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1.
Environ Sci Technol ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34618424

RESUMO

Chlorinated organic pollutants are highly toxic and widespread in the environment, which cause ecological risk and threaten the human health. Chlorinated pollutants are difficult to degrade and mineralize by the conventional advanced oxidation process as the C-Cl bond is resistant to reactive oxygen species oxidation. Herein, we designed a bifunctional Fe/Cu bimetallic single-atom catalyst anchored on N-doped porous carbon (FeCuSA-NPC) for the electro-Fenton process, in which chlorinated pollutants are dechlorinated on single-atom Cu and subsequently oxidized by the ·OH radical produced from O2 conversion on single-atom Fe. Benefitting from the synergistic effect between dechlorination on single-atom Cu and ·OH oxidation on single-atom Fe, the chlorinated organic pollutants can be efficiently degraded and mineralized. The mass activity for chlorinated organic pollutant degradation by FeCuSA-NPC is 545.1-1374 min-1 gmetal-1, excessing the highest value of the reported electrocatalyst. Moreover, FeCuSA-NPC is demonstrated to be pH-universal, long-term stable, and environment friendly. This work provides a new insight into the rational design of a bifunctional electrocatalyst for efficient removal of chlorinated organic pollutants.

2.
J Zhejiang Univ Sci B ; 22(10): 818-838, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34636186

RESUMO

OBJECTIVES: Cardiac hypertrophy and fibrosis are major pathological manifestations observed in left ventricular remodeling induced by angiotensin II (AngII). Low-intensity pulsed ultrasound (LIPUS) has been reported to ameliorate cardiac dysfunction and myocardial fibrosis in myocardial infarction (MI) through mechano-transduction and its downstream pathways. In this study, we aimed to investigate whether LIPUS could exert a protective effect by ameliorating AngII-induced cardiac hypertrophy and fibrosis and if so, to further elucidate the underlying molecular mechanisms. METHODS: We used AngII to mimic animal and cell culture models of cardiac hypertrophy and fibrosis. LIPUS irradiation was applied in vivo for 20 min every 2 d from one week before mini-pump implantation to four weeks after mini-pump implantation, and in vitro for 20 min on each of two occasions 6 h apart. Cardiac hypertrophy and fibrosis levels were then evaluated by echocardiographic, histopathological, and molecular biological methods. RESULTS: Our results showed that LIPUS could ameliorate left ventricular remodeling in vivo and cardiac fibrosis in vitro by reducing AngII-induced release of inflammatory cytokines, but the protective effects on cardiac hypertrophy were limited in vitro. Given that LIPUS increased the expression of caveolin-1 in response to mechanical stimulation, we inhibited caveolin-1 activity with pyrazolopyrimidine 2 (pp2) in vivo and in vitro. LIPUS-induced downregulation of inflammation was reversed and the anti-fibrotic effects of LIPUS were absent. CONCLUSIONS: These results indicated that LIPUS could ameliorate AngII-induced cardiac fibrosis by alleviating inflammation via a caveolin-1-dependent pathway, providing new insights for the development of novel therapeutic apparatus in clinical practice.

3.
Food Funct ; 12(19): 8899-8906, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34606541

RESUMO

Elucidating the organometallic interactions in Baijiu will promote a deeper understanding of the flavour formation mechanism during Baijiu aging. However, the organometallic interactions during aging are difficult to explore because the concentration and status of metals in Baijiu samples are affected by other substances (such as organic acids), and the concentrations of these substances also change dynamically. Hence, the flavour formation mechanism of aged Baijiu was investigated based on a multi-method analysis (i.e. electrochemistry, ICP-MS/OES, and UPLC-Q-Orbitrap-MS/MS), which enabled us to solve the difficulty above. The key finding is that, in the aging period, the organic acids induce the transformation of the metal ion state from the complex state to the free state. As a result, the flavour compound (i.e. the esters) contents in aged Baijiu are regulated by the free metal ion-catalyzed reactions.

4.
Cell Prolif ; : e13133, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34585448

RESUMO

OBJECTIVES: Maternal factors that are enriched in oocytes have attracted great interest as possible key factors in somatic cell reprogramming. We found that surfeit locus protein 4 (Surf4), a maternal factor, can facilitate the generation of induced pluripotent stem cells (iPSCs) previously, but the mechanism remains elusive. MATERIALS AND METHODS: In this study, we investigated the function and mechanism of Surf4 in somatic cell reprogramming using a secondary reprogramming system. Alkaline phosphatase (AP) staining, qPCR and immunofluorescence (IF) staining of expression of related markers were used to evaluate efficiency of iPSCs derived from mouse embryonic fibroblasts. Embryoid body and teratoma formation assays were performed to evaluate the differentiation ability of the iPSC lines. RNA-seq, qPCR and western blot analysis were applied to validate the downstream targets of Surf4. RESULTS: Surf4 can significantly facilitate the generation of iPSCs in a proliferation-independent manner. When co-expressed with Oct4, Sox2, Klf4 and c-Myc (OSKM), Surf4 can activate the response to endoplasmic reticulum (ER) stress at the early stage of reprogramming. We further demonstrated that Hspa5, a major ER chaperone, and the active spliced form of Xbp1 (sXbp1), a major mediator of ER stress, can mimic the effects of Surf4 on somatic cell reprogramming. Concordantly, blocking the unfolded protein response compromises the effect of Surf4 on reprogramming. CONCLUSIONS: Surf4 promotes somatic cell reprogramming by activating the response to ER stress.

5.
Talanta ; 235: 122749, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34517617

RESUMO

Signal output mode is the important part of biosensor. In general, "signal on" and "signal off" are two common output modes. The development of dual signals-based ratio analysis as a powerful diagnostic tool has attracted widespread attention in the biosensor field in recent years. Dual signals ratio sensors with "signal on" and "signal off" are more favored because of their low background signal and better sensitivity and selectivity. In this study, inspired by the idea that EcoR V can cut specific sites of DNA to produce two corresponding fragments, and by using the capturing probe as guy wires, a reliable and sensitive method for EcoR V assay is developed based on the ratio of dual chemiluminescence (CL) signals for the first time. In particular, in the existence of the objective EcoR V, the substrate DNA would be degraded into two double stranded oligonucleotides with blunt ends which include the sequence I and the sequence II, then they can separately compete with two different corresponding capture probes on magnetic beads (MBs). One of capture probe hybridized with the sequence I containing more guanine (G) bases that reacted with the phenylglyoxal (PG) to produce chemical reaction which triggered a positive CL signal output I + CL as "signal-on"; another capture probe is priority to hybridize the sequence II, which triggered the weaker reporter DNA linked with horseradish peroxidase (HRP) probe to fall off the MBs, thereby outputting a negative CL signal I-CL as "signal-off". By comparing the linear relation and the correlation coefficient, the I-CL/I + CL ratio method has better linear relation (0.01-10 U/mL) and higher sensitivity (0.0045 U/mL). In addition, this developed strategy of high selectivity which can directly detect low concentration of target EcoR V in human serum, and thus this dual ratio biosensor might offer a promising detection approach for clinical diagnostics.


Assuntos
Técnicas Biossensoriais , DNA de Cadeia Simples , DNA/genética , DNA de Cadeia Simples/genética , Peroxidase do Rábano Silvestre , Humanos , Luminescência
6.
Bioengineered ; 12(1): 5688-5704, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34546849

RESUMO

α-Actinin1 (ACTN1), an actin cross-linking protein, is implicated in cytokinesis, cell adhesion, and cell migration. In addition, it is involved in the tumorigenesis and development of certain cancers, such as breast cancer. We explored the function of ACTN1 in gastric cancer (GC), which has largely remained unclear. High-throughput sequencing and public microarray datasets from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) revealed the upregulation of ACTN1 in gastric cancer with a poor prognosis. These results were further verified by western blotting (WB), Real-Time Quantitative polymerase chain reaction (RT-qPCR), and immunohistochemistry. We constructed loss and gain of function gastric cancer cells, which revealed the effect of ACTN1 over-expression on promoting GC cell proliferation, invasion, migration, and inhibited apoptosis. Mechanistic studies revealed that ACTN1 regulates the epithelial-mesenchymal transition (EMT) and tumorigenesis of gastric cancer via the AKT/GSK3ß/ß-catenin pathway, confirmed by the inhibitor of AKT MK2206. Altogether, these results demonstrated that ACTN1 could be a promising candidate for gastric cancer treatment.

7.
Curr Probl Cancer ; : 100791, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34538649

RESUMO

Besides traditional treatment strategies, including surgery, radiotherapy, and chemotherapy for lung cancer as the leading cause of cancer incidence and death, immunotherapy has also emerged as a new treatment strategy. The goal of immunotherapy is to stimulate the immune system responses against cancer, using various approaches such as therapeutic vaccines, monoclonal antibodies, immune checkpoint inhibitors, and T-cell therapy. Chimeric antigen receptor (CAR)-T cells, one of the most popular cancer immunotherapy approaches in the last decade, are genetically engineered T-cells to redirect patients' immune responses to recognize and eliminate tumor-associated antigens (TAA)-expressing tumor cells. CAR-T cell therapy provides promising benefits in lung tumors. In this review, we summarize different immunotherapy approaches for lung cancer, the structure of CAR-T cells, currently undergoing CARs in clinical trials, and various TAAs are being investigated as potential targets in designing CAR-T cells for lung cancer.

8.
Curr Opin Genet Dev ; 70: 104-113, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34530248

RESUMO

It has been nearly 60 years since Dr John Gurdon achieved the first cloning of Xenopus by somatic cell nuclear transfer (SCNT). Later, in 2006, Takahashi and Yamanaka published their landmark study demonstrating the application of four transcription factors to induce pluripotency. These two amazing discoveries both clearly established that cell identity can be reprogrammed and that mature cells still contain the information required for lineage specification. Considering that different cell types possess identical genomes, what orchestrates reprogramming has attracted wide interest. Epigenetics, including high-level chromatin structure, might provide some answers. Benefitting from the tremendous progress in high-throughput and multi-omics techniques, we here address the roles and interactions of genome architecture, chromatin modifications, and transcription regulation during somatic cell reprogramming that were previously beyond reach. In addition, we provide perspectives on recent technical advances that might help to overcome certain barriers in the field.

9.
J Xray Sci Technol ; 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34569983

RESUMO

OBJECTIVE: To assess clinical application of applying deep learning image reconstruction (DLIR) algorithm to contrast-enhanced portal venous phase liver computed tomography (CT) for improving image quality and lesions detection rate compared with using adaptive statistical iterative reconstruction (ASIR-V) algorithm under routine dose. METHODS: The raw data from 42 consecutive patients who underwent contrast-enhanced portal venous phase liver CT were reconstructed using three strength levels of DLIRs (low [DL-L]; medium [DL-M]; high [DL-H]) and two levels of ASIR-V (30%[AV-30]; 70%[AV-70]). Objective image parameters, including noise, signal-to-noise (SNR), and the contrast-to-noise ratio (CNR) relative to muscle, as well as subjective parameters, including noise, artifact, hepatic vein-clarity, index lesion-clarity, and overall scores were compared pairwise. For the lesions detection rate, the five reconstructions in patients who underwent subsequent contrast-enhanced magnetic resonance imaging (MRI) examinations were compared. RESULTS: For objective parameters, DL-H exhibited superior image quality of lower noise and higher SNR than AV-30 and AV-70 (all P <  0.05). CNR was not statistically different between AV-70, DL-M, and DL-H (all P >  0.05). In both objective and subjective parameters, only image noise was statistically reduced as the strength of DLIR increased compared with ASIR-V (all P <  0.05). Regarding the lesions detection rate, a total of 45 lesions were detected by MRI examination and all five reconstructions exhibited similar lesion-detection rate (25/45, 55.6%). CONCLUSION: Compared with AV-30 and AV 70, DLIR leads to better image quality with equal lesion detection rate for liver CT imaging under routine dose.

10.
Eur J Pharmacol ; 911: 174509, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34547245

RESUMO

Vascular events can trigger a pathological phenotypic switch in vascular smooth muscle cells (VSMCs), decreasing and disrupting the plasticity and diversity of vascular networks. The development of novel therapeutic approaches is necessary to prevent these changes. We aimed to investigate the effects and associated mechanisms of low-intensity pulsed ultrasound (LIPUS) irradiation on the angiotensin II (AngII)-induced phenotypic switch in VSMCs. In vivo, AngII was infused subcutaneously for 4 weeks to stimulate vascular remodeling in mice, and LIPUS irradiation was applied for 20 min every 2 days for 4 weeks. In vitro, cultured rat aortic VSMCs (RAVSMCs) were pretreated once with LIPUS irradiation for 20 min before 48-h AngII stimulation. Our results showed that LIPUS irradiation prevents AngII-induced vascular remodeling of the whole wall artery without discriminating between adventitia and media in vivo and RAVSMC phenotypic switching in vitro. LIPUS irradiation downregulated miR-17-5p expression and upregulated peroxisome proliferator-activated receptor gamma (PPAR-γ) expression. The PPAR-γ activator rosiglitazone could mimic the favorable effects of LIPUS irradiation on AngII-treated RAVSMCs. In contrast, GW9662 could impede the LIPUS-mediated downregulation of RAVSMC proliferation and inflammation under AngII stimulation conditions in vivo and in vitro. Also, the miR-17-5p agomir has the same effects as GW9662 in vitro. Besides, the inhibitory effects of GW9662 against the anti-remodeling effects of LIPUS irradiation in AngII-induced RAVSMCs could be blocked by pretreatment with the miR-17-5p antagomir. Overall, LIPUS irradiation prevents AngII-induced RAVSMCs phenotypic switching through hampering miR-17-5p and enhancing PPAR-γ, suggesting a new approach for the treatment of vascular disorders.

11.
Microsc Res Tech ; 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488243

RESUMO

STimulated Emission Depletion (STED) microscopy attains super-resolution in biological imaging beyond the diffraction limit. Here, we give a concise protocol to construct a dual-pulse STED setup with one super-continuum laser. Moreover, a flexible and dismountable Bessel modulation module is introduced for potential 2D-stack STED imaging. Experiments and notices are introduced in detail, with discussion on some important check-points for STED, such as detector saturation. Finally, the results validate the system working.

12.
Clin Exp Pharmacol Physiol ; 48(11): 1500-1514, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34343366

RESUMO

Hypoxia-induced cardiac fibrosis is an important pathological process in cardiovascular disorders. This study aimed to determine whether low-intensity pulsed ultrasound (LIPUS), a novel and safe apparatus, could alleviate hypoxia-induced cardiac fibrosis, and to elucidate the underlying mechanisms. Hypoxia (1% O2 ) and transverse aortic constriction (TAC) were performed on neonatal rat cardiac fibroblasts and mice to induce cardiac fibrosis, respectively. LIPUS irradiation was applied for 20 minutes every 6 hours for a total of 2 times in vitro, and every 2 days from 1 week before surgery to 4 weeks after surgery in vivo. We found that LIPUS dose-dependently attenuated hypoxia-induced cardiac fibroblast phenotypic conversion in vitro, and ameliorated TAC-induced cardiac fibrosis in vivo. Hypoxia significantly upregulated the nuclear protein expression of hypoxia-inducible factor-1α (HIF-1α) and DNA methyltransferase 3a (DNMT3a). LIPUS pre-treatment reversed the elevated expression of HIF-1α, and DNMT3a. Further experiments revealed that HIF-1α stabilizer dimethyloxalylglycine (DMOG) hindered the anti-fibrotic effect of LIPUS, and hampered LIPUS-mediated downregulation of DNMT3a. DNMT3a small interfering RNA (siRNA) prevented hypoxia-induced cardiac fibrosis. Results also showed that the mechanosensitive protein-TWIK-related arachidonic acid-activated K+ channel (TRAAK) messenger RNA (mRNA) expression was downregulated in hypoxia-induced cardiac fibroblasts, and TAC-induced hearts. TRAAK siRNA impeded LIPUS-mediated anti-fibrotic effect and downregulation of HIF-1α and DNMT3a. Above results indicated that LIPUS could prevent prolonged hypoxia-induced cardiac fibrosis through TRAAK-mediated HIF-1α/DNMT3a signalling pathway.

13.
Phytochemistry ; 191: 112902, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34384921

RESUMO

Thirteen undescribed diterpenoid quinones were isolated from the dried roots of Salvia miltiorrhiza. Their structures were determined by extensive analysis, including NMR, HRESIMS, and IR. Their absolute configurations were determined by X-ray diffraction, calculated and experimental circular dichroism spectroscopy, and optical rotation. In the evaluation of bioactivities, salviadionether obviously inhibited the proliferation of HCT-116 cells. R-(+)-salmiltiorin E and R-(+)-grandifolia D both showed inhibitory activities on a variety of tumor cells. Salvianone ester A showed strong cytotoxicity to tumor-repopulating cells (TRCs) with an IC50 value of 2.19 µM.


Assuntos
Diterpenos , Salvia miltiorrhiza , Salvia , Diterpenos/farmacologia , Estrutura Molecular , Raízes de Plantas , Quinonas/farmacologia , Rizoma
14.
Brain Behav ; 11(8): e2312, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34333853

RESUMO

OBJECTIVES: To investigate the genetic and clinical features of Chinese sporadic amyotrophic lateral sclerosis (SALS) patients with TARDBP mutations, we carried out a genetic analysis in a cohort of 391 SALS patients and explored the clinical manifestations of patients with TARDBP variants. MATERIALS AND METHODS: The coding region of all five coding exons of TARDBP, exons 2-6, were sequenced for mutations in 391 Chinese SALS patients. The clinical features of patients with TARDBP mutations were described and compared with cases in literatures. RESULTS: Two missense mutations in TARDBP gene, c.1132A > G (p.N378D) and c.1147A > G (p.I383V), were detected in three cases, showing a low frequency (0.77%, 3/391) of TARDBP missense mutations in Chinese SALS patients. Based on a retrospective analysis of literatures, p.N378D mutation mainly presents a phenotype of early onset, whereas p.I383V mutation presents pure ALS or ALS alongside semantic variant primary progressive aphasia (svPPA), a type of frontotemporal dementia (FTD). CONCLUSIONS: Our results demonstrate that TARDBP mutation is a rare cause of Chinese SALS patients and expand the spectrum of phenotype. It is implied that genetic analysis of SALS patients plays a crucial role in uncovering the cause of disease, especially for cases developing early onset or alongside FTD.


Assuntos
Esclerose Amiotrófica Lateral , Proteínas de Ligação a DNA/genética , Esclerose Amiotrófica Lateral/genética , China , Humanos , Mutação , Estudos Retrospectivos
15.
Int J Hyperthermia ; 38(1): 1263-1270, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34404325

RESUMO

PURPOSE: To investigate the effects of ablation time and distance between the radiofrequency ablation (RFA) electrode tip and a large vessel on the ablation zone in beagle livers. METHODS: Sixty-one percutaneous RFA coagulation zones were created near large vessels in 10 beagle livers in vivo. The ablated lesions were divided into four groups based on ablation time and distance between the electrode tip and a large vessel (group A, 3 min 0.5 cm; group B, 3 min 0 cm; group C, 5 min 0.5 cm; group D, 5 min 0 cm). The ablated area, long-axis diameters, short-axis diameters, and vessel wall injury were examined. RESULTS: With a fixed ablation time, the ablation zone created with the electrode tip at 0.5 cm from the large vessel was significantly larger than at 0 cm (p < .05). At a fixed distance between the electrode tip and vessel, the ablation zone created for 5 min was significantly larger than for 3 min (p < .05). The frequency of vessel wall injury in the 0 cm groups was significantly higher than that in the 0.5 cm groups (37.5% vs. 6.9%; p = .003, odds ratio, 7.43). The ratio of width to depth (Dw/Dz) was larger in the 0.5 cm groups than in the 0 cm groups (p < .001). CONCLUSION: The ablation zone increased with longer ablation times and greater distances between the RFA tip and large vessels for perivascular lesions. The distance between the needle tip and blood vessels is an important factor that affects the overall ablation outcome.


Assuntos
Ablação por Cateter , Ablação por Radiofrequência , Animais , Cães , Eletrodos , Fígado/cirurgia , Agulhas
16.
J Colloid Interface Sci ; 605: 863-870, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34371429

RESUMO

HYPOTHESIS: We hypothesize that curved surfaces, including cylindrical surfaces, which go beyond prior experiments using flat surfaces, can significantly influence and alter the phase behavior and self-assembly of dense two-dimensional systems of Brownian colloids. EXPERIMENTS: Here, we report a first experimental study regarding the self-assembly of Brownian square platelets with an edge length L = 2.3 µm on cylindrical surfaces having different curvatures; these platelets are subjected to a depletion attraction in order to form a monolayer above the cylindrical surface, yet have nearly hard interactions within the monolayer. Simulations are also performed to confirm and explain the experimental observations. FINDINGS: Phase diagrams as a function of curvature are determined experimentally. Interestingly, hexagonal rotator crystal structures are observed for tubes having radii > 10.9L, but a tetratic phase is seen instead for the 10.9L tube at the corresponding platelet area fractions. We show that this transition is caused by the curvature-induced orientation-dependence of the depletion attraction between the squares and the underlying cylindrical surface. Brownian dynamics simulation results confirm the experimental observations and also illustrate helical structures formed by squares packing on cylinders. Our results demonstrate a way towards control over the self-assembly of anisotropic particles through curvature and depletion-attraction-induced orientational confinement.

17.
Dermatology ; : 1-11, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34455413

RESUMO

BACKGROUND: Current therapeutic options for atopic dermatitis (AD) are limited. Janus kinase (JAK) inhibitors may be viable alternatives. OBJECTIVES: To assess the efficacy and safety of JAK inhibitors for AD treatment. METHODS: We searched PubMed, Embase, the Cochrane Controlled Register of Trials, Web of Science, Global Resource of Eczema Trials database, and ClinicalTrials.gov from inception to September 1, 2020. Randomized clinical trials (RCTs) comparing JAK inhibitors with placebo/vehicle treatment for AD patients were included. The primary study outcomes included (1) the change (%) from the Eczema Area and Severity Index (EASI) baseline expressed as weighted mean difference (WMD) and 95% confidence interval (95% CI), and (2) the Investigator's Global Assessment (IGA) response and safety outcomes expressed as relative risk (RR) and 95% CI. RESULTS: We included 14 RCTs published in 13 studies (3,822 patients). Treatment with JAK inhibitors significantly improved IGA response (RR 2.83, 95% CI 2.25-3.56, p < 0.001) and EASI score (WMD -28.82, 95% CI -34.48 to -23.16, p < 0.001). JAK inhibitor treatment achieved the largest improvement in both IGA response (RR 3.59, 95% CI 2.66-4.84, p < 0.001) and EASI score (WMD -42.00, 95% CI -48.64 to -35.36, p < 0.001) by week 4 of treatment. Topical JAK inhibitors were significantly more efficacious than oral inhibitors. Upadacitinib treatment for 4 weeks was most effective in reducing EASI score (WMD -53.92, 95% CI -69.26 to -38.58, p < 0.001), while abrocitinib for 4 weeks led to the most effective IGA response (RR 5.47, 95% CI 2.74-10.93, p < 0.001). There was no difference in the frequency of adverse events (AEs) leading to discontinuation; however, JAK inhibitors use, especially abrocitinib, led to a higher incidence of treatment-emergent AEs (RR 1.25, 95% CI 1.10-1.42, p = 0.001). CONCLUSION: Our results imply that JAK inhibitors are an effective and safe AD treatment. Nevertheless, further trials with longer duration and head-to-head comparisons of different JAK inhibitors are needed.

18.
Elife ; 102021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34212857

RESUMO

Mannose-sensitive hemagglutinin (MSHA) pili and flagellum are critical for the surface attachment of Vibrio cholerae, the first step of V. cholerae colonization on host surfaces. However, the cell landing mechanism remains largely unknown, particularly in viscoelastic environments such as the mucus layers of intestines. Here, combining the cysteine-substitution-based labeling method with single-cell tracking techniques, we quantitatively characterized the landing of V. cholerae by directly observing both pili and flagellum of cells in a viscoelastic non-Newtonian solution consisting of 2% Luria-Bertani and 1% methylcellulose (LB+MC). The results show that MSHA pili are evenly distributed along the cell length and can stick to surfaces at any point along the filament. With such properties, MSHA pili are observed to act as a brake and anchor during cell landing which includes three phases: running, lingering, and attaching. Importantly, loss of MSHA pili results in a more dramatic increase in mean path length in LB+MC than in 2% LB only or in 20% Ficoll solutions, indicating that the role of MSHA pili during cell landing is more apparent in viscoelastic non-Newtonian fluids than viscous Newtonian ones. Our work provides a detailed picture of the landing dynamics of V. cholerae under viscoelastic conditions, which can provide insights into ways to better control V. cholerae infections in a real mucus-like environment.

19.
Clin Ther ; 2021 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-34315608

RESUMO

PURPOSE: Osteoarthritis (OA) is a chronic and degenerative disorder associated with joint pain and loss of joint function. It is reported that polyphenols could yield articular benefits in patients with OA through the inhabitation of key inflammatory pathways. This meta-analysis was conducted to assess the efficacy and safety of polyphenol products for OA treatment. METHODS: This study included searches of PubMed, EMBASE, and the Cochrane Library databases from inception to November 6, 2019. Randomized controlled trials (RCTs) comparing polyphenols versus NSAIDs or placebo for human OA were included. Standardized mean differences (SMD) or risk ratios (RRs) were calculated for all relevant outcomes. Meta-analyses were conducted by using random effect models, and heterogeneity was assessed by using the I2 statistic. FINDINGS: A total of 18 RCTs (N = 1724) were eligible for analysis. Polyphenol products showed a significant advantage over placebo on pain relief (SMD, -1.11; 95% CI, -1.35 to -0.87) and functional improvement (SMD, -1.14; 95% CI, -1.38 to -0.90). No differences in safety outcomes were detected between polyphenols and placebo. There were no differences in efficacy outcomes between polyphenols and NSAIDs, although patients receiving polyphenols had a lower but nonsignificant risk of experiencing gastrointestinal dysfunction compared with those treated with NSAIDs. Polyphenols and NSAIDs in combination yielded more significant benefits in efficacy than NSAIDs alone. IMPLICATIONS: The results of our study suggest that polyphenols may be a promising alternative for OA by relieving symptoms while reducing safety risks. However, the generalizability of our results may be limited by the quality and sample size of the available research, as well as the heterogeneity between RCTs. High-quality clinical trials are needed to make meaningful clinical practice recommendations.

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