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.

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.

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.

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.

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.

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.