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1.
Acta Pharmacol Sin ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33024240

RESUMO

DJ-1 is a multifunctional protein associated with cancers and autosomal early-onset Parkinson disease. Besides the well-documented antioxidative stress activity, recent studies show that DJ-1 has deglycation enzymatic activity and anti-ferroptosis effect. It has been shown that DJ-1 forms the homodimerization, which dictates its antioxidative stress activity. In this study, we investigated the relationship between the dimeric structure of DJ-1 and its newly reported activities. In HEK293T cells with Flag-tagged and Myc-tagged DJ-1 overexpression, we performed deletion mutations and point mutations, narrowed down the most critical motif at the C terminus. We found that the deletion mutation of the last three amino acids at the C terminus of DJ-1 (DJ-1 ΔC3) disrupted its homodimerization with the hydrophobic L187 residue being of great importance for DJ-1 homodimerization. In addition, the ability in methylglyoxal (MGO) detoxification and deglycation was almost abolished in the mutation of DJ-1 ΔC3 and point mutant L187E compared with wild-type DJ-1 (DJ-1 WT). We also showed the suppression of erastin-triggered ferroptosis in DJ-1-/- mouse embryonic fibroblast cells was abolished by ΔC3 and L187E, but partially diminished by V51C. Thus, our results demonstrate that the C terminus of DJ-1 is crucial for its homodimerization, deglycation activity, and suppression of ferroptosis.

2.
J Cancer Res Ther ; 16(5): 1148-1150, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33004762

RESUMO

Background: Immunoglobulin G4-related disease (IgG4-RD) is an immune mediated fibro inflammatory condition characterized by abundant IgG4-positive (IgG4+) plasma cell infiltrated lesions and elevated serum IgG4 concentrations. Tubulointerstitial nephritis and glomerular lesions are the most common renal IgG4-RDs. However, solitary mass lesion is rarely observed in renal IgG4-RD. Materials and Methods: We reported a 55-year-old male patient with a space-occupying lesion in the right kidney detected during a routine ultrasound medical examination. Computed tomography indicated a 20 mm × 15 mm × 18 mm mass located at the lower pole of the right kidney. Both T1-weighted imaging and T2-weighted imaging magnetic resonance imaging scans showed a hypointense mass. Diffusion-weighted imaging (b value = 800) showed slightly hyperintensity. Results: The lesion was diagnosed as renal cell carcinoma clinically based on the laboratory and radiological findings and treated with laparoscopic resection. However, the postoperative histological examination results indicated the lesion IgG4-RD of the kidney. Conclusion: We should consider pseudotumor-like IgG4-RD as a differential diagnosis for solitary renal lesion although the incidence is low.

3.
Curr Pharm Des ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33030126

RESUMO

BACKGROUND: Meteorin-like (Metrnl) is a newly identified adipokine implicated in the pathogenesis of type 2 diabetes mellitus (T2DM), yet data on the circulating levels of Metrnl in patients with T2DM are controversial. To derive a more precise estimation on circulating Metrnl levels in T2DM patients, we conducted this meta-analysis. METHODS: The existing studies on the circulating levels of Metrnl in patients with T2DM published up to 16 January 2020 were comprehensively retrieved from PubMed, Web of Science, EMBASE, and The Cochrane library database. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated using random-effects model. Heterogeneity was assessed and quantified by Cochrane's Q and I2 statistic. All statistical analyses were performed using Stata 12.0 software. RESULTS: Nine studies with 867 T2DM patients and 831 normal glucose tolerance (NGT) controls were included in the final analysis according to the inclusion criteria. No significant difference in circulating Metrnl levels was found between T2DM patients and NGT individuals (pooled SMD = -0.429, 95% CI = -1.077 to 0.219). Compared to controls, circulating Metrnl levels were significantly higher in the subgroups with BMI <25 kg/m2, using plasma sample and patient sample size ≥100, while circulating Metrnl levels were significantly lower in subgroups with age ≤50 years and homeostatic model assessment for insulin resistance (HOMA-IR) ≥4. CONCLUSIONS: This meta-analysis indicates no significant change in circulating Metrnl levels in T2DM patients. However, this result may be influenced by age, BMI, sample type, HOMA-IR and patients sample size. Further longitudinal studies are warranted to offer more insights into the relationship between Metrnl and T2DM.

4.
Environ Pollut ; 268(Pt A): 115628, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33049484

RESUMO

Air pollution is an important risk factor for autoimmune diseases, but its association with the recurrence of rheumatoid arthritis (RA) remains unclear so far. This study aimed to investigate the short-term association between traffic-related air pollutants and hospital readmissions for RA in Hefei, China. Data on daily hospital readmissions for RA and traffic-related air pollutants, including particulate matter (PM2.5 and PM10), nitrogen dioxide (NO2), and carbon monoxide (CO), from 2014 to 2018 were retrieved. A time-series approach using generalized linear regression model was employed. The analysis was further stratified by sex, age and season. A total of 1153 readmissions for RA were reported during the study period. A significant association between high-concentration PM2.5 (90th percentile) and RA readmissions was observed on lag1 (relative risk (RR) = 1.09, 95% confidence interval (CI): 1.01-1.19) and lasted until lag3 (RR = 1.06, 95%CI: 1.01-1.12). From lag2 to lag5, high-concentration NO2 (90th percentile) was associated with increased risk of RA readmissions, with the highest RR observed at lag 4 (1.11, 95%CI: 1.05-1.17). Stratified analyses indicated that females and the elderly appeared to be more vulnerable to high-concentration PM2.5 and NO2 exposure. High-concentration PM2.5 and NO2 in cold seasons were consistently significantly associated with increased risk of RA readmissions. Exposure to high-concentration PM2.5 and NO2 was associated with increased risk of RA readmissions. Protective measures against the exposure to high-concentration PM2.5 and NO2 should be taken to reduce the recurrence risk in RA patients, especially in females, the elderly and during cold seasons.

6.
Sci Total Environ ; : 142690, 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33071127

RESUMO

Regional acclimatisation and microbial interactions significantly influence the resilience of reef-building corals facing anthropogenic climate change, allowing them to adapt to environmental stresses. However, the connections between community structure and microbial interactions of the endemic coral microbiome and holobiont acclimatisation remain unclear. Herein, we used generation sequencing of internal transcribed spacer (ITS2) and 16S rRNA genes to investigate the microbiome composition (Symbiodiniaceae and bacteria) and associated potential interactions of endemic dominant coral holobionts (Pocillopora verrucosa and Turbinaria peltata) in the South China Sea (SCS). We found that shifts in Symbiodiniaceae and bacterial communities of P. verrucosa were associated with latitudinal gradient and climate zone changes, respectively. The C1 sub-clade consistently dominated the Symbiodiniaceae community in T. peltata; yet, the bacterial community structure was spatially heterogeneous. The relative abundance of the core microbiome among P. verrucosa holobionts was reduced in the biogeographical transition zone, while bacterial taxa associated with anthropogenic activity (Escherichia coli and Sphingomonas) were identified in the core microbiomes. Symbiodiniaceae and bacteria potentially interact in microbial co-occurrence networks. Further, increased bacterial, and Symbiodiniaceae α-diversity was associated with increased and decreased network complexity, respectively. Hence, Symbiodiniaceae and bacteria demonstrated different flexibility in latitudinal or climatic environmental regimes, which correlated with holobiont acclimatisation. Core microbiome analysis has indicated that the function of core bacterial microbiota might have changed in distinct environmental regimes, implying potential human activity in the coral habitats. Increased bacterial α diversity may lead to a decline in the stability of coral-microorganism symbioses, whereas rare Symbiodiniaceae may help to retain symbioses. Cladocopium, γ-proteobacteria, while α-proteobacteria may have been the primary drivers in the Symbiodiniaceae-bacterial interactions (SBIs). Our study highlights the association between microbiome shift in distinct environmental regimes and holobiont acclimatisation, while providing insights into the impact of SBIs on holobiont health and acclimatisation during climate change.

7.
Plant Signal Behav ; : 1836883, 2020 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-33100175

RESUMO

The circadian clock is a universal timing system that involved in plant physical responses to abiotic stresses. Moreover, OSCA1 is an osmosensor responsible for [Ca2+]i increases induced by osmotic stress in plants. However, there is little information on osmosensor involved osmotic stress-triggered circadian clock responses. Using an aequorin-based Ca2+ imaging assay, we found the gradient (0 mM, 200 mM, 500 mM) osmotic stress (induced by sorbitol) both altered the primary circadian parameter of WT and osca1 mutant. This means the plant switch to a fast day/night model to avoid energy consumption. In contrast, the period of WT and osca1 mutant became short since the sorbitol concentration increased from 0 mM to 500 mM. As the sorbitol concentration increased, the phase of the WT becomes more extensive compared with osca1 mutant, which means WT is more capable of coping with the environmental change. Moreover, the amplitude of WT also becomes broader than osca1 mutant, especially in high (500 mM) sorbitol concentration, indicate the WT shows more responses in high osmotic stress. In a word, the WT has much more flexibility to cope with the osmotic stress than osca1 mutant. It implies the OSCA1 might be involved in the circadian gated plant adaptation to the environmental osmotic stress, which opens an avenue to study Ca2+ processes with other circadian signaling pathways.

8.
Essays Biochem ; 64(5): 683-685, 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33094811

RESUMO

This collection of reviews aims to summarise our current understanding of a fundamental question: how do we deal with DNA damage? After identifying key players that are important for this process, we are now starting to reveal the dynamic organisation of detecting and repairing DNA damage. Reviews in this issue provide an update on the exciting research progress that is happening now in this field and also initiate discussion about future challenges and directions that we are heading to.

9.
Bioengineered ; 11(1): 921-931, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32865156

RESUMO

Exo-inulinases are members of the glycoside hydrolase family 32 and function by hydrolyzing inulin into fructose with yields up to 90-95%. The N-terminal tail contributes to enzyme thermotolerance, which plays an important role in enzyme applications. However, the role of N-terminal amino acid residues in the thermal performance and structural properties of exo-inulinases remains to be elucidated. In this study, three and six residues of the N-terminus starting from Gln23 of the exo-inulinase InuAGN25 were deleted and expressed in Escherichia coli. After digestion with human rhinovirus 3 C protease to remove the N-terminal amino acid fusion sequence that may affect the thermolability of enzymes, wild-type RfsMInuAGN25 and its mutants RfsMutNGln23Δ3 and RfsMutNGln23Δ6 were produced. Compared with RfsMInuAGN25, thermostability of RfsMutNGln23Δ3 was enhanced while that of RfsMutNGln23Δ6 was slightly reduced. Compared with the N-terminal structures of RfsMInuAGN25 and RfsMutNGln23Δ6, RfsMutNGln23Δ3 had a higher content of (1) the helix structure, (2) salt bridges (three of which were organized in a network), (3) cation-π interactions (one of which anchored the N-terminal tail). These structural properties may account for the improved thermostability of RfsMutNGln23Δ3. The study provides a better understanding of the N-terminus-function relationships that are useful for rational design of thermostability of exo-inulinases.

10.
J Invest Dermatol ; 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32918951

RESUMO

Chlamydia trachomatis is the most common bacterial sexually transmitted infection worldwide. Azithromycin is effective in treating Chlamydia infection; however, resistance to this antibiotic is increasing, and it is important that new therapeutic strategies are developed. Here, we demonstrated that inhibitors targeting each kinase in the ERK/RSK cascade significantly decreased the size and number of inclusions, as well as the number of infectious progeny. The suppressive effects of the inhibitors were observed across the Chlamydia serotypes D, E, F, and L1 and across Hela, McCoy, and Vero host cells. When combined with azithromycin, all the inhibitors exerted a synergistic suppressive effect on Chlamydia infection. Knockdown experiments using siRNA demonstrated that ERK1/2 and RSK1 were crucial for Chlamydia infection. Moreover, BVD-523, a first-in-class ERK1/2 inhibitor currently undergoing a phase II clinical trial, suppressed Chlamydia infection both in cell culture and in a mouse model. These observations demonstrated not only that the ERK/RSK pathway plays a critical role in Chlamydia infection, but also that these kinases have potential as targets for host-directed therapy against Chlamydia trachomatis.

11.
Sci Total Environ ; 754: 141598, 2020 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-32916499

RESUMO

In this study, it was found that monochloramine induced the formation of reactive species during ozonation of chloromethylisothiazolinone (CMIT). CMIT was found recalcitrant to chloramine. However, chloramine promoted the degradation of CMIT by ozonation significantly. Hydroxyl radicals contributed most to CMIT degradation (87%) during ozone/chloramine synergistic oxidation process (SOP). The hydroxyl radical exposure during ozone/chloramine SOP was around 7.9 times higher than that of ozonation process. The hydroxyl radical yield of ozone/chloramine SOP was estimated to be 32%. The reaction mechanisms between ozone and chloramine were postulated to include the oxygen transfer reaction to form singlet oxygen, and the formation of hydroxyl radical by the insertion pathway or electron transfer pathway. Chloramine dosage and pH are essential influencing factors. The degradation of CMIT increased from 41% to 74% with increasing chloramine dosage (0-20 µM), and then decreased to 65% when chloramine dosage continually increased to 40 µM. Ozone/chloramine SOP showed better performance at acidic or neutral conditions than basic condition. Based on the intermediates identified, the degradation pathway of CMIT during ozone/chloramine SOP included the oxidation of sulfur atom and the substitution of chlorine group by hydroxyl group. The oxidation of sulfur atom induced lower toxicities of transformation products. The toxicities of hydroxylation products were lower to fish and algae, but higher to daphnia. Based on the GC-ECD results, only trichloromethane (1.94 µg/L) was detected after ozone/chloramine SOP, accounting for 0.17% (µM/µM) of the CMIT removal.

12.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(10): 1154-1157, 2020 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-32924124

RESUMO

OBJECTIVE: To explore the genetic basis for a child with mental retardation. METHODS: The child was subjected to next generation sequencing (NGS). Candidate variant was analyzed with bioinformatic software. RESULTS: NGS revealed that the child has carried a de novo heterozygous c.4035G>C (p.Gln1345His) variant of the ARID1B gene. The variant was unreported previously and may cause instability of the protein structure. CONCLUSION: The de novo missense variant of ARID1B gene may underlie the mental retardation in the child. Above result has enabled genetic counseling and prenatal diagnosis for her family.

13.
Sci Adv ; 6(34): eaaz2978, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32923614

RESUMO

Neurogenesis processes differ in different areas of the cortex in many species, including humans. Here, we performed single-cell transcriptome profiling of the four cortical lobes and pons during human embryonic and fetal development. We identified distinct subtypes of neural progenitor cells (NPCs) and their molecular signatures, including a group of previously unidentified transient NPCs. We specified the neurogenesis path and molecular regulations of the human deep-layer, upper-layer, and mature neurons. Neurons showed clear spatial and temporal distinctions, while glial cells of different origins showed development patterns similar to those of mice, and we captured the developmental trajectory of oligodendrocyte lineage cells until the human mid-fetal stage. Additionally, we verified region-specific characteristics of neurons in the cortex, including their distinct electrophysiological features. With systematic single-cell analysis, we decoded human neuronal development in temporal and spatial dimensions from GW7 to GW28, offering deeper insights into the molecular regulations underlying human neurogenesis and cortical development.

14.
Artigo em Inglês | MEDLINE | ID: mdl-32944772

RESUMO

OBJECTIVES: Several studies have reported increased serum/plasma adiponectin levels in SLE patients. This study was performed to estimate the causal effects of circulating adiponectin levels on SLE. METHODS: We selected nine independent single-nucleotide polymorphisms that were associated with circulating adiponectin levels (P < 5 × 10-8) as instrumental variables from a published genome-wide association study (GWAS) meta-analysis. The corresponding effects between instrumental variables and outcome (SLE) were obtained from an SLE GWAS analysis, including 7219 cases with 15 991 controls of European ancestry. Two-sample Mendelian randomization (MR) analyses with inverse-variance weighted, MR-Egger regression, weighted median and weight mode methods were used to evaluate the causal effects. RESULTS: The results of inverse-variance weighted methods showed no significantly causal associations of genetically predicted circulating adiponectin levels and the risk for SLE, with an odds ratio (OR) of 1.38 (95% CI 0.91, 1.35; P = 0.130). MR-Egger [OR 1.62 (95% CI 0.85, 1.54), P = 0.195], weighted median [OR 1.37 (95% CI 0.82, 1.35), P = 0.235) and weighted mode methods [OR 1.39 (95% CI 0.86, 1.38), P = 0.219] also supported no significant associations of circulating adiponectin levels and the risk for SLE. Furthermore, MR analyses in using SLE-associated single-nucleotide polymorphisms as an instrumental variable showed no associations of genetically predicted risk of SLE with circulating adiponectin levels. CONCLUSION: Our study did not find evidence for a causal relationship between circulating adiponectin levels and the risk of SLE or of a causal effect of SLE on circulating adiponectin levels.

15.
BMC Womens Health ; 20(1): 194, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32891135

RESUMO

BACKGROUND: To investigate the impact of the elevation of tumor-infiltrating lymphocytes (TILs) in different molecular subtypes of primary breast cancer, i.e. each 10% increment of TILs and high-level TILs (TILs≥50%) in tumor, on overall survival (OS) and pathological complete response (pCR) and to compare the presentation of high-level TILs across these molecular subtypes. METHODS: Citation retrieval was performed in the PubMed, Cochrane Library, Embase and Web of Science databases. All statistical calculations were performed by the software of StataSE version 12.0. RESULTS: Twenty-two eligible clinical trials including 15,676 unique patients were included for meta-analysis. Each 10% increment of TILs significantly improved OS in human epidermal growth factor receptor 2 (HER2)-overexpression (pooled Hazard ratio (HR), 0.92; 95% CI, 0.89-0.95) and triple-negative (TN) (pooled HR, 0.90; 95% CI, 0.89-0.92) breast tumors but not in luminal tumor subtype (pooled HR, 1.06; 95% CI, 0.99-1.13). It was also associated with an increased pCR rate in breast cancers (pooled Odds ratio (OR), 1.27; 95% CI, 1.19-13.5). High-level TILs were significantly related with a higher pCR rate (pooled OR, 2.73; 95% CI, 2.40-3.01) than low-level TILs. The HER2-amplified (pooled OR, 3.14; 95% CI, 1.95-5.06) and TN (pooled OR, 4.09; 95% CI, 2.71-6.19) phenotypes of breast cancers expressed significantly more high-level TILs than the luminal tumor subtype, although the presentation of those between the former two subsets was not significantly different (pooled OR, 1.30; 95%CI, 0.83-2.04). CONCLUSIONS: The elevation of TILs in breast tumors predicts favorable prognostic outcomes, particularly in the HER2-overexpression and TN subtypes.

16.
Arch Environ Contam Toxicol ; 79(3): 321-332, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32897393

RESUMO

The purpose of this study was to investigate the association among polycyclic aromatic hydrocarbons (PAHs) exposure and air pollutants and the diversity of microbiota. Daily average concentrations of six common air pollutants were obtained from China National Environmental Monitoring Centre. The PAHs exposure levels were evaluated by external and internal exposure detection methods, including monitoring atmospheric PAHs and urinary hydroxyl-polycyclic aromatic hydrocarbon (OH-PAH) metabolite levels. We analyzed the diversity of environmental and commensal bacterial communities with 16S rRNA gene sequencing and performed functional enrichment with Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Correlation analysis and logistic regression modeling were conducted to evaluate the relationship of PAHs levels with air pollutants and microbial diversity. Correlation analysis found that the concentrations of atmospheric PAHs were significantly positively correlated with those of PM10, NO2, and SO2. There also was a positive correlation between the abundance of the genus Micrococcus (Actinobacteria) and high molecular weight PAHs, and Bacillus, such as genera and low molecular weight PAHs in the atmosphere. Logistic regression showed that the level of urinary 1-OHPyrene was associated with childhood asthma after sex and age adjustment. The level of urinary 1-OHPyrene was significantly positively correlated with that of PM2.5 and PM10. In addition, the level of 1-OHPyrene was positively correlated with oral Prevotella-7 abundance. Functional enrichment analysis demonstrated that PAHs exposure may disturb signaling pathways by the imbalance of commensal microbiota, such as purine metabolism, pyrimidine metabolites, lipid metabolism, and one carbon pool by folate, which may contribute to public health issues. Our results confirmed that atmospheric PAHs and urinary 1-OHPyrene were correlated with part of six common air pollutants and indicated that PAHs pollution may alter both environmental and commensal microbiota communities associated with health-related problems. The potential health and environmental impacts of PAHs should be further explored.

17.
Redox Biol ; 37: 101709, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32905881

RESUMO

OBJECTIVE: The trace element selenium (Se) is needed for regular biosynthesis of selenoproteins, which contribute to antioxidative defense systems and affect redox-regulated signaling. Elevated Se intake and selenoprotein expression levels have been associated with impaired hydrogen peroxide-dependent signaling by insulin, leading to hyperglycemia and insulin resistance. The relation of low Se intake with glucose status and carbohydrate metabolism is poorly known. RESEARCH DESIGN AND METHODS: A cross sectional analysis among healthy subjects residing in two Chinese counties with different habitual Se intakes was conducted. Fasted glucose levels were related to Se concentrations of 5686 adults by linear regression analysis with Se, body mass index, age, thyroid status, insulin and sex as independent variables. RESULTS: Serum Se correlated strongly and positively with glucose in the Se-deficient population. There was no strong relationship of Se and glucose in the non-deficient population. Overt hypoglycemia (serum glucose < 2.8 mM) was observed in 19.2% of this random sample of subjects in the Se-deficient and in 1.4% of the moderately supplied population, respectively. CONCLUSIONS: An adequate Se supply constitutes an important factor for glucose homeostasis in human subjects. The interaction between Se status and glucose control is not limited to hyperglycemia, but apparently extends to hypoglycemia risk in Se deficiency. This newly identified relationship may be of relevance for the course of severe disease including major trauma, sepsis and COVID-19, where Se deficiency has been associated with mortality risk.

18.
BMC Bioinformatics ; 21(1): 396, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32894041

RESUMO

BACKGROUND: MicroRNAs are a class of important small noncoding RNAs, which have been reported to be involved in the processes of tumorigenesis and development by targeting a few genes. Existing studies show that the imbalance between cell proliferation and apoptosis is closely related to the initiation and development of cancers. However, the impact of miRNAs on this imbalance has not been studied systematically. RESULTS: In this study, we first construct a cell fate miRNA-gene regulatory network. Then, we propose a systematical method for calculating the global impact of miRNAs on cell fate genes based on the shortest path. Results on breast cancer and liver cancer datasets show that most of the cell fate genes are perturbed by the differentially expressed miRNAs. Most of the top-identified miRNAs are verified in the Human MicroRNA Disease Database (HMDD) and are related to breast and liver cancers. Function analysis shows that the top 20 miRNAs regulate multiple cell fate related function modules and interact tightly based on their functional similarity. Furthermore, more than half of them can promote sensitivity or induce resistance to some anti-cancer drugs. Besides, survival analysis demonstrates that the top-ranked miRNAs are significantly related to the overall survival time in the breast and liver cancers group. CONCLUSION: In sum, this study can help to systematically study the important role of miRNAs on proliferation and apoptosis and thereby uncover the key miRNAs during the process of tumorigenesis. Furthermore, the results of this study will contribute to the development of clinical therapy based miRNAs for cancers.


Assuntos
Apoptose/genética , Proliferação de Células/genética , MicroRNAs/metabolismo , Biomarcadores/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Bases de Dados Genéticas , Feminino , Redes Reguladoras de Genes , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , MicroRNAs/genética , RNA Mensageiro/metabolismo , Análise de Sobrevida
19.
Medicine (Baltimore) ; 99(39): e22286, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991431

RESUMO

BACKGROUND: At present, the effect of western-medicine (WM) therapy to treat diabetic peripheral neuropathy (DPN) is limited. Moxibustion is a representative external treatment in traditional Chinese medicine that has been beneficial to DPN. We aim to systematically assess the efficacy and safety of moxibustion in treating DPN, following PRISMA guidelines. METHODS: Eight electronic databases were searched to acquire information on eligible trials published from inception to June 1, 2019. We included randomized controlled trials (RCTs) applying moxibustion therapy with a minimum of 14-days treatment duration for DPN patients compared with placebo, no intervention, or conventional WM interventions. The primary outcomes in our study include the sensory-nerve conduction velocity (SNCV) and motor-nerve conduction velocity (MNCV). We used the Cochrane Collaboration Risk of Bias tool to assess the methodological quality of eligible RCTs. Statistical analyses were conducted using Review Manager 5.3. Risk ratios (RR) and mean differences (MD) were calculated with a 95% confidence interval (CI). The χ test was applied to assess the heterogeneity. RESULTS: In total, 11 RCTs were included that involved 927 DPN patients. Compared with the control group, there was an increase in median MNCV (MD = 6.26, 95% CI 2.64-9.89, Z = 3.39, P = .0007) and peroneal MNCV (MD = 6.45, 95% CI 5.30-7.61, P < .00001). There was also an increase in median SNCV (MD = 6.64, 95% CI 3.25-10.03, P = .0001) and peroneal SNCV (MD = 3. 57, 95% CI 2.06-5.09, Z = 4.63, P < .00001) in the treatment groups. The treatment groups receiving moxibustion therapy indicated a more significant improvement in total effectiveness rate (RR = 0.25, 95% CI 0.18-0.37, Z = 7.16, P < .00001). Toronto Clinical Scoring System indicated a significant decrease in the treatment groups (MD = -2.12, 95% CI -2.82 to 1.43, P < .00001). Only 1 study reported that treatment groups experienced no adverse reactions. The other 10 studies did not mention adverse events. CONCLUSIONS: Moxibustion therapy may be an effective and safe option for DPN patients but needs to be verified in further rigorous studies.


Assuntos
Neuropatias Diabéticas/terapia , Medicina Tradicional Chinesa/métodos , Moxibustão/métodos , Condução Nervosa/efeitos dos fármacos , Adulto , Idoso , Estudos de Casos e Controles , Bases de Dados Factuais , Tratamento Farmacológico/normas , Duração da Terapia , Feminino , Humanos , Masculino , Medicina Tradicional Chinesa/efeitos adversos , Pessoa de Meia-Idade , Moxibustão/efeitos adversos , Condução Nervosa/fisiologia , Nervo Fibular/fisiopatologia , Placebos/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Segurança , Resultado do Tratamento , Ocidente
20.
Zhongguo Zhong Yao Za Zhi ; 45(16): 3931-3937, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32893591

RESUMO

This study aimed to investigate the effect and mechanism of ligustilide, the main active ingredient in Ligusticum wallichii, on mitochondria fission after PC12 cell injury induced by oxygen and glucose deprivation/reperfusion(OGD/R). In the experiment, an OGD/R model was established in vitro, and PC12 cells were pre-treated with ligustilide for 3 h, and then the cell viability was detected by CCK-8 method. The effect of different concentrations of ligustilide on the morphology of PC12 cells after OGD/R injury was observed under an inverted microscope. Transmission electron microscopy was used to observe the mitochondrial fission of PC12 cells after OGD/R injury. DCFH-DA immunofluorescence staining method was used to detect intracellular reactive oxygen species(ROS) changes. Changes in mitochondria membrane potential(MMP) were detected by flow cytometry. Hochest 33258 was used to observe the apoptosis of PC12 cells. Western blot was used to detect changes in cytochrome C(Cyt C) content in mitochondria and cytoplasm, and mitochondrial fission-related proteins Drp 1 and Fis 1. All results showed that compared with the model group, ligustilide significantly increased the survival rate of PC12 cells and the number of cells. Further experiments showed that ligustilide inhibited the release of ROS and decline of mitochondrial membrane potential in PC12 cells after OGD/R injury. Moreover, ligustilide reduced the release of Cyt C and promoted the expressions of Drp1 and Fis1 in mitochondrial fission proteins. Verification experiments showed that mitochondrial fission inhibitor mdivi-1 decreased cell survival rate and inhibited fission. The results indicated that ligustilide exerted neuro-protective effects by promoting mitochondrial fission and reducing cell damage. It preliminary proves that the mechanism of ligustilide on ischemic brain injury may be related to the promotion of mitochondrial fission and the maintenance of cell homeostasis.


Assuntos
Glucose , Traumatismo por Reperfusão , 4-Butirolactona/análogos & derivados , Animais , Apoptose , Sobrevivência Celular , Mitocôndrias , Oxigênio , Células PC12 , Ratos , Espécies Reativas de Oxigênio
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