Mitoxantrone 2HCl's adroit activity against cervical cancer replication and maintenance proteins: a multitargeted approach.

Cervical cancer poses a significant global health challenge, ranking as the fourth most common cancer among women worldwide and resulting in approximately 300,000 deaths yearly, predominantly caused by high-risk human papillomavirus strains (HPV), mainly types 16 and 18. The scenario poses the urgent need of the hour to develop effective treatment strategies that can address the complexity of cervical cancer and multitargeted inhibitor designing that holds promise as it can simultaneously target multiple proteins and pathways involved in its progression and have the potential to enhance treatment efficacy, reduce the likelihood of drug resistance. In this study, we have performed multitargeted molecular docking of FDA-approved drugs against cervical cancer replication and maintenance proteins- Xenopus kinesin-like protein-2 (3KND), cell division cycle protein-20 (4N14), MCM2-histone complex (4UUZ) and MCM6 Minichromosome maintenance (2KLQ) with HTVS, SP and XP algorithms and have obtained the docking and MM\GBSA score ranging from -8.492 to -5.189 Kcal/mol and -58.16 to -39.07 Kcal/mol. Further, the molecular interaction fingerprints identified ALA, THR, SER, ASN, LEU, and ILE were among the most interacted residues, leaning towards hydrophobic and polar amino acids. The pharmacokinetics and DFT of the compound have shown promising results. The complexes were simulated for 100 ns to study the stability by computing the deviation, fluctuations, and intermolecular interactions formed during the simulation. This study produced promising results, satisfying the criteria that Mitoxantrone 2HCl can be a multitargeted inhibitor against cervical cancer proteins-however, experimental validation is a must before human use.Communicated by Ramaswamy H. Sarma.

Exploring the promising potential of noscapine for cancer and neurodegenerative disease therapy through inhibition of integrin-linked kinase-1.

Integrin-linked kinase (ILK), a ß1-integrin cytoplasmic domain interacting protein, supports multi-protein complex formation. ILK-1 is involved in neurodegenerative diseases by promoting neuro-inflammation. On the other hand, its overexpression induces epithelial-mesenchymal transition (EMT), which is a major hallmark of cancer and activates various factors associated with a tumorigenic phenotype. Thus, ILK-1 is considered as an attractive therapeutic target. We investigated the binding affinity and ILK-1 inhibitory potential of noscapine (NP) using spectroscopic and docking approaches followed by enzyme inhibition activity. A strong binding affinity of NP was measured for the ILK-1 with estimated Ksv (M-1) values of 1.9 × 105, 3.6 × 105, and 4.0 × 105 and ∆G0 values (kcal/mol) -6.19554, -7.8557 and -8.51976 at 298 K, 303 K, and 305 K, respectively. NP binds to ILK-1 with a docking score of -6.6 kcal/mol and forms strong interactions with active-site pocket residues (Lys220, Arg323, and Asp339). The binding constant for the interaction of NP to ILK-1 was 1.04 × 105 M-1, suggesting strong affinity and excellent ILK-1 inhibitory potential (IC50 of ∼5.23µM). Conformational dynamics of ILK-1 were also studied in the presence of NP. We propose that NP presumably inhibits ILK-1-mediated phosphorylation of various downstream signalling pathways that are involved in cancer cell survival and neuroinflammation.

Structural and energetic analysis of NS5 protein inhibition by small molecules in Japanese encephalitis virus using machine learning and steered molecular dynamics approach.

One of the viral diseases that affect millions of people around the world, particularly in developing countries, is Japanese encephalitis (JE). In this study, the conserved protein of this virus, that is, non-structural protein 5 (NS5), was used as a target protein for this study, and a compound library of 749 antiviral molecules was screened against NS5. The current study employed machine learning-based virtual screening combined with molecular docking. Here, three hits (24360, 123519051 and 213039) had lower binding energies (< -8 kcal/mol) than the control, S-Adenosyl-L-homocysteine (SAH). All the compounds showed significant H-bond interactions with functional residues, which were also observed by the control. Molecular dynamics simulation, MM/GBSA for binding free energy analysis, principal component analysis and free energy landscape were also performed to study the stability of the complex formation. All three compounds had similar root mean square deviation trends, which were comparable to the control, SAH. Post-MD, the 123519051-receptor complex had the highest number of H-bonds (4 to 5) after the control, out of which three exhibited the highest percentage occupancy (50%, 24% and 79%). Both docking and MD, 123519051 showed an H-bond with the residue Gly111, which was also found for the control-protein complex. 123519051 showed the lowest binding free energy with ΔGbind of -89 kJ/mol. Steered molecular dynamics depicted that 123519051 had the maximum magnitude of dissociation (1436.43 kJ/mol/nm), which was more than the control, validating its stable complex formation. This study concluded that 123519051 is a binder and could inhibit the protein NS5 of JE.Communicated by Ramaswamy H. Sarma.

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.

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.

From diagnosis to therapy: The transformative role of lncRNAs in eye cancer management.

The genomic era has brought about a transformative shift in our comprehension of cancer, unveiling the intricate molecular landscape underlying disease development. Eye cancers (ECs), encompassing diverse malignancies affecting ocular tissues, pose distinctive challenges in diagnosis and management. Long non-coding RNAs (lncRNAs), an emerging category of non-coding RNAs, are pivotal actors in the genomic intricacies of eye cancers. LncRNAs have garnered recognition for their multifaceted roles in gene expression regulation and influence on many cellular processes. Many studies support that the lncRNAs have a role in developing various cancers. Recent investigations have pinpointed specific lncRNAs associated with ECs, including retinoblastoma and uveal melanoma. These lncRNAs exert control over critical pathways governing tumor initiation, progression, and metastasis, endowing them with the ability to function as evaluation, predictive, and therapeutic indicators. The article aims to synthesize the existing information concerning the functions of lncRNAs in ECs, elucidating their regulatory mechanisms and clinical significance. By delving into the lncRNAs' expanding relevance in the modulation of oncogenic and tumor-suppressive networks, we gain a deeper understanding of the molecular complexities intrinsic to these diseases. In our exploration of the genomic intricacies of ECs, lncRNAs introduce a fresh perspective, providing an opportunity to function as clinical and therapeutic indicators, and they also have therapeutic benefits that show promise for advancing the treatment of ECs. This comprehensive review bridges the intricate relationship between lncRNAs and ECs within the context of the genomic era.

PVT1 lncRNA in lung cancer: A key player in tumorigenesis and therapeutic opportunities.

The lncRNA PVT1 has emerged as a pivotal component in the intricate landscape of cancer pathogenesis, particularly in lung cancer. PVT1, situated in the 8q24 chromosomal region, has garnered attention for its aberrant expression patterns in lung cancer, correlating with tumor progression, metastasis, and poor prognosis. Numerous studies have unveiled the diverse mechanisms PVT1 contributes to lung cancer pathogenesis. It modulates critical pathways, such as cell proliferation, apoptosis evasion, angiogenesis, and epithelial-mesenchymal transition. PVT1's interactions with other molecules, including microRNAs and proteins, amplify its oncogenic influence. Recent advancements in genomic and epigenetic analyses have also illuminated the intricate regulatory networks that govern PVT1 expression. Understanding PVT1's complex involvement in lung cancer holds substantial clinical implications. Targeting PVT1 presents a promising avenue for developing novel diagnostic biomarkers and therapeutic interventions. This abstract encapsulates the expanding knowledge regarding the oncogenic role of PVT1 in lung cancer, underscoring the significance of further research to unravel its complete mechanistic landscape and exploit its potential for improved patient outcomes.

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.

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.

HOTAIR: A key regulator of the Wnt/ß-catenin signaling cascade in cancer progression and treatment.

The long non-coding RNA (lncRNA) HOTAIR occupies a central position in the complex domain of cancer biology, particularly concerning its intricate interplay with the Wnt/ß-catenin signaling pathway. This comprehensive review explores the multifaceted interactions between HOTAIR and the Wnt/ß-catenin cascade, elucidating their profound function in cancer growth, progression, and therapeutic strategies. The study commences by underscoring the pivotal role of the Wnt/ß-catenin cascade in governing essential cellular activities, emphasizing its dysregulation as a linchpin in cancer initiation and advancement. It introduces HOTAIR as a crucial regulatory entity, influencing gene expression in both healthy and diseased. The core of this review plunges into the intricacies of HOTAIR's engagement with Wnt/ß-catenin signaling. It unravels how HOTAIR, through epigenetic modifications and transcriptional control, exerts its influence over key pathway constituents, including ß-catenin, Wnt ligands, and target genes. This influence drives unchecked cancer cell growth, invasion, and metastasis. Furthermore, the review underscores the clinical significance of the HOTAIR-Wnt/ß-catenin interplay, elucidating its associations with diverse cancer subtypes, patient prognoses, and prospects as a therapy. It provides insights into ongoing research endeavors to develop HOTAIR-targeted treatments and initiatives to facilitate aberrant Wnt/ß-catenin activation. Concluding on a forward-looking note, the article accentuates the broader implications of HOTAIR's involvement in cancer biology, including its contributions to therapy resistance and metastatic dissemination. It underscores the importance of delving deeper into these intricate molecular relationships to pave the way for groundbreaking cancer treatment.

Rational design of multi-epitope-based vaccine by exploring all dengue virus serotypes proteome: an immunoinformatic approach.

Millions of people's lives are being devastated by dengue virus (DENV), a severe tropical and subtropical illness spread by mosquitoes and other vectors. Dengue fever may be self-limiting like a common cold or can rapidly progress to catastrophic dengue hemorrhagic fever or dengue shock syndrome. With four distinct dengue serotypes (DENV1-4), each with the potential to contain antibody-boosting complicated mechanisms, developing a dengue vaccine has been an ambitious challenge. Here, we used a computational pan-vaccinomics-based vaccine design strategy (reverse vaccinology) for all 4 DENV serotypes acquired from different regions of the world to develop a new and safe vaccine against DENV. Consequently, only five mapped epitopes from all the 4 serotypes were shown to be extremely effective for the construction of multi-epitope vaccine constructs. The suggested vaccine construct V5 from eight vaccine models was thus classified as an antigenic, non-allergenic, and stable vaccine model. Moreover, molecular docking and molecular dynamics simulation was performed for the V5 vaccine candidate against the HLAs and TRL2 and 4 immunological receptors. Later, the vaccine sequence was transcribed into the cDNA to generate an expression vector for the Escherichia coli K12 strain. Our research suggests that this vaccine design (V5) has promising potential as a dengue vaccine. However, further experimental analysis into the vaccine's efficacy might be required for the V5 proper validation to combat all DENV serotypes.

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.

Identification of novel STAT3 inhibitors for liver fibrosis, using pharmacophore-based virtual screening, molecular docking, and biomolecular dynamics simulations.

The signal transducer and activator of transcription 3 (STAT3) plays a fundamental role in the growth and regulation of cellular life. Activation and over-expression of STAT3 have been implicated in many cancers including solid blood tumors and other diseases such as liver fibrosis and rheumatoid arthritis. Therefore, STAT3 inhibitors are be coming a growing and interesting area of pharmacological research. Consequently, the aim of this study is to design novel inhibitors of STAT3-SH3 computationally for the reduction of liver fibrosis. Herein, we performed Pharmacophore-based virtual screening of databases including more than 19,481 commercially available compounds and in-house compounds. The hits obtained from virtual screening were further docked with the STAT3 receptor. The hits were further ranked on the basis of docking score and binding interaction with the active site of STAT3. ADMET properties of the screened compounds were calculated and filtered based on drug-likeness criteria. Finally, the top five drug-like hit compounds were selected and subjected to molecular dynamic simulation. The stability of each drug-like hit in complex with STAT3 was determined by computing their RMSD, RMSF, Rg, and DCCM analyses. Among all the compounds Sa32 revealed a good docking score, interactions, and stability during the entire simulation procedure. As compared to the Reference compound, the drug-like hit compound Sa32 showed good docking scores, interaction, stability, and binding energy. Therefore, we identified Sa32 as the best small molecule potent inhibitor for STAT3 that will be helpful in the future for the treatment of liver fibrosis.

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.

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.

Inhibition of Autophagy and the Cytoprotective Role of Smac Mimetic against ROS-Induced Cancer: A Potential Therapeutic Strategy in Relapse and Chemoresistance Cases in Breast Cancer.

With more than a million deaths each year, breast cancer is the top cause of death in women. Around 70% of breast cancers are hormonally responsive. Although several therapeutic options exist, cancer resistance and recurrence render them inefficient and insufficient. The major key reason behind this is the failure in the regulation of the cell death mechanism. In addition, ROS was also found to play a major role in this problem. The therapeutic benefits of Smac mimetic compound (SMC) BV6 on MCF7 were examined in the current study. Treatment with BV6 reduces viability and induces apoptosis in MCF7 breast cancer cells. BV6 suppresses autophagy and has demonstrated a defensive role in cancer cells against oxidative stress caused by H2O2. Overall, the present investigation shows that SMC has therapeutic and cytoprotective potential against oxidative stress in cancer cells. These Smac mimetic compounds may be used as anti-cancer drugs as well as antioxidants alone or in conjunction with other commonly used antioxidants.

Uncontrolled blood pressure among hypertensive adults with rheumatoid arthritis in Saudi Arabia: A cross-sectional study.

ABSTRACT: Despite the availability and advancement of diagnostic and treatments with demonstrated benefits in minimizing cardiovascular morbidity and mortality, hypertension control rates remain suboptimal. Therefore, this research aimed to determine the prevalence of uncontrolled BP in rheumatoid arthritis (RA) patients and understand all potential risk factors for uncontrolled BP.We conducted a cross-sectional study on RA patients in 2 rheumatology clinics in 2 public hospitals in Riyadh. Patients' information such as demographics, comorbidities, drug use, and other clinical data were captured through a review of medical records and supplemented by patient interviews. Multivariate logistic regression was utilized for the analysis to identify the significant factors of uncontrolled BP (systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg).In total, 834 subjects with RA and concomitant BP were involved in this cross-sectional study. The prevalence of uncontrolled BP was found to be 31.65% among all the study population. Multivariate analysis showed that males, subjects above 60 years of age, and smokers had a distinctly higher occurrence of uncontrolled BP. Among the patients with comorbid conditions, those with obesity, hyperlipidemia, diabetes, anemia, cancer, and reflex or gastroesophageal reflux disease also showed a significantly higher risk of uncontrolled BP (P < .05).The rate of uncontrolled BP was found to be alarmingly high in the study population. Age, gender, smoking, diabetes, obesity, hyperlipidemia, cancer, gastroesophageal reflux disease, and osteoporosis are independently linked with lack of BP control.

Assessment of the levels of antispike SARS-CoV-2 IgG antibodies and their association with clinical characteristics in cohort of patients in Saudi Arabia.

Background: Coronavirus disease 2019 (COVID-19) has caused a global public health crisis. The disease is known to be caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, but the detailed characteristics of the immune response to this novel virus have not been fully elucidated yet. In this study, we aimed to determine the level of immunoglobulin G (IgG) antibodies and their correlation with clinical features at three time points postinfection in a group of patients in Saudi Arabia. Method: In this prospective observational study, we collected the demographic and clinical data from 43 polymerase chain reaction (PCR)-confirmed patients and measured the COVID-19 antispike IgG levels at three different visits. Result: The seroconversion rate after COVID-19 infection was 88.4% in the study participants, with no significant changes in the IgG levels through the three visits. The duration of shortness of breath had a significant positive correlation with the IgG level of the patients. Using the logistic regression model, participants having coughs were found to be 12.48 times more likely to develop positive IgG. The IgG levels were less in smokers than nonsmokers [Odds ratio = 6.42 (95% CI 2.11-19.48); P = 0.001]. Conclusion: Positive IgG levels have been developed in most COVID-19 patients and did not significantly change over 3 months following the diagnosis. The level of IgG antibodies was found to be significantly associated with the presence of cough, duration of shortness of breath, and the smoking habit of the patients. These findings have clinical and public health significance and need to be validated in larger studies in different populations.

Human germ/stem cell-specific gene TEX19 influences cancer cell proliferation and cancer prognosis.

BACKGROUND: Cancer/testis (CT) genes have expression normally restricted to the testis, but become activated during oncogenesis, so they have excellent potential as cancer-specific biomarkers. Evidence is starting to emerge to indicate that they also provide function(s) in the oncogenic programme. Human TEX19 is a recently identified CT gene, but a functional role for TEX19 in cancer has not yet been defined. METHODS: siRNA was used to deplete TEX19 levels in various cancer cell lines. This was extended using shRNA to deplete TEX19 in vivo. Western blotting, fluorescence activated cell sorting and immunofluorescence were used to study the effect of TEX19 depletion in cancer cells and to localize TEX19 in normal testis and cancer cells/tissues. RT-qPCR and RNA sequencing were employed to determine the changes to the transcriptome of cancer cells depleted for TEX19 and Kaplan-Meier plots were generated to explore the relationship between TEX19 expression and prognosis for a range of cancer types. RESULTS: Depletion of TEX19 levels in a range of cancer cell lines in vitro and in vivo restricts cellular proliferation/self-renewal/reduces tumour volume, indicating TEX19 is required for cancer cell proliferative/self-renewal potential. Analysis of cells depleted for TEX19 indicates they enter a quiescent-like state and have subtle defects in S-phase progression. TEX19 is present in both the nucleus and cytoplasm in both cancerous cells and normal testis. In cancer cells, localization switches in a context-dependent fashion. Transcriptome analysis of TEX19 depleted cells reveals altered transcript levels of a number of cancer-/proliferation-associated genes, suggesting that TEX19 could control oncogenic proliferation via a transcript/transcription regulation pathway. Finally, overall survival analysis of high verses low TEX19 expressing tumours indicates that TEX19 expression is linked to prognostic outcomes in different tumour types. CONCLUSIONS: TEX19 is required to drive cell proliferation in a range of cancer cell types, possibly mediated via an oncogenic transcript regulation mechanism. TEX19 expression is linked to a poor prognosis for some cancers and collectively these findings indicate that not only can TEX19 expression serve as a novel cancer biomarker, but may also offer a cancer-specific therapeutic target with broad spectrum potential.