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ZPR1 prevents R-loop accumulation, upregulates SMN2 expression and rescues spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by homozygous mutation or deletion of the survival motor neuron 1 (SMN1) gene. A second copy, SMN2, is similar to SMN1 but produces ∼10% SMN protein because of a single-point mutation that causes splicing defects. Chronic low levels of SMN cause accumulation of co-transcriptional R-loops and DNA damage leading to genomic instability and neurodegeneration in SMA. Severity of SMA disease correlates inversely with SMN levels. SMN2 is a promising target to produce higher levels of SMN by enhancing its expression. Mechanisms that regu

Skin commensal bacterium Staphylococcus epidermidis CCSM0287 cell-free supernatant protects HaCaT cells from UVB irradiation-induced photodamage and improves skin barrier function.

Ultraviolet B (UVB) radiation is a major environmental stressor that induces oxidative stress, inflammation, and skin barrier dysfunction. Although Staphylococcus epidermidis (S. epidermidis) is a beneficial skin commensal, current evidence on its protective effects against UVB-induced skin damage has primarily focused on reference strains or a limited number of individual metabolites. The broader photoprotective potential of postbiotics derived from newly isolated skin commensal strains remains insufficiently characterized. Here, we investigated the anti-photodamage activity and underlying me

Cardioprotective Effect of Phase 3 Clinical Anticancer Agent, RRx-001, in Doxorubicin-Induced Acute Cardiotoxicity in Mice.

Anthracycline chemotherapy (e.g., doxorubicin or DOX) is associated with a cumulative dose-dependent cardiac dysfunction that may lead to congestive heart failure, which limits both its use and usefulness in the clinic. The cardiotoxicity may manifest acutely and/or months or years after treatment with doxorubicin has ended. Experimental and human data have demonstrated that angiotensin-converting enzyme/angiotensin-receptor antagonists mediate a cardioprotective effect against anthracycline toxicity. In this study, with the angiotensin receptor blocker, candesartan, as a positive control, we

Silver Nanoparticles Phytofabricated through Azadirachta indica: Anticancer, Apoptotic, and Wound-Healing Properties.

Silver nanoparticles (AgNPs) have unlocked numerous novel disciplines in nanobiotechnological protocols due to their larger surface area-to-volume ratios, which are attributed to the marked reactivity of nanosilver, and due to their extremely small size, which enables AgNPs to enter cells, interact with organelles, and yield distinct biological effects. AgNPs are capable of bypassing immune cells, staying in the system for longer periods and with a higher distribution, reaching target tissues at higher concentrations, avoiding diffusion to adjacent tissues, releasing therapeutic agents or drug

Structural and Functional Characterization of Protein Adhesins and Pili in Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb) is a highly adaptable pathogen whose ability to establish infection and persist within the host is primarily driven by a diverse array of adhesins, surface proteins, and structures that mediate attachment to host cells and tissues. These adhesins play critical roles in bacterial colonization, invasion, immune evasion, and long-term persistence, making them central to Mtb pathogenesis. Mtb adhesins can be broadly categorized based on their structural features, functional roles, and binding specificities. Protein adhesins such as LpqH (the 19-kDa lipoprotein), Ps

Peptide-Based Catalysts Reach the Outer Sphere through Remote Desymmetrization and Atroposelectivity.

Nature's catalytic machinery has provided endless inspiration for chemists. While the enzymatic ideal has yet to be fully realized, the field has made tremendous strides toward synthetic, small-molecule catalysts for a wide array of transformations, often drawing upon biological concepts in their design. One strategy that has been particularly influenced by enzymology is peptide catalysis, wherein oligopeptides are implemented as chiral catalysts in synthetically relevant reactions. The fundamental goal has been to mimic enzymatic active sites by taking advantage of secondary structures that a

The genetic landscape of mutations in Burkitt lymphoma.

Burkitt lymphoma is characterized by deregulation of MYC, but the contribution of other genetic mutations to the disease is largely unknown. Here, we describe the first completely sequenced genome from a Burkitt lymphoma tumor and germline DNA from the same affected individual. We further sequenced the exomes of 59 Burkitt lymphoma tumors and compared them to sequenced exomes from 94 diffuse large B-cell lymphoma (DLBCL) tumors. We identified 70 genes that were recurrently mutated in Burkitt lymphomas, including ID3, GNA13, RET, PIK3R1 and the SWI/SNF genes ARID1A and SMARCA4. Our data implica

Association of testicular germ cell tumor with polymorphisms in estrogen receptor and steroid metabolism genes.

It is generally assumed that the development of testicular germ cell tumor (TGCT) is under endocrine control. In particular, unbalanced androgen/estrogen levels and/or activity are believed to represent the key events for TGCT development and progression. Furthermore, recent evidence has suggested a strong genetic component for TGCT. In this study, we analyzed whether a genetic variation in estrogen receptor (ESR) genes and steroid hormone metabolism genes is associated with TGCT. We genotyped for 17 polymorphic markers in 11 genes in 234 TGCT cases and 218 controls: ESR (ESR1 and ESR2); CYP19

TGF-β2 Promotes Oxidative Stress in Human Trabecular Meshwork Cells by Selectively Enhancing NADPH Oxidase 4 Expression.

PURPOSE: The multifunctional profibrotic cytokine TGF-β2 is implicated in the pathophysiology of primary open angle glaucoma (POAG). While the underlying cause of POAG remains unclear, TGF-β2 dependent remodeling of the extracellular matrix (ECM) within the trabecular meshwork (TM) microenvironment is considered an early pathologic consequence associated with impaired aqueous humor (AH) outflow and elevated IOP. Mitochondrial-targeted antioxidants have been recently shown by our group to markedly attenuate TGF-β2 profibrotic responses, strongly implicating oxidative stress as a key facilitator

Elevated Surfactant Protein Levels and Increased Flow of Cerebrospinal Fluid in Cranial Magnetic Resonance Imaging.

Surfactant proteins (SPs) are a multifunctional group of proteins, responsible for the regulation of rheological properties of body fluids, host defense, and cellular waste clearance. Their concentrations are changed in cerebrospinal fluid (CSF) of patients suffering from communicating hydrocephalus. Hydrocephalic conditions are accompanied by altered CSF flow dynamics; however, the association of CSF-SP concentrations and CSF flow has not yet been investigated. Hence, the aim of this study was to evaluate the association between SP concentrations in the CSF and marked CSF flow phenomena at di

The folate cycle enzyme MTHFD2 induces cancer immune evasion through PD-L1 up-regulation.

Metabolic enzymes and metabolites display non-metabolic functions in immune cell signalling that modulate immune attack ability. However, whether and how a tumour's metabolic remodelling contributes to its immune resistance remain to be clarified. Here we perform a functional screen of metabolic genes that rescue tumour cells from effector T cell cytotoxicity, and identify the embryo- and tumour-specific folate cycle enzyme methylenetetrahydrofolate dehydrogenase 2 (MTHFD2). Mechanistically, MTHFD2 promotes basal and IFN-γ-stimulated PD-L1 expression, which is necessary for tumourigenesis in v

Dose-dependent effects of locally produced microbial phytase on caecal microbiota, hepatic insulin-like growth factor 1 and growth hormone receptor expression, carcass traits, and immune responses in broiler chickens.

BACKGROUND AND AIM: Microbial phytase is extensively used in poultry nutrition to improve phosphorus utilization and reduce the anti-nutritional effects of phytic acid. Beyond nutrient digestibility, phytase may influence intestinal microbiota, immune responses, and growth-related molecular pathways in broiler chickens. However, limited information is available regarding the integrated effects of locally produced microbial phytase on caecal microbial populations, hepatic growth-related gene expression, carcass characteristics, and humoral immunity under the same experimental conditions. Theref

S-RBD-modified and miR-486-5p-engineered exosomes derived from mesenchymal stem cells suppress ferroptosis and alleviate radiation-induced lung injury and long-term pulmonary fibrosis.

BACKGROUND: Radiation-induced lung injury (RILI) is associated with alveolar epithelial cell death and secondary fibrosis in injured lung. Mesenchymal stem cell (MSC)-derived exosomes have regenerative effect against lung injury and the potential to intervene of RILI. However, their intervention efficacy is limited because they lack lung targeting characters and do not carry sufficient specific effectors. SARS-CoV-2 spike glycoprotein (SARS-CoV-2-S-RBD) binds angiotensin-converting enzyme 2 (ACE2) receptor and mediates interaction with host cells. MiR-486-5p is a multifunctional miRNA with ang

Characterization of the enzymatic domains in the modular polyketide synthase involved in rifamycin B biosynthesis by Amycolatopsis mediterranei.

Five clustered polyketide synthase (PKS) genes, rifA-rifE, involved in rifamycin (Rf) biosynthesis in Amycolatopsis mediterranei S699 have been cloned and sequenced (August, P.R. et al., 1998. Chem. Biol. 5, 69-79). The five multifunctional polypeptides constitute a type I modular PKS that contains ten modules, each responsible for a specific round of polyketide chain elongation. Sequence comparisons of the Rf PKS proteins with other prokaryotic modular PKSs elucidated the regions that have an important role in enzyme activity and specificity. The beta-ketoacyl:acyl carrier protein synthase (K

[Recent advances on bioaffinity fishing technology for discovery of active components from natural products].

Natural products have consistently served as an invaluable source for novel drug development， and the efficient and targeted screening of bioactive constituents from these complex mixtures is crucial for advancing drug discovery. Bioaffinity fishing techniques exploit the highly specific interactions between ligands and their biological targets-such as antigen-antibody， enzyme-substrate， and hormone-receptor interactions-to simultaneously separate and identify active compounds from complex natural product extracts. When coupled with liquid chromatography-mass spectrometry， bioaffinity fishing

Mast cell activation and its relation to proinflammatory cytokine production in the rheumatoid lesion.

INTRODUCTION: Increased numbers of mast cells (MCs) are found in the synovial tissues and fluids of patients with rheumatoid arthritis (RA), and at sites of cartilage erosion. MC activation has been reported for a significant proportion of rheumatoid specimens. Because the MC contains potent mediators, including histamine, heparin, proteinases, leukotrienes and multifunctional cytokines, its potential contributions to the processes of inflammation and matrix degradation have recently become evident. Proinflammatory cytokines are important mediators of inflammation, immunity, proteolysis, cell

Novel Strategies for Tumor Treatment: Harnessing ROS-Inducing Active Ingredients from Traditional Chinese Medicine Through Multifunctional Nanoformulations.

Reactive oxygen species (ROS) encompass a diverse group of chemically reactive molecules or ions distinguished by their substantial oxidative potential. Empirical studies have shown that the targeted administration of high toxic concentrations of ROS can effectively induce tumor cell death in various types. Numerous bioactive ingredients derived from traditional Chinese medicine (TCM), recognized for their ROS-inducing properties, have demonstrated significant anti-tumor activity. Nonetheless, their clinical application has been hindered by challenges such as low solubility, limited bioavailab

"Smart" drug delivery: A window to future of translational medicine.

Chemotherapy is the mainstay of cancer treatment today. Chemotherapeutic drugs are non-selective and can harm both cancer and healthy cells, causing a variety of adverse effects such as lack of specificity, cytotoxicity, short half-life, poor solubility, multidrug resistance, and acquiring cancer stem-like characteristics. There is a paradigm shift in drug delivery systems (DDS) with the advent of smarter ways of targeted cancer treatment. Smart Drug Delivery Systems (SDDSs) are stimuli responsive and can be modified in chemical structure in response to light, pH, redox, magnetic fields, and e

Research advances in peptide‒drug conjugates.

Peptide‒drug conjugates (PDCs) are drug delivery systems consisting of a drug covalently coupled to a multifunctional peptide via a cleavable linker. As an emerging prodrug strategy, PDCs not only preserve the function and bioactivity of the peptides but also release the drugs responsively with the cleavable property of the linkers. Given the ability to significantly improve the circulation stability and targeting of drugs in vivo and reduce the toxic side effects of drugs, PDCs have already been extensively applied in drug delivery. Herein, we review the types and mechanisms of peptides, link

Current Status and Perspectives of Protease Inhibitors and Their Combination with Nanosized Drug Delivery Systems for Targeted Cancer Therapy.

In cancer treatments, many natural and synthetic products have been examined; among them, protease inhibitors are promising candidates for anti-cancer agents. Since dysregulated proteolytic activities can contribute to tumor development and metastasis, antagonization of proteases with tailored inhibitors is an encouraging approach. Although adverse effects of early designs of these inhibitors disappeared after the introduction of next-generation agents, most of the proposed inhibitors did not pass the early stages of clinical trials due to their nonspecific toxicity and lack of pharmacological

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