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1.
New Phytol ; 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35510797

RESUMO

• Protein sorting is an essential biological process in all organisms. Trafficking membrane proteins generally relies on the sorting machinery of the Golgi apparatus. However, many proteins have been found to be delivered to target locations via Golgi-independent pathways, but the mechanisms underlying this delivery system remain unknown. • Here, we report that Sec24C mediates the direct secretory trafficking of the phytochelatin transporters ABCC1 and ABCC2 from the endoplasmic reticulum (ER) to prevacuolar compartments (PVCs) in Arabidopsis thaliana. • Genetic analysis showed that the sec24c mutants are hypersensitive to cadmium (Cd) and arsenic (As) treatments due to mislocalization of ABCC1 and ABCC2, which results in defects in the vacuole compartmentalization of the toxic metals. Furthermore, we found that Sec24C recognizes ABCC1 and ABCC2 through direct interactions to mediate their exit from the ER to PVCs, which is independent of BFA-sensitive post-Golgi trafficking pathway. • These findings expand our understanding of Golgi-independent trafficking, which also provide key insights regarding the mechanism of tonoplast protein sorting and open a new perspective on the function of Sec24 proteins.

2.
J Hosp Med ; 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35570695

RESUMO

BACKGROUND: Examine baseline factors associated with a new diagnosis of opioid use disorder (OUD) within 12 months postdischarge among opioid-naïve patients who received an opioid prescription in the inpatient setting. DESIGN/SETTING: Retrospective cohort (surgery and nonsurgery) study of opioid-naive patients who had at least one prescription for an opioid during an inpatient hospitalist between 2014 and 2017. PARTICIPANTS: Twenty-three thousand and thirty-three patients were included. OBJECTIVE: The primary objective was to determine baseline factors associated with a new OUD diagnosis within 12 months of discharge. Baseline covariates included demographic information, clinical characteristics, medication use, characteristics related to index hospital encounter, and discharge location. FINDINGS: 2.1% of the sample had a new diagnosis of OUD within a year after receiving an opioid during hospital admission. Patients between ages 25 and 34 had higher odds of a new OUD diagnosis compared to those 65 years of age and older (odds ratio [OR]: 6.98, 95% confidence interval [CI]: 4.02-12.1 [nonsurgery] and 4.69, 95% CI: 2.63-8.37 [surgery]). Patients from a high opioid geo-rank region had higher odds of OUD diagnosis (OR: 2.08, 95% CI: 1.31-3.31 [nonsurgery] and 1.80, 95% CI: 1.03-3.15 [surgery]). History of nonopioid-related drug disorder, tobacco use disorder, mental health conditions, and gabapentin use 12 months prior to index date and white race were associated with higher odds of new OUD diagnosis. CONCLUSIONS: It is important to identify and evaluate factors associated with developing a new diagnosis of OUD following hospitalization. This can inform pain management strategies within the hospital and at discharge, and prompt clinicians to screen for risk of OUD.

3.
Mitochondrial DNA B Resour ; 7(5): 822-824, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35573590

RESUMO

The complete chloroplast genome sequence of Clematis mandshurica Ruprecht (1867), a specie of the Ranunculaceae family, and its phylogenetic relationships with other species have been reported in this study. The complete chloroplast genome of C. mandshurica is 159,563 bp in length, including a large single-copy (LSC) region of 79,360 bp, a small single-copy (SSC) region of 18,121 bp, and a pair of identical inverted repeat regions (IRs) of 31,041 bp. The genome encodes a total of 132 genes, including 90 protein-coding genes, 34 transfer RNA (tRNA) genes, and eight ribosomal RNA (rRNA) genes. The phylogenetic analysis reveals that C. mandshurica was found to be closest to Clematis taeguensis. The complete chloroplast genome of C. mandshurica contributes to a better understanding of phylogenetic relationships among Clematis species.

4.
Development ; 149(10)2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35502748

RESUMO

Adventitious roots (ARs) are an important type of plant root and display high phenotypic plasticity in response to different environmental stimuli. It is known that photoreceptors inhibit darkness-induced hypocotyl adventitious root (HAR) formation by directly stabilizing Aux/IAA proteins. In this study, we further report that phytochrome-interacting factors (PIFs) plays a central role in HAR initiation by simultaneously inducing the expression of genes involved in auxin biosynthesis, auxin transport and the transcriptional control of root primordium initiation. We found that, on the basis of their activity downstream of phytochrome, PIFs are required for darkness-induced HAR formation. Specifically, PIFs directly bind to the promoters of some genes involved in root formation, including auxin biosynthesis genes YUCCA2 (YUC2) and YUC6, the auxin influx carrier genes AUX1 and LAX3, and the transcription factors WOX5/7 and LBD16/29, to activate their expression. These findings reveal a previously uncharacterized transcriptional regulatory network underlying HAR formation.

5.
Front Immunol ; 13: 830158, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35444644

RESUMO

The alterations of glycosylation, which is a common post-translational modification of proteins, have been acknowledged as key events in breast cancer (BC) oncogenesis and progression. The aberrant expression of glycosyltransferases leads to aberrant glycosylation patterns, posing the diagnostic potential in BC outcomes. The present study aims to establish a glycosyltransferase-based signature to predict BC prognosis and response to immune checkpoint inhibitors. We firstly screened 9 glycosyltransferase genes from The Cancer Genome Atlas (TCGA) database and accordingly established a glyco-signature for predicting the prognosis in BC patients. Patients with BC were successfully divided into high-risk and low-risk groups based on the median cutoff point for risk scores in this signature. Next, the combinational analyses of univariate and multivariate Cox regression, Kaplan-Meier, and receiver operating characteristic (ROC) curves were used to prove that this glyco-signature possessed excellent predictive performance for prognosis of BC patients, as the high-risk group possessed worse outcomes, in comparison to the low-risk group. Additionally, the Gene Set Enrichment Analysis (GSEA) and immunologic infiltration analysis were adopted and indicated that there was a more immunosuppressive state in the high-risk group than that in the low-risk group. The clinical sample validation verified that glycosyltransferase genes were differentially expressed in patients in the low- and high-risk groups, while the biomarkers of antitumor M1 macrophages were increased and N-glycosyltransferase STT3A decreased in the low-risk group. The final in vitro assay showed that the silencing of STT3A suppressed the proliferation and migration of BC cells. Collectively, our well-constructed glyco-signature is able to distinguish the high- and low-risk groups and accordingly predict BC prognosis, which will synergistically promote the prognosis evaluation and provide new immunotherapeutic targets for combating BC.


Assuntos
Neoplasias da Mama , Inibidores de Checkpoint Imunológico , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Feminino , Glicosilação , Glicosiltransferases/genética , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico
6.
J Inflamm Res ; 15: 2461-2476, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35449599

RESUMO

Background: Gap junctions, as one of the major ways to maintain social connections between cells, are now considered as one of the potential regulators of tumor metastasis. However, to date, studies on the relationship between gap junctions and colorectal cancer (CRC) are limited. Methods: We synthesized connexins-coding gene expression data from public Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Bioinformatics analysis was performed using R software and several database resources such as MEXPRESS database, Gene Set Cancer Analysis (GSCA) database, Human Protein Atlas (HPA) database, Tumor Immune Single Cell Hub (TISCH) database, Search Tool for Retrieval of Gene Interaction Relationships (STRING), and Cytoscape software, etc., to investigate the biological mechanisms that may be involved in connexins. Immunofluorescence and immunohistochemical staining were used to validate the expression and localization of GJA4. Results: We found that CRC patients can be divided into two connexin clusters and that patients in cluster C1 had shorter survival than in cluster C2. The infiltration of M1 macrophages and NK cells was lower in cluster C1, while the levels of M2 macrophages and immune checkpoints were higher, indicating an immunosuppressed state in cluster C1. In addition, the epithelial-mesenchymal transition (EMT) phenotype was significantly activated in cluster C1. We observed that GJA4 was up-regulated in colorectal cancer tissues, which was related to poor prognosis. It was mainly expressed in fibroblasts, but the expression levels in normal intestinal epithelial cells were low. Finally, we found that GJA4 was associated with M2 macrophages and may be a potential immunosuppressive factor. Conclusion: We found that there is a significant correlation between abnormal connexins expression and patients' prognosis, and connexins play an important role in stromal-tumor interactions. Connexins, especially GJA4, can help enhance our understanding of tumor microenvironment (TME) and may guide more effective immunotherapeutic strategies.

7.
Molecules ; 27(7)2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-35408528

RESUMO

(1) Background: Carbon quantum dots (CQDs) are a new class of carbon nanomaterials with favorable features, such as tunable luminescence, unique optical properties, water solubility, and lack of cytotoxicity; they are readily applied in biomedicine. (2) Methods: S, N co-doped CQDs were prepared to develop a highly selective and sensitive fluorescence technique for the detection of methotrexate (MTX). For this purpose, citric acid and thiourea were used as C, N, and S sources in a single-step hydrothermal process to prepare the S, N co-doped CQDs, which displayed remarkable fluorescence properties. (3) Results: Two optimal emissions were observed at the excitation/emission wavelengths of 320/425 nm, respectively. The two emissions were significantly quenched in the presence of MTX. Under optimal conditions, MTX was detected in the linear concentration range of 1-300 µmol/L, with the detection limit of 0.33 µmol/L. The sensing mechanism was due to the fact that the effect of the inner filter on MTX and S, N-CQDs causes fluorescence quenching. The contents of MTX in real medicine samples were evaluated with acceptable recoveries of 98-101%. (4) Conclusions: This approach has great potential for detecting MTX in pharmaceutical analysis.


Assuntos
Pontos Quânticos , Carbono , Metotrexato , Nitrogênio , Espectrometria de Fluorescência/métodos
8.
Int J Environ Health Res ; : 1-13, 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35481410

RESUMO

Benzo(a)pyrene (BaP) is an environmental pollutant widely exposed to human beings. While the relationship between BaP and missed abortion is few understood. To explore the association between missed abortion and BaP, genetic polymorphisms of AhR pathway, we recruited 112 cases women with missed abortion and 137 controls women with normal pregnancy from Shanxi, China. The BPDE-DNA adducts level in the case group was higher than that in the control group (P < 0.001). The subjects were categorized according to the tertiles of BPDE-DNA adduct concentrations: T1 (

9.
Signal Transduct Target Ther ; 7(1): 131, 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35459215

RESUMO

Atherosclerosis is a chronic inflammatory vascular disease driven by traditional and nontraditional risk factors. Genome-wide association combined with clonal lineage tracing and clinical trials have demonstrated that innate and adaptive immune responses can promote or quell atherosclerosis. Several signaling pathways, that are associated with the inflammatory response, have been implicated within atherosclerosis such as NLRP3 inflammasome, toll-like receptors, proprotein convertase subtilisin/kexin type 9, Notch and Wnt signaling pathways, which are of importance for atherosclerosis development and regression. Targeting inflammatory pathways, especially the NLRP3 inflammasome pathway and its regulated inflammatory cytokine interleukin-1ß, could represent an attractive new route for the treatment of atherosclerotic diseases. Herein, we summarize the knowledge on cellular participants and key inflammatory signaling pathways in atherosclerosis, and discuss the preclinical studies targeting these key pathways for atherosclerosis, the clinical trials that are going to target some of these processes, and the effects of quelling inflammation and atherosclerosis in the clinic.


Assuntos
Aterosclerose , Inflamassomos , Aterosclerose/complicações , Aterosclerose/tratamento farmacológico , Aterosclerose/genética , Estudo de Associação Genômica Ampla , Humanos , Inflamassomos/metabolismo , Inflamassomos/uso terapêutico , Inflamação/complicações , Inflamação/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Transdução de Sinais/genética
10.
Nat Commun ; 13(1): 1625, 2022 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-35338128

RESUMO

The emergence of multidrug-resistant (MDR) Gram-negative pathogens is an urgent global medical challenge. The old polymyxin lipopeptide antibiotics (polymyxin B and colistin) are often the only therapeutic option due to resistance to all other classes of antibiotics and the lean antibiotic drug development pipeline. However, polymyxin B and colistin suffer from major issues in safety (dose-limiting nephrotoxicity, acute toxicity), pharmacokinetics (poor exposure in the lungs) and efficacy (negligible activity against pulmonary infections) that have severely limited their clinical utility. Here we employ chemical biology to systematically optimize multiple non-conserved positions in the polymyxin scaffold, and successfully disconnect the therapeutic efficacy from the toxicity to develop a new synthetic lipopeptide, structurally and pharmacologically distinct from polymyxin B and colistin. This resulted in the clinical candidate F365 (QPX9003) with superior safety and efficacy against lung infections caused by top-priority MDR pathogens Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae.


Assuntos
Colistina , Polimixina B , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Colistina/farmacologia , Farmacorresistência Bacteriana Múltipla , Lipopeptídeos/farmacologia , Lipopeptídeos/uso terapêutico , Testes de Sensibilidade Microbiana , Polimixinas/farmacologia , Polimixinas/uso terapêutico , Pseudomonas aeruginosa
11.
PLoS Pathog ; 18(3): e1010308, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35231068

RESUMO

The opportunistic pathogen Acinetobacter baumannii possesses stress tolerance strategies against host innate immunity and antibiotic killing. However, how the host-pathogen-antibiotic interaction affects the overall molecular regulation of bacterial pathogenesis and host response remains unexplored. Here, we simultaneously investigate proteomic changes in A. baumannii and macrophages following infection in the absence or presence of the polymyxins. We discover that macrophages and polymyxins exhibit complementary effects to disarm several stress tolerance and survival strategies in A. baumannii, including oxidative stress resistance, copper tolerance, bacterial iron acquisition and stringent response regulation systems. Using the spoT mutant strains, we demonstrate that bacterial cells with defects in stringent response exhibit enhanced susceptibility to polymyxin killing and reduced survival in infected mice, compared to the wild-type strain. Together, our findings highlight that better understanding of host-pathogen-antibiotic interplay is critical for optimization of antibiotic use in patients and the discovery of new antimicrobial strategy to tackle multidrug-resistant bacterial infections.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Animais , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Humanos , Macrófagos , Camundongos , Testes de Sensibilidade Microbiana , Polimixinas/farmacologia , Proteômica
13.
Dis Markers ; 2022: 7550090, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35251376

RESUMO

OBJECTIVE: The aims of our experiment were to compare the microorganisms in meibomian gland secretions from patients with internal hordeolum before and after treatment using hypochlorous acid eyelid wipes, to elucidate the mechanism underlying hypochlorous acid eyelid wipe treatment of internal hordeolum. METHODS: This was a prospective, matched-pair study. A total of eight patients with internal hordeolum who attended the ophthalmology clinic of our hospital from April to August 2020 were included. Meibomian gland secretions were collected from subjects before treatment (Group A) and from patients cured after eyelid cleaning with hypochlorous acid eyelid wipes for 7 days (Group B). Samples were submitted to 16S rRNA high-throughput sequencing, and the resulting data were analyzed to compare the differences in the structure and composition of meibomian gland secretion microbial flora before and after treatment of internal hordeolum. RESULTS: A total of 2127 operational taxonomic units were obtained from the two groups of samples, and there was no significant difference in alpha diversity before and after eyelid cleaning. At the phylum level, there was no significant difference between the two groups. The predominant phyla in Group A included the following: Firmicutes (32.78% ± 20.16%), Proteobacteria (26.73% ± 7.49%), Acidobacteria (10.58% ± 11.45%), Bacteroidetes (9.05% ± 6.63%), Actinobacteria (8.48% ±1.77%), and Chloroflexi (3.15% ± 3.12%), while those in Group B were the following: Proteobacteria (31.86% ± 9.69%), Firmicutes (29.07% ± 24.20%), Acidobacteria (11.33% ± 7.53%), Actinobacteria (7.10% ± 1.98%), Bacteroidetes (5.39% ± 5.17%), and Chloroflexi (3.89% ± 3.67%). Starting from the class level, significant differences in microbial communities were detected before and after eyelid cleaning (P < 0.05). Linear discriminant analysis effect size analysis showed the core flora in Group A microbiome comprising Actinobacteria, Staphylococcus, Staphylococcaceae, Staphylococcus aureus, Ruminococcacea UCg-014, Ruminococcacea-UCG-014, Halomonadaceae, Neisseria, Methylobacterium, Frankiales, and Neisseria sicca, while those in Group B microbial were Streptococcus sp., Blautia, Bifidobacterium pseudocatenulatum, Subdoligranulum, Subdoligranulum variabile, Faecalibacterium, and Faecalibacterium prausnitzii. CONCLUSION: Eyelid cleaning with hypochlorous acid eyelid wipes does not change the biodiversity in the meibomian gland secretions of patients with internal hordeolum. Hypochlorous acid eyelid wipes may affect the internal hordeolum through broad-spectrum antibacterial action to effectively reduce the relative abundance of symbiotic pathogens, such as Staphylococcus, Neisseria, Actinomycetes, and Ruminococcus and increase that of Faecalibacterium prausnitzii and other symbiotic probiotics with anti-inflammatory effects.


Assuntos
Bactérias/genética , Terçol/tratamento farmacológico , Ácido Hipocloroso/uso terapêutico , Glândulas Tarsais/microbiologia , Microbiota , Oxidantes/uso terapêutico , Adulto , Biodiversidade , Feminino , Humanos , Masculino , Estudos Prospectivos , RNA Ribossômico 16S/genética
14.
PLoS One ; 17(3): e0265132, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35320283

RESUMO

Vascular smooth muscle cell (VSMC) subpopulations relevant to vascular disease and injury repair have been depicted in healthy vessels and atherosclerosis profiles. However, whether VSMC subpopulation associated with vascular homeostasis exists in the healthy artery and how are their nature and fate in vascular remodeling remains elusive. Here, using single-cell RNA-sequencing (scRNA-seq) to detect VSMC functional heterogeneity in an unbiased manner, we showed that VSMC subpopulations in healthy artery presented transcriptome diversity and that there was significant heterogeneity in differentiation state and development within each subpopulation. Notably, we detected an independent subpopulation of VSMCs that highly expressed regulator of G protein signaling 5 (RGS5), upregulated the genes associated with inhibition of cell proliferation and construction of cytoskeleton compared with the general subpopulation, and mainly enriched in descending aorta. Additionally, the proportion of RGS5high VSMCs was markedly decreased or almost disappeared in the vascular tissues of neointimal formation, abdominal aortic aneurysm and atherosclerosis. Specific spatiotemporal characterization of RGS5high VSMC subpopulation suggested that this subpopulation was implicated in vascular homeostasis. Together, our analyses identify homeostasis-relevant transcriptional signatures of VSMC subpopulations in healthy artery, which may explain the regional vascular resistance to atherosclerosis at some extent.


Assuntos
Aterosclerose , Músculo Liso Vascular , Proteínas RGS/metabolismo , Aterosclerose/metabolismo , Proliferação de Células , Células Cultivadas , Proteínas de Ligação ao GTP/metabolismo , Humanos , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Neointima/metabolismo
15.
PLoS One ; 17(3): e0264942, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35358189

RESUMO

BACKGROUND: Aortic aneurysm/dissection (AAD) is now encountered more often because of the increasing prevalence of atherosclerosis and hypertension in the population. Despite many therapeutic improvements, in particular timely and successful surgery, in-hospital mortality rates are still higher. Timely identification of patients at high risk will help improve the overall prognosis of AAD. Since early clinical and radiological signs are nonspecific, there is an urgent need for accurate biomarkers. Smooth muscle 22α (SM22α) is a potential marker for AAD because of its abundant expression in vascular smooth muscle, which is involved in development of AAD. METHODS: We prepared three different mouse models, including abdominal aortic aneurysm, neointimal hyperplasia and atherosclerosis. SM22α levels were assessed in serum and vascular tissue of the mice. Next, the relationships between serum SM22α level and vascular lesion were studied in mice. Finally, serum from 41 patients with AAD, 107 carotid artery stenosis (CAS) patients and 40 healthy volunteers were tested for SM22α. Serum levels of SM22α were measured using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with the controls, serum SM22α levels were reduced in the models of aortic aneurysm, neointimal formation and atherosclerosis, and elevated in mice with ruptured aneurysm. Serum SM22α level was negatively correlated with apoptosis rate of vascular smooth muscle cells (VSMC), ratio of intima/ media (I/M) area and plaque size. Patients with AAD had significantly higher serum SM22α levels than patients with only CAS, or normal controls. CONCLUSION: Serum SM22α could be a potential predictive marker for AAD, and regulation of VSMC is a possible mechanism for the effects of SM22α.


Assuntos
Aneurisma Dissecante , Aneurisma Aórtico , Aterosclerose , Aneurisma Dissecante/patologia , Animais , Aneurisma Aórtico/patologia , Aterosclerose/patologia , Biomarcadores/metabolismo , Humanos , Camundongos , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Neointima/patologia
16.
Trials ; 23(1): 226, 2022 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-35313933

RESUMO

INTRODUCTION: Diarrhea-predominant irritable bowel syndrome (IBS-D) is a bowel disease with a high incidence. It significantly reduces the quality of life of patients and affects the patient's daily activities and mental health. No specific therapeutic medications for IBS-D have been found. Published clinical trials suggest that Chinese herbal formula Tongxie Yaofang (TXYF) for IBS-D may be effective. However, high-quality clinical evidence supporting its use in IBS-D is still lacking. This trial aims to evaluate the therapeutic effects and safety of TXYF for IBS-D in adults. METHODS/DESIGN: A randomized, multiple-blind, placebo-controlled trial will be conducted. It will consist of an 8-week intervention followed by a 3-month follow-up period. The target sample size is 96 IBS-D patients aged 18 to 65 years. The eligible participants will be randomly allocated to either TXYF or placebo group in a ratio of 1:1. Participants in the experimental group will take TXYF granules, while participants in the control group will be given TXYF placebo granules. The primary outcome will be the degree of IBS symptom severity measured using the scale of IBS symptom severity score. The secondary outcomes include: (a) stool frequency, and (b) stool consistency measured using the Bristol stool scale, (c) quality of life measured using the scale of IBS-quality of life, (d) anxiety measured using the self-rating anxiety scale, (e) depression measured by the self-rating depression scale, and (f) the safety of using TXYF and placebo. Safety monitoring and assessment will be undertaken throughout treatment. DISCUSSION: Chinese herbal formula TXYF consists of four Chinese herbs: Atractylodes macrocephala Koidz., Paeonia lactiflora Pall ., Citrus × aurantium L ., and Radix saposhnikoviae. It has been used for diarrhea for hundreds of years and may have a potential benefit in treating adults with IBS-D, but due to lack of high-quality evidence, we designed a randomized, multiple-blind, placebo-controlled trial to evaluate its therapeutic effects and safety. This trial will provide important data to guide the clinical practice of TXYF for the treatment of IBS-D in adults. TRIAL REGISTRATION: ISRCTN registry ISRCTN12453166 . Registered on 23 March 2021.


Assuntos
Síndrome do Intestino Irritável , China , Diarreia/diagnóstico , Diarreia/tratamento farmacológico , Fezes , Humanos , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/diagnóstico , Síndrome do Intestino Irritável/tratamento farmacológico , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
17.
Am J Epidemiol ; 2022 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-35279711

RESUMO

The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults comprising 14 established United States (US) prospective cohort studies. Starting as early as 1971, C4R cohorts have collected data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R links this pre-COVID phenotyping to information on SARS-CoV-2 infection and acute and post-acute COVID-related illness. C4R is largely population-based, has an age range of 18-108 years, and reflects the racial, ethnic, socioeconomic, and geographic diversity of the US. C4R ascertains SARS-CoV-2 infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations, and high-quality events surveillance. Extensive pre-pandemic data minimize referral, survival, and recall bias. Data are harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these will be pooled and shared widely to expedite collaboration and scientific findings. This resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including post-acute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term trajectories of health.

18.
Prostaglandins Other Lipid Mediat ; 160: 106634, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35292355

RESUMO

The liver is a parenchymatous organ closely related to immunity, detoxification and metabolism of the three major nutrients. The inflammatory response is a protective mechanism of the body to eliminate harmful stimuli. However, continuous inflammatory stimulation leads to occurrence of many liver diseases and brings great social burden. Resolvin D1, a member of the specialized pro-resolving lipid mediators family, exerts anti-inflammatory, anti-oxidant stress, anti-fibrosis, anti-apoptotic, and anti-tumor effects by binding to ALX/FPR2 or GPR32. RvD1 plays an important role and has great therapeutic potential in liver diseases, which has been validated in multiple models of preclinical disease. This review will provide a detailed summary of the role of RvD1 in different liver diseases, including acute liver injury, liver ischemia/reperfusion injury, non-alcoholic fatty liver disease, liver fibrosis, and liver cancer, so as to help people have a more comprehensive understanding of RvD1 and promote its further research.

19.
Artigo em Inglês | MEDLINE | ID: mdl-35222677

RESUMO

BACKGROUND: Herpes zoster (HZ) is a common infection in individuals with acquired immunodeficiency syndrome (AIDS) patients. Traditional Chinese medicine (TCM) has been used widely in clinical practice for HZ, which remains not supportive of evidence. This review aimed to evaluate the effectiveness and safety of TCM in treating HIV-associated HZ. METHODS: Nine electronic databases were searched for randomized controlled trials (RCTs) testing TCM in treating HIV-associated HZ. Data were extracted on citations, interventions, and outcomes, by two authors independently. For the quality evaluation, Cochrane risk-of-bias tool 2.0 was used. Meta-analyses were performed by Revman5.3 software. Effect estimation presented as risk ratio (RR) for dichotomous data and mean difference (MD) for continuous data with their 95% confidence interval (CI). RESULTS: Twelve RCTs (n = 644) were included; the majority of them had a high or unclear risk of bias. Meta-analysis showed that pain intensity (VAS 0-5) in the Chinese herbal medicine (CHM) group was lower than it in the drugs group (MD = -0.87, 95% CI [-1.69, -0.04], two trials, n = 93). Duration of herpes-related pain (days) of patients in the combination group was shorter than those in the drugs group (MD = -9.19, 95% CI [-16.73, -1.65], n = 144). The incidence of postherpetic neuralgia (PHN) in the combination group was lower than in the drugs group (RR = 0.49, 95% CI [0.25, 0.99], n = 202). As for cure rate (complete absence of pain and herpes), two trials showed that CHM was better than drugs (RR = 1.58, 95% CI [1.13, 2.22], n = 93), five trials showed combination treatment was better than drugs (RR = 1.40, 95% CI [1.08, 1.82], n = 224). The cure rate in the acupuncture group was more than that in the drugs group (RR = 1.99, 95% CI [1.18, 3.36], n = 120). Four trials reported adverse effects and found no serious adverse events occurred. CONCLUSION: CHM and acupuncture demonstrate more benefits than drugs in pain relief, cure rate improvement, and incidence reduction of PHN. However, given the data limitation and TCM therapies' diversity, the conclusions need to be verified in future trials.

20.
Cells ; 11(4)2022 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-35203314

RESUMO

Zonula occludens-1 (ZO-1) is an intracellular scaffolding protein that orchestrates the anchoring of membrane proteins to the cytoskeleton in epithelial and specialized tissue including the heart. There is clear evidence to support the central role of intracellular auxiliary proteins in arrhythmogenesis and previous studies have found altered ZO-1 expression associated with atrioventricular conduction abnormalities. Here, using human cardiac tissues, we identified all three isoforms of ZO-1, canonical (Transcript Variant 1, TV1), CRA_e (Transcript Variant 4, TV4), and an additionally expressed (Transcript Variant 3, TV3) in non-failing myocardium. To investigate the role of ZO-1 on ventricular arrhythmogenesis, we generated a haploinsufficient ZO-1 mouse model (ZO-1+/-). ZO-1+/- mice exhibited dysregulated connexin-43 protein expression and localization at the intercalated disc. While ZO-1+/- mice did not display abnormal cardiac function at baseline, adrenergic challenge resulted in rhythm abnormalities, including premature ventricular contractions and bigeminy. At baseline, ventricular myocytes from the ZO-1+/- mice displayed prolonged action potential duration and spontaneous depolarizations, with ZO-1+/- cells displaying frequent unsolicited (non-paced) diastolic depolarizations leading to spontaneous activity with multiple early afterdepolarizations (EADs). Mechanistically, ZO-1 deficient myocytes displayed a reduction in sodium current density (INa) and an increased sensitivity to isoproterenol stimulation. Further, ZO-1 deficient myocytes displayed remodeling in ICa current, likely a compensatory change. Taken together, our data suggest that ZO-1 deficiency results in myocardial substrate susceptible to triggered arrhythmias.


Assuntos
Miocárdio , Junções Íntimas , Animais , Arritmias Cardíacas/genética , Arritmias Cardíacas/metabolismo , Camundongos , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Sódio/metabolismo , Junções Íntimas/metabolismo , Proteína da Zônula de Oclusão-1/metabolismo
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