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1.
RSC Adv ; 12(3): 1638-1644, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-35425204

RESUMO

Metal-organic framework (MOF) materials provide a versatile and promising platform for constructing heterogeneous photocatalysts with applications in organic transformations. One of the methods for enhancing MOFs' performance in photocatalysis relies on the elaborate design and functionalization of organic linkers. Here we reported a photoactive thiadiazolopyridine (TDP) moiety functionalized UiO-68 isoreticular Zr(iv)-based MOF (denoted as UiO-68-TDP) that was synthesized by the de novo approach of mixed dicarboxylate struts. Under blue LED irradiation and in an open air atmosphere, MOF UiO-68-TDP exhibited a largely higher photocatalytic activity for the synthesis of tetrahydroquinolines by oxidative annulation reaction between N,N-dimethylanilines and maleimides, in comparison to the benzothiadiazole decorated analogue MOF. Besides, UiO-68-TDP can be reused at least three times without significant loss of its photocatalytic activity and its framework was well maintained after these cycles. Furthermore, the related mechanism involving reactive oxygen species was properly proposed.

2.
Pathogens ; 11(4)2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35456135

RESUMO

Feline coronavirus (FCoV) infections present as one of two forms: a mild or symptom-less enteric infection (FEC) and a fatal systemic disease termed feline infectious peritonitis (FIP). The lack of epidemiology of FCoV in central China and the reason why different symptoms are caused by viruses of the same serotype have motivated this investigation. Clinical data of 81 suspected FIP cases, 116 diarrhea cases and 174 healthy cases were collected from veterinary hospitals using body cavity effusion or fecal samples. Risk factors, sequence comparison and phylogenetic studies were performed. The results indicated that FIPV was distinguished from FECV in the average hydrophobicity of amino acids among the cleavage sites of furin, as well as the mutation sites 23,531 and 23,537. FIPV included a higher minimal R-X-X-R recognition motif of furin (41.94%) than did FECV (9.1%). The serotype of FCoV was insignificantly correlated with FIP, and the clade 1 and clade 2 strains that appeared were unique to central China. Thus, it is hypothesized that this, along with the latent variables of an antigenic epitope at positions 1058 and 1060, as well as mutations at the S1/S2 sites, are important factors affecting FCoV transmission and pathogenicity.

3.
Ginekol Pol ; 2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35419800

RESUMO

Human papillomavirus (HPV) is one of the most common sexually transmitted infectious viruses among men and women of reproductive age throughout the world. Pregnant women are susceptible during pregnancy and most infections of them are self-limiting infections, which can be removed by their autoimmunity, while the persistent infections are associated with precancerous lesions and cancer of the anogenital mucosa in women and men. In addition, HPV infection may also affect reproductive health and fertility. The effect of HPV on female fertility requires further study, but HPV influences sperm parameters. Furthermore, whether HPV infection alters the effect of assisted reproductive technology and whether there is an association between it and assisted reproductive technology (ART) outcomes is unknown. It is considered that the relationship between HPV infection and spontaneous abortion (SA), assisted reproductive technology (ART) outcomes and spontaneous preterm birth (sPTB) has profound implications for the medical care of pregnant and infertile women. This paper reviews the relationship between human papillomavirus infection during pregnancy and SA, sPTB and ART in reproduction, and reviews the relationship between human papillomavirus and human fertility by summarizing the recent domestic and foreign literature.

4.
J Healthc Eng ; 2022: 5642907, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35392140

RESUMO

In order to verify the applicability of the erythrocyte fragility test (EFT) carried out by the new fully automatic erythrocyte permeability fragility analyzer RA-800 for thalassemia screening, a total of 100 cases of suspected thalassemia patients who underwent pregnancy examinations at Luohu District People's Hospital are included. The results of a new automatic erythrocyte permeability fragility analyzer RA-800 are compared with the results of the detection system composing of the KOFA erythrocyte fragility test kit currently used in clinical laboratories. The diagnosis confirmed by genetic testing is used as the gold standard to evaluate the applicability of RA-800. The sensitivity, specificity, and accuracy of the new automatic erythrocyte permeability fragility analyzer RA-800 screening for thalassemia were 66.67%, 92.86%, and 85.00%. The KOFA direct colorimetries are 76.67%, 81.43%, and 80.00%. The kappa value for the screening of thalassemia was 0.558, which concludes that the consistency was moderate. The ROC curve indicates that both two methods had diagnostic significance for the diagnostic value of thalassemia. The new automatic erythrocyte permeability fragility analyzer RA-800 is suitable for thalassemia screening, and the performance indexes meet the clinical requirements.


Assuntos
Índices de Eritrócitos , Talassemia , Eritrócitos , Feminino , Humanos , Fragilidade Osmótica , Permeabilidade , Gravidez , Sensibilidade e Especificidade , Talassemia/diagnóstico
5.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 39(4): 438-441, 2022 Apr 10.
Artigo em Chinês | MEDLINE | ID: mdl-35446984

RESUMO

Genetic factors play a key role in human athletic ability, and endurance quality and explosive power quality are the important components of athletic ability. In this review, we aimed to reveal the biological genetic mechanism of human athletic ability at the molecular level through summarizing the relationship between genetic variants and human athletic ability, including endurance quality related genetic markers angiotensin converting enzyme (ACE) gene, creatine kinase MM (CKMM) gene and explosive power quality related genetic markers alpha actinin 3 (ACTN3) gene, angiotensinogen (AGT) gene and interleukin6 (IL6) gene. Meanwhile, we also summarized the distribution of allele frequencies among various populations.


Assuntos
Desempenho Atlético , Actinina/genética , Frequência do Gene , Marcadores Genéticos , Genótipo , Humanos , Polimorfismo Genético
6.
Virol Sin ; 37(1): 94-106, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35234626

RESUMO

Flaviviruses are important arthropod-borne pathogens that represent an immense global health problem. Their unprecedented epidemic rate and unpredictable clinical features underscore an urgent need for antiviral interventions. Dehydroepiandrosterone (DHEA) is a natural occurring adrenal-derived steroid in the human body that has been associated in protection against various infections. In the present study, the plaque assay based primary screening was conducted on 32 synthetic derivatives of DHEA against Japanese encephalitis virus (JEV) to identify potent anti-flaviviral compounds. Based on primary screening, HAAS-AV3026 and HAAS-AV3027 were selected as hits from DHEA derivatives that exhibited strong antiviral activity against JEV (IC50 â€‹= â€‹2.13 and 1.98 â€‹µmol/L, respectively) and Zika virus (ZIKV) (IC50 â€‹= â€‹3.73 and 3.42 â€‹µmol/L, respectively). Mechanism study indicates that HAAS-AV3026 and HAAS-AV3027 do not exhibit inhibitory effect on flavivirus binding and entry process, while significantly inhibit flavivirus infection at the replication stage. Moreover, indirect immunofluorescence assay, Western blot analyses, and quantitative reverse transcription-PCR (qRT-PCR) revealed a potent antiviral activity of DHEA derivatives hits against JEV and ZIKV in terms of inhibition of viral infection, protein production, and viral RNA synthesis in Vero cells. Taken together, our results may provide a basis for the development of new antivirals against flaviviruses.


Assuntos
Infecções por Flavivirus , Flavivirus , Infecção por Zika virus , Zika virus , Animais , Antivirais/farmacologia , Chlorocebus aethiops , Desidroepiandrosterona/farmacologia , Infecções por Flavivirus/tratamento farmacológico , Humanos , Células Vero , Replicação Viral
7.
Sci Rep ; 12(1): 4833, 2022 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-35318408

RESUMO

To study the relationship between preoperative urine culture, bacterial species and infection after percutaneous nephrolithotomy in patients with upper urinary tract stones, and summarize the clinical characteristics of different bacterial infections. From January 2014 and January 2020, 963 patients with upper urinary tract stones who underwent PCNL in the department of urology of Fujian provincial hospital were included in the study. Information included the patient's age, gender, weight, diabetes, chronic disease history, urine routine, preoperative urine culture results, stone size, number of stones, hydronephrosis level, operation time, body temperature, heart rate, blood pressure, breathing rate, hemoglobin, serum creatinine, bilirubin, platelets and whether there was preoperative infection were recorded. 141 patients (14.6%) had a positive urine culture before surgery, and 7 of them had multiple bacterial infections. The most common pathogenic bacteria was Escherichia coli, followed by Enterococcus and Klebsiella pneumoniae. A total of 74 cases (7.7%) of 963 patients with infection after PCNL occurred, 24 cases (32.4%) of infected patients progressed to urinary septic shock. Univariate analysis shown that the probability of infection in patients with long operation time and positive urine culture was significantly higher, and the difference was statistically significant. Further multivariate logistic regression analysis shown that positive urine culture before operation and long operation time were independent risk factors for infection after PCNL. Among the 29 patients with septic shock, 18 cases (62.1%) had a positive urine culture before surgery. The incidence (43.9%) of postoperative infection in Escherichia coli positive patients was significantly higher than that in the negative group, and the difference was statistically significant. The rate of patients with Escherichia coli infection progressing to septic shock was 9 cases (60%). 2 patients with Enterococcus faecium infection and 2 patients with Klebsiella pneumoniae infection all progressed to septic shock. The age of patients with post-PCNL infection caused by Escherichia Coli, Enterococcus faecium and Klebsiella pneumoniae were 58.53 ± 11.73 years, 76.5 years and 74 years.The body temperature of patients with post-PCNL infection caused by Escherichia Coli, Enterococcus faecium and Klebsiella pneumoniae were 39.10 ± 0.25 °C, 39.45 °C and 38.65 °C. The highest pct value of patients with post-PCNL infection caused by Escherichia Coli, Enterococcus faecium and Klebsiella pneumoniae were 80.62 ± 31.45 ng/mL, 24.32 ng/mL and 8.45 ng/mL. The nitrite positive rate of patients with post-PCNL infection caused by Escherichia Coli, Enterococcus faecium and Klebsiella pneumoniae were 64.51%, 16.6% and 0. Postoperative infection of PCNL is significantly correlated with positive preoperative urine culture, and positive preoperative urine culture is an independent risk factor for postoperative infection. The most common pathogen of postoperative infection of PCNL is Escherichia coli, followed by Enterococcus and Klebsiella pneumoniae. Patients with Escherichia coli infection are often positive for nitrite before surgery, mainly manifested by high fever, and PCT is significantly increased (often exceeded 100 ng/ml). Enterococcus faecium and Klebsiella pneumoniae infections mostly occur in elderly patients and often progress to septic shock. Patients with Enterococcus faecium infection have a high fever, and the PCT value is significantly higher (often exceeded 20 ng/ml). Patients with Klebsiella pneumoniae infection have a moderate fever, and the PCT value generally does not exceeded 10 ng/ml. Long operation time is another independent risk factor for PCNL infection.


Assuntos
Infecções Bacterianas , Enterococcus faecium , Infecções por Escherichia coli , Cálculos Renais , Nefrolitotomia Percutânea , Choque Séptico , Cálculos Urinários , Idoso , Infecções Bacterianas/etiologia , Escherichia coli , Infecções por Escherichia coli/microbiologia , Feminino , Humanos , Cálculos Renais/etiologia , Klebsiella pneumoniae , Masculino , Pessoa de Meia-Idade , Nefrolitotomia Percutânea/efeitos adversos , Nitritos , Estudos Retrospectivos , Choque Séptico/etiologia
8.
Eur J Clin Invest ; : e13772, 2022 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-35294777

RESUMO

OBJECTIVE: Clinical guidelines recommend an optimal serum potassium concentration between 4.0 and 5.0 mmol/L in patients with acute myocardial infarction (AMI), which was based on lower-quality evidence from more than 20 years ago. Therefore, it is essential to re-evaluate the range of optimal potassium levels in patients with AMI in intensive care unit (ICU). METHODS: This was a retrospective study based on Philips eICU Collaborative Research Database, which covered 9776 patients with AMI between 2014 and 2015. All patients had more than or equal to 2 serum potassium measurements and were categorized by the mean serum potassium level (<3.5, 3.5-4.5, 4.5-5.5, ≥5.5 mmol/L) and potassium variability (1st, 2nd, and ≥3rd standard deviation (SD)). Binary logistic regression was used to determine the association between mean potassium levels, variability and in-hospital mortality in AMI. RESULTS: Of all 9776 AMI patients in ICU, 8731 (89.3%) patients were included. A total of 69847 potassium measurements were performed in these patients. There was a J-shaped relationship between mean serum potassium level and in-hospital mortality. The lowest mortality (mortality rate, 7.2%; 95% CI, 6.57%-7.76%) was observed in patients with mean potassium level between 3.5 and 4.5 mmol/L and a low potassium variability within the 1st SD. Logistic regression showed that the risk of in-hospital mortality is highest when the mean potassium level ≥5.5 mmol/L (57.6%; 95% Cl, 45.02%-70.24%; multivariable adjusted OR, 14.8; 95% CI, 8.4-26.2) compared to the reference group of 3.5-4.5 mmol/L and potassium variability within the 3rd SD (16.5%; 95% Cl, 15.19%-17.88%; multivariable adjusted OR, 3.3; 95% CI, 2.7-4.1) compared to 1st SD. Several sensitivity analyses confirmed these results. CONCLUSION: Among AMI patients in ICU, the minimum risk of in-hospital mortality was observed in those with mean potassium levels between 3.5 and 4.5 mmol/L or a minimal potassium variability compared to those who had higher or lower values.

9.
Cell Res ; 32(4): 383-400, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34848870

RESUMO

Pig epiblast-derived pluripotent stem cells are considered to have great potential and broad prospects for human therapeutic model development and livestock breeding. Despite ongoing attempts since the 1990s, no stably defined pig epiblast-derived stem cell line has been established. Here, guided by insights from a large-scale single-cell transcriptome analysis of pig embryos from embryonic day (E) 0 to E14, specifically, the tracing of pluripotency changes during epiblast development, we developed an in vitro culture medium for establishing and maintaining stable pluripotent stem cell lines from pig E10 pregastrulation epiblasts (pgEpiSCs). Enabled by chemical inhibition of WNT-related signaling in combination with growth factors in the FGF/ERK, JAK/STAT3, and Activin/Nodal pathways, pgEpiSCs maintain their pluripotency transcriptome features, similar to those of E10 epiblast cells, and normal karyotypes after more than 240 passages and have the potential to differentiate into three germ layers. Strikingly, ultradeep in situ Hi-C analysis revealed functional impacts of chromatin 3D-spatial associations on the transcriptional regulation of pluripotency marker genes in pgEpiSCs. In practice, we confirmed that pgEpiSCs readily tolerate at least three rounds of successive gene editing and generated cloned gene-edited live piglets. Our findings deliver on the long-anticipated promise of pig pluripotent stem cells and open new avenues for biological research, animal husbandry, and regenerative biomedicine.


Assuntos
Camadas Germinativas , Células-Tronco Pluripotentes , Animais , Diferenciação Celular/genética , Linhagem Celular , Suínos , Transcriptoma
10.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 39(1): 108-111, 2022 Jan 10.
Artigo em Chinês | MEDLINE | ID: mdl-34964980

RESUMO

Genetic background can lead to differences in drug effects among different populations when they use the same drug. To delineate the pharmacogenomics and population genetic differences may help to clarify the role of polymorphisms of drug metabolism-related genes in drug effect heterogeneity among different populations. This article has summarized the latest progress on the polymorphisms of drug metabolism-related genes among different populations in China.


Assuntos
Preparações Farmacêuticas , Polimorfismo Genético , China , Humanos , Farmacogenética
11.
Biosens Bioelectron ; 196: 113744, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34736100

RESUMO

An in situ quenching electrochemiluminescence (ECL) biosensor sensitized with the aptamer recognition-induced multi-DNA release was designed for pathogenic bacterial detection. Benefitting from the high binding ability of the aptamer to targets and large enrichment capacity of magnetic bead separation, the proposed sensing system not only exhibited outstanding identification to Staphylococcus aureus (S. aureus) among various bacteria, but also released abundant signal transduction DNAs. One S. aureus initiated the dissociation of four kinds of DNA sequences, achieving a one-to-multiple amplification effect. These multi-DNA strands were further hybridized with capture DNA, which were assembled to an electrode modified with Ru(bpy)32+-conjugated silica nanoparticles (RuSi NPs). Then, glucose oxidase (GOD) was introduced via the functional conjugation of GOD-multi-DNA, leading to the presence of H2O2 by in situ catalysis of GOD on glucose. Relying on the ECL quenching of H2O2 in the Ru(bpy)32+ system, S. aureus was quantified with a linear range from 10 to 107 CFU/mL. In addition, the negative results of non-target bacteria and good recovery efficiency in real samples revealed the system's remarkable selectivity and potential application in infectious food tests.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , DNA , Peróxido de Hidrogênio , Medições Luminescentes , Staphylococcus aureus
12.
Endocr Pract ; 28(3): 333-341, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34922031

RESUMO

OBJECTIVE: To explore whether new glucose-lowering drugs increase the risk of pancreatitis in individuals with type 2 diabetes. This present network meta-analysis aimed to investigate the risk of pancreatitis associated with the use of glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors in the treatment of type 2 diabetes mellitus. METHODS: PubMed, Web of Science, Embase, and the Cochrane Library were searched. The literature was published from the date of their inception to July 21, 2021, including placebo-controlled or head-to-head trials of 2 new glucose-lowering drugs. The relative ratio (RR) and 95% confidence interval (CI) were used to assess the risk of GLP-1 agonists and DPP-4 inhibitors for pancreatitis or pancreatic cancer among patients with type 2 diabetes. RESULTS: Seventeen studies were identified, covered 102 257 participants. The pooled results showed a neutral relationship between GLP-1 agonists and pancreatitis (overall RR, 0.96; 95% CI, 0.31-3.00) or pancreatic cancer (overall RR, 1.10; 95% CI, 0.31-4.10) compared with placebo. Meanwhile, DPP-4 inhibitors were not associated with the increased risk of pancreatitis (overall RR, 1.60; 95% CI, 0.25-11.00) or pancreatic cancer (overall RR, 0.79; 95% CI, 0.26-2.40). Among them, lixisenatide and saxagliptin may be the safest drugs compared with other drugs according to the ranking of probability. Sensitivity and subgroup analysis confirmed the stability of the core results. CONCLUSION: The most obvious finding of this study is that GLP-1 agonists and DPP-4 inhibitors are safe with respect to the risk of pancreatitis and pancreatic cancer compared with placebo. This conclusion may provide useful evidence for correlated clinical researches.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Pancreatite , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Receptor do Peptídeo Semelhante ao Glucagon 1 , Glucose , Humanos , Hipoglicemiantes/efeitos adversos , Metanálise em Rede , Pancreatite/induzido quimicamente , Pancreatite/epidemiologia
13.
Pharmgenomics Pers Med ; 14: 1537-1547, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34876832

RESUMO

INTRODUCTION: Genetic variability in genes encoding drug-metabolizing enzymes may contribute to the heterogeneity of drug responses in different populations. Extensive research in pharmacogenomics in major populations around the world provides us with a great deal of information about drug-related genetic polymorphisms. OBJECTIVE: The purpose of this study was to detect the genetic variation of drug-metabolism-related genes in the five ethnic minorities Daur, Hezhen, Ewenki, Mongolian and Manchu in China, and to analyze the distribution differences among ethnic groups. METHODS: We genotyped 32 SNPs of drug metabolism genes in 882 healthy Chinese volunteers from five ethnic groups. The genotype frequency and allele frequency of the five ethnic groups were calculated, and the different variants among the five ethnic groups were compared by chi-square test. Genetic parameters were analyzed using Popgene software. The genetic structure of five ethnic minorities was analyzed by principal component analysis, and compared with 26 populations. RESULTS: We found that SNPs of genes related to drug metabolism existed diversity in different populations. Among them, rs8192766 and rs9419082 in CYP2E1 showed statistical differences between Daur and Manchu, and NAT2 rs1801280 showed statistical differences between Hezhen and Mongolian. In addition, the five populations we studied had the smallest differences with EAS populations. There was haplotype diversity in CHST3, VKORC1, CYP1A2 and CYP2E1 genes in the five ethnic minorities, and these haplotype polymorphisms were related to the use of corresponding drug doses. Cluster analysis shows that the five ethnic minorities in Heilongjiang Province are clustered together with the EAS populations. CONCLUSION: These results suggest that understanding the diversity of drug-related genetic markers is critical for individualized drug gene therapy programs in ethnic minorities in China as well as in populations highly mixed with these ethnic groups.

14.
Front Pharmacol ; 12: 771804, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34858190

RESUMO

Background: Multiple studies have revealed that idiopathic pulmonary fibrosis (IPF) patients are more at risk for cardiovascular diseases and that many IPF patients receive cardiovascular medications like statins, angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), and anticoagulants. Existing studies have reported divergent findings on the link between cardiovascular medications and fibrotic disease processes. The aim of this study is to synthesize the evidence on the efficacy of cardiovascular medications in IPF. Methods: We searched studies reporting the effect of cardiovascular medications on IPF in the PubMed, Embase, Web of Science, Cochrane Library, and two Chinese databases (China National Knowledge Infrastructure database and China Wanfang database). We calculated survival data, forced vital capacity (FVC) decline, and IPF-related mortality to assess the efficacy of cardiovascular medications in IPF. We also estimated statistical heterogeneity by using I2 and Cochran Q tests, and publication bias was evaluated by risk of bias tools ROBINS-I. Results: A total of 12 studies were included in the analysis. The included studies had moderate-to-serious risk of bias. Statin use was associated with a reduction in mortality (hazard ratio (HR), 0.89; 95% CI 0.83-0.97). Meta-analysis did not demonstrate any significant relationship between statin use and the FVC decline (HR, 0.86; 95% CI 0.73-1.02), ACEI/ARB use, and survival data (HR, 0.92; 95% CI 0.73-1.15) as well as anticoagulant use and survival data (HR, 1.16; 95% CI 0.62-2.19). Conclusion: Our study suggested that there is a consistent relationship between statin therapy and survival data in IPF population. However, there is currently insufficient evidence to conclude the effect of ACEI, ARB, and anticoagulant therapy on IPF population especially to the disease-related outcomes in IPF.

15.
Zhen Ci Yan Jiu ; 46(11): 907-13, 2021 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-34865326

RESUMO

OBJECTIVE: To observe the effect of electroacupuncture (EA) on skeletal muscle adiponectin receptor (Adipor1) / adenylate activated protein kinase (AMPK) / peroxisome proliferator-activated receptor α (PPARα) signaling pathway and skeletal muscle morphology by the secretion of serum adiponectin in Zucker diabetic obese (ZDF) rats, so as to explore its mechanism underlying regulating glucose and lipid metabolism of type 2 diabetes mellitus (T2DM) and improving skeletal muscle insulin resistance (IR). METHODS: Twelve male ZDF rats and six Zucker thin (ZL) rats were selected. The rats were fed with Purina#5008 high-fat diet for four weeks to induce T2DM model after adaptive feeding with normal diet for one week. The ZDF rats were randomly divided into model group and EA group according to blood glucose level after modeling and 6 ZL rats were used as the blank control group. Rats in the EA group were treated with "Pishu" (BL20), EA stimulation of "Yishu" (EX-B3), "Zusanli" (ST36) and "Sanyinjiao" (SP6), once a day and 6 times a week for 4 weeks. Rats of the model and blank control groups were grabbed and fixed in the same way as EA group. Fasting blood glucose (FBG) was measured before and after EA intervention. Serum levels of insulin (INS), C-peptide (C-P), adiponectin (APN) were measured by radioimmunoassay, and those of free fatty acid (FFA), low-density lipoprotein (LDL), cholesterol (TC), triglyceride (TG) content determined by enzyme colorimetry and insulin resistance index (HOMA-IR) was calculated. The protein expression levels of AdipoR1, AMPK and PPARα proteins in the quadriceps femoris tissues were detected by Western blot and histopathological changes of quadriceps femoris muscle were observed by H.E. staining. RESULTS: Compared with the blank control group, the levels of FBG, serum INS, C-P, FFA, LDL, TC, TG and HOMA-IR in the model group were significantly increased (P<0.01, P<0.05), while the levels of serum APN and the expressions of AdipoR1, AMPK and PPARα proteins in the skeletal muscle were significantly decreased (P<0.01, P<0.05). Compared with the model group, the levels of FBG, serum INS, C-P, FFA, LDL, TC and HOMA-IR in the EA group were significantly decreased (P<0.01), and those of serum APN and expression levels of AdipoR1, AMPK and PPARα proteins in the skeletal muscle significantly increased (P<0.01), but the serum TG level had no remarkable change in the EA group (P>0.05). In addition, H.E. staining showed disordered arrangement of skeletal muscle cells, rupture and fuzziness of muscle fibers, enlargement of the space between muscular fibers and infiltration of small number of adipose cells which were relatively milder in the EA group. CONCLUSION: EA can reduce blood glucose and lipid levels, and improve IR in ZDF rats, which may be related to its functions in up-regulating AdipoR1/AMPK/PPARα signaling and in promoting APN secretion.


Assuntos
Diabetes Mellitus Tipo 2 , Eletroacupuntura , Proteínas Quinases Ativadas por AMP/metabolismo , Adiponectina/metabolismo , Animais , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/terapia , Glucose/metabolismo , Metabolismo dos Lipídeos/genética , Masculino , Músculo Esquelético/metabolismo , Obesidade/genética , Obesidade/metabolismo , Obesidade/terapia , PPAR alfa/genética , PPAR alfa/metabolismo , Ratos , Ratos Sprague-Dawley , Ratos Zucker , Transdução de Sinais
16.
Microbiol Spectr ; 9(3): e0166121, 2021 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-34756071

RESUMO

Type I interferon (IFN-I) is a key component of the host innate immune system. To establish efficient replication, viruses have developed several strategies to escape from the host IFN response. Japanese encephalitis virus (JEV) NS1', a larger NS1-related protein, is known to inhibit the mitochondrial antiviral signaling (MAVS)-mediated IFN-ß induction by increasing the binding of transcription factors (CREB and c-Rel) to the microRNA 22 (miRNA-22) promoter. However, the mechanism by which NS1' induces the recruitment of CREB and c-Rel onto the miRNA-22 promoter is unknown. Here, we found that JEV NS1' protein interacts with the host cyclin-dependent kinase 1 (CDK1) protein. Mechanistically, NS1' interrupts the CDC25C phosphatase-mediated dephosphorylation of CDK1, which prolongs the phosphorylation status of CDK1 and leads to the inhibition of MAVS-mediated IFN-ß induction. Furthermore, the CREB phosphorylation and c-Rel activation through the IκBα phosphorylation were observed to be enhanced upon the augmentation of CDK1 phosphorylation by NS1'. The abrogation of CDK1 activity by a small-molecule inhibitor significantly suppressed the JEV replication in vitro and in vivo. Moreover, the administration of CDK1 inhibitor protected the wild-type mice from JEV-induced lethality but showed no effect on the MAVS-/- mice challenged with JEV. In conclusion, our study provides new insight into the mechanism of JEV immune evasion, which may lead to the development of novel therapeutic options to treat JEV infection. IMPORTANCE Japanese encephalitis virus (JEV) is the main cause of acute human encephalitis in Asia. The unavailability of specific treatment for Japanese encephalitis demands a better understanding of the basic cellular mechanisms that contribute to the onset of disease. The present study identifies a novel interaction between the JEV NS1' protein and the cellular CDK1 protein, which facilitates the JEV replication by dampening the cellular antiviral response. This study sheds light on a novel mechanism of JEV replication, and thus our findings could be employed for developing new therapies against JEV infection.


Assuntos
Proteína Quinase CDC2/metabolismo , Vírus da Encefalite Japonesa (Espécie)/imunologia , Evasão da Resposta Imune/imunologia , Interferon beta/imunologia , Proteínas não Estruturais Virais/metabolismo , Replicação Viral/fisiologia , Animais , Proteína Quinase CDC2/antagonistas & inibidores , Proteína de Ligação a CREB/metabolismo , Linhagem Celular Tumoral , Cricetinae , Encefalite Japonesa/imunologia , Células HeLa , Humanos , Imunidade Inata/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , MicroRNAs/genética , Inibidor de NF-kappaB alfa/metabolismo , Fosforilação/genética , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas c-rel/metabolismo , Fosfatases cdc25/metabolismo
17.
Front Genet ; 12: 756802, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745225

RESUMO

Musculoskeletal performance is a complex trait influenced by environmental and genetic factors, and it has different manifestations in different populations. Heilongjiang province, located in northern China, is a multi-ethnic region with human cultures dating back to the Paleolithic Age. The Daur, Hezhen, Ewenki, Mongolian and Manchu ethnic groups in Heilongjiang province may have strong physical fitness to a certain extent. Based on the genetic characteristics of significant correlation between some important genes and skeletal muscle function, this study selected 23 SNPs of skeletal muscle strength-related genes and analyzed the distribution of these loci and genetic diversity in the five ethnic groups. Use Haploview (version 4.1) software to calculate the chi-square and the Hardy-Weinberg equilibrium to assess the difference between the two ethnic groups. Use R (version 4.0.2) software to perform principal component analysis of different ethnic groups. Use MEGA (version 7.0) software to construct the phylogenetic tree of different ethnic groups. Use POPGENE (version 1.32) software to calculate the heterozygosity and the FST values of 23 SNPs. Use Arlequin (version 3.5.2.2) software to analyze molecular variance (AMOVA) among 31 populations. The results showed that there was haplotype diversity of VDR, angiotensin-converting enzyme, ACTN3, EPO and IGF1 genes in the five ethnic groups, and there were genetic differences in the distribution of these genes in the five ethnic groups. Among them, the average gene heterozygosity (AVE_HET) of the 23 SNPs in the five populations was 0.398. The FST values of the 23 SNPs among the five ethnic groups varied from 0.0011 to 0.0137. According to the principal component analysis, the genetic distance of Daur, Mongolian and Ewenki is relatively close. According to the phylogenetic tree, the five ethnic groups are clustered together with the Asian population. These data will enrich existing genetic information of ethnic minorities.

18.
Front Microbiol ; 12: 727236, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34690968

RESUMO

Flaviviruses are the major emerging arthropod-borne pathogens globally. However, there is still no practical anti-flavivirus approach. Therefore, existing and emerging flaviviruses desperately need active broad-spectrum drugs. In the present study, the antiviral effect of steroidal dehydroepiandrosterone (DHEA) and 23 synthetic derivatives against flaviviruses such as Japanese encephalitis virus (JEV), Zika virus (ZIKV), and Dengue virus (DENV) were appraised by examining the characteristics of virus infection both in vitro and in vivo. Our results revealed that AV1003, AV1004 and AV1017 were the most potent inhibitors of flavivirus propagation in cells. They mainly suppress the viral infection in the post-invasion stage in a dose-dependent manner. Furthermore, orally administered compound AV1004 protected mice from lethal JEV infection by increasing the survival rate and reducing the viral load in the brain of infected mice. These results indicate that the compound AV1004 might be a potential therapeutic drug against JEV infection. These DHEA derivatives may provide lead scaffolds for further design and synthesis of potential anti-flavivirus potential drugs.

19.
ACS Appl Mater Interfaces ; 13(37): 44339-44347, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34495631

RESUMO

The criticality of cobalt (Co) has been motivating the quest for Co-free positive electrode materials for building lithium (Li)-ion batteries (LIBs). However, the LIBs based on Co-free positive electrode materials usually suffer from relatively fast capacity decay when coupled with conventional LiPF6-organocarbonate electrolytes. To address this issue, a 1,2-dimethoxyethane-based localized high-concentration electrolyte (LHCE) was developed and evaluated in a Co-free Li-ion cell chemistry (graphite||LiNi0.96Mg0.02Ti0.02O2). Extraordinary capacity retentions were achieved with the LHCE in coin cells (95.3%), single-layer pouch cells (79.4%), and high-capacity loading double-layer pouch cells (70.9%) after being operated within the voltage range of 2.5-4.4 V for 500 charge/discharge cycles. The capacity retentions of counterpart cells using the LiPF6-based conventional electrolyte only reached 61.1, 57.2, and 59.8%, respectively. Mechanistic studies reveal that the superior electrode/electrolyte interphases formed by the LHCE and the intrinsic chemical stability of the LHCE account for the excellent electrochemical performance in the Co-free Li-ion cells.

20.
Front Pharmacol ; 12: 730681, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34475825

RESUMO

Background: Administration of aspirin has the potential for significant side effects of gastrointestinal (GI) injury mainly caused by gastric acid stimulation, especially in long-term users or users with original gastrointestinal diseases. The debate on the optimal treatment of aspirin-induced gastrointestinal injury is ongoing. We aimed to compare and rank the different treatments for aspirin-induced gastrointestinal injury based on current evidence. Methods: We searched PubMed, EMBASE, Cochrane Library (Cochrane Central Register of Controlled Trials), and Chinese databases for published randomized controlled trials (RCTs) of different treatments for aspirin-induced gastrointestinal injury from inception to 1 May 2021. All of the direct and indirect evidence included was rated by network meta-analysis under a Bayesian framework. Results: A total of 10 RCTs, which comprised 503 participants, were included in the analysis. The overall quality of evidence was rated as moderate to high. Eleven different treatments, including omeprazole, lansoprazole, rabeprazole, famotidine, geranylgeranylacetone, misoprostol, ranitidine bismuth citrate, chili, phosphatidylcholine complex, omeprazole plus rebamipide, and placebo, were evaluated in terms of preventing gastrointestinal injury. It was suggested that omeprazole plus rebamipide outperformed other treatments, whereas geranylgeranylacetone and placebo were among the least treatments. Conclusion: This is the first systematic review and network meta-analysis of different treatments for aspirin-induced gastrointestinal injury. Our study suggested that omeprazole plus rebamipide might be considered the best option to treat aspirin-induced gastrointestinal injury. More multicenter, high quality, large sample size randomized controlled trials will confirm the advantages of these medicines in the treatment of aspirin-induced gastrointestinal injury in the future.

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