Cyclic Lipopeptides as Selective Anticancer Agents: In vitro Efficacy on B16F10 Mouse Melanoma Cells.

Objective: In this study, 25 synthetic cyclic lipopeptides (CLPs) were investigated for their anticancer potential against mouse melanoma (B16F10) cells, human prostate cancer (PC-3), human colorectal adenocarcinoma (HT-29) and mouse embryonic fibroblast (NIH3T3) cells.

Methods: The cytotoxic activity of investigated compounds was evaluated using MTT and CV assays. In order to examine the mechanism of action of the most potent compound cell cycle analysis, apoptosis assay, caspase activity, CFSE and DHR staining, DAF-FM, autophagy and immunocytochemistry caspase-3 assays were performed.

Machine learning and molecular dynamics simulations predict potential TGR5 agonists for type 2 diabetes treatment.

Introduction: Treatment of type 2 diabetes (T2D) remains a significant challenge because of its multifactorial nature and complex metabolic pathways. There is growing interest in finding new therapeutic targets that could lead to safer and more effective treatment options. Takeda G protein-coupled receptor 5 (TGR5) is a promising antidiabetic target that plays a key role in metabolic regulation, especially in glucose homeostasis and energy expenditure.

Computer-assisted discovery of natural inhibitors for platelet-derived growth factor alpha as novel therapeutics for thyroid cancer.

Platelet-derived growth factor alpha (PDGFRA) plays a significant role in various malignant tumors. PDGFRA expression boosts thyroid cancer cell proliferation and metastasis. Radiorefractory thyroid cancer is poorly differentiated, very aggressive, and resistant to radioiodine therapy.

Sleep-driven prefrontal cortex coordinates temporal action and multimodal integration.

Cognitive processes such as action planning and decision-making require the integration of multiple sensory modalities in response to temporal cues, yet the underlying mechanism is not fully understood. Sleep has a crucial role for memory consolidation and promoting cognitive flexibility. Our aim is to identify the role of sleep in integrating different modalities to enhance cognitive flexibility and temporal task execution while identifying the specific brain regions that mediate this process.

Prevalence of chronic kidney disease in Saudi Arabia: an epidemiological population-based study.

Background: Chronic kidney disease (CKD) is a prevalent global health issue affecting millions of patients worldwide, impacting quality of life, impeding physical and psychological well-being, causing financial stress, and increasing mortality rates. This study aimed to highlight the prevalence of CKD and its associated risk factors across Saudi Arabia.

Method: This is a cross-sectional study conducted from 2015 to 2022, using data from 42 branches of a major network of diagnostic laboratories in Saudi Arabia, covering the country's 13 administrative areas.

Beyond traditional metrics: evaluating the triglyceride-total cholesterol-body weight index (TCBI) in cardiovascular risk assessment.

Background: Cardiovascular disease (CVD), a non-communicable condition, stands as the primary cause of death globally. This study seeks to evaluate the predictive power of atherogenic indices, which are recognized for their influence on CVD, alongside a newly developed index encompassing all three principal risk factors for CVD, referred to as the triglyceride-total cholesterol-body weight index (TCBI). The primary outcomes evaluated include both the incidence and mortality rates associated with CVD.

Rosae Multiflorae Fructus Extracts Regulate the Differentiation and Vascular Endothelial Cell-mediated Proliferation of Keratinocytes.

Keratinocytes are the primary component of the epidermis, so maintaining the precise balance between proliferation and differentiation is essential for conserving epidermal structure and function. Rosae multiflorae fructus extract (RMFE) has wide application in the cosmetic industry, but the molecular mechanisms underlying beneficial effects on keratinocytes are still not fully understood. In this study, we found that RMFE promoted epidermal differentiation and enhanced the barrier function of normal human epidermal keratinocytes (NHEKs) and three-dimensional epidermis model in culture.

Aescin ameliorates alcohol-induced liver injury. A possible implication of ROS / TNF-alpha / p38MAPK / caspase-3 signalling.

Alcoholic liver disease (ALD) is a commonly known liver disease mediated by prolonged alcohol consumption. Aescin is a triterpene saponin that can manage several conditions, including brain trauma, arthritis, venous congestion, stroke, and thrombophlebitis. Even so, studies illustrating the aescin role in ALD are scarce.

Decoding the Role of Kinesin Superfamily Proteins in Glioma Progression.

Glioma is a highly aggressive and invasive brain tumor with limited treatment options, highlighting the need for novel therapeutic approaches. Kinesin superfamily proteins (KIFs) are a diverse group of motor proteins that play essential roles in cellular processes such as mitosis, intracellular transport, and signal transduction, all of which are crucial for tumorigenesis. This review focuses on the multifaceted role of KIFs in glioma, examining their clinical relevance, contribution to tumor progression, and potential as therapeutic targets.

Total cell N-glycosylation is altered during differentiation of induced pluripotent stem cells to neural stem cells and is disturbed by trisomy 21.

Down syndrome (DS), a genetic condition caused by trisomy 21 (T21), manifests various neurological symptoms, including intellectual disability, early neurodegeneration, and early-onset dementia. N-glycosylation is a protein modification that plays a critical role in numerous neurobiological processes and whose dysregulation is associated with a range of neurological disorders. However, whether N-glycosylation of neural glycoproteins is affected in DS has not been studied.

Expression of miR-15b-5p and toll-like receptor4 as potential novel diagnostic biomarkers for hepatitis C virus-induced hepatocellular carcinoma.

Objectives: Globally, hepatocellular Carcinoma (HCC) ranks seventh in women's cancer and fifth in men's cancer. Early identification can minimize mortality and morbidity. MicroRNAs and Toll-like receptors have been suggested as potential new biomarkers for HCC; Therefore, we explored Toll-like receptor 4 (TLR-4) and miRNA 15b-5p as new non-invasive HCC biomarkers and early detection approaches.

Tracing of Amino Acids Dynamics in Cell Lines Based on O Stable Isotope Labeling.

Metabolite levels and turnover rates are necessary to understand metabolomic dynamics in a living organism fully. Amino acids can play distinct roles in various cellular processes, and their abnormal levels are associated with pathological conditions, including cancer. Therefore, their levels, especially turnover rates, may provide enormous information about a phenotype.

Metabolic Tagging Technology of Exosomes- An Updated Review.

Exosomes are small extracellular vesicles secreted by various cell types, playing a crucial role in intercellular communication by carrying proteins, lipids, and nucleic acids, thus holding significant potential in diagnostics and therapeutics. Accurate labeling of exosomes is vital for studying their biogenesis, trafficking, and functional properties, enabling precise tracking and manipulation. This review examines current labeling techniques, including metabolic glycan labeling, chemical tagging, membrane fluorescent dyes, bio-conjugation, non-covalent labeling, and cell-engineering approaches.

Physalis peruviana calyces extract ameliorate oxidative stress, inflammation, and immune loss in rats-exposed to hexaflumuron.

Background: Hexaflumuron (HFM), a common pesticide, can disrupt the immune system and cause oxidative stress. This study investigated the potential of Physalis peruviana L. calyces extract (PP) to counteract these effects in rats.

The role of 1-Deoxysphingolipids and Polyamines in the pathogenesis of placental syndrome.

Background: Placental syndrome, mainly composed of preeclampsia and fetal growth restriction, has an impact on the health of mother and baby dyads. While impaired placentation is central to their pathophysiology, the underlying molecular mechanisms remain incompletely understood. This study investigates the association between placental syndrome and metabolic alterations in 1-deoxysphingolipids (1-deoxySLs) and polyamines, along with their regulatory enzymes.

Synthesis, HS releasing properties, antiviral and antioxidant activities and acute cardiac effects of nucleoside 5'-dithioacetates.

Hydrogen sulfide (HS) is an endogenous gasotransmitter with cardioprotective and antiviral effects. In this work, new cysteine-selective nucleoside-HS-donor hybrid molecules were prepared by conjugating nucleoside biomolecules with a thiol-activatable dithioacetyl group. 5'-Dithioacetate derivatives were synthesized from the canonical nucleosides (uridine, adenosine, cytidine, guanosine and thymidine), and the putative 5'-thio metabolites were also produced from uridine and adenosine.

Conference report of the 2024 Antimicrobial Resistance Meeting.

The Antimicrobial Resistance - Genomes, Big Data and Emerging Technologies Conference explored key topics including measuring the burden of AMR, global public health pathogen genomics infrastructure and surveillance, translation and implementation of genomics for AMR control, use of techniques such as wastewater surveillance, mathematical and statistical modelling, and Artificial Intelligence (AI) to aid understanding of AMR. This report describes research presented during plenary sessions and discussions, keynote presentations and posters.

Genomics yields biological and phenotypic insights into bipolar disorder.

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

Photothermal nanofiber-mediated photoporation for gentle and efficient intracellular delivery of macromolecules.

Photoporation with free photothermal nanoparticles (NPs) is a promising technology for gentle delivery of functional biomacromolecules into living cells, offering great flexibility in terms of cell types and payload molecules. However, the translational use of photoporation, such as for transfecting patient-derived cells for cell therapies, is hampered by safety and regulatory concerns as it relies on direct contact between cells and photothermal NPs. A solution is to embed the photothermal NPs in electrospun nanofibers, which form a substrate for cell culture.

Stalled ribosome rescue factors exert different roles depending on types of antibiotics in Escherichia coli.

Escherichia coli possesses three stalled-ribosome rescue factors, tmRNA·SmpB (primary factor), ArfA (alternative factor to tmRNA·SmpB), and ArfB. Here, we examined the susceptibility of rescue factor-deficient strains from E. coli SE15 to various ribosome-targeting antibiotics.

Targeting signaling pathways in neurodegenerative diseases: Quercetin's cellular and molecular mechanisms for neuroprotection.

Background: Neurodegenerative diseases (NDs), including Alzheimer's disease, Parkinson's disease, and Huntington's disease, are complex and challenging due to their intricate pathophysiology and limited treatment options.

Methods: This review systematically sourced articles related to neurodegenerative diseases, neurodegeneration, quercetin, and clinical studies from primary medical databases, including Scopus, PubMed, and Web of Science.

Results: Recent studies have included quercetin to impact the cellular and molecular pathways involved in neurodegeneration.

Harnessing the ubiquitin proteasome system as a key player in stem cell biology.

Intracellular proteins take part in almost every body function; thus, protein homeostasis is of utmost importance. The ubiquitin proteasome system (UPS) has a fundamental role in protein homeostasis. Its main role is to selectively eradicate impaired or misfolded proteins, thus halting any damage that could arise from the accumulation of these malfunctioning proteins.

Afobazole alleviates streptozotocin-induced diabetic nephropathy in rats via hypoglycemic, antioxidant, anti-inflammatory, and anti-apoptotic properties: Role of the S1R/Nrf2 antioxidant axis.

Aims: Sigma-1 receptor (S1R) activation was recently identified as a promising target for preventing diabetic nephropathy (DN) by mitigating hypoxia, oxidative stress, and inflammation. This study aimed to investigate the potential reno-protective effect of the S1R agonist afobazole against streptozotocin (STZ)-induced DN in rats compared to metformin.

Materials And Methods: Rats were split into six groups: the normal control group; the diabetic control group received STZ (55 mg/kg i.

Deciphering the bidirectional impact of leukocyte telomere length on multiple sclerosis progression: A Mendelian randomization study.

Observational studies have suggested a link between leukocyte telomere length (LTL) and multiple sclerosis (MS) progression, but the causal relationship remains uncertain. This study investigates the causal association between LTL and MS progression using a bidirectional two-sample Mendelian randomization (MR) approach. We analyzed genome-wide association summary statistics data from 472,174 individuals for LTL and 12,584 MS patients for disease progression.