Congenital Titinopathy: Comprehensive Characterization of the Most Severe End of the Disease Spectrum.

Unlabelled: Congenital titinopathy has recently emerged as one of the most common congenital muscle disorders.

Objective: To better understand the presentation and clinical needs of the under-characterized extreme end of the congenital titinopathy severity spectrum.

Methods: We comprehensively analyzed the clinical, imaging, pathology, autopsy, and genetic findings in 15 severely affected individuals from 11 families.

Polychlorinated biphenyls induced toxicities upon cell lines and stem cells: a review.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants emitted during e-waste activities. Upon release into the environment, PCBs can pose harmful effects to the humans and environment. The present review focused on the effects of PCBs on cell proliferation, apoptosis, functional and developmental toxicity and potential possible molecular mechanisms upon cells and stem cells.

Marine natural products as a source of novel anticancer drugs: an updated review (2019-2023).

Marine natural products have long been recognized as a vast and diverse source of bioactive compounds with potential therapeutic applications, particularly in oncology. This review provides an updated overview of the significant advances made in the discovery and development of marine-derived anticancer drugs between 2019 and 2023. With a focus on recent research findings, the review explores the rich biodiversity of marine organisms, including sponges, corals, algae, and microorganisms, which have yielded numerous compounds exhibiting promising anticancer properties.

Stem Cell Therapy for Diseases of Livestock Animals: An In-Depth Review.

Stem cells are unique, undifferentiated cells that have the ability to both replicate themselves and develop into specialized cell types. This dual capability makes them valuable in the development of regenerative medicine. Current development in stem cell research has widened their application in cell therapy, drug discovery, reproductive cloning in animals, and cell models for various diseases.

Efficacy of Anti-Cancer Immune Responses Elicited Using Tumor-Targeted IL-2 Cytokine and Its Derivatives in Combined Preclinical Therapies.

Effective cancer therapies must address the tumor microenvironment (TME), a complex network of tumor cells and stromal components, including endothelial, immune, and mesenchymal cells. Durable outcomes require targeting both tumor cells and the TME while minimizing systemic toxicity. Interleukin-2 (IL-2)-based therapies have shown efficacy in cancers such as metastatic melanoma and renal cell carcinoma but are limited by severe side effects.

Actinomycete-Derived Pigments: A Path Toward Sustainable Industrial Colorants.

Pigment production has a substantial negative impact on the environment, since mining for natural pigments causes ecosystem degradation, while synthetic pigments, derived from petrochemicals, generate toxic by-products that accumulate and persist in aquatic systems due to their resistance to biodegradation. Despite these challenges, pigments remain essential across numerous industries, including the cosmetic, textile, food, automotive, paints and coatings, plastics, and packaging industries. In response to growing consumer demand for sustainable options, there is increasing interest in eco-friendly alternatives, particularly bio-based pigments derived from algae, fungi, and actinomycetes.

GC/MS Fatty Acid Profile of Marine-Derived Actinomycetes from Extreme Environments: Chemotaxonomic Insights and Biotechnological Potential.

This study investigated the fatty acids (FA) profile of 54 actinomycete strains isolated from marine sediments collected off the Portugal continental coast, specifically from the Estremadura Spur pockmarks field, by GC/MS. Fatty acid methyl esters (FAMEs) were prepared from the ethyl acetate lipidic extracts of these strains and analyzed by gas chromatography-mass spectrometry (GC/MS), with FA identification performed using the NIST library. The identified FAs varied from C12:0 to C20:0, where 32 distinct FAs were identified, including 7 branched-chain fatty acids (BCFAs), 9 odd-chain fatty acids (OCFAs), 8 monounsaturated fatty acids (MUFAs), 6 saturated fatty acids (SFAs), 1 polyunsaturated fatty acid (PUFA), and 1 cyclic chain fatty acid (CCFA).

Dynamics and Insights into the Unique Ecological Guild of Fungi in Bacteria-Bioaugmented Anaerobic Digesters.

Anaerobic digesters host a variety of microorganisms, and they work together to produce biogas. While bacterial and archaeal communities have been well explored using molecular techniques, fungal community structures remain relatively understudied. The present study aims to investigate the dynamics and potential ecological functions of the predominant fungi in bacteria-bioaugmented anaerobic digesters.

Silymarin as a Therapeutic Agent for Hepatocellular Carcinoma: A Multi-Approach Computational Study.

Background: Hepatocellular carcinoma (HCC) is a prevalent and lethal form of liver cancer with limited treatment options. Silymarin, a flavonoid complex derived from milk thistle, has shown promise in liver disease treatment due to its antioxidant, anti-inflammatory, and anticancer properties. This study aims to explore the therapeutic potential of silymarin in HCC through a comprehensive in silico approach.

Lipidomic Signature of Pregnant and Postpartum Females by Longitudinal and Transversal Evaluation: Putative Biomarkers Determined by UHPLC-QTOF-ESI-MS.

Background: Pregnancy induces significant physiological and metabolic changes in the mother to support fetal growth and prepare for childbirth. These adaptations impact various systems, including immune tolerance, metabolism, and endocrine function. While metabolomics has been utilized to study pregnancy-related metabolic changes, comprehensive comparisons between pregnant and non-pregnant states, particularly using ultra-high-performance liquid chromatography coupled with mass spectrometry (UHPLC-MS), remain limited.

Prediction of the Binding to the Nuclear Factor NF-Kappa-B by Constituents from L. Essential Oil.

L. is a plant with various claims of ethnobotanical use, primarily for inflammatory diseases. Chemical studies have already isolated different types of terpenes from the species, and studies have established its pharmacological potential.

Ononin's Antagonistic Activity towards TRPV1: Insights from Molecular Dynamics and Capsaicin-Evoked Calcium Response in DRG Neurons.

Background: The search for effective painkillers has led to intensive research, with a particular focus on the transient receptor potential vanilloid-1 (TRPV1) channel as a possible target.

Methods: One promising candidate is ononin, which is investigated for its binding with TRPV1 through a 200-ns molecular dynamic simulation and analysed via root-meansquare deviation (RMSD), root-mean-square fluctuation (RMSF), hydrogen-bond interactions, radius of gyration (RadGyr), and MM-PBSA energy calculations. The results were further validated experimentally via calcium imaging studies.

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.

Traditional uses, botanical description, phytochemistry, and pharmacological activities of : a review.

Background: is an herbaceous herb belonging to the Phytolaccaceae family. The plant has a long history of usage in traditional medicine for treating a variety of ailments including infectious diseases, edema, inflammation, gastric, and abdominal distress. The traditional use, phytochemistry, and pharmacological properties of are outlined in this article.

Aberrant c-AMP signalling in richter syndrome revealed by single-cell transcriptome and 3D chromatin analysis.

Richter syndrome (RS), characterized by aggressive lymphoma arising from chronic lymphocytic leukaemia (CLL), presents a poor response to treatment and grim prognosis. To elucidate RS mechanisms, paired samples from a patient with DLBCL-RS were subjected to single-cell RNA sequencing (scRNA-seq) and high-throughput chromosome conformation capture (Hi-C) sequencing. Over 10,000 cells were profiled via scRNA-seq, revealing the comprehensive B cell transformation in RS.

Whole-genome evaluation and prophages characterization associated with genome of carbapenem-resistant Acinetobacter baumannii UOL-KIMZ-24-2.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is an emerging threat to healthcare settings in many countries, principally in South Asia. The current study was aimed to identify, evaluate whole-genome and characterize the prophages in genome of CRAB strain, recovered from patients of Lahore General Hospital, Lahore. More than 200 samples were collected and identified by morphological and biochemical tests.

Mitochondria and its epigenetic dynamics: Insight into synaptic regulation and synaptopathies.

Mitochondria, the cellular powerhouses, are pivotal to neuronal function and health, particularly through their role in regulating synaptic structure and function. Spine reprogramming, which underlies synapse development, depends heavily on mitochondrial dynamics-such as biogenesis, fission, fusion, and mitophagy as well as functions including ATP production, calcium (Ca) regulation, and retrograde signaling. Mitochondria supply the energy necessary for assisting synapse development and plasticity, while also regulating intracellular Ca homeostasis to prevent excitotoxicity and support synaptic neurotransmission.

Pretreatment attrition after rifampicin-resistant tuberculosis diagnosis with Xpert MTB/RIF or ultra in high TB burden countries: a systematic review and meta-analysis.

Introduction: The WHO endorsed the Xpert MTB/RIF (Xpert) technique since 2011 as initial test to diagnose rifampicin-resistant tuberculosis (RR-TB). No systematic review has quantified the proportion of pretreatment attrition in RR-TB patients diagnosed with Xpert in high TB burden countries.Pretreatment attrition for RR-TB represents the gap between patients diagnosed and those who effectively started anti-TB treatment regardless of the reasons (which include pretreatment mortality (death of a diagnosed RR-TB patient before starting adequate treatment) and/or pretreatment loss to follow-up (PTLFU) (drop-out of a diagnosed RR-TB patient before initiation of anti-TB treatment).

Biotransformation of Ganoderma lucidum and Hericium erinaceus for ex vivo gut-brain axis modulation and mood-related outcomes in humans: CREB/BDNF signaling and microbiota-driven synergies.

Background: The human gut microbiota plays a crucial role in various aspects of health, extending beyond digestion and nutrient absorption. Ganoderma lucidum (Reishi) and Hericium erinaceus (Lion's Mane), traditional medicinal mushrooms, have garnered interest due to their potential to exert positive health effects. The aim of our study was to investigate the molecular impact of Reishi and Lion's Mane on mood regulation through the gut-brain axis.

Targeting CD84 protein on myeloid-derived suppressor cells as a novel immunotherapy in solid tumors.

Background And Objective: Myeloid-derived suppressor cells (MDSCs) are a crucial and diverse group of cells found in the tumor microenvironment (TME) that facilitate progression, invasion, and metastasis within solid tumors. CD84, a homophilic adhesion molecule expressed on MDSCs, plays a critical role in their accumulation and function within the TME. This study aims to investigate the protein-protein interactions of CD84 using molecular dynamics simulations and to explore potential therapeutic strategies targeting these interactions.

Calothrixin B by docking JAK2 is a potential therapeutic inhibitor for pancreatic ductal adenocarcinoma.

Objectives: Pancreatic cancer, a highly invasive and prognostically unfavorable malignant tumor, consistently exhibits resistance to conventional chemotherapy, leading to substantial side effects and diminished patient quality of life. This highlights the critical need for the discovery of novel, effective, and safe chemotherapy drugs. This study aimed to explore bioactive compounds, particularly natural products, as an alternative for JAK2 protein inhibitor in cancer treatment.

Physico-chemical properties and substrate specificity of α-(1→3)-d-glucan degrading recombinant mutanase from expressed in .

Unlabelled: The gene encoding fungus mutanase (MutA, GH71 family, α-1,3-glucanase, EC 3.2.1.

Assessing spatial sequencing and imaging approaches to capture the molecular and pathological heterogeneity of archived cancer tissues.

Spatial transcriptomics (ST) offers enormous potential to decipher the biological and pathological heterogeneity in precious archival cancer tissues. Traditionally, these tissues have rarely been used and only examined at a low throughput, most commonly by histopathological staining. ST adds thousands of times as many molecular features to histopathological images, but critical technical issues and limitations require more assessment of how ST performs on fixed archival tissues.

Computational structure-based design of antiviral peptides as potential protein-protein interaction inhibitors of rabies virus phosphoprotein and human LC8.

Rabies is a serious zoonotic disease caused by the rabies virus (RABV). Despite the successful development of vaccines and efforts made in drug discovery, rabies is incurable. Therefore, development of novel drugs is of interest to the scientific community.