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Pharmacokinetic and nephroprotective benefits of using Schisandra chinensis extracts in a cyclosporine A-based immune-suppressive regime.

Cyclosporine A (CsA) is a powerful immunosuppressive drug. However, nephrotoxicity resulting from its long-term usage has hampered its prolo … ediated by its antiapoptotic and antioxidant abilities, which caused the attenuation of CsA-induced autophagic cell death. All in all, these findings suggest the prospective use of SCE as an effective adjunct in a CsA-based immunosuppressive regimen.

Autophagic signaling promotes systems-wide remodeling in skeletal muscle upon oncometabolic stress by D2-HG.

OBJECTIVES: Cachexia is a metabolic disorder and comorbidity with cancer and heart failure. The syndrome impacts more than thirty million people worldwide, accounting for 20% of all cancer deaths. In acute myeloid leukemia, somatic mutations of the metabolic enzyme isocitrate dehydrogenase 1 and 2 cause the production of the oncometabolite D2-hydroxyglutarate (D2-HG). Increased production of D2-HG is associated with heart and skeletal muscle atrophy, but the mechanistic links between metabolic and proteomic remodeling remain poorly understood. Therefore, we assessed how oncometabolic stress by

'Aquaporin-omics': mechanisms of aquaporin-2 loss in polyuric disorders.

Animal models of a variety of acquired nephrogenic diabetes insipidus (NDI) disorders have identified a common feature: all such models are associated with the loss of aquaporin-2 (AQP2) from collecting duct principal cells, explaining the associated polyuria. To discover mechanisms of AQP2 loss, previous investigators have carried out either transcriptomics (lithium-induced NDI, unilateral ureteral obstruction, endotoxin-induced NDI) or proteomics (hypokalaemia-associated NDI, hypercalcaemia-associated NDI, bilateral ureteral obstruction), yielding contrasting views. Here, to address whether

The PI4K2A-OSBPL6/ORP6-PS axis mediates lysosomal membrane repair to restore neuronal lipid homeostasis and promote neuronal survival after spinal cord injury.

Dysfunction of the neuronal macroautophagy/autophagy-lysosome system is a critical contributor to neuronal death following spinal cord injury (SCI), but the underlying mechanisms remain elusive. Our study demonstrated that SCI induced impaired autophagic flux and lysosomal membrane permeabilization (LMP) in neurons. By combining in vivo bulk RNA sequencing with validation experiments, we observed the transient upregulation of the membrane repair factor PI4K2A, which was specifically enriched in lysosomes, after SCI. Crucially, ER-MS and IP-MS analyses revealed an interaction between PI4K2A and

The SFTSV Nonstructural Proteins Induce Autophagy to Promote Viral Replication via Interaction with Vimentin.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a newly identified phlebovirus associated with severe hemorrhagic fever in humans. Studies have shown that SFTSV nucleoprotein (N) induces BECN1-dependent autophagy to promote viral assembly and release. However, the function of other SFTSV proteins in regulating autophagy has not been reported. In this study, we identify SFTSV NSs, a nonstructural protein that forms viroplasm-like structures in the cytoplasm of infected cells as the virus component mediating SFTSV-induced autophagy. We found that SFTSV NSs-induced autophagy was incl

Chrysin-loaded PEGylated liposomes protect against alloxan-induced diabetic neuropathy in rats: the interplay between endoplasmic reticulum stress and autophagy.

BACKGROUND: Diabetic neuropathy (DN) is recognized as a significant complication arising from diabetes mellitus (DM). Pathogenesis of DN is accelerated by endoplasmic reticulum (ER) stress, which inhibits autophagy and contributes to disease progression. Autophagy is a highly conserved mechanism crucial in mitigating cell death induced by ER stress. Chrysin, a naturally occurring flavonoid, can be found abundantly in honey, propolis, and various plant extracts. Despite possessing advantageous attributes such as being an antioxidant, anti-allergic, anti-inflammatory, anti-fibrotic, and anticanc

PRDX1 activates autophagy via the PTEN-AKT signaling pathway to protect against cisplatin-induced spiral ganglion neuron damage.

Spiral ganglion neurons (SGNs) are auditory neurons that relay sound signals from the inner ear to the brainstem. The ototoxic drug cisplatin can damage SGNs and thus lead to sensorineural hearing loss (SNHL), and there are currently no methods for preventing or treating this. Macroautophagy/autophagy plays a critical role in SGN development, but the effect of autophagy on cisplatin-induced SGN injury is unclear. Here, we first found that autophagic flux was activated in SGNs after cisplatin damage. The SGN apoptosis and related hearing loss induced by cisplatin were alleviated after co-treatm

Schisandrin B confers multi-organ protection via regulation of mitochondrial homeostasis: mechanistic integration, organ-specific differences, and translational challenges-a review.

Schisandrin B (Sch B) is a dibenzocyclooctadiene lignan derived from plants of the Schisandra genus. Owing to its pronounced lipophilicity, Sch B may readily cross biological membranes and is increasingly discussed in association with the regulation of mitochondrial homeostasis. Mitochondrial dysfunction underlies key pathological processes involved in multi-organ injury and a broad range of chronic diseases, manifested as redox imbalance, reduced mitochondrial membrane potential (ΔΨm), impaired ATP production, mitochondrial DNA (mtDNA) damage, disrupted mitochondrial dynamics, failure of mito

Cardioprotective effects of preconditioning exercise in the female tumor bearing mouse.

Cancer cachexia, a metabolic wasting syndrome, affects up to 80% of cancer patients and leads to the death in up to 20% of cancer patients. While research is growing in the field, there are still no clear diagnostic criteria and cancer cachexia remains an untreated condition. Aerobic exercise has been shown to positively impact cachexia by slowing its development and attenuating muscle loss. The most effective timing, duration, and intensity of exercise as a preventative and protective measure against cancer cachexia remains questionable. Therefore, the purpose of this study was to examine the

POLM inhibits porcine epidemic diarrhea virus replication by degrading multiple viral structural proteins.

Porcine epidemic diarrhea, as a porcine epidemic diarrhea virus (PEDV)-induced infectious intestinal condition typified by diarrhea, emesis, dehydration, and anorexia, leads to death rates as high as 100% among suckling piglets. Given the existing commercial vaccines, it is essential to study host-virus interactions and formulate efficient anti-viral regimes. This study concerned a host factor POLM (a DNA polymerase family member) that exerts an anti-viral effect against PEDV proliferation. Our results indicated that POLM expression was increased following PEDV infection and was regulated by t

Nifedipine induced autophagy through Beclin1 and mTOR pathway in endometrial carcinoma cells.

BACKGROUND: Endometrial carcinoma is one of the most common female tract genital malignant tumors. Nifedipine, an L-type calcium channel antagonist can inhibit cell proliferation of carcinomas. Recent studies indicated that a rise in the free cytosolic calcium ([Ca(2+)](c)) was a potent inducer of autophagy. Here, we investigated the relationship between nifedipine and autophagy in Hec-1A cells. METHODS: Cells were cultured with nifedipine (10 µmol/L) and harvested at different times for counting cell number. MTT assay was applied to evaluate the cell viability and transwell assay to reveal c

The ménage à trois of autophagy, lipid droplets and liver disease.

Autophagic pathways cross with lipid homeostasis and thus provide energy and essential building blocks that are indispensable for liver functions. Energy deficiencies are compensated by breaking down lipid droplets (LDs), intracellular organelles that store neutral lipids, in part by a selective type of autophagy, referred to as lipophagy. The process of lipophagy does not appear to be properly regulated in fatty liver diseases (FLDs), an important risk factor for the development of hepatocellular carcinomas (HCC). Here we provide an overview on our current knowledge of the biogenesis and func

GSDME-N-induced mitochondrial neurotoxicity in early neurodegeneration was suppressed by nicotine via enhancing autophagic flux.

BACKGROUND: Neurodegeneration is a chronic, progressive process initiated by early neurite retraction, a pathological hallmark preceding neuronal death in neurodegenerative disorders such as Parkinson’s disease (PD). Cleavage of gasdermin E (GSDME) releases its N-terminal domain (GSDME-N), which has been shown to mediate mitochondrial dysfunction and the onset of neurodegeneration. However, the therapeutic potential of targeting GSDME-N for early intervention in PD, and whether nicotine, a tobacco component with neuroprotective properties, acts through GSDME modulation remain unexplored. METHO

CASP9 (caspase 9) is essential for autophagosome maturation through regulation of mitochondrial homeostasis.

UNLABELLED: CASP9 (caspase 9) is a well-known initiator caspase which triggers intrinsic apoptosis. Recent studies also suggest various non- … y conjugation system and autophagosome closure and maturation. ABBREVIATIONS: AA: amino acid; ACD: autophagic cell death; ACTB: actin beta; ANXA5: annexin A5; APAF1: apoptotic peptidase activating factor 1; Atg: autophagy related; ATG16L1: autophagy related 16 like 1; BafA1: bafilomycin A1; BCL2: BCL2 apoptosis regulator; BECN1: beclin 1; CARD: caspase recruitment dom …

Ferritinophagy-derived iron causes protein nitration and mitochondrial dysfunction in acetaminophen-induced liver injury.

Acetaminophen (APAP), also known as paracetamol, is a widely used analgesic and antipyretic drug. While the drug is effective and safe at recommended doses, excessive intake can lead to acute liver injury (ALI) due to the formation of the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI), which depletes glutathione (GSH). Despite regulatory efforts, APAP-related liver injury remains a significant health concern. However, the cellular pathways that contribute to APAP-induced hepatotoxicity-particularly those involving iron metabolism-remain incompletely understood. To address this gap, we

Missense mutations in the APOL1 gene are highly associated with end stage kidney disease risk previously attributed to the MYH9 gene.

MYH9 has been proposed as a major genetic risk locus for a spectrum of nondiabetic end stage kidney disease (ESKD). We use recently released sequences from the 1000 Genomes Project to identify two western African-specific missense mutations (S342G and I384M) in the neighboring APOL1 gene, and demonstrate that these are more strongly associated with ESKD than previously reported MYH9 variants. The APOL1 gene product, apolipoprotein L-1, has been studied for its roles in trypanosomal lysis, autophagic cell death, lipid metabolism, as well as vascular and other biological activities. We also show…

Sepsis and the Liver.

BACKGROUND/OBJECTIVES: Sepsis-associated liver injury (SALI) is a critical and often early complication of sepsis, defined by distinct hyper-inflammatory and immunosuppressive phases that shape patient phenotypes. METHODS: Characterizing these phases establishes a foundation for immunomodulation strategies tailored to individual immune responses, as discussed subsequently. RESULTS: The initial inflammatory response activates pathways such as NF-κB and the NLRP3 inflammasome, leading to a cytokine storm that damages hepatocytes and is frequently associated with higher SOFA scores and a higher

Hemochromatosis: Ferroptosis, ROS, Gut Microbiome, and Clinical Challenges with Alcohol as Confounding Variable.

Hemochromatosis represents clinically one of the most important genetic storage diseases of the liver caused by iron overload, which is to be differentiated from hepatic iron overload due to excessive iron release from erythrocytes in patients with genetic hemolytic disorders. This disorder is under recent mechanistic discussion regarding ferroptosis, reactive oxygen species (ROS), the gut microbiome, and alcohol abuse as a risk factor, which are all topics of this review article. Triggered by released intracellular free iron from ferritin via the autophagic process of ferritinophagy, ferropto

Targeting Autophagy with Natural Products as a Potential Therapeutic Approach for Cancer.

Macro-autophagy (autophagy) is a highly conserved eukaryotic intracellular process of self-digestion caused by lysosomes on demand, which is upregulated as a survival strategy upon exposure to various stressors, such as metabolic insults, cytotoxic drugs, and alcohol abuse. Paradoxically, autophagy dysfunction also contributes to cancer and aging. It is well known that regulating autophagy by targeting specific regulatory molecules in its machinery can modulate multiple disease processes. Therefore, autophagy represents a significant pharmacological target for drug development and therapeutic

Совпадение в полном тексте источника
… cell death [ 117 ]. … The curcumin analogue, hydrazinobenzoylcurcumin, can also induce autophagic cell death in human non-small lung epithelial carcinoma (A549) cells [ 121 ]. …

Therapeutic Potential of Autophagy Modulation in Cholangiocarcinoma.

Autophagy is a multistep catabolic process through which misfolded, aggregated or mutated proteins and damaged organelles are internalized in membrane vesicles called autophagosomes and ultimately fused to lysosomes for degradation of sequestered components. The multistep nature of the process offers multiple regulation points prone to be deregulated and cause different human diseases but also offers multiple targetable points for designing therapeutic strategies. Cancer cells have evolved to use autophagy as an adaptive mechanism to survive under extremely stressful conditions within the tumo

Совпадение в полном тексте источника
… The downregulation of Beclin1 in different cancers could indicate that tumor development is closely related to Beclin1-induced autophagic cell death [ 178 , 184 , 185 ]. … Beclin1 downregulation can significantly reduce autophagy to protect tumor cells from autophagic cell death, contributing to the continuous development of tumor cells [ 186 ]. …