Association of Plasma Circulatory Markers, Chlamydia pneumoniae, and High Sensitive C-Reactive Protein in Coronary Artery Disease Patients of India

Plasma inflammatory markers have been shown to be predictors for cardiovascular risk, however, there is no study where the levels of plasma circulatory markers have been evaluated in coronary artery disease patients (CAD pts) positive for C. pneumoniae IgA and high sensitive C-reactive protein (hsCRP) which may help in better understanding of disease pathogenesis. A total of 192 patients and 192 controls attending the Cardiology Outpatient Department of Safdarjung Hospital were enrolled. The levels of plasma circulatory inflammatory markers were evaluated by ELISA. The levels of circulatory plasma markers (IL-4, IL-8, IL-13, ICAM-1, and VCAM-1) were significantly higher, whereas, levels of IL-10 and IFN-γ were significantly lower in CAD pts compared to healthy controls. The levels of IL-4, IL-8, and ICAM-1 (P = .007, .015, and .048) were significantly higher, however, IL-10 and IFN-γ were significantly lower (P < .001, < .001) in C. pneumoniae IgA positive CAD pts. The levels of IL-4, IL-8, IL-13, ICAM-1, and VCAM-1 were higher but not significant and levels of IL-10 and IFN-γ were significantly (P < .001, < .001) lower in hsCRP positive CAD pts. Our study suggested that circulatory cytokines, namely, IL-4, IL-8, and adhesive molecules like ICAM-1 were enhanced after infection with C. pneumoniae whereas in contrast to this IL-10 and IFN-λ were lowered. Suggesting the important role of these cytokines in progression of CAD

Chlamydia pneumoniae heat shock protein 60 is associated with apoptotic signaling pathway in human atheromatous plaques of coronary artery disease patients

SummaryBackgroundChlamydia pneumoniae heat shock protein (HSP) 60 is known to contribute to the activation of inflammation. In addition, there are contradictory reports on C. pneumoniae and their role in activation of pathways (apoptotic/antiapoptotic/necrosis) in coronary artery disease (CAD). Hence, more studies are required to know the actual role of C. pneumoniae in activation of apoptotic/antiapoptotic/necrosis pathways.Methods and resultsIn this study, two sets of patient groups (cHSP60 positive and cHSP60 negative) were included and gene expression was studied by cDNA micro array and real time polymerase chain reaction arrays. Expression of Caspase-3, 8, 9, c-FLIP, PPAR-γ, PGC-1α, and Gsk-3b were also evaluated at protein level by immunoblotting. In cHSP60 positive CAD patients significantly higher (p<0.001) mRNA expression was found for CCL4, CXCL4, CXCL9, IL-8, CD40LG, CD8, TGFβ1, TGFβ2, APOE, EGR1, CTGF, APOB, LDLR, LPA, and LPL, whereas significantly lower (p<0.001) mRNA expression was detected for CD4, IL1F10, IFNA2, and IL-10 as compared to cHSP60 negative CAD patients. Additionally, at protein level expression of Caspase-3 (p=0.027), 8 (p=0.028), and 9 (p=0.037) were higher and c-FLIP (p=0.028) and PPAR-γ (p=0.95) expression were comparable in cHSP60 positive CAD patients compared to cHSP60 negative CAD patients.ConclusionGenes/proteins of pre-apoptotic caspase dependent/independent pathways, chemokines, and inflammatory cytokines receptors were significantly up-regulated in human atheromatous plaques of cHSP60 positive CAD patients suggesting an association of cHSP60 with CAD

Novel tempeh (fermented soyabean) isoflavones inhibit in vivo angiogenesis in the chicken chorioallantoic membrane assay

Anti-angiogenic strategies are emerging as an important tool for the treatment of cancer and inflammatory diseases. In the present investigation we isolated several isoflavones from a tempeh (fermented soyabean) extract. The isolated isoflavones were identified as 5,7,4′-trihydroxyisoflavone (genistein), 7,4′-dihydroxyisoflavone (daidzein), 6,7,4′-trihydroxyisoflavone (factor 2), 7,8,4′-trihydroxyisoflavone (7,8,4′-TriOH) and 5,7,3′,4′-tetrahydroxyisoflavone (orobol). The effects on angiogenesis of these isoflavones were evaluated in the chicken chorioallantoic membrane assay; their capacity to inhibit vascular endothelial growth factor-induced endothelial cell proliferation and expression of the Ets 1 transcription factor, known to be implicated in the regulation of new blood vessel formation, were also investigated. We found that all isoflavones inhibited angiogenesis, albeit with different potencies. Compared with negative controls, which slightly inhibited in vivo angiogenesis by 6·30 %, genistein reduced angiogensis by 75·09 %, followed by orobol (67·96 %), factor 2 (56·77 %), daidzein (48·98 %) and 7,8,4′-TriOH (24·42 %). These compounds also inhibited endothelial cell proliferation, with orobol causing the greatest inhibition at lower concentrations. The isoflavones also inhibited Ets 1 expression, providing some insight into the molecular mechanisms of their action. Furthermore, the chemical structure of the different isoflavones suggests a structure-activity relationship. Our present findings suggest that the new isoflavones might be added to the list of low molecular mass therapeutic agents for the inhibition of angiogenesi

Upregulation of Cellular Bcl-2 by the KSHV Encoded RTA Promotes Virion Production

Apoptosis of virus infected cells can restrict or dampen full blown virus propagation and this can serve as a protective mechanism against virus infection. Consequently, viruses can also delay programmed cell death by enhancing the expression of anti-apoptotic proteins. Human Bcl-2 is expressed on the surface of the mitochondrial membrane and functions as the regulator of the delicate balance between cell survival and apoptosis. In this report, we showed that the replication and transcription activator (RTA) encoded by KSHV ORF 50, a key regulator for KSHV reactivation from latent to lytic infection, upregulates the mRNA and protein levels of Bcl-2 in 293 cells, and TPA-induced KSHV-infected cells. Further analysis revealed that upregulation of the cellular Bcl-2 promoter by RTA is dose-dependent and acts through targeting of the CCN9GG motifs within the Bcl-2 promoter. The Bcl-2 P2 but not the P1 promoter is primarily responsive to RTA. The results of ChIP confirmed the direct interaction of RTA protein with the CCN9GG motifs. Knockdown of cellular Bcl-2 by lentivirus-delivered small hairpin RNA (shRNA) resulted in increased cell apoptosis and decreased virion production in KSHV-infected cells. These findings provide an insight into another mechanism by which KSHV utilizes the intrinsic apoptosis signaling pathways for prolonging the survival of lytically infected host cells to allow for maximum production of virus progeny

Epstein Barr virus: Diseases linked to Infection and Transformation

Epstein-Barr virus (EBV) was first discovered in 1964, and was the first known human tumor virus now shown to be associated with a vast number of human diseases. Numerous studies have been conducted to understand infection, propagation and transformation in various cell types linked to human diseases. However, a comprehensive lens through which virus infection, reactivation and transformation of infected host cells can be visualized is yet to be formally established and will need much further investigation. Several human cell types infected by EBV have been linked to associated diseases. However, whether these are a direct result of EBV infection or indirectly due to contributions by additional infectious agents will need to be fully investigated. Therefore, a thorough examination of infection, reactivation and cell transformation induced by EBV will provide a more detailed view of its contributions that drive pathogenesis. This undoubtedly expand our knowledge of the biology of EBV infection and the signaling activities of targeted cellular factors dysregulated on infection. Furthermore, these insights may lead to identification of therapeutic targets and agents for clinical interventions. Here we review the spectrum of EBV-associated diseases, the role of the encoded latent antigens, and the switch to latency or lytic replication which occurs in EBV infected cells. Furthermore, we describe the cellular processes and critical factors which contribute to cell transformation. We also describe the fate of B-cells and epithelial cells after EBV infection and the expected consequences which contribute to establishment of viral-associated pathologies

Status of Epstein-Barr Virus Coinfection with Helicobacter pylori in Gastric Cancer

Epstein-Barr virus is a ubiquitous human herpesvirus whose primary infection causes mononucleosis, Burkett’s lymphoma, nasopharyngeal carcinoma, autoimmune diseases, and gastric cancer (GC). The persistent infection causes malignancies in lymph and epithelial cells. Helicobacter pylori causes gastritis in human with chronic inflammation. This chronic inflammation is thought to be the cause of genomic instability. About 45%-word population have a probability of having both pathogens, namely, H. pylori and EBV. Approximately 180 per hundred thousand population is developing GC along with many gastric abnormalities. This makes GC the third leading cause of cancer-related death worldwide. Although lots of research are carried out individually for EBV and H. pylori, still there are very few reports available on coinfection of both pathogens. Recent studies suggested that EBV and H. pylori coinfection increases the occurrence of GC as well as the early age of GC detection comparing to individual infection. The aim of this review is to present status on coinfection of both pathogens and their association with GC

A comparative analysis of COVID-19 outbreak on age groups and both the sexes of population from India and other countries

INTRODUCTION: The study of epidemiological outcomes of COVID-19 in the affected countries needs to be conducted to implement an effective strategy. METHODOLOGY: Our study included age and sex-based analysis of epidemiological data of infected and deceased patients from various countries. The patient data was graphically depicted with the slope's calculation to describe a gradual or steep spread of the disease along with subsequent rise or fall in the death reports. RESULTS: Population groups of 20-49 years of age and 50 years-above were highly vulnerable to infection. Interestingly, 20-49 years of age group was most affected in India. However, higher population of the deceased were reported in the 50 years-above in all countries. India and South Korea demonstrated a gradual appearance of COVID-19 positive cases than other countries illustrated by reduced slope %. Further the highest percentage of infected people and deaths were reported from the densely populated states of India. We observed a sex independent prevalence of COVID-19. The BCG and JE vaccine are unique in the vaccination regime of India and South Korea. CONCLUSIONS: Reduced ACE-2 expression in the children's nasal epithelium may be responsible for reduced SARS-CoV-2 susceptibility. Countries showed varying patterns in COVID-19 spread and associated mortality. It may be influenced by factors, such as screening strategy, countries demography, implementation of lockdown, etc. Due to limited evidence, it would be difficult to point to the influence of the virus on either sexes. Although vaccines may stimulate non-specific immunity, experimental proofs are needed to demonstrate the potential of any vaccine against SARS-CoV-2

Assessment of Mental Stress among Medical Undergraduate Students of a tertiary health care centre of Bihar, India

Background: Studies done across the world reveals that psychological morbidity like stress is commonly present in medical undergraduate students. Aim: To find out the prevalence of stress among medical undergraduate students. Materials and Method: Across sectional study was conducted among 150 medical undergraduates to assess their levels of stress by using Kessler 10 (K10) psychological distress scale. Stress was categorized into none, mild, moderate and severe categories.Result: The total prevalence of stress was 62.6% and the prevalence of severe stress was 21.3%.Conclusion: Students should receive consultation on how to manage and cope up with stress. Preventive mental health services, supportive learning environment and student counseling services need to be made available and accessible to curb this morbidity