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1.
Curr Microbiol ; 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33649996

RESUMO

We analyzed the complete genome of the bacteria Brevibacillus laterosporus Bl-zj. Its genome has a total length of 5,202,546 bp with 4594 annotated genes. The functional groups included transporters, pathogen-host interaction factors, antibiotic resistance genes, virulence factor, and secreted proteins were predicted, and carbon and nitrogen metabolism and transporters were mapped. A total of 34 genes possibly involved in algae-lysing processes were further screened, including 8 virulence factors, 18 secreted proteases, and 8 antibiotic-resistant genes, which could be playing important roles in host identification, invasion, and the destruction of algal cells. This study will provide a theoretical framework for the algicidal mechanism of algae-lysing bacteria and possible application to algal control.

2.
Mol Oncol ; 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33528867

RESUMO

Most cancer-related deaths result from the progressive growth of metastases. Patients with peritoneal metastatic (PM) colorectal cancer have reduced overall survival. Currently, it is still unclear why colorectal cancer (CRC) cells home to and proliferate inside the peritoneal cavity, and there is no effective consolidation therapy for improved survival. Using a proteomic approach, we found that key enzymes of fatty acid oxidation (FAO) were decreased in patients with PM colorectal cancer. Furthermore, we confirmed that carnitine palmitoyltransferase IA (CPT1A), a rate-limiting enzyme of FAO, was expressed at significantly low levels in patients with PM colorectal cancer, as determined by RT-qPCR, IHC, and GEO dataset analysis. However, lipidomics revealed no difference in FFA levels between PM and non-PM primary tumors. Here, we showed that cancer-associated fibroblasts (CAFs) promote the proliferation, migration, and invasion of colon cancer cells via upregulating CPT1A to actively oxidize FAs and conduct minimal glycolysis. In addition, coculture-induced glycolysis increased in cancer cells while fatty acid catabolism decreased with lower adiponectin levels. Importantly, inhibition of glycolysis significantly reduced the survival of CRC cells after incubation with conditioned medium from CAFsCPT1A -OE in vitro and impaired the survival and growth of organoids derived from CRC-PM. Finally, we found that directly blocking FAO in CAFsCPT1A -OE with etomoxir inhibits migration and invasion in vitro and decreases tumor growth and intraperitoneal dissemination in vivo, revealing a role for CAF CPT1A in promoting tumor growth and invasion. In conclusion, our results suggest the possibility of testing FAO inhibition as a novel approach and clinical strategy against CAF-induced colorectal cancer with peritoneal dissemination/metastases.

3.
Emerg Microbes Infect ; 10(1): 291-304, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33538646

RESUMO

Effective treatments for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgently needed. Dexamethasone has been shown to confer survival benefits to certain groups of hospitalized patients, but whether glucocorticoids such as dexamethasone and methylprednisolone should be used together with antivirals to prevent a boost of SARS-CoV-2 replication remains to be determined. Here, we show the beneficial effect of methylprednisolone alone and in combination with remdesivir in the hamster model of SARS-CoV-2 infection. Treatment with methylprednisolone boosted RNA replication of SARS-CoV-2 but suppressed viral induction of proinflammatory cytokines in human monocyte-derived macrophages. Although methylprednisolone monotherapy alleviated body weight loss as well as nasal and pulmonary inflammation, viral loads increased and antibody response against the receptor-binding domain of spike protein attenuated. In contrast, a combination of methylprednisolone with remdesivir not only prevented body weight loss and inflammation, but also dampened viral protein expression and viral loads. In addition, the suppressive effect of methylprednisolone on antibody response was alleviated in the presence of remdesivir. Thus, combinational anti-inflammatory and antiviral therapy might be an effective, safer and more versatile treatment option for COVID-19. These data support testing of the efficacy of a combination of methylprednisolone and remdesivir for the treatment of COVID-19 in randomized controlled clinical trials.

4.
Stem Cell Reports ; 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33626333

RESUMO

Enteroviruses, such as EV-A71 and CVA16, mainly infect the human gastrointestinal tract. Human coronaviruses, including SARS-CoV and SARS-CoV-2, have been variably associated with gastrointestinal symptoms. We aimed to optimize the human intestinal organoids and hypothesize that these optimized intestinal organoids can recapitulate enteric infections of enterovirus and coronavirus. We demonstrate that the optimized human intestinal organoids enable better simulation of the native human intestinal epithelium, and that they are significantly more susceptible to EV-A71 than CVA16. Higher replication of EV-A71 than CVA16 in the intestinal organoids triggers a more vigorous cellular response. However, SARS-CoV and SARS-CoV-2 exhibit distinct dynamics of virus-host interaction; more robust propagation of SARS-CoV triggers minimal cellular response, whereas, SARS-CoV-2 exhibits lower replication capacity but elicits a moderate cellular response. Taken together, the disparate profile of the virus-host interaction of enteroviruses and coronaviruses in human intestinal organoids may unravel the cellular basis of the distinct pathogenicity of these viral pathogens.

5.
Food Funct ; 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33625409

RESUMO

Ulcerative colitis is a recrudescent intestinal inflammation coupled with diarrhea, weight loss, pus, and blood stool, which seriously impacts the quality of patient life. d-Pinitol, which can be a food supplement isolated from the food plant-like soybeans, Ceratonia siliqua Linn and Bruguiera gymnorrhiza, has been proved to show anti-oxidative and anti-inflammatory effects. However, the potential mechanism of d-pinitol still remains ill-defined contemporarily. In the current study, the therapeutic effect and potential mechanisms of d-pinitol against colitis were investigated. Oxidative stress and inflammation of experimental colitis were caused by 3% DSS treatment once daily for 7 days. During DSS treatment, the mice of the positive drug group and three other groups were orally administered SASP or d-pinitol once daily. Clinical symptoms were analyzed, and macroscopic scores were calculated. The levels of oxidative and inflammatory cytokines were measured using assay kits and RT-PCR. Additionally, the protein expression of the Nrf2/ARE pathway and PPAR-γ was measured by Western blot. Results showed that d-pinitol enormously alleviated DSS-induced bodyweight loss, colon shortening, and histological injuries, achieving a therapeutic efficacy superior to SASP. Moreover, the oxidative stress and colonic inflammatory response were mitigated. d-pinitol not only significantly activated the Nrf2/ARE signaling pathway via facilitating the translocation of Nrf2 from sitoplazma to cytoblast, upregulating the protein expression levels of GCLC, GCLM, HO-1, and NQO1, but also improved the PPAR-γ level by binding to the active site of PPAR-γ, when suppressing NF-κB p65 and IκBα phosphorylation. In conclusion, d-pinitol exhibited a dramatic anti-colitis efficacy by activating the Nrf2/ARE pathway and PPAR-γ. Hence, d-pinitol may be a promising therapeutic drug against UC in the future.

6.
Ann Palliat Med ; 2021 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-33549016

RESUMO

BACKGROUND: The complete resection of primary duodenal adenocarcinoma (PDA) offers a chance for a cure, but the clinical and pathological characteristics of survivors have not been well studied. METHODS: Patients with stage I-III PDA who underwent surgical resection between 2013 and 2018 were identified retrospectively and followed until December 2019. All patients are from the Cancer Hospital Chinese Academy of Medical Sciences. The clinical and pathological information of the patients, such as age, gender, tumor location, operative procedure, pathologic features, TNM stage, common presenting symptoms, lymph node dissection status, serum tumor markers, etc., was collected in detail. The KaplanMeier method and a Cox proportional hazards model were used for the survival analysis. RESULTS: In total, 85 patients with PDA were eligible for this study. Among these patients, 48 were male (56.5%), 37 were female (43.5%), the median age was 59 (range, 22-79) years, 44 (51.8%) patients were aged <60 years, and 41 (48.2%) patients were aged ≥60 years. The 1-, 3-, and 5-year survival rates were 93.7%, 79.4%, and 64.9%, respectively. The median overall survival (OS) was 27 months (range, 2-82 months), and the median follow-up was 27 months (range, 3-82 months). The patients with stage III disease had the worst prognosis (P=0.001). The univariate analysis showed that lymph node positivity (P=0.000), the N stage (P=0.000), the TNM stage (P=0.001) and carbohydrate antigen 19-9 (CA19-9) positivity (P=0.038) were related to OS. However, the total number of lymph nodes (LN) retrieved (P=0.723), tumor differentiation (P=0.136), carcinoembryonic antigen (CEA) (P=0.812), gender (P=0.477), operation type (P=0.860), tumor size (P=0.869), tumor site (P=0.120), age (P=0.733), intraoperative blood loss (P=0.660), and intraoperative blood transfusion (P=0.748) were not correlated with OS. The multivariate analysis suggested that the lymph node status was an independent prognostic risk factor for OS. CONCLUSIONS: In our study the median OS was 27 months (range, 2-82 months), and the 5-year survival rates was 64.9%. The lymph node status was the only prognostic factor for OS in PDA.

7.
PLoS One ; 16(2): e0245876, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33571243

RESUMO

NUDIX hydrolase type 5 (NUDT5) is a kind of ADP-ribose pyrophosphatase and nucleotide metabolizing enzyme in cell metabolism. Previous studies have shown NUDT5 expression affected chromosome remodeling, involved in cell adhesion, cancer stem cell maintenance and epithelial to mesenchyme transition in breast cancer cells. Nevertheless, the role of NUDT5 in breast cancer progression and prognosis has not yet been systematically studied. This study explored the association of NUDT5 with the tumor development and poor prognosis in patients with breast cancer. Our results show that the levels of NUDT5 were upregulated in breast cancer cell lines and breast tumor tissues, and the expression of NUDT5 in breast tumor tissues increased significantly when compared with adjacent non-tumorous tissues by immunohistochemical staining of tissue microarrays. Breast cancer patients with high NUDT5 expression had a worse prognosis than those with low expression of NUDT5. In addition, the knockdown of NUDT5 suppressed breast cancer cell lines proliferation, migration and invasion, and dramatically inhibited the AKT phosphorylation at Thr308 and expression of Cyclin D1. The opposite effects were observed in vitro following NUDT5 rescue. Our findings indicated that the high expression of NUDT5 is probably involved in the poor prognosis of breast cancer via the activation of the AKT / Cyclin D pathways, which could be a prognostic factor and potential target in the diagnosis and treatment of breast cancer.

8.
J Asian Nat Prod Res ; : 1-11, 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33506714

RESUMO

Six new triterpenes, uncarinic acids KP (1-6), along with 24 known analogues, were isolated as minor constituents of an aqueous decoction of the hook-bearing stems of Uncaria rhynchophylla (Gou-teng). By comprehensive spectroscopic data analysis, their structures were elucidated as derivatives of olean-12-en-28-oic acid and urs-12-en-28-oic acid with different oxidized forms at C-3, C-6, and/or C-23, respectively. Cell-based preliminary bioassay showed that the (E)-/(Z)-coumaroyloxy and (E)-/(Z)-feruloyloxy units at C-27 of olean-12-en-28-oic acid and urs-12-en-28-oic acid played roles in their bioactivities.

9.
Arthritis Res Ther ; 23(1): 45, 2021 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-33514418

RESUMO

INTRODUCTION: Behcet's syndrome (BS) is a complex, heterogeneous disorder. However, classification of its subgroups is still debated. The purpose of this study was to investigate the clinical features and aggregation of patients with BS in China, based on manifestations and organ involvements. METHODS: This was a cross-sectional study of BS patients in Huadong Hospital of Fudan University between September 2012 and January 2020. We calculated relative risks (RRs) of clinical variables according to sex. Moreover, we conducted a hierarchical cluster analysis applied according to eighteen variables to determine subgroups of patients. RESULTS: A total of 860 BS patients were included. Male sex was associated with ocular involvement (RR 2.32, 95% CI 1.67, 3.22, P < 0.0001), vascular involvement (RR 2.00, 95% CI 1.23, 3.23, P = 0.004), cardiac lesion (RR 5.46, 95% CI 2.33, 12.77, P < 0.0001), and central nervous system involvement (RR 2.95, 95% CI 1.07, 6.78, P = 0.007) and was negatively associated with genital ulcers (RR 0.84, 95% CI 0.79, 0.91, P < 0.0001). Five clusters (C1-C5) were observed. C1 (n = 307) showed the skin and mucosa type. In C2 (n = 124), all had articular involvement, barely having major organ involvement except for 18 cases with intestinal lesions. In C3 (n = 156), the gastrointestinal type, 144 patients presented with intestinal involvement, and 36 patients with esophageal ulcers. In C4 (n = 142), all subjects presented with uveitis. C5 (n = 131) consisted of 44 patients with cardiac lesions, 58 with vascular involvement, and 26 cases having central nervous system involvement. CONCLUSION: Our analysis confirmed sex differences in phenotypes of BS. Cluster analysis identified gastrointestinal, uveitis, and cardiovascular involvement cluster separately in different subsets, which represents the most commonly involved organs. Further research is required to replicate and clarify the patterns of phenotype in BS.

10.
Free Radic Res ; : 1-12, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33470868

RESUMO

More and more evidence support the concept that RNA oxidation plays a substantial role in the progress of multiple diseases; however, only a few studies have reported RNA oxidation caused by microbial pathogens. Urinary 8-oxo-7,8-dihydroguanosine (8-oxo-Gsn) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dGsn), which are broadly used as indicators of oxidative damage of RNA and DNA, were analyzed in this study to determine which can be used as a biomarker of infection in challenged with Vibrio parahaemolyticus (V. parahaemolyticus). In this work, 24 specific-pathogen-free (SPF) male SD rats were randomly divided into two groups: an infection group and a phosphate-buffered saline (PBS) control group. Our results proved that 8-oxo-Gsn rather than 8-oxo-dGsn was significantly increased after challenged with V. parahaemolyticus in urine and tissue samples of SD rats compared with the PBS control group. Simultaneously, white blood cells (WBCs) counts, intestinal inflammation and inflammatory factors (including CRP, IL-6, IL-1ß, TNF-α, IL-10, and IL-17A) were also increased sharply. Which has more clinical value is that the trend of urinary 8-oxo-Gsn was consistent with WBCs, intestinal inflammation and all kinds of inflammatory factors. More importantly is that urinary 8-oxo-Gsn of infection group was positively correlated with WBCs and various inflammatory cytokines. In a word, our results demonstrated that as a systemic RNA oxidation biomarker, we hope 8-oxo-Gsn can be used as a biomarker of the severity of microbial pathogens infection, rather than a specific biomarker of microbial pathogens infection.

11.
Nat Commun ; 12(1): 134, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33420022

RESUMO

Understanding the factors that contribute to efficient SARS-CoV-2 infection of human cells may provide insights on SARS-CoV-2 transmissibility and pathogenesis, and reveal targets of intervention. Here, we analyze host and viral determinants essential for efficient SARS-CoV-2 infection in both human lung epithelial cells and ex vivo human lung tissues. We identify heparan sulfate as an important attachment factor for SARS-CoV-2 infection. Next, we show that sialic acids present on ACE2 prevent efficient spike/ACE2-interaction. While SARS-CoV infection is substantially limited by the sialic acid-mediated restriction in both human lung epithelial cells and ex vivo human lung tissues, infection by SARS-CoV-2 is limited to a lesser extent. We further demonstrate that the furin-like cleavage site in SARS-CoV-2 spike is required for efficient virus replication in human lung but not intestinal tissues. These findings provide insights on the efficient SARS-CoV-2 infection of human lungs.


Assuntos
/metabolismo , /transmissão , Ácidos Siálicos/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Ligação Viral , Animais , Células CACO-2 , Linhagem Celular Tumoral , Chlorocebus aethiops , Cricetinae , Furina/metabolismo , Células HEK293 , Heparitina Sulfato/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Intestinos/virologia , Pulmão/patologia , Pulmão/virologia , Síndrome Respiratória Aguda Grave/patologia , Células Vero , Internalização do Vírus , Replicação Viral/fisiologia
12.
Clin Infect Dis ; 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33515458

RESUMO

BACKGROUND: Mass vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is ongoing amidst widespread transmission during the Coronavirus Disease 2019 (COVID-19) pandemic. Disease phenotypes of SARS-CoV-2 exposure occurring around the time of vaccine administration have not been described. METHODS: Two-dose (14 days apart) vaccination regimen with a formalin-inactivated whole virion SARS-CoV-2 in golden Syrian hamster model was established. To investigate the disease phenotypes of a one-dose regimen given 3 days prior (D-3), 1 (D1) or 2 (D2) days after, or on the day (D0) of virus challenge, we monitored the serial clinical severity, tissue histopathology, virus burden, and antibody response of the vaccinated hamsters. RESULTS: The one-dose vaccinated hamsters had significantly lower clinical disease severity score, body weight loss, lung histology score, nucleocapsid protein expression in lung, infectious virus titres in the lung and nasal turbinate, inflammatory changes in intestines and a higher serum neutralizing antibody or IgG titre against the spike receptor-binding domain or nucleocapsid protein when compared to unvaccinated controls. These improvements were particularly noticeable in D-3, but also in D0, D1 and even D2 vaccinated hamsters to varying degrees. No increased eosinophilic infiltration was found in the nasal turbinate, lung, and intestine after virus challenge. Significantly higher serum titre of fluorescent foci microneutralization inhibition antibody was detected in D1 and D2 vaccinated hamsters at day 4 post-challenge compared to controls despite undetectable neutralizing antibody titre. CONCLUSIONS: Vaccination just before or soon after exposure to SARS-CoV-2 does not worsen disease phenotypes and may even ameliorate infection.

13.
Pharmacol Res Perspect ; 9(1): e00718, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33508175

RESUMO

Cytochrome P450 2C9 (CYP2C9) is one of the most important drugs metabolizing enzymes and accounts for the metabolism of about 13%-17% of clinical drugs. Like other members in CYP2 family, CYP2C9 gene exhibits great genetic polymorphism among different races and individuals. CYP2C9*18 is one CYP2C9 allelic variant identified in a Southeast Asian population and is estimated to cause the amino acid substitutions of I359L and D397A in CYP2C9 enzyme simultaneously. Limited by the low expression level in bacteria and COS-7 cells, no valuable enzyme kinetics have been reported on this CYP2C9 variant. In this study, the baculovirus-based system was used for the high expression of recombinant CYP2C9 s in insect cells. As a result, together with I359L substitution, D397A could significantly decrease the protein expression of CYP2C9.18 in insect cells, although substitution of D397A alone had no effect on the expression of CYP2C9 in vitro. As compared with that of wild-type enzyme, both CYP2C9.18 variant and D397A variant could decrease more than 80% of the catalytic activity of CYP2C9 enzyme toward three probe substrates, suggesting that caution should be exercised when patients carrying CYP2C9*18 taking medicines metabolized by CYP2C9 enzyme with a narrow therapeutic window.

14.
Biochim Biophys Acta Mol Cell Res ; 1868(1): 118895, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33096144

RESUMO

MutT Homolog 1 (MTH1) is a mammalian 8-oxodGTPase for sanitizing oxidative damage to the nucleotide pool. Nudix type 5 (NUDT5) also sanitizes 8-oxodGDP in the nucleotide pool. The role of MTH1 and NUDT5 in non-small-cell lung cancer (NSCLC) progression and metastasis remains unclear. In the present study, we reported that MTH1 and NUDT5 were upregulated in NSCLC cell lines and tissues, and higher levels of MTH1 or NUDT5 were associated with tumor metastasis and a poor prognosis in patients with NSCLC. Their suppression also restrained tumor growth and lung metastasis in vivo and significantly inhibited NSCLC cell migration, invasion, cell proliferation and cell cycle progression while promoting apoptosis in vitro. The opposite effects were observed in vitro following MTH1 or NUDT5 rescue. In addition, the upregulation of MTH1 or NUDT5 enhanced the MAPK pathway and PI3K/AKT activity. Furthermore, MTH1 and NUDT5 induce epithelial-mesenchymal transition both in vitro and in vivo. These results highlight the essential role of MTH1 and NUDT5 in NSCLC tumor tumorigenesis and metastasis as well as their functions as valuable markers of the NSCLC prognosis and potential therapeutic targets.

15.
Drug Des Devel Ther ; 14: 5129-5141, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33262574

RESUMO

Aim: We aimed to systematically examine the effects of enzymatic activity of 38 human CYP2C9 alleles and 21 human CYP3A4 alleles, including wild-type CYP2C9.1 and CYP3A4.1, which contain the 24 CYP2C9 novel alleles (*36-*60) and 6 CYP3A4 novel alleles (*28-*34) newly found in the Chinese population, on sildenafil metabolism through in vitro experiment. Methods: The recombinant cytochrome P450 alleles protein of CYP2C9 and CYP3A4 expressed in insect baculovirus expression system were reacted with 10-500 µM sildenafil for 30 minutes at 37°C, and the reaction was terminated by cooling to -80°C immediately. Next, we used ultra-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) detection system to detect sildenafil and its active metabolite N-desmethyl sildenafil. Results: The intrinsic clearance (Vmax/Km) values of most CYP2C9 variants were significantly altered when compared with the wild-type CYP2C9*1, with most of these variants exhibiting either reduced Vmax and/or increased Km values. Four alleles (CYP2C9*11, *14, *31, *49) exhibited no markedly decreased relative clearance (1-fold). The relative clearance of the remaining thirty-three variants exhibited decrease in different levels, ranging from 1.81% to 88.42%. For the CYP3A4 metabolic pathway, when compared with the wild-type CYP3A4*1, the relative clearance values of four variants (CYP3A4*3, *10, *14 and *I335T) showed significantly higher relative clearance (130.7-134.9%), while five variants (CYP3A4*2, *5, *24, *L22V and *F113I) exhibited sharply reduced relative clearance values (1.80-74.25%), and the remaining nine allelic variants showed no statistical difference. In addition, the kinetic parameters of two CYP3A4 variants (CYP3A4*17 and CYP3A4*30) could not be detected, due to the defect of the CYP3A4 gene. Conclusion: These findings were the first evaluation of all these infrequent CYP2C9 and CYP3A4 alleles for sildenafil metabolism; when treating people who carry these CYP2C9 and CYP3A4 variants, there should be more focus on the relation of dose intensity, side effects and therapeutic efficacy when administering sildenafil. The study will provide fundamental data on effect of CYP2C9 and CYP3A4 allelic variation on sildenafil metabolism for further clinical research.

16.
Zhongguo Gu Shang ; 33(11): 1085-8, 2020 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-33269864

RESUMO

Osteoarthritis(OA) is a common clinical disease. The incidence of OA increases significantly with age, and the quality of life of patients is seriously affected. In the pathogenesis of OA, cartilage degeneration is the main cause. There are many long non-coding RNA (lncRNA) specifically expressed in osteoarthritis, which is closely related to the occurrence and development of osteoarthritis. Based on the latest research from 2014 to 2019, this paper summarizes the differential expression of lncRNA in osteoarthritis, the mechanism of lncRNA regulating chondrocyte function, and the mechanism of lncRNA regulating cartilage matrix metabolism. The fact that the expression of lncRNA is altered at different stages of OA development indicates that lncRNA can be developed forlife. The biomarkers and therapeutic targets can provide reference for the prevention, treatment and research of osteoarthritis.

17.
Biomed Res Int ; 2020: 8893621, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33354574

RESUMO

Materials and Methods: The chemical compositions of EFH were identified using LC-ESI-MS. The mice with 3% DSS-induced UC were administered EFH (200, 400, and 800 mg/kg), sulfasalazine (SASP, 200 mg/kg), and azathioprine (AZA, 13 mg/kg) for 10 days via daily gavage. The colonic inflammation was evaluated by the disease activity index (DAI), colonic length, histological scores, and levels of inflammatory mediators. The gut microbiota was characterized by 16S rRNA gene sequencing and analysis. Results: LC-ESI-MS analysis showed that EFH was rich in alkaloids and flavones. The results indicated that EFH significantly improved the DAI score, relieved colon shortening, and repaired pathological colonic variations in colitis. In addition, proteins in the NF-κB pathway were significantly inhibited by EFH. Furthermore, EFH recovered the diversity and balance of the gut microbiota. Conclusions: EFH has protective effects against DSS-induced colitis by keeping the balance of the gut microbiota and suppressing the NF-κB pathway.

18.
Lancet Microbe ; 1(3): e111-e118, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33230504

RESUMO

Background: The role of subclinical severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in perpetuating the COVID-19 pandemic is unknown because population seroprevalence data are absent. We aimed to establish the sensitivity and specificity of our enzyme immunoassay and microneutralisation assay, and the seroprevalence of SARS-CoV-2 in Hong Kong before and after the pandemic, as well as in Hong Kong residents evacuated from Hubei province, China. Methods: We did a multicohort study in a hospital and university in Hong Kong. We evaluated the sensitivity of our enzyme immunoassay and microneutralisation assay with RT-PCR data from patients positive for SARS-CoV-2 and the specificity of our enzyme immunoassay and microneutralisation assay with archived serum samples collected before 2019. We compared the seropositivity of the general population of Hong Kong before and after the pandemic had begun, and determined the seropositivity of Hong Kong residents evacuated from Hubei province, China, in March, 2020. Findings: Between Feb 26 and March 18, 2020, we assessed RT-PCR samples from 45 patients who had recovered from COVID-19 to establish the sensitivity of our enzyme immunoassay and microneutralisation assay. To establish the specificity of these assays, we retrieved archived serum. The sensitivity was 91·1% (41 of 45 [95% CI 78·8-97·5]) for the microneutralisation assay, 57·8% (26 of 45 [42·2-72·3]) for anti-nucleoprotein IgG, 66·7% (30 of 45 [51·1-80·0]) for anti-spike protein receptor binding domain (RBD) IgG, and 73·3% (33 of 45 [58·1-85·4]) for enzyme immunoassay (either positive for anti-nucleoprotein or anti-RBD IgG). The specificity was 100% (152 of 152 [95% CI 97·6-100·0]) for both the enzyme immunoassay and microneutralisation assay. Among the Hong Kong general population, 53 (2·7%) of 1938 were enzyme immunoassay positive, but of those who were positive, all 53 were microneutralisation negative, and no significant increase was seen in the seroprevalence between April 12, 2018, and Feb 13, 2020. Among asymptomatic Hubei returnees, 17 (4%) of 452 were seropositive with the enzyme immunoassay or the microneutralisation assay, with 15 (88%) of 17 seropositive with the microneutralisation assay, and two familial clusters were identified. Interpretation: Our serological data suggest that SARS-CoV-2 is a new emerging virus. The seropositivity rate in Hubei returnees indicates that RT-PCR-confirmed patients only represent a small proportion of the total number of cases. The low seroprevalence suggests that most of the Hong Kong and Hubei population remain susceptible to COVID-19. Future waves of the outbreak are inevitable without a vaccine or antiviral prophylaxis. The role of age-related cross reactive non-neutralising antibodies in the pathogenesis of COVID-19 warrants further investigation. Funding: Richard and Carol Yu, May Tam Mak Mei Yin, Shaw Foundation (Hong Kong), Michael Tong, Marina Lee, and the Government Consultancy Service (see acknowledgments for full list).

19.
Clin Chim Acta ; 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33181151

RESUMO

BACKGROUND: Cerebrocardiac syndrome (CCS) is a common complication after severe traumatic brain injury (sTBI) and its occurrence obviously increases the risk of a poor outcome. Macrophage migration inhibitory factor (MIF) acts as an inflammatory cytokine and its circulating concentration are related to acute heart and brain injury. The aim of this study was to examine the association of serum concentration of MIF with posttraumatic CCS. METHODS: From January 2016 to February 2019, 116 sTBI patients and 116 healthy controls with similar age and gender percentage were recruited. Relationship between serum MIF concentration and CCS was assessed using multivariate analysis. RESULTS: Serum MIF concentration of patients were significantly higher than those among controls. Serum MIF concentration were intimately correlated with Glasgow coma scale scores (t = -5.553, P < 0.001) and serum C-reactive protein concentration (t = 5.320, P < 0.001) in a multivariate linear regression model. 61 patients (52.6%) displayed CCS. Under ROC curve analylsis, there was a strong discriminatory ability for CCS regarding serum MIF concentration (area under curve, 0.834; 95% confidence interval, 0.754-0.897). Serum MIF concentration were highly associated with CCS independent of other confounding factors (odds ratio, 5.608; 95% CI: 1.896-16.587). CONCLUSIONS: Increased MIF in serum may be a useful biomarker for early detection of CCS after head trauma.

20.
Transl Androl Urol ; 9(5): 2242-2250, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33209689

RESUMO

Background: Clear cell renal carcinoma (CCRCC) is a multigene-related tumor. The aim of the present study was to analyze the expression of breast cancer 1-associated protein 1 (BAP1), Ki-67, and inhibitor of differentiation-1 (Id-1) in CCRCC patients and their correlation with clinical features and prognosis. Methods: A total of 45 CCRCC patients who were diagnosed and treated at our hospital from January 2016 to January 2018 were included in the present study. BAP1, Ki-67, and Id-1 protein expression in the CCRCC tissue group and adjacent mucosa group was compared. The correlation between BAP1, Ki-67, and Id-1 proteins, and the clinical characteristics and the prognosis of CCRCC patients, were analyzed. Multiple logistic regression was used to analyze the risk factors that affect the prognosis of CCRCC patients. Results: The negative rate of BAP1 in the CCRCC group was higher than that in the adjacent mucosa group. There were more patients with a Ki-67 index >10 and a higher Id-1-positive rate in the CCRCC tissue group. BAP-1, Ki-67 index, and Id-1 protein expression were not correlated with age, sex, surgical method, microscopic necrosis, and degree of sarcomatoid characteristics of CCRCC patients (P>0.05), but were related to tumor diameter, pathological stage, TNM stage, and World Health Organization (WHO)/Internal Society of Urologic Pathology (ISUP) grade. The Kaplan-Meier survival curve showed that the average survival time of the BAP1-negative group, Ki-67 index >10 group, and Id-1 protein-positive group was shorter than that of the BAP1-positive group, Ki-67 index ≤10 group, and Id-1 protein-negative group, respectively. Pathological staging, WHO/ISUP classification, negative BAP1, Ki-67 index >10, and positive Id-1 protein were independent risk factors affecting CCRCC patients (P<0.05). Conclusions: The expression of BAP1 in CCRCC patients decreased, and the expression of Ki-67 and Id-1 protein increased. Abnormal expression levels of BAP1, Ki-67, and Id-1 proteins were involved in the occurrence and development of CCRCC, and closely related to the prognosis of patients. These can be used as molecular markers for predicting the prognosis of CCRCC patients and as potential targets for tumor treatment.

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