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1.
J Zhejiang Univ Sci B ; 21(11): 911-920, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33150774

RESUMO

OBJECTIVE: To investigate the value of optic disc retinal nerve fiber layer (RNFL) thickness in the diagnosis of diabetic peripheral neuropathy (DPN). METHODS: Ninety patients with type 2 diabetes, including 60 patients without DPN (NDPN group) and 30 patients with DPN (DPN group), and 30 healthy participants (normal group) were enrolled. Optical coherence tomography (OCT) was used to measure the four quadrants and the overall average RNFL thickness of the optic disc. The receiver operator characteristic curve was drawn and the area under the curve (AUC) was calculated to evaluate the diagnostic value of RNFL thickness in the optic disc area for DPN. RESULTS: The RNFL thickness of the DPN group was thinner than those of the normal and NDPN groups in the overall average ((101.07± 12.40) µm vs. (111.07±6.99) µm and (109.25±6.90) µm), superior quadrant ((123.00±19.04) µm vs. (138.93±14.16) µm and (134.47±14.34) µm), and inferior quadrant ((129.37±17.50) µm vs. (143.60±12.22) µm and (144.48±14.10) µm), and the differences were statistically significant. The diagnostic efficiencies of the overall average, superior quadrant, and inferior quadrant RNFL thicknesses, and a combined index of superior and inferior quadrant RNFL thicknesses were similar, and the AUCs were 0.739 (95% confidence interval (CI) 0.635-0.826), 0.683 (95% CI 0.576-0.778), 0.755 (95% CI 0.652-0.840), and 0.773 (95% CI 0.672-0.854), respectively. The diagnostic sensitivity of RNFL thickness in the superior quadrant reached 93.33%. CONCLUSIONS: The thickness of the RNFL in the optic disc can be used as a diagnostic method for DPN.

2.
Vet Med Sci ; 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33161653

RESUMO

China has a long history of pig rearing, and it currently raises and consumes approximately half of the pigs in the world. Major improvements have been made in pig farming in China in the last four decades with the growing application of new livestock farming technologies. Among the new improvements, the use of antibiotics in pig farming is a common but not well-documented practise. In order to understand the behaviour of the farmers regarding antibiotic use in pig farming, we conducted a household survey in four townships of L County in Yunnan Province, China, during August 2014 and April 2015. In this survey, 404 farmer households were interviewed using a questionnaire. Among the farmers interviewed, 89% reported easy access to antibiotics, 83.7% reported experience of self-purchasing antibiotics, and 40.3% reported that they often used antibiotics in pig farming mainly for the prevention and treatment of pig diseases. These farmers identified 20 antibiotics that they had used in pig farming 6 months before the survey. Of these, 11 and 8 antibiotics have been categorised under 'critically important' and 'highly important' antimicrobial groups, respectively, by the World Health Organization (WHO), and 12 and 8 have been categorised under the 'Watch' and 'Access' groups, respectively, as per the 2019 WHO AWaRe classification of antibiotics. Factors associated with the behaviour of self-purchasing antibiotics included types of farms, sources of antibiotics, and previous experiences of pig diseases: those who were smallholders, buying antibiotics from veterinary drugstores and village vets, and whose pigs had suffered diseases previously were more likely to self-purchase antibiotics for their pigs. Farmers who cleaned their pigsties less frequently and those whose pigs had suffered from diseases used antibiotics more frequently as compared to their peer farmers.

3.
Nat Commun ; 11(1): 5683, 2020 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-33173058

RESUMO

Clinical efficacy of treatments against non-obstructive azoospermia (NOA), which affects 1% of men, are currently limited by the incomplete understanding of NOA pathogenesis and normal spermatogenic microenvironment. Here, we profile >80,000 human testicular single-cell transcriptomes from 10 healthy donors spanning the range from infant to adult and 7 NOA patients. We show that Sertoli cells, which form the scaffold in the testicular microenvironment, are severely damaged in NOA patients and identify the roadmap of Sertoli cell maturation. Notably, Sertoli cells of patients with congenital causes (Klinefelter syndrome and Y chromosome microdeletions) are mature, but exhibit abnormal immune responses, while the cells in idiopathic NOA (iNOA) are physiologically immature. Furthermore, we find that inhibition of Wnt signaling promotes the maturation of Sertoli cells from iNOA patients, allowing these cells to regain their ability to support germ cell survival. We provide a novel perspective on the development of diagnostic methods and therapeutic targets for NOA.

4.
MMWR Morb Mortal Wkly Rep ; 69(44): 1617-1621, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33151923

RESUMO

Stroke is the fifth leading cause of death in the United States (1). In 2017, on average, a stroke-related death occurred every 3 minutes and 35 seconds in the United States, and stroke is a leading cause of long-term disability (1). To prevent mortality or long-term disability, strokes require rapid recognition and early medical intervention (2,3). Common stroke signs and symptoms include sudden numbness or weakness of the face, arm, or leg, especially on one side; sudden confusion or trouble speaking; sudden trouble seeing in one or both eyes; sudden trouble walking, dizziness, or loss of balance; and a sudden severe headache with no known cause. Recommended action at the first sign of a suspected stroke is to quickly request emergency services (i.e., calling 9-1-1) (2). Public education campaigns have emphasized recognizing stroke signs and symptoms and the importance of calling 9-1-1, and stroke knowledge increased 14.7 percentage points from 2009 to 2014 (4). However, disparities in stroke awareness have been reported (4,5). Knowledge of the five signs and symptoms of stroke and the immediate need to call emergency medical services (9-1-1), collectively referred to as "recommended stroke knowledge," was assessed among 26,076 adults aged ≥20 years as part of the 2017 National Health Interview Survey (NHIS). The prevalence of recommended stroke knowledge among U.S. adults was 67.5%. Stroke knowledge differed significantly by race and Hispanic origin (p<0.001). The prevalence of recommended stroke knowledge was highest among non-Hispanic White adults (71.3%), followed by non-Hispanic Black adults (64.0%) and Hispanic adults (57.8%). Stroke knowledge also differed significantly by sex, age, education, and urbanicity. After multivariable adjustment, these differences remained significant. Increasing awareness of the signs and symptoms of stroke continues to be a national priority. Estimates from this report can inform public health strategies for increasing awareness of stroke signs and symptoms.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Acidente Vascular Cerebral/diagnóstico , Adulto , Idoso , Despacho de Emergência Médica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , População Rural/estatística & dados numéricos , Fatores Socioeconômicos , Inquéritos e Questionários , Estados Unidos , População Urbana/estatística & dados numéricos , Adulto Jovem
5.
J Psychiatr Res ; 130: 333-341, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32889355

RESUMO

PURPOSE: Codeine-containing cough syrup (CCS) is considered among the most popular drugs of abuse in adolescents worldwide. Accurate prediction and identification of CCS dependent (CCSD) users are crucial. This study aimed to identify a brain-connectome-based predictor of CCSD using a machine learning model based on a ten-fold cross-validation logistic regression (LR) classifier. METHODS: 40 CCSD users and 40 healthy control (HC) subjects underwent functional magnetic resonance imaging to construct weight functional networks. Partial correlation analysis was used to analyze relations between abnormal network metrics and clinical characteristics (BIS total scores, CCS abuse duration, and mean CCS dose) in CCSD. A ten-fold cross-validation LR classifier was used to classify CCSD users and HC subjects. RESULTS: The CCSD group showed significantly abnormal nodes and connections in the right posterior cingulate, right middle insula, bilateral prefrontal cortex, parietal lobe, temporal lobe, occipital lobe, and cerebellum. Furthermore, higher characteristic path length and lower clustering coefficient (Cp), global efficiency, and local efficiency (Eloc) were observed in the global topologies in CCSD. The abnormal global properties (Cp and Eloc) and node properties of the prefrontal cortex were significantly correlated with clinical characteristics (BIS-11 scores, CCS abuse duration) in CCSD. The LR classifier models demonstrated accuracy, sensitivity, specificity, precision, and AUC of 82.5%, 82.5%, 82.5%, 76.8%, and 82.5%. CONCLUSIONS: These data demonstrate that abnormal functional connectome may be closely linked to clinical characteristics in CCSD. Functional connectome-based biomarkers can be a powerful tool for personalized diagnosis of CCSD in the future.

6.
World J Surg Oncol ; 18(1): 251, 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32958079

RESUMO

BACKGROUND: It has been demonstrated that simultaneous resection of both primary colorectal lesion and metastatic hepatic lesion is a safe approach with low mortality and postoperative complication rates. However, there are some controversies over which kind of surgical approach is better. The aim of study was to compare the efficacy and safety of laparoscopic surgeries and open surgeries for simultaneous resection of colorectal cancer (CRC) and synchronous colorectal liver metastasis (SCRLM). METHODS: A systemic search of online database including PubMed, Web of Science, Cochrane Library, and Embase was performed until June 5, 2019. Intraoperative complications, postoperative complications, and long-term outcomes were synthesized by using STATA, version 15.0. Cumulative and single-arm meta-analyses were also conducted. RESULTS: It contained twelve studies with 616 patients (273 vs 343, laparoscopic surgery group and open surgery group, respectively) and manifested latest surgical results for the treatment of CRC and SCRLM. Among patients who underwent laparoscopic surgeries, they had lower rates of postoperative complications (OR = 0.66, 95% CI: 0.46 to 0.96, P = 0.028), less intraoperative blood loss (weight mean difference (WMD) = - 113.31, 95% CI: - 189.03 to - 37.59, P = 0.003), less time in the hospital and recovering after surgeries (WMD = - 2.70, 95% CI: - 3.99 to - 1.40, P = 0.000; WMD = - 3.20, 95% CI: - 5.06 to - 1.34, P = 0.001), but more operating time (WMD = 36.57, 95% CI: 7.80 to 65.35, P = 0.013). Additionally, there were no statistical significance between two kinds of surgical approaches in disease-free survival and overall survival. Moreover, cumulative meta-analysis indicated statistical difference in favor of laparoscopic surgery in terms of morbidity was firstly detected in the 12th study in 2018 (OR = 0.66, 95% CI: 0.46 to 0.96, P = 0.028) as the 95% CI narrowed. CONCLUSION: Compared with open surgeries, laparoscopic surgeries are safer (postoperative complications and intraoperative blood loss) and more effective (length of hospital stay and postoperative stay), and it can be considered as the first option for management of SCRLM in high-volume laparoscopic centers. TRIAL REGISTRATION: CRD42020151176.

8.
Aging (Albany NY) ; 12(17): 16867-16886, 2020 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-32952128

RESUMO

At present, there are few studies focused on the relationship between copper (Cu) and oxidative stress, apoptosis, or inflammatory responses in animal and human lungs. This study was conducted to explore the effects of Cu on pulmonary oxidative stress, apoptosis and inflammatory responses in mice orally administered with 0 mg/kg (control), 10 mg/kg, 20 mg/kg, and 40 mg/kg of CuSO4 for 42 days. The results showed that CuSO4 increased ROS production, and MDA, 8-OHdG and NO contents as well as iNOS activities and mRNA expression levels. Meanwhile, CuSO4 reduced the activities and mRNA expression levels of antioxidant enzymes (GSH-Px, CAT, and SOD) and GSH contents, and ASA and AHR abilities. Also, CuSO4 induced apoptosis, which was accompanied by decreasing Bcl-2, Bcl-xL mRNA expression levels and protein expression levels, and increasing Bax, Bak, cleaved-caspase-3, cleaved-caspase-9 mRNA, and protein expression levels, and Bax/Bcl-2 ratio. Concurrently, CuSO4 caused inflammation by increasing MPO activities and activating the NF-κB signalling pathway, and down-regulating the mRNA and protein expression levels of anti-inflammatory cytokines (IL-2, IL-4, IL-10). In conclusion, the abovementioned findings demonstrated that over 10 mg/kg CuSO4 can cause oxidative stress, apoptosis, and inflammatory responses, which contribute to pulmonary lesions and dysfunction in mice.

9.
Oxid Med Cell Longev ; 2020: 7151946, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32963699

RESUMO

Vascular endothelial senescence induced by high glucose and palmitate (HG/PA) contributes to endothelial dysfunction, which leads to diabetic cardiovascular complications. Reduction of endothelial senescence may attenuate these pathogenic processes. This study is aimed at determining whether Ginseng-Sanqi-Chuanxiong (GSC) extracts, traditional Chinese medicine, can ameliorate human aortic endothelial cell (HAEC) senescence under HG/PA-stressed conditions and further explore the underlying mechanism. We found that GSC extracts significantly increased antisenescent activity by reducing the HG/PA-induced mitochondrial ROS (mtROS) levels in senescent HAECs. GSC extracts also induced cellular mitophagy formation, which mediated the effect of GSC extracts on mtROS reduction. Apart from this, the data showed that GSC extracts stimulated mitophagy via the AMPK pathway, and upon inhibition of AMPK by pharmacological and genetic inhibitors, GSC extract-mediated mitophagy was abolished which further led to reverse the antisenescence effect. Taken together, these data suggest that GSC extracts prevent HG/PA-induced endothelial senescence and mtROS production by mitophagy regulation via the AMPK pathway. Thus, the induction of mitophagy by GSC extracts may provide a novel therapeutic candidate for cardiovascular protection in metabolic syndrome.

10.
Glob Chang Biol ; 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32926493

RESUMO

Forest ecosystems are an important sink for terrestrial carbon sequestration. Hence, accurate modeling of the intra- and interannual variability of forest photosynthetic productivity remains a key objective in global biology. Applying climate-driven leaf phenology and growth in models may improve predictions of the forest gross primary productivity (GPP). We used a dynamic non-structural carbohydrates (NSC) model (FORCCHN2) that couples leaf development and phenology to investigate the relationships among photosynthesis and environmental factors. FORCCHN2 simulates spring and autumn phenological events from heat and chilling, respectively. Leaf area index data from satellites along with climate data estimated localized phenological parameters. NSC limitation, immediate temperature, accumulated heat, and growth potential comprised a daily leaf-growth model. Functionally, leaf growth was decoupled from photosynthesis. Leaf biomass determined overall photosynthetic production. We compared this model with outputs of the other six terrestrial biospheric models and with observations from the North American Carbon Program Site Interim Synthesis in 18 forest sites. This model improved the predicted performance of yearly GPP with a 57%-210% increase in correlation (median) and up to a 102% reduction in biases (median), compared to three prognostic models and three prescribed models. At the North America continental scale, the model predicted the average annual GPP of 7.38 Pg C/year from forest ecosystems during 1985-2016. The results showed an increasing trend of GPP in North America (1.0 Pg C/decade). The inclusion of climate-driven phenology and growth has a significant potential for improving dynamic vegetation models, and promotes a further understanding of the complex relationship between environment and photosynthesis.

11.
Helicobacter ; 25(6): e12754, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32876377

RESUMO

The rapid development of microbiota research has remolded our view of human physiological and pathological processes. Among all the gastrointestinal microorganisms, Helicobacter pylori (H pylori) is probably the most notorious constituent. Although half of the adults worldwide are infected with H pylori, their clinical manifestations vary widely, suggesting other microorganisms beyond H pylori may play a role in determining clinical outcomes. Recently, many studies have put effort into elucidating the crosstalk within the human microbiota, some of which specifically explored the interplay between H pylori and other gastrointestinal microbial members. In this work, we reviewed these potential interactions. Meanwhile, the impacts of H pylori eradication therapy on gastrointestinal microbial homeostasis were summarized in terms of diversity, composition, functional capacity, and antibiotic resistance.

12.
Steroids ; 163: 108726, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32889051

RESUMO

The main purpose of this study was to evaluate the estrogenic properties of total flavonoids (TFs) and five flavonoid monomers (cardamonin (Car), pinostrobin chalcone (PC), wogonin (Wo), chrysin (Chr) and Pinocembrin (PI)) from leaves of Carya cathayensis Sarg (LCC). TFs from LCC were isolated and determined using HPLC. The 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry were performed to assess the effects of flavonoids on cell proliferation and cell cycle, respectively. The molecular docking technique was applied to investigate binding conformations of the monomers from LCC to the estrogen receptor ERα and ERß. Gene and protein expression patterns were assessed using quantitative real-time PCR (qRT-PCR) and western blot, respectively. The results showed that TFs, Car, PC, Wo and Chr promoted proliferation of MCF-7 cells and cell transition from the G1 to S phase, and inhabitation of MCF-7 cell proliferation was observed after the treatment of PI. Molecular docking studies confirmed ERs as molecular targets for the monomers. TFs, Car, PC, Wo and Chr from LCC promoted gene expression of ERα, ERß, progesterone receptor (PR) and pS2. Our collective results demonstrated that TFs and monomers from LCC may exert ER agonist activity through competitively bind to ER, inducing ER upregulation and active ER to estrogen response element (ERE)- independent gene regulation. As an abundant natural product, LCC may provide a novel medicinal source for treatment of diseases caused by estrogen deficiency.

13.
Cancer Manag Res ; 12: 6069-6075, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32765104

RESUMO

Background: More and more studies show that platelets are closely related to the occurrence and development of tumors. This study aims to explore the predictive value of peripheral blood platelet count on the prognosis of breast cancer patients with ipsilateral supraclavicular lymph node (ISLN) metastasis. Methods: Eighty-five breast cancer patients with ISLN metastasis in the Affiliated Cancer Hospital of Zhengzhou University were collected retrospectively in this study. Chi-square test was used to analyze the correlation between clinical pathological data and platelet count. DFS rate was estimated by K-M curve and Log Rank test was performed. Univariate and multivariate Cox regression were used to determine the prognostic value of platelets. Time-dependent Cox regression was used to further analyze the correlation between peripheral blood platelets and prognosis to determine the stability of the results. Results: The pathological complete response rate of ISLN after neoadjuvant chemotherapy (NAC) was 51.8%. Platelet count was correlated with PR status of breast cancer at first visit (P=0.01). After a median follow-up of 30 months, multivariate Cox analysis showed that high platelet count (HR=3.18, 95% CI=1.13-8.93, P=0.028), premenopausal status (HR=0.40, 95% CI=0.17-0.97, P=0.043), and ISLN pathological failure (HR=0.25 95%, CI=0.10-0.62, P<0.01) were associated with poor prognosis. K-M curve analysis showed that the prognosis of patients with a high platelet count was worse than that of patients with low platelet count (HR=5.32, 95% CI=2.41-11.75, P<0.01). To further verify the stability of this result, multivariate time-dependent Cox model also suggested that higher platelet level was related to poor prognosis (HR=1.009, 95% CI=1.003-1.016, P<0.01). Meanwhile, menopausal status (HR=0.32, 95% CI=0.14-0.76, P=0.01) and sPCR (HR=0.29, 95% CI=0.12-0.70, P=0.01) were also independent predictors of DFS. Conclusion: Platelets have important predictive value for the prognosis of breast cancer patients with ISLN metastasis, which indicates that platelet count can be used to distinguish high-risk patients so as to obtain clinical benefits.

14.
Contemp Clin Trials ; 96: 106101, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32771432

RESUMO

The control strategies preventing subclinical transmission differed among countries. A stochastic transmission model was used to assess the potential effectiveness of control strategies at controlling the COVID-19 outbreak. Three strategies included lack of prevention of subclinical transmission (Strategy A), partial prevention using testing with different accuracy (Strategy B) and complete prevention by isolating all at-risk people (Strategy C, Taiwan policy). The high probability of containing COVID-19 in Strategy C is observed in different scenario, had varied in the number of initial cases (5, 20, and 40), the reproduction number (1.5, 2, 2.5, and 3.5), the proportion of at-risk people being investigated (40%, 60%, 80%, to 90%), the delay from symptom onset to isolation (long and short), and the proportion of transmission that occurred before symptom onset (<1%, 15%, and 30%). Strategy C achieved probability of 80% under advantageous scenario, such as low number of initial cases and high coverage of epidemiological investigation but Strategy B and C rarely achieved that of 60%. Considering the unsatisfactory accuracy of current testing and insufficient resources, isolation of all at-risk people, as adopted in Taiwan, could be an effective alternative.


Assuntos
Infecções Assintomáticas/epidemiologia , Controle de Doenças Transmissíveis , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Humanos , Período de Incubação de Doenças Infecciosas , Modelos Teóricos , Pandemias/prevenção & controle , Isolamento de Pacientes , Pneumonia Viral/prevenção & controle , Quarentena , Taiwan/epidemiologia
15.
Environ Monit Assess ; 192(9): 569, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32770276

RESUMO

Hydrocarbon contamination due to anthropogenic activities is a major environmental concern worldwide. The present study focuses on biochar prepared from fruit and vegetable waste and sewage sludge using a thermochemical approach and its application for the enhanced bioremediation (biostimulation and bioaugmentation) of diesel-polluted soil. The biochar was characterized using FTIR (Fourier-transform infrared spectroscopy), elemental analysis, surface area analysis, and pore analysis. Adsorption experiments showed that hydrocarbon degradation was attributed to biological processes rather than adsorption. The study found that various biochar amendments could significantly increase the rate of hydrocarbon biodegradation with removal efficiencies > 70%. Bioaugmentation using cow dung further improved the removal efficiency to 82%. Treatments showing the highest degree of removal efficiency indicated the presence of 27 different bacteria phyla with Proteobacteria and Actinobacteria as the most abundant phyla. The present study concludes that biochar amendments have great potential for enhancing the bioremediation of soils contaminated with diesel range hydrocarbons.


Assuntos
Petróleo , Poluentes do Solo/análise , Animais , Biodegradação Ambiental , Bovinos , Carvão Vegetal , Monitoramento Ambiental , Feminino , Hidrocarbonetos , Solo , Microbiologia do Solo
16.
Artigo em Inglês | MEDLINE | ID: mdl-32851523

RESUMO

Co-transport of biochar (BC) colloids with coexisting organic contaminants (OCs) in soil involves complex interactions among BC colloids, OCs, and soil particles, which is significant for the environmental application and risk assessment of BC and yet has not been well addressed. This study explored co-transports of three typical OCs (i.e., phenanthrene (PHN), atrazine (ATZ), and oxytetracycline (OTC)) and BC colloids obtained from bulk BCs with different charring temperatures (200-700 °C) and particle sizes (250 nm, 500 nm, and 1 µm) in a soil column of 9 cm in height. Considerable transport of BC colloids alone was observed and the maximum breakthrough concentration (C/Co) increased from 0.08 to 0.77 as the charring temperature decreased from 700 to 200 °C. The mobilities of PHN, OTC, and ATZ alone were very low but were greatly increased by co-transports with BC colloids, and their maximum C/Co values were within 0.05-0.33, 0.03-0.44, and 0.05-0.62, respectively, in the absence and presence of various BC colloids. The enhancement effect of BC colloids on the OC transport decreased with increasing charring temperature or particle size of BC colloids. BC colloids mainly acted as a vehicle to facilitate the transport of OCs, and dissolved organic carbon from BC colloids also contributed to the increased mobility of OCs in dissolved form. These findings provide new insights into co-transport of BC colloids and contaminants in soil.

17.
Oxid Med Cell Longev ; 2020: 6829271, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32685099

RESUMO

Obesity has developed into a considerable health problem in the whole world. Escherichia coli (E. coli) can cause nosocomial pneumonia and induce cell apoptosis during injury and infection. Normal (lean) and diet-induced obesity mice (DIO, fed with high-fat diet) were chosen to perform nasal instillation with E. coli to establish a nonfatal acute pneumonia model. At 0 h, 12 h, 24 h, and 72 h postinfection, lung tissues were obtained to measure cell apoptosis. As shown in this study, both lean and DIO mice exhibited histopathological lesions of acute pneumonia and increased cell apoptosis in the lung infected with E. coli. Interestingly, the relative mRNA and protein expressions associated with either endoplasmic reticulum stress or death receptor apoptotic pathway were all dramatically increased in the DIO mice after infection, while only significant upregulation of death receptor apoptotic pathway in the lean mice at 72 h. These results indicated that the DIO mice executed excess cell apoptosis in the nonfatal acute pneumonia induced by E. coli infection through endoplasmic reticulum stress and death receptor apoptotic pathway.

18.
Artigo em Inglês | MEDLINE | ID: mdl-32602613

RESUMO

Entangled proteins have attracted significant research interest. Herein, we report the first rationally designed lasso proteins, or protein [1]rotaxanes, by using a p53dim-entwined dimer for intramolecular entanglement and a SpyTag-SpyCatcher reaction for side-chain ring closure. The lasso structures were confirmed by proteolytic digestion, mutation, NMR spectrometry, and controlled ligation. Their dynamic properties were probed by experiments such as end-capping, proteolytic digestion, and heating/cooling. As a versatile topological intermediate, a lasso protein could be converted to a rotaxane, a heterocatenane, and a "slide-ring" network. Being entirely genetically encoded, this robust and modular lasso-protein motif is a valuable addition to the topological protein repertoire and a promising candidate for protein-based biomaterials.

19.
J Dig Dis ; 21(8): 454-461, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32621394

RESUMO

OBJECTIVE: To clarify the pathological characteristics of granuloma and granulomatous lymphangitis in patients with non-neoplastic bowel diseases and to compare their significance in the differential diagnosis of Crohn's disease (CD) and intestinal tuberculosis (ITB). METHODS: Altogether 78 cases with CD, 11 with ITB and 33 suffering from other non-neoplastic bowel diseases were included. All patients underwent a partial enterectomy and histopathological examination. Pathological sections were reviewed retrospectively. Detailed morphological features and the distribution of granulomas and granulomatous lymphangitis in the three groups were analyzed and compared. RESULTS: Significant differences in the features of granuloma were observed in CD compared with ITB, including the presence of Langhans giant cells, caseous necrosis, coalescence, hyaline change, onionskin changes, and their frequency and size. Granulomatous lymphangitis was significantly more frequent in CD than in other non-neoplastic bowel diseases (P < 0.0001). The rate was also higher than that of granuloma in CD (P = 0.0004). It more often manifested within the mucosal layer of the small bowel (55.4%) in CD whereas it tended to be located within the deep layers of the intestinal wall in other diseases. It can be divided into four types, but types 1 and 2 appeared relatively specific to CD. CONCLUSIONS: Granuloma and granulomatous lymphangitis were not specific in CD. However, by combining morphology and distribution, their manifestations could assist in the differentiation of CD from other non-neoplastic bowel diseases. Furthermore, granulomatous lymphangitis showed better diagnostic performance than granulomas in the mucosal layer of the small bowel.

20.
Gut Microbes ; 12(1): 1788900, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-32684087

RESUMO

The enrichment of Enterotoxigenic Bacteroides fragilis (ETBF) has been identified in CRC patients and associated with worse prognosis. Cancer stem cells (CSCs) play essential roles in CRC development. However, whether ETBF is involved in CSCs regulation is unknown. To clarify the role of ETBF in CSCs properties, we performed extreme limited dilution assays (ELDA) in nude mice injected with ETBF-treated or untreated CRC cells subcutaneously, tumor organoids culture in azoxymethane (AOM) mouse model after gavaging with or without ETBF, and cell sphere formation assay after incubating CRC cell lines with or without ETBF. The results indicated that ETBF increased the stemness of CRC cells in vivo and in vitro. Furthermore, ETBF enhanced the expression of core stemness transcription factors Nanog homeobox (NANOG) and sex determining region Y-box 2 (SOX2). Histone H3 Lysine 9 trimethylation (H3K9me3) is critical in regulating CSCs properties. As an epigenetic and transcriptional regulator, JmjC-domain containing histone demethylase 2B (JMJD2B) is essential for embryonic stem cell (ESC) transformation and H3K9me3 demethylation. Mechanistically, ETBF infection significantly upregulated JMJD2B levels in CRC cell lines and nude mice xenograft model. JMJD2B epigenetically upregulated NANOG expression via demethylating its promoter H3K9me3, to mediate ETBF-induced stemness of CRC cells. Subsequently, we found that the Toll-like receptor 4 (TLR4) pathway, activated by ETBF, contributed to the enhanced expression of JMJD2B via nuclear transcription factor nuclear factor of activated T cells 5 (NFAT5). Finally, in human CRC samples, the amount of ETBF positively correlated with nuclear NFAT5, JMJD2B, and NANOG expression levels. In summary, ETBF upregulated JMJD2B levels in a TLR4-NFAT5-dependent pathway, and played an important role in stemness regulation, which promoted colorectal carcinogenesis.

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