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.

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.

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.

Glutathione S transferase T1 gene polymorphism and its promoter methylation are associated with breast cancer susceptibility in Egyptian women.

BACKGROUND: Breast cancer (BC) is one of the leading causes of cancer mortality in women. Glutathione S-transferase (GSTT1) is involved in activation of detoxification reactions and catalysis of chemicals conjugation with glutathione. GSTT1 genotype is a limiting factor for some environmental diseases. Epigenetic changes have an essential role in BC through inappropriate interaction between genomic and environmental risk factors. AIM: This study was directed to explore the association of BC risk with GSTT1 genetic variations and its methylation status in Egyptian women. DESIGN AND METHODS: This study included 100 healthy women as the control group and 100 patients were clinically and histologically diagnosed with breast cancer. All blood samples were used for genomic DNA extraction. GSTT1 genotyping was accomplished by multiplex PCR and methylation-specific PCR was used to analyze the GSTT1 promoter methylation status. RESULTS: Breast cancer patients showed significant incidence of null GSTT1 in relation to controls (p = 0.004). GSTT1 gene promoter methylation status showed significant difference between hypermethylated and unmethylated patients when compared with healthy subjects (p = 0.005). GSTT1 promoter methylation status was not significantly associated with null genotype. There was no significant association between GSTT1-null genotypes and BC stage in cases with or without family history, but for promotor methylation, there was significant association with stage III and IV breast cancer disease. CONCLUSION: GSTT1 null genetic variant and promoter hypermethylation in the GSTT region of the gene may be considered as critical risk factors for BC in Egyptian women.

Exploration of Community Care Awareness about COVID-19 Sterilization.

BACKGROUND: COVID-19 affects millions of people worldwide so WHO declared the COVID-19 pandemic on 11 March 2020. Since the vaccine is in the early trial phase and until it proves its efficacy, the need of finding alternative methods, which can help to curb this pandemic is urgent, so its prevention depends on standard infection control measures. This study's aim is to assess the knowledge, awareness, and practice level of Taif population towards Corona Virus disease - 2019 (COVID-19) sterilization. METHODS: A cross sectional study was conducted on 504 participants by administering a well-structured questionnaire comprising three sections including demographics, knowledge, attitude, and practice among the general population in Taif governorate KSA, over a duration of three months from July until September 2020. The descriptive analysis was carried out for demographics and dependent variables using the statistical program for social sciences. The t-test was used to detect any relationship between knowledge and practice score percentage of the general population response with respect to their gender and level of education. A p-value of < 0.05 was considered statistically significant. RESULTS: A total of 504 respondents willingly participated in the survey, there is a highly significant difference in the knowledge score percentage in respondents aged between 41 - 60 years old in comparison to the age group < 20 - 40 years old also between urban residence in comparison to rural residence, and a highly significant difference in the knowledge and practice score percentage in post graduate respondents in comparison to undergraduate. In addition, there was a significant difference in the practice score percentage in respondents aged between 41 - 60 years old in comparison to age group < 20 - 40, and a highly significant difference was seen in the practice score percentage in respondents living in urban areas in comparison to rural areas. CONCLUSIONS: The suggestion of this study was that knowledge and practice gaps among population, especially in the young age group, had to be covered by holding training programs through workshops or to include courses in the curriculum of ministry of health.

Vitamin D and Hypoxia-Inducible Factor (HIF-1α) Serum Levels as Markers for Progression of Nephropathy in Type 2 Diabetic Patients.

BACKGROUND: Vitamin D is a locally acting hormone, which plays a major role in skeletal health. Previous studies reported an important role of vitamin D in modulation of inflammatory response. We aimed to investigate the role of vitamin D deficiency and hypoxia-inducible factor (HIF-1α) as markers for the progression of diabetic nephropathy in Saudi patients with type 2 diabetes mellitus (T2DM). METHODS: We included 174 Saudi patients with T2DM in addition to 60 healthy control subjects. Patients were classified according to urinary Albumin to Creatinine Ratio (ACR) into three groups: Group AI: ACR < 30 µg/mg, Group AII: ACR levels of 30 - 300 µg/mg and Group AIII: ACR > 300 µg/mg. We estimated fasting blood glucose, HbA1c, lipid profile, serum creatinine, hemoglobin concentration (Hb), estimated glomerular filtration rate (eGFR), urine albumin/creatinine ratio, serum 25 hydroxyvitamin D, calcium, parathyroid hormone (PTH), tumor necrosis factor (TNF-α), C- reactive protein (CRP), and hypoxia-inducible factor (HIF-1α). RESULTS: There was a significant difference among studied groups regarding serum levels of vitamin D, calcium, PTH, TNF-α, CRP, and HIF-1α levels. The level of vitamin D was lower in diabetic patients in comparison to the controls and was significantly related to the severity of renal nephropathy as indicated by the level of albumin in urine. Moreover, vitamin D levels showed significant negative correlation with the inflammatory markers: TNF-α, CRP, and HIF-1α levels. CONCLUSIONS: Vitamin D deficiency and elevated HIF-1α serum levels showed a significant correlation to progression of nephropathy in Saudi patients with T2DM.

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.

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.

Circulating Long Non-Coding RNA GAS5: A Non-Invasive Molecular Marker for Prognosis, Response to Treatment and Survival in Non-Small Cell Lung Cancer.

Circulating long non-coding RNAs (lncRNA) are dysregulated in several diseases, especially cancers, e.g. non-small-cell lung cancer (NSCLC). Of specific notice in this regard is growth arrest-specific 5 gene (lncRNA GAS5), which is principally recognised as a tumor suppressor gene in numerous cancers. Functionally, GAS5 is involved in arresting cellular growth and induction of apoptosis. We analysed plasma GAS5 expression by qRT-PCR in 100 patients with NSCLC before and after tumour resection surgery. We reported a downregulation of GAS5 expression in NSCLC tissue and plasma, which showed elevation after surgery. Downregulation of GAS5 was associated with poor prognosis of NSCLC patients.

Profiling Inflammatory Cytokines in a Cohort Study of Egyptian Patients with COVID-19 Infection.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic is an international public health emergency with major disruptions and devastating health consequences resulting from the associated cytokine storm syndrome. The aim of our research was to assess the inflammatory biomarkers and risk factors associated with severity of (COVID-19) patients. METHODS: A cross-sectional study was conducted and included 150 Egyptian patients with COVID-19. Patients were classified into mild, moderate, and severe according to the clinical and CT chest findings. Blood samples were collected from patients for laboratory assessment of inflammatory biomarkers. RESULTS: Our results showed significant negative correlation between oxygen saturation percent and serum levels of inflammatory markers. The correlations were statistically significant with IL-6, CRP, ferritin, LDH, and D-dimer which can be used as sensitive biomarkers for assessment of the risk of severity of infection in COVID 19 patients. CONCLUSIONS: The study revealed that the risk factors associated with severity of COVID 19 infection included older age, male gender, presence of underlying chronic disease, and increased levels of inflammatory biomarkers: CRP, LDH, ferritin, IL-6, and D-dimer.

Assessment of neutralizing interleukin-4 effect on CD133 gene expression in colon cancer cell line.

Colorectal cancer may be maintained by cancer stem-like cells (CSCs) that express the cell surface marker CD133. CSCs (CD133+cells) exhibits greater resistance to the chemotherapy and this resistance may be mediated in part by an autocrine response to IL4. The aim of the study was to assess the effect of anti-IL4 antibody alone or in combination with chemotherapy on the CD133 expression andthe tumor growth. We used Caco cell line in our experiments and the samples were as the following; untreated colorectal cell line, cells treated by chemotherapy, cells treated by anti-IL4 antibody in 3doses (2.5, 5, 10µg/ml), cells treatedby combination of chemotherapy and anti-IL4 antibody in 3 doses. Results of our in vitro studies demonstrated that anti-IL4 inhibited growth of Caco cell line in a dose-dependent manner revealing a 32.11% inhibition at the highest concentration (10µg/ml). There was further significant inhibition by combination of anti IL4 and chemotherapy in a dose response manner when compared to group treated by chemotherapy only. These effects were associated with decreased expression of CD133 in tumor cells also. Lastly, anti-IL4 antibody stimulated apoptosis. Our study suggested that neutralizing of IL4 by anti IL4 antibody affect the CD133+ cells may be by increasing their apoptosis. The effects of anti IL4 antibody either, alone or in combination with chemotherapy, inhibited the tumor growth and decreased the viable tumor cells. Furthermore, neutralizing of IL4 increased the efficacy of chemotherapy treatment.

Polymorphisms of DNA repair genes OGG1 and XPD and the risk of age-related cataract in Egyptians.

PURPOSE: To analyze the association of the polymorphisms of xeroderma pigmentosum complementation group D (XPD) and 8-oxoguanine glycosylase-1 (OGG1) genes with the risk of age-related cataract (ARC) in an Egyptian population. METHODS: This case-control study included 150 patients with ARC and 50 controls. Genotyping of XPD Asp³¹²Asn was performed by amplification refractory mutation system PCR assay and genotyping of OGG1 Ser³²6Cys was carried out by PCR including confronting two-pair primers. RESULTS: The Asn/Asn genotype of XPD gene was significantly associated with increased risk of ARC (odds ratio [OR] = 2.74, 95% confidence interval [CI] = 1.01-7.43, p = 0.04) and cortical cataract (OR = 5.06, 95% CI = 1.70-15.05, p = 0.002). The Asn³¹² allele was significantly associated with an increased risk of ARC (OR = 1.75, 95% CI 1.06-2.89, p = 0.03) and cortical cataract (OR = 2.81, 95% CI = 1.56-5.08, p<0.001). The OGG1 Cys/Cys genotype frequency was significantly higher in ARC (OR = 4.13, 95% CI = 0.93-18.21, p = 0.04) and the Cys(³²6 allele (OR = 1.85, 95% CI = 1.07-3.20, p = 0.03). Moreover, the Cys/Cys genotype of the OGG1 gene was significantly higher in cortical cataract (OR = 6.00, 95% CI = 1.24-28.99, p = 0.01) and the Cys³²6 allele was also significantly associated with cortical cataract (OR = 2.45, 95% CI = 1.30-4.63, p = 0.005). CONCLUSIONS: The results suggest that the Asn/Asn genotype and Asn³¹² allele of XPD polymorphism, as well as the Cys/Cys genotype and Cys³²6 allele of the OGG1 polymorphism, may be associated with increased risk of the development of ARC, particularly the cortical type, in the Egyptian population.

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.

Multitargeted Docking, DFT-Based Optimisation, Pharmacokinetics, and MD Simulation Reveal 6-Oxidopamine HBr as a Multitargeted Inhibitor of Cervical Cancer Proteins.

BACKGROUND: Cervical cancer originates in the cervix, the lower part of the uterus, and results from the uncontrolled growth of abnormal cervical cells, forming malignant tumours. It poses a major global health challenge, calling for innovative drug design strategies to enhance treatment outcomes. METHOD: In this study, we have screened the FDA-approved drug library against four proteins, MCM10, MCM6, DNA polymerase epsilon subunit-2, and TBK1, which are essential for DNA replication, DNA repair, and cellular signalling pathways, which are dysregulated in cervical cancer cells, leading to uncontrolled growth. We have used the multisampling algorithms for screening using HTVS, SP, and XP docking; identified 6- oxidopamine HBr (C8H12BrNO3), which is used to create a model of Parkinson's disease in animals, and obtained the docking score ranging from -5.057 to -8.871 Kcal/mol. The poses were filtered with MM\GBSA score ranging from -21.67 to -27.63 Kcal/mol. We performed QM-based DFT and pharmacokinetics studies and compared them with the standard values, suggesting that the compound can be used in cervical cancer proteins. RESULT: The P-L complex's interaction fingerprints have resulted in the most interacting residues, 4THR, 4SER, and 4LYS, showing the compound's interaction pattern. CONCLUSION: Further, the stability of 6-oxidopamine HBr in complex with each protein was evaluated with 100ns MD simulation in the SPC water model in a neutralised state to analyse the deviation, fluctuations, and intermolecular interactions that have proven the compound to have a better inhibitory effect against each protein and that it can be used for cervical cancer; however, experimental validation is suggested before human use.

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.

Restoration of renal hemodynamics and functions by Nigella sativa administration in dinitrophenol-induced hypoxia in rat's animal model.

Objective: Hypoxia is one of the principal causes of renal diseases. This study aimed to evaluate the effects of Nigella sativa on dinitrophenol (DNP)-induced hypoxia renal damage in rats. Methods: Forty adult male rats were incorporated in this study. The rats were divided into four groups: control group, N. sativa group, DNP hypoxic group, and DNP + N. sativa group receiving N. sativa (400 mg/kg body weight). Serum and renal tissue erythropoietin (EPO) hormone and hypoxia-inducible factor-2α (HIF-2α) levels were measured. Renal oxidative stress biomarkers, inflammatory biomarkers, renal hemodynamics, and histopathological examination were evaluated. Results: Administration of N. sativa highly significantly normalized serum EPO level, HIF-2α (P < 0.001 for each) in DNP + N. sativa treated rats as compared to DNP hypoxic rats. Furthermore, it highly significantly improved renal oxidative stress evident by decreased renal tissues malondialdehyde and increased superoxide dismutase, total thiol, and catalase activity (P < 0.001 for each). Furthermore, a highly significant decline of renal intercellular adhesion molecule-1, myeloperoxidase, and interleukin-6 was observed in DNP + N. sativa rats (P < 0.001 for each). Improvements in renal hemodynamics and kidney functions were also found after N. sativa administration (with P < 0.001 for all parameters). In addition, N. sativa treatment reduced renal histopathological changes of the DNP + N. sativa group. Our results were statistically analyzed using the Prism software package (GraphPad version 8.0). Conclusion: N. sativa has an alleviating effect on DNP-induced hypoxia renal damage and can restore kidney functions in rats' animal models. These effects were through antioxidant, anti-inflammatory, and hemodynamic mechanisms.

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.

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.