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1.
Int Immunopharmacol ; 103: 108467, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34933161

RESUMO

Growing evidence indicates that synovial hypoxia-inducible factor 1α (HIF-1α) can be as a promising target for RA therapy. We previously reported that AMSP-30 m as a novel HIF-1α inhibitor had potent activities of anticancer metastasis. This study clarified the therapeutic effects of HIF-1α inhibitor AMSP-30 m on adjuvant-induced arthritis (AIA) in rats and explored the possible mechanisms. AMSP-30 m was given intraperitoneally to AIA rats, and its therapeutic effects and anti-inflammatory activity were evaluated. The influences of AMSP-30 m on synovial apoptosis, angiogenesis and sonic hedgehog (Shh) pathway were examined. We found that, accompanied with the inhibition of synovial HIF-1α expression, AMSP-30 m had potent anti-arthritic and anti-inflammatory effects on AIA rats, evidenced by the reduction in paw swelling, arthritis index, histopathological scores, and the production of IL-1ß, IL-6, TNF-α in serum and synovial tissues. AMSP-30 m reduced synovial Ki67 expression and increased TUNEL-positive index, indicating its anti-proliferative and pro-apoptotic effects on AIA synovial cells, which was related to reducing Bcl-2 protein level and increasing Bax, cleaved caspase 3 protein levels. Additionally, AMSP-30 m showed anti-angiogenic effects within AIA synovium, indicated by the reduction of synovial VEGF expression and blood vessels number (especially CD31+/αSMA- immature vessels, but not CD31+/αSMA+ mature vessels). Moreover, AMSP-30 m inhibited the activation of synovial Shh pathway, suggested by the reduction of pathway-related proteins, like Shh, Smo, Gli-1, cyclin D1 and c-Myc. Collectively, HIF-1α inhibitor AMSP-30 m exerted potent anti-arthritic effects on AIA rats possibly by promoting synovial apoptosis, reducing synovial angiogenesis and inhibiting Shh pathway.


Assuntos
Artrite Experimental , Proteínas Hedgehog , Subunidade alfa do Fator 1 Induzível por Hipóxia , Sinoviócitos , Animais , Apoptose/efeitos dos fármacos , Artrite Experimental/tratamento farmacológico , Proteínas Hedgehog/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Ratos , Membrana Sinovial/patologia , Sinoviócitos/metabolismo
2.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-20033118

RESUMO

BackgroundsSince December 2019, a novel coronavirus epidemic has emerged in Wuhan city, China and then rapidly spread to other areas. As of 20 Feb 2020, a total of 2,055 medical staff confirmed with coronavirus disease 2019 (COVID-19) caused by SARS-Cov-2 in China had been reported. We sought to explore the epidemiological, clinical characteristics and prognosis of novel coronavirus-infected medical staff. MethodsIn this retrospective study, 64 confirmed cases of novel coronavirus-infected medical staff admitted to Union Hospital, Wuhan between 16 Jan, 2020 to 15 Feb, 2020 were included. Two groups concerned were extracted from the subjects based on duration of symptoms: group 1 ([≤]10 days) and group 2 (>10 days). Epidemiological and clinical data were analyzed and compared across groups. The Kaplan-Meier plot was used to inspect the change in hospital discharge rate. The Cox regression model was utilized to identify factors associated with hospital discharge. FindingsThe median age of medical staff included was 35 years old. 64% were female and 67% were nurses. None had an exposure to Huanan seafood wholesale market or wildlife. A small proportion of the cohort had contact with specimens (5%) as well as patients in fever clinics (8%) and isolation wards (5%). Fever (67%) was the most common symptom, followed by cough (47%) and fatigue (34%). The median time interval between symptoms onset and admission was 8.5 days. On admission, 80% of medical staff showed abnormal IL-6 levels and 34% had lymphocytopenia. Chest CT mainly manifested as bilateral (61%), septal/subpleural (80%) and ground-glass (52%) opacities. During the study period, no patients was transferred to intensive care unit or died, and 34 (53%) had been discharged. Higher body mass index (BMI) ([≥] 24 kg/m2) (HR 0.14; 95% CI 0.03-0.73), fever (HR 0.24; 95% CI 0.09-0.60) and higher levels of IL-6 on admission (HR 0.31; 95% CI 0.11-0.87) were unfavorable factors for discharge. InterpretationIn this study, medical staff infected with COVID-19 have relatively milder symptoms and favorable clinical course, which may be partly due to their medical expertise, younger age and less underlying diseases. Smaller BMI, absence of fever symptoms and normal IL-6 levels on admission are favorable for discharge for medical staff. Further studies should be devoted to identifying the exact patterns of SARS-CoV-2 infection among medical staff.

3.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-779424

RESUMO

Objective To understand the relationship between the concentration of air pollutants and daily emergency department visits for different diseases (circulatory system disease, digestive system disease, nervous system disease and respiratory system disease) in Guangzhou, Guangdong Province. Methods The daily average concentrations of sulfur dioxide (SO2), nitrogen dioxide (NO2, carbon monoxide (CO) and PM2.5 and the daily maximum 8-hour concentrations of O3, the daily average temperature, the relative humidity and cause -specific emergency department visits of the four major diseases from 2015 to 2017 were collected in Guangzhou. Semi-parametric generalized additive model was used to analyze the relationship between the concentration of pollutants and daily cause-specific emergency department visits. Results The daily average concentrations of SO2, NO2, CO, O3 and PM2.5 during the study period were 13.24 μg /m3, 45.96 μg /m3, 0.97 mg /m3, 123.77 μg /m3 and 36.22 μg /m3, respectively. For circulatory system disease,the independently significant associations of SO2 with emergency department visits in single-pollutant models (2.91%, 95% CI: 1.00%-4.85%), and multipollutant models (4.39%, 95% CI: 1.22%-7.67%) were observed. Conclusion The ambient SO2 increases the risk of emergency department visits due to circulatory diseases in Guangzhou. Comprehensive prevention and control measures should be taken to reduce the emission of SO2.

4.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-250483

RESUMO

Leguminous related SSR primers were collected, core primers used for Astragali Radix and Hedysari Radix identification were screened and validated by using molecular marker techniques. 6 core primers were selected from 101 pairs of primers, the molecular weight of PCR products was 100-500 bp, which formed 7-12 electrophoresis bands with 55 amplified loci. The percentage of polymorphic loci was 100%, and the average polymorphism information content was 0.371. According to the results of cluster analysis, obtained core primer could completely distinguish 62 mixture samples of Astragali Radix and Hedysari Radix in similarity coefficient of 0.46. Core primers and the corresponding characteristics from gel electrophoresis were tagged. The results provide identification basis for Astragali Radix and Hedysari Radix.

5.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-262769

RESUMO

<p><b>OBJECTIVE</b>Atrial natriuretic peptide (ANP) is a cardiac hormone with many biological effects. Hypersecretion may lead to hyponatremia. This study examined the umbilical ANP levels in high risk neonates.</p><p><b>METHODS</b>A total of 117 high risk neonates born between June, 2004 and June, 2005 were divided into Simple asphyxia and Normal score groups according to their Apgar's scores. The Simple asphyxia group was subdivided into Mild (n=20) and Severe asphyxia groups (n=17), and the Normal score group was subdivided into Infection (n=25) and Non-infection groups (n=55). Forty normal neonates were used as the Control group. The samples of umbilical cord blood were collected at delivery and the umbilical ANP levels were measured by radioimmunoassay. Meanwhile the sodium levels in the peripheral vein were measured.</p><p><b>RESULTS</b>The mean umbilical ANP levels in high risk neonates were significantly higher than those in the normal neonates. A more significant increase of the umbilical ANP level was observed in premature infants (1.46 +/- 0.39 ng/mL), and neonates with serious infection (1.16 +/- 0.35 ng/mL) and with severe asphyxia (2.12 +/- 0.46 ng/mL) compared with the normal neonates (0.62 +/- 0.33 ng/mL; P < 0.01). The serum sodium level was negatively correlated with the umbilical ANP level (r=-0.99, P < 0.01).</p><p><b>CONCLUSIONS</b>The umbilical ANP levels increased significantly in the high risk neonates, suggesting high risk neonates are susceptible to hyponatremia.</p>


Assuntos
Humanos , Recém-Nascido , Fator Natriurético Atrial , Sangue , Sangue Fetal , Química , Hiponatremia , Risco , Sódio , Sangue
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