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Objective: Diabetic nephropathy (DN) is a serious complication that may occur during the later stages of diabetes, and can be further exacerbated by podocyte damage. Piperazine ferulate (PF) has well-defined nephroprotective effects and is used clinically in the treatment of chronic nephritis and other kidney diseases. However, the renoprotective effects and mechanisms of PF on DN are not clear. This study aims to investigate the protective effect of PF on DN and its mechanism of action, to inform the clinical application of PF in DN treatment. Methods: Network pharmacology was performed to predict the mechanism of action of PF in DN. Male Sprague Dawley rats were intraperitoneally injected with STZ (60 mg/kg) to establish a DN model, and then assessed for renal injury after 12 weeks of administration. In vitro, rat podocytes were treated with 25 mmol/L glucose and cultured for 24 h, followed by an assessment of cell injury. Results: Our results showed that PF significantly improved renal function, reduced renal pathological changes, decreased inflammatory response, and alleviated podocyte damage in DN rats. PF also attenuated glucose-induced podocyte injury in vitro. Regarding molecular mechanisms, our study demonstrated that PF downregulated the expression of genes and proteins related to AGE-RAGE-mediated inflammatory signaling. Conclusion: In summary, PF exerts its renoprotective effects by decreasing inflammation and protecting against podocyte injury through the inhibition of the AGE/RAGE/NF-κB/NLRP3 pathway. Overall, these data support the clinical potential of PF as a renoprotective agent in DN.
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AIMS: Diabetic kidney disease (DKD) significantly impairs quality of life in individuals with diabetes mellitus (DM). The influence of the Dietary Inflammatory Index (DII) on DKD, which is associated with adverse health outcomes, is not well-understood. METHODS: We analyzed 2712 subjects from the National Health and Nutrition Examination Survey (NHANES) spanning 2011-2018, aiming to elucidate the relationship between DII and DKD. RESULTS: DKD was diagnosed in 1016 participants (37.46%). Elevated DII levels were significantly associated with an increased DKD risk, as evidenced by multivariate logistic regression (Odds Ratio [OR] = 1.40, 95% Confidence Interval [CI] 1.12-1.75, P < 0.05). Further analysis after adjusting for covariates highlighted a notable non-linear correlation between DII and DKD risk, at DII values below 0.45, the risk of DKD increases with higher DII levels, whereas it stabilizes beyond this point. Subgroup analysis additionally revealed that diabetic men have a significantly higher DKD risk compared to women (P < 0.05). CONCLUSION: Our study indicates a pronounced link between higher DII scores and increased risk of DKD among DM patients. These findings underscore the paramount importance of dietary management in DM treatment, stressing the need for interventions focused on reducing dietary inflammation to decelerate DKD progression.
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Acute kidney injury (AKI) is characterized by a sudden decline in renal function. Traditional Chinese medicine has employed Fuzi for kidney diseases; however, concerns about neurotoxicity and cardiotoxicity have constrained its clinical use. This study explored mesaconine, derived from processed Fuzi, as a promising low-toxicity alternative for AKI treatment. In this study, we assessed the protective effects of mesaconine in gentamicin (GM)-induced NRK-52E cells and AKI rat models in vitro and in vivo, respectively. Mesaconine promotes the proliferation of damaged NRK-52E cells and down-regulates intracellular transforming growth factor ß1 (TGF-ß1) and kidney injury molecule 1 (KIM-1) to promote renal cell repair. Concurrently, mesaconine restored mitochondrial morphology and permeability transition pores, reversed the decrease in mitochondrial membrane potential, mitigated mitochondrial dysfunction, decreased ATP production, inhibited inflammatory factor release, and reduced early apoptosis rates. In vivo, GM-induced AKI rat models exhibited elevated AKI biomarkers, in which mesaconine was effectively reduced, indicating improved renal function. Mesaconine enhanced superoxide dismutase activity, reduced malondialdehyde content, alleviated inflammatory infiltrate, mitigated tubular and glomerular lesions, and downregulated NF-κB (nuclear factor-κb) p65 expression, leading to decreased tumor necrosis factor-α (TNF-α) and IL-1ß (interleukin-1ß) levels in GM-induced AKI animals. Furthermore, mesaconine inhibited the expression of renal pro-apoptotic proteins (Bax, cytochrome c, cleaved-caspase 9, and cleaved-caspase 3) and induced the release of the anti-apoptotic protein bcl-2, further suppressing apoptosis. This study highlighted the therapeutic potential of mesaconine in GM-induced AKI. Its multifaceted mechanisms, including the restoration of mitochondrial dysfunction, anti-inflammatory and antioxidant effects, and apoptosis mitigation, make mesaconine a promising candidate for further exploration in AKI management.
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Aconitum , Injúria Renal Aguda , Apoptose , Rim , Mitocôndrias , Ratos Sprague-Dawley , Animais , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/patologia , Apoptose/efeitos dos fármacos , Aconitum/química , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Masculino , Ratos , Linhagem Celular , Rim/efeitos dos fármacos , Rim/patologia , Gentamicinas/toxicidade , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Aconitina/análogos & derivados , Aconitina/farmacologia , Aconitina/uso terapêutico , Modelos Animais de Doenças , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Humanos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , DiterpenosRESUMO
Chronic kidney disease (CKD) is a type of chronic disease in which multiple factors are responsible for the structural and functional disorders of the kidney. Piperazine ferulate (PF) has anti-platelet and anti-fibrotic effects, and its mechanism of action remains to be elucidated. This study aimed to investigate the protective effect of PF against CKD in rats and to determine its mechanism of action. Network pharmacology was used to predict potential PF action targets in the treatment of CKD and to further validate them. A rat model of CKD was established; blood was collected, etc., for the assessment of the renal function; renal pathologic damage was examined using hematoxylin and eosin (HE) staining and Masson staining; changes in the levels of TGF-ß1 and α-SMA were determined with ELISA; EPOR, FN, and COL I expression were detected utilizing immunohistochemistry; and HIF-1α, HIF-2α, and EPO protein molecules were analyzed deploying western blotting. PF reduces Scr, BUN, and 24 h UP levels; decreases FN and COL I expression; and attenuates renal injury. Additionally, PF inhibited TGF-ß1 and stimulated the production of HIF-1α and HIF-2α, which downregulated α-SMA and upregulated EPO. PF attenuated the progression of the CKD pathology, and the mechanism of its action is possibly associated with the promotion of HIF-1α/HIF-2α/EPO production and TGF-ß1 reduction.
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Nefrectomia , Ratos Sprague-Dawley , Insuficiência Renal Crônica , Fator de Crescimento Transformador beta1 , Animais , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/prevenção & controle , Masculino , Fator de Crescimento Transformador beta1/metabolismo , Ratos , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo , Eritropoetina/farmacologia , Piperazinas/farmacologia , Piperazina/farmacologia , Modelos Animais de Doenças , Ácidos Cumáricos/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Postpartum depression (PPD) is a common psychiatric disorder in women after childbirth. Per data from epidemiologic studies, PPD affects about 5%-26.32% of postpartum mothers worldwide. Biological factors underlying this condition are multiple and complex and have received extensive inquiries for the roles they play in PPD. Chinese herbal medicine (CHM), which is widely used as a complementary and alternative therapy for neurological disorders, possesses multi-component, multi-target, multi-access, and low side effect therapeutic characteristics. CHM has already shown efficacy in the treatment of PPD, and a lot more research exploring the mechanisms of its potential therapeutic effects is being conducted. AIM OF THE REVIEW: This review provides an in-depth and comprehensive overview of the underlying mechanisms of PPD, as well as samples the progress made in researching the potential role of CHM in treating the disorder. MATERIALS AND METHODS: Literature was searched comprehensively in scholarly electronic databases, including PubMed, Web of Science, Scopus, CNKI and WanFang DATA, using the search terms "postpartum depression", "genetic", "hormone", "immune", "neuroinflammation", "inflammation", "neurotransmitter", "neurogenesis", "brain-gut axis", "traditional Chinese medicine", "Chinese herbal medicine", "herb", and an assorted combination of these terms. RESULTS: PPD is closely associated with genetics, as well as with the hormones, immune inflammatory, and neurotransmitter systems, neurogenesis, and gut microbes, and these biological factors often interact and work together to cause PPD. For example, inflammatory factors could suppress the production of the neurotransmitter serotonin by inducing the regulation of tryptophan-kynurenine in the direction of neurotoxicity. Many CHM constituents improve anxiety- and depression-like behaviors by interfering with the above-mentioned mechanisms and have shown decent efficacy clinically against PPD. For example, Shen-Qi-Jie-Yu-Fang invigorates the neuroendocrine system by boosting the hormone levels of hypothalamic pituitary adrenal (HPA) and hypothalamic pituitary gonadal (HPG) axes, regulating the imbalance of Treg/T-helper cells (Th) 17 and Th1/Th2, and modulating neurotransmitter system to play antidepressant roles. The Shenguiren Mixture interferes with the extracellular signal-regulated kinase (ERK) pathway to enhance the number, morphology and apoptosis of neurons in the hippocampus of PPD rats. Other herbal extracts and active ingredients of CHM, such as Paeoniflorin, hypericin, timosaponin B-III and more, also manage depression by remedying the neuroendocrine system and reducing neuroinflammation. CONCLUSIONS: The pathogenesis of PPD is complex and diverse, with the main pathogenesis not clear. Still, CHM constituents, like Shen-Qi-Jie-Yu-Fang, the Shenguiren Mixture, Paeoniflorin, hypericin and other Chinese Medicinal Formulae, active monomers and Crude extracts, treats PPD through multifaceted interventions. Therefore, developing more CHM components for the treatment of PPD is an essential step forward.
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Antracenos , Depressão Pós-Parto , Medicamentos de Ervas Chinesas , Glucosídeos , Monoterpenos , Perileno/análogos & derivados , Humanos , Feminino , Animais , Ratos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Depressão Pós-Parto/tratamento farmacológico , Medicina Tradicional Chinesa , Fatores Biológicos , NeurotransmissoresRESUMO
To establish pathological features of skeletal muscle post-stroke and to provide a background for promising interventions. Adult male SD rats were selected and randomly divided into a control group, a sham group, and a middle cerebral artery occlusion (MCAO) group. The tolerance and capability of exercise were separately collected on days 1, 3, 5, and 7 after the MCAO operation. The neurological deficits, brain infarct volume, soleus histopathology, mRNA-seq analysis, flow cytometry, immunofluorescence, and protein expression analysis were performed on the seventh day. Rats in the MCAO group showed that soleus tissue weight, pulling force, exercise capacity, endurance, and muscle structure were significantly decreased. Moreover, the RNA sequencing array revealed that mitochondrial-mediated autophagy was the critical pathological process, and the result of transcriptomic findings was confirmed at the translational level. The mitochondrial membrane potential and the mfn2 and p62 protein expression were decreased, and the Beclin-1, ATG5, Parkin, PINK1, LC3B, and Drp1 expression were upregulated; these results were consistent with immunohistochemistry. This is the first report on the pathological features of limbic symptoms on day 7 after MCAO surgery in rats. In addition, we further confirmed that autophagy is one of the main causative mechanisms of reduced muscle function after stroke.
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Phellinus spp., an important medicinal fungus mushroom extensively cultivated and consumed in East Asia for over 2000 years, is traditionally considered a precious food supplement and medicinal ingredient. Published studies showed that the polysaccharides are major bioactive macromolecules from Phellinus spp. (PPs) with multiple health-promoting effects, including immunomodulatory, anti-cancer, anti-inflammatory, hepatoprotective, hypoglycemic, hypolipidemic, antioxidant, and other bioactivities. Although the polysaccharides extracted from the fruiting body, mycelium, and fermentation broth of Phellinus spp. have been extensively studied for the extraction and purification methods, structural characteristics, and pharmacological activities, the knowledge for their structures and bioactivity relationship, toxicologic effects, and pharmacokinetic profile is limited. This review systematically summarizes the recent progress in the isolation and purification, chemical structures, bioactivities, and the underlying mechanisms of PPs. Information from this review provides insights into the further development of polysaccharides from PPs as therapeutic agents and functional foods.
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Agaricales , Agaricales/química , Anti-Inflamatórios , Antioxidantes/química , Micélio , Phellinus , Polissacarídeos/químicaRESUMO
BACKGROUND: Piperazine ferulate (PF) is widely used in chronic nephritis and nephrotic syndrome in clinic. PF can improve diseases related inflammation by inhibiting the activation of nuclear factor kappa-B (NF-κB) signal. Acute kidney injury (AKI) is usually associated with the occurrence and development of renal inflammation. However, the nephroprotective effect and anti-inflammatory mechanisms of PF on AKI are not clear. PURPOSE: This study aimed to investigate the nephroprotective effects of PF on gentamicin (GM) induced AKI in rats and its potential mechanisms. METHODS: Male Sprague Dawley (SD) rats were intraperitoneally injected with GM (100 mg/kg/day) with or without PF (50 and 100 mg/kg/day) for 7 consecutive days. In vitro, the NRK-52e cells were exposed to GM (7 mg/ml) with or without PF (62.5 µg/ml) treatment. The renal injury and cell damage were assessed subsequently. RESULTS: Our findings showed that PF treatment can significantly improve renal function, reduce renal pathological changes, and attenuate inflammatory response in rats treated with gentamicin. Besides, PF could significantly reduce the cell damage and cellular inflammatory response. In terms of mechanisms, our study revealed that PF can evidently inhibit the activation of NF-κB and nod-like receptor family pyrin domain protein 3 (NLRP3) inflammasome. Meanwhile, it could down regulate the expressions of protein and gene of p-IKKα, p-IKKß, p-p65, p65, p50, p105, NLRP3 and IL-1ß. CONCLUSION: Our findings showed that PF may improve inflammation by inhibiting the NF-κB/NLRP3 pathway, so as to attenuate AKI.
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Undaria pinnatifida, one of the most widespread seafood consumed in China and many other nations, has been traditionally utilized as an effective therapeutically active substance for edema, phlegm elimination and diuresis, and detumescence for more than 2000 years. Numerous studies have found that polysaccharides of U. pinnatifida play an indispensable role in the nutritional and medicinal value. The water extraction and alcohol precipitation method are the most used method. More than 40 U. pinnatifida polysaccharides (UPPs) were successfully isolated and purified from U. pinnatifida, whereas only few of them were well characterized. Pharmacological studies have shown that UPPs have high-order structural features and multiple biological activities, including anti-tumor, antidiabetic, immunomodulatory, antiviral, anti-inflammatory, antioxidant, anticoagulating, antithrombosis, antihypertension, antibacterial, and renoprotection. In addition, the structural characteristics of UPPs are closely related to their biological activity. In this review, the extraction and purification methods, structural characteristics, biological activities, clinical settings, toxicities, structure-activity relationships and industrial application of UPPs are comprehensively summarized. The structural characteristics and biological activities as well as the underlying molecular mechanisms of UPPs were also outlined. Furthermore, the clinical settings and structure-activity functions of UPPs were highlighted. Some research perspectives and challenges in the study of UPPs were also proposed.
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Undaria , Polissacarídeos/química , Undaria/químicaRESUMO
MicroRNAs (miRNAs) serve as gene silencers involved in essential cell functions. The role of miR-206 and E74-like factor 3 (Elf3) has been identified in osteoarthritis (OA), while the effect of exosomal miR-206 from bone marrow mesenchymal stem cells (BMSCs) in OA remains largely unknown. Thus, we aim to explore the role of exosomal miR-206 from BMSCs in OA with the involvement of Elf3. BMSCs and BMSC-derived exosomes (BMSC-exos) were obtained and identified. OA mouse models were constructed by anterior cruciate ligament transection and then treated with BMSC-exos or BMSC-exos containing miR-206 mimic/inhibitor. The expression of miR-206, Elf3, inflammatory factors, osteocalcin (OCN) and bone morphogenetic protein 2 (BMP2) in mouse femoral tissues was assessed. The pathological changes in mouse femur tissues were observed. The mouse osteoblasts were identified and treated with untransfected or transfected BMSC-exos, and then, the expression of miR-206, Elf3, OCN and BMP2 was determined. The alkaline phosphatase (ALP) activity, calcium deposition level, OCN secretion, proliferation, apoptosis and cell cycle arrest in osteoblasts were measured. MiR-206 was down-regulated while Elf3 was up-regulated in OA animal and cellular models. Exosomal miR-206 ameliorated inflammation and increased expression of OCN and BMP2 in mouse femoral tissues. Moreover, exosomal miR-206 promoted ALP activity, calcium deposition level, OCN secretion and proliferation and inhibited apoptosis in OA osteoblasts. Overexpressed Elf3 reversed miR-206 up-regulation-induced effects on OA osteoblasts. BMSC-derived exosomal miR-206 promotes proliferation and differentiation of osteoblasts in OA by reducing Elf3. Our research may provide novel targets for OA treatment.
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Proteínas de Ligação a DNA/antagonistas & inibidores , Exossomos/genética , Células-Tronco Mesenquimais/citologia , MicroRNAs/farmacologia , Osteoartrite/prevenção & controle , Osteoblastos/citologia , Fatores de Transcrição/antagonistas & inibidores , Animais , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Proteínas de Ligação a DNA/metabolismo , Modelos Animais de Doenças , Exossomos/metabolismo , Células-Tronco Mesenquimais/metabolismo , Camundongos , MicroRNAs/genética , Osteoartrite/genética , Osteoartrite/metabolismo , Osteoartrite/patologia , Osteoblastos/metabolismo , Fatores de Transcrição/metabolismoRESUMO
OBJECTIVE: This study was performed to depict the patterns of change in the perioperative hemoglobin (Hb) concentration and hematocrit (Hct) and to identify the optimal timing of Hb and Hct measurement in patients undergoing total knee arthroplasty (TKA). METHODS: This prospective observational study involved 302 consecutive patients who underwent TKA. The patients were kept in hospital for 1 full week postoperatively. Hb and Hct measurements were performed preoperatively and on days 1 to 7 postoperatively and then during clinic visits at 1, 3, and 6 months postoperatively. RESULTS: The Hb concentration and Hct decreased during the first few days postoperatively and reached a nadir on postoperative day 4 and 3, respectively; they then recovered in the following days. Significant differences in the Hb concentration and Hct were detected between the preoperative period and day 1, between days 1 and 2, between days 2 and 3, between day 7 and 1 month, and between 1 and 3 months. A significant difference in the Hct was also detected between 3 and 6 months. CONCLUSION: The optimal timing of Hb and Hct measurement is on postoperative day 3 or 4. This timing accurately reflects ongoing hidden blood loss to better guide blood transfusions.