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1.
Chemosphere ; 286(Pt 3): 131963, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34426263

RESUMO

BACKGROUND: Exposure to air pollution has been linked with altered immune function in adults, but little is known about its effects on early life. This study aimed to investigate the effects of exposure to air pollution during prenatal and postnatal windows on cell-mediated immune function in preschoolers. METHODS: Pre-school aged children (2.9 ± 0.5 y old, n = 391) were recruited from a mother-child cohort study in Wuhan, China. We used a spatial-temporal land use regression (LUR) model to estimate exposures of particulate matter with aerodynamic diameters ≤2.5 µm (PM2.5) and ≤10 µm (PM10), and nitrogen dioxide (NO2) during the specific trimesters of pregnancy and the first two postnatal years. We measured peripheral blood T lymphocyte subsets and plasma cytokines as indicators of cellular immune function. We used multiple informant models to examine the associations of prenatal and postnatal exposures to air pollution with cell-mediated immune function. RESULTS: Prenatal exposures to PM2.5, PM10, and NO2 during early pregnancy were negatively associated with %CD3+ and %CD3+CD8+ cells, and during late pregnancy were positively associated with %CD3+ cells. Postnatal exposures to these air pollutants during 1-y or 2-y childhood were positively associated with IL-4, IL-5, IL-6, and TNF-α. We also observed that the associations of prenatal or postnatal air pollution exposures with cellular immune responses varied by child's sex. CONCLUSIONS: Our results suggest that exposure to air pollution during different critical windows of early life may differentially alter cellular immune responses, and these effects appear to be sex-specific.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Criança , Pré-Escolar , Estudos de Coortes , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Feminino , Humanos , Imunidade Celular , Masculino , Dióxido de Nitrogênio/análise , Dióxido de Nitrogênio/toxicidade , Material Particulado/análise , Material Particulado/toxicidade , Gravidez
2.
Zhongguo Zhong Yao Za Zhi ; 46(20): 5372-5381, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34738441

RESUMO

Due to the limited resource of bear bile powder, the major raw material of Tanreqing Capsules(TRQ), cultured bear bile powder is used as a replacement to develop the Tanreqing Capsules Substitute(TRQS). An LC-MS/MS method was established in this study for simultaneous quantitation of 8 compounds from TRQS in rat plasma: tauroursodeoxycholic acid(TUDCA), taurocheno-deoxycholic acid(TCDCA), ursodeoxycholic acid(UDCA), chenodeoxycholic acid(CDCA), ferulic acid, wogonoside, baicalin, and forsythoside A. Thereby, the pharmacokinetic behaviors of TRQ and TRQS were evaluated. Concentration of endogenous compounds TUDCA, TCDCA, UDCA, and CDCA was determined with the stable isotope surrogate analytes: D4-TUDCA, D4-TCDCA, D4-UDCA, and D4-CDCA. Plasma samples were extracted by acetonitrile-induced protein precipitation. The LC conditions are as follows: Waters BEH C_(18) column(2.1 mm×100 mm, 1.7 µm), mobile phase of 10 mmol·L~(-1) ammonium formate aqueous solution(containing 0.01% formic acid) and acetonitrile-methanol mixture(1∶5). MS conditions are as below: multiple reaction monitoring(MRM), ESI~(+/-). Concentration of UDCA, CDCA, TUDCA, and TCDCA was corrected with a response factor, which is the ratio between the responses recorded for the surrogate and the authentic analyte at the equal concentration. Each of the plasma components showed good linearity(r > 0.995 1). Accuracy and precision met the criteria(inter-day RSD<7.0%, RE 89.98%-112.0%; intra-day RSD<12%, RE 90.41%-111.2%). The recovery was 64.83%-119.9% and matrix effect was 87.15%-113.8%. The validated method was applied for pharmacokinetic study of TRQS and TRQ(po, 0.94 g·kg~(-1)). There was no significant difference in C_(max) and AUC_(0-24 h) of baicalin, UDCA, TUDCA, and TCDCA between the two groups, indicating similar pharmacokinetic behaviors between TRQS and TRQ in rats.


Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Animais , Cápsulas , Cromatografia Líquida , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem
3.
Zhongguo Zhong Yao Za Zhi ; 46(19): 5130-5136, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34738411

RESUMO

Due to the profound theoretical rationale, perfect diagnosis and treatment system, and characteristic medicinal resources, Tibetan medicine has been passed down to the present day as one of the four traditional medicine systems all over the world. With the development of modern society and the change in people's concept of seeking medical services, Tibetan medicine has gradually attracted wide attention by virtue of its natural, green and safe diagnosis and treatment characteristics, which enables it to be vigo-rously developed and inherited. There are numerous ancient books on Tibetan medicine, covering a large number of ancient prescriptions, which has laid a solid foundation for later scholars to thoroughly investigate the diagnosis and treatment rules in Tibetan medicine and apply them to modern clinical practice. Screening the classic prescriptions that meet modern clinical needs from those numerous ancient books is a new direction in the inheritance and development of Tibetan medicine. On the basis of historical origin and current application status of ancient prescriptions in Tibetan medicine, this paper preliminarily elaborated the definition of classic prescriptions of Tibetan medicine and their general screening principles and precautions, and also discussed the modern inheritance paths of classic prescriptions in Tibetan medicine from basic research, post-marketing evaluation, and the development of novel preparations. Considering the shortcomings in the present study, the key technical issues mentioned need to be more deeply explored and analyzed in future studies.


Assuntos
Medicina Tradicional Tibetana , Medicina Tradicional , Humanos , Prescrições
4.
Biology (Basel) ; 10(11)2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34827069

RESUMO

Brassica yellows virus (BrYV) is a tentative species of the genus Polerovirus, which has at least three genotypes (A, B, and C) in China. The P0 protein of BrYV-A (P0BrA) has been identified as a viral suppressor of RNA silencing (VSR), which can also induce cell death in infiltrated Nicotiana benthamiana leaves. In this study, we demonstrated that the cell death induced by P0BrA was accompanied by the accumulation of reactive oxygen species (ROS) and increased Pathogenesis-related protein genes-1 (PR1) expression. Meanwhile, this cell death phenotype was delayed by salicylic acid (SA) pretreatment. Biological function comparison of the three P0 proteins showed that transiently expressed P0BrB or P0BrC induced a significantly delayed and milder cell death response compared with P0BrA. However, like P0BrA, they also suppressed local and systemic RNA silencing. Six residues of P0BrA essential for inducing cell death were identified by comparative analysis and amino acid substitution assay. We also show that all three BrYV genotypes have synergistic interactions with pea enation mosaic virus 2 (PEMV 2) in N. benthamiana. This study provides theoretical guidance for controlling the viral disease caused by poleroviruses in the future.

5.
Hepatol Int ; 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34843069

RESUMO

BACKGROUND: Mesenchymal stem cell (MSC) infusion was reported to improve liver function in patients with decompensated liver cirrhosis (DLC); however, whether the medication can improve outcome of these patients is poorly understood. METHODS: This prospective, open-labeled, randomized controlled study enrolled 219 patients with HBV-related DLC who were divided into control group (n = 111) and umbilical cord-derived MSC (UC-MSC)-treated group (n = 108), then all of them received a follow-up check from October 2010 to October 2017. The treated patients received three times of UC-MSC infusions at 4-week intervals plus conventional treatment that was only used for control group. The overall survival rate and HCC-free survival rate were calculated as primary endpoints and the liver function and adverse events associated with the medication were also evaluated. RESULTS: During the follow-up check period from 13 to 75th months, there was a significantly higher overall survival rate in the treated group than the control group, while the difference of the hepatocellular carcinoma event-free survival rate between the treated and control groups was not observed during the 75-month follow-up. UC-MSC treatment markedly improved liver function, as indicated by the levels of serum albumin, prothrombin activity, cholinesterase, and total bilirubin during 48 weeks of follow-up. No significant side effects or treatment-related complications were observed in the UC-MSC group. CONCLUSIONS: Therapy of UC-MSC is not only well tolerated, but also significantly improves long-term survival rate, as well as the liver function in patients with HBV-related DLC. UC-MSC medication, therefore, might present a novel therapeutic approach for the disease.

6.
Plant Sci ; 312: 111024, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34620429

RESUMO

Fruit coloration is an appearance trait that directly affects the commercial value and market competitiveness of apples. The red color of apple fruit is mainly affected by anthocyanin accumulation, and the synthesis of anthocyanin is affected by various factors. The critical roles of hormones and environmental factors during apple anthocyanin biosynthesis are described. This review also elaborates the specific mechanisms of the responses of internal genes to stress and changes in anthocyanin when apples are exposed to different environmental stressors. This study provides direction for future research on apple anthocyanin and is a reference for anthocyanin studies in other species.


Assuntos
Adaptação Fisiológica/fisiologia , Antocianinas/biossíntese , Poluentes Ambientais/efeitos adversos , Malus/genética , Malus/metabolismo , Pigmentação/fisiologia , Reguladores de Crescimento de Plantas/metabolismo , Adaptação Fisiológica/genética , Antocianinas/genética , Vias Biossintéticas/genética , Produtos Agrícolas/genética , Produtos Agrícolas/metabolismo , Pigmentação/genética , Reguladores de Crescimento de Plantas/genética
7.
Toxicology ; 464: 153013, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34718031

RESUMO

Patulin is a secondary metabolite mainly secreted by fungi and is the most common mycotoxin found in apples and apple-based products. For the past few years, numerous studies suggested the wide distribution and toxicity of patulin. In this study, we investigated the toxic effect of patulin on mouse oocytes and its possible mechanisms. The results showed that patulin treatment did not affect meiotic resumption, but inhibited oocyte maturation as indicated by failure of first polar body extrusion. Further mechanistic study showed that patulin treatment disturbed normal spindle assembly, chromosome alignment and morphology. We also found increased oxidative stress by testing the level of ROS and decreased mitochondrial membrane potential, indicating mitochondria dysfunction. In summary, our results suggest that patulin treatment causes oocyte meiotic arrest by disturbing normal spindle assembly and chromosome alignment, which may be caused by dysfunctions of mitochondria.

8.
Int Immunopharmacol ; 101(Pt B): 108236, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34653727

RESUMO

Diabetic nephropathy (DN) is a main complication of diabetes and often develops into end-stage nephropathy. Histologically, DN progresses as the gradual loss of podocytes with the loss of glomerular podocytes being the earliest sign of DN. Pyroptosis is a new type of programmed cell death and has been mechanistically correlated with podocyte injury in DN. The current study aimed to evaluate the protective effects of carnosine on glomerular podocytes in DN, both in vivo and in vitro. Using high glucose-treated cultured MPC5 cells and a streptozotocin (STZ)-induced diabetic mouse model, we evaluated the effects of carnosine on alleviating podocyte injury in DN. We found that carnosine significantly reversed albuminuria and histopathological lesions and alleviated renal inflammatory and pyroptosis responses in STZ-induced diabetic mice for 12 weeks. The results also showed that carnosine strongly inhibited podocyte inflammation and podocyte pyroptosis in vitro. Cellular Thermal Shift Assay (CETSA) and molecular docking results revealed that mechnaistically caspase-1 was the target of carnosine. We then found that silencing caspase-1 eliminated the protective effect of carnosine. Interestingly, we also found that caspase-1 and gasdermin D expression were increased in renal biopsy tissue of patients with DN. Our study is the first to demonstrate the novel role of carnosine in alleviating podocyte injury by inhibiting pyroptosis via the targeting of caspase-1. Carnosine may have potential as a therapeutic agent in treating DN by targeting caspase-1.

9.
J Org Chem ; 86(21): 15544-15557, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34570502

RESUMO

A facile and versatile method for generating radicals from Csp3-H bonds under metal-free and organic-peroxide-free conditions was developed. By combining safe persulfate and low-toxic quaternary ammonium salt, a wide variety of Csp3-H compounds including ethers, (hetero)aromatic/aliphatic ketones, alkylbenzenes, alkylheterocycles, cycloalkanes, and haloalkanes were selectively activated to generate the corresponding C-centered radicals, which could be further captured by N-arylacrylamides to deliver the valuable functionalized oxindoles. Good functional group tolerance was demonstrated. The useful polycarbonyl compound and esters were also modified with the strategy. Moreover, the combination can also be applied to the practical coupling between simple haloalkanes and N-hydroxyphthalimide (NHPI).

10.
Cell Death Dis ; 12(10): 883, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34580275

RESUMO

Protein phosphatase 6 (PP6) is a member of the PP2A-like subfamily, which plays significant roles in numerous fundamental biological activities. We found that PPP6C plays important roles in male germ cells recently. Spermatogenesis is supported by the Sertoli cells in the seminiferous epithelium. In this study, we crossed Ppp6cF/F mice with AMH-Cre mice to gain mutant mice with specific depletion of the Ppp6c gene in the Sertoli cells. We discovered that the PPP6C cKO male mice were absolutely infertile and germ cells were largely lost during spermatogenesis. By combing phosphoproteome with bioinformatics analysis, we showed that the phosphorylation status of ß-catenin at S552 (a marker of adherens junctions) was significantly upregulated in mutant mice. Abnormal ß-catenin accumulation resulted in impaired testicular junction integrity, thus led to abnormal structure and functions of BTB. Taken together, our study reveals a novel function for PPP6C in male germ cell survival and differentiation by regulating the cell-cell communication through dephosphorylating ß-catenin at S552.

11.
Psychiatry Investig ; 18(10): 943-948, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34555889

RESUMO

OBJECTIVE: To investigate the relation between nicotinic acetylcholine receptor subunit (nAChR) genes and schizophrenia, and the relation between tag single nucleotide polymorphism (rs1317286, rs1044396, rs6494212, rs16969968, and rs684513) and schizophrenia in Han Chinese people. METHODS: The protein-protein interaction (PPI) network among nAChR protein and 350 proteins encoded by schizophrenia-related susceptibility genes was constructed through the String database to explore whether nAChR genes were associated with schizophrenia in these known databases. Then, five single nucleotide polymorphisms (SNPs) of CHRNA3 (rs1317286), CHRNA4 (rs1044396), CHRNA7 (rs6494212), and CHRNA5 (rs16969968, rs684513) were analyzed in a sample of 1,035 schizophrenic patients and 816 healthy controls. The interaction between the markers was analyzed using multifactor dimensionality reduction (MDR) software. Power analysis was performed using the Quanto program. RESULTS: There are no significant differences in genotype or allele distribution were identified between the patients and controls (p>0.05). The haplotypes constructed by four markers rs1317286, rs6494212, rs16969968, and rs684513 were not associated with schizophrenia either. However, a significant association between models made of rs1317286, rs1044396, rs6494212, and rs684513 and schizophrenia was revealed in interaction analysis (p<0.05). CONCLUSION: The nAChR protein may have effects on the development of schizophrenia through the interaction with proteins encoded by schizophrenia-related susceptibility genes, but no relation was found between selected polymorphisms and schizophrenia in the collected Han Chinese people. However, interaction analysis suggested four-SNP model has an important effect on schizophrenia.

12.
Plant Cell Rep ; 40(12): 2357-2368, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34468851

RESUMO

KEY MESSAGE: We found that the apple wax related gene played a role in changing plant epidermal permeability and enhancing plant resistance to drought stress by increasing wax accumulation. The content and composition of epidermal wax in plants are affected by genetic and environmental factors. The KCS gene encodes the ß-ketoalionyl-CoA synthetase, which is a rate-limiting enzyme in the synthesis of very-long-chain fatty acids (VLCFAs). In this study, we identified the MdKCS2 gene from apple as a homolog of Arabidopsis AtKCS2. The KCS protein is localized on the endoplasmic reticulum membrane. MdKCS2 exhibited the highest expression in apple pericarp, and was induced by abiotic stresses, such as drought and salt. Transgenic analysis indicated that the MdKCS2 improved the resistance to abiotic stress in apple calli. Ectopic expression of MdKCS2 in Arabidopsis increased the content of wax in leaves and stems, changed the permeability of cuticle of leaves, and enhanced plant drought resistance.

13.
Zhongguo Zhong Yao Za Zhi ; 46(13): 3446-3454, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34396765

RESUMO

Qingkailing Injection is one of the most commonly used traditional Chinese medicine injections with significant clinical application for the treatment of multiple diseases. This study aims to analyze the systematic reviews( SRs) of Qingkailing Injection,in order to provide reference for the clinical application of Qingkailing Injection and the development of relevant clinical practice guidelines. We searched CNKI,CBM,Wanfang,VIP,Pub Med,Cochrane Library and EMbase to collect SRs from the time of database establishment to August 2020. The eligible SRs were included according to the inclusion and exclusion criteria. AMSTAR 2 was used to assess the methodological quality. The diseases,drugs in combinations and results were extracted and analyzed. A total of 24 SRs were selected,including 10 for the treatment of acute cerebrovascular diseases,9 for respiratory infections,2 for viral hepatitis,1 for chronic obstructive pulmonary disease,and two for the adverse effects of Qingkailing Injection. Only three entries of AMSTAR 2 item were fully reported by over 70%,and the rest were reported by less than 70%,with no report about item 2,3 and 10. Twenty-nine outcome indicators were correlated with the included SRs,of which three mostly frequent outcomes were effectiveness,adverse reaction,and neurological deficit scores,showing a good efficacy of Qingkailing Injection. The common severe adverse reaction was anaphylaxis,and mild adverse reactions were skin and mucous membrane reactions. The most frequently combined drug was antibiotics,mainly Penicillin and Penicillin+Pioneeromycin. The existing evidences showed that the methodological quality of SRs of Qingkailing Injection needed to be improved and Qingkailing Injection had an obvious efficacy. However,the selection of outcome indicators for clinical trials and SRs shall be standardized,and the reporting of basic information,such as drug combination,shall be strengthened to provide more powerful clinical services.


Assuntos
Medicamentos de Ervas Chinesas , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Injeções , Medicina Tradicional Chinesa , Revisões Sistemáticas como Assunto
14.
FEMS Microbiol Ecol ; 97(9)2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34415012

RESUMO

SAR92 is one of the few examples of a widely distributed, abundant oligotroph that can be cultivated to study pathways of carbon oxidation in ocean systems. Genomic evidence for SAR92 suggests that this gammaproteobacterium might be a primary consumer of polysaccharides in the epipelagic zone, its main habitat. Here, we investigated cell growth, polysaccharide utilization gene expression, and carbohydrate-active enzyme abundance of a culturable SAR92 strain, HTCC2207, grown with different polysaccharides. Xylan and laminarin, two polysaccharides mainly produced by phytoplankton, supported the growth of HTCC2207 better than other polysaccharides. HTCC2207 possessed polysaccharide utilization loci (PULs) consisting of TonB-dependent receptor (TBDR) and glycoside hydrolase (GH) family genes. GH genes such as GH17 and GH3 presented no substrate-specificity and were induced by different sugar substrates, while expressions of GH16, GH10 and GH30 were enhanced in the glucose-treatment but suppressed in the polysaccharide-treatment, indicating complex polysaccharide utilization by HTCC2207. Metabolic pathways for laminarin and xylan were re-constructed in HTCC2207 based on the PULs genes and other predicted carbohydrate-active enzymes. This study reveals features of the epipelagic niche of SAR92 and provide insight into the biogeochemical cycling of labile, high-molecular carbohydrate compounds in the surface ocean.


Assuntos
Gammaproteobacteria , Polissacarídeos , Fitoplâncton , Especificidade por Substrato , Xilanos
15.
Sci Total Environ ; 799: 149444, 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34365263

RESUMO

To date, dermal/hand-to-mouth exposure to chemicals in the e-waste recycling environment has not been sufficiently understood, and the importance of dermal absorption of chemicals in e-waste dismantling workers remains controversial. In this study, we utilized hand wipes and matched sera to characterize dermal/hand-to-mouth exposure to PCBs for e-waste dismantling workers, and potential effects on thyroid hormones were also assessed. PCB loadings in hand wipes varied from 0.829-265 ng wipe-1 (11.3-2850 ng m-2 wipe-1), with 37.2 ng wipe-1 (432 ng m-2 wipe-1) as the median value. Serum concentrations of PCBs ranged from 32.3-3410 ng g-1 lipid weight (lw) with 364 ng g-1 lw as the median value. Between wipes and sera, lower-chlorinated congeners (e.g. CB-28, -66, -74, -99,-105 and -118) showed significant associations (p < 0.01), but higher-chlorinated congeners (e.g. CB-138, -153, -156, -170, and -180) did not. These lower-chlorinated CBs were the major contributors to estimated dermal/hand-to-mouth average daily doses (ADDs) and the hazard index (HI). Correspondingly, their estimated contributions to serum levels by dermal absorption were also significant, with the contribution of CB-28 being as high as 21.4%. As a consequence, dermal absorption of some low-chlorinated congeners was a non-negligible route for e-waste dismantling workers. Although insignificant association was shown between serum PCBs and thyroid hormones, the potential health risk should be of concern due to the high levels of PCBs observed in workers' sera.


Assuntos
Resíduo Eletrônico , Poluentes Ambientais , Bifenilos Policlorados , China , Resíduo Eletrônico/análise , Poluentes Ambientais/análise , Humanos , Bifenilos Policlorados/análise , Reciclagem
16.
J Genet Genomics ; 48(11): 984-993, 2021 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-34393089

RESUMO

Exposure to intense noise can damage cochlear hair cells, leading to hearing loss in mammals. To avoid this constraint, most mammals have evolved in relatively quiet environments. Echolocating bats, however, are naturally exposed to continuous intense sounds from their own and neighboring sonar emissions for maintaining sonar directionality and range. Here, we propose the presence of intense noise resistance in cochlear hair cells of echolocating bats against noise-induced hearing loss (NIHL). To test this hypothesis, we performed noise exposure experiments for laboratory mice, one nonecholocating bat species, and five echolocating bat species. Contrary to nonecholocating fruit bats and mice, the hearing and the cochlear hair cells of echolocating bats remained unimpaired after continuous intense noise exposure. The comparative analyses of cochleae transcriptomic data showed that several genes protecting cochlear hair cells from intense sounds were overexpressed in echolocating bats. Particularly, the experimental examinations revealed that ISL1 overexpression significantly improved the survival of cochlear hair cells. Our findings support the existence of protective effects in cochlear hair cells of echolocating bats against intense noises, which provides new insight into understanding the relationship between cochlear hair cells and intense noises, and preventing or ameliorating NIHL in mammals.

17.
Environ Toxicol ; 36(11): 2322-2332, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34418280

RESUMO

Long noncoding RNAs (lncRNAs) are known to be the important regulators in cancer progression. However, the role of lncRNA FAM66C (FAM66C) is yet to be investigated in intrahepatic cholangiocarcinoma (ICC). This study aimed to investigate the effects and related mechanisms of FAM66C in ICC. Human ICC tissues and cell lines were collected. The expression levels of FAM66C, hsa-miR-23b-3p (miR-23b-3p), and KCND2 were detected by qRT-RCR. The transfection experiments were employed to measure the effect of FAM66C on cell viabilities, migration, and invasion in ICC cells by CCK-8, transwell assays. Glycolysis was investigated by glucose consumption, lactate production and ATP levels. The dual-luciferase reporter and RNA pull down assays were conducted as a means of confirming the interactions between FAM66C, miR-23b-3p, and KCND2. Furthermore, the levels of the EMT-associated proteins (KCND2, GLUT1, PKM2, and LDHA) in ICC cells were detected by western blot. FAM66C was increased in ICC tissues and cells, increased cell viability, glycolysis, migration and invasion, and decreased apoptosis were shown in FAM66C overexpressing cells. Mechanistic analyses revealed that FAM66C regulated the downstream target gene KCND2 by sponging miR-23b-3p. FAM66C effect on ICC was further validated in murine xenograft assays. FAM66C knockdown cells gave rise to tumors that were smaller in size, consistent with the role of FAM66C as a promoter of in vivo tumor growth. These data revealed that FAM66C was able to drive ICC tumor progression and glycolytic activity via the miR-23b-3p/KCND2 axis, indicating FAM66C may be a viable target for treating ICC.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , MicroRNAs , RNA Longo não Codificante , Animais , Neoplasias dos Ductos Biliares/genética , Ductos Biliares Intra-Hepáticos/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Colangiocarcinoma/genética , Regulação Neoplásica da Expressão Gênica , Glicólise/genética , Humanos , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Canais de Potássio Shal
18.
Acta Pharmacol Sin ; 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34253875

RESUMO

Diabetic kidney disease (DKD) is one of the microvascular complications of diabetes mellitus and a major cause of end-stage renal disease with limited treatment options. Wogonin is a flavonoid derived from the root of Scutellaria baicalensis Georgi, which has shown a potent renoprotective effect. But the mechanisms of action in DKD are not fully elucidated. In this study, we investigated the effects of wogonin on glomerular podocytes in DKD using mouse podocyte clone 5 (MPC5) cells and diabetic mice model. MPC5 cells were treated with high glucose (30 mM). We showed that wogonin (4, 8, 16 µM) dose-dependently alleviated high glucose (HG)-induced MPC5 cell damage, accompanied by increased expression of WT-1, nephrin, and podocin proteins, and decreased expression of TNF-α, MCP-1, IL-1ß as well as phosphorylated p65. Furthermore, wogonin treatment significantly inhibited HG-induced apoptosis in MPC5 cells. Wogonin reversed HG-suppressed autophagy in MPC5 cells, evidenced by increased ATG7, LC3-II, and Beclin-1 protein, and decreased p62 protein. We demonstrated that wogonin directly bound to Bcl-2 in MPC5 cells. In HG-treated MPC5 cells, knockdown of Bcl-2 abolished the beneficial effects of wogonin, whereas overexpression of Bcl-2 mimicked the protective effects of wogonin. Interestingly, we found that the expression of Bcl-2 was significantly decreased in biopsy renal tissue of diabetic nephropathy patients. In vivo experiments were conducted in STZ-induced diabetic mice, which were administered wogonin (10, 20, 40 mg · kg-1 · d-1, i.g.) every other day for 12 weeks. We showed that wogonin administration significantly alleviated albuminuria, histopathological lesions, and p65 NF-κB-mediated renal inflammatory response. Wogonin administration dose-dependently inhibited podocyte apoptosis and promoted podocyte autophagy in STZ-induced diabetic mice. This study for the first time demonstrates a novel action of wogonin in mitigating glomerulopathy and podocytes injury by regulating Bcl-2-mediated crosstalk between autophagy and apoptosis. Wogonin may be a potential therapeutic drug against DKD.

19.
Yi Chuan ; 43(7): 642-653, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34284980

RESUMO

As a serine/threonine kinase, NIMA-related kinases (NEKs) play important roles in the regulation of cell cycle, and involve in several cellular activities such as centrosome separation, spindle assembly, chromatin condensation, nuclear envelope breakdown, spindle assembly checkpoint signaling, cytokinesis, cilia formation and DNA damage response. In this review, we summarize the component, structural characteristics and functions of NEK family in mitosis and meiosis based on the relevant researches in recent years, providing a reference for the further study on the roles of NEKs in the regulation of cell cycle and a theoretical basis for the clinical diagnosis and treatment of tumors.


Assuntos
Proteínas de Ciclo Celular , Proteínas Serina-Treonina Quinases , Ciclo Celular , Proteínas de Ciclo Celular/metabolismo , Mitose , Quinase 1 Relacionada a NIMA , Transdução de Sinais
20.
Int J Mol Med ; 48(3)2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34278465

RESUMO

It has been previously reported that macrophages may be involved in diabetic nephropathy (DN) development. Furthermore, Bruton's tyrosine kinase (BTK) may participate in macrophage activation and lead to the release of inflammatory mediators. The main aim of the present study was to analyze the association between renal BTK expression and clinical indicators. Moreover, BTK knockout mice were used to establish a diabetic model for further research. The results demonstrated that BTK was activated in the kidneys of patients with DN and was associated with the progression of proteinuria, creatinine levels, estimated glomerular filtration rate and pathological changes in the kidneys of patients with DN. Furthermore, BTK knockout was observed to reduce urinary protein excretion, alleviate renal injury and decrease renal inflammation in diabetic mice. This protection may be attributed to BTK­induced suppression of the activation of the Nod­like receptor (NLR) family pyrin domain containing 3 inflammasome. Collectively, it has been demonstrated in the present study that BTK may be a potential target for DN treatment.

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