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1.
J Environ Sci Health B ; : 1-8, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983315

RESUMO

Acetylcholinesterase (AChE) is an enzyme that catalyzes acetylcholine into choline and acetic acid. Conventional pesticides, including organophosphates and carbamates target and inhibit the activity of AChE. To obtain more pesticide precursors that meet the safety requirements, more than 200 compounds were screened. Tirotundin and parthenolide identified as potential neurotoxins to nematodes were isolated from Tithonia diversifolia and Chrysanthemum parthenium, respectively. Their IC50 values were 6.89 ± 0.30 and 5.51 ± 0.23 µg/mL, respectively against the AChE isolated from Caenorhabditis elegans. AChE was inhibited in a dose-dependent manner using the two compounds. And the Lineweaver-Burk and Dixon plots indicated that tirotundin and parthenolide were reversible inhibitors against AChE, both inhibiting AChE in a mixed-type competitive manner and demonstrating these compounds may possess dual binding site AChE inhibitors. LC50 values of tirotundin and parthenolide against C. elegans were 9.16 ± 0.21 and 7.23 ± 0.48 µg/mL, respectively. These results provide a certain theoretical basis for the development and utilization of novel pesticides.

2.
eNeuro ; 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34996774

RESUMO

Spinal cord injury (SCI) is a devastating condition. Splenectomy may play a protective role in the development of SCI. However, little is known about whether the timing of splenectomy affects the outcome after SCI. Investigation into splenectomy after SCI would provide insight into how the timing can be selected following SCI to improve neurological outcomes. Rats were randomized into a sham group, a nonsplenectomized group (NonSPX), four splenectomized groups with the surgery performed immediately, 6 h, 12 h, and 24 h after SCI (SPX0, SPX6, SPX12, and SPX24, respectively). Rats were subjected to severe contusive SCI at the level of the third thoracic vertebra. At different time points following SCI, BBB score was used to assess the recovery of injury. The animals in each group were randomly selected for tissue collection at day 3, 14, and 28 after surgery. Then, immunohistochemistry of immunologic cells was performed and inflammatory mediators were determined. Our study showed that splenectomy within 6 h after SCI improved BBB scores as compared to splenectomy more than 12 h after SCI from 6 to 28 days after SCI, and decrease the immune cell responses to SCI. Protein levels of IL-1ß and TNF-α were significantly elevated in nonsplenectomized group compared to sham group. No difference was observed in IL-10 at the lesion site between splenectomised and nonsplenectomized groups at 3 days post-SCI. The study demonstrates that splenectomy within 6h after SCI would lessen the development of SCI and improve outcome.Significance StatementThe pathophysiologic changes in SCI involve secondary injury from the immune and inflammation system. The spleen is the largest immune organ in the mammalian lymphatic system. In animals, both splenectomy before or immediately after brain injury can alleviate the acute brain injury. However, splenectomy after SCI has not been extensively studied. Our study indicates that the splenectomy within 6 h after SCI limits neuroinflammatory pathology and improves neurological recovery. Our results implicate splenectomy could prove to be a therapeutic option to reduce injury in modulating the immune response following SCI. Therefore, the present study may form a novel strategy for biological and clinical research in SCI in the future.

3.
J Diabetes ; 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35001531

RESUMO

BACKGROUND: Research on the relationship between creatinine to body weight ratios (Cre/BW ratios) and the prevalence of diabetes is still lacking. The intention of this research was to explore the potential relationship between Cre/BW ratio and diabetes prevalence in Chinese adults. METHODS: This retrospective study was conducted on 199 526 patients in the Chinese Rich Healthcare Group from 2010 to 2016. The participants were divided into four groups on the basis of the quartiles of the Cre/BW ratios. Multivariate multiple imputation and dummy variables were used to handle missing values. Multivariate regression analysis was applied to detect the relationship between Cre/BW and diabetes. A smoothing plot was also used to identify whether there were nonlinear relationships. RESULTS: After handling missing values and adjusting for potential confounders, the multivariate Cox regression analysis results showed that Cre/BW was inversely correlated with diabetes risk (hazard ratio [HR]: 0.268; 95% confidence interval [CI]: 0.229-0.314, p < 0.00001). For men, the HR of incident diabetes was 0.255 (95% CI: 0.212-0.307) and for women it was 0.297 (95% CI: 0.218-0.406). Moreover, sensitivity analysis confirmed the stability of the results. Furthermore, the smoothing plot revealed that there was a saturation effect between Cre/BW and the incidence of diabetes. CONCLUSIONS: This study demonstrated that increased Cre/BW is negatively correlated with diabetes in Chinese adults. It also found that Cre/BW has a nonlinear relationship with the incidence of diabetes.

4.
Eur J Med Chem ; 227: 113903, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34653770

RESUMO

Further clinical development of PF74, a lead compound targeting HIV-1 capsid, is impeded by low antiviral activity and inferior metabolic stability. By modifying the benzene (region I) and indole of PF74, we identified two potent compounds (7m and 7u) with significantly improved metabolic stability. Compared to PF74, 7u displayed greater metabolic stability in human liver microsomes (HLMs) with half-life (t1/2) 109-fold that of PF74. Moreover, mechanism of action (MOA) studies demonstrated that 7m and 7u effectively mirrored the MOA of compounds that interact within the PF74 interprotomer pocket, showing direct and robust interactions with recombinant CA, and 7u displaying antiviral effects in both the early and late stages of HIV-1 replication. Furthermore, MD simulation corroborated that 7u was bound to the PF74 binding site, and the results of the online molinspiration software predicted that 7m and 7u had desirable physicochemical properties. Unexpectedly, this series of compounds exhibited better antiviral activity than PF74 against HIV-2, represented by compound 7m whose anti-HIV-2 activity was almost 5 times increased potency over PF74. Therefore, we have rationally redesigned the PF74 chemotype to inhibitors with novel structures and enhanced metabolic stability in this study. We hope that these new compounds can serve as a blueprint for developing a new generation of HIV treatment regimens.

5.
Eur J Med Chem ; 227: 113966, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34749200

RESUMO

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unprecedented in human history. As a major structural protein, nucleocapsid protein (NPro) is critical to the replication of SARS-CoV-2. In this work, 17 NPro-targeting phenanthridine derivatives were rationally designed and synthesized, based on the crystal structure of NPro. Most of these compounds can interact with SARS-CoV-2 NPro tightly and inhibit the replication of SARS-CoV-2 in vitro. Compounds 12 and 16 exhibited the most potent anti-viral activities with 50% effective concentration values of 3.69 and 2.18 µM, respectively. Furthermore, site-directed mutagenesis of NPro and Surface Plasmon Resonance (SPR) assays revealed that 12 and 16 target N-terminal domain (NTD) of NPro by binding to Tyr109. This work found two potent anti-SARS-CoV-2 bioactive compounds and also indicated that SARS-CoV-2 NPro-NTD can be a target for new anti-virus agents.


Assuntos
Antivirais/química , Proteínas do Nucleocapsídeo de Coronavírus/antagonistas & inibidores , Fenantridinas/química , SARS-CoV-2/metabolismo , Animais , Antivirais/metabolismo , Antivirais/farmacologia , Antivirais/uso terapêutico , Sítios de Ligação , COVID-19/tratamento farmacológico , COVID-19/virologia , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Proteínas do Nucleocapsídeo de Coronavírus/metabolismo , Desenho de Fármacos , Humanos , Cinética , Simulação de Acoplamento Molecular , Fenantridinas/metabolismo , Fenantridinas/farmacologia , Fenantridinas/uso terapêutico , Fosfoproteínas/antagonistas & inibidores , Fosfoproteínas/metabolismo , Ligação Proteica , Estrutura Terciária de Proteína , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/fisiologia , Células Vero
6.
Front Pharmacol ; 12: 726158, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34867329

RESUMO

Sheng-Ji Hua-Yu (SJHY) formula has been proved to reduce the severity of diabetic wound healing without significant adverse events in our previous clinical trials. However, based on multi-target characteristics, the regulatory network among herbs, ingredients, and hub genes remains to be elucidated. The current study aims to identify the biomarkers of the SJHY formula for the treatment of diabetic wound healing. First, a network of components and targets for the SJHY formula was constructed using network pharmacology. Second, the ClusterONE algorithm was used to build a modular network and identify hub genes along with kernel pathways. Third, we verified the kernel targets by molecular docking to select hub genes. In addition, the biomarkers of the SJHY formula were validated by animal experiments in a diabetic wound healing mice model. The results revealed that the SJHY formula downregulated the mRNA expression of Cxcr4, Oprd1, and Htr2a, while upregulated Adrb2, Drd, Drd4, and Hrh1. Besides, the SJHY formula upregulated the kernel pathways, neuroactive ligand-receptor interaction, and cAMP signaling pathway in the skin tissue homogenate of the diabetic wound healing mice model. In summary, this study identified the potential targets and kernel pathways, providing additional evidence for the clinical application of the SJHY formula for the treatment of diabetic wound healing.

7.
Front Cardiovasc Med ; 8: 766571, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34869680

RESUMO

Background: A variety of supraventricular arrhythmias (SVAs) may occur in patients with hypertrophic cardiomyopathy (HCM). The characteristics and long-term ablation outcomes of different types of SVAs in HCM have not been comprehensively investigated. Methods: We retrospectively enrolled 101 consecutive patients with HCM who were referred to the electrophysiology and arrhythmia service from May 2010 to October 2020. The clinical features and ablation outcomes were analyzed. Results: Seventy-eight patients had SVAs, which comprised 50 (64.1%) cases of atrial fibrillation (AF), 16 (20.5%) of atrial flutter (AFL), 15 (19.2%) of atrioventricular reentrant tachycardia (AVRT), 11 (14.1%) of atrial arrhythmia (AT), and 3 (3.8%) of atrioventricular nodal reentrant tachycardia (AVNRT). Thirty-four patients underwent catheter ablation and were followed up for a median (interquartile range) of 58.5 (82.9) months. There was no recurrence in patients with non-AF SVAs. In patients with AF, the 1- and 7-year AF-free survival rates were 87.5 and 49.5%, respectively. A receiver operator characteristic analysis showed that a greater left ventricular end-diastolic dimension (LVEDD) was associated with a higher recurrence of AF, with an optimum cutoff value of 47 mm (c-statistic = 0.91, p = 0.011, sensitivity = 1.00, specificity = 0.82). In Kaplan-Meier analysis, patients with a LVEDD ≥ 47 mm had worse AF-free survival than those with a LVEDD <47 mm (log-rank p = 0.014). Conclusions: In this unique population of HCM, AF was the most common SVA, followed in order by AFL, AVRT, AT, and AVNRT. The long-term catheter ablation outcome for non-AF SVAs in HCM is satisfactory. A greater LVEDD predicts AF recurrence after catheter ablation in patients with HCM.

8.
Ann Palliat Med ; 10(11): 11643-11652, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34872289

RESUMO

BACKGROUND: Chronic eczema has the characteristics of a long treatment cycle and repeated attacks, which seriously affects the daily life and work of patients. Topical glucocorticoids are the first-line treatment for chronic eczema. This study aimed to retrospectively analyze the effects of halometasone cream combined with Simiao pill on the efficacy and expression of serum leukotriene B4 (LTB4) and thymic stromal lymphopoietin (TSLP) in patients with eczema, and identify the factors influencing its clinical efficacy. METHODS: We retrospectively collected the medical records of 195 patients with chronic eczema treated in the dermatology department from January 2020 to May 2021, and divided them into two groups according to medication: 98 cases were treated with halometasone cream (control group) and 97 cases were treated with halometasone ointment combined with Simiao pill (observation group). The severity of eczema, quality of life, clinical efficacy, LTB4 and TSLP levels, and safety were compared between the two groups. Multivariate logistic regression analysis was used to determine the independent factors affecting clinical efficacy. RESULTS: After treatment, the Eczema area and severity index (EASI) and Dermatology Life Quality Index (DLQI) scores in the observation group were markedly lower than those of the control group (P<0.05). The total clinical effective rate of the observation group was 88.8%, which was notably higher than that of the control group 70.1% (P=0.001). The concentrations of serum LTB4 and TSLP in the observation group were markedly lower than those in the control group (P<0.05). Logistic regression analysis showed that the treatment regimen, digestive system symptoms, heavy aching limbs, and damp-heat tongue and pulse were independent factors affecting the curative effect of the patients (P<0.05). CONCLUSIONS: Simiao pill combined with halometasone cream can effectively improve chronic eczema and enhance the clinical efficacy of treatment, which may be related to the reduction of serum LTB4 and TSLP levels. The treatment plan, digestive system symptoms, heavy aching limbs, and damp-heat tongue and pulse are the main factors that affecting the clinical curative effect. Thus, clinical intervention programs should be made according to the above factors to improve the quality of life of patients.

9.
Medicine (Baltimore) ; 100(50): e28194, 2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34918675

RESUMO

BACKGROUND: It is known to all that the incidence of insomnia is becoming higher and higher with the increase of people's life stress. To some extent, it has brought about bad effects on people's life, work, study, and health, such as mental exhaustion, low work efficiency, and mood irritability. Now there are medications and non-medications methods for insomnia. As one of the treatments for insomnia, western medicine is to prolong the sleeping time and improve the anxious mood. However, taking western medicine to treat insomnia can also be accompanied by some adverse reactions at the same time, such as drug dependence, an allergic reaction, and so on. Traditional Chinese medicine therapy is based on syndrome differentiation and holistic concept. Shumian capsules (SM) are a kind of proprietary Chinese medicine for insomnia, which have the effect of relieving depression and calming the mind. But there are no studies on the efficacy and safety of SM in the treatment of insomnia. Therefore, I will provide a systematic review and meta-analysis to evaluate the efficacy and safety of SM for insomnia. METHODS: All the studies searched were from PubMed, EMBASE, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, and WanFang databases, and the studies types included in the analysis were all randomized controlled trials. All the retrieval contents were completed independently by 2 researchers, and a third reviewer would be involved when there existed any disagreement. The eligible studies were screened out according to the inclusion criteria and exclusion criteria, and some useful information was extracted and made into a feature table, including the year of the included studies, the age, and disease course of the participants in the studies and intervention methods, etc. Cochrane risk-of-bias tool was used to evaluate the quality of literature and meta-analysis was conducted by RevMan 5.4 software. RESULTS: A total of 9 articles including 709 participants were included in the study after screening out. The primary outcomes of statistical analysis were cure rate and total effective rate, while the secondary outcomes included Pittsburgh sleep quality index score and incidence of adverse reactions. The results showed that Pittsburgh sleep quality index score of the SM group and Western medicine group were statistically significant (MD = -0.50, 95% confidence interval [CI] = [-0.78, -0.22], P = .0005). The total effective rate of the SM group was slightly higher than that of the Western medicine group, but there was no statistical significance (relative risk [RR] = 1.03, 95% CI = [0.95,1.13], P = .43). CONCLUSION: This meta-analysis provides evidence for the efficacy and safety of SM in the treatment of insomnia, and provides a new idea for the clinical treatment of insomnia. But more research is needed to support further evidence.

10.
Zhonghua Nan Ke Xue ; 27(3): 201-207, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-34914300

RESUMO

Objective: To investigate the effects of morinda officinalis how (MOH) on SPAG11T and microRNA-210 (miR-210) in the testis tissue of SD rats with varicocele (VC). METHODS: Forty SD rats were randomly divided into four groups of an equal number: blank control, VC model control, low-dose MOH and high-dose MOH. The rats in the former two groups were treated intragastrically with normal saline and those in the latter two with MOH extract at 200 and 400 mg/kg/d, respectively, all for 30 days. Then, the testis tissues of the rats were harvested for measurement of the levels of SOD, MDA and AI and determination of the expressions of vimentin, sperm-associated antigen 11T (SPAG11T) protein and RNA, and miR-210. RESULTS: There were no statistically significant differences in the testicular and epididymal weights among the four groups of rats (P > 0.05). Compared with the rats in the VC model control group, those in the MOH groups showed a remarkably increased SOD content (P < 0.05) but a decreased MDA level and AI in the testis tissue (P < 0.05). The expression of vimentin mRNA in the testis tissue was significantly reduced in the VC model control in comparison with that in the blank control group (0.18 ± 0.03 vs 1.00 ± 0.02), but dramatically up-regulated after treated with low-dose MOH (0.68 ± 0.07) and high-dose MOH (0.92 ± 0.08) (F = 432.901, P< 0.01). The level of SPAG11T mRNA was also remarkably decreased in the VC model control group compared with the blank controls (0.32 ± 0.04 vs 1.00 ± 0.05), but markedly elevated after treated with low-dose MOH (0.61 ± 0.09) and high-dose MOH (0.82 ± 0.13) (F = 117.423, P< 0.01). The level of testicular miR-210, however, was significantly increased in the VC model controls compared with the blank controls (1.39 ± 0.12 vs 1.00 ± 0.06), but decreased in both the low-dose MOH (1.17 ± 0.08) and high-dose MOH groups (1.09 ± 0.08) (F = 36.136, P< 0.01). CONCLUSIONS: MOH extract can up-regulate the expressions of vimentin and SPAG11T and inhibit that of miR-210 in the testis tissue of varicocele rats.


Assuntos
MicroRNAs , Morinda , Extratos Vegetais , Varicocele , beta-Defensinas/genética , Animais , Masculino , MicroRNAs/genética , Morinda/química , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley , Testículo
11.
Chin Med J (Engl) ; 2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34924501

RESUMO

BACKGROUND: Delayed graft function (DGF) is the main cause of renal function failure after kidney transplantation. This study aims at investigating the value of hypothermic machine perfusion (HMP) parameters combined with perfusate biomarkers on predicting DGF and the time of renal function recovery after deceased donor (DD) kidney transplantation. METHODS: HMP parameters, perfusate biomarkers and baseline characteristics of 113 DD kidney transplantations from January 1, 2019 to August 31, 2019 in the First Affiliated Hospital of Xi'an Jiaotong University were retrospectively analyzed using univariate and multivariate logistic regression analysis. RESULTS: In this study, the DGF incidence was 17.7% (20/113); The multivariate logistic regression results showed that terminal resistance (OR: 1.879, 95% CI 1.145-3.56) and glutathione S-transferase (GST)(OR = 1.62, 95% CI 1.23-2.46) were risk factors for DGF; The Cox model analysis indicated that terminal resistance was an independent hazard factor for renal function recovery time (HR = 0.823, 95% CI 0.735-0.981). The model combining terminal resistance and GST (AUC = 0.888, 95% CI: 0.842-0.933) significantly improved the DGF predictability compared with the use of terminal resistance (AUC = 0.756, 95% CI 0.693-0.818) or GST alone (AUC = 0.729, 95% CI 0.591-0.806). CONCLUSION: According to the factors analyzed in this study, the combination of HMP parameters and perfusate biomarkers displays a potent DGF predictive value.

12.
Front Aging Neurosci ; 13: 763331, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34790113

RESUMO

Objective: Parkinson's disease (PD) is the second most common neurodegenerative disease in the elderly. In early stages of PD, patients typically display normal brain magnet resonance imaging (MRI) in routine screening. Advanced imaging approaches are necessary to discriminate early PD patients from healthy controls. In this study, microstructural changes in relevant brain regions of early PD patients were investigated by using quantitative MRI methods. Methods: Cerebral MRI at 3T was performed on 20 PD patients in early stages and 20 age and sex matched healthy controls. Brain relative proton density, T1, T2, and T2' relaxation times were measured in 14 regions of interest (ROIs) in each hemisphere and compared between patients and controls to estimate PD related alterations. Results: In comparison to matched healthy controls, the PD patients revealed decreased relative proton density in contralateral prefrontal subcortical area, upper and lower pons, in ipsilateral globus pallidus, and bilaterally in splenium corporis callosi, caudate nucleus, putamen, thalamus, and mesencephalon. The T1 relaxation time was increased in contralateral prefrontal subcortical area and centrum semiovale, putamen, nucleus caudatus and mesencephalon, whereas T2 relaxation time was elevated in upper pons bilaterally and in centrum semiovale ipsilaterally. T2' relaxation time did not show significant changes. Conclusion: Early Parkinson's disease is associated with a distinct profile of brain microstructural changes which may relate to clinical symptoms. The quantitative MR method used in this study may be useful in early diagnosis of Parkinson's disease. Limitations of this study include a small sample size and manual selection of the ROIs. Atlas-based or statistical mapping methods would be an alternative for an objective evaluation. More studies are necessary to validate the measurement methods for clinical use in diagnostics of early Parkinson's disease.

13.
Front Med (Lausanne) ; 8: 666062, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34746161

RESUMO

Background: The potential of washed microbiota transplantation (WMT) in Crohn's disease (CD) has been reported. This study aimed to explore the suitable timing of WMT in patients with CD complicated with malnutrition. Methods: This is a randomized, open-label study. Patients with active CD complicated with malnutrition were included and 1:1 randomized to undergo WMT at day 1 (group WMT-DAY1) or day 8 (group WMT-DAY8). The observation duration was 15 days. Exclusive enteral nutrition (EEN) was administered in both groups. The primary outcome was the improvement in nutritional parameters at day 8 and day 15 in two groups. The secondary outcome was the rate of clinical remission at day 15 in two groups. Results: Totally 19 patients completed the trial. At day 8, the lymphocyte count, albumin and prealbumin increased significantly compared to those at day 1 in group WMT-DAY1 (p = 0.018, p = 0.028, p = 0.028, respectively), while no significant increase in any nutritional parameter was shown in group WMT-DAY8. At day 15, albumin increased significantly compared to that at day 1 in both groups (p < 0.05), while significant increase in prealbumin was only shown in group WMT-DAY1 (p = 0.004) compared to that at day 1. The rate of clinical remission at day 15 in group WMT-DAY1 and group WMT-DAY8 was 87.5% (7/8) and 72.7% (8/11), respectively (p = 0.603). Conclusion: EEN combined with immediate WMT intervention could rapidly improve the nutritional status and induce clinical remission in malnourished patients with CD. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02897661.

14.
BMC Cancer ; 21(1): 1209, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34772393

RESUMO

BACKGROUND: To identify candidate key genes and pathways related to resting mast cells in meningioma and the underlying molecular mechanisms of meningioma. METHODS: Gene expression profiles of the used microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. GO and KEGG pathway enrichments of DEGs were analyzed using the ClusterProfiler package in R. The protein-protein interaction network (PPI), and TF-miRNA- mRNA co-expression networks were constructed. Further, the difference in immune infiltration was investigated using the CIBERSORT algorithm. RESULTS: A total of 1499 DEGs were identified between tumor and normal controls. The analysis of the immune cell infiltration landscape showed that the probability of distribution of memory B cells, regulatory T cells (Tregs), and resting mast cells in tumor samples were significantly higher than those in the controls. Moreover, through WGCNA analysis, the module related to resting mast cells contained 158 DEGs, and KEGG pathway analysis revealed that the DEGs were dominant in the TNF signaling pathway, cytokine-cytokine receptor interaction, and IL-17 signaling pathway. Survival analysis of hub genes related to resting mast cells showed that the risk model was constructed based on 9 key genes. The TF-miRNA- mRNA co-regulation network, including MYC-miR-145-5p, TNFAIP3-miR-29c-3p, and TNFAIP3-hsa-miR-335-3p, were obtained. Further, 36 nodes and 197 interactions in the PPI network were identified. CONCLUSION: The results of this study revealed candidate key genes, miRNAs, and pathways related to resting mast cells involved in meningioma development, providing potential therapeutic targets for meningioma treatment.

16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1570-1576, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34627442

RESUMO

OBJECTIVE: To investigate the expressions of microRNAs in peripheral blood of patients with primary immune thrombocytopenia(ITP) and its correlation with the imbalance of Th1/Th2 cells. METHODS: Thirty patients with ITP (ITP group) and 15 healthy people (control group) were enrolled.Real-time polymerase chain reaction (RT-PCR) was used to detect the expressions of six miRNAs (miR-107,miR-205-5p,miR-138-5p,miR-326,miR-1827,miR-185-5p) and Th1-specific transcription factor T-bet mRNA and Th2-specific transcription factor GATA-3 mRNA in the peripheral blood of the two groups. Th1 and Th2 cells were detected by flow cytometry. The expressions of Th1-cytokines TNF-α and IFN-γ and Th2-cytokines IL-4 and IL-10 were detected by AimPlex multiple immunoassays for Flow. The expression difference of miRNAs, mRNA, Th1, Th2 cells and cytokines of the two groups were compared, and the correlations of miRNAs to mRNA, Th1, Th2 cells and cytokines were analyzed in ITP group. RESULTS: The expressions of miRNAs(miR-107, miR-205-5p, miR-138-5p, miR-326, miR-1827, miR-185-5p)and Th2-specific transcription factor GATA-3 mRNA of the patients in ITP group were significantly decreased (P<0.05) as compared with those in control, while the expressions of Th1 cells and Th1-specific transcription factor T-bet mRNA and Th1-cytokines TNF-α were significantly increased (P<0.05), also for the ratios of T-bet mRNA/GATA-3 mRNA and Th1/Th2 cells were significantly increased (P<0.05). The relative expressions of miR-107, miR-205-5p, miR-138-5p in ITP patients were negatively correlated with Th2 cells (r=-0.411, r=-0.593, r=-0.403,P<0.05) and the relative expression of miR-1827 was negatively correlated with TNF-α (r=-0.390). CONCLUSION: The relative expressions of the six miRNAs in peripheral blood of patients with ITP are significantly decreased, which result in the increasing ratio of T-bet mRNA/GATA-3 mRNA, then lead to the imbalance of Th1/Th2.


Assuntos
MicroRNAs , Púrpura Trombocitopênica Idiopática , Humanos , RNA Mensageiro , Células Th1 , Células Th2
17.
Jpn J Ophthalmol ; 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34655347

RESUMO

PURPOSE: To investigate the association between metabolic syndrome (MetS) and diabetic retinopathy (DR), as well as the association between MetS and retinal vessel caliber, among Chinese patients with type 2 diabetes mellitus in north-eastern China. STUDY DESIGN: Cross-sectional study. PATIENTS AND METHODS: The patients were recruited from a community-based study, the Fushun Diabetic Retinopathy Cohort Study (FS-DIRECT). The presence of DR was determined using a modified version of the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. The central retinal arteriolar equivalent (CRAE) and the central retinal venular equivalent (CRVE) were identified by use of Integrative Vessel Analysis software. The presence of MetS was defined according to the Joint Interim Statement proposed in 2009. RESULTS: The prevalence of DR was significantly higher among female patients with MetS than among those without it (47.2% vs 30.9%, P = 0.002), and it increased as the number of MetS components increased (P = 0.003). Furthermore, the presence of MetS (odds ratio 2.43, 95% CI 1.39-4.26) as well as higher numbers of MetS components were significantly associated with DR in female patients, after adjustment for potential risk factors. Patients with MetS (multivariate ß coefficient, 95% CI - 6.9, - 10.0, to - 3.8) or a higher number of Mets components tended to have significantly smaller CRAE. CONCLUSION: In this study cohort, female patients with MetS had a higher prevalence of DR. Patients tended to have thinner central retinal arterioles as the number of MetS components increased.

19.
Liver Int ; 2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34719118

RESUMO

BACKGROUND AND AIMS: Neuropsychiatric symptoms in hepatitis C (HCV) patients resemble those of patients with autoimmune hepatitis (AIH) or primary biliary cholangitis (PBC), whilst the mechanisms behind them are unknown. Here we looked for cerebral metabolic and/or microstructural alterations in patients with HCV, AIH or PBC as possible causes behind these symptoms. METHODS: Patients with HCV infection (n = 17), AIH (n = 14) or PBC (n = 11) and age-adjusted healthy controls (n = 18) underwent brain magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS) and psychometric assessment of memory and attention. Brain relative proton density (PD) and T2 relaxation time (T2) were determined in 17 regions of interest (ROIs), as were the concentrations of N-acetyl-aspartate, choline, creatine, myo-inositol and glutamine + glutamate in frontal- (fWM) and parietal white matter (pWM). One-way analysis of variance and Kruskal-Wallis tests were used for group comparison. Correlations between altered neuropsychological findings and MRI/MRS observations were estimated with the Spearman ρ test. RESULTS: HCV, AIH and PBC patients revealed similar alterations in brain PD and metabolites compared to controls: significantly decreased PD in 7/17 ROIs in the HCV group, 16/17 ROIs in the PBC group and 14/17 ROIs in the AIH group, significantly increased N-acetyl-aspartate in fWM in all patients, significantly increased choline in the PBC group in both fWM and pWM, in the AIH group only in pWM and with a trend in the HCV group in pWM. Correlation analysis did not reveal significant associations between MRI/MRS alterations and neuropsychological dysfunction. CONCLUSION: The findings suggest similar pathophysiological mechanisms behind neuropsychiatric symptoms associated with HCV infection, AIH and PBC.

20.
Chin Med J (Engl) ; 134(23): 2874-2881, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34711716

RESUMO

BACKGROUND: The complement system plays an important role in the immune response to transplantation, and the diagnostic significance of peritubular capillary (PTC) C4d deposition (C4d+) in grafts is controversial. The study aimed to fully investigate the risk factors for PTC C4d+ and analyze its significance in biopsy pathology of kidney transplantation. METHODS: This retrospective study included 124 cases of kidney transplant with graft biopsy and donor-specific antibody (DSA) testing from January 2017 to December 2019 in a single center. The effects of recipient pathological indicators, eplet mismatch (MM), and DSAs on PTC C4d+ were examined using univariate and multivariate logistic regression analyses. RESULTS: In total, 35/124 (28%) were PTC C4d+, including 21 with antibody-mediated rejection (AMR), eight with renal tubular injury, three with T cell-mediated rejection, one with glomerular disease, and two others. Univariate analysis revealed that DSAs (P < 0.001), glomerulitis (P < 0.001), peritubular capillaritis (P < 0.001), and human leukocyte antigen (HLA) B eplet MM (P = 0.010) were the influencing factors of PTC C4d+. According to multivariate analysis, DSAs (odds ratio [OR]: 9.608, 95% confidence interval [CI]: 2.742-33.668, P < 0.001), glomerulitis (OR: 3.581, 95%CI: 1.246-10.289, P = 0.018), and HLA B eplet MM (OR: 1.166, 95%CI: 1.005-1.353, P = 0.042) were the independent risk factors for PTC C4d+. In receiver operating characteristic curve analysis, the area under the curve was increased to 0.831 for predicting PTC C4d+ when considering glomerulitis, DSAs, and HLA B eplet MM. The proportions of HLA I DSAs and PTC C4d+ in active antibody-mediated rejection were 12/17 and 15/17, respectively; the proportions of HLA class II DSAs and PTC C4d+ in chronic AMR were 8/12 and 7/12, respectively. Furthermore, the higher the PTC C4d+ score was, the more serious the urinary occult blood and proteinuria of recipients at the time of biopsy. CONCLUSIONS: PTC C4d+ was mainly observed in AMR cases. DSAs, glomerulitis, and HLA B eplet MM are the independent risk factors for PTC C4d+.

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