Search Results (12,063)

Non-alcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder that can progress to non-alcoholic steatohepatitis (NASH), in which lipotoxicity, oxidative stress, apoptosis, and impaired autophagy contribute to liver injury. 14-Deoxy-11,12-didehydroandrographolide (deAND), a bioactive diterpenoid from Andrographis paniculata, has shown anti-inflammatory and antioxidant activities, but its role in NASH-associated lipotoxicity remains unclear. This study investigated the protective effects and underlying mechanisms of deAND using palmitic acid (PA)-treated AML12 hepatocytes and a choline-deficient, L-amino acid-defined, high-fat-diet (CDAHFD)-induced mouse model of NASH. In AML12 cells, PA impaired autophagic flux and reduced the expression of the mitophagy-associated proteins PINK1 and Parkin and increased p62, LC3-II, reactive oxygen species production, and apoptotic signaling. deAND treatment restored autophagic flux and increased PINK1 and Parkin expression, enhanced antioxidant defense-related proteins, including HO-1, GCLM, and GPX2, and reduced oxidative stress and apoptosis. The protective effects of deAND were attenuated by autophagy inhibitors, supporting the involvement of autophagy regulation. In CDAHFD-fed mice, deAND reduced hepatic steatosis, inflammation, fibrosis, apoptosis, and autophagy dysregulation. These findings suggest that deAND alleviates lipotoxic liver injury by restoring autophagic homeostasis and reducing oxidative stress. Full article

Background: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss and is strongly driven by oxidative stress and inflammation. This study investigated the protective effects of cynarin against sodium iodate (NaIO₃)-induced retinal pigment epithelium (RPE) injury, focusing on the MAPK and NF-κB signaling pathways. Materials and Methods: Human ARPE-19 cells were exposed to NaIO₃, and cell viability was assessed by the MTT assay. Protein expression of MAPK components (p38, JNK, ERK) and the NF-κB pathway was analyzed by Western blotting, and pro-inflammatory cytokine (IL-1β, IL-6, TNF-α) mRNA expression was measured by RT-qPCR. In vivo, NaIO₃-induced retinal degeneration in C57BL/6 mice was treated with cynarin (3 or 10 mg/kg) for seven days, and retinal changes were evaluated by fundus photography, fluorescein angiography, and OCT. Results: Cynarin preserved ARPE-19 cell viability without cytotoxicity. It significantly attenuated NaIO₃-induced p38 and JNK phosphorylation, IκB degradation, and NF-κB activation while downregulating IL-1β, IL-6, and TNF-α expression. In vivo, cynarin reduced drusen-like lesions, hyperfluorescent abnormalities, and retinal thinning, and dose-dependently suppressed ocular pro-inflammatory cytokines. Conclusions: Cynarin protects against oxidative stress-induced retinal degeneration by suppressing MAPK and NF-κB inflammatory signaling, representing a promising therapeutic candidate for preventing or delaying NaIO₃-induced dry AMD-like retinal injury. Full article

Background: Gastrointestinal (GI) involvement is increasingly recognised in paediatric SARS-CoV-2 infection and multisystem inflammatory syndrome in children (MIS-C), but severe GI bleeding remains rare. Its pathogenesis in this setting is multifactorial: direct viral injury, hyperinflammatory microvascular damage, treatment-related mucosal injury, and coagulopathy may all contribute, and the relative role of each is often difficult to disentangle. Case Presentation: A previously healthy 12-year-old boy underwent appendectomy for perforated appendicitis with peritonitis. On postoperative Day 1, he developed high fever and was found to be SARS-CoV-2 PCR-positive; SARS-CoV-2 IgM and IgG were also positive. He met the positive clinical elements of the CDC 2023 case definition for MIS-C (persistent fever, multisystem involvement—gastrointestinal, hepatic, haematological, and markedly elevated inflammatory markers), although perforated appendicitis with peritonitis is a sufficient alternative explanation and the diagnosis cannot be regarded as secure (see Discussion). Treatment included broad-spectrum antibiotics (meropenem, amikacin, metronidazole), methylprednisolone 2 mg/kg/day, and intravenous immunoglobulin (IVIG) 2 g/kg. On Day 4 in the paediatric intensive care unit (PICU), the patient developed sudden haematemesis with fresh blood through the nasogastric tube and haemodynamic collapse. Coagulation studies revealed prolonged INR (1.6) and reduced prothrombin activity (42%). The patient was stabilised with packed red blood cells, fresh frozen plasma, and intravenous vitamin K. Fibrogastroscopy demonstrated diffuse mucosal bleeding without ulcers or anatomical defects; histology showed mucosal hyperaemia, mixed basal inflammation with intraepithelial lymphocytes, and small erosions. Melena persisted for several days. The child recovered fully and was discharged after 20 days with substantially improved but not fully normalised laboratory values (residual mild anaemia, Hb 110 g/L, and elevated CRP 32.7 mg/L and D-dimer 5.88 mg/L). Conclusions: Severe upper GI bleeding is a rare but life-threatening event in children with severe SARS-CoV-2 infection and MIS-C. In our case, several mechanisms may have acted in combination, although none could be confirmed individually: possible direct viral enterocyte injury via ACE-2 receptors, hyperinflammatory microangiopathy, high-dose corticosteroid-related mucosal injury, possible broad-spectrum antibiotic-associated vitamin K deficiency, and postoperative critical-illness stress. Their relative contributions cannot be determined from a single retrospective case. Bleeding occurred despite continuous PPI prophylaxis, suggesting that PPI cover alone is insufficient when multiple risk factors coexist; the clinical implication is that risk-factor-based (rather than universal) PPI prophylaxis, together with monitoring of vitamin K-dependent coagulation, should be considered in critically ill children receiving high-dose corticosteroids and prolonged broad-spectrum antibiotics. Full article

Vitiligo is a chronic acquired depigmenting disorder characterized by progressive melanocyte loss. Its pathogenesis involves a multifactorial interplay among oxidative stress, impaired melanocyte regeneration, immune-mediated cytotoxicity, and neuroendocrine dysregulation. In recent years, traditional Chinese medicine (TCM)-derived active ingredients have attracted increasing research interest as potential interventions for vitiligo, although most isolated compounds remain at the preclinical stage. This review summarizes pharmacological and natural compounds applied in vitiligo treatment and highlights their regulatory mechanisms on core pathogenic modules. A comprehensive analysis of natural and semisynthetic active ingredients is provided, covering their preclinical and clinical evidence, mechanisms of action, and therapeutic relevance. Multiple ingredients, including baicalein, quercetin, curcumin, paeoniflorin, kaempferol, glycyrrhizin, and epigallocatechin-3-gallate (EGCG), have demonstrated antioxidant, anti-inflammatory, immunomodulatory, and neuroprotective effects that are involved in the pathogenesis of vitiligo. Some TCM-derived interventions, such as Ginkgo biloba L. extract and compound glycyrrhizin, have been evaluated clinically, whereas most isolated active compounds, including baicalein and quercetin, remain at the preclinical stage. Overall, TCM-derived active ingredients represent a promising therapeutic strategy for vitiligo. However, continued translational and clinical research is still required to optimize formulations, dosing regimens, and safety profiles, thereby facilitating their integration into routine clinical practice. Full article

Coronary artery disease is a leading cause of morbidity and mortality in modern medicine. In contrast, surgical myocardial revascularization via coronary artery bypass grafting (CABG) remains the gold standard of treatment for complex multivessel disease. The great saphenous vein remains the most frequently used conduit due to its availability and technical simplicity, but its long-term patency is significantly inferior to that of arterial grafts. The primary pathological process responsible for vein graft failure is intimal hyperplasia, which represents a complex response of the vascular wall to surgical trauma, vein arterialization, inflammation, and hemodynamic stress. This process is characterized by endothelial dysfunction, inflammatory cell activation, proliferation and migration of vascular smooth muscle cells, and extracellular matrix remodeling. Underpinning these alterations are numerous molecular pathways, including NF-κB, MAPK, PI3K/Akt, TGF-β, and mTOR signaling, as well as substantial contributions from oxidative stress, cytokines, growth factors, and microRNAs. Contemporary research indicates that the phenotypic transformation of vascular smooth muscle cells constitutes the central event in the development of intimal hyperplasia. Understanding the cellular and molecular mechanisms underlying this disease’s onset enables the development of novel therapeutic strategies to preserve long-term graft patency. This review paper aims to provide a systematic overview of current knowledge regarding the molecular and cellular mechanisms of intimal hyperplasia development in vein grafts following CABG. Full article

Retinal degeneration is characterized by progressive photoreceptor loss driven by oxidative stress and chronic inflammation, yet effective mutation-independent therapeutic strategies remain limited. Lycium barbarum polysaccharides (LBPs) possess antioxidant and anti-inflammatory activities; however, the structural features responsible for their retinal protective effects remain poorly defined. In this study, crude LBP was fractionated by DEAE-cellulose ion-exchange chromatography, and the most bioactive fraction, LBPF2, was identified using H₂O₂-injured 661W cone photoreceptor-like cells. LBPF2 was subsequently characterized by high-performance anion-exchange chromatography, SEC-MALLS-RI, GC–MS methylation analysis, and one- and two-dimensional NMR spectroscopy, and its protective effects were evaluated in H₂O₂-treated 661W cells and rd10 mice. LBPF2 was identified as a homogeneous glucose-rich polysaccharide with an average molecular weight of approximately 41 kDa and a backbone mainly composed of →4)-α-D-Glcp-(1→ and →4,6)-α-D-Glcp-(1→ residues. LBPF2 reduced oxidative stress, inflammation, and apoptosis in H₂O₂-treated 661W cells, preserved retinal morphology, improved electroretinographic responses and partial retention of rhodopsin immunoreactivity relative to untreated rd10 mice, and restored redox homeostasis in rd10 mice. Pharmacological inhibition of Nrf2 using ML385 attenuated these protective effects, supporting the involvement of Nrf2/HO-1 signaling. Collectively, these findings identify LBPF2 as a structurally characterized neuroprotective polysaccharide that mitigates retinal degeneration through coordinated regulation of oxidative stress and inflammation and highlight its therapeutic potential for retinal degenerative diseases. Full article

Jania rubens (J. rubens), a Mediterranean red seaweed, is rich in bioactive compounds with potential medicinal applications. This study investigates the therapeutic potential of Lebanese J. rubens through in vitro evaluation of its anti-diabetic, anti-coagulant, anti-inflammatory and anti-hemolytic activities. Various extracts were prepared and characterized using GC-MS and HPLC. Biological activities were assessed through α-amylase inhibition assays, effects on prothrombin time and partial thromboplastin time, anti-inflammatory activity and anti-hemolytic activity. Significant α-amylase inhibition was observed with dichloromethane/methanol and lipid extracts, comparable to acarbose. All types of extracts prolonged PT and PTT, with the lipid extract showing the strongest effect at higher concentrations. Additionally, dichloromethane/methanol extracts exhibited potent anti-hemolytic activity. Moreover, all extracts showed strong anti-inflammatory activity, achieving levels of inhibition of heat-induced BSA denaturation comparable to diclofenac. Characterization revealed 11 amino acids in the protein extracts, and significant fatty acids in the lipid profile. The crude extracts contained diverse compounds, including flavonoids, aldehydes, diterpenoids, terpenoids, fatty acids, and sterol esters, which may contribute to the observed biological activities. These results highlight J. rubens as a potential reservoir of bioactive compounds with promising in vitro activities related to diabetes, thrombotic disorders, inflammation, and oxidative stress. Further research is needed to isolate the active compounds, validate their efficacy in vivo, assess safety, and elucidate the underlying mechanisms. Full article

Background: Precision nutrition and nutrigenomics have emerged as promising strategies to personalize dietary interventions according to individual genetic, metabolic, and molecular characteristics. However, the potential of nutrigenomic-guided nutraceutical interventions to modulate biological aging pathways remains poorly characterized. Objective: This study aimed to map and synthesize the available evidence from human studies evaluating personalized nutraceutical interventions based on nutrigenomic approaches and their effects on biomarkers associated with biological aging. Methods: A scoping review was conducted following the Joanna Briggs Institute methodology and PRISMA-ScR guidelines. PubMed/MEDLINE, Embase, Scopus, and Web of Science were searched for studies published between 2021 and 2026. Eligible studies included adults aged ≥18 years receiving personalized nutraceutical interventions informed by genetic, genomic, metabolomic, or other molecular data. Outcomes included biomarkers of cellular aging, inflammation, oxidative stress, immunometabolism, and related pathways. Results: Twenty-one studies were included. Interventions involved omega-3 fatty acids, polyphenols, Nigella sativa, vitamin D, methyl-donor micronutrients, fermented papaya preparation, and other nutraceutical preparations and functional food-based interventions. Four major themes emerged: multi-omic stratification approaches, biological aging biomarkers, redox-inflammatory modulation, and applications in metabolic disorders. Most studies demonstrated favorable effects on intermediate molecular biomarkers, including inflammatory cytokines, oxidative stress markers, lipid metabolism, endothelial function, and DNA methylation signatures. However, evidence directly demonstrating slowing of biological aging through validated biomarkers such as epigenetic clocks or telomere dynamics remains limited. Conclusions: Personalized nutraceutical interventions exhibit biological plausibility for modulating pathways associated with healthy aging. Nevertheless, robust longitudinal studies incorporating validated biomarkers of biological aging and clinically meaningful outcomes are needed before their widespread implementation in precision medicine. Full article

Bone remodeling is a dynamic and tightly regulated process that maintains skeletal homeostasis through a balance between bone formation by osteoblasts and bone resorption by osteoclasts. Disruption of this balance contributes to the development of bone-related disorders, particularly osteopenia, osteoporosis and osteogenesis imperfecta, which weaken, deform, or cause fractures. Increasing evidence indicates that oxidative stress and chronic inflammation impair osteoblast functions while promoting osteoclast differentiation and activity. Heme oxygenase-1 (HO-1) is a stress-inducible enzyme with cytoprotective, antioxidant, and anti-inflammatory properties. Besides its primary role in cellular defense against oxidative stress and inflammatory damage, HO-1 has been shown to be involved in both osteoblast differentiation and osteoclastogenesis. Through its interaction with key regulatory systems, including the receptor activator of nuclear factor κB (RANK)–receptor activator of nuclear factor κB ligand (RANKL)–osteoprotegerin axis and redox-sensitive signaling pathways, HO-1 contributes to maintenance of optimal bone remodeling. The enzyme also plays a role in modulating metabolic processes in the bone. This review highlights the role of HO-1 in bone formation, bone resorption, and related pathophysiologic conditions. Furthermore, the therapeutic potential of HO-1 as a target for bone disorders is discussed. Full article

Heart failure (HF) is a systemic syndrome in which prognosis depends on cardiac dysfunction, congestion, cardiorenal and cardiohepatic interactions, inflammation, and metabolic dysregulation. The liver is exposed to elevated systemic venous pressure and reduced forward flow, and contributes to albumin and coagulation factor synthesis, bile acid metabolism, iron homeostasis, and the acute-phase response. Cardiohepatic injury involves hemodynamic stress, sinusoidal endothelial dysfunction, oxidative stress, inflammatory signaling, fibrogenesis, and altered metabolic regulation. Congestive hepatopathy is associated with right-sided HF, tricuspid regurgitation (TR), pulmonary hypertension, and elevated central venous pressure, whereas hypoxic hepatitis develops during low-output states, shock, or acute circulatory deterioration. These mechanisms may coexist, producing congestive/cholestatic, hypoperfusive/ischemic and mixed/systemic reserve profiles. Composite liver-related scores, including Model for End-Stage Liver Disease (MELD), MELD excluding International Normalized Ratio (MELD-XI), MELD with sodium (MELD-Na), MELD-Albumin and albumin–bilirubin (ALBI) score, may reflect congestion, hepatorenal dysfunction, nutritional status and reduced systemic reserve. This review summarizes hemodynamic and molecular mechanisms of cardiohepatic injury, liver-related biomarkers and composite scores, with emphases on advanced HF, left ventricular assist device (LVAD) therapy and heart transplantation. Liver-related abnormalities remain underrecognized in HF. Their serial interpretation may support risk stratification, but composite scores should complement rather than replace comprehensive clinical assessment. Full article

Excessive short-term ethanol intake often causes acute intoxication and multi-organ damage, especially to the liver and brain. Thus, developing safe and effective preparations for hangover relief, liver protection, and brain function regulation is of great practical significance. In this study, we fabricated a thermosensitive chitosan (CS)–sea cucumber peptide (SCP) hydrogel (CS–SCP gel) loaded with SCP using NaHCO₃ as a crosslinker and characterized its properties. Kunming mouse models of anti-intoxication and acute alcohol-induced liver and brain injuries were established. The anti-intoxication and organ-protective effects of the CS–SCP gel were comprehensively evaluated through behavioral observation, liver histopathology, and biochemical assays of serum and liver, kidney, and brain tissues. The CS–SCP gel exhibited a phase transition temperature of 35.7 °C, a water absorption rate of 1015.47%, and a cumulative peptide release of 74.83% within 330 min. In mice, it prolonged the latency to drunkenness; shortened alcohol-induced sleep and sobering time; reduced blood ethanol, transaminase, and lipid levels; upregulated hepatic antioxidant enzymes; downregulated pro-inflammatory cytokines, and alleviated lipid peroxidation. It also enhanced brain antioxidant capacity, suppressed cerebral inflammatory cytokines, and maintained cholinergic neurotransmitter homeostasis. Collectively, with sustained release, CS–SCP gel is expected to prolong the pharmacological action of SCP, enhance therapeutic efficacy, and protect against alcohol-induced liver and brain injury through the regulation of oxidative stress and attenuation of inflammation. Full article

Hepatic encephalopathy (HE) is a complex complication of liver failure involving oxidative stress, astroglial activation, mitochondrial dysfunction, and multiorgan disturbances along the gut–liver–brain axis. This study investigated the therapeutic effects of liraglutide (LIRA) in a thioacetamide (TAA)-induced rat model of HE. Thirty male Sprague–Dawley rats were assigned to control, TAA, and TAA+LIRA 100, 200, or 400 µg/kg groups. HE was induced with TAA (200 mg/kg, intraperitoneally) for three consecutive days, followed by subcutaneous LIRA treatment for 14 days. Serum biochemical parameters, tissue oxidative and inflammatory markers, histopathology, and Nrf2, MFN2, AKT1, mTOR, GFAP, and VEGFA immunoreactivity were evaluated. TAA caused marked hepatic and cerebral structural injury, increased serum and brain glutamine concentrations, disrupted redox homeostasis, elevated MPO activity, and increased cerebral GFAP and multiorgan VEGFA immunoreactivity. LIRA partially improved hepatic and cerebral histopathology, reduced glutamine disturbances, attenuated selected oxidative, nitrosative, and inflammatory alterations, and modulated Nrf2, MFN2, AKT1, mTOR, GFAP, and VEGFA immunoreactivity in a tissue- and dose-specific manner. The 200 µg/kg dose produced the most consistent overall improvement, whereas the 400 µg/kg dose was less favorable for several endpoints. LIRA may therefore alleviate multiorgan stress associated with experimental HE, although further studies are required to confirm functional and mechanistic relevance. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the most prevalent chronic liver diseases worldwide, involving multiple pathological mechanisms such as lipid metabolism disorders, oxidative stress, chronic inflammation, insulin resistance, and dysregulation of the gut–liver axis. Currently, there remains a lack of effective and long-term safe therapeutic strategies for MASLD, necessitating the development of novel interventions. Plant-derived exosome-like nanovesicles (PELNs) represent naturally secreted nanoscale vesicles derived from plant cells. Their advantages, including extensive availability, high biocompatibility, low immune activation, remarkable stability, and convenient oral administration, make them attractive platforms for therapeutic delivery. PELNs can not only encapsulate natural bioactive compounds such as polyphenols, alkaloids, terpenoids, and polysaccharides but also serve as drug delivery vehicles to achieve liver-targeted transport and synergistic therapy. Current evidence for PELNs in MASLD is predominantly preclinical. In vitro studies have provided mechanistic insights into their effects on lipid metabolism, oxidative stress, inflammatory signaling, and hepatocellular injury, whereas animal studies have demonstrated improvements in hepatic steatosis and related metabolic abnormalities for selected PELNs. A smaller number of studies have investigated tissue distribution, oral uptake, or preliminary biosafety. However, systematic pharmacokinetic, long-term toxicological, and target-species clinical evidence remains insufficient. Accordingly, the therapeutic effects discussed in this review should be interpreted primarily as preclinical findings, and the applicability of PELNs in veterinary practice remains to be established. Full article

Background/Objectives: Manganese (Mn) is a neurotoxic trace element whose excessive accumulation in the brain can induce hippocampal damage via oxidative stress, mitochondrial dysfunction, neuroinflammation, and apoptosis. This study investigated whether honokiol (HNK) and its liposomal nanoformulation (HNK-LNPs) can ameliorate Mn-induced hippocampal neurotoxicity by modulating key antioxidant and mitochondrial regulatory pathways. Methods: Male Wistar rats were subjected to Mn exposure to induce hippocampal neurotoxicity and were treated with HNK or HNK-LNPs. We assessed oxidative status via NRF2/HO-1 signaling, antioxidant defenses (glutathione, GPx, SOD, CAT), and oxidative indices (ROS, MDA). Neuroinflammatory markers (NF-κB, TNF-α, IL-1β, IL-6, Iba-1), mitochondrial respiratory chain function and ATP levels, SIRT1/PGC-1α signaling, and neurotransmitter homeostasis were evaluated. We analyzed apoptosis using Bax, Bcl-2, caspase-3, and cytochrome c, along with histopathological and ultrastructural examination of the hippocampus. Results: Mn exposure was associated with NRF2/HO-1 downregulation, depleted endogenous antioxidants, increased ROS and MDA levels, and increased NF-κB–driven neuroinflammation and microglial Iba-1 expression. Mn was further associated with reduced ATP synthesis, dysregulation of SIRT1/PGC-1α signaling, and disrupted neurotransmitter balance, with a pro-apoptotic shift (elevated Bax, caspase-3, cytochrome c; reduced Bcl-2) and neuronal degeneration. Co-treatment with HNK, and more prominently with HNK-LNPs, was associated with reversing these alterations, restoring antioxidant and mitochondrial pathways, dampening inflammatory cascades, normalizing neurotransmitters, and favoring neuronal survival, with many indices approaching control values and consistently surpassing free HNK. Conclusions: Liposomal encapsulation significantly enhances honokiol’s neuroprotection against Mn-induced hippocampal neurotoxicity, likely via improved CNS bioavailability and coordinated modulation of NRF2/HO-1 and SIRT1/PGC-1α pathways. These findings support HNK-LNPs as a promising multi-mechanistic therapeutic strategy for metal-induced and related neurotoxic brain disorders. Full article

Numerous types of environmental toxicants alter human metabolomics, directly or indirectly, through gut microbial dysbiosis, upsetting immune homeostasis. Environmental toxicants capable of these direct and indirect effects have included heavy metals, pesticides, herbicides, polychlorinated biphenyl (PCB) congeners, and endocrine-disrupting chemicals. The cell and molecular events induced by some diverse toxicants are reviewed, along with their potential additive, synergistic, and antagonistic effects on immune homeostasis (increasing proinflammatory immune cell activation and suppressing immunoregulation), which leads to systemic oxidative stress (OS). As people are exposed in varying degrees to countless chemicals and environmental factors over a lifetime, it is challenging to correlate specific diagnoses to any single toxicant or exposure, which is often a key challenge in linking environmental exposure to health outcomes. However, many toxicants have the common mechanistic effect of OS. The effects of toxicants are more pronounced with aging due to cumulative exposures and immunoaging (immunosenescence), with chronic low-grade inflammation referred to as “inflammaging”. The cell and molecular mechanisms of toxicants include altered calcium flux, mitochondrial dysfunction, and increased levels of damage-associated molecular patterns (alarmins) that trigger an inflammatory response and possibly promote autoimmune and neurological disorders. OS skews type-1 immunity for defenses against pathogens and cancers more toward type-2 immune responses to self-antigens (autoimmunity). The toxicants may directly affect the innate and adaptive immune cells inducing this skewing, or they may modify portions of gut microbial species and strains and their production of metabolites that indirectly affect systemic immunity. These latter toxicant influences require metabolomic analysis of the differential structures and activities of the microbial metabolites. The damaging effects of OS and inflammation disrupting immune homeostasis and leading to disorders are reviewed and discussed. The need for well-designed studies that allow for standardized comparison of exposures and related effects are emphasized, and their real-world limitations noted. Full article