RESUMO
Apoptosis is proved responsible for renal damage during ischemia/reperfusion. The regulation for renal apoptosis induced by ischemia/reperfusion injury (IRI) has still been unclearly characterized to date. In the present study, we investigated the regulation of histone acetylation on IRI-induced renal apoptosis and the molecular mechanisms in rats with the application of curcumin possessing a variety of biological activities involving inhibition of apoptosis. Sprague–Dawley rats were randomized into four experimental groups (SHAM, IRI, curcumin, SP600125). Results showed that curcumin significantly decreased renal apoptosis and caspase-3/-9 expression and enhanced renal function in IRI rats. Treatment with curcumin in IRI rats also led to the decrease in expression of p300/cyclic AMP response element-binding protein (CBP) and activity of histone acetyltransferases (HATs). Reduced histone H3 lysine 9 (H3K9) acetylation was found near the promoter region of caspase-3/-9 after curcumin treatment. In a similar way, SP600125, an inhibitor of c-Jun N-terminal kinase (JNK), also attenuated renal apoptosis and enhanced renal function in IRI rats. In addition, SP600125 suppressed the binding level of p300/CBP and H3K9 acetylation near the promoter region of caspase-3/-9, and curcumin could inhibit JNK phosphorylation like SP600125. These results indicate that curcumin could attenuate renal IRI via JNK/p300/CBP-mediated anti-apoptosis signaling.
RESUMO
Apoptosis is proved responsible for renal damage during ischemia/reperfusion. The regulation for renal apoptosis induced by ischemia/reperfusion injury (IRI) has still been unclearly characterized to date. In the present study, we investigated the regulation of histone acetylation on IRI-induced renal apoptosis and the molecular mechanisms in rats with the application of curcumin possessing a variety of biological activities involving inhibition of apoptosis. Sprague–Dawley rats were randomized into four experimental groups (SHAM, IRI, curcumin, SP600125). Results showed that curcumin significantly decreased renal apoptosis and caspase-3/-9 expression and enhanced renal function in IRI rats. Treatment with curcumin in IRI rats also led to the decrease in expression of p300/cyclic AMP response element-binding protein (CBP) and activity of histone acetyltransferases (HATs). Reduced histone H3 lysine 9 (H3K9) acetylation was found near the promoter region of caspase-3/-9 after curcumin treatment. In a similar way, SP600125, an inhibitor of c-Jun N-terminal kinase (JNK), also attenuated renal apoptosis and enhanced renal function in IRI rats. In addition, SP600125 suppressed the binding level of p300/CBP and H3K9 acetylation near the promoter region of caspase-3/-9, and curcumin could inhibit JNK phosphorylation like SP600125. These results indicate that curcumin could attenuate renal IRI via JNK/p300/CBP-mediated anti-apoptosis signaling.
RESUMO
BackgroundProtecting health care workers (HCWs) during the coronavirus disease 2019 (COVID-19) pandemic is essential. Serologic testing can identify HCWs who had minimally symptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections that were missed by occupational screening based on daily symptom and temperature checks. Recent studies report conflicting results regarding the impact of occupational factors on SARS-CoV-2 seropositivity amongst HCWs. MethodsThe study population included all hospital workers at an academic medical center in Orange County, California. SARS-CoV-2 seropositivity was assessed from a fingerstick blood specimen using a coronavirus antigen microarray, which compares IgM and IgG antibodies against a panel of SARS-CoV-2 antigens with positive and negative controls to identify prior SARS-CoV-2 infection with 98% specificity and 93% sensitivity. Demographic, occupational, and clinical factors were surveyed and their effect on seropositivity estimated using multivariable logistic regression analysis. ResultsAmongst 1,557 HCWs with complete data, SARS-CoV-2 seropositivity was 10.8%. Risk factors for increased seropositivity included male gender, exposure to COVID-19 outside of work, working in food or environmental services, and working in COVID-19 units. Amongst the 1,103 HCW who were seropositive but missed by occupational screening, additional risk factors included younger age and working in administration. ConclusionsSARS-CoV-2 seropositivity is significantly higher than reported case counts even amongst HCWs who are meticulously screened. Seropositive HCWs missed by occupational screening were more likely to be younger, work roles without direct patient care, or have COVID-19 exposure outside of work. Key PointsSARS-CoV-2 seropositivity risk factors amongst health care workers included male gender, nonoccupational exposure, food or environmental services role, and COVID-19 unit location. Those missed by occupational screening were younger, in roles without direct patient care, or exposed outside of work.
RESUMO
To detect the presence of antibodies in blood against SARS-CoV-2 in a highly sensitive and specific manner, here we describe a robust, inexpensive ($200), 3D-printable portable imaging platform (TinyArray imager) that can be deployed immediately in areas with minimal infrastructure to read coronavirus antigen microarrays (CoVAMs) that contain a panel of antigens from SARS-CoV-2, SARS-1, MERS, and other respiratory viruses. Application includes basic laboratories and makeshift field clinics where a few drops of blood from a finger prick could be rapidly tested in parallel for the presence of antibodies to SARS-CoV-2 with a test turnaround time of only 2-4 h. To evaluate our imaging device, we probed and imaged coronavirus microarrays with COVID-19-positive and negative sera and achieved a performance on par with a commercial microarray reader 100x more expensive than our imaging device. This work will enable large scale serosurveillance, which can play an important role in the months and years to come to implement efficient containment and mitigation measures, as well as help develop therapeutics and vaccines to treat and prevent the spread of COVID-19.