Search Results (2,223)

Background: Chronic Kidney Disease (CKD) is a major global health issue, with diabetes being its primary cause and cardiovascular disease contributing significantly to patient mortality. Recently, two classes of medications—sodium–glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs)—have shown promise in protecting both kidney and heart health beyond their effects on blood sugar control. Methods: We conducted a narrative review summarizing the findings of different clinical trials and mechanistic studies evaluating the effect of SGLT2i and GLP-1 RAs on kidney function, cardiovascular outcomes, and overall disease progression in patients with CKD and DKD. Results: SGLT2i significantly mitigate kidney injury by restoring tubuloglomerular feedback, reducing intraglomerular hypertension, and attenuating inflammation, fibrosis, and oxidative stress. GLP-1 RAs complement these effects by enhancing endothelial function, promoting weight and blood pressure control, and exerting direct anti-inflammatory and anti-fibrotic actions on renal tissues. Landmark trials—CREDENCE, DAPA-CKD, and EMPA-KIDNEY—demonstrate that SGLT2i reduce the risk of kidney failure and renal or cardiovascular death by 25–40% in both diabetic and non-diabetic CKD populations. Likewise, trials such as LEADER, SUSTAIN, and AWARD-7 confirm that GLP-1 RAs slow renal function decline and improve cardiovascular outcomes. Early evidence suggests that using both drugs together may offer even greater benefits through multiple mechanisms. Conclusions: SGLT2i and GLP-1 RAs have redefined the therapeutic landscape of CKD by offering organ-protective benefits that extend beyond glycemic control. Whether used individually or in combination, these agents represent a paradigm shift toward integrated cardiorenal-metabolic care. A deeper understanding of their mechanisms and clinical utility in both diabetic and non-diabetic populations can inform evidence-based strategies to slow disease progression, reduce cardiovascular risk, and improve long-term patient outcomes in CKD. Full article

Parkinson’s disease (PD), a progressive neurodegenerative disorder, imposes growing clinical and socioeconomic burdens worldwide. Despite landmark discoveries in dopamine biology and α-synuclein pathology, translating mechanistic insights into effective, personalized interventions remains elusive. Recent advances in molecular profiling, neuroimaging, and computational modeling have broadened the understanding of PD as a multifactorial systems disorder rather than a purely dopaminergic condition. However, critical gaps persist in diagnostic precision, biomarker standardization, and the translation of bench side findings into clinically meaningful therapies. This review critically examines the current landscape of PD research, identifying conceptual blind spots and methodological shortfalls across pathophysiology, clinical evaluation, trial design, and translational readiness. By synthesizing evidence from molecular neuroscience, data science, and global health, the review proposes strategic directions to recalibrate the research agenda toward precision neurology. Here I highlight the urgent need for interdisciplinary, globally inclusive, and biomarker-driven frameworks to overcome the fragmented progression of PD research. Grounded in the Accelerating Medicines Partnership-Parkinson’s Disease (AMP-PD) and the Parkinson’s Progression Markers Initiative (PPMI), this review maps shared biomarkers, open data, and patient-driven tools to faster personalized treatment. In doing so, it offers actionable insights for researchers, clinicians, and policymakers working at the intersection of biology, technology, and healthcare delivery. As the field pivots from symptomatic relief to disease modification, the road forward must be cohesive, collaborative, and rigorously translational, ensuring that laboratory discoveries systematically progress to clinical application. Full article

The recent discovery of TIGR-Tas (Tandem Interspaced Guide RNA–Targeting Systems) marks a major advance in the field of genome editing, introducing a new class of compact, programmable DNA-targeting systems that function independently of traditional CRISPR-Cas pathways. TIGR-Tas effectors use a novel dual-spacer guide RNA (tigRNA) to recognize both strands of target DNA without requiring a protospacer adjacent motif (PAM). These Tas proteins introduce double-stranded DNA cuts with characteristic 8-nucleotide 3′ overhangs and are significantly smaller than Cas9, offering delivery advantages for in vivo editing. Structural analyses reveal homology to box C/D snoRNP proteins, suggesting a previously unrecognized evolutionary lineage of RNA-guided nucleases. This review positions TIGR-Tas at the forefront of a new wave of RNA-programmable genome-editing technologies. In parallel, I provide comparative insight into the diverse and increasingly modular CRISPR-Cas systems, including Cas9, Cas12, Cas13, and emerging effectors like Cas3, Cas10, CasΦ, and Cas14. While the CRISPR-Cas universe has revolutionized molecular biology, TIGR-Tas systems open a complementary and potentially more versatile path for programmable genome manipulation. I discuss mechanistic distinctions, evolutionary implications, and potential applications in human cells, synthetic biology, and therapeutic genome engineering. Full article

Segregative phase separation technology demonstrates substantial potential for precise molecular fractionation in food and biomaterial applications. The investigation elucidates the causal relationship between viscosity variations and phase separation dynamics, which govern molecular fractionation in GA/HPMC composite systems. By conducting a comparative analysis of two GA subtypes (CGA and SGA) and three HPMC grades with controlled viscosity gradients, we utilized gel permeation chromatography-multi-angle laser light scattering (GPC-MALLS) coupled with rheological characterization to elucidate the critical relationship between continuous phase viscosity and fractionation efficiency. Notably, increasing HPMC viscosity significantly intensified phase separation, resulting in selective enrichment of arabinogalactan-protein complexes: from 6.3% to 8.5% in CGA/HPMC systems and from 27.3% to 36.5% in SGA/HPMC systems. Further mechanistic investigation revealed that elevated HPMC viscosity enhances thermodynamic incompatibility while slowing interfacial mass transfer, synergistically driving component redistribution. These findings establish a quantitative viscosity–fractionation relationship, offering theoretical insights for optimizing GA/HPMC systems in emulsion stabilization, microencapsulation, and functional biopolymer purification via viscosity-mediated phase engineering. Full article

This study systematically investigated the corrosion evolution and protective mechanisms of X80 pipeline steel in Xinjiang’s saline soil environments under freeze–thaw cycling conditions. Combining regional soil characterization with laboratory-constructed corrosion systems, we employed electrochemical impedance spectroscopy, potentiodynamic polarization, and surface analytical techniques to quantify temporal–spatial corrosion behavior across 30 freeze–thaw cycles. Experimental results revealed a distinctive corrosion resistance pattern: initial improvement (cycles 1–10) attributed to protective oxide layer formation, followed by accelerated degradation (cycles 10–30) due to microcrack propagation and chloride accumulation. Synchrotron X-ray diffraction analyses identified sulfate–chloride ion synergism as the primary driver of localized corrosion disparities in heterogeneous soil matrices. A comparative evaluation of asphalt-coated specimens demonstrated a 62%–89% corrosion rate reduction, with effectiveness directly correlating with coating integrity and thickness (200–500 μm range). Molecular dynamics simulations using Materials Studio revealed atomic-scale ion transport dynamics at coating–substrate interfaces, showing preferential Cl⁻ permeation through coating defects. These multiscale findings establish quantitative relationships between environmental stressors, coating parameters, and corrosion kinetics, providing a mechanistic framework for optimizing protective coatings in cold-region pipeline applications. Full article

Background: Rehmannia glutinosa, a traditional Chinese herb, is commonly used to treat vascular-related disorders. Sepsis-associated vascular endothelial dysfunction is closely associated with mitochondrial damage. This study investigated the protective effects of secondary metabolites from R. glutinosa against LPS-induced mitochondrial dysfunction in endothelial cells, providing potential therapeutic insights into sepsis-related vascular complications. Methods: Phytochemical profiling of fresh R. glutinosa roots was conducted, and the structures of new secondary metabolites (1 and 2) were elucidated through comprehensive spectroscopic analysis and ECD calculations. UPLC-Q-TOF-MS/MS characterized phenylethanoid glycosides. Mitochondrial function was assessed by measuring the membrane potential, ROS levels, and TOM20/DRP1 expression in LPS-injured HUVECs. Results: Two novel eremophilane-type sesquiterpenes, remophilanetriols J (1) and K (2), along with five known phenylethanoid glycosides (3–7), were isolated from the fresh roots of R. glutinosa. UPLC-Q-TOF-MS/MS analysis revealed unique fragmentation pathways for phenylethanoid glycosides (3–7). In LPS-injured HUVECs, all compounds collectively restored the mitochondrial membrane potential, attenuated ROS accumulation, and modulated TOM20/DRP1 expression. In particular, remophilanetriol K (2) exhibited potent protective effects at a low concentration (1.5625 μM). Conclusions: This study identifies R. glutinosa metabolites as potential therapeutics for sepsis-associated vascular dysfunction by preserving mitochondrial homeostasis. This study provides a mechanistic basis for the traditional use of R. glutinosa and offers valuable insights into the development of novel therapeutics targeting mitochondrial dysfunction in sepsis. Full article

Background/Objectives: Banhasasim-tang (BHSST) is a traditional herbal formula commonly used to treat gastrointestinal (GI) disorders and has been considered a potential therapeutic option for irritable bowel syndrome (IBS). This study aimed to explore the molecular targets and underlying mechanisms of BHSST in IBS using a combination of network pharmacology, molecular docking, molecular dynamics simulations, and in vivo validation. Methods: Active compounds in BHSST were screened based on drug-likeness and oral bioavailability. Potential targets were predicted using ChEMBL, and IBS-related targets were obtained from GeneCards and DisGeNET. A compound–target–disease network was constructed and analyzed via Gene Ontology and KEGG pathway enrichment. Compound–target interactions were further assessed using molecular docking and molecular dynamics simulations. The in vivo effects of eudesm-4(14)-en-11-ol, elemol, and BHSST were evaluated in a zymosan-induced IBS mouse model. Results: Twelve BHSST-related targets were associated with IBS, with enrichment analysis identifying TNF signaling and apoptosis as key pathways. In silico simulations suggested stable binding of eudesm-4(14)-en-11-ol to TNF-α and kanzonol T to PIK3CD, whereas elemol showed weak interaction with PRKCD. In vivo, eudesm-4(14)-en-11-ol improved colon length, weight, stool consistency, TNF-α levels, and pain-related behaviors—effects comparable to those of BHSST. Elemol, however, showed no therapeutic benefit. Conclusions: These findings provide preliminary mechanistic insight into the anti-inflammatory potential of BHSST in IBS. The integrated in silico and in vivo approaches support the contribution of specific components, such as eudesm-4(14)-en-11-ol, to its observed effects, warranting further investigation. Full article

Trichomes are specialized epidermal structures that protect plants from environmental stresses, regulated by transcription factors integrating hormonal and environmental cues. This study investigates the roles of two C2H2 zinc finger proteins, GIS2 and ZFP8, in regulating trichome patterning in Arabidopsis thaliana. Using dexamethasone-inducible overexpression lines, transcriptomic profiling, and chromatin immunoprecipitation, we identified 142 GIS2- and 138 ZFP8-associated candidate genes involved in sterol metabolism, senescence, and stress responses. GIS2 positively and directly regulated the expression of SQE5, linked to sterol biosynthesis and drought tolerance, and repressed SEN1, a senescence marker associated with abscisic acid and phosphate signaling. ZFP8 modulated stress-related target genes, including PR-4 and SPL15, with partial functional overlap between GIS family members. Spatially, GIS2 functions in inflorescence trichomes via integrating gibberellin-cytokinin pathways, while ZFP8 influences leaf trichomes through cytokinin and abscisic acid signal. Gibberellin treatment stabilized GIS2 protein and induced SQE5 expression, whereas SEN1 repression was gibberellin-independent. Chromatin immunoprecipitation and DEX-CHX experiment confirmed GIS2 binding to SQE5 and SEN1 promoters at conserved C2H2 motifs. These findings highlight hormone-mediated transcriptional regulation of trichome development by GIS2 and ZFP8, offering mechanistic insight into signal integration. The results provide a foundation for future crop improvement strategies targeting trichome-associated stress resilience. Full article

Cadmium (Cd)-induced pulmonary toxicity is closely associated with ferroptosis, a regulated form of cell death characterized by iron-dependent lipid peroxidation (LPO). Luteolin (Lut) is a natural flavonoid compound that exists in many plants. In this study, we used human bronchial epithelial BEAS-2B cells to explore the impact of ferroptosis in the inhibition of Cd-induced BEAS-2B cells proliferation. BEAS-2B cells were exposed to Cd (5 μM) with/without Lut (10 μM), ferroptosis modulators (Ferrostatin-1 (Fer-1)/Erastin), or nuclear factor erythroid 2-related factor 2 (Nrf2) regulators (tert-butylhydroquinone (TBHQ)/ML385). Viability, iron content, reactive oxygen species (ROS), LPO, mitochondrial membrane potential (MMP), and glutathione peroxidase (GSH-PX) activity were assessed. Exposure to Cd significantly decreased cell viability, increased intracellular iron levels, ROS production, and LPO activity, while simultaneously reducing MMP and GSH-PX activity. Fer-1 mitigated Cd-induced cytotoxicity, but Erastin intensified these effects. Mechanistically, Cd exposure suppressed the Nrf2/Solute Carrier Family 7 Member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway, which plays a crucial role in maintaining redox homeostasis. Activation of Nrf2 using TBHQ mitigated oxidative stress and upregulated the expression of key proteins within this pathway, while inhibition of Nrf2 with ML385 exacerbated cellular damage. Notably, Lut treatment could significantly alleviate Cd-induced cytotoxicity, oxidative stress, and downregulation of Nrf2/SLC7A11/GPX4 proteins. These findings demonstrate that ferroptosis is a critical mechanism underlying Cd-mediated lung epithelial injury and identify Lut as a promising therapeutic candidate via its activation of Nrf2-driven antioxidant defense mechanisms. This study provides novel insights into molecular targets for the prevention and treatment of Cd-associated pulmonary disorders. Full article

The brown planthopper (BPH), Nilaparvata lugens, is the most destructive insect pest of rice. BPH infestations severely threaten rice yield worldwide. The gustatory receptor NlGr23 plays a critical role in mediating the repulsive reaction to oxalic acid of the BPH. We integrated transcriptomic and proteomic analyses to determine the metabolic and behavioral consequences of NlGr23 silencing. The RNAi-mediated knockdown of NlGr23 increased body weight and honeydew production, indicating enhanced feeding activity. The results of multiomics profiling revealed disrupted lipid homeostasis, identifying 187 differentially expressed genes and 150 differentially expressed proteins. These genes were enriched in pathways including glycerophospholipid metabolism, fatty acid biosynthesis, and AMPK signaling. The results of biochemical assays showed that NlGr23 silencing elevated triacylglycerol levels by 68.83%, and reduced glycerol and free fatty acid levels, suggesting impaired lipolysis. The NlGr23 loss-of-function mutation mechanistically activates the AMPK pathway, suppresses lipid breakdown, and promotes energy storage. This study established NlGr23 as a key regulator linking chemosensation to metabolic reprogramming, providing new insights into gustatory receptor-mediated energy homeostasis in the BPH. Full article

The zebrafish (Danio rerio) has emerged as a powerful model organism for investigating the mechanisms of post-traumatic stress disorder (PTSD), offering unique advantages in translational relevance, genetic trackability, and cost-effectiveness. As a logical continuation of our recent systematic review, this manuscript critically examines the spectrum of experimental strategies used to model PTSD in zebrafish, with a focus on the comparative efficacy and validity of acute, chronic, and complex stress paradigms. Among these, 14–15-day chronic unpredictable stress (CUS/UCS) protocols are identified as the gold standard, reliably inducing core PTSD-like phenotypes—such as anxiety-like behavior, cortisol dysregulation, and neuroinflammatory gene activation. We discuss the influence of environmental, developmental, and genetic factors on stress responses, and highlight the importance of standardized behavioral and molecular endpoints for model validation. While alternative paradigms—including acute, social, pharmacological, and predator-based models—offer mechanistic insights, their translational relevance remains limited without further refinement. We conclude by outlining future directions for zebrafish-based PTSD research, emphasizing the need for protocol harmonization, integration of multi-modal readouts, and exploration of individual variability to enhance the translational value of this model system. Full article

Studies have shown that sodium-glucose cotransporter type 2 (SGLT2) inhibitors not only help lower blood glucose levels but also offer cardioprotective effects, reduce the progression of heart failure, and may even slow the progression of aortic stenosis. The mechanisms of these beneficial properties are thought to involve multiple pathways, including reducing inflammation, oxidative stress, and improving cellular energy metabolism. Advancing knowledge about the mechanisms of action of these drugs and their effects on the course of the aforementioned diseases has become the subject of intensive clinical and scientific research. This publication aims to provide insight into the role of SGLT2 inhibitors in the context of diabetes mellitus, heart failure and acute coronary syndrome, through clinical analysis, mechanistic insights and comparison of the effects of these drugs. Full article

Plants are constantly exposed to environmental stressors such as drought, salinity, and extreme temperatures, which threaten their growth and productivity. To counter these challenges, they employ complex molecular defense systems, including epigenetic modifications that regulate gene expression without altering the underlying DNA sequence. This review comprehensively examines the emerging roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) as central signaling molecules orchestrating epigenetic changes in response to abiotic stress. In addition, biotic factors such as pathogen infection and microbial interactions are considered for their ability to trigger ROS/RNS generation and epigenetic remodeling. It explores how ROS and RNS influence DNA methylation, histone modifications, and small RNA pathways, thereby modulating chromatin structure and stress-responsive gene expression. Mechanistic insights into redox-mediated regulation of DNA methyltransferases, histone acetyltransferases, and microRNA expression are discussed in the context of plant stress resilience. The review also highlights cutting-edge epigenomic technologies such as whole-genome bisulfite sequencing (WGBS), chromatin immunoprecipitation sequencing (ChIP-seq), and small RNA sequencing, which are enabling precise mapping of stress-induced epigenetic landscapes. By integrating redox biology with epigenetics, this work provides a novel framework for engineering climate-resilient crops through the targeted manipulation of stress-responsive epigenomic signatures. Full article

Metastatic breast cancer (BC) spread underscores the need for novel prognostic biomarkers. This study investigated CCR4-NOT Transcription Complex Subunit 7 (CNOT7) and leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) in BC progression and natural killer (NK) cell resistance. In the current study, 90 female BC patients (46 non-metastatic, 44 metastatic) were analyzed. CNOT7 and LAIR-1 protein levels were measured in serum via ELISA and CNOT7 expression in tissue by immunohistochemistry (IHC). In silico tools explored related pathways. Computational analyses, including in silico bioinformatics and molecular docking, explored gene functions, interactions, and ligand binding to CNOT7 and LAIR-1. CNOT7 serum levels were significantly elevated in metastatic patients (mean 4.710) versus non-metastatic patients (mean 3.229, p < 0.0001). Conversely, LAIR-1 serum levels were significantly lower in metastatic (mean 56.779) versus non-metastatic patients (mean 67.544, p < 0.0001). High CNOT7 was found in 50% (45/90) of cases, correlating with higher tumor grade, hormone receptor negativity, and increased lymph node involvement. Elevated CNOT7 and lower LAIR-1 levels were associated with worse overall survival. Pathway analysis linked CNOT7 to the PI3K/AKT/mTOR pathway. Computational findings elucidated CNOT7′s cellular roles, gene/protein interaction networks for LAIR-1/CNOT7, and distinct ligand binding profiles. High CNOT7 levels are associated with advanced BC stages and poor clinical outcomes, which suggests its utility as a prognostic biomarker. The inverse relationship between CNOT7 and LAIR-1 provides mechanistic insights into BC progression and immune evasion, further supported by in silico investigations. Full article

Prolonged high-dose administration of synthetic glucocorticoids (GCs) leads to limb muscle atrophy and weakness, yet its underlying mechanisms remain incompletely understood. Muscle fibers and muscle satellite cells (MSCs) are essential for skeletal muscle development and associated pathologies. This study demonstrates that dexamethasone (Dex) induced MSC-derived extracellular vesicles (EVs) impair myogenesis in muscle fiber-like cells (MFLCs) via inducible nitric oxide synthase (iNOS) suppression. High-throughput sequencing revealed a marked upregulation of miR-335-5p in MSC-derived EVs following Dex treatment. Mechanistically, EV miR-335-5p targeted MAPK11, leading to iNOS downregulation and subsequent UPS activation in MFLCs, which directly promoted muscle protein degradation. Collectively, our findings identify the EV miR-335-5p/MAPK11/iNOS axis as a critical mediator of GC-induced muscle atrophy, offering novel insights into therapeutic strategies targeting EV-mediated signaling in muscle wasting disorders. Full article