Deciphering Binding Potential of Naphthalimide-Coumarin Conjugate with c-MYC G-Quadruplex for Developing Anticancer Agents: A Spectroscopic and Molecular Modeling Approach.

It has been well accumulated that G-quadruplex (G4-DNA) has great anticancer relevance, and various heterocyclic moieties have been synthesized and examined as potent G4-DNA binders with promising anticancer activity. Here, we have synthesized a series of naphthalimide-triazole-coumarin conjugates by substituting various amines and further examine their anticancer activity against 60 human cancer cell lines at 10 μM. One and five dose concentration results reveal low values of MG-MID GI for compounds including (3.

Immunohistochemical Expression of PD-L1 and CTLA-4 in Triple Negative Breast Cancer and Their Prognostic Associations.

Objective: Programmed Death-Ligand 1 (PD-L1) and Cytotoxic T Lymphocyte -Associated Antigen-4 (CTLA-4) are presently considered as prognostic markers and therapeutic targets in numerous human malignancies. The goal of this study was to determine whether PD-L1 and CTLA-4 might be used to predict patients' survival in Triple Negative Breast Cancer (TNBC).

Methods: This retrospective cohort study analyzed 100 primary TNBC cases that had surgical resection at the Oncology Center of Mansoura University (OCMU), Faculty of Medicine, Egypt.

Interleukin-17A and Interleukin-17F Gene Polymorphisms in Egyptian Patients with Chronic Hepatitis C and Hepatocellular Carcinoma.

Objective: Interleukin IL-17A and IL-17F are critical cytokines involved in inflammatory processes. Genetic variations in IL-17A and IL-17F might be linked to chronic hepatitis C (CHC) and an increased risk of hepatocellular carcinoma (HCC), a cancer associated with long-term inflammation. This study aims to examine the relationship between specific polymorphisms in IL-17A (rs2275913) and IL-17F (rs763780) and their association with HCV-related HCC in an Egyptian population.

The p16 Immunostaining Predicts the Risk of Recurrence in Prostate Cancer.

Objective: This study aimed to investigate the influence of p16 immunohistochemical expression on the biochemical recurrence rate of pT2-pT3 prostate cancer.

Materials And Methods: A total of 488 pT2-pT3 stage prostate adenocarcinomas undergoing radical prostatectomy were included in this study. Following a review of Gleason classification and retrieval of sociodemographic and clinicopathological data, as well as the date of last consultation and biochemical recurrence, immunohistochemistry for p16 was performed.

Emerging Research and Future Directions on Doxorubicin: A Snapshot.

Doxorubicin, a widely used anthracycline antibiotic, has been a cornerstone in cancer chemotherapy since the 1960s. In addition to doxorubicin, anthracycline chemotherapy medications include daunorubicin, idarubicin, and epirubicin. For many years, doxorubicin has been the chemotherapy drug of choice for treating a broad variety of cancers.

Kidney function estimation equations: a narrative review.

Glomerular filtration rate (GFR) as a marker of kidney function is important in health and disease management because decreased kidney function is associated with all-cause and cardiovascular mortality, progression of kidney disease, predisposition to acute kidney injury (AKI), and for drug dosage modification. While measured glomerular filtration rate (mGFR) is acknowledged as the most accurate method for evaluating kidney function, it is at present not feasible to be applied in the clinical arena. Estimated glomerular filtration rate (eGFR) is preferred due to its convenience, cost-effectiveness, and seamless integration into standard clinical practice for kidney function evaluation.

Synergistic antimicrobial activity of essential oils mixture of Moringa oleifera, Cinnamomum verum and Nigella sativa against Staphylococcus aureus using L-optimal mixture design.

The urgent need to address the growing problem of antimicrobial resistance in multidrug-resistant bacteria requires the development of pioneering approaches to treatment. The present study aims to evaluate the antimicrobial potential of the essential oils (EOs) of Moringa oleifera (moringa), Cinnamomum verum (cinnamon), and Nigella sativa (black seed) and the synergistic effect of the mixture of these oils against Staphylococcus aureus MCC 1351. Statistical modeling revealed cinnamon oil had the highest individual antimicrobial potency, followed by black seed oil.

Attitudes towards healthy eating and its determinants among older adults in a deprived region of Hungary: implications for the National Healthy Aging Program.

A healthy diet is a key determinant of successful aging. However, the psychological, social, and physiological changes associated with ageing often disrupt dietary behaviours. Hungary has one of the highest rates of chronic age-related diseases in the European Union, exacerbated by unhealthy dietary patterns and rapid population aging.

Pharmacoinformatics-based screening and construction of a neutralizing anti-SARS-CoV-2 camelidae nanobody drug conjugate.

Nanobodies or variable antigen-binding domains (VH) derived from heavy chain-only antibodies (HcAb) occurring in the Camelidae family offer certain superior physicochemical characteristics like enhanced stability, solubility, and low immunogenicity compared to conventional antibodies. Their efficient antigen-binding capabilities make them a preferred choice for next-generation small biologics. In the present work, we design an anti-SARS-CoV-2 bi-paratopic nanobody drug conjugate by screening a nanobody database.

Study of cathelicidin (LL-37) immunoexpression in the skin of vitiligo patients.

Vitiligo is a pigmentary disorder acquired and caused by the loss or destruction of melanocytes from the epidermis. There is strong proof that vitiligo is mainly an autoimmune disease. Cathelicidin (LL37), an antimicrobial polypeptide, is an important part of the innate immune system and has a role in different skin autoimmune diseases.

Effect of Vitamin D Supplementation on Lipid Profile in Overweight or Obese Women: A Meta-analysis and Systematic Review of Randomized Controlled Trials.

Context: Previous studies have explored the relationship between vitamin D and lipid profile in individuals with obesity or overweight women, but the results have been inconsistent.

Objective: This meta-analysis and systematic review of randomized controlled trials (RCTs) was conducted to assess the effect of vitamin D on lipid profile in women who are overweight or obese.

Data Sources: A meticulous search strategy was used across the Scopus, PubMed/Medline, Web of Science, and Embase databases up to June 2024.

P-P Coupling and Terminal Metal-Phosphorus Intermediates.

Terminal metal-phosphorus (M-P) complexes are of significant contemporary interest as potential platforms for P-atom transfer (PAT) chemistry. Decarbonylation of metal-phosphaethynolate (M-PCO) complexes has emerged as a general synthetic approach to terminal M-P complexes. M-P complexes that are stabilized by strong M-P multiple bonds are kinetically persistent and isolable.

Carboxy-Amidated AamAP1-Lys has Superior Conformational Flexibility and Accelerated Killing of Gram-Negative Bacteria.

C-terminal amidation of antimicrobial peptides (AMPs) is a frequent minor modification used to improve antibacterial potency, commonly ascribed to increased positive charge, protection from proteases, and a stabilized secondary structure. Although the activity of AMPs is primarily associated with the ability to penetrate bacterial membranes, hitherto the effect of amidation on this interaction has not been understood in detail. Here, we show that amidation of the scorpion-derived membranolytic peptide AamAP1-Lys produces a potent analog with faster bactericidal activity, increased membrane permeabilization, and greater Gram-negative membrane penetration associated with greater conformational flexibility.

Restoring cefepime activity against multidrug-resistant KPC-producing by combination with boronic acid inhibitors, MB076 and S02030.

Foremost in the design of new β-lactamase inhibitors (BLIs) are the boronic acid transition state inhibitors (BATSIs). Two highly potent BATSIs being developed are S02030 and MB076 strategically designed to be active against cephalosporinases and carbapenemases, especially KPC. When combined with cefepime, S02030 and MB076 demonstrated potent antimicrobial activity against laboratory and clinical strains of expressing a variety of class A and class C β-lactamases, including and .

Machine learning reveals the dynamic importance of accessory sequences for outbreak clustering.

Unlabelled: Bacterial typing at whole-genome scales is now feasible owing to decreasing costs in high-throughput sequencing and the recent advances in computation. The unprecedented resolution of whole-genome typing is achieved by genotyping the variable segments of bacterial genomes that can fluctuate significantly in gene content. However, due to the transient and hypervariable nature of many accessory elements, the value of the added resolution in outbreak investigations remains disputed.

Conformational flexibility is a critical factor in designing broad-spectrum human norovirus protease inhibitors.

Unlabelled: Human norovirus (HuNoV) is a leading cause of gastroenteritis worldwide and is associated with significant morbidity, mortality, and economic impact. There are currently no licensed antiviral drugs for the treatment of HuNoV-associated gastroenteritis. The HuNoV protease plays a critical role in the initiation of virus replication by cleaving the polyprotein.

Evaluation of tumor-colonizing strains using the chick chorioallantoic membrane model.

The chick embryo chorioallantoic membrane (CAM) tumor model is a valuable preclinical model for studying the tumor-colonizing process of serovar Typhimurium. It offers advantages such as cost-effectiveness, rapid turnaround, reduced engraftment issues, and ease of observation. In this study, we explored and validated the applicability of the partially immune-deficient CAM tumor model.

Developmental and environmental effects on VTC2-dependent leaf ascorbate accumulation and functions.

In nature, environmental conditions strongly fluctuate, frequently subjecting plants to periods of immediate photo-oxidative stress. The small molecule ascorbate allows plants to cope with such stress conditions. Ascorbate scavenges reactive oxygen species and enables the rapid and full induction of photoprotective non-photochemical quenching (NPQ).

Design for Telecom-Wavelength Quantum Emitters in Silicon Based on Alkali-Metal-Saturated Vacancy Complexes.

Defect emitters in silicon are promising contenders as building blocks of solid-state quantum repeaters and sensor networks. Here, we investigate a family of possible isoelectronic emitter defect complexes from a design standpoint. We show that the identification of key physical effects on quantum defect state localization can guide the search for telecom-wavelength emitters.

Astaxanthin Alleviates Lung Injury by Regulating Oxidative Stress, Inflammatory Response, P2X7 Receptor, NF-κB, Bcl-2, and Caspase-3 in LPS-Induced Endotoxemia.

Sepsis remains the leading cause of multiple-organ injury due to endotoxemia. Astaxanthin (ASTA), widely used in marine aquaculture, has an extraordinary potential for antioxidant and anti-inflammatory activity. Purinergic receptor (e.

Inhibition of HMGA2 binding to AT-rich DNA by its negatively charged C-terminus.

The mammalian high mobility group protein AT-hook 2 (HMGA2) is a small DNA-binding protein that specifically targets AT-rich DNA sequences. Structurally, HMGA2 is an intrinsically disordered protein (IDP), comprising three positively charged 'AT-hooks' and a negatively charged C-terminus. HMGA2 can form homodimers through electrostatic interactions between its 'AT-hooks' and C-terminus.

Tissue-invasive Pathogens in Periodontitis Patients and Their Correlation with Pro-inflammatory Markers: An Analytical Case-control Study.

Aim: Tissue-invasive bacteria have been proposed to be a crucial factor in the etiopathogenesis of periodontitis, with the probable interaction of tissue-invasive bacteria with the innate immune response through inflammasomes, perpetuating periodontal attachment loss. This study aims to reveal the correlation between such tissue-invasive bacteria in upregulating inflammasomes and pro-inflammatory cytokines.

Materials And Methods: This study recruited a total of 10 patients with stage III/IV and grade C periodontitis based on the bone loss to age ratio.

Investigation into the effect of phenylalanine gating on anaerobic haem breakdown using the energy landscape approach.

We have recently demonstrated a novel anaerobic NADH-dependent haem breakdown reaction, which is carried out by a range of haemoproteins. The Yersinia enterocolitica protein, HemS, is the focus of further research presented in the current paper. Using conventional experimental methods, bioinformatics, and energy landscape theory (ELT), we provide new insight into the mechanism of the novel breakdown process.

Pathogenicity assessment of genetic variants identified in patients with severe hypertriglyceridemia: novel cases of Familial Chylomicronemia Syndrome from the Dyslipidemia Registry of the Spanish Atherosclerosis Society.

Purpose: Genetic testing is required to confirm a diagnosis of familial chylomicronemia syndrome (FCS). We assessed the pathogenicity of variants identified in the FCS canonical genes to diagnose FCS cases.

Methods: 245 patients with severe hypertriglyceridemia underwent next-generation sequencing.

Analyzing Pathophysiology and Immune Cells and Their Cytokines and Mediators in Precision-Cut Slices of the Murine Lung.

Understanding the dynamic pathophysiology of diseases in the lung, such as asthma and chronic asthma, chronic obstructive pulmonary disease, and lung cancer, is crucial for the treatment, analysis, and outcome of these diseases. Unlike other traditional models, we suggest a protocol that is sustainable and reproducible and offers different analysis methods while maintaining in vivo lung architecture and immune dynamics. This protocol allows one to study the pathophysiological changes, including changes to the immune cells, cytokines, and mediators, in 30 precision-cut lung slices from a single murine lung.