Protocol for Oligonucleotides Characterization Using Hydrophilic Interaction Chromatography.

Oligonucleotides (ONs) are an increasingly popular category of molecules in the pharmaceutical landscape, particularly attractive for the treatment of genetic and rare diseases. However, analyzing these molecules presents significant challenges, due to their highly hydrophilic nature, multiple negative charges, and the presence of closely related impurities resulting from the complex solid-phase synthesis process. Ion pairing reverse-phase liquid chromatography (IP-RPLC) is the preferred technique for ONs analysis but is not ideal for mass spectrometry (MS) coupling.

Regenerating Locus Coeruleus-Norepinephrine (LC-NE) Function: A Novel Approach for Neurodegenerative Diseases.

Pathological changes in the locus coeruleus-norepinephrine (LC-NE) neurons, the major source of norepinephrine (NE, also known as noradrenaline) in the brain, are evident during the early stages of neurodegenerative diseases (ND). Research on both human and animal models have highlighted the therapeutic potential of targeting the LC-NE system to mitigate the progression of ND and alleviate associated psychiatric symptoms. However, the early and widespread degeneration of the LC-NE system presents a significant challenge for direct intervention in ND.

Epstein-Barr Virus-Induced 3 Attributes to TLR7-Mediated Splenomegaly.

Epstein-Barr virus-induced 3 (EBI3) functions as a component of the heterodimer cytokine IL-27, which regulates innate and acquired immune responses. The expression of EBI3 gene is induced by Toll-like receptors (TLRs). Repeated treatment with imiquimod (IMQ), a TLR7 agonist, induces splenomegaly and cytopaenia due to increased splenic function.

Novel Quinoline Schiff-Bases as Mtb DNA Gyrase Inhibitors - A Combined In Vitro and In Silico Study.

A new series of quinoline Schiff-bases was designed, synthesized, and characterized using 1H NMR, 13C NMR, and HRMS analysis. Further, all the compounds were screened for their antitubercular, antibacterial, and antifungal activity, and the minimum inhibitory concentrations (MICs) were determined. Among all, compound 7f displayed a significantly potent broad-spectrum antitubercular and antimicrobial activity against most of the tested strains of bacteria and fungi, with MIC values in the range of 1.

Cysteine S-conjugate sulfoxide β-lyase activity for human ACCS.

1-Aminocyclopropane-1-carboxylate synthase (ACCS) catalyzes the conversion of S-adenosyl-methionine to 1-aminocyclopropane-1-carboxylate (ACC), a rate-limiting step in ethylene biosynthesis. A gene encoding a putative ACCS protein was identified in the human genome two decades ago. It has been shown to not exhibit any canonical ACC synthase activity and its true function remains obscure.

Effects of intra-class peer mentorship intervention programme on the academic performances of academically underperforming medical students in Nigeria.

Background: A significant gap exists in understanding the effectiveness of intra-class (same-class) level peer mentorship programmes designed to enhance academic performance, well-being, and student involvement among underperforming medical students. This study assessed the effectiveness of intra-class (same-class) peer mentorship programme on the academic performances, subjective well-being and school engagement of academically underperforming medical students in Nigeria.

Methods: This was a quasi-experimental research consisting of the pretest-posttest control design at Nnamdi Azikiwe University, Awka, Nigeria.

Investigating the role of intratumoral Streptococcus mitis in gastric cancer progression: insights into tumor microenvironment.

Growing evidence implicates that intratumoral microbiota are closely linked to cancer progression; however, research on the role of these microbiota in the development of gastric cancer remains limited. Here, using 16 S rRNA sequencing, tumor tissue proteomics and serum cytokines analysis, we identified enrichment of specific microbial communities within tumors of gastric cancer patients, possibly affecting the tumor microenvironment by immune modulation, metabolic processes, and inflammatory responses. Based on the results of in vivo experiments and intratumoral microbiota analysis, we found that Streptococcus mitis can inhibit gastric cancer progression via suppressing M2 macrophage polarization and infiltration, as well as altering the intratumoral microbial community.

Intestinal neutrophil extracellular traps promote gut barrier damage exacerbating endotoxaemia, systemic inflammation and progression of diabetic retinopathy in type 2 diabetes.

Aims/hypothesis: Within the small intestine, neutrophils play an integral role in preventing bacterial infection. Upon interaction with bacteria or bacteria-derived antigens, neutrophils initiate a multi-staged response of which the terminal stage is NETosis, formation of protease-decorated nuclear DNA into extracellular traps. NETosis has a great propensity to elicit ocular damage and has been associated with diabetic retinopathy and diabetic macular oedema (DME) progression.

Different essential oils can inhibit Candida albicans biofilm formation on acrylic resin by suppressing aspartic proteinase: In vitro and in silico approaches.

Introduction: Cymbopogon martini, Syzygium aromaticum, and Cupressus sempervirens are used for antimicrobial purposes in the worldwide. Both their extracts and essential oil contents are rich in active ingredients.

Objective: The aim of this study was to investigate the inhibitory effect of Cymbopogon martini essential oil (CMEO), Syzygium aromaticum essential oil (SAEO) and Cupressus sempervirens essential oil (CSEO) on Candida albicans biofilm formation on heat-polymerized polymethyl methacrylate (PMMA) samples in vitro and in silico.

Effectiveness of Pelvic Floor Muscle and Education-based Therapies on Bladder, Bowel, Vaginal, Sexual, Psychological Function, Quality of Life, and Pelvic Floor Muscle Function in Females Treated for Breast Cancer: A Systematic Review.

Purpose Of Review: Breast malignancy is the most common cancer in females. Symptoms of pelvic floor disorders and sexual dysfunction secondary to systemic cancer treatment may occur. Non-surgical, non-pharmaceutical conservative therapies, namely pelvic floor muscle (PFM) and education-based therapies, could be beneficial to reduce these symptoms in this population.

Ginsenoside Rd protects against acute liver injury by regulating the autophagy NLRP3 inflammasome pathway.

Ginsenoside Rd (Rd) is a bioactive compound predominantly found in Panax ginseng C.A. Meyer and Panax notoginseng (Burkill) F.

Assessment of retinal pigment epithelium tears in eyes with submacular hemorrhage secondary to age-related macular degeneration.

To assess retinal pigment epithelium (RPE) tears in eyes which underwent pars plana vitrectomy (PPV) for submacular hemorrhage (SMH) secondary to age-related macular degeneration and to investigate the prognostic factors of visual outcomes. This study was a retrospective, observational case series that included 24 eyes of 24 patients who underwent PPV with subretinal tissue plasminogen activator and air for SMH. RPE tears were investigated using spectral-domain or swept-source optical coherence tomography images with raster scan, combined confocal scanning laser ophthalmoscope near-infrared images and color fundus photographs.

FGF-based drug discovery: advances and challenges.

The fibroblast growth factor (FGF) family comprises 15 paracrine-acting and 3 endocrine-acting polypeptides, which govern a multitude of processes in human development, metabolism and tissue homeostasis. Therapeutic endocrine FGFs have recently advanced in clinical trials, with FGF19 and FGF21-based therapies on the cusp of approval for the treatment of primary sclerosing cholangitis and metabolic syndrome-associated steatohepatitis, respectively. By contrast, while paracrine FGFs were once thought to be promising drug candidates for wound healing, burns, tissue repair and ischaemic ailments based on their potent mitogenic and angiogenic properties, repeated failures in clinical trials have led to the widespread perception that the development of paracrine FGF-based drugs is not feasible.

Substrates, regulation, cellular functions, and disease associations of P4-ATPases.

P4-ATPases, a subfamily of the P-type ATPase superfamily, play a crucial role in translocating membrane lipids from the exoplasmic/luminal leaflet to the cytoplasmic leaflet. This process generates and regulates transbilayer lipid asymmetry. These enzymes are conserved across all eukaryotes, and the human genome encodes 14 distinct P4-ATPases.

Characterization of Bozitinib as a potential therapeutic agent for MET-amplified gastric cancer.

Hyperactive c-Met signaling pathway caused by altered MET is a common mechanism underlying gastric cancer and represents an attractive target for the treatment of gastric cancer with MET alterations. However, no c-Met kinase inhibitors are currently approved specifically for the treatment of c-Met-amplified gastric cancer. Recently, bozitinib, a highly selective c-Met kinase inhibitor, has shown remarkable potency in selectively inhibiting MET-altered non-small cell lung cancer and secondary glioblastoma.

Activation of Wnt/β-catenin in neural progenitor cells regulates blood-brain barrier development and promotes neuroinflammation.

The central nervous system (CNS) requires specialized blood vessels to support neural function within specific microenvironments. During neurovascular development, endothelial Wnt/β-catenin signaling is required for BBB development within the brain parenchyma, whereas fenestrated blood vessels that lack BBB properties do not require Wnt/β-catenin signaling. Here, we used zebrafish to further characterize this phenotypic heterogeneity of the CNS vasculature.

α-Copaene is a potent repellent against the Asian Citrus Psyllid Diaphorina citri.

The Asian Citrus Psyllid (ACP), Diaphorina citri, severely threatens citrus production worldwide by transmitting the greening (= Huanglongbing)-causing bacterium Candidatus Liberibacter asiaticus. There is growing evidence that the push-pull strategy is suitable to partially mitigate HLB by repelling ACP with transgenic plants engineered to produce repellents and attracting the vector to plants with a minimal disease transmission rate. Species that pull ACP away from commercial citrus plants have been identified, and transgenic plants that repel ACP have been developed.

PARP inhibition-associated heterochromatin confers increased DNA replication stress and vulnerability to ATR inhibition in SMARCA4-deficient cells.

DNA replication stress (RS), a prevalent feature of various malignancies, arises from both genetic mutations and genotoxic exposure. Elevated RS levels increase the vulnerability of cancer cells to ataxia telangiectasia and Rad3-related kinase inhibitors (ATRis). Here, we screened for DNA damage response inhibitors that enhance ATRi-induced cytotoxicity using SWI/SNF complex-deficient cells and identified a potent synergy between ATRi and poly(ADP-ribose) polymerase inhibitor (PARPi), particularly in SMARCA4-deficient cells.

The role of nutritional vitamin D in CKD-MBD in children and adults with CKD, on dialysis and after kidney transplantation - a European consensus statement.

Vitamin D deficiency is common in patients with chronic kidney disease (CKD) and associates with poor outcomes. Current clinical practice guidelines recommend supplementation with nutritional vitamin D as for the general population. However, recent large-scale, clinical trials in the general population failed to demonstrate a benefit of vitamin D supplementation on skeletal or non-skeletal outcomes, fueling a debate on the rationale for screening for and correcting vitamin D deficiency, both in non-CKD and CKD populations.

Deep eutectic solvents in analysis, delivery and chemistry of pharmaceuticals.

Deep eutectic solvents (DES) have an emerging scientific role, assisting modern pharmaceutics. They are uniquely supporting the resolution of crucial issues, such as the effective extraction and isolation of bio-actives. They act as media and catalysts for pharmaceutical drug synthesis, and as green solvents and modifiers in pharmaceutical analysis.

Abiraterone acetate fixed-dosed combinations with ibuprofen-based therapeutic eutectic and deep eutectic solvents.

In recent years, deep eutectic solvents (DESs) with their outstanding solubilization properties have emerged as strong candidates for oral enabling formulations of poorly soluble drugs. This study explores the use of drug-based therapeutic DESs (THEDESs) to solubilize a poorly soluble compound with the aim of providing a fixed-dose combination of two complementary therapeutic agents. Specifically, potential anticancer effects of ibuprofen (IBU) are harnessed in a novel type of THEDES to dissolve higher amounts of abiraterone acetate (AbAc), an antitumor agent.

Promising LOX proteins for cartilage-targeting osteoarthritis therapy.

Osteoarthritis (OA) is the most affected joint disease worldwide, touching millions of people every year. It is caused by a progressive degeneration of articular cartilage, causing pain and limited mobility. Among the pathways involved in cartilage homeostasis, "LOX" proteins (referring to three distinct protein families, very often confused in the literature) play a prominent role.

Flower-like Biomimetic Enzyme for Rapid and Sensitive Detection of Zearalenone in Vegetable Oil Deodorizer Distillate.

In order to achieve high quality production of vitamin E and plant sterols, it is necessary to conduct rapid and accurate detection of fungal toxins in their production raw material (vegetable oil deodorizer distillate, VODD). In this study, the flower-like biomimetic enzyme of silver-doped ZnO was synthesized through wet chemical method and in-situ reduction method. Based on above work, a flower-like biomimetic enzyme modified glass carbon electrode was fabricated, and its excellent detection capability against fungal toxins zearalenone was confirmed through electrochemical analysis.

Nivolumab plus ipilimumab versus nivolumab in microsatellite instability-high metastatic colorectal cancer (CheckMate 8HW): a randomised, open-label, phase 3 trial.

Background: CheckMate 8HW prespecified dual primary endpoints, assessed in patients with centrally confirmed microsatellite instability-high or mismatch repair-deficient status: progression-free survival with nivolumab plus ipilimumab compared with chemotherapy as first-line therapy and progression-free survival with nivolumab plus ipilimumab compared with nivolumab alone, regardless of previous systemic treatment for metastatic disease. In our previous report, nivolumab plus ipilimumab showed superior progression-free survival versus chemotherapy in first-line microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer in the CheckMate 8HW trial. Here, we report results from the prespecified interim analysis for the other primary endpoint of progression-free survival for nivolumab plus ipilimumab versus nivolumab across all treatment lines.