Chlordiazepoxide against signalling, receptor and regulatory proteins of breast cancer: a structure-based in-silico approach.

Among the most prevalent forms of cancer are breast, lung, colon-rectum, and prostate cancers, and breast cancer is a major global health challenge, contributing to 2.26 million cases with approximately 685,000 deaths worldwide in 2020 alone, typically beginning in the milk ducts or lobules that produce and transport milk during lactation and it is becoming challenging to treat as the tissues are developing resistance, which makes urgent calls for new multitargeted drugs. The multitargeted drug design provides a better solution, simultaneously targeting multiple pathways, even when the drug resists one, it remains effective for others. In this study, we included four crucial proteins that perform signalling, receptor, and regulatory action, namely- NUDIX Hydrolases, Dihydrofolate Reductase, HER2/neu Kinase and EGFR and performed multitargeted molecular docking studies against human-approved drugs using HTVS, SP and extra precise algorithms and filtered the poses with MM\GBSA, suggested a benzodiazepine derivative chlordiazepoxide, used as an anxiolytic agent, can be a multitargeted inhibitor with docking and MM\GBSA score ranging from - 4.628 to - 7.877 and - 18.59 to - 135.86 kcal/mol, respectively, and the most interacted residues were 6ARG, 6GLU, 3TRP, and 3VAL. The QikProp-based ADMET and DFT computations showed the suitability and stability of the drug candidate followed by 100 ns MD simulation in water and MMGBSA on trajectories, resulting in stable performance and many intermolecular interactions to make the complexes stable, which favours that chlordiazepoxide can be a multitargeted breast cancer inhibitor. However, experimental validation is needed before its use.

Serum Pro-Inflammatory Cytokines and Leptin as Potential Biomarkers for Treatment Response and Toxicity in Locally Advanced Squamous Cell Carcinoma of the Head and Neck.

Squamous cell carcinoma of the head and neck (HNSCC) is a globally prevalent form of cancer with significant morbidity and mortality rates. The present study examines the relationship of serum pro-inflammatory cytokines and leptin levels with the effectiveness of therapy in individuals with HNSCC and their potential role as biomarkers for treatment response and toxicity. Induction chemotherapy and concomitant chemoradiotherapy were evaluated for efficacy and safety in 52 individuals with HNSCC. Both response and toxicity were evaluated, and serum levels of pro-inflammatory cytokines Interlukin-1 beta (IL-1ß), Interlukin-2 (IL-2), Interlukin-6 (IL-6), and Tumor Necrosis Factor-Alpha (TNF-α) and leptin were measured using enzyme-linked immunoassay before and after treatment. Before treatment, these measurements were made in comparison with a control group with 50 healthy people. The results showed that serum cytokines and leptin levels varied depending on the response to treatment, with patients who had a complete or partial response (PR) showing significant decreases in IL-1 ß, IL-6, and TNF-α levels and significant increases in IL-2 and leptin levels after treatment, with an improvement in cachexia. These results imply that variations in serum pro-inflammatory cytokines and leptin levels are likely related to the therapeutic effectiveness in HNSCC and may act as biomarkers for treatment response.

Delineated 3-1-BenCarMethInYlPro-Phosphonic Acid's Adroit Activity against Lung Cancer through Multitargeted Docking, MM\GBSA, QM-DFT and Multiscale Simulations.

Lung cancer is a pervasive and challenging disease with limited treatment options, with global health challenges often present with complex molecular profiles necessitating the exploration of innovative therapeutic strategies. Single-target drugs have shown limited success due to the heterogeneity of this disease. Multitargeted drug designing is imperative to combat this complexity by simultaneously targeting multiple target proteins and pathways, which can enhance treatment efficacy and overcome resistance by addressing the dynamic nature of the disease and stopping tumour growth and spread. In this study, we performed the molecular docking studies of Drug Bank compounds with a multitargeted approach against crucial proteins of lung cancer such as heat shock protein 5 (BIP/GRP78) ATPase, myosin 9B RhoGAP, EYA2 phosphatase inhibitor, RSK4 N-terminal kinase, and collapsin response mediator protein-1 (CRMP-1) using HTVS, SP with XP algorithms, and poses were filtered using MM\GBSA which identified [3-(1-Benzyl-3-Carbamoylmethyl-2-Methyl-1h-Indol-5-Yloxy)-Propyl-]-Phosphonic Acid (3-1-BenCarMethIn YlPro-Phosphonic Acid) (DB02504) as multitargeted drug candidate with docking and MM\GBSA score ranges from -5.83 to -10.66 and -7.56 to -50.14 Kcal/mol, respectively. Further, the pharmacokinetic and QM-based DFT studies have shown complete acceptance results, and interaction fingerprinting reveals that ILE, GLY, VAL, TYR, LEU, and GLN were among the most interacting residues. The 100 ns MD simulation in the SPC water model with NPT ensemble showed stable performance with deviation and fluctuations <2 Å with huge interactions, making it a promising multitargeted drug candidate; however, experimental studies are needed before use.

Computational insights into overcoming resistance mechanisms in targeted therapies for advanced breast cancer: focus on EGFR and HER2 co-inhibition.

In the present study, the formation of a heterodimer involving both epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) has been explored as a potential therapeutic mechanism to inhibit the progression of breast cancer. Virtual screening using molecular docking resulted in the three hit compounds (ZINC08382411, ZINC08382438, and ZINC08382292) with minimum binding scores and commonly binding to both receptors. Further, MD simulation analysis of these complexes illustrated the high stability of these compounds with EGFR and HER2. RMSD showed that ZINC08382411 displayed the most stable RMSD of 2 - 3 Å when bound to both receptors, suggesting to have strong compatibility with the active site of the receptor. Hydrogen bond analysis showed that ZINC08382411 forms the maximum number of H-bonds (2 to 3) in both EGFR and HER2 bound complexes, with the highest occupancy of 62% and 79%, respectively. Binding free energy calculation showed that ZINC08382411 possesses maximum affinity towards both the receptors with ΔGbind = -129.628 and -164.063 kJ/mol, respectively. This approach recognizes the significance of EGFR and HER2 in breast cancer development and aims to disrupt their collaborative signaling, which is known to promote the antagonistic behavior of cancer cells. By focusing on this EGFR/HER2 heterodimer, the study offers a promising avenue for identifying a potential candidate (ZINC08382411) that may inhibit breast cancer cell growth and potentially improve patient outcomes. The study's findings may contribute to the ongoing efforts to advance breast cancer treatment strategies.Communicated by Ramaswamy H. Sarma.

Molecular screening reveals Variolin B as a multitargeted inhibitor of lung cancer: a molecular docking-based fingerprinting and molecular dynamics simulation study.

Lung Cancer is the topmost death causing cancer and results from smoking, air pollution, cigar, exposure to asbestos or radon-like substances, and genetic factors. The cases of Lung Cancer in south Asian developing nations are being seen most due to heavy pollution and unbalanced lifestyle and putting a considerable burden on healthcare systems. The Food and Drug Administration of the USA has approved almost 100 drugs against SCLC and NSLC and a few drugs that are given to minimise the side effect of anticancer drugs. However, the drugs are shown to be resistant at significantly higher stages and non-affective on cancerous cells and have long-term side effects due to designing the drug by keeping one protein/gene target while designing or repurposing the drugs. In this study, we have taken five main lung cancer protein targets- Nerve growth factor protein (1SG1), Apoptosis inhibitor survivin (1XOX), Heat shock protein (3IUC), Protein tyrosine phosphate (3ZM3), Aldo-keto reductase (4XZL) and screened the complete prepared Drug Bank library of 155888 compounds and identified Variolin B (DB08694) as a multitargeted inhibitor against lung cancer using HTVS, SP and XP sampling algorithms followed by MM\GBSA calculation to sort the best pose. Variolin B is a natural marine antitumor and antiviral compound, so we analysed the ADMET properties and interaction patterns and then simulated all five P-L complexes for 100 ns in water using the NPT ensemble to check its selves against lung cancer. The docking results, ADMET and fingerprints have shown a good performance, and RMSD and RMSF results were with least deviation and fluctuations (<2Å) and produced a huge contact with other residues making the complex stable. The complexes initially fluctuated and deviated due to changes in the solute medium and sudden heat and stabilise after a few ns. However, extensive experimental validation is required before human use.Communicated by Ramaswamy H. Sarma.

Variolin B from sea sponge against lung cancer: a multitargeted molecular docking with fingerprinting and molecular dynamics simulation study.

Lung Cancer is the one that causes more fatalities in the world compared to other cancers, and its uniqueness is that it can be found in both males and females. However, recent data has shown that males are more affected due to lifestyle habits like smoking, tobacco consumption and inhaling polluted air. The World Health Organization has kept lung cancer on its priority list as it causes 1.8 million deaths worldwide each year, and the predictions show that the cases are going to increase year by year, and by 2050, there can be 3.8 million new cases and 3.2 million deaths, and the global health system is not prepared for it. Also, finding drug candidates that can help shrink cancerous cells and lead to their death is essential to reduce global mortality. The system needs drug compounds that can inhibit multiple paths together not to enter drug resistance quickly and to reduce costs. Our study identified a compound named Variolin B (DB08694) that belongs to the organic compounds class of pyrrolopyridines. The identified compound can inhibit multiple proteins, drastically reducing the global burden. Variolin B was identified as a potential candidate against lung cancer using the multisampling algorithm such as HTVS, SP, and XP, followed by MM\GBSA calculations showing the docking score of -9.245 Kcal/mol to -5.92 Kcal/mol. Also, we have validated it with ADMET predictions and molecular fingerprinting to analyse the interaction patterns. Further, the study was extended to molecular dynamics simulations for 100 ns to understand the complex stability and simulative interactions. The complex's overall molecular dynamics simulation helped us understand that the identified candidate is stable with the lowest deviation and fluctuations.Communicated by Ramaswamy H. Sarma.

Exploring the lncRNA-VEGF axis: Implications for cancer detection and therapy.

Cancer is a complicated illness that spreads indefinitely owing to epigenetic, genetic, and genomic alterations. Cancer cell multidrug susceptibility represents a severe barrier in cancer therapy. As a result, creating effective therapies requires a better knowledge of the mechanisms driving cancer development, progress, and resistance to medications. The human genome is predominantly made up of long non coding RNAs (lncRNAs), which are currently identified as critical moderators in a variety of biological functions. Recent research has found that changes in lncRNAs are closely related to cancer biology. The vascular endothelial growth factor (VEGF) signalling system is necessary for angiogenesis and vascular growth and has been related to an array of health illnesses, such as cancer. LncRNAs have been identified to alter a variety of cancer-related processes, notably the division of cells, movement, angiogenesis, and treatment sensitivity. Furthermore, lncRNAs may modulate immune suppression and are being investigated as possible indicators for early identification of cancer. Various lncRNAs have been associated with cancer development and advancement, serving as cancer-causing or suppressing genes. Several lncRNAs have been demonstrated through research to impact the VEGF cascade, resulting in changes in angiogenesis and tumor severity. For example, the lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) has been shown to foster the formation of oral squamous cell carcinoma and the epithelial-mesenchymal transition by stimulating the VEGF-A and Notch systems. Plasmacytoma variant translocation 1 (PVT1) promotes angiogenesis in non-small-cell lung cancer by affecting miR-29c and boosting the VEGF cascade. Furthermore, lncRNAs regulate VEGF production and angiogenesis by interacting with multiple downstream signalling networks, including Wnt, p53, and AKT systems. Identifying how lncRNAs engage with the VEGF cascade in cancer gives beneficial insights into tumor biology and possible treatment strategies. Exploring the complicated interaction between lncRNAs and the VEGF pathway certainly paves avenues for novel ways to detect better accurately, prognosis, and cure cancers. Future studies in this area could open avenues toward the creation of innovative cancer therapy regimens that enhance the lives of patients.

Mesenchymal stem cells and their extracellular vesicles in urological cancers: Prostate, bladder, and kidney.

Mesenchymal stem cells (MSCs) are recognized for their remarkable ability to differentiate into multiple cell types. They are also known to possess properties that can fight cancer, leading to attempts to modify MSCs for use in anticancer treatments. However, MSCs have also been found to participate in pathways that promote tumor growth. Many studies have been conducted to explore the potential of MSCs for clinical applications, but the results have been inconclusive, possibly due to the diverse nature of MSC populations. Furthermore, the conflicting roles of MSCs in inhibiting tumors and promoting tumor growth hinder their adaptation to anticancer therapies. Antitumorigenic and protumorigenic properties of MSCs in urological cancers such as bladder, prostate, and renal are not as well established, and data comparing them are still limited. MSCs hold significant promise as a vehicle for delivering anticancer agents and suicide genes to tumors. Presently, numerous studies have concentrated on the products derived from MSCs, such as extracellular vesicles (EVs), as a form of cell-free therapy. This work aimed to review and discuss the current knowledge of MSCs and their EVs in urological cancer therapy.

The Association of Vitamin D, Growth/Differentiation Factor 5 (GDF-5) Gene Polymorphism, and Serum GDF-5 Protein in Obese Patients With Knee Osteoarthritis.

Background and objective Osteoarthritis (OA) is influenced by genetics and environmental factors, including vitamin D deficiency. This study aimed to investigate the association between vitamin D levels, growth/differentiation factor 5 (GDF-5) gene polymorphism, and serum GDF-5 in obese females with knee OA (KOA) in Saudi Arabia. Methodology The study enrolled 60 female patients with OA and 60 healthy females as controls. Blood samples were collected to evaluate the GDF-5 T>C (rs143383) polymorphism using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The study also measured serum levels of vitamin D, GDF-5, calcium, uric acid, lipid profiles, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR), and assessed the participants' BMI. Results The study demonstrated that KOA patients had reduced vitamin D levels in their bodies, along with GDF-5 and calcium. However, they had increased levels of uric acid, lipid profile, CRP, and ESR. Strong correlations were observed between vitamin D levels, lipid profile, CRP, ESR, BMI, GDF-5 gene polymorphisms, and GDF-5 protein. Genotype analysis showed KOA patients had TT (30%), TC (50%), and CC (20%) genotypes, while the control group showed TT (22%), TC (35%), and CC (43%) genotypes. Allele analysis revealed a noteworthy association between the T allele and KOA; the C allele was more common in the control group. Conclusions The study findings provide valuable insights into the association of vitamin D levels with GDF-5 T>C (rs143383) polymorphism, GDF-5 protein, and inflammatory markers in obese Saudi females with KOA. These findings suggest potential associations between these biomarkers and the pathogenesis or progression of KOA.

Influence of COVID-19 infection/vaccination on menstrual regularity and hormonal function in Saudi females of reproductive age.

The COVID-19 pandemic has had a profound impact on women's health, particularly on their menstrual cycles. The menstrual cycle serves as a crucial indicator of fertility and reproduction. Objectives: This study aimed to examine the impact of COVID-19 infection and vaccination on menstrual regularity in Saudi women of childbearing age. Additionally, it sought to explore the potential effects of COVID-19 vaccination on serum hormonal levels during the follicular phase of the menstrual cycle, along with their relationship with Vit.D. Methods: This case‒control study investigated the impact of COVID-19 infection and vaccination on menstrual regularity and hormonal function in Saudi women of reproductive age. Data were collected from 79 women who attended the Outpatient Department of Obstetrics and Gynaecology at King Faisal Medical Complex in Taif, Saudi Arabia. All participants had received COVID-19 vaccines. The data collection process was comprehensive, encompassing various participant characteristics, such as demographic information, history of COVID-19 infection, and details about menstrual patterns before and after infection and vaccination. Furthermore, hormonal measurements, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), oestradiol, prolactin, thyroid-stimulating hormone (TSH), and vitamin D (Vit.D) levels, were extracted from the participants' medical records. Results: Among the participants, 39.24 % had a history of COVID-19 infection, and following the infection, there was a significant increase in the proportion of women experiencing irregular menstruation. After receiving the COVID-19 vaccine, 72.15 % of the participants continued to have irregular menstrual cycles. The study found that a considerable number of participants had menstrual cycles outside the normal range, with 43.80 % having cycles shorter than 21 days and 35.10 % having cycles longer than 35 days. Comparing participants with regular and irregular cycles after COVID-19 vaccination, no significant changes were observed in most hormonal levels. However, the prolactin hormone showed a significant increase in participants with irregular cycles, while Vit.D levels were significantly decreased in this group. Conclusion: The study findings indicate a higher prevalence of irregular menstruation among participants, particularly after vaccination. Notably, irregular menstrual cycles were found to be associated with elevated levels of prolactin hormone and decreased levels of Vit.D.

Molecular patterns of alpha-thalassemia in the kingdom of Saudi Arabia: identification of prevalent genotypes and regions with high incidence.

BACKGROUND: Alpha-thalassemia (α-thalassemia) is one of the most common monogenic diseases in Saudi Arabia and is associated with significant morbidity. Premarital testing programs in Saudi Arabia reduce the burden of hemoglobinopathy disorders, and ongoing monitoring is required. We aimed to explore the molecular nature of α-globin genes and identify the most common genotypes and regions with a high risk of α-thalassemia in Saudi Arabia. METHODS: This retrospective study was conducted between January 2021 and December 2022. Six hundred twenty-five samples from patients with microcytic hypochromic anemia in Saudi Arabia were analyzed using reverse dot blot hybridization (RDBH)-based multiplex-PCR, which screens for the known 21 mutations of α-globin genes. RESULTS: Seven mutations in the α-globin gene were identified in 88.96% (556) patients. The most frequent abnormality of a-globin genes was -α3.7 (62.3%), followed by α2IVS1(-5nt) (20.7%) and α2 polyA-1 (α2T.Saudi) (14.1%). Interestingly, α2 polyA-2 (α2T.Turkish) was identified in Saudi and presented with -MED, causing Haemoglobin H disease. The incidence of α-thalassemia in Saudi Arabia's cities showed significant differences (P = 0.004). Jeddah City had the highest percentage of cases (25%), followed by Makkah (23%), Taif (13.3%), and Al-Ahassa (12.4%). CONCLUSION: The study provides current knowledge about the molecular nature of α- thalassemia, highlights the common genotypes that could contribute to disease occurrence in the Saudi population, and sheds light on Saudi regions with a high incidence. It also recommends further studies in a larger population and with differently composed molecular assays to verify these findings.

Association Between Serum Uric Acid Levels and Oxido-Inflammatory Biomarkers With Coronary Artery Disease in Type 2 Diabetic Patients.

BACKGROUND: Cardiovascular disease signifies a major cause of morbidity and mortality among patients with type 2 diabetes mellitus (T2DM). Serum uric acid (SUA) levels are elevated during the initial phases of impaired glucose metabolism. This work was designed to explore the association between SUA levels, serum oxido-inflammatory biomarkers, and the risk of coronary artery disease (CAD) in T2DM patients as the primary outcome. The secondary outcome was to assess the prognostic role of SUA in the prediction of the risk of CAD in T2DM patients. METHODS: In this case-control study, we enrolled 110 patients with T2DM who were further divided into patients with CAD and without CAD. In addition, 55 control participants were stringently matched to cases by age. RESULTS: Diabetic patients with CAD had significantly higher serum levels of the inflammatory biomarkers and the oxidative malondialdehyde but significantly lower levels of serum total antioxidant capacity (TAC) compared with the controls and diabetic patients without CAD. Significant positive correlations existed between SUA levels and serum levels of the inflammatory biomarkers and malondialdehyde, while a significant negative correlation existed between SUA levels and serum TAC. SUA demonstrated an accepted discrimination ability. SUA can differentiate between T2DM patients with CAD and patients without CAD, an area under the curve of 0.759. CONCLUSIONS: Elevated serum levels of SUA and oxido-inflammatory biomarkers are associated with an increased risk of CAD in T2DM. SUA levels reflect the body's inflammatory status and oxidant injury in T2DM. SUA could be utilized as a simple biomarker in the prediction of CAD risk in T2DM.

Soluble Programmed Death-Ligand 1 (sPD-L1) as a Promising Marker for Head and Neck Squamous Cell Carcinoma: Correlations With Clinical and Demographic Characteristics.

Background and objective Head and neck squamous cell carcinoma (HNSCC) is a prevalent cancer type that affects the mucosal lining of the upper aerodigestive tract. Soluble programmed death-ligand 1 (sPD-L1) is a significant factor in hindering T cells' function, which prevents cancer cells from being detected by the immune system. This means that sPD-L1 is an essential component in the immune evasion of cancer. This study aimed to explore the potential of sPD-L1 as a prognostic biomarker for patients with HNSCC undergoing concurrent chemotherapy and radiation therapy. Methodology The study included 106 patients with locally advanced HNSCC who received three courses of induction chemotherapy followed by concurrent chemoradiation and 60 healthy subjects as controls. sPD-L1 levels were measured using an enzyme-linked immunosorbent assay (ELISA) kit, and the cutoff value was determined based on receiver operating characteristic (ROC) curve analysis. Results The results showed that sPD-L1 levels were significantly higher in HNSCC patients compared to healthy controls, with a cutoff value of 31.51 pg/mL. Higher sPD-L1 levels were associated with poorer overall survival rates. Conclusions These findings suggest that sPD-L1 may serve as a valuable prognostic biomarker for HNSCC patients undergoing concurrent chemotherapy and radiation therapy. The study highlights the importance of exploring new biomarkers and therapeutic strategies for HNSCC to improve patient outcomes and reduce morbidity and mortality rates associated with this disease.

In vitro studies on the pharmacological potential, anti-tumor, antimicrobial, and acetylcholinesterase inhibitory activity of marine-derived Bacillus velezensis AG6 exopolysaccharide.

In the current study, Bacillus velezensis AG6 was isolated from sediment samples in the Red Sea, identified by traditional microbiological techniques and phylogenetic 16S rRNA sequences. Among eight isolates screened for exopolysaccharide (EPS) production, the R6 isolate was the highest producer with a significant fraction of EPS (EPSF6, 5.79 g L-1). The EPSF6 molecule was found to have a molecular weight (Mw) of 2.7 × 104 g mol-1 and a number average (Mn) of 2.6 × 104 g mol-1 when it was analyzed using GPC. The FTIR spectrum indicated no sulfate but uronic acid (43.8%). According to HPLC, the EPSF6 fraction's monosaccharides were xylose, galactose, and galacturonic acid in a molar ratio of 2.0 : 0.5 : 2.0. DPPH, H2O2, and ABTS tests assessed EPSF6's antioxidant capabilities at 100, 300, 500, 1000, and 1500 µg mL-1 for 15, 60, 45, and 60 minutes. The overall antioxidant activities were dose- and time-dependently increased, and improved by increasing concentrations from 100 to 1500 µg mL-1 after 60 minutes and found to be 91.34 ± 1.1%, 80.20 ± 1.4% and 75.28 ± 1.1% respectively. Next, EPSF6 displayed considerable inhibitory activity toward the proliferation of six cancerous cell lines. Anti-inflammatory tests were performed using lipoxygenase (5-LOX) and cyclooxygenase (COX-2). An MTP turbidity assay method was applied to show the ability of EPSF6 to inhibit Gram-positive bacteria, Gram-negative bacteria, and antibiofilm formation. Together, this study sheds light on the potential pharmacological applications of a secondary metabolite produced by marine Bacillus velezensis AG6. Its expected impact on human health will increase as more research and studies are conducted globally.

Role of Fork-Head Box Genes in Breast Cancer: From Drug Resistance to Therapeutic Targets.

Breast cancer has been acknowledged as one of the most notorious cancers, responsible for millions of deaths around the globe. Understanding the various factors, genetic mutations, comprehensive pathways, etc., that are involved in the development of breast cancer and how these affect the development of the disease is very important for improving and revitalizing the treatment of this global health issue. The forkhead-box gene family, comprising 19 subfamilies, is known to have a significant impact on the growth and progression of this cancer. The article looks into the various forkhead genes and how they play a role in different types of cancer. It also covers their impact on cancer drug resistance, interaction with microRNAs, explores their potential as targets for drug therapies, and their association with stem cells.

Evaluation of TET Family Gene Expression and 5-Hydroxymethylcytosine as Potential Epigenetic Markers in Non-small Cell Lung Cancer.

BACKGROUND/AIM: DNA methylation is the most studied epigenetic modification in cancer. Ten-eleven translocation enzymes (TET) catalyze the oxidation of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) in the DNA. In the current research, we aimed to evaluate the role of 5-hmC and TET enzymes in non-small cell lung cancer (NSCLC) patients and their possible association with outcomes. PATIENTS AND METHODS: ELISA was used to measure the 5-hmC levels in genomic DNA and qRT-PCR was used to evaluate TET1, TET2, and TET3 mRNAs expression levels in NSCLC tissues and their paired normal controls. RESULTS: The levels of 5-hmC were significantly lower in NSCLC tissues than in normal tissues, with a mean ±SD of 0.28±0.37 vs. 1.84±0.58, respectively (t=22.77, p<0.0001), and this reduction was correlated with adverse clinical features. In addition, all TET genes were significantly down-regulated in NSCLC tissues in comparison to their matched normal tissues. The mean±SD level of TET1-mRNA was 38.48±16.38 in NSCLC vs. 80.65±11.25 in normal tissues (t=21.33, p<0.0001), TET2-mRNA level in NSCLC was 5.25±2.78 vs. 9.52±1.01 in normal tissues (t=14.48, p<0.0001), and TET3-mRNA level in NSCLC was 5.21±2.8 vs. 9.51±0.86 in normal tissues (t=14.75, p<0.0001). Downregulation of TET genes was correlated with poor clinical features. CONCLUSION: 5-HmC levels as well as TET1, TET2, and TET3 mRNA levels were reduced in NSCLC tissues. The reduced levels of 5-hmC and TET mRNAs were associated with adverse clinical features, suggesting that the level of 5-hmC may serve as a valuable prognostic biomarker for NSCLC.

Novel Insight Into the Relationship of Vitamin D Hydroxylase and Vitamin D With Obesity in Patients With Type 2 Diabetes Mellitus.

BACKGROUND: In patients with type 2 diabetes mellitus (T2DM) and obesity, there is often a vitamin D deficiency, which is crucial for many physiological processes. The enzyme 25-D hydroxylase activates vitamin D, and its status has been linked to glucose and lipid metabolism in these patients. This study investigates the correlation between the levels of 25-D hydroxylase and 25-hydroxyvitamin D, and their impact on glucose and lipid metabolism in Saudi patients with T2DM and obesity. METHODS: This study involved 150 Saudi participants (ages 35-70) of both genders from King Faisal Medical Complex in Taif. The participants were divided into control, type 2 diabetic, and obese diabetic patient groups, with 50 subjects in each group. Serum levels of 25(OH) vitamin D and 25-D hydroxylase were measured using ELISA. In contrast, an automatic analyzer for chemistry tests was used to measure fasting blood glucose (FBG), aspartate transaminase (AST), alanine transaminase (ALT), and lipid profile levels. Hemoglobin A1c (HbA1c)% was analyzed using the automatic glycosylated hemoglobin analyzer. In addition, the body mass index (BMI) value was calculated using the equation (BMI = weight in kilograms/height in meters squared). RESULTS: In obese with T2DM and T2DM patient groups, there were significant increases (p < 0.0001) in BMI, FBG, HbA1c%, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), AST, and ALT levels and significant decreases (p < 0.0001) in 25(OH) vitamin D, 25-D hydroxylase, and high-density lipoprotein cholesterol (HDL-C) levels compared to the control group. There were significant positive correlations between vitamin D with 25-D hydroxylase and HDL-C and negative correlations with HbA1c%, FBG, TC, TG, LDL-C, ALT, AST, and BMI in the studied patient groups. CONCLUSIONS: This study shows that lower levels of the enzyme 25-D hydroxylase are linked to reduced vitamin D levels in people with T2DM and obese diabetic patients. Additionally, there was a notable correlation between vitamin D levels and BMI, lipid profile, FBG, HbA1c%, AST, and ALT levels.

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.

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.