Mesenchymal stem cells biological and biotechnological advances: Implications for clinical applications.

BACKGROUND: Mesenchymal stem cells (MSCs) are multipotent stem cells that are able to differentiate into multiple lineages including bone, cartilage, muscle and fat. They hold immunomodulatory properties and therapeutic ability to treat multiple diseases, including autoimmune and chronic degenerative diseases. In this article, we reviewed the different biological properties, applications and clinical trials of MSCs. Also, we discussed the basics of manufacturing conditions, quality control, and challenges facing MSCs in the clinical setting. METHODS: Extensive review of the literature was conducted through the databases PubMed, Google Scholar, and Cochrane. Papers published since 2015 and covering the clinical applications and research of MSC therapy were considered. Furthermore, older papers were considered when referring to pioneering studies in the field. RESULTS: The most widely studied stem cells in cell therapy and tissue repair are bone marrow-derived mesenchymal stem cells. Adipose tissue-derived stem cells became more common and to a lesser extent other stem cell sources e.g., foreskin derived MSCs. MSCs therapy were also studied in the setting of COVID-19 infections, ischemic strokes, autoimmune diseases, tumor development and graft rejection. Multiple obstacles, still face the standardization and optimization of MSC therapy such as the survival and the immunophenotype and the efficiency of transplanted cells. MSCs used in clinical settings displayed heterogeneity in their function despite their extraction from healthy donors and expression of similar surface markers. CONCLUSION: Mesenchymal stem cells offer a rising therapeutic promise in various diseases. However, their potential use in clinical applications requires further investigation.

An Overlooked Disease: Minimal Autonomous Cortisol Secretion (MACS). A Narrative Review.

BACKGROUND: A far more common disease than Cushing's syndrome is subclinical hypercortisolism or mild autonomous cortisol secretion (MACS), with an overall prevalence of 0.2-2%. OBJECTIVE: This review aims to shed light on the prevalence, screening and diagnostic criteria, comorbidities, and management of Mild Autonomous Cortisol Secretion (MACS). METHODS: Studies eligible targeted MACS regarding prevalence, screening, comorbidities, management, and clinical outcome. This is a mini-review. IRB approval was not needed. RESULTS: The 1 mg Dexamethasone suppression test (DST) remains the first screening test. MACS is associated with adverse cardiometabolic and renal outcomes, osteoporosis and osteopenia, immunodeficiency, depression, coagulopathy, and sarcopenia. Surgery is the gold standard treatment. Medical therapy is recommended when surgery is contraindicated or not feasible. Clinically silent hypercortisolism is a frequent entity that necessitates early detection and treatment. The production of cortisol should be looked at as a spectrum where subtle, undetectable levels can still be produced. They know its association with adverse health outcomes. CONCLUSION: MACS is no longer considered an asymptomatic disorder; repeated hormonal and functional tests are crucial to prevent multiorgan damage.

Cholera Infection Risks and Cholera Vaccine Safety in Pregnancy.

Introduction: Discuss the impact of cholera infection on pregnant women, fetus, and neonates and review the safety of cholera vaccines in pregnancy. Methods: This study was carried out as a narrative review during November 2022. A thorough literature review was conducted on the following databases: PubMed, Scopus, SciELO, CINAHL, Web of Science, and ScienceDirect. The following parameters were assessed from the included studies: type of cholera vaccine, cholera symptoms, cholera treatment, effect of cholera on pregnancy, effect of cholera treatment on pregnancy, effect of cholera vaccine on pregnancy, risk factors for fetuses and neonates, and prevention of cholera. The authors independently extracted data from the 24 included studies. Results: Cholera infection is a serious threat on pregnancy as it could lead to increased stillbirths and neonatal death. Fetal death was shown to occur mainly in the third trimester as most of the pregnant women infected with cholera had spontaneous abortions even after controlling for other confounding variables such as maternal age, dehydration level, and vomiting. Neonatal death was attributed mainly to congenital malformations and low Apgar scores with no improvements. Besides, cholera vaccines have shown to be safe in pregnancy and have proven to lower fetal and neonatal malformations among vaccinated compared to nonvaccinated pregnant women. Conclusion: This narrative summarizes the different complications due to cholera infection in pregnancy. It also reviews the safety of cholera vaccine administration in pregnant women.

The selective anti-proliferative and pro-apoptotic effect of A. cherimola on MDA-MB-231 breast cancer cell line.

BACKGROUND: Herbal medicines have been a major target for numerous studies through the past years as an alternative treatment for cancer, mainly due to their minimal effects on normal healthy cells. Annona cherimola, popularly known as Cherimoya, is an edible natural fruit rich in phytochemical components and known to possess various biological activities. Previous studies have reported the anti-cancerous effect of A. cherimola ethanolic leaf extract (AELE) on leukemia. This study aims at studying the potential anti-cancer activity of this extract in vitro in two different breast cancer cell lines, namely MDA-MB-231 and MCF-7, in addition to investigating its toxicity on normal mesenchymal stem cells. METHODS: The anti-proliferative effect of AELE was evaluated via cell viability assay. Propidium iodide staining, Cell Death Detection ELISA and flow cytometry analysis of Annexin V binding were used to assess cell cycle progression, DNA fragmentation and apoptosis induction, respectively. Protein expression was determined via Western Blot analysis to decipher the underlying apoptotic molecular mechanism induced upon AELE treatment. RESULTS: The anti-proliferative effect of the extract was found to be selective on the triple-negative breast cancer cell line (MDA-MB-231) in a time- and dose-dependent manner with an IC50 of 390.2 µg/mL at 48 h, with no cytotoxic effects on normal murine mesenchymal stem cells. The pro-apoptotic effect was confirmed by the increase in cellular and DNA fragmentation, flipping of the phosphatidylserine moiety to the outer leaflet, and the increase in Annexin V binding. The underlying molecular mechanism revealed the involvement of the mitochondrial pathway, as shown by alterations in mitochondrial permeability and the upregulation of cytochrome c expression. CONCLUSION: All the data presented in our study suggest that AELE exhibits a selective anti-proliferative and pro-apoptotic effect on the chemo-resistant MDA-MB-231 breast cancer cells, providing evidence for the anti-tumor effects of A. cherimola.