The role of mesenchymal stem cells in the treatment and pathogenesis of psoriasis.

Psoriasis, a prevalent inflammatory skin condition impacting millions globally, continues to pose treatment challenges, despite the availability of multiple therapies. This underscores the demand for innovative treatments. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic option due to their capacity to modulate the immune system and facilitate tissue healing. Recent research indicates that MSCs don't just work through direct cell-to-cell interactions but also release extracellular vesicles (EVs), containing various bioactive substances like proteins, lipids, and nucleic acids. This article explores our current knowledge of psoriasis's origins and the potential utilization of MSCs and their EVs, particularly exosomes, in managing the condition. Additionally, we delve into how MSCs and EVs function in therapy, including their roles in regulating immune responses and promoting tissue repair. Lastly, we discuss the obstacles and opportunities associated with translating MSC-based treatments for psoriasis into clinical practice.

In-silico and in-vitro studies revealed alpha-amyrin as a potent pnhibitor of TLR2 for the therapeutics of bacterial infection and sepsis.

This study employed a multifaceted approach to investigate the inhibitory potential of alpha-amyrin against TLR2, a key player in bacterial infection and sepsis. A high-resolution TLR2 model was constructed using Swiss-MODEL, exhibiting excellent quality with 100% sequence identity and coverage. Cavity detection revealed five significant cavities on TLR2. Molecular docking identifies alpha-amyrin as a potent inhibitor, displaying a strong binding affinity of -8.6 kcal/mol. Comprehensive analyses, including ADMET predictions, PASS analysis, and SwissTargetPrediction, affirm alpha-amyrin's drug-like properties and diverse biological activities. Cytotoxicity assays on HEK-293 cells confirm its safety, and fluorescence-based inhibition assays provide empirical evidence of its inhibitory potency on TLR2 enzymatic activity. Further validations in HUVECs show a significant decrease in TLR2 mRNA expression (p<0.01) and activity (p<0.05) upon alpha-amyrin treatment. In conclusion, this integrative study positions alpha-amyrin as a promising therapeutic candidate for TLR2 inhibition, emphasizing its potential in combating bacterial infections with safety and efficacy.

Application of mesenchymal stem cells derived from the umbilical cord or Wharton's jelly and their extracellular vesicles in the treatment of various diseases.

Mesenchymal stem cells (MSCs) originating from the umbilical cord (UC) or Wharton's jelly (WJ) have attracted substantial interest due to their potential to augment therapeutic approaches for a wide range of disorders. These cells demonstrate a wide range of capabilities in the process of differentiating into a multitude of cell types. Additionally, they possess a significant capacity for proliferation and are conveniently accessible. Furthermore, they possess a status of being immune-privileged, exhibit minimal tumorigenic characteristics, and raise minimal ethical concerns. Consequently, they are well-suited candidates for tissue regeneration and the treatment of diseases. Additionally, UC-derived MSCs offer a substantial yield compared to other sources. The therapeutic effects of these MSCs are closely associated with the release of nanosized extracellular vesicles (EVs), including exosomes and microvesicles (MVs), containing lipids, microRNAs, and proteins that facilitate intercellular communication. Due to their reduced tumorigenic and immunogenic characteristics, in addition to their convenient manipulability, EVs have arisen as a viable alternative for the management of disorders. The favorable characteristics of UC-MSCs or WJ-MSCs and their EVs have generated significant attention in clinical investigations encompassing diverse pathologies. Therefore, we present a review encompassing current preclinical and clinical investigations, examining the implications of UC-MSCs in diverse diseases, including those affecting bone, cartilage, skin, liver, kidney, neural, lung, cardiovascular, muscle, and retinal tissues, as well as conditions like cancer, diabetes, sepsis, and others.

Recent advances in immunotherapy in cancer treatment.

Immunotherapy has emerged as a transformative approach in cancer treatment, leveraging the body's own immune system to recognize and eradicate cancer cells. This review provides an overview of the recent advances and aspects in immunotherapy in cancer biology, from established therapies like checkpoint inhibitors and CAR-T cells to emerging innovative approaches and the challenges associated with their clinical translation.   The exploration includes an examination of checkpoint inhibitors, elucidating the mechanisms behind programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors. Recent clinical successes and ongoing trials demonstrate the efficacy of checkpoint inhibitors across diverse malignancies, underscoring the potential for durable responses and improved patient outcomes. CAR-T cell therapy represents a groundbreaking avenue in immunotherapy, involving the genetic modification of a patient's T cells to express chimeric antigen receptors (CARs) for targeted cancer cell recognition. Furthermore, the review touches on the challenges associated with immunotherapy, including resistance mechanisms and adverse effects. Insightful discussions on overcoming resistance through combination therapies, adaptive treatment strategies, and emerging technologies underscore the ongoing efforts to enhance the long-term efficacy of immunotherapeutic interventions. In summary, this extensive review provides a comprehensive overview of recent advances in immunotherapy in cancer biology, highlighting the transformative impact of these therapies on patient outcomes, the challenges faced, and the promising directions for future research and clinical applications.

Chitosan Nanoparticles Alleviated the Adverse Effects of Sildenafil on the Oxidative Stress Markers and Antioxidant Enzyme Activities in Rats.

Sildenafil (SF) is widely used for erectile dysfunction and other conditions, though with limitations regarding oral absorption and adverse effects. Despite nanotechnological improvements, the effect of nanocarriers on SF hepatotoxicity has not been documented to date. This study aimed at assessing the impact of chitosan nanoparticles either uncoated (CS NPs) or Tween 80-coated (T-CS NPs) on the effects of SF on oxidative stress markers and antioxidant enzyme activities in rats. Test SF-CS NPs prepared by ionic gelation were uniform positively charged nanospheres (diameter 178-215 nm). SF was administered intraperitoneally to male rats (1.5 mg/kg body weight) in free or nanoencapsulated forms as SF-CS NPs and T-SF-CS NPs for 3 weeks. Free SF significantly suppressed the activity of the antioxidant enzymes glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), and superoxide dismutase (SOD), as well as the levels of glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) as in an indirect measure of free radicals. Interestingly, SF-CS NPs and T-SF-CS-NPs treatments significantly attenuated the inhibitory effects of SF on the activity of these enzymes whereas, GST activity was inhibited. Moreover, the protein expression of GST was downregulated upon treatment of rats with free SF, SF-CS-NPs, and T-SF CS-NPs. In contrast, the activity and protein expression of GPx was induced by SF-CS NPs and T-SF-CS-NPs treatments. The histopathological study showed that SF induced multiple adverse effects on the rat liver architecture which were markedly suppressed particularly by T-SF-CS NPs. In conclusion, chitosan nanoencapsulation of SF counteracted the adverse effects of SF on the activity of antioxidant enzymes and liver architecture. Findings might have significant implications in improving the safety and efficacy of SF treatment of the widely expanding disease conditions.

Global Lipidome Profiling Revealed Multifaceted Role of Lipid Species in Hepatitis C Virus Replication, Assembly, and Host Antiviral Response.

Hepatitis C virus (HCV) is a major human pathogen that requires a better understanding of its interaction with host cells. There is a close association of HCV life cycle with host lipid metabolism. Lipid droplets (LDs) have been found to be crucial organelles that support HCV replication and virion assembly. In addition to their role in replication, LDs also have protein-mediated antiviral properties that are activated during HCV infection. Studies have shown that HCV replicates well in cholesterol and sphingolipid-rich membranes, but the ways in which HCV alters host cell lipid dynamics are not yet known. In this study, we performed a kinetic study to check the enrichment of LDs at different time points of HCV infection. Based on the LD enrichment results, we selected early and later time points of HCV infection for global lipidomic study. Early infection represents the window period for HCV sensing and host immune response while later infection represents the establishment of viral RNA replication, virion assembly, and egress. We identified the dynamic profile of lipid species at early and later time points of HCV infection by global lipidomic study using mass spectrometry. At early HCV infection, phosphatidylinositol phospholipids (PIPs), lysophosphatidic acid (LPA), triacyl glycerols (TAG), phosphatidylcholine (PC), and trihexosylceramides (Hex3Cer) were observed to be enriched. Similarly, free fatty acids (FFA), phosphatidylethanolamine (PE), N-acylphosphatidylethanolamines (NAPE), and tri acylglycerols were enriched at later time points of HCV infection. Lipids enriched at early time of infection may have role in HCV sensing, viral attachment, and immune response as LPA and PIPs are important for immune response and viral attachment, respectively. Moreover, lipid species observed at later infection may contribute to HCV replication and virion assembly as PE, FFA, and triacylglycerols are known for the similar function. In conclusion, we identified lipid species that exhibited dynamic profile across early and later time points of HCV infection compared to mock cells, which could be therapeutically relevant in the design of more specific and effective anti-viral therapies.

Students' perception of asynchronous versus synchronous distance learning during COVID-19 pandemic in a medical college, southwestern region of Saudi Arabia.

BACKGROUND: COVID-19 preventive measures required a drastic shift to online teaching-learning in most of countries. Institutions used different combinations of live online lectures (synchronous) requiring students to attend the class in real-time, as well as recorded lectures uploaded by the instructors to be accessed by students as per their own convenience (asynchronous). We undertook this study to assess and compare the perceptions of students regarding their learning experiences in the synchronous versus asynchronous mode of instruction using  their teaching-learning during the compulsory online mode of instruction at the peak of the COVID-19 pandemic. METHODOLOGY: This cross-sectional questionnaire-based study received responses from 122 final-year medical students studying at the College of Medicine, King Khalid University, Abha, Saudi Arabia. An online 5-point Likert scale-based questionnaire was used to collect data regarding experience and perception towards synchronous and asynchronous learning. Statistical analysis was done using Statistical Package for Social Sciences (SPSS) version 21.0. A P-value less than 0.05 was considered significant. RESULT: All the students found both synchronous and asynchronous learning to be equally satisfying, enjoyable and comfortable. No statistically significant difference was found when both the methods were analyzed for enhancement of knowledge. The students opined that asynchronous learning helped them manage their time better whereas synchronous learning encouraged more interaction during the live lectures. CONCLUSION: Overall, the students' perceptions regarding both synchronous and asynchronous online learning were positive. As both methods have their advantages/limitations, a mix of both synchronous and asynchronous methods may be adopted depending upon the content of the topic and the desired learning outcomes.

Unraveling activity of crucial domain HABD protein in dengue virus.

Dengue virus (DENV) causes dengue, which is a very common mosquito-borne viral disease. The global incidence of dengue has increased dramatically in recent decades. About half of the world's population is now at risk. This virus is widespread throughout the tropics, which are influenced by rainfall, temperature, and humidity; however, severe dengue has a higher risk of death when not managed timely. To describe Dengue virus helicase ATP binding domain (HABD) protein in biochemically characterized. Sequences analysis, structure modeling, secondary structure prediction, ATPase assay, unwinding assay, RNA binding assay. HABD has RNA-dependent ATPase and helicase activity which are crucial proteins that participate in the unwinding of double-stranded DNA or RNA by utilizing ATP. RNA binding proteins and DEAD-box RNA helicases have been revealed to contribute to viral replication. Moreover, DEAD-box RNA helicases have been demonstrated to be involved in several features of cellular metabolism of RNA, for example, transcription, splicing, biogenesis, ribosomal processing of RNA, etc. In the present study, we have mainly focused on the Dengue virus's helicase ATP binding domain (HABD) and observed that HABD contains RNA-dependent ATPase and unwinding activity at different concentrations and time points.

Glucose and oleic acid mediate cellular alterations in GLP-1-induced insulin-positive differentiating UCBMSCs.

Coordinated effects of glucose and oleic acid on glucagon-like peptide-1 (GLP-1) mediated differentiation of insulin-positive differentiating umbilical cord mesenchymal stromal cells (dUCBMSCs) was studied using a co-culture of NCI-H716 (GLP-1+) and UCBMSCs (insulin+). The addition of 2.5 mM glucose increased the proliferation of NCI-H716 cells by 30% and induced transformation of UCBMSCs into insulin-secreting cells in 18 days as compared to 22 days in control cells. Oleic acid (25 µM) showed decrease in cell proliferation, autophagy, and apoptosis in NCI-H716 cells while no effect was observed in dUCBMSCs. Prolonged glucose and oleic acid resulted in apoptosis and cell cycle changes in dUCBMSCs after day 18 while higher concentrations resulted in cell death. Additionally, the expression of FAS and ACC mRNA was observed in NCI-H716 and dUCBMSCs post 24-hr addition of glucose and/or oleic acid. Absorption of oleic acid was high in NCI-H716 compared to dUCBMSCs. Taken together, optimal concentrations of glucose and oleic acid could be a key factor in stimulating intrinsic GLP-1, which in turn stimulates differentiating MSCs in a glucose-dependent manner. PRACTICAL APPLICATIONS: The aim of this article was to study whether differentiating or differentiated MSCs after mobilization or post-transplant would require optimal glucose and oleic acid to naturally stimulate intrinsic GLP-1, or otherwise, the high or long-term overload of glucose or oleic acid could result in inhibition of differentiated cells resulting in failure of insulin secretion.

Iodine Deficiency Disorders as a Predictor of Stunting among Primary School Children in the Aseer Region, Southwestern Saudi Arabia.

OBJECTIVES: To investigate the present occurrence of stunting and explore the role of iodine deficiency disorders (IDDs) as a predictor of stunting among primary school children in the Aseer Region. METHODS: In a cross-sectional investigation on school children in the Aseer region, thyroid enlargement was evaluated clinically. Urine was collected to evaluate iodine content. RESULTS: The present study involved 3046 school-age pupils. The study disclosed a total goiter rate of 24.0% (95% CI: 22.5-25.5%). The median urinary iodine content (UIC) was 17.0 µg/L. A prevalence of stunting (height for age z score of less than -2) of 7.8% (95% CI: 6.9-8.8%) was found. In a logistic regression model, pupils having clinical goiter (aOR = 1.739; 95% CI: 1.222-2.475) and students having UIC of less than 17 µg/L (aOR = 1.934; 95% CI: 1.457-2.571) were considerably related with stunting. In the receiver operating characteristic (ROC) curve, urinary iodine content to forecast stunting was good (AUC = 0.611, 95% CI: 0.594-0.629). The curve recognized the optimum cutoff point of urinary iodine content to be ≤19.0 µg/L. The sensitivity was 59.66% (95% CI: 53.1-66.0) and the specificity was 57.62% (95% CI: 55.8-59.5). Conclusion: The present study showed that stunting among school-aged children presents a mild public health problem. On the other hand, a severe iodine deficiency situation was revealed among school children in the Aseer region. Continuous monitoring of iodine status among school children is therefore necessary. Concerted interventions that blend nutrition-sensitive with nutrition-specific approaches are expected to influence decreasing stunting significantly.

Clinical and Biochemical Predictors of Nonalcoholic Fatty Liver Disease among Type 2 Diabetes Mellitus Patients at Primary Health Care Level in South Western Saudi Arabia.

OBJECTIVES: To predict the role of different clinical and biochemical parameters in identifying nonalcoholic fatty liver disease (NAFLD) among patients with type 2 diabetes mellitus (T2DM) in Abha city, southwestern Saudi Arabia. METHODS: A stratified random sample was selected. A detailed clinical and biochemical examinations were performed. Using portable abdominal ultrasound examination, NAFLD was identified. The study used receiver operating characteristic (ROC) analysis. RESULTS: The study covered 237 T2DM patients. NAFLD was detected among 174 patients. Area under the curve (AUC) calculations showed that the ability of age, duration of DM in years, and body mass index to predict NAFLD was poor (AUC < 0.6). Similarly, biochemical factors like HbA1c%, AST, cholesterol, triglycerides, HDL, LDL, and VLDL were poor in discriminating between those with and without NAFLD among T2DM. On the other hand, the ability of ALT to predict NAFLD among T2DM was good (AUC = 0.701, 95% CI: 0.637-0.761). The analysis identified the optimal cutoff point of ALT to be ≤22.1 nmol/L. The corresponding sensitivity was 60.7% (95% CI: 53.0-68.0) and specificity was 62.5% (95% CI: 49.5-74.3). CONCLUSIONS: Early identification of NAFLD among T2DM is important. A threshold cutoff value of 22.1 nmol/L of ALT has been identified to predict NAFLD. They should be referred for ultrasound examination for NAFLD.

Acetaldehyde-induced oxidative modifications and morphological changes in isolated human erythrocytes: an in vitro study.

Acetaldehyde is a toxic, mutagenic and carcinogenic metabolite of alcohol which can bind to proteins, DNA and several other cellular macromolecules. Chronic alcohol consumption increases intracellular acetaldehyde levels which enhances the generation of reactive oxygen and nitrogen species (ROS and RNS). In this study, we have examined the effect of acetaldehyde on human erythrocytes under in vitro conditions. Treatment of human erythrocytes with different concentrations of acetaldehyde (0.05-2 mM) for 24 h at 37 °C increased intracellular generation of ROS and RNS. It also increased oxidation of proteins and lipids but decreased glutathione, total sulphhydryl and free amino group content. Methemoglobin level was increased accompanied by a decrease in methemoglobin reductase activity. Acetaldehyde impaired the antioxidant defence system and lowered the total antioxidant capacity of the cell. It decreased the activity of metabolic and membrane-bound enzymes and altered erythrocyte morphology. Our results show that acetaldehyde enhances the generation of ROS and RNS that results in oxidative modification of cellular components. This will lower the oxygen transporting ability of blood and shorten erythrocyte lifespan (red cell senescence).

Effect of Hypovitaminosis D on Lipid Profile in Hypothyroid Patients in Saudi Arabia.

BACKGROUND: Hypothyroidism is believed to be associated with dyslipidemia and is considered a risk factor for the development of atherosclerotic cardiovascular diseases (ASCVD). Vitamin D, due to its steroid hormone action, retains cell function and controls the metabolism of lipids. Therefore, the present study was carried out to show the association of the risk factors of ASCVD and deficiency of thyroid hormones and vitamin D levels since no previous studies have been performed on Saudi patients before. Methodology. A retrospective cohort study was carried out on 400 hypothyroid patients. Medical records of those patients were followed up and were classified as normal and hypothyroid patients according to their thyroid-stimulating hormone levels. TSH, vitamin D, and lipid profiles were determined using the ELISA technique. RESULT: Total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels were significantly higher in hypothyroid patients than those in the normal group. We have found a significant correlation between TSH levels and the risk factors of ASCVD (total cholesterol, triglycerides, and LDL-C). Moreover, a significant correlation between vitamin D levels and the risk factors of ASCVD (total cholesterol, triglycerides, and LDL-C) has been found. In addition, there is a correlation between deficiency of Vit D and low-TSH levels (95% CI 1.092-4.05) indicating a higher risk for the development of ASCVD among those patients. CONCLUSION: Hypothyroid and vitamin D-deficient patients must be screened regularly at an early stage to predict and also to prevent cardiovascular diseases. Moreover, an adequate supply of vitamin D and TH should be given to those patients to prevent cardiovascular diseases at an early stage.

Awareness and Attitude of University Students About Screening and Testing for Hemoglobinopathies: Case Study of the Aseer Region, Saudi Arabia.

Hemoglobinopathies can disturb a patient's life style leading to community problems. Premarital screening is an important tool to control and minimize hemoglobinopathies. This study aimed to assess and improve the awareness and attitude of King Khalid University (KKU) [Abha, Kingdom of Saudi Arabia (KSA)] students in the Aseer Region, regarding hemoglobinopathies and the National Premarital Screening Programme (NPMS) in addition to screening for hemoglobin (Hb) variants of students who agreed to participate. This study was an interventional educational prospective study of electronic-lectures (e-lectures) that addressed some important issues of hemoglobinopathies and premarital screening. Six hundred and eleven students were interviewed during the academic year 2017/2018, using closed-ended questionnaires that distributed before and after intervention. Blood samples were taken from 114 students who agreed to check their Hb type by the D-10 Hemoglobin Testing System. The results revealed significant changes in knowledge and attitude of students toward hemoglobinopathies and premarital counseling after intervention. These results reflected the need for easily accessible and continuous health education programs for students to increase their awareness and attitude toward hemoglobinopathies. Laboratory results for 114 students revealed seven cases with microcytic hypochromic anemia (6.1%); they were all females. Blood screening for Hb variants revealed another two females (1.75%) with sickle cell trait (Hb AS). Electronic-health (E-health) is an efficient tool for improving the awareness and attitude of the community toward hemoglobinopathies. Screening blood tests for detection of hemoglobinopathies should be provided to young adults at an earlier stage (before marriage) to decrease the incidence of hereditary diseases in the community.

Effects of Weight Reduction After Sleeve Gastrectomy on Metabolic Variables in Saudi Obese Subjects in Aseer Province of Kingdom of Saudi Arabia.

OBJECTIVES: The objectives of this study were to investigate the occurrence of oxidative stress, status of protective antioxidants enzymes, inflammatory biomarkers, and some metabolic health variables in the blood and to compare the results between those of the normal controls and obese patients submitted to sleeve gastrectomy-induced weight loss over a 1-year follow-up period. MATERIALS AND METHODS: A prospective study was conducted in Aseer Central Hospital and Abha Private Hospital in the Kingdom of Saudi Arabia from January 2012 to January 2013 on 50 normal (BMI = 22-25 kg/m2) control subjects and 50 obese (BMI = 45-50 kg/m2) patients. A subset of 20 men and 80 women patients, aged 20-45 years, was included. The systemic blood cell counts were determined by Beckman Coulter UniCel analyzer. The occurrence of oxidative stress, the status of antioxidant enzyme system in the blood, levels of serum hepatic enzymes, cardiovascular risk factors, and serum sodium, potassium, copper, and zinc levels were determined by spectrophotometric procedures. The concentration of TSH and T4 were analyzed by Siemens Immunoassay System. RESULTS: Group 1 (Obese: preoperative) This group compared with the normal controls exhibited significant (p < 0.05) increase in inflammatory biomarkers, a significant (p < 0.05) rise in hepatic enzymes, a significant (p < 0.05) decrease in serum total bilirubin. Concentration of serum total cholesterol (TC), triacylglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and fasting blood glucose(FBG) were significantly (p < 0.05) increased, but HDL cholesterol (HDL-C) was significantly depleted (p < 0.05). Serum urea and creatinine contents were significantly (p < 0.05) decreased. Serum copper and zinc levels were significantly (p < 0.05) increased. Group 2: Sleeve Gastrectomy Surgery (Obese: postoperative) This group compared with the obese group, preoperatively, demonstrated a profound reduction in body weight (-32%) as well as in BMI (-29%). Serum malondialdehyde, a stress index, was significantly (p < 0.001) inhibited and conversely, activities of antioxidant enzymes: superoxide dismutase(Cu-Zn SOD), glutathione peroxidase (GPx), glutathione-S-transferase (GST), glucose-6-phosphate dehydrogenase (G6PDH), and vitamin C, were remarkably (p < 0.001) increased. Furthermore, remarkable improvements in deranged metabolic variables approaching normality were discernible. Inflammatory biomarkers in the blood and hepatic enzymes in serum were significantly (p < 0.001) decreased. Levels of TC, TG, LDL-C, FBG, and HDL-C in serum exhibited significant (p < 0.05) reductions, a reversal toward normality. Serum albumin and total bilirubin concentrations were significantly increased (p < 0.001). Serum sodium, potassium, copper, zinc, and TSH levels were significantly (p < 0.001) decreased. CONCLUSIONS: Obesity is a chronic disease of multifactorial origin and resulted in perturbations of whole body metabolism in this study. It is thus likely that this imbalance was associated with an inhibition in protective antioxidants and occurrence of oxidative stress. The staging concept of sleeve gastrectomy is a safe and effective approach with remarkable efficacy in sustaining weight loss and bringing back normal metabolism of variables in tissues over a 1-year follow-up period.