OBJECTIVE: To investigate the underlying mechanism of "Zhibian" (BL54)-toward-"Shuidao" (ST28) acupuncture technique for improving reproductive function in mice with asthenospermia by regulating ferroptosis pathway. METHODS: Sixty male C57BL/6 mice were randomly divided into a blank group, a model group, an acupuncture group and a Fer-1 group, 15 mice in each one. Except the blank group, the intraperitoneal injection with cyclophosphamide (50·kg^-1·d^-1) was administered to establish the asthenospermia model in the mice of the rest 3 groups for 5 consecutive days. In the acupuncture group, "Zhibian" (BL54)-toward-"Shuidao" (ST28) acupuncture technique was operated in the mice, for 20 min each time; and in the Fer-1 group, Fer-1 solution (1 mg/kg) was injected intraperitoneally. The interventions of these two groups were delivered once daily and for 2 consecutive weeks. The testicular wet weight was measured and the testicular coefficient was calculated. Using sperm quality detection system, the sperm quality was detected. With ELISA used, the contents of testosterone (T), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in the serum were detected. With HE staining, testicular and epididymal morphology was observed. Immunofluorescence was used to detect the expression of reactive oxygen species (ROS) in the testes. Biochemical assay was conducted to determine the contents of malondialdehyde (MDA), reduced glutathione (GSH), and total iron ion (TFe) in the testicular tissue. Transmission electron microscopy was used to examine mitochondrial structure of the testis, while JC-1 staining was used to assess mitochondrial membrane potential in the testicular tissue. Fluorescence quantitative PCR and Western blot analyses were employed to measure the mRNA and protein expression of solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), and acyl-CoA synthetase long-chain family member 4 (ACSL4) in the testicular tissue. RESULTS: Compared with the blank group, in the model group, the testicular wet weight and testicular coefficient decreased (P<0.01); the sperm concentration and sperm motility reduced (P<0.01), and the contents of T, FSH, and LH decreased in the serum (P<0.01); and the seminiferous tubules in the testis showed loose structure and deformed lumen, sperm cells were disorganized and the sperm numbers reduced; the tubular walls became thinner, and sperm numbers in the lumen less; the expression of ROS in testicular tissue, as well as the contents of MDA and TFe increased (P<0.01), and the content of GSH decreased (P<0.01); and the numbers of mitochondria reduced, the structure of cristae was serious damaged, and mitochondrial membrane potential level declined (P<0.01); the mRNA and protein expression of SLC7A11, GPX4, and FTH1 decreased (P<0.01), while the mRNA and protein expression of ACSL4 increased (P<0.01). In comparison with the model group, the acupuncture and Fer-1 groups showed the increase of testicular wet weight and coefficient (P<0.01), sperm concentration and motility (P<0.01), and the serum contents of T, FSH, and LH (P<0.01); and the improvements in testicular and epididymal histopathology; ROS expression and the contents of MDA and TFe decreased (P<0.01), and the content of GSH elevated (P<0.05); the mitochondrial structure and numbers were ameliorated and mitochondrial membrane potential rose (P<0.01). Besides, in comparison with the model group, the mRNA expression of SLC7A11 was higher (P<0.05, P<0.01), the mRNA and protein expression of GPX4 and FTH1 increased (P<0.01, P<0.05), and the mRNA and protein expression of ACSL4 decreased (P<0.01) in the acupuncture and the Fer-1 groups; and the protein expression of SLC7A11 was higher in the Fer-1 group (P<0.05). CONCLUSION "Zhibian" (BL54)-toward-"Shuidao" (ST28) acupuncture technique may improve the reproductive capacity in the mice with asthenospermia by alleviating ferroptosis-induced cellular damage and ameliorating testicular function.
Animals ; Male ; Ferroptosis ; Mice ; Acupuncture Therapy ; Mice, Inbred C57BL ; Asthenozoospermia/metabolism* ; Humans ; Acupuncture Points ; Testis/metabolism* ; Luteinizing Hormone/metabolism* ; Malondialdehyde/metabolism* ; Reproduction ; Testosterone/metabolism*

OBJECTIVE: To observe the effects of electroacupuncture (EA) with different frequencies on spermatogenic function, testicular morphology and oxidative stress in oligoasthenospermia (OAT) rats, and to explore the mechanism and the optimal parameters of EA for OAT. METHODS: Sixty SPF-grade male SD rats were randomly divided into a solvent control group, a model group, a 2 Hz EA group, a 100 Hz EA group and a 2 Hz/100 Hz EA group, with 12 rats in each group. Except for the solvent control group, the other 4 groups were administered ornidazole suspension (800 mg·kg^-1·d^-1) by gavage for 28 d to establish the OAT model. Starting from the 1st of modeling, EA was applied at "Guanyuan" (CV4), "Qihai" (CV6) and bilateral "Sanyinjiao" (SP6) and "Zusanli" (ST36) in the 3 EA groups, continuous wave of 2 Hz, continuous wave of 100 Hz, and disperse-dense wave of 2 Hz/100 Hz were used in the 2 Hz EA group, the 100 Hz EA group, and the 2 Hz/100 Hz EA group, respectively, with current intensity of 1-3 mA, 30 min a time, once every other day, for 28 consecutive days. After intervention, the testicular index was calculated, epididymal sperm quality was assessed, and the fertility ability was observed; morphology of testicular tissue was observed by HE staining, and the Johnson score was calculated; the positive expression of reactive oxygen species (ROS) in testicular tissue was detected by immunofluorescence; the activity of superoxide dismutase (SOD) and catalase (CAT), as well as the level of malondialdehyde (MDA) in testicular tissue were measured by ELISA; the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in testicular tissue was detected by Western blot. RESULTS: Compared with the solvent control group, in the model group, the testicular index, sperm concentration, sperm motility and the number of offspring were decreased (P<0.01), the seminiferous tubules atrophied and the Johnson score decreased (P<0.01); the activity of SOD and CAT, as well as the protein expression of Nrf2 and HO-1 in testicular tissue were decreased (P<0.01); the sperm deformity rate, the positive expression of ROS and the MDA level in testicular tissue were increased (P<0.01). Compared with the model group, in the 2 Hz EA group, the 100 Hz EA group and the 2 Hz/100 Hz EA group, the testicular index, sperm concentration, sperm motility and the number of offspring were increased (P<0.05, P<0.01), the pathological morphology of testicular tissue improved and the Johnson scores increased (P<0.01); the activity of SOD and CAT, as well as the protein expression of Nrf2 and HO-1 in testicular tissue were increased (P<0.05, P<0.01); the sperm deformity rate, the positive expression of ROS and the MDA level in testicular tissue were decreased (P<0.05, P<0.01). Compared with the 2 Hz EA group, in the 2 Hz/100 Hz EA group, the testicular index, sperm concentration, sperm motility, as well as the CAT activity and HO-1 protein expression in testicular tissue were increased (P<0.01, P<0.05); the positive expression of ROS was decreased (P<0.01). Compared with the 100 Hz EA group, in the 2 Hz/100 Hz EA group, the testicular index was increased (P<0.01), the positive expression of ROS in testicular tissue was decreased (P<0.01). CONCLUSION EA with 2 Hz continuous wave, 100 Hz continuous wave, and 2 Hz/100 Hz disperse-dense wave can all improve the spermatogenic arrest and reduce the level of oxidative stress in testicular tissue in OAT rats, the mechanism may be related to up-regulating the protein expression of Nrf2 and HO-1 and improving oxidative stress. EA with disperse-dense wave of 2 Hz/100 Hz shows the optimal effect.
Male ; Animals ; Electroacupuncture ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Spermatogenesis ; Oligospermia/genetics* ; Humans ; Testis/metabolism* ; Superoxide Dismutase/metabolism* ; Asthenozoospermia/genetics* ; Acupuncture Points ; Malondialdehyde/metabolism*

This study investigates the mechanism by which Xintong Granules improve myocardial ischemia-reperfusion injury(MIRI) through the regulation of gut microbiota and their metabolites, specifically short-chain fatty acids(SCFAs). Rats were randomly divided based on body weight into the sham operation group, model group, low-dose Xintong Granules group(1.43 g·kg~(-1)·d~(-1)), medium-dose Xintong Granules group(2.86 g·kg~(-1)·d~(-1)), high-dose Xintong Granules group(5.72 g·kg~(-1)·d~(-1)), and metoprolol group(10 mg·kg~(-1)·d~(-1)). After 14 days of pre-administration, the MIRI rat model was established by ligating the left anterior descending coronary artery. The myocardial infarction area was assessed using the 2,3,5-triphenyltetrazolium chloride(TTC) staining method. Apoptosis in tissue cells was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL) assay. Pathological changes in myocardial cells and colonic tissue were observed using hematoxylin-eosin(HE) staining. The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6), creatine kinase MB isoenzyme(CK-MB), and cardiac troponin T(cTnT) in rat serum were quantitatively measured using enzyme-linked immunosorbent assay(ELISA) kits. The activities of lactate dehydrogenase(LDH), creatine kinase(CK), and superoxide dismutase(SOD) in myocardial tissue, as well as the level of malondialdehyde(MDA), were determined using colorimetric assays. Gut microbiota composition was analyzed by 16S rDNA sequencing, and fecal SCFAs were quantified using gas chromatography-mass spectrometry(GC-MS). The results show that Xintong Granules significantly reduced the myocardial infarction area, suppressed cardiomyocyte apoptosis, and decreased serum levels of pro-inflammatory cytokines(TNF-α, IL-1β, and IL-6), myocardial injury markers(CK-MB, cTnT, LDH, and CK), and oxidative stress marker MDA. Additionally, Xintong Granules significantly improved intestinal inflammation in MIRI rats, regulated gut microbiota composition and diversity, and increased the levels of SCFAs(acetate, propionate, isobutyrate, etc.). In summary, Xintong Granules effectively alleviate MIRI symptoms. This study preliminarily confirms that Xintong Granules exert their inhibitory effects on MIRI by regulating gut microbiota imbalance and increasing SCFA levels.
Animals ; Gastrointestinal Microbiome/drug effects* ; Rats ; Male ; Myocardial Reperfusion Injury/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Apoptosis/drug effects* ; Humans ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/genetics* ; Malondialdehyde/metabolism*

Through a comprehensive analysis combining network pharmacology prediction and transcriptomics, this study systematically explained the multi-target mechanism of Cyanotis arachnoidea(CA) Gel in improving melasma. A melasma model was induced in female SD rats by progesterone injection combined with ultraviolet B(UVB) irradiation for 40 consecutive days, while the blank control group was only fed routinely. After successful model establishment, the rats were randomly divided into five groups and administered different doses of CA ethanol extract gel(high, medium, and low doses) or arbutin Gel(positive control), which were applied once daily for 28 consecutive days. Subsequently, the levels of superoxide dismutase(SOD), malondialdehyde(MDA), and tyrosinase(TYR) in the skin, serum, and liver tissues were measured. Hematoxylin-eosin(HE) staining and Masson-Fontana staining were used to observe the pathological changes in the tissues. Network pharmacology combined with transcriptomics was employed to identify core targets and pathways, and the differential gene expression was validated by quantitative real-time PCR(qPCR). Pharmacodynamic experiments showed that CA Gel significantly increased SOD activity and decreased MDA and TYR levels in the skin, serum, and liver of model rats. It also improved epidermal thickening, inflammatory infiltration, collagen loss, and melanin deposition. Network pharmacology analysis showed that CA mainly regulated core targets such as signal transducer and activator of transcription 3(STAT3), epidermal growth factor receptor(EGFR), and interleukin-6(IL-6), and modulated the phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT) and interleukin-17(IL-17) signaling pathways. Transcriptomic analysis showed that CA Gel significantly downregulated the gene expression of heat shock protein 90β family member 1(Hsp90b1), heat shock protein 90α family member 1(Hsp90aa1), and the key steroid synthesis enzyme cytochrome P450 family 17 subfamily A member 1(Cyp17a1), while upregulating thioredoxin 1(Txn1). qPCR results confirmed that CA Gel regulated oxidative stress and inflammatory response by inhibiting the IL-17 signaling pathway and steroid hormone synthesis. This study, for the first time, reveals the molecular mechanism of CA Gel in improving melasma through multi-target synergistic regulation of oxidative stress, inflammatory response, and hormone metabolism pathways, providing a scientific basis for the treatment of pigmentation diseases with traditional Chinese medicine.
Animals ; Rats ; Female ; Rats, Sprague-Dawley ; Network Pharmacology ; Drugs, Chinese Herbal/administration & dosage* ; Melanosis/metabolism* ; Transcriptome/drug effects* ; Humans ; Superoxide Dismutase/genetics* ; Signal Transduction/drug effects* ; Malondialdehyde/metabolism*

OBJECTIVES: To determine the neuroprotective effects of berberine hydrochloride (BBR) against lead-induced injuries on the hippocampus of rats. METHODS: Wistar rats were exposed orally to doses of 100 and 500 ppm lead acetate for 1 and 2 months to develop subchronic and chronic lead poisening models, respectively. For treatment, BBR (50 mg/kg daily) was injected intraperitoneally to rats poisoned with lead. At the end of the experiment, the spatial learning and memory of rats were assessed using the Morris water maze test. Hippocampal tissue changes were examined by hematoxylin and eosin staining. The activity of antioxidant enzymes catalase, superoxide dismutase, glutathione peroxidase, and malondialdehyde levels as parameters of oxidative stress and antioxidant status of the hippocampus were evaluated. RESULTS: BBR reduced cognitive impairment in rats exposed to lead (P<0.05 or P<0.01). The resulting biochemical changes included a decrease in the activity of antioxidants and an increase in lipid peroxidation of the hippocampus of lead-exposed rats (P<0.05 or P<0.01), which were significantly modified by BBR (P<0.05). BBR also increased the density of healthy cells in the hippocampus of leadexposed rats (P<0.05). Significant changes in tissue morphology and biochemical factors of the hippocampus were observed in rats that received lead for 2 months (P<0.05). Most of these changes were insignificant in rats that received lead for 1 month. CONCLUSION BBR can improve oxidative tissue changes and hippocampal dysfunction in lead-exposed rats, which may be due to the strong antioxidant potential of BBR.
Animals ; Hippocampus/pathology* ; Rats, Wistar ; Antioxidants/pharmacology* ; Berberine/therapeutic use* ; Cognition/drug effects* ; Male ; Lead Poisoning/metabolism* ; Chronic Disease ; Oxidative Stress/drug effects* ; Maze Learning/drug effects* ; Rats ; Lipid Peroxidation/drug effects* ; Malondialdehyde/metabolism*

OBJECTIVES: To investigate the inhibitory effect of FER-1 on methylglyoxal-induced ferroptosis in cultured mouse alveolar macrophages. METHODS: MH-S cells derived from mouse alveolar macrophages treated with 90 μg/mL methylglyoxal, 10 μmol/mL FER-1MG+FER-1, or both were examined for intracellular reactive oxygen species (ROS), malondialdehyde (MDA) and ferrous ion (Fe²⁺) levels and changes in mitochondrial membrane potential. Western blotting was performed to detect the protein expression levels of glutathione peroxidase 4 (GPX4) and long-chain acyl-CoA synthase 4 (ACSL4). RESULTS: Methylglyoxal treatment of MH-S cells for 24 h significantly decreased the protein expression level of GPX4, upregulated the protein expression of ACSL4, increased intracellular concentrations of ferrous ions, ROS and MDA, caused loss of mitochondrial membrane potential, and decreased cell viability. Treatment of the cells with FER-1 effectively attenuated these detrimental effects of methylglyoxal in MH-S cells by increasing GPX4 expression, reducing ACSL4 expression and intracellular ferrous ions, ROS and MDA levels, and restoring the mitochondrial membrane potential. CONCLUSIONS Methylglyoxal can induce ferroptosis in MH-S cells in a dose-dependent manner, and FER-1 can rescue the cells from methylglyoxal-induced ferroptosis.
Animals ; Ferroptosis/drug effects* ; Mice ; Pyruvaldehyde ; Macrophages, Alveolar/drug effects* ; Reactive Oxygen Species/metabolism* ; Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism* ; Membrane Potential, Mitochondrial/drug effects* ; Coenzyme A Ligases/metabolism* ; Malondialdehyde/metabolism* ; Cell Survival/drug effects*

The purpose of this study is to investigate whether chrysin reduces cerebral ischemia-reperfusion injury(CIRI) by inhi-biting ferroptosis in rats. Male SD rats were randomly divided into a sham group, a model group, high-, medium-, and low-dose chrysin groups(200, 100, and 50 mg·kg~(-1)), and a positive drug group(Ginaton, 21.6 mg·kg~(-1)). The CIRI model was induced in rats by transient middle cerebral artery occlusion(tMCAO). The indexes were evaluated and the samples were taken 24 h after the operation. The neurological deficit score was used to detect neurological function. The 2,3,5-triphenyl tetrazolium chloride(TTC) staining was used to detect the cerebral infarction area. Hematoxylin-eosin(HE) staining and Nissl staining were used to observe the morphological structure of brain tissues. Prussian blue staining was used to observe the iron accumulation in the brain. Total iron, lipid pero-xide, and malondialdehyde in serum and brain tissues were detected by biochemical reagents. Real-time quantitative polymerase chain reaction(RT-qPCR), immunohistochemistry, and Western blot were used to detect mRNA and protein expression of solute carrier fa-mily 7 member 11(SLC7A11), transferrin receptor 1(TFR1), glutathione peroxidase 4(GPX4), acyl-CoA synthetase long chain family member 4(ACSL4), and prostaglandin-endoperoxide synthase 2(PTGS2) in brain tissues. Compared with the model group, the groups with drug intervention showed restored neurological function, decreased cerebral infarction rate, and alleviated pathological changes. The low-dose chrysin group was selected as the optimal dosing group. Compared with the model group, the chrysin groups showed reduced content of total iron, lipid peroxide, and malondialdehyde in brain tissues and serum, increased mRNA and protein expression levels of SLC7A11 and GPX4, and decreased mRNA and protein expression levels of TFR1, PTGS2, and ACSL4. Chrysin may regulate iron metabolism via regulating the related targets of ferroptosis and inhibit neuronal ferroptosis induced by CIRI.
Rats ; Male ; Animals ; Rats, Sprague-Dawley ; Ferroptosis ; Signal Transduction ; Brain Ischemia/metabolism* ; Cyclooxygenase 2/metabolism* ; RNA, Messenger ; Cerebral Infarction ; Reperfusion Injury/metabolism* ; Malondialdehyde ; Infarction, Middle Cerebral Artery

Objective: To construct paraquat (PQ) poisoning rat model and to explore the effect of pirfenidone (PFD) on PQ-induced pulmonary fibrosis. Methods: In April 2017, male 6-8 week-old Wistar rats were selected, and PQ was administered intraperitoneally at one time. PFD was administered by gavage 2 hours after poisoning. The daily gavage doses were 100, 200 and 300 mg/kg, and the rats were divided into physiological saline group, PQ group, PQ+PFD 100 group, PQ+PFD 200 group, PQ+PFD 300 group, with 10 rats in each group at each observation time point. The pathological changes of lung tissue at different time points (the 1st, 3rd, 7th, 14th, 28th, 42nd and 56th days) after poisoning and the effect of PFD intervention with different dose on PQ-induced pulmonary fibrosis were observed. Pathological evaluation of lung tissue was performed by Ashcroft scale method. The PQ+PFD 200 group was selected to further explore the pathological changes of lung tissue, the contents of hydroxyproline and malondialdehyde in lung tissue were determined.And the tumor necrosis factor (TNF) -α, interleukin (IL) -6, transforming growth factor (TGF) -β1, fibroblast growth factor (FGF) -B, platelet-derived growth factor (PDGF) -AB, insulin-like growth factor (IGF) -1 and PQ concentrations in serum and lung tissue were determined. Results: On the 1st to 7th day after PQ exposure, rats developed lung inflammation, which was aggravated on the 7th to 14th day, and pulmonary fibrosis appeared on the 14th to 56th day. Compared with PQ group, the Ashcroft scores of lung fibrosis in PQ+PFD 200 group and PQ+PDF 300 group decreased significantly in 7th and 28th day (P<0.05), while the Ashcroft score of lung fibrosis in PQ+PFD 100 group had no significant difference (P>0.05). After PQ exposure, the content of hydroxyproline in lung tissue increased gradually and reached the peak value on the 28th day. Compared with the PQ group, the contents of hydroxyproline in the PQ+PFD 200 group decreased at the 7th, 14th and 28th day, and the contents of malondialdehyde decreased at the 3rd and 7th day, the differences were statistically significant (P<0.05). The levels of TNF-α, IL-6 in rat serum and lung tissue reached the peak value on the 7th day after PQ exposure, and the levels of TGF-β1, FGF-B and IGF-1 in rat serum and lung tissue reached the peak value on the 14th day after PQ exposure, and the level of PDGF-AB in rat serum and lung tissue reached the peak value on the 28th day after PQ exposure. Compared with PQ group, the level of serum IL-6 in PQ+PFD 200 group decreased significantly on the 7th day, and serum TGF-β1, FGF-B, PDGF-AB and IGF-1 on the 14th and 28th day were decreased significantly (P<0.05). The levels of TNF-α, IL-6 in lung tissue of rats in PQ+PFD 200 group on the 7th day decreased significantly, and the levels of TGF-β1, FGF-B and IGF-1 in lung tissue of rats on the 14th day were significantly decreased, and the level of PDGF-AB in lung tissue of rats on the 28th day were significantly decreased (P<0.05) . Conclusion: PFD partially alleviates the PQ-induced lung inflammation and fibrosis by inhibiting oxidative stress, reducing the levels of pro-inflammatory and pro-fibrotic cytokines in serum and lung tissue, but does not affect the concentrations of PQ in serum and lung tissue.
Male ; Rats ; Animals ; Pulmonary Fibrosis/chemically induced* ; Insulin-Like Growth Factor I ; Paraquat ; Transforming Growth Factor beta1 ; Hydroxyproline ; Interleukin-6 ; Tumor Necrosis Factor-alpha ; Rats, Wistar ; Malondialdehyde

OBJECTIVES: To investigate the effect and mechanism of lipid nanoparticle (LNP) delivery of small interfering RNA (siRNA) targeting Cyp2e1 gene on subacute alcoholic liver injury in mice. METHODS: siRNA targeting Cyp2e1 gene was encapsulated in LNP (si-Cyp2e1 LNP) by microfluidic technique and the resulting LNPs were characterized. The optimal dose of si-Cyp2e1 LNP administration was screened. Forty female C57BL/6N mice were randomly divided into blank control group, model control group, si-Cyp2e1 LNP group, LNP control group and metadoxine group. The subacute alcoholic liver injury mouse model was induced by ethanol feeding for 10 d plus ethanol gavage for the last 3 d. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, and the superoxide dismutase (SOD) activity as well as malondialdehyde, reactive oxygen species, glutathione, triacylglycerol, total cholesterol contents in liver tissue were measured in each group, and liver index was calculated. The expression of genes related to oxidative stress, lipid synthesis and inflammation in each group of mice were measured by realtime RT-PCR. RESULTS: Compared with the model control group, the levels of liver index, serum ALT, AST activities, malondialdehyde, reactive oxygen species, triacylglycerol, total cholesterol contents in liver tissue decreased, but the SOD activity as well as glutathione increased in the si-Cyp2e1 LNP group (all P<0.01). Hematoxylin-eosin staining result showed disorganized hepatocytes with sparse cytoplasm and a large number of fat vacuoles and necrosis in the model control group, while the si-Cyp2e1 LNP group had uniformly sized and arranged hepatocytes with normal liver tissue morphology and structure. Oil red O staining result showed si-Cyp2e1 LNP group had lower fat content of the liver compared to the model control group (P<0.01), and no fat droplets accumulated. Anti-F4/80 monoclonal antibody fluorescence immunohistochemistry showed that the si-Cyp2e1 LNP group had lower cumulative optical density values compared to the model control group (P<0.01) and no significant inflammatory reaction. Compared with the model control group, the expression of catalytic genes P47phox, P67phox and Gp91phox were reduced (all P<0.01), while the expression of the antioxidant enzyme genes Sod1, Gsh-rd and Gsh-px were increased (all P<0.01). The mRNA expression of the lipid metabolism genes Pgc-1α and Cpt1 were increased (all P<0.01) and the lipid synthesis-related genes Srebp1c, Acc and Fasn were decreased (all P<0.01); the expression of liver inflammation-related genes Tgf-β, Tnf-α and Il-6 were decreased (all P<0.01). CONCLUSIONS The si-Cyp2e1 LNP may attenuate subacute alcoholic liver injury in mice mainly by reducing reactive oxygen levels, increasing antioxidant activity, blocking oxidative stress pathways and reducing ethanol-induced steatosis and inflammation.
Animals ; Female ; Mice ; Antioxidants/metabolism* ; Cholesterol/metabolism* ; Ethanol/pharmacology* ; Glutathione/pharmacology* ; Inflammation ; Lipids/pharmacology* ; Liver ; Malondialdehyde/pharmacology* ; Mice, Inbred C57BL ; Oxidative Stress ; Reactive Oxygen Species/metabolism* ; RNA, Small Interfering/pharmacology* ; Superoxide Dismutase ; Triglycerides/metabolism* ; Cytochrome P-450 CYP2E1/metabolism*

BACKGROUND: It remains unclear whether circulating malondialdehyde (MDA) levels change in people with diabetic retinopathy (DR). This systematic review compared circulating MDA levels in diabetic people with and without DR. METHODS: PubMed, Medline (Ovid), Embase (Ovid), and Web of Science were searched for case-control studies conducted before May 2022 in English that compared circulating MDA levels in people with and without DR. The following MeSH search terms were used: ("malondialdehyde" or "thiobarbituric acid reactive substances [TBARS]" or "lipid peroxidation" or "oxidative stress") and "diabetic retinopathy." Newcastle-Ottawa Quality Assessment Scale was used to evaluate the quality of the included studies. Random-effects pairwise meta-analysis pooled the effect size with standardized mean difference (SMD) and 95% confidence intervals (CIs). RESULTS: This meta-analysis included 29 case-control studies with 1680 people with DR and 1799 people with diabetes but not DR. Compared to people without DR, the circulating MDA levels were higher in those with DR (SMD, 0.897; 95% CI, 0.631 to 1.162; P  < 0.001). The study did not identify credible subgroup effects or publication bias and the sensitivity analysis confirmed the robustness of the study. CONCLUSIONS: Circulating MDA levels are higher in people with DR compared to those without. Future comparative studies that use more specific methods are required to draw firm conclusions. REGISTRATION PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42022352640.
Humans ; Diabetic Retinopathy ; Malondialdehyde ; Oxidative Stress ; Case-Control Studies ; Diabetes Mellitus