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1.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 53(3): 404-408, 2022 May.
Artigo em Chinês | MEDLINE | ID: mdl-35642146

RESUMO

Objective: To summarize the clinical characteristics and treatment experience of gastric primary lymphoma with acute upper gastrointestinal bleeding as the primary manifestation, and to provide support for clinical treatment. Methods: Information on gastric primary lymphoma patients admitted to the Department of Gastroenterology, West China Hospital of Sichuan University between January 2010 and March 2021 for acute upper gastrointestinal bleeding was retrospectively collected. Data on endoscopic morphology, tumor staging, pathology typing, severity of bleeding, risks of rebleeding, treatment and inhospital prognosis were documented and analyzed. Results: A total of 25 patients with a mean age of 57.2 years were included in the study, all of whom presented clinically with melena (100%), 9 (36%) had hematemesis, and 6 (24%) was accompanied with abdominal pain. Twenty, or 80%, of the gastric lymphoma patients with bleeding as the primary manifestation showed endoscopically a tumor-forming phenotype (Yao Classification), mostly involving the middle and lower parts of the gastric body (44% and 32%, respectively). After conservative treatment with medication, rebleeding occurred in 4 patients during hospitalization. One of them required endoscopic hemostasis, two required surgical resection to stop the bleeding, and one decided not to undergo any further treatment. Only one patient died from infection and no death resulted directly from severe bleeding. Conclusion: Gastric primary lymphoma presenting acute upper gastrointestinal bleeding as the sole clinical manifestation rarely occurs, but when the condition does occur, it shows a wide range of endoscopic involvement. It has a higher risk of rebleeding, and endoscopic or surgical treatment may be attempted when conservative medication treatment for acute upper gastrointestinal bleeding fails.


Assuntos
Linfoma não Hodgkin , Neoplasias Gástricas , Doença Aguda , Hemorragia Gastrointestinal/complicações , Hemorragia Gastrointestinal/terapia , Humanos , Linfoma não Hodgkin/complicações , Estudos Retrospectivos , Neoplasias Gástricas/complicações , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia
2.
Front Pharmacol ; 13: 819826, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35645824

RESUMO

Ilex rotunda Thunb (IR) is a traditional Chinese medicine used for the clinical treatment of gastric ulcers and duodenal ulcers; however, the effect of IR on ulcerative colitis (UC) and its underlying mechanism remains unclear. This study investigated the therapeutic effect of IR on UC mice induced by dextran sulfate sodium (DSS) as well as the potential underlying mechanism. The main components of IR were analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Then we established a model of UC mice by administering 2.0% DSS for 7 days followed by 2 weeks of tap water for three cycles and administered IR. On day 56, the disease activity index (DAI), colon length, pathological changes, and inflammatory response of the colon tissue of mice were assessed. The oxidative stress and apoptosis of colon tissue were detected, and the integrity of the intestinal mucosal barrier was evaluated to assess the effect of IR. Furthermore, the relationship between oncostatin M (OSM) and its receptor (OSMR) in addition to the IR treatment of UC were evaluated using a mouse model and Caco2 cell model. The results showed that IR significantly alleviated the symptoms of UC including rescuing the shortened colon length; reducing DAI scores, serum myeloperoxidase and lipopolysaccharide levels, pathological damage, inflammatory cell infiltration and mRNA levels of interleukin one beta, tumor necrosis factor alpha, and interleukin six in colon tissue; alleviating oxidative stress and apoptosis by decreasing kelch-like ECH-associated protein 1 expression and increasing nuclear factor-erythroid factor 2-related factor 2 and heme oxygenase-1 protein expression; and promoting the regeneration of epithelial cells. IR also promoted the restoration of the intestinal mucosal barrier and modulated the OSM/OSMR pathway to alleviate UC. It was found that IR exerted therapeutic effects on UC by restoring the intestinal mucosal barrier and regulating the OSM/OSMR pathway.

3.
Front Cell Dev Biol ; 10: 833579, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35646922

RESUMO

Objective: Accumulating literatures suggested that long non-coding RNAs (lncRNAs) were involved in tumorigenesis and cancer progression in lung adenocarcinoma (LUAD). However, the precise regulatory mechanism of lncRNA Lung cancer-associated transcript 1 (LUCAT1) in LUAD is not well defined. In this study, we aimed to investigate the biological function and mechanism of lncRNA LUCAT1 in regulating tumor migration and glycolysis of LUAD. Methods: High throughput sequencing was performed to identify differentially expressed lncRNAs between LUAD patients and healthy controls. The expression levels of LUCAT1 in LUAD clinical specimens or cell lines were evaluated by In situ hybridization (ISH) and quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Functional experiments, including wound-healing, transwell invasion assays, glucose absorption, lactate metabolism and tumor xenograft experiments were conducted to identify the biological functions of LUCAT1 in LUAD. Silencing of LUCAT1, over-expression of LUCAT1 and miR-4316 were generated in LUAD cell lines to verify the regulatory mode of LUCAT1-mir-4316-VEGFA axis. Results: Our findings revealed that lncRNA LUCAT1 was significantly up-regulated in LUAD serum exosomes, tumor tissues, and LUAD cells in comparison with corresponding controls. Receiver operating characteristic curve (ROC) analysis indicated that the area under the curve (AUC) value of serum exosomal LUCAT1 reached 0.852 in distinguishing LUAD patients from healthy individuals. High expression of LUCAT1 in LUAD patient tissues was associated with enhanced Lymph Node Metastasis (LNM), advanced Tumor Node Metastasis (TNM) stage and poorer clinical outcome in LUAD patients. Knockdown of LUCAT1 inhibited LUAD cell metastasis and glycolysis in vitro as well as tumor metastasis in vivo, while overexpression of LUCAT1 induced a promoted LUAD metastasis and glycolysis. Furthermore, mechanistic investigations revealed that LUCAT1 elevated LUAD cell metastasis and glycolysis by sponging miR-4316, which further led to the upregulation of VEGFA. Finally, the regulatory axis LUCAT1-miR-4316-VEGFA was verified in LUAD. Conclusion: Our present research suggested that LUCAT1 facilitate LUAD cell metastasis and glycolysis via serving as a competing endogenous RNA to regulate miR-4316/VEGFA axis, which provided a novel diagnostic marker and therapeutic target for LUAD patients.

4.
Molecules ; 27(11)2022 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-35684541

RESUMO

Traditional Chinese Medicine is generally used as a decoction to guard health. Many active ingredients in the decoction are chemical ingredients that are not usually paid attention to in phytochemical research, such as polysaccharides, etc. Based on research interest in Chinese herbal decoction, crude polysaccharides from G. wilfordii (GCP) were purified to obtain two relatively homogeneous polysaccharides, a neutral polysaccharide (GNP), and an acid polysaccharide (GAP) by various chromatographic separation methods, which were initially characterized by GC-MS, NMR, IR, and methylation analysis. Studies on the hepatoprotective activity of GCP in vivo showed that GCP might be a potential agent for the prevention and treatment of acute liver injury by inhibiting the secretion levels of ALT, AST, IL-6, IL-1ß, TNF-α, and MDA expression levels, increasing SOD, and the GSH-Px activity value. Further, in vitro assays, GNP and GAP, decrease the inflammatory response by inhibiting the secretion of IL-6 and TNF-α, involved in the STAT1/T-bet signaling pathway.


Assuntos
Geranium , Polissacarídeos , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Geranium/química , Humanos , Interleucina-6/metabolismo , Fígado/metabolismo , Polissacarídeos/química , Polissacarídeos/farmacologia , Fator de Necrose Tumoral alfa/metabolismo
5.
Adv Parasitol ; 116: 187-209, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35752448

RESUMO

Though traditional medicines have been developed through practice for thousands of years, limited research has discussed the research and development (R&D) pattern of traditional medicines. China's discovery of artemisinin accumulated valuable experiences to explore traditional medicine under low-resource settings. With limited R&D resources, China mobilized all domestic research units at different levels and departments to develop artemisinin collaboratively. The discovery of artemisinin not only based on valuable experiential wisdom of traditional medicine, but also relied on excellent synergy among all units. In this study, we reviewed the story of how artemisinin was discovered in China, summarized key factors for new drug development from traditional medicines under limited resources, and raised suggestions to utilize traditional medicines in low- and middle-income countries. This case suggested that the vitality of traditional medicine could be extended by promoting new drug development based on modern methods and collaboration.


Assuntos
Artemisininas , Países em Desenvolvimento , China , Medicina Tradicional , Pesquisa
6.
Sci Rep ; 12(1): 9914, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35705619

RESUMO

Mutations in the FERM domain containing 7 (FRMD7) gene have been proven to be responsible for infantile nystagmus (IN). The purpose of this study is to investigate FRMD7 gene mutations in patients with IN, and to evaluate the nystagmus intensity among patients with and without FRMD7 mutations. The affected males were subdivided into three groups according to whether or not having FRMD7 mutations and the types of mutations. Fifty-two mutations were detected in FRMD7 in 56 pedigrees and 34 sporadic patients with IN, including 28 novel and 24 previous reported mutations. The novel identified mutations further expand the spectrum of FRMD7 mutations. The parameters of nystagmus intensity and the patients' best corrected visual acuity were not statistically different among the patients with and without identified FRMD7 mutations, and also not different among patients with different mutant types. The FERM-C domain, whose amino acids are encoded by exons 7, 8 and 9, could be the harbor region for most mutations. Loss-of-function is suggested to be the common molecular mechanism for the X-linked infantile nystagmus.


Assuntos
Proteínas do Citoesqueleto , Doenças Genéticas Ligadas ao Cromossomo X , Proteínas de Membrana , Nistagmo Congênito , Proteínas do Citoesqueleto/genética , Análise Mutacional de DNA , Doenças Genéticas Ligadas ao Cromossomo X/genética , Humanos , Masculino , Proteínas de Membrana/genética , Mutação , Nistagmo Congênito/genética , Linhagem
8.
Int J Mol Sci ; 23(12)2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35742851

RESUMO

Biomimetic microenvironments are important for controlling stem cell functions. In this study, different microenvironmental conditions were investigated for the stepwise control of proliferation and chondrogenic differentiation of human bone-marrow-derived mesenchymal stem cells (hMSCs). The hMSCs were first cultured in collagen porous sponges and then embedded with or without collagen hydrogels for continual culture under different culture conditions. The different influences of collagen sponges, collagen hydrogels, and induction factors were investigated. The collagen sponges were beneficial for cell proliferation. The collagen sponges also promoted chondrogenic differentiation during culture in chondrogenic medium, which was superior to the effect of collagen sponges embedded with hydrogels without loading of induction factors. However, collagen sponges embedded with collagen hydrogels and loaded with induction factors had the same level of promotive effect on chondrogenic differentiation as collagen sponges during in vitro culture in chondrogenic medium and showed the highest promotive effect during in vivo subcutaneous implantation. The combination of collagen sponges with collagen hydrogels and induction factors could provide a platform for cell proliferation at an early stage and subsequent chondrogenic differentiation at a late stage. The results provide useful information for the chondrogenic differentiation of stem cells and cartilage tissue engineering.


Assuntos
Condrogênese , Células-Tronco Mesenquimais , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Colágeno/farmacologia , Humanos , Hidrogéis/farmacologia
9.
Ying Yong Sheng Tai Xue Bao ; 33(6): 1563-1571, 2022 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-35729134

RESUMO

The chamber method is widely used to measure CO2 and CH4 flux in inland water. However, the designs of chamber used in various studies are different and lack unified standards, which would affect the observation results. To clarify the impacts of chamber characteristics, including light transmittance, air pressure difference inside and outside the chamber, and gas mixing degree in the chamber, on CO2 and CH4 flux measurements at the water-air interface, we compared the effects of transparent/opaque chamber, the chamber with/without air pressure equalizing device and fan on CO2 and CH4 flux measurements in the aquaculture pond, based on the multi-channel closed dynamic chamber system. The results showed that, during the daytime in summer, compared with the transparent chamber which could measure the actual CO2 flux, when CO2 was emitted from the pond, the opaque chamber overestimated the CO2 flux by 90%; when CO2 was absorbed by the pond, the opaque chamber underestimated the CO2 flux by 50%. The CH4 diffusion flux measured by the opaque chamber was 40% lower than that measured by the transparent chamber. There was no significant difference between CO2 and CH4 flux measured by the chamber with and without air pressure equalizing device. CO2 flux observed by the chamber without fan had poor representativeness, being 20% higher than that observed by the chamber with fan. Moreover, CH4 flux emitted through different pathways could not be distinguished using the chamber without fan. Therefore, when the chamber method was used to observe the CO2 and CH4 flux at the water-air interface, the chamber shall be transparent and be installed with fan.


Assuntos
Dióxido de Carbono , Metano , Aquicultura , Óxido Nitroso , Estações do Ano , Água
10.
Zhongguo Zhong Yao Za Zhi ; 47(10): 2802-2810, 2022 May.
Artigo em Chinês | MEDLINE | ID: mdl-35718500

RESUMO

To expeditiously assess the efficacy and safety of Binghuang Fule Ointment in the treatment of eczema, we screened out the papers with randomized controlled trials(RCTs) for studying the efficacy of Binghuang Fule Ointment in the treatment of eczema from CNKI, VIP, Wanfang, SinoMed, PubMed, Web of Science, Cochrane Library, and EMbase and then performed Meta-analysis of the included studies via RevMan 5.4. A total of 19 studies were included, involving 1 919 cases(973 cases in the experimental group and 946 cases in the control group). Meta-analysis results showed that Binghuang Fule Ointment combined with conventional western medicine had better efficacy score index(clinical effectiveness ≥60%)(RR=1.32, 95%CI[1.13, 1.55], P=0.000 4) and lower recurrence rate(RR=0.37, 95%CI[0.20, 0.65], P=0.000 7) than conventional western medicine alone. The adverse reactions(RR=1.05, 95%CI[0.52, 2.15], P=0.88) did not show significant difference between the two groups. The application of Binghuang Fule Ointment alone had better efficacy score index(clinical effectiveness≥60%)(RR=1.20, 95%CI[1.09, 1.33], P=0.000 3) than conventional western medicine alone and the adverse reactions(RR=0.92, 95%CI[0.45, 1.89], P=0.82) insignificantly different from conventional western medicine alone. Binghuang Fule Ointment alone or combined with conventional western medicine demonstrated better effective in remission of symptoms and signs(clinical effectiveness)(RR=1.41, 95%CI[1.07, 1.85], P=0.01) than conventional western medicine alone. Compared with the single application of western medicine, Binghuang Fule Ointment alone or combined with conventional western medicine has better curative effect, low recurrence rate, and equivalent safety in the treatment of eczema. Nevertheless, owing to the low quality of the included papers, randomized controlled trials with large sample size, multiple centers, high methodological quality are needed to further verify the efficacy and safety of Binghuang Fule Ointment in the treatment of eczema.


Assuntos
Medicamentos de Ervas Chinesas , Eczema , Medicamentos de Ervas Chinesas/efeitos adversos , Eczema/tratamento farmacológico , Humanos , Pomadas , Resultado do Tratamento
11.
Zhongguo Zhong Yao Za Zhi ; 47(11): 3111-3117, 2022 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-35718536

RESUMO

In this study, TreeAge Pro was used to build a decision tree model for Qilong Capsules in the treatment of ischemic stroke. We compared the economy between Qilong Capsules + conventional therapy vs conventional therapy in the treatment of ischemic stroke to guide the rational allocation of health resources in clinical practice. The cost parameters in the study were obtained from Menet and the relevant literature published recently. Meanwhile, the efficacy parameter [mean reduction in National Institute of Health stroke scale(NIHSS) score after treatment] was employed to evaluate the short-term economic performance of the two therapies based on a prospective real-world cohort study. The time span of simulation was 24 weeks, and the robustness of this study was verified by sensitivity analysis. Qilong Capsules + conventional therapy and conventional therapy had the direct medical costs of CNY 22 546.50, 21 160.50 and the effectiveness of 2.08, 1.59 points, respectively. The incremental cost-effectiveness ratio(ICER) of the two groups was CNY 2 811.36. That is, compared with conventional therapy, Qilong Capsules + conventional therapy in the treatment of ischemic stroke costed CNY 2 811.36 for each additional point reduction in NIHSS score. If the patient is willing to pay more than CNY 2 811.36, Qilong Capsules + conventional therapy is more economical. The result of sensitivity analysis verified that the ICER was robust. Thus, on the basis of the assumption that per capita disposable income in 2020 is the threshold of patients' willingness to pay, Qilong Capsules + conventional therapy is more economical than conventional therapy alone in the treatment of ischemic stroke.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Cápsulas , Estudos de Coortes , Análise Custo-Benefício , Humanos , AVC Isquêmico/tratamento farmacológico , Estudos Prospectivos , Anos de Vida Ajustados por Qualidade de Vida , Acidente Vascular Cerebral/tratamento farmacológico
13.
Front Genet ; 13: 879974, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35692832

RESUMO

Ovarian reserve (OR) is mainly determined by the number of primordial follicles in the ovary and continuously depleted until ovarian senescence. With the development of assisted reproductive technology such as ovarian tissue cryopreservation and autotransplantation, growing demand has arisen for objective assessment of OR at the histological level. However, no specific biomarkers of OR can be used effectively in clinic nowadays. Herein, bulk RNA-seq datasets of the murine ovary with the biological ovarian age (BOA) dynamic changes and single-cell RNA-seq datasets of follicles at different stages of folliculogenesis were obtained from the GEO database to identify gene signature correlated to the primordial follicle pool. The correlations between gene signature expression and OR were also validated in several comparative OR models. The results showed that genes including Lhx8, Nobox, Sohlh1, Tbpl2, Stk31, and Padi6 were highly correlated to the OR of the primordial follicle pool, suggesting that these genes might be used as biomarkers for predicting OR at the histological level.

14.
Waste Manag ; 149: 239-247, 2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35752111

RESUMO

Steam gasification of spirit-based distillers' grains (SDGs) was performed in a fixed-bed reactor under different microwave pretreatment (MWP) approaches with or without addition of red mud (RM). The effects of MWP on the gasification rate, total gas yield, H2/CO, and gasification mechanism of action were investigated. The results showed that RM could enhance the effect of MWP. The gasification rate, total gas yield and H2/CO increased by 21.29%, 8.23% and 16.08%, respectively. In addition, RM and MWP had a synergistic effect on the catalytic gasification reaction. This was because MWP disrupted the complete ordered surface structure of the SDGs, allowing a large number of inherent alkali and alkaline earth metal ions to dissolve onto the surface and combine with the catalytically active material in RM to form a uniformly dispersed bimetallic catalyst. The catalytic mechanism consisted of an active-site catalytic mechanism and a bimetallic synergistic catalytic mechanism. Therefore, the combination of MWP and SDGs steam gasification is a promising, clean, efficient hydrogen-rich synthesis gas technology.

15.
Korean J Radiol ; 2022 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-35695316

RESUMO

OBJECTIVE: To develop a model incorporating radiomic features and clinical factors to accurately predict acute ischemic stroke (AIS) outcomes. MATERIALS AND METHODS: Data from 522 AIS patients (382 male [73.2%]; mean age ± standard deviation, 58.9 ± 11.5 years) were randomly divided into the training (n = 311) and validation cohorts (n = 211). According to the modified Rankin Scale (mRS) at 6 months after hospital discharge, prognosis was dichotomized into good (mRS ≤ 2) and poor (mRS > 2); 1310 radiomics features were extracted from diffusion-weighted imaging and apparent diffusion coefficient maps. The minimum redundancy maximum relevance algorithm and the least absolute shrinkage and selection operator logistic regression method were implemented to select the features and establish a radiomics model. Univariable and multivariable logistic regression analyses were performed to identify the clinical factors and construct a clinical model. Ultimately, a multivariable logistic regression analysis incorporating independent clinical factors and radiomics score was implemented to establish the final combined prediction model using a backward step-down selection procedure, and a clinical-radiomics nomogram was developed. The models were evaluated using calibration, receiver operating characteristic (ROC), and decision curve analyses. RESULTS: Age, sex, stroke history, diabetes, baseline mRS, baseline National Institutes of Health Stroke Scale score, and radiomics score were independent predictors of AIS outcomes. The area under the ROC curve of the clinical-radiomics model was 0.868 (95% confidence interval, 0.825-0.910) in the training cohort and 0.890 (0.844-0.936) in the validation cohort, which was significantly larger than that of the clinical or radiomics models. The clinical radiomics nomogram was well calibrated (p > 0.05). The decision curve analysis indicated its clinical usefulness. CONCLUSION: The clinical-radiomics model outperformed individual clinical or radiomics models and achieved satisfactory performance in predicting AIS outcomes.

16.
Sci Rep ; 12(1): 7298, 2022 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-35508582

RESUMO

Recipients of solid organ transplantation (SOT) rely on life-long immunosuppression (IS), which is associated with significant side effects. Extracorporeal photochemotherapy (ECP) is a safe, existing cellular therapy used to treat transplant rejection by modulating the recipient's own blood cells. We sought to induce donor-specific hypo-responsiveness of SOT recipients by infusing ECP-treated donor leukocytes prior to transplant. To this end, we utilized major histocompatibility complex mismatched rodent models of allogeneic cardiac, liver, and kidney transplantation to test this novel strategy. Leukocytes isolated from donor-matched spleens for ECP treatment (ECP-DL) were infused into transplant recipients seven days prior to SOT. Pre-transplant infusion of ECP-DL without additional IS was associated with prolonged graft survival in all models. This innovative approach promoted the production of tolerogenic dendritic cells and regulatory T-cells with subsequent inhibition of T-cell priming and differentiation, along with a significant reduction of donor-specific T-cells in the spleen and grafts of treated animals. This new application of donor-type ECP-treated leukocytes provides insight into the mechanisms behind ECP-induced immunoregulation and holds significant promise in the prevention of graft rejection and reduction in need of global immune suppressive therapy in patients following SOT.


Assuntos
Fotoferese , Aloenxertos , Animais , Modelos Animais de Doenças , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Humanos , Camundongos , Linfócitos T Reguladores , Transplante Homólogo
17.
J Colloid Interface Sci ; 622: 135-146, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35490617

RESUMO

The nanostructured antimicrobial agents, self-assembled by the antimicrobial peptides (AMPs), represent an intriguing platform for the treatment of pathogens. Although the structural characteristics significantly influence antimicrobial functionality, the role of chirality is usually ignored and still unclear. Herein, two homochiral AMPs (all L- or all D-amino acids), including C16-LV4LR4 (LL) and C16-DV4DR4 (DD), and a heterochiral AMP with alternating D-/L-amino acids, C16-DV4LR4 (DL), were self-assembled into left-handed, right-handed, and right-handed helical nanofibers, respectively. The valine configuration determined the supramolecular chirality of the nanofibers. However, the DL molecules exhibited a highly aggregated propensity to form more stable helical nanofibers with a lower degree of twist and a larger helical pitch. This characteristic resulted in the optimal antimicrobial activity of the DL nanofibers against both Gram-negative and Gram-positive bacteria. Furthermore, the membrane permeability assay confirmed the higher activity for damaging the cell membrane by the DL nanofibers. These results demonstrated the significance of molecular chirality in directing the self-assembly of the amphiphilic peptides, eventually affecting their antimicrobial activity. This study opens up the possibility to fabricate promising nanostructured antimicrobial materials by controlling the chirality and structure of the materials.


Assuntos
Nanofibras , Nanoestruturas , Aminoácidos/química , Antibacterianos/química , Antibacterianos/farmacologia , Nanofibras/química , Peptídeos/química
18.
Front Immunol ; 13: 880315, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35603194

RESUMO

Mycobacterium tuberculosis (Mtb), as an important intracellular pathogen, can invade and survive in macrophages and is capable of escaping the clearance of immune system. Despite decades of research efforts, the precise mechanism of immune escape and the virulence factors encoded by Mtb involved remain to be explored. Mtb-specific genomic regions of deletion (RD)-encoded proteins and PE/PPE family proteins have been implicated in immune evasion. Here, we screened more than forty RD-encoded proteins which might be involved in facilitating bacterial survival in macrophages, and found that a Mtb PPE68/Rv3873 protein, encoded by Mtb-RD1, is essential for efficient Mtb intracellular survival in macrophages. In terms of mechanism, we found that the ubiquitin ligase (E3) Makorin Ring Finger Protein 1 (MKRN1) of macrophage interacted with PPE68 and promoted the attachment of lysine (K)-63-linked ubiquitin chains to the K166 site of PPE68. K63-ubiquitination of PPE68 further bound src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP1) to suppress K63-linked polyubiquitin chains of tumor necrosis factor receptor-associated factor 6 (TRAF6), and then remarkably suppressed TRAF6-driven NF-κB and AP-1 signaling and TNF-α, IL-6 and NO production. We demonstrate that the K63-linked ubiquitination of PPE68 by MKRN1 contributed to the PPE68-mediated mycobacterial immune escape. Our finding identifies a previously unrecognized mechanism by which host MKRN1-mediated-ubiquitination of mycobacterial PPE protein suppresses innate immune responses. Disturbing the interaction between host MKRN1 ubiquitin system and mycobacterial PPE protein might be a potential therapeutic target for tuberculosis.


Assuntos
Mycobacterium tuberculosis , Proteínas de Bactérias , Imunidade Inata , Fator 6 Associado a Receptor de TNF/genética , Fator 6 Associado a Receptor de TNF/metabolismo , Ubiquitinação , Ubiquitinas/metabolismo
19.
Sci Adv ; 8(21): eabn2031, 2022 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-35613269

RESUMO

High-performance broadband infrared (IR)/terahertz (THz) detection is crucial in many optoelectronic applications. However, the spectral response range of semiconductor-based photodetectors is limited by the bandgaps. This paper proposes a ratchet structure based on the GaAs/AlxGa1-xAs heterojunction, where the quasi-stationary hot hole distribution and intravalence band absorption from light or heavy hole states to the split-off band overcome the bandgap limit, ensuring an ultrabroadband photoresponse from near-IR to THz region (4 to 300 THz). The peak responsivity of the proposed structure can reach 7.3 A/W, which is five orders of magnitude higher than that of the existing broadband photon-type detector. Because of the ratchet effect, the proposed photodetector has a bias-tunable photoresponse characteristic and can operate in the photovoltaic mode with a broad photocurrent spectrum (18 to 300 THz). This work not only demonstrates a broadband photon-type THz/IR photodetector but also provides a method to study the light-responsive ratchet.

20.
Nat Med ; 2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35614233

RESUMO

The post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-also referred to as Long COVID-have been described, but whether breakthrough SARS-CoV-2 infection (BTI) in vaccinated people results in post-acute sequelae is not clear. In this study, we used the US Department of Veterans Affairs national healthcare databases to build a cohort of 33,940 individuals with BTI and several controls of people without evidence of SARS-CoV-2 infection, including contemporary (n = 4,983,491), historical (n = 5,785,273) and vaccinated (n = 2,566,369) controls. At 6 months after infection, we show that, beyond the first 30 days of illness, compared to contemporary controls, people with BTI exhibited a higher risk of death (hazard ratio (HR) = 1.75, 95% confidence interval (CI): 1.59, 1.93) and incident post-acute sequelae (HR = 1.50, 95% CI: 1.46, 1.54), including cardiovascular, coagulation and hematologic, gastrointestinal, kidney, mental health, metabolic, musculoskeletal and neurologic disorders. The results were consistent in comparisons versus the historical and vaccinated controls. Compared to people with SARS-CoV-2 infection who were not previously vaccinated (n = 113,474), people with BTI exhibited lower risks of death (HR = 0.66, 95% CI: 0.58, 0.74) and incident post-acute sequelae (HR = 0.85, 95% CI: 0.82, 0.89). Altogether, the findings suggest that vaccination before infection confers only partial protection in the post-acute phase of the disease; hence, reliance on it as a sole mitigation strategy may not optimally reduce long-term health consequences of SARS-CoV-2 infection. The findings emphasize the need for continued optimization of strategies for primary prevention of BTI and will guide development of post-acute care pathways for people with BTI.

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