Activation Of Kinase Research Articles (Page 1)

The overexpression or activation of C-terminal Src kinase (CSK) has been recognized as a pivotal factor in the progression of hepatocellular carcinoma (HCC), positioning CSK as a promising therapeutic target. Despite this potential, no CSK-specific inhibitors have been developed for HCC treatment to date. Addressing this gap, our study established a robust virtual screening protocol that integrates energy-based screening techniques with machine learning methodologies. Through this systematic approach, we identified a novel compound, 6, exhibiting potent CSK inhibitory activity, as evidenced by an IC50 value of 675 nM in a homogeneous time-resolved fluorescence (HTRF) bioassay. Notably, this compound demonstrated significant growth inhibition in Huh-7 and Huh-6 cell lines, along with the suppression of clone formation. To elucidate the underlying mechanism, we conducted molecular dynamics simulations, which revealed critical binding interactions between compound 6 and CSK. Specifically, residues Phe333 and Met269 were found to play essential roles in mediating these interactions, providing valuable insights into the compound's mode of action.

Increasing clinical and experimental evidence suggests that the upper and lower jaw exhibit pronounced functional and structural disparities that cannot be explained solely by classical anatomical differences. A central, yet unresolved question is whether periodontal ligament stem cells (PDLSCs) from these distinct regions display site-specific molecular signaling patterns in response to mechanical stress. We propose that PDLSCs derived from maxillary and mandibular regions activate distinct kinase signaling networks upon mechanical stimulation, thereby establishing a jaw-specific mechanobiological fingerprint. PDLSCs were isolated from seven healthy donor teeth and exposed to a static compressive force of 2g/cm2. Kinase activity was profiled using a high-throughput PamChip® peptide arrays that target both protein tyrosine kinases (PTKs) and serine/threonine kinases (STKs). Downstream pathway enrichment analyses were conducted using the Wikipathways, Gene Ontology (GO), KEGG, and Enriched pathways databases. Mechanical stimulation induced distinct kinase activation signatures depending on jaw origin. Maxillary PDLSCs displayed a predominance of STK activation, while mandibular cells showed a relative reduction in PTK signaling. Only two PTKs and four STKs were consistently regulated across both regions, supporting the presence of a region-specific mechanotransduction profile. These findings support our hypothesis that localized differences in kinase signaling may constitute a molecular basis for the clinically observed jaw-specific phenomena, such as heterogeneous orthodontic tooth movement and alveolar bone remodeling. Jaw-dependent mechanotransduction pathways can therefore be considered key determinants of periodontal biology and may provide a basis for follow-up studies aimed at enabling the development of personalized orthodontic and regenerative strategies.

Hypoxia and angiogenesis are crucial hallmarks of cancer that play key roles in the development and progression of colorectal cancer (CRC). However, the transcriptional mechanism underlying hypoxia induced angiogenesis (HIA) remain elusive. This study aimed to explore the regulatory networks, molecular mechanisms, and prognostic value of HIA-related genes. We collected multi-omics data, including chromatin immunoprecipitation sequencing (ChIP-seq), bulk RNA-seq, single cell RNA-seq, spatial transcriptomics, and microarray data from CRC patients and cell lines. Computational methods, including single sample gene set enrichment analysis (ssGSEA), signature-related gene analysis (SRGA), consensus clustering, and others, were utilized to explore the correlation between hypoxia and angiogenesis, identify the HIA-related genes, and establish the risk scoring system based on HIA-related genes. The role of mannose phosphate isomerase (MPI) was validated using quantitative real-time PCR (RT-qPCR), Co-immunoprecipitation (Co-IP), western blot, colony formation, tube formation assay, and subcutaneous xenograft tumor models in vitro and in vivo. We identified 12 HIA-related genes that are transcriptionally activated by hypoxia-inducible factors (HIFs) and functionally implicated in angiogenesis in CRC. Based on the differentially expressed genes among HIA-related CRC subtypes, we constructed a prognostic scoring system termed HIAscore. Patients with high HIAscore was correlated with poor survival, aggressive phenotype, and immunosuppressive tumor microenvironment. Spatial analysis revealed sequestration regions between epithelial cells with higher HIAscore and T/I/NK cells, hindering their infiltration. Particularly, MPI was found to interact with lactate dehydrogenase A (LDHA), and promote proliferation and angiogenesis of CRC through phosphorylation and activation of Janus kinase 2/signal transducers and activators of transcription 3 (JAK2/STAT3) signaling pathways. This study depicts the transcriptional landscape linking hypoxia and angiogenesis in CRC, and identifies MPI as a novel regulator of this process.

Neuroinflammation plays a central role in a wide spectrum of neurological diseases, driven generally by reactive microglia and astrocytes. Inflammatory stimulation of microglia and astrocytes leads to a metabolic shift from oxidative phosphorylation (OXPHOS) to glycolysis, which is required to support pro-inflammatory effector functions. This metabolic reprogramming is associated with impaired mitochondrial dynamics, including reduced biogenesis, increased fragmentation, and loss of membrane potential. Targeting microglia and astrocyte metabolism may offer a novel therapeutic approach for modulating neuroinflammation and restoring homeostatic immune functions. Here, we examined the potential of 2-Deoxy-D-Glucose (2DG), a glycolysis inhibitor, to attenuate neuroinflammation by restoring mitochondrial dynamics. In BV2 and primary glial cultures, low-dose 2DG reversed LPS-induced metabolic reprogramming, restoring OXPHOS, reducing mitochondrial fragmentation, and enhancing biogenesis. In vivo, it preserved spare respiratory capacity and increased complex-V activity in brain mitochondria from LPS-treated mice without affecting oxidative stress. At a mechanistic level, 2DG restored activation of AMP-activated protein kinase, a master regulator of mitochondrial dynamics. In conjunction with these metabolic effects, 2DG suppressed LPS-induced pro-inflammatory gene expression while enhancing markers associated with the resolution of inflammation and tissue repair. Critically, systemic low-dose 2DG reduced neuroinflammation and restored immune homeostasis in two LPS-induced mouse models, highlighting its therapeutic potential in neurological disorders.

KRASG12D is a common oncogenic driver mutation in diverse cancers, including non-small cell lung cancer, colorectal cancer, and pancreatic cancer. KRASG12D inhibitors have recently progressed into clinical trials but will likely face innate or acquired drug resistance similar to that which has been observed for KRASG12C inhibitors, such as activation of receptor tyrosine kinases, KRAS-independence, and reactivation of RAS-MAPK signaling. This study investigates heterobifunctional small molecule dual inhibitors that simultaneously target both KRASG12D and protein chaperone HSP90 in KRASG12D-mutated cancer cell lines and patient-derived organoids. Our findings reveal that the efficacy of the clinical-stage KRASG12D inhibitor MRTX1133 varies, with notable resistance being observed in some cell line and organoid models. In contrast, KRASG12D-HSP90 dual inhibitors were found to broadly display superior effectiveness in inducing apoptosis, reducing cell viability, and suppressing key downstream signaling pathways such as AKT and ERK1/2 in MRTX1133-resistant models. The rationale for targeting HSP90, which is preferentially activated in cancer cells, alongside KRASG12D, arises from the ability of HSP90 inhibition to destabilize substrate client proteins that are essential for cancer cell survival and have also been implicated in resistance to KRAS inhibitors. This dual inhibitor approach presents a promising new strategy to combat de novo and acquired drug resistance in KRASG12D-mutated cancers and potentially paves the way for improved clinical outcomes by addressing the complex molecular mechanisms underlying cancer cell evolution that enables resistance to conventional inhibitors.

Stem cell adhesion and migration are fundamental processes in tissue regeneration and repair; however, their efficiency in vivo is often limited by the complexity of the microenvironment. Endogenous bioelectrical cues, such as electric fields present during development and wound healing, play a critical role in guiding these cellular behaviors. Piezoelectric biomaterials, which can convert mechanical stimuli into electrical signals, have recently emerged as promising platforms for recapitulating these bioelectric cues without the need for external power sources. In this mini-review, we summarize the recent advances in the use of piezoelectric scaffolds to modulate stem cell adhesion and migration. We highlight the underlying mechanisms, including integrin/focal adhesion kinase activation, calcium signaling, and electrotaxis, which mediate enhanced adhesion, focal adhesion maturation, and directed cell migration. Representative applications in bone, cartilage, nerve, and muscle tissue engineering are discussed, with an emphasis on how piezoelectric scaffolds improve regeneration by providing dynamic and self-sustained electrical stimulation. Finally, we outline the major challenges, such as balancing piezoelectric output with biocompatibility, controlling in vivo stimulation parameters, and elucidating precise sensing mechanisms, and propose future directions for clinical translation. By integrating insights from materials science, mechanobiology, and regenerative medicine, piezoelectric biomaterials hold strong potential as next-generation smart scaffolds for orchestrating stem cell behavior and accelerating functional tissue repair.

The extracellular matrix is dynamic in composition and performs protective, trophic, supportive, and regulatory functions. Degradation of individual extracellular matrix components will lead to metabolic disorders of the entire muscle tissue. The progression of metabolic syndrome is accompanied by changes in the quantitative and qualitative composition of extracellular matrix. Activation of p38 mitogen-activated protein kinase also leads to increased production of extracellular matrix and changes its qualitative composition. Currently, the role of p38 mitogen-activated protein kinase activation during metabolic syndrome in the processes of skeletal muscle extracellular matrix degradation is not well understood. The aim of this work was to determine the effect of the administration of a specific inhibitor of p38 mitogen-activated protein kinase (SB203580) on the content of glycosaminoglycans, their individual fractions, the concentration of free L-hydroxyproline and sialic acids in the biceps femoris muscle of rats under conditions of metabolic syndrome modeling. The study was conducted on 24 sexually mature male Wistar rats weighing 200-260 g. The animals were randomly divided into 4 groups of 6 animals each. Group I – control. Group II – MetS group. MetS was reproduced by adding 20% fructose solution to the standard vivarium diet as the sole source of drinking water for 60 days. Group III – group of SB203580 administration at a dose of 2 mg/kg intraperitoneally once every 3 days for 60 days. Group IV – the group of combined effects of SB203580 administration and MetS reproduction. Animals were removed from the experiment under thiopental anesthesia by taking blood from the right ventricle of the heart. The object of the study was a 10% homogenate of rat biceps muscle, in which the total content of glycosaminoglycans, the content of individual glycosaminoglycans fractions, free L-hydroxyproline and sialic acids were studied. The combination of p38 MAPK blockade by administration of SB203580 and MetS modeling reduces the total glycosaminoglycans content in the biceps femoris muscle of rats by 22.0% compared to the MetS group. The content of the heparin-heparan fraction under these conditions increases by 24.4%, and the concentration of the chondroitin and keratan-dermatan fractions of glycosaminoglycans decreases by 28.8% and 38.6%, respectively, when compared with the indicators of the MetS group. The content of free L-hydroxyproline and sialic acids decreases by 19.2% and 15.8%, respectively, compared to the MetS group. Activation of p38 mitogen-activated protein kinase in the biceps femoris muscle of rats under conditions of metabolic syndrome prevents the degradation of proteoglycans and glycoproteins, reduces the intensity of collagen fiber breakdown, and promotes the restoration of the fractional composition of glycosaminoglycans. This work is a fragment of the initiative SRW No. 0124U000092 “High- and low-intensity phenotypes of systemic inflammatory response: molecular mechanisms and new medical technologies for their prevention and correction.”

Introduction: The Hippo pathway is an intracellular pathway that negatively regulates cell survival. Experimental evidence demonstrated that the activation of mammalian sterile 20-like kinase 1 (MST1), the core component of the Hippo Pathway, leads to dilated cardiomyopathy and heart failure. However, the role of MST1 in endothelial dysfunction caused by cardiovascular risk factors has not yet been investigated. Hypothesis: We tested the hypothesis that MST1 activation in response to metabolic stress may exert detrimental endothelial effects. Methods: We studied MST1 activity in endothelial cells (HUVECs) treated with metabolic stress (high glucose, HG; oxidized low-density lipoproteins, oxLDL). Adenoviruses overexpressing either a wild type (AD-MST1) or a dominant negative form of MST1 (AD-DN-MST1) were used for overexpression and inhibition studies, respectively. Angiogenesis, apoptosis, oxidative stress, nitric oxide (NO), RAC1/NOX2 activity were assessed. We studied endothelial function in mesenteric arteries isolated from mice with endothelial-specific deletion of MST1 (MST1eKO) subjected to HG or oxLDL treatment. We also analyzed MST1 levels in peripheral blood mononuclear cells (PBMCs) from patients with coronary artery disease (CAD). Results: Endogenous levels of MST1 increase in response to HG or ox-LDL (p<0.05). Forced overexpression of MST1 by AD-MST1 induces apoptosis (p<0.001), impairs angiogenesis (p<0.001) and NO metabolism (p<0.001) in HUVECs. Inhibition of MST1 rescues the deleterious endothelial effects of both HG and oxLDL. Mechanistically, we demonstrated that AD-MST1 promotes RAC1/NOX2-induced oxidative stress (p<0.01). Pharmacological or genetic RAC1/NOX2 inhibition rescues endothelial dysfunction induced by MST1 overexpression. We also observed that endothelial-dependent relaxation, oxidative stress and NO production are preserved in MST1eKO mice undergoing metabolic stress (p<0.001). Finally, we found that MST1, NOX2 and RAC1 levels were significantly higher in patients with CAD compared to those without, and MST1 correlated with CAD severity, evaluated by the SYNTAX Score (rho=0.209, p=0.028). Conclusion: This study provides novel evidence that MST1 activation plays a pivotal role in endothelial/vascular dysfunction induced by cardiovascular risk factors. Inhibition of MST1 may be considered a potential strategy for the prevention of cardiovascular diseases.

Background: Phosphoglucomutase 1 (PGM1) is essential for converting glucose 1-phosphate to glucose 6-phosphate, playing a pivotal role in glycolysis, glycogen metabolism, and glycosylation. PGM1 deficiency can result in a variety of clinical symptoms, including congenital malformations, hypoglycemia, hormonal imbalances, hepatopathy, and notably, severe Dilated Cardiomyopathy (DCM) and myopathy. Although oral D-galactose supplementation has shown some improvement in selected clinical abnormalities for PGM1-deficient patients, it has not been effective in alleviating severe DCM or associated myopathy. The pathophysiology of DCM and myopathy in PGM1-deficiency remains largely unknown thereby impeding the development of effective therapeutic interventions. This study aims to investigate the unresolved molecular mechanisms underlying the DCM phenotype in PGM1 deficiency. Hypothesis: We hypothesize that impaired glucose metabolism due to PGM1-deficiency leads to early mitochondrial dysfunction characterized by disrupted TCA cycle and reduced substrate utilization. Methods and Results: To delineate the pathophysiology of cardiac dysfunctions in PGM1-deficiency, we previously developed a cardiomyocyte-specific Pgm1 conditional knockout ( Pgm1 - i cKO) mouse model. Four weeks post Pgm1 deletion, we observed altered steady-state levels of TCA cycle metabolites, including reduced succinate, fumarate, and aspartate. Using in vivo stable isotope tracing and mitochondrial functional assessments, we showed a compensatory increase in 13C labeling of TCA cycle intermediates 2 weeks after Pgm1 deletion, followed by a reduced malate and aspartate levels after 4 weeks. These defects were associated with a progressive decline in mitochondrial utilization of pyruvate, palmitoyl carnitine and alpha-ketoglutarate, but not succinate in Pgm1-i cKO hearts. The results of our study also revealed disruption of mitochondrial respiration as early as four weeks following Pgm1 -deletion. Furthermore, as early as four weeks after Pgm1 deletion, the Pgm1-i cKO heart exhibited aberrant activation of protein kinase B (AKT) and mammalian target of rapamycin (mTOR) signaling. We postulate that disruption of glucose metabolism leads to cellular energy deficiency and increased metabolic stress, resulting in compensatory signaling pathways. Conclusions: Our findings reveal metabolic dysregulation in the Pgm1-deficient heart during the development of dilated cardiomyopathy.

Myocardial infarction(MI) is a leading cause of heart failure and death. Beyond the initial ischemic insult, persistent inflammation and metabolic dysfunction critically impair recovery from the MI, highlighting the need to uncover molecular pathways that drive these maladaptive responses. Transcriptomic profiling of human and murine infarcted hearts revealed upregulation of Dedicator of Cytokinesis 2 (DOCK2), a Rac-specific GEF, linked to immune cell trafficking and inflammation, prompting investigation into its pathological role in MI. Using a murine model of MI, we found that genetic ablation of DOCK2 (DOCK2-/-) conferred significant and sustained cardioprotection. Transthoracic echocardiography revealed that DOCK2-/- mice exhibited significantly higher left ventricular ejection fraction and improved fractional shortening, along with reduced left ventricular end systolic diameter and end systolic volume, indicating preserved systolic function and attenuation of adverse ventricular remodeling. TUNEL staining demonstrated significantly reduced cardiomyocyte apoptosis in DOCK2-/- hearts, while picrosirius red staining at 28 days revealed a marked reduction in myocardial fibrosis. Mechanistically, DOCK2 deletion enhanced myocardial energetic efficiency, as indicated by increased ATP production and activation of the AMP-activated protein kinase (AMPK)–acetyl-CoA carboxylase (ACC)–carnitine palmitoyltransferase 1 (CPT1) regulatory axis, consistent with a metabolic shift away from fatty acid oxidation toward glycolysis, a pathway that yields more ATP per oxygen molecule under ischemic conditions. This reprogramming was accompanied by the upregulation of key antioxidant defenses. Transcriptomic profiling further revealed suppression of inflammatory gene signatures alongside enhanced glycolytic and angiogenic pathways. These metabolic and transcriptional changes converged to promote vascular regeneration, as evidenced by increased proliferation of CD31 endothelial cells, elevated capillary density in the infarct border zone, and enhanced microvessel formation in Matrigel plug assays. DOCK2 deletion attenuated nuclear factor kappa B activation, reduced pro-inflammatory cytokine expression, and limited infiltration of neutrophils and macrophages. Together, these findings position DOCK2 as a central regulator of the inflammatory–metabolic axis in myocardial infarction, highlighting DOCK2 as a compelling therapeutic target for cardiac repair.

Background. The investigation of allelic variability in the FGB gene (rs1800790), combined with a comprehensive analysis of its proteomic activity and the structure of key molecular pathways, represents a critical approach for advancing the molecular epidemiology of COVID‑19, particularly in the context of risk modeling, treatment, and prevention of severe complications. Objective. To determine the features of the allelic state, proteomic activity and major superpathways of FGB gene (rs1800790) interactions in COVID-19 patients. Participants and methods. 197 patients with SARS-CoV2 infection and COVID-associated community-acquired pneumonia (COVID-19) were examined. The FGB gene (rs1800790) polymorphism genotyping performed by Real-Time PCR based method (CFX96 Touch, BioRad, Microsoft, USA) using specific complementary TaqMan probes (VIC and FAM). FGB gene-gene interaction, functional relationships and proteomic activities were constructed by the “STRING Interaction Network” program using opened Human database “GeneCard”. Results. The FGB gene (rs1800790) allelic distribution in surveyed residents of central Ukraine is most similar to certain European (British people of England and Scotland, residents of Northern and Western Europe) and some East Asian populations. The closest FGB gene-gene interactions are established for genes encoding various proteins that provide different hemocoagulation pathways: F13B, F2, CALR, LPA, and ALDH2. The 5 major superpathways of FGB (rs1800790) gene interaction were identified (GeneCard): signal transduction pathway (renin-angiotensin system) through paradoxical or moderate activation of BRAF, MAP2K and MAPK kinases (interaction strength F=0.91); through the cascade of Toll-like receptors (TLR7/8, TLR4) (F=0.83-0.85); signaling pathways of hemostatic system pathology (F=0.50-0.59) and immune system (F=0.38-0.44); reaction to increased platelet cytosolic Ca2+- their activation, signaling and aggregation (F=0.51). Conclusions. This study reveals some features of the FGB gene (rs1800790) allelic state, its proteomic activity, and the major superpathways of FGB gene-gene interactions, which determines its role in the thrombotic complications formation or coagulopathy in COVID-19 patients.

General stress-response of vertebrates to fluctuations of environmental conditions are conservative, and includes rapid release of neurotransmitters into blood. In amphibians, physiological effects of catecholamines (CA) on red blood cell (RBC) functions have been studied fragmentally despite the presence of adrenoreceptors on RBC membranes. In the present work the influence of epinephrine on RBC stability to hypoosmotic stress as well as intracellular reactive oxygen species (ROS) production levels and mitochondrial membrane potential have been studied on RBCs of marsh frogs Pelophylax ridibundus (in vitro). Additionally, the involvement of cAMP/Adenylate cyclase/protein kinase A (cAMP/AC/PKA) pathway in regulation of these processes have been evaluated. We showed that increase of RBC stability to hypoosmotic shock is mediated by activation of β-adrenoreceptors and independent from cAMP/PKA pathway. Lysis of RBCs treated with epinephrine occurred at lower osmolarities compared to non-stimulated cells and changes in RBC membrane properties were rapid (after 5 min incubation) and stable (following 60 min incubation). Addition of epinephrine to RBC suspensions or activation of cAMP/AC/PKA pathway (forskolin and cBIMPS) was associated with a reduction of ROS concentration in cytoplasm and enhanced mitochondrial membrane potential. The results of the present work provide novel insights into the cellular mechanisms of adrenergic RBC stimulation and pathways involved into signal transduction within the context of environmental stress. Stimulating effects of epinephrine on RBC membrane stability and mitochondrial activity is probably important for adaptation of frogs to unfavorable habitat conditions, seasonal activity and other stress factors.

c-Jun N-terminal kinase (JNK) activation has been shown to play a crucial role in the development of various types of cancer. IQ-1S is a JNK inhibitor based on the 11H-indeno[1,2-b]quinoxalin-11-one scaffold. The aim of this study was to investigate the antiproliferative effect of IQ-1S on MCF7 breast cancer cells in both two-dimensional (2D) monolayer and 3D multicellular spheroid test-systems. Non-adherent, non-tethered 3D objects were generated from single MCF7 breast cancer cells in a hydrogel array. IQ-1S was added directly to the cells seeded in the hydrogel array. MCF7 spheroids were grown for 7 days. Spheroid size, growth rate, and morphology were assessed at single-object resolution. The study revealed significant differences in the size, morphology and some vital characteristics of breast cancer 3D objects when treated with the JNK inhibitor compared to vehicle (dimethyl sulfoxide)-treated controls. Spheroids treated with IQ-1S (20 μM) after 7 days are significantly smaller than the control objects. This difference was not attributable to variations in the initial number of cells seeding for the spheroid formation. Morphological examinations showed that 3D multicellular objects grown from IQ-1S-treated cells lose their regular, round morphology, in contrast to control spheroids. Furthermore, cell proliferation measured using a label-free impedance monitoring platform was reduced in monolayer (2D) culture of MCF7 cells in the presence of 10 and 20 μM IQ-1S. MCF7 cells in 2D culture treated with IQ-1S (20 μM) for 72 and 153 h showed a significant increase in apoptosis as assessed by flow cytometry with annexin V/propidium iodide staining. An in silico evaluation showed that compound IQ-1S has generally satisfactory ADME (absorption, distribution, metabolism, and excretion) properties and high bioavailability. We conclude that IQ-1S effectively inhibits the growth of 3D spheroids and MCF7 cells in 2D culture and has a high potential for use in preclinical tumor growth models.

Hashimoto’s thyroiditis (HT) is the most common autoimmune thyroid disorder, characterized by progressive lymphocytic infiltration, follicular destruction, tissue fibrosis, and an elevated risk of thyroid carcinoma. While the precise mechanisms underlying HT remain incompletely defined, emerging evidence implicates dysregulated sphingolipid (SPL) metabolism, particularly the sphingosine-1-phosphate (S1P) signaling axis, as a central contributor to disease pathogenesis. S1P, a bioactive lipid mediator, integrates metabolic and immunological cues to regulate immune cell trafficking, cytokine production, apoptosis, and fibroblast activation. Aberrant activation of the sphingosine kinase (SPHK)/sphingosine-1-phosphate (S1P)/S1P receptor (S1PR) pathway has been linked to persistent T helper 1 (Th1) cell recruitment, signal transducer and activator of transcription 3 (STAT3)-mediated immune polarization, epithelial–mesenchymal transition, extracellular matrix remodeling, and the establishment of a chronic inflammatory and fibrotic microenvironment. Moreover, S1P signaling may foster a pro-tumorigenic niche, providing a mechanistic explanation for the strong epidemiological association between HT and papillary thyroid carcinoma. This review summarizes current insights into the role of SPL metabolism in HT, highlighting its potential as a mechanistic link between autoimmunity, fibrosis, and carcinogenesis.

Two tail protein-derived capsule depolymerases from phage vB_KpnS_GH-K1 are effective against pneumonia caused by K2 serotype Klebsiella pneumoniae.

Diabetic retinopathy in focus: Update on treatment advances, pharmaceutical approaches, and new technologies.

Spinal p38 MAPK/PGC-1α/SIRT3 signaling pathway mediates remifentanil-induced hyperalgesia in rats via ROS release and NR2B activation.

EPA-enriched phospholipids and DHA-enriched phospholipids prevent dexamethasone-induced skeletal muscle atrophy via regulating protein turnover and mitochondrial quality.

Calcium-dependent Activation of Adenosine Monophosphate-activated Protein Kinase Regulates Sulfane Sulfur Production During Hypoxia in Endothelial Cells

Breast milk lacking anti-human immunodeficiency virus activity promotes exocytosis of HIV from the mother's mammary epithelium and transcytosis of virus via the infant's tonsil and intestinal epithelial cells.