Exploring molecular mechanisms, therapeutic strategies, and clinical manifestations of Huntington's disease.

Huntington's disease (HD) is a paradigm of a genetic neurodegenerative disorder characterized by the expansion of CAG repeats in the HTT gene. This extensive review investigates the molecular complexities of HD by highlighting the pathogenic mechanisms initiated by the mutant huntingtin protein. Adverse outcomes of HD include mitochondrial dysfunction, compromised protein clearance, and disruption of intracellular signaling, consequently contributing to the gradual deterioration of neurons. Numerous therapeutic strategies, particularly precision medicine, are currently used for HD management. Antisense oligonucleotides, such as Tominersen, play a leading role in targeting and modulating the expression of mutant huntingtin. Despite the promise of these therapies, challenges persist, particularly in improving delivery systems and the necessity for long-term safety assessments. Considering the future landscape, the review delineates promising directions for HD research and treatment. Innovations such as Clustered regularly interspaced short palindromic repeats associated system therapies (CRISPR)-based genome editing and emerging neuroprotective approaches present unprecedented opportunities for intervention. Collaborative interdisciplinary endeavors and a more insightful understanding of HD pathogenesis are on the verge of reshaping the therapeutic landscape. As we navigate the intricate landscape of HD, this review serves as a guide for unraveling the intricacies of this disease and progressing toward transformative treatments.

Elucidating the Impact of Deleterious Mutations on IGHG1 and Their Association with Huntington's Disease.

Huntington's disease (HD) is a chronic, inherited neurodegenerative condition marked by chorea, dementia, and changes in personality. The primary cause of HD is a mutation characterized by the expansion of a triplet repeat (CAG) within the huntingtin gene located on chromosome 4. Despite substantial progress in elucidating the molecular and cellular mechanisms of HD, an effective treatment for this disorder is not available so far. In recent years, researchers have been interested in studying cerebrospinal fluid (CSF) as a source of biomarkers that could aid in the diagnosis and therapeutic development of this disorder. Immunoglobulin heavy constant gamma 1 (IGHG1) is one of the CSF proteins found to increase significantly in HD. Considering this, it is reasonable to study the potential involvement of deleterious mutations in IGHG1 in the pathogenesis of this disorder. In this study, we explored the potential impact of deleterious mutations on IGHG1 and their subsequent association with HD. We evaluated 126 single-point amino acid substitutions for their impact on the structure and functionality of the IGHG1 protein while exploiting multiple computational resources such as SIFT, PolyPhen-2, FATHMM, SNPs&Go mCSM, DynaMut2, MAESTROweb, PremPS, MutPred2, and PhD-SNP. The sequence- and structure-based tools highlighted 10 amino acid substitutions that were deleterious and destabilizing. Subsequently, out of these 10 mutations, eight variants (Y32C, Y32D, P34S, V39E, C83R, C83Y, V85M, and H87Q) were identified as pathogenic by disease phenotype predictors. Finally, two pathogenic variants (Y32C and P34S) were found to reduce the solubility of the protein, suggesting their propensity to form protein aggregates. These variants also exhibited higher residual frustration within the protein structure. Considering these findings, the study hypothesized that the identified variants of IGHG1 may compromise its function and potentially contribute to HD pathogenesis.

Medicinal and chemosensing applications of chitosan based material: A review.

Chitosan (CTS), has emerged as a highly intriguing biopolymer with widespread applications, drawing significant attention in various fields ranging from medicinal to chemosensing. Key characteristics of chitosan include solubility, biocompatibility, biodegradability and reactivity, making it versatile in numerous sectors. Several derivatives have been documented for their diverse therapeutic properties, such as antibacterial, antifungal, anti-diabetic, anti-inflammatory, anticancer and antioxidant activities. Furthermore, these compounds serve as highly sensitive and selective chemosensor for the detection of various analytes such as heavy metal ions, anions and various other species in agricultural, environmental and biological matrixes. CTS derivatives interacting with these species and give analytical signals. In this review, we embark on an exploration of the latest advancements in CTS-based materials, emphasizing their noteworthy contributions to medicinal chemistry spanning the years from 2021 to 2023. The intrinsic biological and physiological properties of CTS make it an ideal platform for designing materials that interact seamlessly with biological systems. The review also explores the utilization of chitosan-based materials for the development of colorimetric and fluorimetric chemosensors capable of detecting metal ions, anions and various other species, contributing to advancements in environmental monitoring, healthcare diagnostics, and industrial processes.

Identification of potential inhibitors of tropomyosin receptor kinase B targeting CNS-related disorders and cancers.

Tropomyosin receptor kinase B (TrkB), also known as neurotrophic tyrosine kinase receptor type 2 (NTRK2), is a protein that belongs to the family of receptor tyrosine kinases (RTKs). NTRK2 plays a crucial role in regulating the development and maturation of the central nervous system (CNS) and peripheral nervous system (PNS). Elevated TrkB expression levels observed in different pathological conditions make it a potential target for therapeutic interventions against neurological disorders, including depression, anxiety, Alzheimer's disease, Parkinson's disease, and certain types of cancer. Targeting TrkB using small molecule inhibitors is a promising strategy for the treatment of a variety of neurological disorders. In this research, a systematic virtual screening was carried out on phytoconstituents found in the IMPPAT library to identify compounds potentially inhibiting TrkB. The retrieved compounds from the IMPPAT library were first filtered using Lipinski's rule of five. The compounds were then sorted based on their docking score and ligand efficiency. In addition, PAINS, ADMET, and PASS evaluations were carried out for selecting drug-like compounds. Finally, in interaction analysis, we found two phytoconstituents, Wedelolactone and 3,8-dihydroxy-1-methylanthraquinone-2-carboxylic acid (DMCA), which possessed considerable docking scores and specificity on the TrkB ATP-binding pocket. The selected compounds were further assessed employing molecular dynamics (MD) simulations and essential dynamics. The results revealed that the elucidated compounds bind well with the TrkB binding pocket and lead to fewer conformations fluctuations. This study highlighted using phytoconstituents, Wedelolactone and DMCA as starting leads in developing novel TrkB inhibitors.Communicated by Ramaswamy H. Sarma.

Identification of natural product-based effective inhibitors of spleen tyrosine kinase (SYK) through virtual screening and molecular dynamics simulation approaches.

Spleen tyrosine kinase (SYK) is a non-receptor tyrosine kinase that plays an essential role in signal transduction across different cell types. In the context of allergy and autoimmune disorders, it is a crucial regulator of immune receptor signaling in inflammatory cells such as B cells, mast cells, macrophages, and neutrophils. Developing SYK kinase inhibitors has gained significant interest for potential therapeutic applications in neurological and cancer-related conditions. The clinical use of the most advanced SYK inhibitor, Fostamatinib, has been limited due to its unwanted side effects. Thus, a more targeted approach to SYK inhibition would provide a more comprehensive treatment window. In this study, we used a virtual screening approach to identify potential SYK inhibitors from natural compounds from the IMPPAT database. We identified two compounds, Isolysergic acid and Michelanugine, which showed strong affinity and specificity for the SYK binding pocket. All-atom molecular dynamics (MD) simulations were also performed to explore the stability, conformational changes, and interaction mechanism of SYK in complexes with the identified compounds. The identified compounds might have the potential to be developed into promising SYK inhibitors for the treatment of various diseases, including autoimmune disorders, cancer, and inflammatory diseases. This work aims to identify potential phytochemicals to develop a new protein kinase inhibitor for treating advanced malignancies by providing an updated understanding of the role of SYK.Communicated by Ramaswamy H. Sarma.

Targeting Cathepsin L in Cancer Management: Leveraging Machine Learning, Structure-Based Virtual Screening, and Molecular Dynamics Studies.

Cathepsin L (CTSL) expression is dysregulated in a variety of cancers. Extensive empirical evidence indicates their direct participation in cancer growth, angiogenic processes, metastatic dissemination, and the development of treatment resistance. Currently, no natural CTSL inhibitors are approved for clinical use. Consequently, the development of novel CTSL inhibition strategies is an urgent necessity. In this study, a combined machine learning (ML) and structure-based virtual screening strategy was employed to identify potential natural CTSL inhibitors. The random forest ML model was trained on IC50 values. The accuracy of the trained model was over 90%. Furthermore, we used this ML model to screen the Biopurify and Targetmol natural compound libraries, yielding 149 hits with prediction scores >0.6. These hits were subsequently selected for virtual screening using a structure-based approach, yielding 13 hits with higher binding affinity compared to the positive control (AZ12878478). Two of these hits, ZINC4097985 and ZINC4098355, have been shown to strongly bind CTSL proteins. In addition to drug-like properties, both compounds demonstrated high affinity, ligand efficiency, and specificity for the CTSL binding pocket. Furthermore, in molecular dynamics simulations spanning 200 ns, these compounds formed stable protein-ligand complexes. ZINC4097985 and ZINC4098355 can be considered promising candidates for CTSL inhibition after experimental validation, with the potential to provide therapeutic benefits in cancer management.

Deciphering the binding mechanism of an anti-cancer phytochemical plumbagin with calf thymus DNA using biophysical and in silico techniques.

Plumbagin (PLM), a plant derivative, is well known for a wide range of therapeutic effects in humans including anti-cancer, anti-inflammatory, anti-oxidant, and anti-microbial. Cytotoxic and genotoxic potential of this phytochemical has been studied which demands further insight. DNA being a major target for several drugs was taken to study against PLM to understand its effects on the cellular system. UV-Vis spectroscopy has indicated the binding of PLM to ctDNA and dye displacement assays have confirmed the formation of PLM-ctDNA complex. The insignificant changes in circular dichroism spectra suggested that PLM is not affecting the structural makeup of the ctDNA, hence the binding could be peripheral and not intercalating. Further, the relative viscosity and minimal change in melting temperature upon the complex formation supported this finding and confirmed the groove binding of PLM. Molecular docking analysis and simulation studies also show PLM as a minor groove binder to DNA and provide details on the interaction dynamics of PLM-DNA complex. Docking followed by a 100 ns simulation reveals the negative Gibbs free energy change (∆G = -6.6 kcal mol-1), and the formation of a stable complex. The PLM- DNA complex with stable dynamics was further supported by different parameters including RMSD, RMSF, SASA, Rg, and the energy profile of interaction. This study provides an insight into the cytotoxic and genotoxic mechanism of PLM which can be a crucial step forward to exploit its therapeutic potential against several diseases including cancer.

Genome-Wide Analysis of Kidney Renal Cell Carcinoma: Exploring Differentially Expressed Genes for Diagnostic and Therapeutic Targets.

Kidney renal cell carcinoma (KIRC) is the most common type of renal cancer. Kidney malignancies have been ranked in the top 10 most frequently occurring cancers. KIRC is a prevalent malignancy with a poor prognosis. The disease has risen for the last 40 years, and robust biomarkers for KIRC are needed for precision/personalized medicine. In this bioinformatics study, we utilized genomic data of KIRC patients from The Cancer Genome Atlas for biomarker discovery. A total of 314 samples were used in this study. We identified many differentially expressed genes (DEGs) categorized as upregulated or downregulated. A protein-protein interaction network for the DEGs was then generated and analyzed using the Search Tool for the Retrieval of Interacting Genes plugin of Cytoscape. A set of 10 hub genes was selected based on the Maximum Clique Centrality score defined by the CytoHubba plugin. The elucidated set of genes, that is, CALCA, CRH, TH, CHAT, SLC18A3, FSHB, MYH6, CAV3, KCNA4, and GBX2, were then categorized as potential candidates to be explored as KIRC biomarkers. The survival analysis plots for each gene suggested that alterations in CHAT, CAV3, CRH, MYH6, SLC18A3, and FSHB resulted in decreased survival of KIRC patients. In all, the results suggest that genomic alterations in selected genes can be explored to inform biomarker discovery and for therapeutic predictions in KIRC.

Identifying promising GSK3ß inhibitors for cancer management: a computational pipeline combining virtual screening and molecular dynamics simulations.

Glycogen synthase kinase-3 (GSK3ß), a serine/threonine protein kinase, has been discovered as a novel target for anticancer drugs. Although GSK3ß is involved in multiple pathways linked to the etiology of various cancers, no specific GSK3ß inhibitor has been authorized for cancer therapy. Most of its inhibitors have toxicity effects therefore, there is a need to develop safe and more potent inhibitors. In this study, a library of 4,222 anti-cancer compounds underwent rigorous computational screening to identify potential candidates for targeting the binding pocket of GSK3ß. The screening process involved various stages, including docking-based virtual screening, physicochemical and ADMET analysis, and molecular dynamics simulations. Ultimately, two hit compounds, BMS-754807 and GSK429286A, were identified as having high binding affinities to GSK3ß. BMS-754807 and GSK429286A exhibited binding affinities of -11.9, and -9.8 kcal/mol, respectively, which were greater than that of the positive control (-7.6 kcal/mol). Further, molecular dynamics simulations for 100 ns were employed to optimize the interaction between the compounds and GSK3ß, and the simulations demonstrated that the interaction was stable and consistent throughout the study. These hits were also anticipated to have good drug-like properties. Finally, this study suggests that BMS-754807 and GSK429286A may undergo experimental validation to evaluate their potential as cancer treatments in clinical settings.

Identification of Small Molecule Inhibitors of Human Cytomegalovirus pUL89 Endonuclease Using Integrated Computational Approaches.

Replication of Human Cytomegalovirus (HCMV) requires the presence of a metal-dependent endonuclease at the C-terminus of pUL89, in order to properly pack and cleave the viral genome. Therefore, pUL89 is an attractive target to design anti-CMV intervention. Herein, we used integrated structure-based and ligand-based virtual screening approaches in combination with MD simulation for the identification of potential metal binding small molecule antagonist of pUL89. In this regard, the essential chemical features needed for the inhibition of pUL89 endonuclease domain were defined and used as a 3D query to search chemical compounds from ZINC and ChEMBL database. Thereafter, the molecular docking and ligand-based shape screening were used to narrow down the compounds based on previously identified pUL89 antagonists. The selected virtual hits were further subjected to MD simulation to determine the intrinsic and ligand-induced flexibility of pUL89. The predicted binding modes showed that the compounds reside well in the binding site of endonuclease domain by chelating with the metal ions and crucial residues. Taken in concert, the in silico investigation led to the identification of potential pUL89 antagonists. This study provided promising starting point for further in vitro and in vivo studies.

Biochemical features and therapeutic potential of α-Mangostin: Mechanism of action, medicinal values, and health benefits.

α-Mangostin (α-MG) is a natural xanthone obtained from the pericarps of mangosteen. It exhibits excellent potential, including anti-cancer, neuroprotective, antimicrobial, antioxidant, and anti-inflammatory properties, and induces apoptosis. α-MG controls cell proliferation by modulating signaling molecules, thus implicated in cancer therapy. It possesses incredible pharmacological features and modulates crucial cellular and molecular factors. Due to its lesser water solubility and pitiable target selectivity, α-MG has limited clinical application. As a known antioxidant, α-MG has gained significant attention from the scientific community, increasing interest in extensive technical and biomedical applications. Nanoparticle-based drug delivery systems were designed to improve the pharmacological features and efficiency of α-MG. This review is focused on recent developments on the therapeutic potential of α-MG in managing cancer and neurological diseases, with a special focus on its mechanism of action. In addition, we highlighted biochemical and pharmacological features, metabolism, functions, anti-inflammatory, antioxidant effects and pre-clinical applications of α-MG.

In Silico Screening and Molecular Dynamics Simulation Studies in the Identification of Natural Compound Inhibitors Targeting the Human Norovirus RdRp Protein to Fight Gastroenteritis.

Norovirus (HNoV) is a leading cause of gastroenteritis globally, and there are currently no treatment options or vaccines available to combat it. RNA-dependent RNA polymerase (RdRp), one of the viral proteins that direct viral replication, is a feasible target for therapeutic development. Despite the discovery of a small number of HNoV RdRp inhibitors, the majority of them have been found to possess a little effect on viral replication, owing to low cell penetrability and drug-likeness. Therefore, antiviral agents that target RdRp are in high demand. For this purpose, we used in silico screening of a library of 473 natural compounds targeting the RdRp active site. The top two compounds, ZINC66112069 and ZINC69481850, were chosen based on their binding energy (BE), physicochemical and drug-likeness properties, and molecular interactions. ZINC66112069 and ZINC69481850 interacted with key residues of RdRp with BEs of -9.7, and -9.4 kcal/mol, respectively, while the positive control had a BE of -9.0 kcal/mol with RdRp. In addition, hits interacted with key residues of RdRp and shared several residues with the PPNDS, the positive control. Furthermore, the docked complexes showed good stability during the molecular dynamic simulation of 100 ns. ZINC66112069 and ZINC69481850 could be proven as potential inhibitors of the HNoV RdRp in future antiviral medication development investigations.

Assessing the adverse effects of COVID-19 vaccine in different scenarios in Saudi Arabia: A cross-sectional study.

OBJECTIVES: To assess the different side effects of COVID-19 vaccines at different scenarios in Saudi Arabia. METHODS: This cross-sectional study sought to investigate the side effects of COVID-19 vaccines through an online survey of 2,718 participants in Saudi Arabia. RESULTS: People can manage their expectations about vaccine side effects and deal with symptoms better by knowing beforehand that they are likely to experience mild side effects for a short period, symptoms that are manifested regardless of age, and infection before or after vaccination. There are certain uncommon side effects that affect more people who got infected, and not before vaccination; there are side effects that disproportionately impact women, and also the side effects that wane after the second dose. CONCLUSION: These findings can assist in evaluating the concerns regarding vaccine acceptance. The public should be made aware that they are likely to experience at least one side effect, with temporary post-injection inflammation, musculoskeletal pain, fever, and headache as the most commonly reported side effects across the board. However, the common symptoms are mild to moderate, and the side effects last for a short period for most people.

Targeting inhibition of microtubule affinity regulating kinase 4 by Harmaline: Strategy to combat Alzheimer's disease.

Microtubule-affinity regulating kinase 4 (MARK4) is linked with the development of cancer, diabetes and neurodegenerative diseases. Due to its direct role in the hyperphosphorylation of tau protein, MARK4 is considered as an attractive target to fight Alzheimer's disease (AD) and neuroinflammation. In the present study, we have selected Harmaline (HAR), an alkaloid of Paganum harmala, to investigate its MARK4 inhibitory potential and its binding mechanism. Molecular docking and fluorescence binding studies were carried out to estimate the binding affinity of the HAR with the MARK4. We observed an excellent binding affinity of HAR to the MARK4 (K = 107 M-1), further complemented by isothermal titration calorimetric measurements. In addition, HAR significantly inhibits the kinase activity of MARK4 (IC50 value of 4.46 µM). Structural investigations suggested that HAR binds to the active site pocket and forms several non-covalent interactions with biologically important residues of MARK4. All-atom molecular dynamics simulation studies further advocated that the MARK4-HAR complex is stabilized throughout the trajectory of 200 ns and causes a little conformational change. All these findings suggest that HAR is a potential MARK4 inhibitor that can be implicated in managing MARK4-associated diseases, including AD.

Identification of human immunodeficiency virus -1 E protein-targeting lead compounds by pharmacophore based screening.

OBJECTIVES: To identify potential compounds by seeking the knowledge of molecular interactions between human immunodeficiency virus (HIV) glycoprotein (gp) 120 protein and anti-HIV drug (BMS-488043). METHODS: This study is a computational structure-based drug design study, carried out at University of Taif, Saudi Arabia and African Genome Centre (AGC), Mohammed VI Polytechnic University, Benguerir, Morocco from January 2021 to March 2022. Initially, using the docked structure of gp120 with BMS-488043, a structure-based pharmacophore model was created. The generated model was utilized for virtual screening of the ZINC and ChemBridge database in order to identify hit compounds. To further assess the time-dependent stability of the selected complexes, computer simulation was performed. RESULTS: From pharmacophore-based screening, 356 hits were obtained from both the database. The docking studies of the retrieved hit compounds reveal that all the compounds fit into the binding site of gp120. However, based on the significant interactions with the crucial residues and docking scores four compounds were suggested as potential hits. MD simulation of ChemBridge14695864 and ZINC06893293 in complex with gp120 suggested that both compounds significantly stabilized the receptor. CONCLUSION: These findings could aid in the design of effective drugs against HIV by inhibiting the interaction between gp120 and CD4.

Seroprevalence of IgM and IgG Against SARS-CoV-2 after Two Doses of Pfizer-BioNTech COVID-19 Vaccine in Women with Breast Cancer.

BACKGROUND: This study evaluates the seroprevalence of immunoglobulin M (IgM) and G (IgG) antibodies against SARS-CoV-2 after two doses of Pfizer-BioNTech COVID-19 vaccination from women with breast cancer in Jazan city Kingdom of Saudi Arabia, antibody detections were performed one month and three months after the administration of the second dose. METHODS: Overall, 103 breast cancer patients were included. Individuals who had had two doses of Pfizer-BioNTech vaccine, patients who were earlier diagnosed with COVID-19 infection, had not finalized immunization plan, or who received the second dose recently were excluded from the study. The antibodies detection test was run according to the manufacturer's directions of Viva Diag™ SARS-CoV-2 IgM/IgG Rapid Test (COVID-19 IgM/IgG Rapid Test). RESULTS: This study included 62 (60.2%) and 41 (39.8%) patients with invasive ductal carcinoma and invasive lobular carcinoma, respectively. The age, median and interquartile range (IQR) was 54.0 (26) years. Regarding reactivity of antibodies, after one month IgM antibody showed 64 (62.1%) positive and 39 (37.9%) negative while IgG antibody showed positive results in all patients. After three months IgM antibody showed 44 (42.7%) positive and 59 (57.3%) negative, while IgG showed 87 (84.5%) positive and 16 (15.5%) negative. There were significant differences in the IgM and IgG seropositivity. There were 19.3% patients with ductal carcinoma who were positive and then turned negative versus 17.7% who were positive and then turned negative, respectively (p < 0.001). There were significant differences in IgM antibody positivity among different age groups. CONCLUSIONS: Our results recommend the importance of screening for an antibody response for breast cancer patient after immunization in order to reveal persons who need early and late extra enhancing vaccine dose. Upcoming studies recommended to estimate different methods that raise cancer patients' immune response.

CRISPR-Cas Genome Editing Technique for Fish Disease Management: Current Study and Future Perspective.

Scientists have discovered many ways to treat bacteria, viruses, and parasites in aquaculture; however, there is still an impossibility in finding a permanent solution for all types of diseases. In that case, the CRISPR-Cas genome-editing technique can be the potential solution to preventing diseases for aquaculture sustainability. CRISPR-Cas is cheaper, easier, and more precise than the other existing genome-editing technologies and can be used as a new disease treatment tool to solve the far-reaching challenges in aquaculture. This technique may now be employed in novel ways, such as modifying a single nucleotide base or tagging a location in the DNA with a fluorescent protein. This review paper provides an informative discussion on adopting CRISPR technology in aquaculture disease management. Starting with the basic knowledge of CRISPR technology and phages, this study highlights the development of RNA-guided immunity to combat the Chilodonella protozoan group and nervous necrosis virus (NNV) in marine finfish. Additionally, we highlight the immunological application of CRISPR-Cas against bacterial diseases in channel catfish and the white spot syndrome virus (WSSV) in shrimp. In addition, the review summarizes a synthesis of bioinformatics tools used for CRISPR-Cas sgRNA design, and acceptable solutions are discussed, considering the limitations.

Association of Vitamin D Deficiency, Dyslipidemia, and Obesity with the Incidence of Coronary Artery Diseases in Type 2 Diabetic Saudi Patients.

BACKGROUND: Diabetes mellitus type 2 (T2DM) is a chronic metabolic disease associated with vascular complications. We aimed to evaluate the relationship of vitamin D deficiency, dyslipidemia, and obesity with the incidence of coronary artery disease in type 2 diabetes mellitus. METHODS: The study included 200 Saudi adult subjects, aged 40 - 60 years, of both genders, attending King Abdulaziz Specialist Hospital in Taif city. Subjects were divided into four groups; 50 subjects each: Control group, type 2 diabetic, type 2 diabetic with coronary artery disease, and type 2 diabetic obese patients having body mass index (BMI) ≥ 30 kg/m2. Serum vitamin D (25-OH-D), fasting blood glucose (FBG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), and glycosylated hemoglobin (HbA1c) levels were estimated. RESULTS: Serum vitamin D and HDL-C in the three diabetic patient groups were significantly decreased (p < 0.001) compared to the control group. Among patient groups, the levels in the diabetic coronary and diabetic obese patients were significantly decreased as compared to the diabetic patient group (p < 0.001). FBG levels, HbA1c%, TC, TG, LDL-C levels, and BMI in all diabetic patient groups were significantly higher (p < 0.001) in comparison to control. Significant negative correlations were observed between serum vitamin D and FBG, HbA1c%, TC, TG, LDL-C levels, and BMI whereas positive correlations with HDL-C in all diabetic patient groups. CONCLUSIONS: The deficiency status of 25-OH-D is associated with dyslipidemia in type 2 Saudi diabetic patients, specifically those complicated with obesity and coronary artery diseases.

Relation of Hypoxia Inducible Factor, Dyslipidemia and CAD Saudi Patients With Type 2 Diabetes.

BACKGROUND/AIM: Type 2 diabetes (T2DM) is a metabolic condition associated with an increased risk of death, morbidity, and vascular problems. This study investigated the association of HIF-1α and dyslipidemia with the incidence of coronary artery disease in Saudi patients with T2DM. PATIENTS AND METHODS: This study included 100 Saudi patients aged 40-60 years who were attending King Abdulaziz Specialist Hospital in Taif, as well as 50 healthy controls. All were divided into three groups of 50 subjects each: control, patients with T2DM, and patients with T2DM with coronary complications. Serum levels of HIF-1α, fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c %), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were estimated. RESULTS: Serum HIF-1α, FBG, HbA1c %, TC, TG, and LDL-C levels were significantly increased in both groups of patients with diabetes (p<0.001) relative to the control group. Among patient groups, their levels were significantly increased in patients with coronary complications as compared to patients with diabetes (p<0.001). Serum HDL-C levels in both groups of patients with diabetes were significantly lower (p<0.001) than those in the control group. When HDL-C levels were compared between the two patient groups, its levels in patients with diabetes with coronary complications were significantly lower (p<0.001). Significant positive correlations were observed between serum HIF-1α and each of FBG, HbA1c %, TC, TG, and LDL-C levels, whereas negative correlations were observed with HDL-C in both groups of patients with diabetes. CONCLUSION: Increased serum HIF-1α levels are linked to dyslipidaemia in Saudi patients with T2DM, particularly those with coronary artery disease.

Evaluation of CD4+:CD8+ Ratio in Patients With Cervical Cancer and the Levels of Inflammatory Markers.

BACKGROUND/AIM: Cervical cancer remains a major public health concern. The ratio of CD4+:CD8+ T-cells is used to evaluate the immune system function. This study aimed to explore the CD4+:CD8+ T-cell ratio in relation to the glycemic status, inflammatory markers, vitamin D, and vitamin B12 in patients with early diagnosed cervical cancer. PATIENTS AND METHODS: This is a cross-sectional study. Blood samples were collected for flow cytometry analysis. Information regarding Papanicolaou (Pap) smears and colposcopy investigations were collected from 152 women with type 2 diabetes admitted to East Jeddah Hospital, Jeddah, Saudi Arabia, between January 2018 and January 2021. RESULTS: Patients with early cervical carcinoma and a higher CD4+:CD8+ ratio (>1.2) had a higher C-reactive protein (CRP) level than those with a lower CD4+:CD8+ ratio (Mean±SD=13.75±13.3 vs. 10.85±8.1; p-value=0.034). Patients with early cervical carcinoma, diabetes, and higher CD4+:CD8+ ratio (>1.2) had a higher blood HbA1c percent than those with a lower CD4+:CD8+ ratio. CONCLUSION: A high CD4+:CD8+ T-cells ratio was associated with an increased HbA1c% and CRP levels in women with diabetes diagnosed with early cervical carcinoma, which can induce inflammation in early diagnosed patients with cervical cancer.