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1.
J Ethnopharmacol ; 265: 113345, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32890713

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Periploca sepium Bunge (P. sepium) is used in traditional Chinese medicine (TCM) for the treatment of autoimmune diseases, particularly rheumatoid arthritis. Periploca sepium periplosides (PePs), isolated from the root bark of P. sepium, characterized as the cardiac glycosides-free pregnane glycosides fraction, is expected to possess therapeutic potential on inflammatory arthritis. AIM OF THE STUDY: The current study is designed to evaluate the anti-nociceptive, anti-inflammatory and anti-arthritic activities effects of the PePs. MATERIALS AND METHODS: The anti-nociceptive activity of PePs was examined in the writhing test and hot-plate test in mice. The anti-inflammatory activity of PePs was determined by the 2, 4-dinitro-1-fluorobenzene (DNFB)-induced ear edema model and the carrageenan induced paw edema model in mice. The anti-arthritic activity of PePs was investigated by evaluating the joint inflammation and arthritis pathology in rat adjuvant induced arthritis (AIA) and murine collagen induced arthritis (CIA). Phytohaemagglutinin M (PHA-M) -elicited human peripheral blood mononuclear cells (PBMCs) were further applied to assess the suppressive activity of PePs on IFN-γ and IL-17 production. RESULTS: PePs treatment markedly decreased the acetic acid-induced visceral nociceptive response and increased the hot-plate pain threshold. Further, oral administration of PePs exhibited anti-inflammatory activity by decreasing DNFB-induced ear edema in mice and carrageenan-induced paw edema in rats. Moreover, oral treatment of PePs ameliorated joint swelling and attenuated bone erosion in rodent arthritis, and the therapeutic benefits were partially attributed to the suppression of proinflammatory cytokines such IFN-γ and IL-17. Moreover, PePs suppressed the proliferation as well as IFN-γ and IL-17 secretion in PHA-M-elicited human PBMCs in a concentration dependent manner. CONCLUSIONS: Taken together, our results justified the traditional use of Periploca sepium Bunge for the treatment of diseases associated with inflammation and pain.

2.
J Invest Dermatol ; 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33188780

RESUMO

Patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) show diverse endocrine and non-endocrine manifestations initiated by self-reactive T cells due to AIRE mutation-induced defective central tolerance. A large number of American APECED patients suffer from early-onset cutaneous inflammatory lesions accompanied by an infiltration of T cells and myeloid cells. The role of myeloid cells in this setting remains to be fully investigated. In this study, we characterize the autoinflammatory phenotypes in the skin of both APECED-like kinase-dead Ikkα knockin (KA/KA) mice and APECED patients. We found a marked infiltration of autoreactive CD4 T cells, macrophages, and neutrophils; elevated uric acid; and increased NLRP3, a major inflammasome component. Depleting autoreactive CD4 T cells or ablating Ccl2/Cxcr2 genes significantly attenuated the inflammasome activity, inflammation, and skin phenotypes in KA/KA mice. Importantly, treatment with an NLRP3 inhibitor reduced skin phenotypes and decreased infiltration of CD4 T cells, macrophages, and neutrophils. These results suggest that increased myeloid cell infiltration contributes to autoreactive CD4 T cell-mediated skin autoinflammation. Thus, our findings reveal that the combined infiltration of macrophages and neutrophils is required for autoreactive CD4 T cell-mediated skin disease pathogenesis and that the NLRP3-dependent inflammasome is a potential therapeutic target for the cutaneous manifestations of autoimmune diseases.

3.
Cell Rep ; 33(5): 108345, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33147460

RESUMO

Bat cells and tissue have elevated basal expression levels of antiviral genes commonly associated with interferon alpha (IFNα) signaling. Here, we show Interferon Regulatory Factor 1 (IRF1), 3, and 7 levels are elevated in most bat tissues and that, basally, IRFs contribute to the expression of type I IFN ligands and high expression of interferon regulated genes (IRGs). CRISPR knockout (KO) of IRF 1/3/7 in cells reveals distinct subsets of genes affected by each IRF in an IFN-ligand signaling-dependent and largely independent manner. As the master regulators of innate immunity, the IRFs control the kinetics and maintenance of the IRG response and play essential roles in response to influenza A virus (IAV), herpes simplex virus 1 (HSV-1), Melaka virus/Pteropine orthoreovirus 3 Melaka (PRV3M), and Middle East respiratory syndrome-related coronavirus (MERS-CoV) infection. With its differential expression in bats compared to that in humans, this highlights a critical role for basal IRF expression in viral responses and potentially immune cell development in bats with relevance for IRF function in human biology.


Assuntos
Quirópteros/imunologia , Regulação da Expressão Gênica/imunologia , Fator Regulador 1 de Interferon/imunologia , Fator Regulador 7 de Interferon/imunologia , Viroses/imunologia , Animais , Herpesvirus Humano 1/imunologia , Vírus da Influenza A/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Orthoreovirus/imunologia
4.
J Hazard Mater ; : 124376, 2020 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-33144008

RESUMO

Chromium (Cr) is one of the most toxic pollutants that has accumulated in terrestrial and aqueous systems, posing serious risks towards living beings on a worldwide scale. The immobilization, removal, and detoxification of active Cr from natural environment can be accomplished using multiple advanced materials. Biochar, a carbonaceous pyrolytic product made from biomass waste, is considered as a promising material for the elimination of Cr contamination. The preparation and properties of biochar as well as its remediation process for Cr ions have been well investigated. However, the distinct correlation of the manufacturing, characteristics, and mechanisms involved in the remediation of Cr contamination by various designed biochars is not summarized. Herein, this review provides information about the production, modification, and characteristics of biochars along with their corresponding effects on Cr stabilization. Biochar could be modified via physical, hybrid, chemical, and biological methods. The remediating mechanisms of Cr contamination using biochars involve adsorption, reduction, electron shuttle, and photocatalysis. Moreover, the coexisting ions and organic pollutants change the pattern of the remediating process of biochar in actual Cr contaminated water and soil. Finally, the present limitations and future perspectives are proposed.

5.
Expert Rev Neurother ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33146570

RESUMO

BACKGROUND: Relatively little is known about the use of disease-modifying drugs (DMDs) for multiple sclerosis (MS) in the population-based universal healthcare setting. This study aimed to describe the characteristics of a population-based cohort with MS and their DMD exposure in four Canadian provinces. METHODS: We identified all adults (aged ≥18 years) with MS using linked population-based health administrative data. Individuals were followed from the most recent of their first MS or demyelinating event or 01/January/1996(study entry), to the earliest of death, emigration, or 31/March/2018(study end). Cohort characteristics examined included sex, age, socioeconomic status, and comorbidity burden. RESULTS: Overall, 10,418/35,894 (29%) of MS cases filled a DMD prescription during the 22-year study period. Most were women (n=7,683/10,418;74%), and 17% (n=1,745/10,418) had some comorbidity (Charlson Comorbidity Index≥1) at study entry. Nearly 20% (n=1,745/10,418) were aged ≥50 when filling their first DMD; the mean age was 39.6 years. CONCLUSIONS: Almost 1 in 6 people with MS had at least some comorbidity, and nearly 1 in 6 were ≥50 years old at the time of their first DMD. As these individuals are typically excluded from clinical trials, findings illustrate the need to understand the harms and benefits of DMD use in these understudied groups.

6.
Int J Nanomedicine ; 15: 8249-8260, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33149573

RESUMO

Introduction: Lung cancer is one of the most aggressive forms of cancer that leads to a high mortality rate amongst several cancer types and it is a widely recurrent cancer globally. The use of zinc oxide nanoparticles (ZnONPs) in the formulation of sun cream, food flavors, and colorings due to its varied biological properties. The extensive significance of nanoparticles encourages their production but the approaches are a common challenge in concluding the direct beneficial effect for the disease treatment. Hence, in the present study, zinc oxide-loaded syringic acid (ZnO-SYR) phytochemical was used to elucidate the therapeutic effect against lung cancer. Methods: The ZnO-SYR nanoparticles were synthesized and characterized by UV-visible spectroscopy, X-ray diffraction, dynamic light scattering, and FT-IR analysis. The characterized ZnO-SYR was tested on in vivo mouse model of lung cancer (benzo(a)pyrene (BAP)) and in vitro A549 cells. Results: The results demonstrated the significant restoration of body weight with attenuated serum marker enzymes compared to BAP-treated animals. In addition, cytokine estimation revealed ameliorated levels of TNF-α, interleukins, IL-6, IL-1ß with evidenced histological observations in ZnO-SYR-treated mice compared to BAP-induced lung cancer mice. Discussion: Furthermore, cytotoxicity analysis demonstrated the altered mitochondrial membrane potential (MMP), with a profound increase in reactive oxygen species (ROS) levels, and apoptosis mechanism by ZnO-SYR compared to control cells. The conclusions of the present study put forward an evident confirmation of the protective and beneficial effects of zincoxide-loaded syringic acid against the BAP-induced lung cancer model.

7.
Mol Cancer Res ; 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33154093

RESUMO

Diffuse large B-cell lymphoma (DLBCL) is the major type of aggressive B-cell lymphoma. High-grade B-cell lymphoma (HGBCL) with MYC/BCL2 double-hit (DH) represents a distinct entity with dismal prognosis after standard immunochemotherapy in the current WHO lymphoma classification. However, whether TP53 mutation synergizes with MYC abnormalities (MYC rearrangement and/or Myc protein overexpression) contributing to HGBCL-like biology and prognosis is not well investigated. In this study, DLBCL patients with MYC/TP53 abnormalities demonstrated poor clinical outcome, high-grade morphology, and distinct gene-expression signatures. To identify more effective therapies for this distinctive DLBCL subset, novel MYC/TP53/BCL-2 targeted agents were investigated in DLBCL cells with MYC/TP53 dual alterations or HGBCL-MYC/BCL2-DH. A BET inhibitor INCB057643 effectively inhibited cell viability and induced apoptosis in DLBCL/HGBCL cells regardless of MYC/BCL2/TP53 status. Combining INCB057643 with a MDM2-p53 inhibitor DS3032b significantly enhanced cytotoxicity in HGBCL-DH without TP53 mutation, while combining with the BCL-2 inhibitor venetoclax displayed potent therapeutic synergy in DLBCL/HGBCL cells with and without concurrent TP53 mutation. Reverse-phase protein arrays revealed the synergistic molecular actions by INCB057643, DS3032b and venetoclax to induce cell cycle arrest and apoptosis and to inhibit AKT/MEK/ERK/mTOR pathways, as well as potential drug-resistance mechanisms mediated by upregulation of MCL-1 and RAS/RAF/mTOR pathways. In summary, these findings support sub-classification of DLBCL/HGBCL with dual MYC/TP53 alterations which demonstrates distinct pathobiological features and dismal survival with standard therapy therefore requiring additional targeted therapies. Implications: The clinical and pharmacologic studies suggest recognizing DLBCL with concomitant TP53 mutation and MYC abnormalities as a distinctive entity necessary for precision oncology practice.

8.
Surg Endosc ; 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33156385

RESUMO

BACKGROUND: Postoperative complication rates after laparoscopic pancreaticoduodenectomy (LPD) remain high despite improvements in perioperative management. Measurements on computed tomography imaging of intra-abdominal tissue have not been thoroughly investigated as predictors of mortality and morbidity following LPD. The aim of this study was to assess whether the ratio of abdominal depth and body mass index (AD/BMI ratio) could predict postoperative complications following LPD. METHODS: We retrospectively analyzed 231 patients who underwent LPD and had a computed tomography scan between 2014 and 2018. Demographic, radiologic, and pathologic data were correlated to the occurrence of postoperative complications. Propensity score matching was performed to minimize selection biases associated with the comparison of retrospective data between the high and low AD/BMI ratio groups. Univariate and multivariate analyses were also performed to assess the risk factors for postoperative complications. RESULTS: Of the 102 patients identified for propensity score matching analysis, 29 patients (28.4%) experienced postoperative complications. Patients with a high AD/BMI ratio had a higher prevalence of overall complications (45.1% vs. 11.8%, P < 0.001), postoperative pancreatic fistula (17.6% vs. 2.00%, P = 0.008), delayed gastric emptying (33.3% vs. 3.90%, P < 0.001), and intra-abdominal abscess (17.6% vs. 0, P = 0.002). In the multivariate analysis, an AD/BMI ratio greater than 2.7 (m3/[kg·103]; OR = 6.16, 95% confidence interval [1.04-36.4], P = 0.045) was the only independent predictive factor of postoperative complications. CONCLUSIONS: The preoperative AD/BMI ratio is a predictor of postoperative complications following LPD.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33156500

RESUMO

The widespread existence of antibiotics has caused inevitable influence on ecology and humans. In this study, we screened the most commonly used antibiotics, and 64 antibiotics were detected in Shanghai, an international metropolis. Most of the target substances were detected in all 46 water samples including main rivers and districts in Shanghai, with concentrations ranging from 0.02 to 502.43 ng L-1. In particular, sulfadiazine (502.43 ng L-1) had the highest maximum concentration. Besides, risk quotients based on fish suggested that sulfonamides had a medium risk (0.12) in Shanghai. Correlation studies had shown that most compounds with frequencies exceeding 60% were significantly positively correlated with the total concentration. Based on further analysis, sulfadiazine, sulfamerazine, and sulfapyridine were screened as indicators to reflect the pollution status of antibiotics in Shanghai for a long time. The screening conditions for these indicators include detection rate (> 60%), maximum concentration (> 100 ng L-1), RQ (> 0.01), and correlation (> 0). In addition, population density may be the main factor for antibiotic pollution through regional comparison. In a word, this work can systematically reflect the overall situation of Shanghai antibiotics and provide support for global data comparison in the future. Meanwhile, we provided the potential indicators that can be applied in the long term and economical monitoring of antibiotics.

10.
J Hazard Mater ; : 124540, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33221075

RESUMO

Specific to strongly acidic wastewater, the traditional lime neutralization produces massive hazardous waste and present serious environmental risks. Thus, the recycling of purified wastewater after the contained contaminants being removed has been proposed. However, among these contaminants, chloride ion (Cl(-I)) is rather difficult to remove. This study proposes a new method to remove Cl(-I) using thermal activated persulfate (PS). Under optimized conditions, above 96% of initial Cl(-I) was removed from the actual wastewater, and the residual Cl(-I) was below 158 mg/L, which satisfies the requirement of Cl(-I) concentration for wastewater recycling. Furthermore, the mechanism was investigated. In the strongly acidic wastewater, the high concentration of H+ prompted the thermal activation process of PS through two pathways. (1) H+ prompted the transformation of S2O82- into HSO4- and SO4, and then into HSO5- that was finally transformed into ·OH and ·SO4- at above 70 â„ƒ. (2) H+ prompted the production of ·OH through the transformation of ·SO4- into ·HSO4 and the cleavage of ·HSO4. The key step for Cl(-I) removal was identified as the formation of ·Cl or ·Cl2- from the oxidation of Cl(-I) by ·SO4- and ·OH, and their contribution ratios were estimated to be 67.4% and 32.6%, respectively.

11.
Toxicol Appl Pharmacol ; : 115336, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33212065

RESUMO

Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related death worldwide. The abnormal activation of glycolytic metabolism and PTEN/AKT signaling in NSCLC cells are highly correlated with their proliferation abilities and viability. Ligustilide is one of the major bioactive components of multiple Chinese traditional medicine including Angelica sinensis and Ligusticum. Ligustilide exposure inhibits the proliferation and viability of multiple cancer cell lines in vitro. However, the impact of ligustilide to the progression of NSCLC and its detailed pharmacological mechanisms remain unclear. In this research, CCK-8 and colony formation assay were performed to demonstrate ligustilide treatment inhibited the viability and proliferation ability of NSCLC cells in vitro. Caspase-3/-7 activity assay and nucleosome ELISA assay were utilized to show ligustilide promoted the apoptosis of NSCLC cells. Metabolic analysis and qRT-PCR assay were used to demonstrated that ligustilide dampened aerobic glycolysis of NSCLC cells. Nude mice were exposed to 5 mg/kg ligustilide and ligustilide inhibited orthotopic NSCLC growth in vivo. qRT-PCR and Western blot analysis were performed to substantiate the regulatory function of ligustilide to PTEN/AKT signaling in NSCLC cells. Overall, this study revealed that ligustilide regulated the proliferation, apoptosis and aerobic glycolysis of NSCLC cells through PTEN/AKT signaling pathway.

12.
Asian J Androl ; 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33159026

RESUMO

The present study aimed to determine whether the number of patients with symptomatic benign prostatic hyperplasia (BPH) who preferred surgery decreased during the past 11 years at our center (West China Hospital, Chengdu, China), and whether this change affected the timing of surgery and the physical condition of surgical patients. This retrospective study included 57 557 patients with BPH treated from January 2008 to December 2018. Of these, 5427 patients were treated surgically. Surgical patients were divided into two groups based on the time of treatment (groups 8-13 and groups 13-18). The collected data comprised the percentage of all patients with BPH who underwent surgery, baseline characteristics of surgical patients, rehabilitation time, adverse events, and hospitalization costs. The surgery rates in groups 8-13 and groups 13-18 were 10.5% and 8.5% (P < 0.001), respectively. The two groups did not clinically differ regarding patient age and prostate volume. The rates of acute urinary retention and renal failure decreased from 15.0% to 10.6% (P < 0.001) and from 5.2% to 3.1% (P < 0.001), respectively. In groups 8-13 and groups 13-18, the mean catheterization times were 4.0 ± 1.7 days and 3.3 ± 1.6 days (P < 0.001), respectively, and the mean postoperative hospitalization times were 5.1 ± 2.4 days and 4.2 ± 1.8 days (P < 0.001), respectively. The incidences of unplanned second surgery and death reduced during the study period. The surgery rate decreased over time, which suggests that medication was chosen over surgery. However, the percentage of late complications of BPH also decreased over time, which indicates that the timing of surgery was not delayed.

13.
J Hematol Oncol ; 13(1): 148, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33148342

RESUMO

The XPO1 inhibitor selinexor was recently approved in relapsed/refractory DLBCL patients but only demonstrated modest anti-DLBCL efficacy, prompting us to investigate the prognostic effect of XPO1 in DLBCL patients and the rational combination therapies in high-risk DLBCL. High XPO1 expression (XPO1high) showed significant adverse prognostic impact in 544 studied DLBCL patients, especially in those with BCL2 overexpression. Therapeutic study in 30 DLBCL cell lines with various molecular and genetic background found robust cytotoxicity of selinexor, especially in cells with BCL2-rearranged (BCL2-R+) DLBCL or high-grade B-cell lymphoma with MYC/BCL2 double-hit (HGBCL-DH). However, expression of mutant (Mut) p53 significantly reduced the cytotoxicity of selinexor in overall cell lines and the BCL2-R and HGBCL-DH subsets, consistent with the favorable impact of XPO1high observed in Mut-p53-expressing patients. The therapeutic effect of selinexor in HGBCL-DH cells was significantly enhanced when combined with a BET inhibitor INCB057643, overcoming the drug resistance in Mut-p53-expressing cells. Collectively, these data suggest that XPO1 worsens the survival of DLBCL patients with unfavorable prognostic factors such as BCL2 overexpression and double-hit, in line with the higher efficacy of selinexor demonstrated in BCL2-R+ DLBCL and HGBCL-DH cell lines. Expression of Mut-p53 confers resistance to selinexor treatment, which can be overcome by combined INCB057643 treatment in HGBCL-DH cells. This study provides insight into the XPO1 significance and selinexor efficacy in DLBCL, important for developing combination therapy for relapsed/refractory DLBCL and HGBCL-DH.

14.
J Proteomics ; : 104023, 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33130111

RESUMO

Large-scale and long-term metabolomic studies have attracted widespread attention in the biomedical studies yet remain challenging despite recent technique progresses. In particular, the ineffective way of experiment integration and limited capacity in metabolite annotation are known issues. Herein, we constructed an online tool MMEASE enabling the integration of multiple analytical experiments with an enhanced metabolite annotation and enrichment analysis (https://idrblab.org/mmease/). MMEASE was unique in capable of (1) integrating multiple analytical blocks; (2) providing enriched annotation for >330 thousands of metabolites; (3) conducting enrichment analysis using various categories/sub-categories. All in all, MMEASE aimed at supplying a comprehensive service for large-scale and long-term metabolomics, which might provide valuable guidance to current biomedical studies. SIGNIFICANCE: To facilitate the studies of large-scale and long-term metabolomic analysis, MMEASE was developed to (1) achieve the online integration of multiple datasets from different analytical experiments, (2) provide the most diverse strategies for marker discovery, enabling performance assessment and (3) significantly amplify metabolite annotation and subsequent enrichment analysis. MMEASE aimed at supplying a comprehensive service for long-term and large-scale metabolomics, which might provide valuable guidance to current biomedical studies.

15.
Biomed Pharmacother ; 133: 110937, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33217689

RESUMO

BACKGROUND: Compound sophorae decoction (CSD), a Chinese Herbal decoction, is frequently clinically prescribed for patients suffered from ulcerative colitis (UC) characterized by bloody diarrhea. Yet, the underlying mechanism about how this formulae works is remain elusive. METHODS: In the present study, the experimental colitis in C57BL/6 J mice was induced by oral administration of standard diets containing 3% dextran sodium sulfate (DSS), and CSD was given orally for treatment at the same time. The clinical symptoms including stool and body weight were recorded each day, and colon length and its histopathological changes were observed. Apoptosis of colonic epithelium was studied by detecting protein expression of cleaved caspase-3, and cell proliferation by Ki-67 immunohistochemistry. Tight junction complex like ZO-1 and occludin were also determined by transmission electron microscope and immunofluorescence. The concentration of FITC-dextran 4000 was measured to evaluate intestinal barrier permeability and possible signaling pathway was investigated. Mucin2 (MUC2) and notch pathway were tested through western blot. The M1/M2 ratio in spleen and mesenteric lymph nodes were detected by flow cytometry. And the mRNA levels of iNOS and Arg1 were examined by qRT-PCR. RESULTS: CSD could significantly alleviate the clinical manifestations and pathological damage. Body weight loss and DAI score of mice with colitis were improved and shortening of colon was inhibited. The administration of CSD was able to reduce apoptotic epithelial cells and facilitate epithelial cell regeneration. Increased intestinal permeability was reduced in DSS-induced colitis mice. In addition, CSD treatment obviously up-regulated the expression of ZO-1 and occludin and the secretion of MUC2, regulated notch signaling, and decreased the ratio of M1/M2. CONCLUSIONS: These data together suggest that CSD can effectively mitigate intestinal inflammation, promote phenotypic change in macrophage phenotype and enhance colonic mucosal barrier function by, at least in part, regulating notch signaling in mice affected by DSS-induced colitis.

16.
Proc Natl Acad Sci U S A ; 117(46): 28939-28949, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33106404

RESUMO

Bats have emerged as unique mammalian vectors harboring a diverse range of highly lethal zoonotic viruses with minimal clinical disease. Despite having sustained complete genomic loss of AIM2, regulation of the downstream inflammasome response in bats is unknown. AIM2 sensing of cytoplasmic DNA triggers ASC aggregation and recruits caspase-1, the central inflammasome effector enzyme, triggering cleavage of cytokines such as IL-1ß and inducing GSDMD-mediated pyroptotic cell death. Restoration of AIM2 in bat cells led to intact ASC speck formation, but intriguingly resulted in a lack of caspase-1 or consequent IL-1ß activation. We further identified two residues undergoing positive selection pressures in Pteropus alecto caspase-1 that abrogate its enzymatic function and are crucial in human caspase-1 activity. Functional analysis of another bat lineage revealed a targeted mechanism for loss of Myotis davidii IL-1ß cleavage and elucidated an inverse complementary relationship between caspase-1 and IL-1ß, resulting in overall diminished signaling across bats of both suborders. Thus we report strategies that additionally undermine downstream inflammasome signaling in bats, limiting an overactive immune response against pathogens while potentially producing an antiinflammatory state resistant to diseases such as atherosclerosis, aging, and neurodegeneration.

17.
Medicine (Baltimore) ; 99(42): e22759, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33080742

RESUMO

BACKGROUND: Cancer-related fatigue (CRF) is considered a common complication of cancer or cancer treatment, which has a serious adverse effect on the life and of cancer patients, leading to a decline in their quality of life (QoL). The existing clinical trials revealed that acupuncture has a positive effect on CRF, and there are fewer adverse events confirmed in the corresponding systematic review. However, in recent years, new studies on using acupuncture to treat CRF were conducted, so in order to evaluate its efficacy, an updated systematic review. This protocol provides research methods for systematic review and meta-analysis of the safety and effectiveness of acupuncture for the treatment of CRF. METHODS: We will searched the randomized controlled trial literature of acupuncture treatment for CRF in 4 English and 4 Chinese databases, including PubMed, MEDLINE, Web of Science, Cochrane Central Register of Controlled Trials (Central), China National Knowledge Infrastructure (CNKI), China Biomedical Literature Database(CBM), China Science Journal Database (VIP), and Wanfang Database. Simultaneously, other resources are manually retrieved which include reference lists of identified publications, conference articles, and grey literature. We also included the clinical randomized controlled trials of acupuncture treatment for CRF in the study. The search language is limited to Chinese and English. Two trained reviewers independently completed research screening, data extraction, and research quality assessment. RevMan (V.5.3) software was used to perform data statistical analysis and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to evaluate the quality of evidence. RESULTS: This study is based on past and present clinical evidence to comprehensively evaluate the effectiveness and safety of acupuncture treatment for CRF. CONCLUSION: Through this systematic review, we will provide the latest high-quality evidence of whether acupuncture treatment for CRF is effective and safe and also provide a theoretical basis for clinicians to choose acupuncture for the treatment of CRF. SYSTEMATIC REVIEW REGISTRATION: INPLASY 202090049.


Assuntos
Terapia por Acupuntura , Fadiga/terapia , Metanálise como Assunto , Neoplasias/complicações , Revisões Sistemáticas como Assunto , Fadiga/etiologia , Humanos , Projetos de Pesquisa
18.
BMC Geriatr ; 20(1): 399, 2020 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046005

RESUMO

BACKGROUND: There is a link between hyperglycemia and mechanical functions of muscle. However, existing evidence of the association between hyperglycemia and weaker muscle strength is limited and inconsistent. We examined whether glycemic status was associated with relative grip strength (RGS) in older Chinese. METHODS: In 2008-2012, 9180 participants (2516 men and 6664 women) from the Guangzhou Biobank Cohort Study had fasting and 2-h post-load glucose measured. Glycemic status was categorized as normoglycaemia, prediabetes (i.e., impaired fasting glucose and/or impaired glucose tolerance) and diabetes. RGS was assessed using a Jamar Hydraulic Hand Dynamometer divided by body mass index. General linear model was used to assess the association of glycemic status with RGS. RESULTS: After adjusting for age, smoking status, alcohol use, physical activity, health status, body fat percentage and waist circumference, in men, hyperglycemia was associated with a lower RGS, with the RGS being 1.38 (95% confidence interval (CI) = 1.34, 1.42) in normoglycaemia, 1.35 (95% CI = 1.30, 1.39) in prediabetes, 1.33 (95% CI = 1.29, 1.38) in newly diagnosed diabetes and 1.32 (95% CI = 1.27, 1.37) in known diabetes (P for trend < 0.001). The association of glycemic status with RGS was non-significant in women. Among the normoglycaemic group, no association was found between fasting glucose and RGS in men, whereas a significantly inverse association was found in women, with adjusted ß for RGS per mmol/l increase in fasting glucose being - 0.05 to - 0.04 (P values from 0.002 to 0.03). CONCLUSIONS: Higher fasting glucose was associated with reduced grip strength in a dose-response manner, and the association was significant even in women with normoglycaemia. Our findings suggest that lowering glucose across the whole range might be important in preserving muscle strength, especially in aging women.

19.
Front Endocrinol (Lausanne) ; 11: 571037, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33071977

RESUMO

Background: Diabetes has been found to increase severity and mortality under the current pandemic of coronavirus disease of 2019 (COVID-19). Up to date, the clinical characteristics of diabetes patients with COVID-19 and the risk factors for poor clinical outcomes are not clearly understood. Methods: The study was retrospectively carried out on enrolled diabetes patients with laboratory confirmed COVID-19 infection from a designated medical center for COVID-19 from January 25th, 2020 to February 14th, 2020 in Wuhan, China. The medical record was collected and reviewed. Univariate and multivariate analyses were performed to assess the risk factors associated with the severe events which were defined as a composite endpoint of admission to intensive care unit, the use of mechanical ventilation, or death. Results: A total of 52 diabetes patients with COVID-19 were finally included in the study. 21 (40.4%) patients had developed severe events in 27.50 (IQR 12.25-35.75) days follow-up, 15 (28.8%) patients experienced life-threatening complications and 8 patients died with a recorded mortality rate of 15.4%. Only 13 patients (41.9%) were in optimal glycemic control with HbA1c value of <7.0%. In addition to general clinical characteristics of COVID-19, the severe events diabetes patients showed higher counts of white blood cells and neutrophil, lower lymphocytes (40, 76.9%), high levels of hs-CRP, erythrocyte sedimentation rate (ESR) and procalcitonin (PCT) as compared to the non-severe diabetes patients. Mild higher level of cardiac troponin I (cTNI) (32.0 pg/ml; IQR 16.80-55.00) and D-dimer (1.70 µg/L, IQR 0.70-2.40) were found in diabetes patients with severe events as compared to the non-severe patients (cTNI:20.00 pg/ml, IQR5.38-30.00, p = 0.019; D-dimer: 0.70 µg/L, IQR 0.30-2.40, p = 0.037). After adjusting age and sex, increased level of cTNI was found to significantly associate with the incidence of severe events (HR: 1.007; 95% CI: 1.000-1.013; p = 0.048), Furthermore, using of α-glucosidase inhibitors was found to be the potential protectant for severe events (HR: 0.227; 95% CI: 0.057-0.904; p = 0.035). Conclusion: Diabetes patients with COVID-19 showed poor clinical outcomes. Vigorous monitoring of cTNI should be recommended for the diabetes patients with COVID-19. Usage of α-glucosidase inhibitors could be a potential protectant for the diabetes patients with COVID-19.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/mortalidade , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Pneumonia Viral/mortalidade , Índice de Gravidade de Doença , Idoso , Glicemia/análise , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
20.
Curr Med Sci ; 40(5): 858-870, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33123901

RESUMO

Given the rapid increase in the prevalence of chronic diseases in aging populations, this prospective study including 17 707 adults aged ≥45 years from China Health and Retirement Longitudinal Study was used to estimate the associations between chronic disease, multimorbidity, and depression among middle-aged and elderly adults in China, and explore the mediating factors. Depressive symptoms were assessed using the 10-item Centre for Epidemiological Studies Depression Scale (CES-D-10) questionnaire. Twelve chronic physical conditions, including hypertension, diabetes, dyslipidemia, cancer, chronic lung disease, liver disease, heart failure, stroke, kidney disease, arthritis or rheumatism, asthma, digestive disease were assessed. The prevalence rates for physical multimorbidity and depression (CES-D-10 ≥10) were 43.23% and 36.62%, respectively. Through multivariable logistic models and generalized estimating equation (GEE) models, we found all 12 chronic physical conditions, and multimorbidity were significantly associated with depression. Both mobility problems and chronic pain explained more than 30% of the association for all chronic conditions, with particularly high percentages for stroke (51.56%) and cancer (51.06%) in mobility problems and cancer (53.35%) in chronic pain. Limited activities of daily living (ADL) explained 34.60% of the stroke-cancer relationship, while sleep problems explained between 10.15% (stroke) and 14.89% (chronic lung disease) of the association. Individuals with chronic diseases or multimorbidity are significantly more likely to be depressed. Functional symptoms involving limitations of ADL and mobility difficulties mediated much of the association between chronic diseases and incident depression. These symptoms could be targeted for interventions to ameliorate the incidence of depression among individuals with chronic conditions.

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