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1.
Zhongguo Zhong Yao Za Zhi ; 46(2): 426-435, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33645132

RESUMO

This study aimed to explore the effect of Salviae Miltiorrhizae Radix et Rhizoma, its stems and leaves on the diversity of intestinal microflora in rats with diabetic kidney injury. Diabetic rats model was established by feeding high glucose and high fat diet and 5% glucose solution with intraperitoneal injection of 30 mg·kg~(-1) streptozocin(STZ). The rats were randomly divided into normal group, model group, irbesartan control group, Huangkui Capsules control group, as well as low, middle and high dose groups of Sal-viae Miltiorrhizae Radix et Rhizoma, its stems and leaves. After administration for 2 weeks, 16 S rRNA technique was used to analyze the diversity of intestinal microflora in the feces of each group. The results showed rats in the model group developed renal tubular epithelial vacuole degeneration and a large amount of inflammatory cell infiltration in the renal interstitium. A small amount of inflammatory cell infiltration was seen in each administration group. The kidney structure of rats in irbesartan group, Huangkui Capsules group, high-dose group of Salviae Miltiorrhizae Radix et Rhizoma and its stem water extract, as well as high dose group of Salviae Miltiorrhizae Radix et Rhizoma and its stem ethnol extract group was close to the normal group. The diversity and structure of intestinal flora in the model group were significantly different from those in the normal group. Each administration group improved the fecal flora diversity in rats with diabetic kidney injury to a certain extent, especially the high dose of Salviae Miltiorrhizae Radix et Rhizoma and its stems water extract. Different flora were found in feces of diabetic nephropathy model rats on class, order, family and genus levels. On families and genera levels, the relative abundance of Bifidobacterium, Turicibacter, Peptostreptococcaceae, Desulfovibrio, and SMB53 showed an upward trend in model group, but that of Lactobacillus, Clostridium, Rikenella, Rumen fungi showed a downward trend. The administration groups can improve the relative abundance of the above intestinal flora in the model rats to a normal-like level. The results of this study provide a reference for resource utilization and further development of Salviae Miltiorrhizae Radix et Rhizoma.


Assuntos
Diabetes Mellitus Experimental , Nefropatias Diabéticas , Medicamentos de Ervas Chinesas , Microbioma Gastrointestinal , Salvia miltiorrhiza , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Ratos
2.
Anaesthesia ; 76 Suppl 1: 127-135, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33426661

RESUMO

Diabetes is the most common metabolic condition worldwide and about 20% of surgical patients will have this condition. It is a major risk-factor for worse outcomes after surgery including mortality; infective and non-infective complications; and increased length of stay. However, diabetes is a modifiable risk-factor, and programs to improve medical management have the potential to reduce peri-operative complications and the risk of harm. Regional anaesthesia has well-documented benefits in promoting the restoration of function but there are legitimate concerns that the incidence of complications of regional anaesthesia in patients with diabetes is higher. The aim of this review is to explore in detail the various potential advantages and disadvantages of regional anaesthesia in patients with diabetes. This, in turn, will allow practitioners to undertake more informed shared decision-making and potentially modify their anaesthetic technique for patients with diabetes.


Assuntos
Anestesia por Condução/métodos , Diabetes Mellitus , Complicações do Diabetes , Nefropatias Diabéticas/complicações , Humanos , Complicações Pós-Operatórias/etiologia
3.
Kidney Int ; 99(2): 301-303, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33509348

RESUMO

Risks of kidney failure and heart failure are markedly reduced by inhibition of the sodium glucose cotransporter 2 (SGLT2) in patients with diabetic kidney disease. In a post hoc analysis of the Study of Diabetic Nephropathy with Atrasentan (SONAR) trial, drop-in SGLT2 inhibitor usage during the atrasentan enrichment period led to greater reduction in albuminuria compared with atrasentan alone. These data support the hypothesis of greater longer-term kidney protection by combination SGLT2 inhibition and endothelin A receptor antagonism that could be tested in future clinical trials.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Albuminúria/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/etiologia , Antagonistas dos Receptores de Endotelina , Taxa de Filtração Glomerular , Glucose , Humanos , Sódio , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos
5.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 37(1): 8-15, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33441223

RESUMO

Objective To investigate the expression of pleckstrin homology(PH) domain leucine-rich repeats protein phosphatase 1 (PHLPP1) in renal tissue of patients with diabetic nephropathy (DN) and its effect on podocyte autophagy and apoptosis, and to explore its related mechanism. Methods Immunohistochemistry was used to detect PHLPP1 expression in renal tissue of patients with DN and non-diabetes, and immunofluorescence histochemical staining was used to detect the co-expression of nephrin and PHLPP1 to determine the localization of PHLPP1 in podocytes. Human glomerular podocyte cell line was cultured in normal glucose (NG) and high glucose (HG) media. The expression of PHLPP1 mRNA was detected by real-time quantitative PCR. Small interfering RNA of PHLPP1 (si-PHLPP1) targeting down-regulation of PHLPP1 was transfected into podocytes by Lipofectamine transient transfection technology, and the transfection efficiency was assessed by real-time PCR. According to the different treatment of podocytes, the cells were divided into NG group (podocytes cultured with normal glucose media), HG group (podocytes cultured with high glucose medium), HG combined with si-PHLPP1 group (podocytes transfected with si-PHLPP1 were cultured in high glucose medium), and HG combined with HCQ group (podocytes treated with hydroxychloroquine and high glucose medium). The formation of autophagic vesicles was observed by transmission electron microscope, and the protein expression levels of LC3, P62, PI3K, mTOR, p-mTOR, cleaved caspase 3 (c-caspase-3), AKT, p-AKT were detected by Western blotting. Annexin V-FITC/PI staining combined with flow cytometry was used to detect apoptosis. Results PHLPP1 was highly expressed in the renal tissue of patients with DN, and it was mainly expressed in the glomerular podocyte. The HG culture medium could promote the expression of PHLPP1 mRNA in podocytes in a time-dependent manner. Compared with NG group, the autophagy level of podocytes, the expression of PI3K and the phosphorylation level of mTOR in the HG group, HG combined with si-PHLPP1 group and HG combined with HCQ group were significantly reduced; the apoptosis rate and c-caspase-3 protein expression level were significantly enhanced; the phosphorylation level of AKT in the HG combined with si-PHLPP1 group significantly increased, but it in the other two groups significantly decreased. Compared with HG group, the apoptosis rate and c-caspase-3 protein expression in the HG combined with si-PHLPP1 group were significantly reduced, while autophagy level, PI3K protein expression and phosphorylation level of mTOR and Akt protein were significantly elevated. The autophagy level of HG combined with HCQ group was significantly inhibited, the apoptosis rate and c-caspase-3 protein expression were significantly raised, and other indicators showed no significant changes. Conclusion PHLPP1 is highly expressed in renal tissue of patients with DN, and the down-regulated expression of PHLPP1 in podocytes can promote the autophagy of podocytes and reduced the apoptosis of podocytes by activating PI3K/AKT/mTOR pathway.


Assuntos
Nefropatias Diabéticas , Podócitos , Apoptose , Autofagia , Nefropatias Diabéticas/genética , Regulação para Baixo , Glucose , Humanos , Proteínas Nucleares/genética , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosfoproteínas Fosfatases/genética , Podócitos/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
6.
Artigo em Inglês | MEDLINE | ID: mdl-33461698

RESUMO

Irbesartan, (2-butyl-3-({4-[2-(2H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)-1,3-diazaspiro[4.4]non-1-en-4-one), is a member of non-peptide angiotensin II receptor antagonists used worldwide in the treatment of hypertension and diabetic nephropathy in hypertensive patients with type 2 diabetes, elevated serum creatinine, and proteinuria. Irbesartan can be used alone or in combination with other antihypertensive agents (e.g., hydrochlorothiazide). These combination products are indicated for hypertension in patients with uncontrolled hypertension with monotherapy or first line in patients not expected to be well controlled with monotherapy. Irbesartan is also indicated for the treatment of diabetic nephropathy in patients with type 2 diabetes and hypertension, an elevated serum creatinine, and proteinuria. Irbesartan exerts its action mainly via a selective blockade action on AT1 receptors and the consequent reduced pressor effect of angiotensin II. This article discusses, by a critical comprehensive review of the literature on irbesartan in terms of its description, names, formulae, elemental composition, appearance, and therapeutic uses. The article also discusses the methods for preparation of irbesartan, its physical-chemical properties, analytical methods for its determination, pharmacological-toxicological properties, and dosing information.


Assuntos
Antagonistas de Receptores de Angiotensina/farmacologia , Nefropatias Diabéticas/tratamento farmacológico , Hipertensão , Irbesartana/farmacologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Diabetes Mellitus Tipo 2 , Humanos , Hipertensão/tratamento farmacológico , Irbesartana/uso terapêutico
7.
Chem Biol Interact ; 337: 109396, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33508306

RESUMO

Aging as one of intrinsic biological processes is a risk factor for many chronic diseases. Kidney disease is a global problem and health care burden worldwide. The diagnosis of kidney disease is currently based on serum creatinine and urea levels. Novel biomarkers may improve diagnostic accuracy, thereby allowing early prevention and treatment. Over the past few years, advances in genome analyses have identified an emerging class of noncoding RNAs that play critical roles in the regulation of gene expression and epigenetic reprogramming. Long noncoding RNAs (lncRNAs) are pervasively transcribed in the genome and could bind DNA, RNA and protein. Emerging evidence has demonstrated that lncRNAs played an important role in all stages of kidney disease. To date, only some lncRNAs were well identified and characterized, but the complexity of multilevel regulation of transcriptional programs involved in these processes remains undefined. In this review, we summarized the lncRNA expression profiling of large-scale identified lncRNAs on kidney diseases including acute kidney injury, chronic kidney disease, diabetic nephropathy and kidney transplantation. We further discussed a number of annotated lncRNAs linking with complex etiology of kidney diseases. Finally, several lncRNAs were highlighted as diagnostic biomarkers and therapeutic targets. Targeting lncRNAs may represent a precise therapeutic strategy for progressive renal fibrosis.


Assuntos
Nefropatias/patologia , Rim/metabolismo , RNA Longo não Codificante/metabolismo , Envelhecimento , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/patologia , Proteína Forkhead Box O1/química , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismo , Humanos , Nefropatias/genética , Nefropatias/terapia , Transplante de Rim , RNA Longo não Codificante/genética
8.
PLoS Pathog ; 17(1): e1009153, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33395426

RESUMO

Neuropilin-1 (NRP-1), a member of a family of signaling proteins, was shown to serve as an entry factor and potentiate SARS Coronavirus 2 (SARS-CoV-2) infectivity in vitro. This cell surface receptor with its disseminated expression is important in angiogenesis, tumor progression, viral entry, axonal guidance, and immune function. NRP-1 is implicated in several aspects of a SARS-CoV-2 infection including possible spread through the olfactory bulb and into the central nervous system and increased NRP-1 RNA expression in lungs of severe Coronavirus Disease 2019 (COVID-19). Up-regulation of NRP-1 protein in diabetic kidney cells hint at its importance in a population at risk of severe COVID-19. Involvement of NRP-1 in immune function is compelling, given the role of an exaggerated immune response in disease severity and deaths due to COVID-19. NRP-1 has been suggested to be an immune checkpoint of T cell memory. It is unknown whether involvement and up-regulation of NRP-1 in COVID-19 may translate into disease outcome and long-term consequences, including possible immune dysfunction. It is prudent to further research NRP-1 and its possibility of serving as a therapeutic target in SARS-CoV-2 infections. We anticipate that widespread expression, abundance in the respiratory and olfactory epithelium, and the functionalities of NRP-1 factor into the multiple systemic effects of COVID-19 and challenges we face in management of disease and potential long-term sequelae.


Assuntos
/imunologia , Neuropilina-1/imunologia , Internalização do Vírus , /patologia , Nefropatias Diabéticas/imunologia , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/virologia , Humanos , Memória Imunológica , Bulbo Olfatório/imunologia , Bulbo Olfatório/patologia , Bulbo Olfatório/virologia , Mucosa Respiratória/imunologia , Mucosa Respiratória/patologia , Mucosa Respiratória/virologia , Linfócitos T/imunologia , Linfócitos T/patologia
9.
Chem Biol Interact ; 335: 109332, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33387473

RESUMO

Renal fibrosis is a major cause of renal failure in diabetic nephropathy. Tropisetron is an antagonist of the 5HT3 receptor that exhibits anti-fibrosis effects. The present research aimed to investigate the protected role of tropisetron against renal fibrosis of diabetic nephropathy and its molecular mechanisms. For this purpose, male Wistar rats were allocated into 5 groups of control, tropisetron, diabetes, tropisetron + diabetes, and glibenclamide + diabetes (n = 7). After induction of type 1 diabetes with a single injection of STZ, tropisetron (3 mg/kg) and glibenclamide (1 mg/kg) were given to the rats daily by intraperitoneal injection for 2 weeks. The obtained data revealed that the treatment of diabetic rats with tropisetron led to a significant decrease in the elevated blood glucose, serum cystatin c, and urinary total protein (UTP) level, indicating the improvement of the impaired kidney function. Moreover, the results of Masson's trichrome staining showed that fibrosis attenuated in the kidney of diabetic rats after tropisetron treatment. RT-PCR and Western blotting revealed that TGF-ß1, the apoptotic mediator, and p53 were considerably declined in the kidney of diabetic rats in response to tropisetron treatment. Meanwhile, the expressions of matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinase-2 (MMP-2) were increased. These notable effects were equipotent with glibenclamide, as a standard drug, suggesting that tropisetron can alleviate renal fibrosis in diabetic nephropathy. Our data indicate that tropisetron could improve kidney function and attenuate renal fibrosis through regulation of TGF-ß1, p53, and expression of extracellular matrix metalloproteinases.


Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Fibrose/tratamento farmacológico , Rim/efeitos dos fármacos , Substâncias Protetoras/uso terapêutico , Tropizetrona/uso terapêutico , Animais , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/patologia , Fibrose/patologia , Fibrose/prevenção & controle , Glucose/metabolismo , Rim/patologia , Masculino , Proteínas/metabolismo , Ratos Wistar , Estreptozocina
10.
Medicine (Baltimore) ; 100(1): e23702, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33429738

RESUMO

BACKGROUND: Diabetic peripheral neuropathy is a common complication of diabetes and the main cause of disability. At present, there is no specific therapeutic regimen. Mecobalamin is often used as a neurotrophic drug, and its long-term effects are not satisfactory when used alone. Clinical practice indicates that traditional Chinese medicine injection with mecobalamin has a therapeutic advantage in treating diabetic peripheral neuropathy while it lacks evidence-based medicine. In this scheme, the efficacy and safety of traditional Chinese medicine injection with mecobalamin in treating diabetic peripheral neuropathy has been studied. METHODS: Computers were used to search the English database (PubMed, the Cochrane Library, Embase, Web of Science), and Chinese database (CNKI, Wanfang, CBMDISC, VIP). Besides, manual searching was conducted to search for Baidu Scholar, CHICTR, Google Scholar. During the establishment of the database to November 2020, a randomized controlled trial on traditional Chinese medicine injection with mecobalamin in treating diabetic peripheral neuropathy was conducted. There were 2 researchers independently conducting data extraction and quality evaluation of literature on the included studies, RevMan5.3 was performed for meta-analysis on the included literature. RESULTS: In this study, the efficacy and safety of traditional Chinese medicine injection with mecobalamin in treating diabetic peripheral neuropathy was evaluated by the total effective rate, motor nerve conduction velocity, sensory nerve conduction velocity, adverse reactions, and glucose metabolism level. CONCLUSION: This study can provide an evidence-based basis on the clinical applications of traditional Chinese medicine injection with mecobalamin in the treatment of diabetic peripheral neuropathy. ETHICS AND DISSEMINATION: The study does not involve patient privacy or rights and does not require approval from an ethics committee. The results may be published in peer-reviewed journals or disseminated at relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/KPW5E.


Assuntos
Protocolos Clínicos , Nefropatias Diabéticas/tratamento farmacológico , Medicina Tradicional Chinesa/normas , Vitamina B 12/análogos & derivados , Humanos , Medicina Tradicional Chinesa/métodos , Metanálise como Assunto , Revisões Sistemáticas como Assunto , Vitamina B 12/farmacologia , Vitamina B 12/normas , Vitamina B 12/uso terapêutico
11.
Adv Exp Med Biol ; 1307: 521-551, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32329028

RESUMO

Diabetes mellitus (DM) is the first cause of end stage chronic kidney disease (CKD). Animal models of the disease can shed light on the pathogenesis of the diabetic nephropathy (DN) and novel and earlier biomarkers of the condition may help to improve diagnosis and prognosis. This review summarizes the most important features of animal models used in the study of DN and updates the most recent progress in biomarker research.


Assuntos
Biomarcadores , Nefropatias Diabéticas , Modelos Animais de Doenças , Animais , Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas/diagnóstico , Rim
12.
Gene ; 765: 145076, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32860899

RESUMO

Circular RNAs (circRNAs) play vital roles in the development of diabetic nephropathy (DN). In this study, we investigated the function of circ_0037128 and molecular mechanism via which it regulates diabetic nephropathy development. It was found that expression of circ_0037128 was significantly increased in mouse DN model and high glucose treated mesangial cells (MCs), and circ_0037128 loss-of-function led to reduced cell proliferation and fibrosis in vitro. Moreover, miR-17-3p acts as competitive endogenous RNA (ceRNA) that directly interacts with circ_0037128 through its miRNA response elements (MREs). Consistently, expression of miR-17-3p was remarkably down-regulated in DN model, and negatively regulated cell proliferation and fibrosis. Further investigations revealed that AKT3 was the putative target of miR-17-3p, whose expression was elevated in DN model. In conclusion, we have characterized the function of a novel circ_0037128 and illustrated the significance of circ_0037128-miR-17-3p-AKT3 axis in DN pathogenesis.


Assuntos
Ácidos Nucleicos Livres/genética , Ácidos Nucleicos Livres/metabolismo , Nefropatias Diabéticas/genética , Animais , Movimento Celular/genética , Proliferação de Células/genética , Diabetes Mellitus/genética , Modelos Animais de Doenças , Fibrose/genética , Regulação Neoplásica da Expressão Gênica/genética , Camundongos , MicroRNAs/genética
13.
Gene ; 765: 145065, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32889056

RESUMO

PURPOSE: The aim of the present study was to investigate expression levels of circular RNA HIPK3 (circHIPK3) in mice with diabetic nephropathy (DN) and the role of circHIPK3 in rat mesangial cells (MCs). METHODS: Quantitative real-time polymerase chain reaction was performed to detect expression levels of circHIPK3, miR-185, cyclin D1, proliferating cell nuclear antigen (PCNA), transforming growth factor-ß1 (TGF-ß1), collagen Ⅰ (Col. Ⅰ), and fibronectin (FN) in mice with DN and rat mesangial cells. Luciferase assay was performed to investigate the binding sites of circHIPK3 and miR-185. Silencing cells of circHIPK3 and miR-185 were constructed using cell transfection assay. RESULTS: Our results revealed that the levels of 24-hour urinary albumin and urinary 8-hydroxy-2'-deoxyguanosine (8-OH-dG) from diabetic mice increased considerably. Up-regulation of circHIPK3 was observed in the renal tissues of mice with DN. Similarly, circHIPK3 expression in rat mesangial cells increased significantly in a microenvironment of high glucose. A loss-of-function experiment indicated that down-regulation of circHIPK3 inhibited cell proliferation and significantly decreased mRNA abundance of cyclin D1, PCNA, TGF-ß1, Col. I, and FN in MCs. Luciferase assay demonstrated that circHIPK3 can specifically sponge miR-185, and silencing of miR-185 can reverse the effects of knocking down circHIPK3 on cell proliferation and mRNA abundance of cyclin D1, PCNA, TGF-ß1, Col. I, and FN in MCs. CONCLUSION: Overall, circHIPK3 exhibits a promotive function in DN by sponging miR-185 and this evidence suggests that circHIPK3 might be a biomarker or therapeutic target for DN.


Assuntos
Nefropatias Diabéticas/genética , MicroRNAs/genética , Proteínas Serina-Treonina Quinases/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Diabetes Mellitus Experimental/genética , Nefropatias Diabéticas/fisiopatologia , Regulação da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica , Fluxo Gênico/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , RNA Circular/genética , Ratos , Fator de Crescimento Transformador beta1/metabolismo
14.
Gene ; 765: 145114, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32891769

RESUMO

The current study aimed to investigate the role and underlying mechanisms of circ_LARP4 in diabetic nephropathy (DN). Here, mouse mesangial cells (SV40-MES13) were cultured with 30 mM glucose to establish a DN cellular model. The qRT-PCR results indicated that circ_LARP4 expression was downregulated in the DN cellular model compared to that in the control cells. As determined by an MTT assay, circ_LARP4 overexpression via the circ_LARP4 overexpression (OE) plasmids inhibited the cell proliferation rate. As determined by an Annexin V/PI kit and flow cytometry, circ_LARP4 overexpression increased the cell apoptosis rate. As measured by Western blot, circ_LARP4 overexpression enhanced BAX expression but reduced Bcl-2 expression, also suggesting an enhancement of cell apoptosis. Moreover, regarding cell fibrosis, circ_LARP4 overexpression reduced the mRNA levels of fibrosis markers, including fibronectin, collagen I and collagen IV. Interestingly, miR-424 was found to be reduced in the DN cellular model after transfection with the circ_LARP4 OE plasmids. In addition, restoration of miR-424 expression with the miR-424 mimics reversed the negative effects of circ_LARP4 overexpression on cell proliferation and fibrosis. In conclusion, circ_LARP4 was lower in the DN cellular model than in normal cells, and circ_LARP4 overexpression resulted in decreased cell proliferation and cell fibrosis but increased cell apoptosis in the DN cellular model by sponging miR-424.


Assuntos
DNA Circular/genética , Células Mesangiais/metabolismo , Proteínas/genética , Animais , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Nefropatias Diabéticas/genética , Fibrose , Glucose/metabolismo , Células Mesangiais/fisiologia , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro/metabolismo , Transdução de Sinais/genética
15.
Biomed Pharmacother ; 133: 111061, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33378964

RESUMO

QiDiTangShen granules (QDTS), a traditional Chinese herbal medicine, have been used in clinical practice for treating diabetic kidney disease for several years. In our previous study, we have demonstrated that QDTS displayed good efficacy on reducing proteinuria in mice with diabetic nephropathy (DN). However, the exact mechanism by which QDTS exerts its reno-protection remains largely unknown. To ascertain whether QDTS could target the gut microbiota-bile acid axis, the db/db mice were adopted as a mouse model of DN. After a 12-week of treatment, we found that QDTS significantly reduced urinary albumin excretion (UAE), and attenuated the pathological injuries of kidney in the db/db mice, while the body weight and blood glucose levels of those mice were not affected. In addition, we found that QDTS significantly altered the gut microbiota composition, and decreased serum levels of total bile acid (TBA) and BA profiles such as ß-muricholic acid (ß-MCA), taurocholic acid (TCA), tauro ß-muricholic acid (Tß-MCA) and deoxycholic acid (DCA). These BAs are associated with the activation of farnesoid X receptor (FXR), which is highly expressed in kidney. However, there was no significant difference between QDTS-treated and -untreated db/db mice regarding the renal expression of FXR, indicating that other mechanisms may be involved. Conclusively, our study revealed that QDTS significantly alleviated renal injuries in mice with DN. The gut microbiota-bile acid axis may be an important target for the reno-protection of QDTS in DN, but the specific mechanism merits further study.


Assuntos
Ácidos e Sais Biliares/sangue , Nefropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Rim/efeitos dos fármacos , Animais , Biomarcadores/sangue , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/microbiologia , Nefropatias Diabéticas/patologia , Modelos Animais de Doenças , Disbiose , Fezes/microbiologia , Intestinos/microbiologia , Intestinos/patologia , Rim/metabolismo , Rim/ultraestrutura , Masculino , Proteinúria/sangue , Proteinúria/microbiologia , Proteinúria/prevenção & controle
16.
J Ethnopharmacol ; 266: 113474, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33068650

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba extract (GbE) is derived from a medicinal plant and suggested as a treatment for diabetic nephropathy (DN), but the mechanism was not clarified. AIM OF STUDY: The present study investigated whether GbE prevented DN via activation of heme oxygenase (HO)-1. MATERIALS AND METHODS: Streptozotocin-induced diabetic mice were fed a high-fat diet to generate DN. Human and murine podocytes were used for the in vitro study. RESULTS: GbE improved renal function via decreasing glomerular hypertrophy, the kidney/body weight ratio, and albuminuria in DN mice. GbE reversed the reduction of synaptopodin and nephrin and enhanced HO-1 expression in the kidneys of DN mice. GbE decreased the enhancement of TNF-α, IL-6, fibronectin, and lipid accumulation in the glomeruli of DN mice. GbE attenuated the uptake of oxidized low-density lipoprotein and reduced the production of ROS in high glucose-stimulated podocytes, and HO-1 inhibitor treatment abrogated the protective effects of GbE. Nuclear factor erythroid 2-related factor 2 (Nrf-2) siRNA significantly abolished the beneficial effects of GbE via decreased HO-1 expression and enhanced TNF-α and IL-6 levels. CONCLUSIONS: GbE protected podocytes against hyperglycemia and prevented the development of DN via Nrf-2/HO-1 activation. Our findings provide further mechanistic insight into the potential use of GbE in clinical DN.


Assuntos
Anti-Inflamatórios/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Extratos Vegetais/farmacologia , Animais , Células Cultivadas , Diabetes Mellitus Experimental/complicações , Dieta Hiperlipídica , Heme Oxigenase-1/metabolismo , Humanos , Hiperglicemia/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos DBA , Fator 2 Relacionado a NF-E2/metabolismo , Podócitos/efeitos dos fármacos , Podócitos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Estreptozocina
17.
Lancet Diabetes Endocrinol ; 9(1): 22-31, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33338413

RESUMO

BACKGROUND: Dapagliflozin reduces the risk of kidney failure and heart failure in patients with chronic kidney disease. We aimed to investigate the effects of dapagliflozin on kidney, cardiovascular, and mortality outcomes according to presence or absence of type 2 diabetes and according to underlying cause of chronic kidney disease, reported as diabetic nephropathy, chronic glomerulonephritides, ischaemic or hypertensive chronic kidney disease, or chronic kidney disease of other or unknown cause. METHODS: DAPA-CKD was a multicentre, double-blind, placebo-controlled, randomised trial done at 386 study sites in 21 countries, in which participants with a urinary albumin-to-creatinine ratio of 200-5000 mg/g and an estimated glomerular filtration rate (eGFR) of 25-75 mL/min per 1·73m2 were randomly assigned (1:1) to dapagliflozin 10 mg once daily or matching placebo, as an adjunct to standard care. The primary outcome was a composite of sustained decline in eGFR of at least 50%, end-stage kidney disease, or kidney-related or cardiovascular death. Secondary efficacy outcomes were a kidney-specific composite (the same as the primary outcome but excluding cardiovascular death), a composite of cardiovascular death or hospital admission for heart failure, and all-cause mortality. In this study, we conducted a prespecified subgroup analysis of the DAPA-CKD primary and secondary endpoints by presence or absence of type 2 diabetes and by aetiology of chronic kidney disease. DAPA-CKD is registered with ClinicalTrials.gov, NCT03036150. FINDINGS: The study took place between Feb 2, 2017, and June 12, 2020. 4304 participants were randomly assigned (2152 to dapagliflozin and 2152 to placebo) and were followed up for a median of 2·4 years (IQR 2·0-2·7). Overall, 2906 (68%) participants had a diagnosis of type 2 diabetes, of whom 396 (14%) had chronic kidney disease ascribed to causes other than diabetic nephropathy. The relative risk reduction for the primary composite outcome with dapagliflozin was consistent in participants with type 2 diabetes (hazard ratio [HR] 0·64, 95% CI 0·52-0·79) and those without diabetes (0·50, 0·35-0·72; pinteraction=0·24). Similar findings were seen for the secondary outcomes: kidney-specific composite outcome (0·57 [0·45-0·73] vs 0·51 [0·34-0·75]; Pinteraction=0·57), cardiovascular death or hospital admission for heart failure (0·70 [0·53-0·92] vs 0·79 [0·40-1·55]; Pinteraction=0·78), and all-cause mortality (0·74 [0·56-0·98] vs 0·52 [0·29-0·93]; Pinteraction=0·25). The effect of dapagliflozin on the primary outcome was also consistent among patients with diabetic nephropathy (n=2510; HR 0·63, 95% CI 0·51-0·78), glomerulonephritides (n=695; 0·43, 0·26-0·71), ischaemic or hypertensive chronic kidney disease (n=687; 0·75, 0·44-1·26), and chronic kidney disease of other or unknown cause (n=412; 0·58, 0·29-1·19; Pinteraction=0·53), with similar consistency seen across the secondary outcomes. The proportions of participants in the dapagliflozin and placebo groups who had serious adverse events or discontinued study drug due to adverse events did not vary between those with and those without type 2 diabetes. INTERPRETATION: Dapagliflozin reduces the risks of major adverse kidney and cardiovascular events and all-cause mortality in patients with diabetic and non-diabetic chronic kidney disease. FUNDING: AstraZeneca.


Assuntos
Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/uso terapêutico , Insuficiência Cardíaca/induzido quimicamente , Falência Renal Crônica/induzido quimicamente , Adulto , Idoso , Compostos Benzidrílicos/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/epidemiologia , Método Duplo-Cego , Feminino , Glucosídeos/efeitos adversos , Insuficiência Cardíaca/epidemiologia , Humanos , Rim/efeitos dos fármacos , Rim/patologia , Rim/fisiopatologia , Falência Renal Crônica/epidemiologia , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/epidemiologia , Resultado do Tratamento
18.
Medicine (Baltimore) ; 99(52): e23821, 2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33350769

RESUMO

BACKGROUND: Diabetic nephropathy is a frequent microvascular complication of diabetes mellitus that causes end-stage renal disease most of the time. In China, Shenkang injection is one of widely used traditional Chinese medicine for treating chronic kidney disease, but its efficacy and safety have not yet been clarified. We will systematically review the current randomized controlled trial (RCT) evidence to summarize the efficacy and safety of Shenkang injection in treating diabetic nephropathy. METHODS: We will search 7 literature databases including PubMed, EMBASE, Cochrane Library, Sinomed, Chinese National Knowledge Infrastructure, Wanfang, and VIP. Two trial registry platforms will also be searched. The time frame of the search will be from the inceptions of the databases to December 31, 2020. RCTs assessing Shenkang injection combined with basic treatments versus basic treatments alone for treating diabetic nephropathy will be included. The risk of bias within the individual RCTs will be evaluated using criteria proposed by the Cochrane Handbook 5.1.0. The primary outcomes to be investigated are glomerular filtration rate and serum creatinine; the secondary outcome will include 24-hour urine albumin excretion rate, blood urea nitrogen, fasting blood glucose, postprandial blood glucose, hemoglobin A1c, total cholesterol, triglyceride, response to treatment, and incidence of adverse events. The effect data of individual RCTs by performing random-effects model meta-analysis. Statistical heterogeneity will be measured by the Cochran Q test and I-squared statistics. Three subgroup analyses, set based on clinical experience, will be performed to explore the sources of heterogeneity. Sensitivity analyses excluding RCTs with high risk of bias and using fixed effect model will be done to test the robustness of the meta-analytic results. Publication bias across included RCTs will be evaluated by funnel plots and Egger test. RESULTS: This study will provide systematic review on the efficacy and safety of Shenkang Injection as adjuvant therapy in patients with diabetic nephropathy by rigorous quality assessment and reasonable data synthesis. The results will be submitted to a peer-reviewed journal for publication. CONCLUSION: This systematic review will provide the best evidence currently on Shenkang Injection as adjuvant therapy in patients with diabetic nephropathy. INPLASY REGISTRATION NUMBER: INPLASY2020110014.


Assuntos
Nefropatias Diabéticas/terapia , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Medicina Tradicional Chinesa , Metanálise como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Resultado do Tratamento
19.
Diab Vasc Dis Res ; 17(6): 1479164120971220, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33371732

RESUMO

INTRODUCTION: Diabetes mellitus is a progressive disease with cardiovascular complications. We evaluated the impact of a glucagon like peptide-1 (GLP-1) receptor agonist and sodium glucose cotransporter 2 (SGLT-2) inhibitors dapagliflozin and empagliflozin on renal and cardiac function in type 2 diabetes patients with renal impairment. MATERIALS AND METHODS: A total of 156 patients referred with suboptimal glycemic control were assigned to Group G (GLP-1): n = 72 or Group S (SGLT-2 inhibitor)-dapagliflozin (n = 52) or empagliflozin (n = 32). Renal function was assessed every 3 months for 36 months. Cardiovascular parameters were evaluated every 12 months for 36 months. RESULTS: Compared with baseline, HbA1c and systolic blood pressure significantly decreased in both groups (p < 0.05). The estimated glomerular filtration rate decreased, but without significance. Albuminuria decreased significantly in both groups and then subsequently increased after 30 months in Group S. Diastolic cardiac function, assessed by E/e' or left atrial volume index, decreased only in Group G at 36 months. CONCLUSIONS: The GLP-1 receptor agonist and SGLT-2 inhibitors were effective for glycemic and blood pressure control and for maintaining renal function. The GLP-1 receptor agonist improved diastolic function at 36 months.


Assuntos
Albuminúria/tratamento farmacológico , Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Glucosídeos/uso terapêutico , Incretinas/uso terapêutico , Rim/efeitos dos fármacos , Liraglutida/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Idoso , Albuminúria/diagnóstico , Albuminúria/etiologia , Albuminúria/fisiopatologia , Compostos Benzidrílicos/efeitos adversos , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/fisiopatologia , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Glucosídeos/efeitos adversos , Humanos , Incretinas/efeitos adversos , Rim/fisiopatologia , Liraglutida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Rigidez Vascular/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos
20.
Medicine (Baltimore) ; 99(50): e23303, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327258

RESUMO

Diabetes mellitus (DM) is an independent risk factor for the development of kidney disease. This study assesses the prevalence and determinants of asymptomatic kidney disease in individuals with DM attending health facilities in OR Tambo district, Eastern Cape, South Africa.In this cross-sectional analysis, medical data of 327 individuals receiving care for DM in primary health care centers in OR Tambo district, Eastern Cape between June and November 2013 were reviewed. Significant kidney disease was defined as estimated glomerular filtration rate less than 60 mL/min/1.73 m in accordance with the guidelines of the Society of Endocrinology, Metabolism and Diabetes of South Africa (2017).One-quarter of the 327 participants (n = 80) had significant kidney disease. Female sex [odds ratio (OR) = 5.2; 95% confidence interval (95% CI) 1.2-23.5], never used alcohol (OR = 13.4; 95% CI 2.5-72.1), hypertension (OR = 16.2; 95% CI 2.0-130.0), triglyceride (TG)/high-density lipoprotein (HDL) ratio (OR = 1.2; 95% CI 1.0-1.5), current smoker (OR = 1127.9; 95% CI 162.9-7808.9), former smoker (OR = 13.3; 95% CI 4.1-41.4), and longer duration of diabetes (OR = 4.6; 95% CI 1.6-13.0) were the independent determinants of significant kidney disease among the participants. A significant dose--effect relationship exists between renal disease and smoking status (P < .0001), duration of DM (P < .001), glycemic status (P = .025), and body mass index (P = .003).There is a high rate of undiagnosed kidney disease in this setting, which was independently associated with female sex and presence of other cardiovascular risk factors. Strategic interventions targeting screening and monitoring of renal functions in individuals with DM are urgently needed in this region.


Assuntos
Nefropatias Diabéticas/epidemiologia , Doenças Assintomáticas/epidemiologia , Estudos Transversais , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/patologia , Feminino , Taxa de Filtração Glomerular , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , África do Sul/epidemiologia
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