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1.
BMC Res Notes ; 13(1): 506, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33187555

RESUMO

OBJECTIVES: A pneumonia associated with 2019 novel coronavirus (2019-nCoV, subsequently named SARS-CoV2) emerged worldwide since December, 2019. We aimed to describe the epidemiological characteristics of 2019 coronavirus disease (COVID-19) in Shaanxi province of China. RESULTS: 1. Among the 245 patients, 132 (53.9%) were males and 113 (46.1%) were females. The average age was 46.15 ± 16.43 years, ranging from 3 to 89 years. 2. For the clinical type, 1.63% (4/245) patients were mild type, 84.90% (208/245) were moderate type, 7.76% (19/245) were severe type, 5.31% (13/245) were critical type and only 0.41% (1/245) was asymptomatic. 3. Of the 245 patients, 116 (47.35%) were input case, 114 (46.53%) were non-input case, and 15 (6.12%) were unknown exposure. 4. 48.57% (119/245) cases were family cluster, involving 42 families. The most common pattern of COVID-19 family cluster was between husband and wife or between parents and children.

2.
Analyst ; 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33216074

RESUMO

Here a novel strategy is reported of assembling silanized carbon dots (CDs) with porous silica templates to form fluorescent CD-based silica (FCS) colloids with uniformly packed CDs throughout the silica matrix. Dendritic silica spheres with highly accessible central-radial pores are adopted as a powerful absorbent host, which can form Si-O bonds with silane to directly fix the silanized CDs. The appropriate loading content of CDs on the inner surface of dendritic silica spheres is beneficial for the maximum fluorescence intensity of FCS colloids. High-quality silanized CDs endow multiple CD embedded silica spheres with excellent properties, including good fluorescence performance, excellent colloidal/optical stabilities and convenient biofunctionalization. The integration of these FCS colloids with a lateral flow strip platform provides an ultra-sensitive, specific and robust immunoassay method for the Zika NS1 protein with a visual detection limit of 10 pg mL-1, and has been successfully applied to the detection of Zika virus in clinical samples. In addition, we also prepared conventional Au NP-based lateral flow test strips and applied them to the detection of Zika NS1 protein. By comparison, the detection limit of immunofluorescent CD-based silica (iFCS)-based lateral flow test strips is 100-fold lower than that of Au NP-based lateral flow strips.

3.
Crit Rev Oncol Hematol ; 156: 103114, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33045493

RESUMO

BACKGROUND: Extended endocrine therapy (EET) with aromatase inhibitors (AIs) therapy can further reduce the risk of recurrence in breast cancer patients. But the conclusion that whether EET with AIs increases the risk of some side effects compared with nonextended endocrine therapy (NEET) is still controversial and not exhaustive. METHODS: We searched for Randomized controlled trials (RCT) trials published in EMBASE and PubMed between March 2008 and December 2019. Studies comparing the side effects of adjuvant EET with those of NEET were included. The objective was to determine whether EET with AIs increases the risk of side effects compared with NEET. RESULTS: Overall, 11 trials comprising 24,187 participants were identified. EET with AIs increased the risk of cardiotoxicity [odds ratio (OR) 1.19, 95 % confidence interval (CI) 1.04-1.36; P < 0.05; 438 vs 423], bone pain (OR 1.18, 95 % CI 1.02-1.36; P < 0.05; 446 vs 404), osteoporosis (OR 1.53, 95 % CI 1.35-1.72; P < 0.05; 866 vs 641), fractures (OR 1.33, 95 % CI 1.18-1.50; P < 0.05; 596 vs 438), arthralgia (OR 1.27, 95 % CI 1.19-1.36; P < 0.05; 2404 vs 2060), myalgia (OR 1.29, 95 % CI 1.16-1.43; P < 0.05; 960 vs 776), and hot flashes (OR 1.40, 95 % CI 1.15-1.69; P < 0.05; 2418 vs 2174) and was associated with opposite risk of vaginal bleeding (OR 0.74, 95 % CI 0.59-0.92; P < 0.05; 148 vs 197). However, the extended therapy did not increase the risk of hypertension (OR 1.03, 95 % CI 0.80-1.33; P = 0.80; 364 vs 353), hypercholesterolemia (OR 1.03, 95 % CI 0.91-1.16; P = 0.62; 643 vs 627), vaginal dryness (OR 1.19, 95 % CI 1.00-1.42; P = 0.05; 294 vs 257), fatigue (OR 1.20, 95 % CI 0.96-1.50; P = 0.12; 1501 vs 1462), dizziness (OR 1.04, 95 % CI 0.92-1.17; P = 0.55; 614 vs 595), headaches (OR 1.06, 95 % CI 0.95-1.18; P = 0.30; 885 vs 848), constipation (OR 0.91, 95 % CI 0.79-1.04; P = 0.15; 480 vs 522), nausea (OR 1.83, 95 % CI 0.49-6.83; P =0.37; 340 vs 325), and dyspnea (OR 0.96, 95 % CI 0.82-1.13; P = 0.64; 340 vs 351). The risk of grade ≥ 3 hot flashes increased following extended endocrine therapy (OR 2.01, 95 % CI 1.23-3.29; P < 0.05; 47 vs 23). We observed no evidence for a difference in the risk of grade ≥3 fatigue, arthralgia, myalgia, bone pain, osteoporosis, fractures, hypertension, and headache between both endocrine therapies. Secondary outcomes shows that after receive EET with AIs, patients can benefit from the control of the local recurrence, distant recurrence, contralateral breast cancer, and second cancers. CONCLUSIONS: Compared with NEET, EET with AIs significantly increased the risk of cardiotoxicity, bone pain, osteoporosis, fractures, hot flashes, arthralgia, myalgia, and grade ≥3 hot flashes, and EET with AIs can reduced the risks of local recurrence, distant recurrence, contralateral breast cancer, and second cancers. These findings offer an important guide for clinicians and patients.


Assuntos
Neoplasias da Mama , Segunda Neoplasia Primária , Antineoplásicos Hormonais/efeitos adversos , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Feminino , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Pós-Menopausa , Tamoxifeno/uso terapêutico
4.
JAMA Netw Open ; 3(10): e2020312, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33048129

RESUMO

Importance: One of the most recent treatment regimens used for hormone receptor (HR)-positive, ERBB2 (formerly HER2)-negative metastatic breast cancer is treatment with the cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors and endocrine therapy (ET). Objective: To assess overall survival (OS), progression-free survival (PFS), objective response rate, and adverse events, especially grades 3 and 4 adverse events, among patients with HR-positive, ERBB2-negative metastatic breast cancer who were treated with CDK4/6 inhibitors plus ET vs ET alone. Data Sources: A systematic search of PubMed, Embase, the main oncology conference of the European Society of Medical Oncology, and the American Society of Clinical Oncology and the San Antonio Breast Cancer Symposium databases for randomized clinical trials of CDK4/6 inhibitors plus ET vs ET for HR-positive, ERBB2-negative metastatic breast cancer. Searches were performed up to March 30, 2020. Study Selection: A total of 472 records were assessed in PubMed and Embase by 2 authors, including studies, international meeting reports, and reviews. Inclusion criteria were English-language phase 2 or 3 randomized clinical trials of HR-positive, ERBB2-negative metastatic breast cancer, with patients randomly assigned to receive CDK4/6 inhibitors plus ET or ET alone, and having OS or PFS outcomes. The exclusion criteria were phase 1 trials, retrospective studies, or studies without survival outcomes. Excluding the references, 16 articles were relevant. After excluding studies based on exclusion criteria, 9 studies were considered eligible for this meta-analysis. Data Extraction and Synthesis: Two researchers independently extracted data and assessed potential bias. Data assessment followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. The results were pooled using a fixed-effect model. Main Outcomes and Measures: Study heterogeneity was assessed using the I2 statistic. Hazard ratios (HRs) and 95% CIs were used to evaluate PFS, OS, and subgroup analyses. Overall response and 95% CIs were used to evaluate the objective response rate and grade 3 or 4 adverse events. The primary outcome was OS. Results: In total, 9 studies that included a total of 5043 patients with metastatic breast cancer were assessed in this meta-analysis. Overall, the addition of CDK4/6 inhibitors to ET was associated with a statistically significant benefit to OS (HR, 1.33; 95% CI, 1.19-1.48; P < .001). Compared with ET alone, treatment with CDK4/6 inhibitors plus ET was associated with improved OS for the following subgroups: first-line therapy (HR, 1.35; 95% CI, 1.18-1.54; P < .001), second-line therapy (HR, 1.30; 95% CI, 1.09-1.54; P < .001), premenopausal women (HR, 1.32; 95% CI, 1.04-1.66; P < .001), postmenopausal women (HR, 1.34; 95% CI, 1.18-1.52; P < .001), visceral metastasis (HR, 1.31; 95% CI, 1.12-1.53; P < .001), bone-only metastasis (HR, 1.22; 95% CI, 0.88-1.68; P < .001), age younger than 65 years (HR, 1.25; 95% CI, 1.06-1.49; P < .001), and age 65 years or older (HR, 1.38; 95% CI, 1.11-1.72; P < .001). The addition of CDK4/6 inhibitors to ET was also associated with significant PFS benefit (HR, 1.84; 95% CI, 1.70-1.98; P < .001) and objective response rate benefit (odds ratio, 2.02; 95% CI, 1.61-2.53; P < .001). However, the use of CDK4/6 inhibitors in combination with ET was associated with significantly increased risk of grade 3 or 4 adverse events compared with ET alone, including neutropenia (HR, 57.05; 95% CI, 38.26-85.05; P < .001), leukopenia (HR, 36.36; 95% CI, 19.35-68.34; P < .001), and diarrhea (HR, 4.97; 95% CI, 2.84-8.69; P < .001). Conclusions and Relevance: This meta-analysis indicated that, compared with ET alone, treatment with CDK4/6 inhibitors plus ET was associated with significantly improved OS, PFS, and objective response rate among patients with HR-positive, ERBB2-negative metastatic breast cancer.

5.
Chem Biodivers ; 17(11): e2000566, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32954632

RESUMO

The AcOEt extract of Artemisia argyi-derived fungus Trichoderma koningiopsis QA-3 showed potent inhibitory activity against pathogenic bacteria. Fractionation of the extract resulted in the isolation of three new polyketides (1-3) and two new terpenoids (4 and 5), together with three known metabolites (6-8). Their chemical structures were analyzed by NMR spectra, ECD, HR-ESI-MS or HR-EI-MS, optical rotation, and X-ray crystallographic data, as well as by comparison with literature reports. In the antibacterial assays, 3-hydroxyharziandione (4) showed potent activity against human pathogen Escherichia coli with an MIC value of 0.5 µg/mL, while 6-(3-hydroxypent-1-en-1-yl)-2H-pyran-2-one exhibited strong activity against marine-derived aquatic pathogen Micrococcus luteus with an MIC value of 1.0 µg/mL.

7.
Sleep Med ; 75: 151-155, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32858354

RESUMO

BACKGROUND: Obstructive sleep apnea (OSA) is known to be highly associated with reflux diseases. There is evidence that continuous positive airway pressure (CPAP) can decrease the clinical symptoms of gastroesophageal reflux (GER) in OSA patients, but whether CPAP can decrease nocturnal laryngopharyngeal reflux (LPR) episodes is still lack of strong evidence. OBJECTIVE: To investigate the efficiency of CPAP on LPR and the relationship between LPR, GER and OSA. STUDY DESIGN: retrospective study. METHODS: Forty adult patients who had confirmed OSA by polysomnography and suspected LPR were enrolled. Their results of synchronous polysomnography and 24 h esophageal and oropharyngeal Dx-pH monitoring were analyzed. Twenty-seven OSA patients were treated with CPAP on the second night. The nocturnal reflux parameters with and without CPAP treatment were compared. RESULTS: 15.0% and 42.5% of OSA patients were associated with LPR and GER through Dx-pH monitoring respectively. Nevertheless, more than one reflux attack falling below pH6.0 of oropharynx during sleep time was detected in 80.0% patients. There was a significant inverse correlation between the lowest/mean pH values of oropharynx and obstructive apnea index (OAI), so was the lowest pH values of esophagus. Significant positive correlation was calculated between the total number of reflux episodes below pH6.0 of oropharynx and apnea-hypopnea index (AHI)/OAI/hypopnea index (HI). A similar positive correlation was also significant between AHI/OAI and GER parameters. The assessment of the efficacy of CPAP treatment showed significant difference both in GER and LPR related parameter. CONCLUSIONS: OSA patients have a higher incidence of nocturnal LPR and GER. CPAP treatment can effectively reduce both GER and LPR attacks while disordered sleep events reduced in OSA patients.

8.
Biomark Med ; 14(8): 675-682, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32613842

RESUMO

Aim: The discrimination of renal cell carcinoma from renal angiomyolipoma (RAML) is crucial for the effective treatment of each. Materials & methods: Serum samples were analyzed by nuclear magnetic resonance spectroscopy-based metabolomics and a number of metabolites were further quantified by HPLC-UV. Results: Clear-cell renal carcinoma (ccRCC) was characterized by drastic disruptions in energy, amino acids, creatinine and uric acid metabolic pathways. A logistic model for the differential diagnosis of RAML from ccRCC was established using the combination of serum levels of uric acid, the ratio of uric acid to hypoxanthine and the ratio of hypoxanthine to creatinine as variables with area under the curve of the receiver operating characteristic curve value of 0.907. Conclusion: Alterations in serum purine metabolites may be used as potential metabolic markers for the differential diagnosis of ccRCC and RAML.

9.
J Cell Mol Med ; 2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32697380

RESUMO

The aberrant expression of human sirtuin 2 (SIRT2) has been detected in various types of cancer; however, the biological roles, underlying mechanisms and clinical significance of SIRT2 dysregulation in human colorectal cancer (CRC) remain unclear. The results of this study demonstrate that compared with paired normal tissues, SIRT2 expression is significantly decreased in CRC tissues. SIRT2 loss has been correlated with clinicopathological characteristics, including distant metastasis, lymph node metastasis and American Joint Committee on Cancer (AJCC) stage; this loss serves as an independent factor that indicates a poor prognosis for patients with CRC. Further gain- and loss-of-function analyses have demonstrated that SIRT2 suppresses CRC cell proliferation and metastasis both in vivo and in vitro. Mechanistically, miR-212-5p was identified to directly target the SIRT2 3'-untranslated region (3'-UTR), leading to SIRT2 down-regulation. The ectopic expression of SIRT2 reverses the effect of miR-212-5p overexpression on CRC cell colony formation, invasion, migration and proliferation. Clinically, an inverse correlation was found between miR-212-5p and SIRT2 expression. High miR-212-5p expression has been found to result in a poor prognosis and aggressive clinicopathological characteristics in patients with CRC. Taken together, these results suggest that SIRT2, targeted by miR-212-5p, acts as a tumour suppressor in CRC and that the miR-212-5p/SIRT2 axis is a promising prognostic factor and potential therapeutic target in CRC.

10.
Am J Physiol Cell Physiol ; 319(3): C579-C588, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32608990

RESUMO

Identification of specific biomarkers for ischemic stroke is necessary due to their abilities to improve treatment outcomes. Many studies have demonstrated the involvement of microRNAs (miRNAs) in the pathogenesis and complications of ischemic stroke and patient outcomes. We found that the expression of miR-874-3p was downregulated in clinical samples of ischemic stroke. Thus the present study explored the potential role of miR-874-3p in ischemic stroke and related mechanisms. A mouse model of ischemic stroke was constructed by middle cerebral artery occlusion. The relationship among miR-874-3p, C-X-C motif chemokine ligand 12 (CXCL12), and the Wnt/ß-catenin pathway was explored by dual luciferase reporter assay and Western blot analysis. Angiogenesis and brain tissue apoptosis were evaluated by immunofluorescence staining and TUNEL staining, respectively. ELISA was introduced to measure levels of inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin (IL)-1, IL-6, IL-8, and IL-10 in brain tissues. Primary hippocampal neuronal cells were isolated from the mouse model of ischemic stroke and incubated with human umbilical vein endothelial cells (HUVECs) for HUVEC tube formation. High expression of CXCL12 and low expression of miR-874-3p were confirmed in ischemic stroke. In addition, miR-874-3p was found to target and downregulate CXCL12, thus reducing TNF-α, IL-1, IL-6, and IL-8 levels, but enhancing IL-10 level. Collectively, upregulating miR-874-3p inhibits CXCL12 expression to promote angiogenesis and inhibit inflammation in ischemic stroke mice by activating the Wnt/ß-catenin pathway, which may provide a new direction of ischemic stroke treatment.


Assuntos
Quimiocina CXCL12/metabolismo , Inflamação/metabolismo , MicroRNAs/genética , Acidente Vascular Cerebral/metabolismo , Animais , Apoptose/fisiologia , Isquemia Encefálica/genética , Isquemia Encefálica/metabolismo , Camundongos , Neurônios/metabolismo , Acidente Vascular Cerebral/genética , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima
11.
Neuropharmacology ; 177: 108242, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-32712277

RESUMO

Cholesterol plays vital roles in many central physiological and pathological processes. As a key component in the cell membrane, cholesterol can regulate a variety of ion channels, including ligand-gated ion channels (LGICs). However, relatively little is known about the molecular detail and in vivo consequence of cholesterol-LGIC interaction. Here, we reveal that membrane cholesterol depletion significantly inhibits the potentiating effects of dehydroxylcannabidiol (DH-CBD) on glycine-activated currents (IGly) in HEK 293T cells expressing α1/α3 glycine receptors (GlyRs). Simvastatin considerably decreases cholesterol levels and DH-CBD-induced potentiation of IGly in the spinal cord of mice. Simvastatin also significantly decreases DH-CBD analgesia in acute and chronic pain of mice. The cholesterol levels in the dorsal horn of spinal cord, measured by mass spectrometry imaging, are specifically correlated with cannabinoid potentiation of spinal GlyRs and cannabinoid-induced analgesia. These findings suggest that spinal cholesterol is critical for the efficacy of glycinergic cannabinoid-induced analgesia.

12.
Theranostics ; 10(16): 7335-7350, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32641995

RESUMO

Introduction: Colorectal cancer (CRC) frequently harbors KRAS mutations that result in chemoresistance and metastasis. MicroRNAs (miRNAs) are usually dysregulated and play important regulatory roles in tumor progression. However, the KRAS mutation-responsive miRNA profile in CRC remains uninvestigated. Methods: miR-139-5p was identified and evaluated by small RNA sequencing, qRT-PCR and in situ hybridization. The roles of miR-139-5p in CRC cells with and without KRAS mutation were determined by Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry and transwell assays in vitro and by tumorigenesis and metastasis assays in vivo. Microarrays followed by bioinformatic analyses, luciferase reporter assays and Western blotting were applied for mechanistic studies. Results: miR-139-5p was significantly downregulated in KRAS-mutated CRC cells and tissues compared with their wild-type counterparts. Low miR-139-5p expression was associated with aggressive phenotypes and poor prognosis in CRC patients. miR-139-5p overexpression inhibited CRC cell proliferation, migration and invasion in vitro, sensitized tumors to chemotherapy, and impaired tumor growth and metastasis in vivo. Transcriptomic profiling identified multiple modulators in the Ras (JUN and FOS) and Wnt (CTNNB1 and DVL1) signaling pathways and the epithelial-to-mesenchymal transition (EMT) process (ZEB1) as direct targets of miR-139-5p, and inverse correlations were confirmed in CRC clinical tissues. Aberrantly activated Wnt signaling in KRAS-mutant cells was demonstrated to transcriptionally repress miR-139-5p through TCF4, forming a miR-139-5p/Wnt signaling double-negative feedback loop. Conclusions: We identified miR-139-5p as a KRAS-responsive miRNA and demonstrated its involvement in CRC progression. KRAS mutation disrupted the miR-139-5p/Wnt signaling reciprocal negative feedback mechanism, which might cause miR-139-5p downregulation and derepression of oncogenic signaling pathways and EMT. These results reveal a transcriptional regulatory mode of KRAS-driven malignant transformation and highlight miR-139-5p as a novel regulator of crosstalk between the Ras and Wnt signaling pathways in CRC.

13.
Artigo em Inglês | MEDLINE | ID: mdl-32670896

RESUMO

Quiescin sulfhydryl oxidase (QSOX), present in a wide variety of eukaryotic species, catalyzes the insertion of disulfide bonds into unfolded, reduced proteins. Here we characterized the QSOX protein from the rodent malaria parasite Plasmodium berghei (PbQSOX), which is conserved in all sequenced malaria parasite species. The PbQSOX protein was not expressed in asexual erythrocytic stages, but was most abundantly expressed in ookinetes. Indirect immunofluorescence assays revealed PbQSOX was not only localized in cytoplasm of gametocytes, gametes and ookinetes, but also expressed on the surface of gametes and ookinetes. Western blot identified extracellular presence of PbQSOX in the culture medium of ookinetes suggestive of secretion. Pbqsox deletion (Δpbqsox) did not affect asexual intraerythrocytic development, but reduced exflagellation of male gametocytes as well as formation and maturation of ookinetes. Pbqsox deletion also led to a significant increase in the reduced thiol groups of ookinete surface proteins, suggesting that it may play a role in maintaining the integrity of disulfide bonds of surface proteins, which might be needed for ookinete development. Mosquitoes that fed on Δpbqsox-infected mice showed a significant reduction in ookinete and oocyst numbers compared to those fed on wild-type parasite-infected mice. Further, both polyclonal mouse antisera and a monoclonal antibody against the recombinant PbQSOX exhibited substantial transmission-blocking activities in in vitro and mosquito feeding assays, suggesting QSOX is a potential target for blocking parasite transmission.

14.
Breast Cancer Res Treat ; 182(1): 67-77, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32394350

RESUMO

PURPOSE: Platinum plays an important role in the treatment of triple-negative breast cancer (TNBC) in neoadjuvant and metastatic settings. However, its role in an adjuvant setting remains unclear. METHODS: In this non-inferior randomized phase 2 trial, we randomly assigned 308 chemotherapy-naive patients with histologically confirmed TNBC after primary surgery to receive either six cycles of TP (docetaxel: 75 mg/m2 or paclitaxel 175 mg/m2 d1; carboplatin AUC = 5, day 1), or four cycles of EC (epirubicin: 90 mg/m2; cyclophosphamide: 600 mg/m2, day 1) followed by four cycles of T (docetaxel: 75 mg/m2 or paclitaxel 175 mg/m2, day 1). The primary end point was the disease-free survival (DFS) rate at 5 years. Both regimens were repeated every 3 weeks. The prognostic and predictive value of germline breast cancer gene mutations and programmed death ligand-1 (PD-L1) expression was evaluated. RESULTS: At a median follow-up of 66.9 months, the 5-year DFS rate was 85.8% in the EC-T arm, and 84.4% in the TP arm (p non-inferiority = 0.034, p log-rank = 0.712). The 5-year overall survival (OS) rate was 94.4% in the EC-T arm and 93.5% in the TP arm (p = 0.770). Patients in the TP arm showed better compliance and experienced significantly lower frequencies of G3/4 neutrocytopenia and G3/4 alopecia, but higher rates of G1-4 thrombocytopenia than those in the EC-T arm. Patients with PD-L1 expressing tumors showed significantly improved DFS and OS. CONCLUSIONS: This study indicates that carboplatin plus taxanes could be a feasible adjuvant chemotherapy for patients with early TNBC who are cannot tolerate intensive chemotherapy with anthracycline.

15.
J Dig Dis ; 21(4): 199-204, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: covidwho-42091

RESUMO

An epidemic of an acute respiratory syndrome caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, now known as coronavirus disease 2019 (COVID-19), beginning in December 2019, has attracted an intense amount of attention worldwide. As the natural history and variety of clinical presentations of this disease unfolds, extrapulmonary symptoms of COVID-19 have emerged, especially in the digestive system. While the respiratory mode of transmission is well known and is probably the principal mode of transmission of this disease, a possibility of the fecal-oral route of transmission has also emerged in various case series and clinical scenarios. In this review article, we summarize four different aspects in published studies to date: (a) gastrointestinal manifestations of COVID-19; (b) microbiological and virological investigations; (c) the role of fecal-oral transmission; and (d) prevention and control of SARS-CoV-2 infection in the digestive endoscopy room. A timely understanding of the relationship between the disease and the digestive system and implementing effective preventive measures are of great importance for a favorable outcome of the disease and can help climnicians to mitigate further transmission by taking appropriate measures.


Assuntos
Infecções por Coronavirus/transmissão , Infecção Hospitalar/prevenção & controle , Doenças do Sistema Digestório , Endoscopia do Sistema Digestório/normas , Gastroenterologia/normas , Controle de Infecções/normas , Pneumonia Viral/transmissão , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Infecções por Coronavirus/virologia , Infecção Hospitalar/etiologia , Infecção Hospitalar/virologia , Doenças do Sistema Digestório/diagnóstico , Doenças do Sistema Digestório/etiologia , Doenças do Sistema Digestório/microbiologia , Doenças do Sistema Digestório/virologia , Unidades Hospitalares/normas , Humanos , Pandemias , Equipamento de Proteção Individual/normas , Pneumonia Viral/complicações , Pneumonia Viral/virologia
16.
Mol Ther Nucleic Acids ; 20: 400-408, 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32244167

RESUMO

Hammerhead ribozyme-based aptazyme (HHAz), inheriting the advantages of small size and high efficiency from the RNA-cleaving ribozyme and the specific recognition ability of aptamers to specific targets, exhibits the huge potential to be a transgene expression regulator. Herein, we report a selection strategy for HHAz by using a toxin protein IbsC as the reporter to offer a positive phenotype, thus realizing an easy-operating, time- and labor-saving selection of HHAz variants with desired properties. Based on this strategy, we obtained a new HHAz (TAP-1), which could react sensitively toward the extracellular regulatory molecule, theophylline, both in prokaryotic and eukaryotic systems. With fluorescent protein reporter, the intracellular switching efficiencies of TAP-1 and other reported theophylline-dependent HHAzs has been quantitatively evaluated, showing that TAP-1 not only exhibits the best downregulating ability at high concentration of theophylline but also maintains high activity with 0.1 mM theophylline, which is a safe concentration in the human body.

17.
J Dig Dis ; 21(4): 199-204, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32267098

RESUMO

An epidemic of an acute respiratory syndrome caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, now known as coronavirus disease 2019 (COVID-19), beginning in December 2019, has attracted an intense amount of attention worldwide. As the natural history and variety of clinical presentations of this disease unfolds, extrapulmonary symptoms of COVID-19 have emerged, especially in the digestive system. While the respiratory mode of transmission is well known and is probably the principal mode of transmission of this disease, a possibility of the fecal-oral route of transmission has also emerged in various case series and clinical scenarios. In this review article, we summarize four different aspects in published studies to date: (a) gastrointestinal manifestations of COVID-19; (b) microbiological and virological investigations; (c) the role of fecal-oral transmission; and (d) prevention and control of SARS-CoV-2 infection in the digestive endoscopy room. A timely understanding of the relationship between the disease and the digestive system and implementing effective preventive measures are of great importance for a favorable outcome of the disease and can help climnicians to mitigate further transmission by taking appropriate measures.


Assuntos
Infecções por Coronavirus/transmissão , Infecção Hospitalar/prevenção & controle , Doenças do Sistema Digestório , Endoscopia do Sistema Digestório/normas , Gastroenterologia/normas , Controle de Infecções/normas , Pneumonia Viral/transmissão , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Infecções por Coronavirus/virologia , Infecção Hospitalar/etiologia , Infecção Hospitalar/virologia , Doenças do Sistema Digestório/diagnóstico , Doenças do Sistema Digestório/etiologia , Doenças do Sistema Digestório/microbiologia , Doenças do Sistema Digestório/virologia , Unidades Hospitalares/normas , Humanos , Pandemias , Equipamento de Proteção Individual/normas , Pneumonia Viral/complicações , Pneumonia Viral/virologia
18.
Nucleic Acids Res ; 48(8): 4396-4404, 2020 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-32187359

RESUMO

Frameshift mutations are generally considered to be lethal because it could result in radical changes of the protein sequence behind. However, the protein of frameshift mutants of a type I toxin (ibsc) was found to be still toxic to bacteria, retaining the similar function as wild-type protein to arrest the cellular growth by impairing the membrane's integrity. Additionally, we have verified that this observation is not an individual event as the same phenomenon had been found in other toxins subsequently. After analyzing the coding sequence of these genes, we proposed a hypothesis to search this kind of hidden gene, through which a dihydrofolate reductase-encoding gene (dfrB3) was found out. Like the wild-type reductase, both +1 and -1 frame-shifted proteins of dfrB3 gene were also proved to catalyze the reduction of dihydrofolate to tetrahydrofolate by using NADPH.


Assuntos
Toxinas Bacterianas/genética , Mutação da Fase de Leitura , Escherichia coli K12/genética , Genes Bacterianos , Tetra-Hidrofolato Desidrogenase/genética , Tetra-Hidrofolato Desidrogenase/metabolismo
19.
Mar Drugs ; 18(3)2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32188169

RESUMO

Soil-borne pathogens, including phytopathogenic fungi and root-knot nematodes, could synergistically invade vegetable roots and result in serious economic losses. The genus of Trichoderma has been proven to be a promising reservoir of biocontrol agents in agriculture. In this study, the search for antagonistic metabolites from a marine-derived fungus, Trichoderma longibrachiatum, obtained two structural series of sesquiterpenes 1-6 and cyclodepsipeptides 7-9. Notably, the novel 1 was a rare norsesquiterpene characterized by an unprecedented tricyclic-6/5/5-[4.3.1.01,6]-decane skeleton. Their structures were elucidated by extensive spectroscopic analyses, while the absolute configuration of novel 1 was determined by the comparison of experimental and calculated ECD spectra. The novel 1 and known 2 and 3 showed significant antifungal activities against Colletotrichum lagrnarium with MIC values of 8, 16, and 16 µg/mL respectively, even better than those of the commonly used synthetic fungicide carbendazim with 32 µg/mL. They also exhibited antifungal potential against carbendazim-resistant Botrytis cinerea. Cyclodepsipeptides 7-9 showed moderate nematicidal activities against the southern root-knot nematode (Meloidogyne incognita). This study constitutes the first report on the antagonistic effects of metabolites from T. Longibrachiatum against soil-borne pathogens, also highlighting the integrated antagonistic potential of marine-derived T. Longibrachiatum as a biocontrol agent.

20.
Oncogene ; 39(17): 3522-3540, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32111984

RESUMO

Metastasis is a major cause of high recurrence and poor survival of patients with colorectal cancer (CRC), although the mechanisms associated with this process remain poorly understood. In this study, we report a novel mechanism by which SOX13 promotes CRC metastasis by transactivating SNAI2 and c-MET. SOX13 overexpression was significantly correlated with more aggressive clinicopathological features of CRC and indicated poor prognosis in two independent cohorts of CRC patients (cohort I, n = 363; cohort II, n = 390). Overexpression of SOX13-promoted CRC migration, invasion, and metastasis, whereas SOX13 downregulation caused the opposite effects. Further mechanistic investigation identified SNAI2 and MET as important target genes of SOX13 using serial deletion and site-directed mutagenesis luciferase reporter and chromatin immunoprecipitation (ChIP) assays, as well as functional complementation analyses. In addition, SOX13 was shown to be a direct target of HGF/STAT3 signaling, and the c-MET inhibitor crizotinib blocked the HGF/STAT3/SOX13/c-MET axis, significantly inhibiting SOX13-mediated CRC migration, invasion and metastasis. Moreover, in clinical CRC tissues, SOX13 expression was positively correlated with the expression of SNAI2, c-MET, and HGF. CRC patients with positive coexpression of SOX13/SNAI2, SOX13/c-MET, or HGF/SOX13 exhibited a worse prognosis. In summary, SOX13 is a promising prognostic biomarker in patients with CRC, and blocking the HGF/STAT3/SOX13/c-MET axis with crizotinib could be a new therapeutic strategy to prevent SOX13-mediated CRC metastasis.


Assuntos
Autoantígenos/metabolismo , Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas Proto-Oncogênicas c-met/biossíntese , Fatores de Transcrição SOXD/metabolismo , Fatores de Transcrição da Família Snail/biossíntese , Ativação Transcricional , Animais , Autoantígenos/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Metástase Neoplásica , Proteínas Proto-Oncogênicas c-met/genética , Fatores de Transcrição SOXD/genética , Fatores de Transcrição da Família Snail/genética
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