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1.
J Cell Biochem ; 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34237164

RESUMO

Microtubules play crucial role in process of mitosis and cell proliferation, which have been considered as attractive drug targets for anticancer therapy. The aim of this study was to discover novel and chemically diverse tubulin inhibitors for treatment of cancer. In this investigation, the multilayer virtual screening methods, including common feature pharmacophore model, structure-based pharmacophore model and molecular docking, were developed to screen BioDiversity database with 30,000 compounds. A total of 102 compounds were obtained by the virtual screening, and further filtered by diverse chemical clusters with desired properties and PAINS analysis. Finally, 50 compounds were selected and submitted to the biological evaluation. Among these hits, hits 8 and 30 with novel scaffolds displayed stronger antiproliferative activity on four human tumor cells including Hela, A549, MCF-7, and HepG2. Moreover, the two hits were subsequently submitted to molecular dynamic simulations of 90 ns with the aim of exploring the stability of ligand-protein interactions into the binding pocket, and further probing the mechanism of the interaction between tubulin and hits. The molecular dynamic simulation results revealed there had stronger interactions between tubulin and hits in equilibrium state. Therefore, the hits 8 and 30 have been well characterized as lead compounds for developing new tubulin inhibitors with potential anticancer activity.

2.
Dis Markers ; 2021: 5574472, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34257746

RESUMO

Regulatory T cells (Tregs) expressing the Foxp3 transcription factor are indispensable for the maintenance of immune system homeostasis. Tregs may lose Foxp3 expression or be reprogrammed into cells that produce proinflammatory cytokines, for example, Th1-like Tregs, Th2-like Tregs, Th17-like Tregs, and Tfh-like Tregs. Accordingly, selective therapeutic molecules that manipulate Treg lineage stability and/or functional activity might have the potential to improve aberrant immune responses in human disorders. In particular, the transcription factor Helios has emerged as an important marker and modulator of Tregs. Therefore, the current review focuses on recent findings on the expression, function, and mechanisms of Helios, as well as the patterns of Foxp3+ Tregs coexpressing Helios in various human disorders, in order to explore the potential of Helios for the improvement of many immune-related diseases. The studies were selected from PubMed using the library of the Nanjing Medical University in this review. The findings of the included studies indicate that Helios expression stabilizes the phenotype and function of Foxp3+ Tregs in certain inflammatory environments. Further, Tregs coexpressing Helios and Foxp3 were identified as a specific phenotype of stronger suppressor immune cells in both humans and animal models. Importantly, there is ample evidence that Helios-expressing Foxp3+ Tregs are relevant to various human disorders, including connective tissue diseases, infectious diseases, solid organ transplantation-related immunity, and cancer. Thus, Helios+Foxp3+CD4+ Tregs could be a valuable target in human diseases, and their potential should be explored further in the clinical setting.

3.
Oxid Med Cell Longev ; 2021: 5040326, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34257801

RESUMO

The function and mechanism underlying the suppression of human osteosarcoma cells by ginsenoside-Rg5 (Rg5) was investigated in the present study. MG-63, HOS, and U2OS cell proliferation was determined by MTT assay after Rg5 treatment for 24 h. Rg5 inhibited human osteosarcoma cell proliferation effectively in a dose-dependent manner. The range of effective inhibitory concentrations was 160-1280 nM. Annexin V-FITC and PI double-staining assay revealed that Rg5 induced human osteosarcoma cell apoptosis. Western blotting, qRT-PCR, and FACS experiments revealed that Rg5 inhibited human osteosarcoma cells via caspase-3 activity which was related to the LC3-mediated autophagy pathway. Rg5 decreased the phosphorylation of PI3K, Akt, and mTORC1 activation. In contrast, LC3-mediated autophagy and caspase-3 activity increased significantly. A PI3K/AKT stimulator, IGF-1, reversed Rg5-induced cell autophagy and apoptosis in MG-63 cells. Collectively, the current study demonstrated that Rg5 induced human osteosarcoma cell apoptosis through the LC3-mediated autophagy pathway. Under physiological conditions, activation of PI3K/AKT/mTORC1 inhibits LC3 activity and caspase-3-related cell apoptosis. However, Rg5 activated LC3 activity by inhibiting the activation of PI3K/AKT/mTORC1. The present study indicated that Rg5 could be a promising candidate as a chemotherapeutic agent against human osteosarcoma.

4.
J Diabetes ; 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34259386

RESUMO

BACKGROUND: Type 2 diabetes is increasingly diagnosed at a younger age worldwide and in China. Limited data are available regarding the association between age at diabetes diagnosis and risks of albuminuria. This study sought to examine the independent effect of age at diagnosis of type 2 diabetes on the risk of albuminuria. METHODS: We used data from a nationwide multicenter study with 207,961 participants in mainland China. Age, sex, and study site were matched for 31,366 screen-detected type 2 diabetes and 31,366 normal controls. Age, sex, study site, and diabetes duration were matched for 7,490 self-reported type 2 diabetes and 7,490 normal controls. Risks of having albuminuria in matched type 2 diabetes vs. controls were examined using multivariable logistic regression analysis in strata of age at diabetes diagnosis. RESULTS: Although the absolute rate of albuminuria is higher in older adults, the odds ratio of albuminuria in type 2 diabetes vs. matched controls decreased with increasing age at diagnosis. For participants with diabetes diagnosed at an age of <50, 50-59, 60-69, or ≥70 years, the multivariable adjusted risk of albuminuria increased by 81%, 60%, 45%, and 33% for screen-detected diabetes, and 135%, 121%, 90%, and 58% for self-reported diabetes compared with their normal controls, respectively. CONCLUSIONS: A younger age at diagnosis of type 2 diabetes is associated with a more significantly elevated risk of albuminuria than an older age at diagnosis in Chinese adults.

5.
Sci Rep ; 11(1): 14134, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34239017

RESUMO

Advanced gastric cancer (GC) is one of the most lethal cancer types, thus a better understanding of its biology in patients is urgently needed. MicroRNA (miR)-29a is a known tumor suppressive miR that is related to metastasis, but its clinical relevance in GC remains ambiguous. Here, using a large GC patient cohort we hypothesized that low expression of miR-29a in GC is associated with aggressive cancer biology and worse survival. We demonstrated that low miR-29a GC enriched cell proliferation, apoptosis, metastasis, and angiogenesis related gene sets, as well as the higher expression of related genes. Low miR-29a GC was associated with less anti-cancer immune cell infiltration as well as immune related scoring. Low miR-29a GC demonstrated a worse overall survival (OS) as well as disease specific survival (DSS) compared with high expressing miR-29a GC. Notably, low miR-29a expression was the only factor, other than residual tumor status, to be an independent prognostic biomarker of worse OS and DSS. In conclusion, low miR-29a GC was associated with aggressive cancer biology and worse OS as well as DSS. Additionally, low expression of miR-29a was an independent prognostic biomarker of OS and DSS in gastric cancer patients.

6.
Biochem Biophys Res Commun ; 569: 125-131, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34243068

RESUMO

The interaction between various types of hepatic cells is related to liver fibrosis. Recent studies demonstrated that fine particulate matter (PM2.5) exposure is an important risk factor for the occurrence of liver fibrosis, but its molecular mechanism is still obscure. In this study, we aimed to investigate whether transforming growth factor- ß1 (TGF- ß1) secreted from PM2.5-treated hepatocytes (L-O2) are shuttled to hepatic stellate cells (HSCs) and to establish their effects on HSCs. We have observed that the conditioned medium from L-O2 cells stimulated with PM2.5 induced the activation of LX-2 cells, and at the same time, the same results were obtained when we co-cultured LX-2 in PM2.5-exposed L-O2 cells. In addition, analysis of L-O2 cells stimulated with PM2.5 revealed significant increases in TGF-ß1 expression. Moreover, we found that the TGF-ß1 receptor inhibitor, SB-525334, decreases the proliferation and migration of LX-2 cells in the co-culture system. In addition, the expression of α-smooth muscle actin and type I collagen in LX-2 cells induced by PM2.5-treated L-O2 cells were also blocked by pretreated with SB-525334. These observations imply that PM2.5 induces TGF- ß1expression in hepatocytes, which leads to HSCs activation.

7.
Preprint | medRxiv | ID: ppmedrxiv-21260122

RESUMO

We report the first local transmission of the Delta SARS-CoV-2 variant in mainland China. All 167 infections could be traced back to the first index case. The investigation on daily sequential PCR testing of the quarantined subjects indicated the viral load of the first positive test of Delta infections was [~]1000 times higher than that of the 19A/19B strains infections back in the initial epidemic wave of 2020, suggesting the potential faster viral replication rate and more infectiousness of the Delta variant at the early stage of the infection. The 126 high-quality sequencing data and reliable epidemiological data indicated some minor intra-host single nucleotide variants (iSNVs) could be transmitted between hosts and finally fixed in the virus population during the outbreak. The minor iSNVs transmission between donor-recipient contribute at least 4 of 31 substitutions identified in the outbreak suggesting some iSNVs could quickly arise and reach fixation when the virus spread rapidly. Disease control measures, including the frequency of population testing, quarantine in pre-symptomatic phase and enhancing the genetic surveillance should be adjusted to account for the increasing prevalence of the Delta variant at global level.

8.
Magn Reson Chem ; 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34212405

RESUMO

The local structural, electronic, optical, and electron paramagnetic resonance (EPR) properties are uniformly studied for Cu2+ -doped rutile (TiO2 ) crystals by using the density functional theory (DFT) calculations. The local cation-oxygen bond lengths and planar bond angle, band gap, Mulliken charge and overlapping population, density of state (DOS), and UV-Vis absorption spectra are calculated for pure and copper-doped rutile. The smaller overlapping population of Cu-O bonds in the doped system than Ti-O bonds in pure rutile reflects weaker orbital admixtures or covalency of the former. Compared with pure rutile, Cu2+ doping leads to significant redshift of the UV-Vis absorption band and the narrow impurity band in visible and near-infrared regions arising from the Cu2+ d-d transitions and narrowing of the band gap by about 0.636 eV, possibly suggesting enhancement of visible light activity. The Cu dopant induces a spin magnetic moment of 0.74 µB for the doped rutile. The calculated UV-Vis absorption spectra and spin Hamiltonian parameters for copper-doped rutile show reasonable agreement with the experimental data and some improvement related to the previous perturbation formula calculations. Present systematic studies would be helpful to understand the mechanisms of the enhancement in the optical and magnetic properties of this material with transition-metal (especially Cu2+ ) dopants.

9.
Eur J Pharmacol ; 908: 174317, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34270989

RESUMO

Endothelial cell dysfunction is a prominent feature of diabetic cardiovascular complications, and endothelial cell senescence is considered to be an important contributor to endothelial dysfunction. Discoidin domain receptor 1 (DDR1) has been reported to be involved in atherogenesis and cerebral ischemia/reperfusion injury. In this study, we aimed to explore the role of DDR1 in endothelial cell senescence under diabetic conditions and elucidate the underlying mechanisms. A diabetic rat model was established by a single intraperitoneal injection of streptozocin (STZ) (60 mg/kg), which showed an increase in senescence-associated ß-galactosidase (SA-ß-gal) staining signal of thoracic aortic endothelium, impaired vascular structure and function, accompanied by an up-regulation of DDR1. Next, we verified the role of DDR1 in endothelial senescence and the underlying mechanisms in high glucose-treated human umbilical vein endothelial cells (HUVECs). Consistent with the in vivo findings, high glucose induced endothelial senescence, impaired endothelial function and elevated DDR1 expression, accompanied by the elevation of senescence-related genes p53 and p21 expression, and these effects were reversed by DDR1 siRNA. DDR1 has been documented to be a potential target of miR-199a-3p. Here, we found that miR-199a-3p was down-regulated by high glucose in the aorta tissue and HUVECs, while miR-199a-3p mimic significantly suppressed increased endothelial senescence and elevated DDR1 induced by high glucose. In conclusion, our data demonstrated that miR-199a-3p/DDR1/p53/p21 signaling pathway was involved in endothelial senescence under diabetic conditions, and therapeutic targeting DDR1 would be exploited to inhibit endothelial senescence owing to high glucose exposure.

10.
Zool Res ; 42(4): 469-477, 2021 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-34213093

RESUMO

Mutations of PTEN-induced kinase I (PINK1) cause early-onset Parkinson's disease (PD) with selective neurodegeneration in humans. However, current PINK1 knockout mouse and pig models are unable to recapitulate the typical neurodegenerative phenotypes observed in PD patients. This suggests that generating PINK1 disease models in non-human primates (NHPs) that are close to humans is essential to investigate the unique function of PINK1 in primate brains. Paired single guide RNA (sgRNA)/Cas9-D10A nickases and truncated sgRNA/Cas9, both of which can reduce off-target effects without compromising on-target editing, are two optimized strategies in the CRISPR/Cas9 system for establishing disease animal models. Here, we combined the two strategies and injected Cas9-D10A mRNA and two truncated sgRNAs into one-cell-stage cynomolgus zygotes to target the PINK1 gene. We achieved precise and efficient gene editing of the target site in three newborn cynomolgus monkeys. The frame shift mutations of PINK1 in mutant fibroblasts led to a reduction in mRNA. However, western blotting and immunofluorescence staining confirmed the PINK1 protein levels were comparable to that in wild-type fibroblasts. We further reprogramed mutant fibroblasts into induced pluripotent stem cells (iPSCs), which showed similar ability to differentiate into dopamine (DA) neurons. Taken together, our results showed that co-injection of Cas9-D10A nickase mRNA and sgRNA into one-cell-stage cynomolgus embryos enabled the generation of human disease models in NHPs and target editing by pair truncated sgRNA/Cas9-D10A in PINK1 gene exon 2 did not impact protein expression.

11.
Nutr Cancer ; : 1-9, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34192986

RESUMO

A limited number of studies have demonstrated the role of Lactococcus lactis (L. lactis) in human colorectal cancers (CRCs). The association of L. lactis abundance with the density of natural killer (NK) cells has not been investigated before. In this study, the L. lactis abundance in 60 CRC specimens, 20 adenoma (AD) specimens, and 29 normal colorectal tissues (NCs) specimens was investigated using the fluorescence in situ hybridization of 16S ribosomal RNA. The density of NK cells was detected using immunofluorescence in 28 CRC specimens, 12 AD specimens, and 22 NC specimens. The presence of L. lactis in NCs (48.28%) was detected significantly higher than that in the AD (20.00%, P = .044) and CRC (23.33%, P = .018) specimens. The abundance of L. lactis in NCs (32.73 ± 7.24) was also found to be significantly higher than that in AD (8.91 ± 5.89, P = .029) and CRC (5.63 ± 1.67, P = .003) specimens. In addition, the density of NKp30+ NK cells in NCs (51.14 ± 4.84) was significantly higher than that in the AD (6.10 ± 1.31) and CRC (1.72 ± 0.40) specimens (P < .001). Moreover, a positive association of L. lactis abundance with NKp30+ NK cells density in the colorectal samples (P < .001) was observed. The low abundance of L. lactis in the CRC tissues was associated with the decreased NK cells, which suggested that this might contribute to the progression of CRC by decreasing the number of NK cells.Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2021.1944649.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34152084

RESUMO

BACKGROUND: The myelodysplastic syndrome (MDS) is a high-risk hemocytopenia easily converted to acute myeloid leukemia. CD47 plays an important role in regulating phagocytosis, and its role in the pathogenesis of MDS is unclear. METHODS: CD47 and PI3K/AKT/mTOR on CD34+ CD38- cells were detected by flow cytometry. NF-κB, PI3K, AKT, PTEN, and mTOR mRNA overexpressed in CD34+ CD38- CD47+ cells were performed by real-time quantitative transcriptase-polymerase chain reaction. Phagocytic capacity of macrophages was measured with carboxyfluorescein succinimidyl ester and fluorescent microspheres. Sorted CD34+ CD38- CD47+ cells were injected into NOD-Prkdcscid Il2rgnull mice. RESULTS: The expression of CD47 on CD34+ CD38- cells of the patients in high-risk MDS based on IPSS-R/WPSS score was higher than that in low-risk MDS and controls. The signaling pathway of PI3K/AKT/mTOR is active in CD34+ CD38- CD47+ cells of MDS patients. CD47 overexpressing CD34+ CD38- cells has antiphagocytosis. CD47 overexpressing leukemia stem cell (LSC) -transplanted mice has a short survival time. The macrophages originated from MDS might elicit a pro-tumor response in MDS by inhibiting phagocytosis. CONCLUSIONS: Phagocytosis checkpoints are impaired in MDS. High expression of CD47 on CD34+CD38- cells indicates poor clinical prognosis in MDS.

13.
Front Endocrinol (Lausanne) ; 12: 673976, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34135862

RESUMO

Background: Diabetic kidney disease (DKD) is a kind of common microvascular complication of diabetes. This study aims to explore the possible links between blood sugar level and albuminuria, providing the exact cut point of the "risk threshold" for blood glucose with DKD. Methods: The relationship between blood glucose and albuminuria was modeled using linear and logistic regression in the REACTION study cohorts (N= 8932). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression model. Two-slope linear regression was used to simulate associations between blood glucose and ACR. Results: We found that the increase in ACR was accompanied by increased HbA1c, with a turning point at 5.5%. The positive correlation remained highly significant (P<0.001) when adjusted for age, sex, marital status, education, smoking status, drinking status, BMI, waistline, SBP and DBP. In subgroup analyses including gender, obesity, hypertension, and smoking habits, the relationship was significant and stable. Conclusions: We determined a risk threshold for HbA1c associated with albuminuria in a Chinese population over the age of 40. HbA1c ≥ 5.5% was positively and independently associated with ACR. These results suggest the necessity of early blood glucose control and renal function screening for DKD in at-risk populations.

14.
Biochem Med (Zagreb) ; 31(2): 020709, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34140832

RESUMO

Introduction: The prognostic value of D-dimer (DD) in sepsis remains controversial. This study aimed to investigate the performance of DD for predicting sepsis mortality in the hospital and for identifying its potential correlates. Materials and methods: The clinical and laboratory data of adult sepsis patients were extracted from the Medical Information Mart for Intensive Care III (MIMIC III, v1.4) database using the structured query language (SQL). The database contains critical illness admitted to the intensive care unit at Beth Israel Deaconess Medical Center between June 2001 and October 2012. The association between DD and mortality was investigated with receiver operating characteristic (ROC) curve, restricted cubic spline and logistic regression analysis. Subgroup analysis was also used for identifying DD correlates. Results: The study population consisted of 358 sepsis patients. Those who died during hospital stay (N = 160) had significantly higher DD values than those who survived (N = 198). The area under the ROC curve (AUC) of DD was 0.59 (P < 0.010). In subgroup analysis, white blood cell (WBC) count > 18 x109/L and vasopressor therapy significantly decreased DD diagnostic performance. Categorical DD value was independently associated with hospital mortality after sequential organ failure score (SOFA) and blood lactate adjustment. Restricted cubic spline analysis revealed a U-shape relationship between DD and in-hospital mortality. Discussion: We conclude that the accuracy of DD for predicting in-hospital sepsis mortality depends on WBC count and vasopressor therapy. Both low and extremely elevated DD values are associated with higher risk of death.

15.
Medicine (Baltimore) ; 100(24): e26341, 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34128882

RESUMO

BACKGROUND: Hydatidiform mole (HM) is more common as molar pregnancy. It is a disease classified under the category of gestational trophoblastic diseases, which could metastasize after originating in the placenta. A majority of females suffering from molar pregnancies are curable by evacuating retained products of conception and the patient's fertility is preserved. In some cases, the growth perseveres and leads to gestational trophoblastic neoplasia, which is an extremely malicious condition that needs chemo-based treatment. There is a possibility to lessen the risk of gestational trophoblastic disease in females with HM through the administration of prophylactic chemo. Yet, there is controversy regarding prophylactic chemotherapy administered pre-or-post removal of HM to curtail the malignant sequelae. Therefore, we will conduct this research to assess both the efficacy as well as security of using prophylactic chemotherapy to treat HM. METHODS: In the preliminary review, the authors will search for randomized controlled trials involving prophylactic chemotherapy to treat HM. The literature search is carried out in the following electronic databases from their inception to May 2021: Chinese National Knowledge Infrastructure, Chinese BioMedical Literature, and WanFang database are the three Chinese language databases. Web of Science, PubMed, Cochrane Library, and EMBASE are the four English language databases. The authors will also perform a manual search through the bibliographies in related literature to find extra articles and ongoing studies. Two independent authors will assess the literature according to an inclusion criteria, use a specialized data collection table to extract data, and use the Cochrane 'Risk of bias' tool for evaluating any possible bias risk in the selected articles. Data synthesis and statistical operations are completed with the RevMan software (v. 5.3). RESULTS: The present systematic analysis provides a rationalized synthesis of existing evidence related to the use of prophylactic chemotherapy in the treatment of HM. CONCLUSION: Our findings will summarize the current evidences for prophylactic chemotherapy in the treatment of HM. ETHICS AND DISSEMINATION: An ethics approval is nonrequired because pre published results will be used. REGISTRATION NUMBER: DOI 10.17605/OSF.IO/6QV52 (https://osf.io/6qv52/).


Assuntos
Anticarcinógenos/uso terapêutico , Mola Hidatiforme/prevenção & controle , Metanálise como Assunto , Revisões Sistemáticas como Assunto , Neoplasias Uterinas/prevenção & controle , Antineoplásicos/uso terapêutico , Protocolos Clínicos , Feminino , Humanos , Mola Hidatiforme/tratamento farmacológico , Recidiva Local de Neoplasia/prevenção & controle , Gravidez , Neoplasias Uterinas/tratamento farmacológico
16.
J Cell Mol Med ; 25(14): 6746-6759, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34132026

RESUMO

Fibrosis serves a critical role in driving atrial remodelling-mediated atrial fibrillation (AF). Abnormal levels of the transcription factor PU.1, a key regulator of fibrosis, are associated with cardiac injury and dysfunction following acute viral myocarditis. However, the role of PU.1 in atrial fibrosis and vulnerability to AF remain unclear. Here, an in vivo atrial fibrosis model was developed by the continuous infusion of C57 mice with subcutaneous Ang-II, while the in vitro model comprised atrial fibroblasts that were isolated and cultured. The expression of PU.1 was significantly up-regulated in the Ang-II-induced group compared with the sham/control group in vivo and in vitro. Moreover, protein expression along the TGF-ß1/Smads pathway and the proliferation and differentiation of atrial fibroblasts induced by Ang-II were significantly higher in the Ang-II-induced group than in the sham/control group. These effects were attenuated by exposure to DB1976, a PU.1 inhibitor, both in vivo and in vitro. Importantly, in vitro treatment with small interfering RNA against Smad3 (key protein of TGF-ß1/Smads signalling pathway) diminished these Ang-II-mediated effects, and the si-Smad3-mediated effects were, in turn, antagonized by the addition of a PU.1-overexpression adenoviral vector. Finally, PU.1 inhibition reduced the atrial fibrosis induced by Ang-II and attenuated vulnerability to AF, at least in part through the TGF-ß1/Smads pathway. Overall, the study implicates PU.1 as a potential therapeutic target to inhibit Ang-II-induced atrial fibrosis and vulnerability to AF.

17.
J Affect Disord ; 292: 295-304, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34134028

RESUMO

BACKGROUND: Suicidality is common in people living with HIV/AIDS. However, the prevalence estimates of the suicidality vary between studies. Here, we performed a systematic review and estimated the prevalence of suicidal behavior in this population. METHODS: Systematic search of PubMed, Embase, Web of Science, CINAHL, Scopus and PsycINFO for relevant studies published before August 29, 2020. A random-effects model was used to pool the estimates of the prevalence of suicidal ideation, attempts and plans, which were also stratified by continent or region and screening instrument from the studies included in this meta-analysis. RESULTS: Suicide prevalence data were extracted from 36 studies(n=32,818) from 15 countries. The overall pooled crude prevalence estimates of suicidal ideation, plans, and attempts were 20.9% [95% confidence interval (CI) 16.5-21.6%],8.1% (95% CI 5.4-11.3%), and 7.5% (95% CI 5.7-9.5%), respectively. For lifetime suicidal ideation and attempts prevalence, this was 22.4% (95% CI 15.9-29.8%), and 12.0% (95% CI 6.9- 18.1%), respectively. Summary prevalence estimates ranged across assessment modalities from 6.5% to 33.7%. Pooled estimates were generally higher for females, as compared with males (risk ratios in the range 1.48-1.85). The leave-one-out analysis showed that no single study significantly affected the final pooled results.

18.
Complement Ther Med ; 60: 102744, 2021 Jun 06.
Artigo em Inglês | MEDLINE | ID: covidwho-1252645

RESUMO

INTRODUCTION: Chinese patent medicine (CPM) is an indispensable part of traditional Chinese medicine. Coronavirus Disease 2019 (COVID-19) manifests is an acute respiratory infectious disease. This systematic review aimed to evaluate the therapeutic effects and safety of oral CPM for COVID-19. METHODS: We included randomized controlled trials (RCTs) that tested oral CPM for the treatment of COVID-19 identified from publications in CNKI, Wanfang, VIP, Web of Science, SinoMed, PubMed, Embase, BioRxiv, MedRxiv and arXiv before November 2nd, 2020. The risk of bias for each trial was assessed using the Cochrane Risk of Bias Tool 2.0. RevMan 5.4 software was used for data analyses. The certainty of the evidence was assessed using the online GRADEpro tool. RESULTS: Seven RCTs including 1079 participants were identified. The overall bias was assessed as "-high risk of bias" for all included trials. Oral CPM investigated were: Lianhua Qingwen capsule/granules (LHQW), Jinhua Qinggan granules (JHQG), Huoxiang Zhengqi dripping pills (HXZQ), Toujie Quwen granules (TJQW) and Lianhua Qingke granules (LHQK). Compared with conventional western therapy alone for people with COVID-19: regarding the main outcomes, the results showed that oral CPM combined with conventional western therapy improved cure rate (RR = 1.20, 95 % CI 1.04-1.38, involving LHQW and TJQW), reduced aggravation rate (RR = 0.50, 95 % CI 0.29 - 0.85, involving LHQW, JHQG, LHQK and TJQW); with regard to additional outcomes, the results showed that add-on oral CPM shortened the duration of fever, cough and fatigue, improved the recovery rate of cough and fatigue, and increased the improvement and recovery rate of chest CT manifestations. There were some differences in therapeutic effects among various CPMs for the same COVID-19 outcome. The use of TJQW and LHQG appeared not to increase the risk of adverse events, but JHQG may cause mild diarrhea. CONCLUSION: Low-certainty or very low-certainty evidence demonstrated that oral CPM may have add-on potential therapeutic effects for patients with non-serious COVID-19. These findings need to be further confirmed by well-designed clinical trials with adequate sample sizes.

19.
Transpl Immunol ; 68: 101430, 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34147608

RESUMO

BACKGROUND: We investigated the impact of de novo donor-specific anti-human leukocyte antigen antibodies (dnDSAs) on long-term death-censored graft survival and renal allograft rejection in kidney transplant recipients. METHODS: The sample for this retrospective cohort study comprised 121 recipients of kidney transplants with negative complement-dependent cytotoxicity crossmatches to their deceased donors. Recipients were divided into two groups: dnDSAs+ (n = 31) and dnDSAs- (n = 90). We evaluated rejection and long-term graft survival rates in the recipients along with pathologic changes in the transplanted kidneys. RESULTS: DnDSAs were identified in 31/121 patients (25.6%). The graft survival rate in the dnDSAs+ group was 87.1% (27/31) and that of the dnDSAs- group was 97.8% (88/90). The dnDSAs+ group had lower graft survival rates than patients without dnDSAs (p = 0.007). There was no difference in the graft survival rates between patients with high DSA mean fluorescence intensity (≥4000) and those with low intensity (<4000) (p = 0.669). There was also no difference in the graft survival rates of patients with HLA class I, II, and I + II dnDSAs (p = 0.571). The presence of dnDSA in serum was associated with a higher incidence of antibody- and T-cell-mediated rejection (p < 0.0001). Banff scores for arterial fibrointimal and arteriolar hyalin, thickening as well as C4d deposition differed for the dnDSAs+ and dnDSAs- groups (p < 0.05). CONCLUSION: DnDSAs were found to be associated with decreased long-term graft survival rates and increased rejection rates, often accompanied by C4d deposition.

20.
Appl Microbiol Biotechnol ; 105(13): 5341-5355, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34180006

RESUMO

When microorganisms invade a host, the innate immune system first recognizes the pathogen-associated molecular patterns of these microorganisms through pattern recognition receptors (PRRs). Toll-like receptors (TLRs) are known transmembrane PRRs existing in both invertebrates and vertebrates. Upon ligand recognition, TLRs initiate a cascade of signaling events; promote the pro-inflammatory cytokine, type I interferon, and chemokine expression; and play an essential role in the modulation of the host's innate and adaptive immunity. Therefore, it is of great significance to improve our understanding of antimicrobial immune responses by studying the role of TLRs and their signal molecules in the host's defense against invading microbes. This paper aims to summarize the specificity of TLRs in recognition of conserved microbial components, such as lipoprotein, lipopolysaccharide, flagella, endosomal nucleic acids, and other bioactive metabolites derived from microbes. This set of interactions helps to elucidate the immunomodulatory effect of TLRs and the signal transduction changes involved in the infectious process and provide a novel therapeutic strategy to combat microbial infections.


Assuntos
Anti-Infecciosos , Imunidade Inata , Imunidade Adaptativa , Animais , Transdução de Sinais , Receptores Toll-Like
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