Search Results (195)

Autophagy has a potential regulatory effect on spermatogenesis and testicular development. Dynamic alterations in the testicular autophagy of prepubertal mice were analyzed, and the relationship between autophagy levels and testicular development was clarified using C57BL/6 mice aged 1, 2, 4, 6, and 8 weeks. Transmission electron microscopy was used to identify autophagic vacuoles. The expression of autophagy-related proteins and PI3K/AKT/mTOR signaling pathway-related proteins was determined using Western blotting. Localization of microtubule-associated protein light chain 3 (LC3) and sequestosome 1 (p62) in testicular tissues was determined using immunofluorescence and immunohistochemistry. Autophagic vacuoles in spermatogenic cells increased gradually from weeks 1 to 4, peaked at 2 weeks, decreased sharply at 6 weeks, and were undetectable at 8 weeks. The expression of Beclin 1 autophagy-related protein, LC3-II, and p62 was highest at 2 weeks among the five age groups, whereas LC3-II and p62 were mainly localized in spermatogonia and spermatocytes. Moreover, low mTOR expression and its increased expression were detected at 1–2 weeks and 2–8 weeks, respectively. These results show that testicular autophagic levels exhibit a dynamic pattern of “increase (1–2 weeks) followed by a decrease (2–8 weeks),” providing a reference in determining the relationship between autophagy levels and testicular development. Full article

Nutritional and cooling strategies to abate the negative effects of heat stress during the dry period have been used to improve the performance of dairy cattle. The objective of this study was to evaluate the effects of feeding an immunomodulatory supplement (OmniGen-AF^®, OMN) before, during, and after exposure to either heat stress or active cooling during the dry period on immune function and mammary development in dairy cows. During late lactation (at least 60 d before dry off), cows were provided with evaporative cooling systems (shade, fans, and soakers) and assigned to two groups: placebo (56 g/d of AB20^® top-dressed; CON) or OmniGen-AF^® (OMN, 56 g/d top-dressed). Cows were dried off ~46 d before the expected calving date and further split into evaporative cooling (shade, fans, and soakers; CL) or heat stress (only shade; HT) pens. Thus, after dry off, there were four treatment groups: heat stress with placebo (HT, n = 17), HT with OMN supplementation (HT + OMN, n = 19), CL with placebo (CL, n = 16), and CL with OMN supplementation (CL + OMN, n = 11). From a subset of cows (n = 6–8 per group), four blood samples were collected during the dry period (−43, −39, −32, and −21 d relative to calving) to evaluate neutrophil function and blood hematology. In addition, mammary biopsies (4–6 cows/treatment) were collected at −43, −39, −32, and −21 d relative to calving to evaluate mammary gland gene expression and histology, i.e., Tdt dUTP nick-end labeling (TUNEL) and Ki67. Genes related to autophagy, apoptosis, and cell proliferation were analyzed by qRT-PCR. Relative to CL, HT downregulated the expression of beclin-2 (BECN2) but upregulated the expression of beclin-1 (BECN1) on days −43 and −39 relative to calving, respectively. Also, relative to CL, HT upregulated the expression of BAX and FAS on day −39 relative to calving. These differences in gene expression were followed by HT cows having a lower total cell apoptosis rate during involution relative to CL cows. Further to these effects, HT leads to a lower alveoli number relative to CL cows. As in the CL treatment, OMN cows have a higher total cell apoptosis rate and alveoli number relative to CON cows. In addition, OMN cows have higher total cell proliferation relative to CON. Prolactin (PRL) and cortisol concentrations were evaluated during the dry period at days −45, −26, −3, and −1 relative to calving. Relative to CL, HT cows had higher PRL at day −45 but lower PRL on day −1 relative to calving, and a similar trend was observed for cortisol concentrations. In summary, HT impacts mammary gland gene expression, compromises mammary involution, reduces alveoli number, and alters hormone dynamics throughout the dry period. Following the same trends as the CL treatment, OMN increases mammary gland turnover by having a higher cell apoptosis and cell proliferation rate and lower connective tissue relative to CON cows. Full article

Alzheimer’s disease (AD) is a neurodegenerative disorder that significantly impacts the lives of patients and their families. The pathological features of AD include the accumulation of amyloid-β (Aβ) and Tau, which disrupt neuronal function and communication, ultimately leading to neuronal loss and brain atrophy. Efforts to understand the molecular mechanisms underlying these pathological changes have led to advancements in diagnostic techniques and potential therapeutic interventions. However, the complexity of AD necessitates further research to develop more effective treatments and, ideally, preventive measures. Extensive research suggests that diminishing mTOR signaling increases lifespan and health span across various species. Increased PI3K/mTOR signaling has been linked to the progression of AD pathology, leading to neuronal degeneration and impairments in cognitive function. In this study, we explored the therapeutic potential of PF-04691502, a dual PI3K/mTOR inhibitor, in Alzheimer’s disease (AD)-like pathology using male and female B6.Cg-Tg(APPswe, PSEN1dE9)85Dbo/Mmjax mice (APP/PS1), a well-established transgenic model of AD. Eighteen-month-old APP/PS1 and wild-type mice received oral administration of PF-04691502 at a dose of 1 mg/kg for 12 weeks. Following the treatment period, spatial learning and memory were evaluated using the Morris water maze. Subsequently, the mice brains were collected for neuropathological and biochemical assessments. Our findings showed that PF-04691502 enhanced cognitive performance in APP/PS1 mice and significantly reduced insoluble Aβ accumulation in the brain. Mechanistically, these effects were associated with enhanced autophagy induction. Treatment with PF-04691502 increased the LC3-II/LC3-I ratio, upregulated Beclin-1, and elevated LAMP-2 levels, indicative of stimulated autophagosome formation and lysosomal activity. Overall, these preclinical results suggest that PF-04691502 holds promise as a potential therapeutic agent for AD and other aging-related neurodegenerative diseases involving mTOR pathway dysregulation. Full article

Autophagy is a conserved catabolic pathway that degrades intracellular cargo through the lysosomal system. Canonically, this process is orchestrated by the autophagy-related (Atg)5-Atg7 conjugation system, which facilitates the formation of microtubule-associated protein 1 light chain 3 (LC3)-decorated double-membrane vesicles known as autophagosomes. However, accumulating evidence has revealed the existence of an Atg5-Atg7-independent, alternative autophagy pathway that still relies on upstream regulators such as the unc-51 like autophagy activating kinase 1 (Ulk1) kinase and the Beclin1 complex. In this review, we provide a comprehensive overview of the role of the Beclin1 complex in canonical autophagy and highlight its emerging importance in alternative autophagy. Notably, the recent identification of transmembrane protein 9 (TMEM9) as a lysosomal protein that interacts with Beclin1 to promote member RAS oncogene family 9 (Rab9)-dependent autophagosome formation has significantly advanced our understanding of alternative autophagy regulation. Furthermore, this Ulk1-Rab9-Beclin1-dependent mitophagy has been shown to mediate to mitochondrial quality control in the heart, thereby contributing to cardioprotection under ischemic and metabolic stress conditions. We further examine how the Beclin1 complex functions as a central scaffold in both canonical and alternative autophagy, with a focus on its modulation by novel factors such as TMEM9 and the potential therapeutic implications of these regulatory mechanisms. Full article

Ischemic stroke induces complex neuroinflammatory cascades, where microglial autophagy and mitophagy serve dual roles in both injury amplification and tissue repair. This scoping review synthesized current evidence on their regulatory mechanisms and therapeutic implications. Literature was identified via PubMed and Embase, yielding 79 records, from which 39 original research articles and 13 review papers were included after eligibility screening. Search terms included “microglia,” “autophagy,” and “ischemic stroke.” Protective autophagy was frequently associated with AMPK activation, mTOR inhibition, and mitophagy pathways such as PINK1/Parkin and BNIP3/NIX, facilitating mitochondrial clearance, M2 polarization, and anti-inflammatory signaling. Therapeutic agents such as rapamycin, Tat-Beclin 1, and Urolithin A consistently demonstrated neuroprotection in preclinical stroke models. In contrast, excessive or prolonged autophagic activation was linked to inflammasome amplification, oxidative stress, and phagoptosis. Limited human studies reported associations between elevated serum ATG5 levels or ATG7 polymorphisms and worse clinical outcomes, suggesting preliminary translational relevance. These findings support the potential of phase-specific modulation of microglial autophagy as a therapeutic avenue for stroke, although further validation in human models and development of autophagy biomarkers are needed for clinical application. Full article

Sprouty-related proteins with enabled/vasodilator-stimulated phosphoprotein homology 1 (EVH1) domain (SPREDs) are negative regulators of the Ras/MAPK signaling pathway and are known to modulate developmental and endocrine processes. While the roles of SPRED1 and SPRED2 are increasingly understood, the physiological relevance of SPRED3 remains elusive. To elucidate its function, we generated SPRED3 knockout (KO) mice and performed phenotypic, molecular, and hormonal analyses. SPRED3-deficient mice exhibited growth retardation and a non-Mendelian genotype distribution. X-Gal staining revealed Spred3 promoter activity in the thyroid, adrenal gland, pituitary, cerebral cortex, and kidney. Hormonal profiling identified elevated thyroid-stimulating hormone (TSH) and reduced thyroxine (T₄) levels, indicating primary hypothyroidism. Thyroidal extracellular signal-regulated kinase (ERK) signaling was mildly reduced in SPRED3 KO mice, and immunoblotting revealed altered expression of autophagy regulators, including reduced sequestosome 1 (p62), increased autophagy-related gene 5 (ATG5), as well as an elevated microtubule-associated protein 1 light chain 3 (LC3) II/I ratio and a decreased pBeclin/Beclin ratio in SPRED3 KO mice. Our findings indicate that SPRED3 is involved in thyroidal homeostasis and plays a regulatory role in autophagy processes within the thyroid gland. Full article

Cocaine misuse induces microglial activation and neuroinflammation, contributing to neurodegeneration and behavioral impairments. Prior studies have shown that cocaine induces mitochondrial dysfunction, dysregulated mitophagy, and lysosomal impairment in microglia. Here, we investigated the therapeutic potential of N-acetylcysteine (NAC) in mitigating cocaine-induced microglial activation and neuroinflammation. Mouse primary microglial cells (MPMs) were pretreated with NAC (5 mM) for 1 h prior to cocaine exposure (10 µM, 24 h) and analyzed for markers of microglial activation, mitophagy, and lysosomal integrity using Western blot, Seahorse assays, lysosomal pH, and membrane potential measurements. In vivo, C57BL/6N mice received NAC (200 mg/kg, i.p.) 1 h before daily cocaine injections (20 mg/kg, i.p.) for 7 days. Behavioral assays (open field, novel object recognition) and brain biomarker analyses (frontal cortex, hippocampus) were performed. Cocaine exposure elevated CD11b, mitophagy markers (PINK1, PARK, and DLP1), and autophagy proteins (Beclin1, and p62), while impairing mitochondrial and lysosomal functions. NAC pretreatment restored mitochondrial and lysosomal function, reduced reactive oxygen species, and normalized protein expression. In vivo, NAC also alleviated cocaine-induced microglial activation and behavioral deficits. These findings highlight NAC as a promising therapeutic agent to counteract cocaine-mediated neuroinflammation and neurotoxicity. Full article

Background: Renal injury is a critical health issue in pet dogs, often exacerbated by drug-induced nephrotoxicity such as gentamicin (GM). This study investigated the protective effects of ergosterol (Erg), a natural compound from edible mushrooms, against GM-induced damage in Madin–Darby canine kidney (MDCK) cells. Methods: MDCK cells were treated with GM (0.5–3 mmol/L) for 12 h to establish injury. Erg (1 to 32 μg/mL) was pretreated for 12 h before GM exposure (2 mmol/L). Cell viability, nitric oxide (NO), lactate dehydrogenase (LDH), oxidative stress markers (SOD, GSH, CAT, MDA), inflammatory cytokines (IL-1β, IL-6, TNF-α), renal function indicators (Scr, BUN), and autophagy/apoptosis-related proteins (ATG5, Beclin1, P62, BAX, BCL-2) were assessed via CCK-8, ELISA, fluorescence staining, and Western blot. Statistical significance (p < 0.05) was determined by ANOVA and LSD post hoc tests. Results: GM (2 mmol/L) significantly reduced cell viability (p < 0.01) and elevated NO and LDH levels (p < 0.01). Erg pretreatment (4–8 μg/mL) restored cell viability (p < 0.01), suppressed NO (p < 0.01) and LDH release (p < 0.01), and enhanced antioxidant enzyme activities (SOD, GSH, CAT; p < 0.01). Erg attenuated GM-induced reactive oxygen species (ROS) overproduction (p < 0.01) and decreased pro-inflammatory cytokines (IL-1β, IL-6, TNF-α; p < 0.01). Renal markers Scr and BUN were reduced (p < 0.01). Mechanistically, Erg upregulated autophagy proteins ATG5 and Beclin1 (p < 0.01), reduced P62 accumulation (p < 0.01), and lowered the BAX/BCL-2 ratio (p < 0.01). Conclusions: Erg protects MDCK cells from GM-induced nephrotoxicity by restoring autophagy flux, suppressing mitochondrial apoptosis, and mitigating oxidative stress and inflammation. These findings highlight Erg’s potential as a natural therapeutic agent for canine renal injury. Further in vivo studies are needed to validate its clinical efficacy. Full article

The intestine is an important immune organ of aquatic animals and it plays an essential role in maintaining body health and anti-oxidative stress. To investigate the toxic effects of deltamethrin in intestinal tissue of Chinese mitten crabs (Eriocheir sinensis), 120 healthy crabs were randomly divided into two experimental groups (blank control group and deltamethrin-treated group), with three replicates in each group. After being treated with deltamethrin for 24 h, 48 h, 72 h, and 96 h, intestinal tissues were collected aseptically to assess the effects of deltamethrin on oxidative stress, immunity, apoptosis-related genes, and the structure of microflora in intestinal tissues. Additionally, correlations between gut microbiota composition and intestinal tissue damage-associated genes were analyzed. The results demonstrated that prolonged exposure to deltamethrin induced oxidative stress damage in intestinal tissue. Compared with the blank control group, the expression of autophagy-related genes B-cell lymphoma/Leukemia-2 (bcl-2), c-Jun N-terminal kinase (jnk), Microtuble-associated protein light chain 3 (lc3c), Cysteine-dependent Aspartate-specific Protease 8 (caspase 8), BECN1(beclin1), oxidative stress damage-related genes MAS1 proto-oncogene (mas), Glutathione Peroxidase (gpx), kelch-like ECH-associated protein 1 (keap1), Sequestosome 1 (p62), Interleukin-6 (il-6), and immune-related genes Lipopolysaccharide-induced TNF-alpha Factor (litaf), Heat shock protein 90 (hsp90) and prophenoloxidase (propo) in the deltamethrin treatment group were significantly up-regulated at 96 h (p < 0.05 or p < 0.01). Additionally, 16S rRNA sequencing showed that the diversity of intestinal flora in the deltamethrin-treated group was significantly higher compared with the blank control group (p < 0.01). Analysis of the differences in the composition of intestinal flora at the genus level showed that the relative abundance of Candidatus Bacilloplasma in the deltamethrin treatment group was significantly lower than that in the blank control group (p < 0.01). In contrast, the relative abundances of Flavobacterium, Lachnospiraceae_NK4A136_group, Acinetobacter, Chryseobacterium, Lacihabitans, Taibaiella, Hydrogenophaga, Acidovorax, and Undibacterium were significantly higher than those in the blank control group (p < 0.05 or p < 0.01). Pearson correlation analysis revealed that Malaciobacter, Shewanella, and Prevotella exhibited significant positive correlations with gene indicators (jnk, gpx, lc3c, litaf, hsp90), while Dysgonomonas, Vibrio, and Flavobacterium demonstrated significant negative correlations with multiple gene indicators (caspase 8, p62, il-16, keap1, jnk, etc). These results demonstrate that deltamethrin significantly impacts the gut microbiota, immune function, and antioxidant capacity of E. sinensis. The changes in gut microbiota have correlations with the biomarkers of intestinal tissue injury genes, indicating that gut microbiota plays a crucial role in deltamethrin-induced intestinal tissue damage. These insights contribute to a better understanding of the ecological risks associated with deltamethrin exposure in aquatic organisms. Full article

The pandemic of coronavirus disease 2019 (COVID-19), brought about by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has significantly impacted public health and the economy. A fundamental aspect of addressing this virus lies in elucidating the mechanisms through which it induces disease. Our study reveals that Non-structural protein 6 (NSP6) of SARS-CoV-2 promotes the initiation of autophagy by activating Beclin1. In the later stage of autophagy, however, NSP6 causes a blockage in the autophagy–lysosome degradation via the inhibition of Mucolipin 1 (MLN1). The single nucleotide polymorphism (SNP) L37F in NSP6, which is associated with asymptomatic infection, similarly enhances the initiation of autophagy but displays a reduced ability to impede lysosome-dependent degradation. In summary, we demonstrated the dual-regulation mechanism of NSP6 in autophagy, which may be one of the reasons for targeting cellular autophagy to induce viral pathogenesis. This finding may provide promising new directions for future research and clinical interventions. Full article

Retinoic acid (RA) is commonly used to differentiate SH-SY5Y neuroblastoma cells. This effect is sustained by a specific modulation of gene transcription, leading to marked changes in cellular proteins. In this scenario, autophagy may be pivotal in balancing protein synthesis and degradation. The present study analyzes whether some autophagy-related proteins and organelles are modified during RA-induced differentiation of SH-SY5Y cells. RA-induced effects were compared to those induced by starvation. SH-SY5Y cells were treated with a single dose of 10 µM RA or grown in starvation, for 3 days or 7 days. After treatments, cells were analyzed at light microscopy and transmission electron microscopy to assess cell morphology and immunostaining for specific markers (nestin, βIII-tubulin, NeuN) and some autophagy-related proteins (Beclin 1, LC3). We found that both RA and starvation differentiate SH-SY5Y cells. Specifically, cell differentiation was concomitant with an increase in autophagy proteins and autophagy-related organelles. However, the effects of a single dose of 10 μM RA persist for at least 7 days, while prolonged starvation produces cell degeneration and cell loss. Remarkably, the effects of RA are modulated in the presence of autophagy inhibitors or stimulators. The present data indicate that RA-induced differentiation is concomitant with an increased autophagy. Full article

Metabolic cardiomyopathy, encompassing diabetic and obese cardiomyopathy, is an escalating global health concern, driven by the rising prevalence of metabolic disorders such as insulin resistance, type 1 and type 2 diabetes, and obesity. These conditions induce structural and functional alterations in the heart, including left ventricular dysfunction, fibrosis, and ultimately heart failure, particularly in the presence of coronary artery disease or hypertension. Autophagy, a critical cellular process for maintaining cardiac homeostasis, is frequently disrupted in metabolic cardiomyopathy. This review explores the role of autophagy in the pathogenesis of high-fat diet (HFD) and streptozotocin (STZ)-induced metabolic cardiomyopathy, focusing on non-selective and selective autophagy pathways, including mitophagy, ER-phagy, and ferritinophagy. Key proteins and genes such as PINK1, Parkin, ULK1, AMPK, mTOR, ATG7, ATG5, Beclin-1, and miR-34a are central to the regulation of autophagy in metabolic cardiomyopathy. Dysregulated autophagic flux impairs mitochondrial function, promotes oxidative stress, and drives fibrosis in the heart. Additionally, selective autophagy processes such as lipophagy, regulated by PNPLA8, and ferritinophagy, modulated by NCOA4, play pivotal roles in lipid metabolism and iron homeostasis. Emerging therapeutic strategies targeting autophagy, including plant extracts (e.g., curcumin, dihydromyricetin), endogenous compounds (e.g., sirtuin 3, LC3), and lipid/glucose-lowering drugs, offer promising avenues for mitigating the effects of metabolic cardiomyopathy. Despite recent advances, the precise mechanisms underlying autophagy in this context remain poorly understood. A deeper understanding of autophagy’s regulatory networks, particularly involving these critical genes and proteins, may lead to novel therapeutic approaches for treating metabolic cardiomyopathy. Full article

Autophagy is a vital cellular pathway in eukaryotic cells, including neurons, where it plays significant roles in neurodevelopment and maintenance. A crucial step in autophagy is the formation of the class III phosphatidylinositol 3-kinase complex 1 (PI3KC3-C1), which is essential for initiating autophagosome biogenesis. Beclin 1 is the key component of PI3KC3-C1, and its interactors have been reported to affect autophagy. The brain-enriched adaptor protein FE65 has been shown to interact with Alzheimer’s disease amyloid precursor protein (APP) to alter the processing of APP. Additionally, FE65 has been implicated in various cellular pathways, including autophagy. We demonstrate here that FE65 positively regulates autophagy. FE65, through its C-terminus, has been shown to interact with Beclin 1. Notably, the overexpression of FE65 enhances Beclin 1-mediated autophagy, whereas this process is attenuated in FE65 knockout cells. Moreover, the stimulatory effect of FE65 on Beclin 1-mediated autophagy is diminished by an FE65 C-terminus deletion mutant that disrupts the FE65–Beclin 1 interaction. Lastly, we have found that the FE65-Beclin 1 interaction modulates the kinase activity of the PI3KC3-C1 complex. Together, we have identified FE65 as a novel Beclin 1 interactor, and this interaction potentiates autophagy. Full article

Background and Objectives: High fructose intake is associated with non-alcoholic fatty liver disease (NAFLD), a chronic liver disease that is on the rise worldwide. New alternatives for treatment, such as bioactive phytochemicals, are needed. The aim of this study was to investigate the beneficial role of resveratrol in treating non-alcoholic steatohepatitis (NASH). Materials and Methods: Sixty male albino rats were allocated to three groups: group I, the normal control group; group II, the fructose-enriched diet group (FED), which was fed a 70% fructose diet for six weeks to induce NASH; and group III, the resveratrol–FED group (RES + FED), which was given the same FED diet plus an oral dose of 70 mg/kg resveratrol (RES) every day for an additional six weeks. We performed histological evaluations and assessed blood lipids and liver enzymes to study resveratrol’s impact on NASH. Quantitative real-time PCR was used to assess the mRNA expression of nuclear factor E2-related factor 2 (Nrf2) in the liver samples. ELISA was used to measure Beclin 1, AMPK, IL-6, and the DNA-binding activity of Nrf2. Oxidative stress indicators, including GSH, SOD, and MDA, were evaluated spectrophotometrically. Results: Resveratrol effectively alleviated the biochemical and histopathological abnormalities associated with NASH, improving autophagy by raising Beclin 1 levels while reducing inflammation by decreasing IL-6 levels. Furthermore, resveratrol restored the liver architecture and the oxidative balance, as evidenced by the decreased MDA levels and improved antioxidant status via elevated GSH and SOD activities, as well as the activation of the AMPK/Nrf2 signaling axis. Conclusions: This study specifically examines resveratrol’s therapeutic effects in a high-fructose diet-induced NASH model, focusing on the AMPK/Nrf2 signaling pathway to address oxidative stress and autophagy, providing novel insights into its molecular mechanism of action. Resveratrol reduces NASH by boosting autophagy and activating the AMPK/Nrf2 pathway. These findings underscore the potential of resveratrol as a promising therapeutic agent that can support treatment alongside conventional medications in the management of non-alcoholic steatohepatitis (NASH). Full article

Oxidative stress, endoplasmic reticulum (ER) stress, and alterations in autophagy activity have been described as prominent factors mediating many pathological processes in chronic kidney disease (CKD). The accumulation of misfolded proteins in the ER may stimulate the unfolded protein response (UPR). The interplay between autophagy and UPR in hemodialysis (HD) patients remains unclear. The aim of the present study was to explore the associations between serum oxidative stress markers, autophagy activity, and ER stress markers in the peripheral blood mononuclear cells (PBMCs) of patients on HD. Autophagy and ER stress-related protein expression levels in PBMCs were measured using western blotting. The redox state of human serum albumin was measured via high-performance liquid chromatography. Levels of the microtubule associated protein light chain 3 (LC3)-II, BECLIN1, and p62/SQSTM1 proteins were significantly increased in PBMCs of HD patients compared to healthy subjects. The PBMCs in HD patients also displayed augmented glucose-regulated protein 78 kDa (GRP78), phosphorylated eukaryotic translation initiation factor 2, subunit 1 alpha (p-eIF2α), and activating transcription factor 6 (ATF6) levels (p < 0.05). Additionally, nuclear factor erythroid 2 (NF-E2)-related factor 2 (NRF2) levels were elevated in the PBMCs of HD patients, compared to those of healthy subjects. Correlation analysis showed that the redox status of albumin was significantly correlated with the p62 protein level in PBMCs. Compared to healthy controls, we found elevated autophagosome formation in HD patients. Increased expression of ER stress markers was also observed in HD patients. Furthermore, increased p62 expression was positively correlated with the protein expression of NRF2, as well as a reduced form of serum albumin (human mercaptalbumin; HMA), in HD patients. Full article