case [...] Read more.
This review examines three bodies of literature related to herb–drug interactions: case reports, clinical studies, evaluations found in six drug interaction checking resources. The aim of the study is to examine the congruity of resources and to assess the degree to which case reports signal for further study. A qualitative review of case reports seeks to determine needs and perspectives of case report authors. Methods: Systematic search of Medline identified clinical studies and case reports of interacting herb–drug combinations. Interacting herb–drug pairs were searched in six drug interaction resources. Case reports were analyzed qualitatively for completeness and to identify underlying themes. Results: Ninety-nine case-report documents detailed 107 cases. Sixty-five clinical studies evaluated 93 mechanisms of interaction relevant to herbs reported in case studies, involving 30 different herbal products; 52.7% of these investigations offered evidence supporting reported reactions. Cohen’s kappa found no agreement between any interaction checker and case report corpus. Case reports often lacked full information. Need for further information, attitudes about herbs and herb use, and strategies to reduce risk from interaction were three primary themes in the case report corpus. Conclusions: Reliable herb–drug information is needed, including open and respectful discussion with patients. Full article
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Communication
Anti-Inflammatory Effects of Morinda citrifolia Extract against Lipopolysaccharide-Induced Inflammation in RAW264 Cells
Medicines 2021, 8(8), 43; https://0-doi-org.brum.beds.ac.uk/10.3390/medicines8080043 - 04 Aug 2021
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Abstract
Leaves of Morinda citrifolia (noni) have been used in Polynesian folk medicine for the treatment of pain and inflammation, and their juice is very popular worldwide as a functional food supplement. This study aimed to demonstrate that M. citrifolia seed extract exerts anti-inflammatory [...] Read more.
Leaves of Morinda citrifolia (noni) have been used in Polynesian folk medicine for the treatment of pain and inflammation, and their juice is very popular worldwide as a functional food supplement. This study aimed to demonstrate that M. citrifolia seed extract exerts anti-inflammatory effects on RAW264 cells stimulated by lipopolysaccharide. To confirm the inhibitory effect of M. citrifolia seed extract, we assessed the production of nitric oxide (NO) and inflammatory cytokines. The M. citrifolia seed extract showed a significant inhibition of NO production, with no effect on cell viability, and was more active than M. citrifolia seed oil, leaf extract, and fruit extract. The M. citrifolia seed extract was found to reduce the expression of inducible NO synthase and tumor necrosis factor-alpha of pro-inflammatory cytokines. These results suggest that the anti-inflammatory effect of M. citrifolia seed extract is related to a reduction in the expression of inflammatory mediators and support its potential therapeutic use. Full article
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Article
Psychometric Properties of the Greek Version of the Medical Office on Patient Safety Culture in Primary Care Settings
Medicines 2021, 8(8), 42; https://0-doi-org.brum.beds.ac.uk/10.3390/medicines8080042 - 26 Jul 2021
Viewed by 859
Abstract
Background: Safety culture is considered one of the most crucial premises for further development of patient care in healthcare. During the eight-year economic crisis (2010–2018), Greece made significant reforms in the way the primary health care system operates, aiming at the more efficient [...] Read more.
Background: Safety culture is considered one of the most crucial premises for further development of patient care in healthcare. During the eight-year economic crisis (2010–2018), Greece made significant reforms in the way the primary health care system operates, aiming at the more efficient operation of the system without degrading issues of safety and quality of the provided health services. In this context, this study aims to validate a specialized tool—the Medical Office Survey on Patient Safety Culture (MOSPSC)—developed by the Agency for Healthcare Research and Quality (AHRQ) to evaluate primary care settings in terms of safety culture and quality. Methods: Factor analysis determined the correlation of the factor structure in Greek data with the original questionnaire. The relation of the factor analysis with the Cronbach’s coefficient alpha was also determined, including the construct validity. Results: Eight composites with 34 items were extracted by exploratory factor analysis, with acceptable Cronbach’s alpha coefficients and good construct validity. Consequently, the composites jointly explained 62% of the variance in the responses. Five items were removed from the original version of the questionnaire. As a result, three out of the eight composites were a mixture of items from different compounds of the original tool. The composition of the five factors was similar to that in the original questionnaire. Conclusions: The MOSPSC tool in Greek primary healthcare settings can be used to assess patient safety culture in facilities across the country. From the study, the patient safety culture in Greece was positive, although few composites showed a negative correlation and needed improvement. Full article
(This article belongs to the Special Issue PROTAC—From Bench to Bed)
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Review
Purification and Biological Function of Caldecrin
Medicines 2021, 8(8), 41; https://0-doi-org.brum.beds.ac.uk/10.3390/medicines8080041 - 23 Jul 2021
Viewed by 1043
Abstract
Blood calcium homeostasis is critical for biological function. Caldecrin, or chymotrypsin-like elastase, was originally identified in the pancreas as a serum calcium-decreasing factor. The serum calcium-decreasing activity of caldecrin requires the trypsin-mediated activation of the protein. Protease activity-deficient mature caldecrin can also reduce [...] Read more.
Blood calcium homeostasis is critical for biological function. Caldecrin, or chymotrypsin-like elastase, was originally identified in the pancreas as a serum calcium-decreasing factor. The serum calcium-decreasing activity of caldecrin requires the trypsin-mediated activation of the protein. Protease activity-deficient mature caldecrin can also reduce serum calcium concentration, indicating that structural processing is necessary for serum calcium-decreasing activity. Caldecrin suppresses the differentiation of bone-resorbing osteoclasts from bone marrow macrophages (BMMs) by inhibiting receptor activator of NF-κB ligand (RANKL)-induced nuclear factor of activated T-cell cytoplasmic 1 expression via the Syk–PLCγ–Ca2+ oscillation-calcineurin signaling pathway. It also suppresses mature osteoclastic bone resorption by RANKL-stimulated TRAF6–c-Src–Syk–calcium entry and actin ring formation. Caldecrin inhibits lipopolysaccharide (LPS)-induced osteoclast formation in RANKL-primed BMMs by inducing the NF-κB negative regulator A20. In addition, caldecrin suppresses LPS-mediated M1 macrophage polarization through the immunoreceptor triggering receptor expressed on myeloid cells (TREM) 2, suggesting that caldecrin may function as an anti-osteoclastogenic and anti-inflammatory factor via TREM2. The ectopic intramuscular expression of caldecrin cDNA prevents bone resorption in ovariectomized mice, and the administration of caldecrin protein also prevents skeletal muscle destruction in dystrophic mice. In vivo and in vitro studies have indicated that caldecrin is a unique multifunctional protease and a possible therapeutic target for skeletal and inflammatory diseases. Full article
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Article
Comparison of G8 and ISAR Screening Results in Geriatric Urology
Medicines 2021, 8(8), 40; https://0-doi-org.brum.beds.ac.uk/10.3390/medicines8080040 - 22 Jul 2021
Viewed by 978
Abstract
Background: The G8 and ISAR scores are two different screening tools for geriatric risk factors and frailty. The aim of this study was to compare the G8 and ISAR screening results in a cohort of urogeriatric patients to help clinicians to better understand [...] Read more.
Background: The G8 and ISAR scores are two different screening tools for geriatric risk factors and frailty. The aim of this study was to compare the G8 and ISAR screening results in a cohort of urogeriatric patients to help clinicians to better understand and choose between the two tests. Methods: We retrospectively evaluated 100 patients at the age of 75 and above who were treated for different urological conditions. All routinely and prospectively underwent G8 and ISAR screening tests. A G8 score ≤ 14 and an ISAR score > 2 were considered positive. The results for the two tests were compared and correlated to clinical data. Results: The mean age of the patients was 83 y (min. 75–max. 101); 78 of the patients were male, while 22 were female; 58 of the patients were G8-positive, while 42 were G8-negative; and 24 were ISAR-positive, while 76 ISAR were negative. All the ISAR-positive patients were also G8-positive. There was a significant negative correlation between the G8 and ISAR scores (r = −0.77, p < 0.001). Both tests correlated significantly with the Charlson comorbidity index, length of stay, number of coded diagnosis, and Braden score (p < 0.05). Conclusion: Both tests are significantly correlated with each other and to clinical data related to geriatric frailty. However, the G8 score has a much higher rate of positive tests, which limits its use in daily routine, and the ISAR score is therefore preferable. For “fit” geriatric patients, however, a negative G8 score can be of great use as a confirmatory test for further decision making. Full article
(This article belongs to the Special Issue PROTAC—From Bench to Bed)
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