Sour Tamarind Is More Antihypertensive than the Sweeter One, as Evidenced by In Vivo Biochemical Indexes, Ligand-Protein Interactions, Multitarget Interactions, and Molecular Dynamic Simulation.

This research investigated the antihypertensive effects of tamarind products and compared their potentials based on an animal model's data verified by molecular docking, multitarget interactions, and dynamic simulation assays. GC-MS-characterized tamarind products were administered to cholesterol-induced hypertensive albino rat models. The two-week-intervened animals were dissected to collect their serum and organs and respectively subjected to analyses of their hypertension-linked markers and tissue architectures. The lead biometabolites of tamarinds interacted with eight target receptors in the molecular docking and dynamic simulation studies and with multitarget in the network pharmacological analyses. The results show that the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), C-reactive protein (CRP), troponin I, and lipid profiles were maximally reinstated by the phenolic-enriched ripened sour tamarind extract compared to the sweet one, but the seed extracts had a smaller influence. Among the tamarind's biometabolites, ϒ-sitosterol was found to be the best ligand to interact with the guanylate cyclase receptor, displaying the best drug-likeliness with the highest binding energy, -9.3 Kcal. A multitargeted interaction-based degree algorithm and a phylogenetic tree of pathways showed that the NR3C1, REN, PPARG, and CYP11B1 hub genes were consistently modulated by ϒ-sitosterol to reduce hypertension and related risk factors. The dynamic simulation study showed that the P-RMSD values of ϒ-sitosterol-guanylate cyclase were stable between 75.00 and 100.00 ns at the binding pocket. The findings demonstrate that ripened sour tamarind extract may be a prospective antihypertensive nutraceutical or supplement target affirmed through advanced preclinical and clinical studies.

Role of TaqMan array card in determining causative organisms of acute febrile illness in hospitalized patients.

BACKGROUND: Acute febrile illness (AFI) is a prevalent disease in developing countries that is difficult to diagnose due to the diversity of infectious organisms and the poor quality of clinical diagnosis. TaqMan array card (TAC) can detect up to 35 AFI-associated organisms in 1.5 h, addressing diagnostic demands. In this study, we aimed to evaluate the role of TAC in determining the causative organisms in hospitalized AFI patients. METHODS: The study had a cross-sectional design and enrolled 120 admitted patients with persistent fever for three or more days from the medicine ward of Chittagong Medical College Hospital (CMCH) and Bangladesh Institute of Tropical and Infectious Diseases Hospital (BITID). Blood samples were collected and then subjected to automated BacT/Alert blood culture, microbial culture, TAC assay, and typhoid/paratyphoid test. RESULTS: The total number of study participants was 120, among them 48 (40%) samples showed a positive result in TAC card, 29 (24.16%) were TP positive and nine (7.51%) were culture positive. The number of organisms detected by the TAC card was 13 bacteria, three viruses, one protozoan, and one fungus. The sensitivity and specificity of the TAC assay for different bacterial pathogen compared to blood culture was 44.44%, and 90.99%, respectively. In contrast, the TP test had a sensitivity and specificity of 100% and 80%, respectively, compared to the blood culture test. CONCLUSION: TAC can be a handful tool for detecting multiple organisms in AFI with high specificity which can facilitate early diagnosis of different pathogens contributing to AFI.

Bacterial and viral etiology of acute respiratory infection among the Forcibly Displaced Myanmar Nationals (FDMNs) in fragile settings in Cox's Bazar- a prospective case-control study.

The leading infectious cause of death in children worldwide is lower acute respiratory infection (LARI), particularly pneumonia. We enrolled a total of 538 acute respiratory infection (ARI) cases according to WHO criteria and age-sex matched 514 controls in the Forcibly Displaced Myanmar National (FDMN) refugee camps in Cox's Bazar, Bangladesh, between June 2018 and March 2020 to investigate the role of bacteria, viruses, and their co-infection patterns and observe Streptococcus pneumoniae (S. pneumoniae) serotype distribution. According to the etiological findings, children ≤5 years of age have a higher bacterial positivity (90%) and viral positivity (34%) in nasopharyngeal samples (NPS) compared to those >5 years of age, in both ARI cases as well as for the control group. Among the bacteria, S. pneumoniae was predominant in both cases and controls (85% and 88%). Adenovirus (ADV)(34), influenza virus A and B (IFV-A, B)(32,23), and respiratory syncytial virus (RSV)(26) were detected as the highest number among the viruses tested for the ARI cases. The total number of viruses was also found higher in ≤5 years of age group. Within this group, positive correlation was observed between bacteria and viruses but negative correlation was observed between bacteria. Both single and co-infection for viruses were found higher in the case group than the control group. However, co-infection was significantly high for Streptococcus aureus (S. aureus) and Haemophilus influenzae b (H. influenza b) (p<0.05). Additionally, semi-quantitative bacterial and viral load was found higher for the ARI cases over control considering Cycle threshold (Ct)≤30. Pathogen identification from blood specimens was higher by qRT-PCR than blood culture (16% vs 5%, p<0.05). In the S. pneumoniae serotype distribution, the predominant serotypes in ARI cases were 23F, 19A, 16F, 35B, 15A, 20 and 10F, while 11A, 10A, 34, 35A and 13 serotypes were predominant in the control group. Pathogen correlation analysis showed RSV positively correlated with human metapneumovirus (HMPV), S. aureus and H. influenza b while S. pneumoniae was negatively correlated with other pathogens in ≤5 years age group of ARI cases. However, in >5 years age group, S. aureus and H. influenza b were positively correlated with IFVs, and S. pneumoniae was positively correlated with HMPV and ADV. Logistic regression data for viruses suggested among the respondents in cases were about 4 times more likely to be RSV positive than the control. Serotype distribution showed 30% for PCV10 serotypes, 41% for PCV13 and 59% for other serotypes. Also, among the 40 serotypes of S. pneumoniae tested, the serotypes 22F, Sg24, 9V, 38, 8, and 1 showed strong positive correlation with viruses in the case group whereas in the control group, it was predominant for serotypes 14, 38, 17F and 39 ARI cases were prevalent mostly in monsoon, post-monsoon, and winter periods, and peaked in September and October. Overall these region-specific etiological data and findings, particularly for crisis settings representing the FDMNs in Cox's Bazar, Bangladesh, is crucial for disease management and disease prevention control as well as immunization strategies more generally in humanitarian crisis settings.

Reduced IFN-γ levels along with changes in hematologic and immunologic parameters are key to COVID-19 severity in Bangladeshi patients.

The manifestation of coronavirus disease 2019 (COVID-19) severity and mortality has been associated with dysregulation of the immune response, often influenced by racial disparities and conferred by changes in hematologic and immunologic parameters. These biological and hematologic parameters as well as cytokine profiles were investigated in a cohort of 61 COVID-19-positive patients (categorized into mild, moderate, and severe groups) from Bangladesh using standard analytical methods. The data reported that the interleukin (IL)-4 and IL-6 levels were significantly increased, whereas the levels of interferon (IFN)-γ were significantly reduced in patients with severe COVID-19 (p < 0.05) compared with those in patients with mild and/or moderate COVID-19. The extent of erythrocyte sedimentation rate (ESR); neutrophil count; and levels of ferritin, C-reactive protein (CRP), and D-dimer (p < 0.05) were found to be significantly increased, whereas the white blood cell (WBC), lymphocyte, eosinophil, and platelet counts (p < 0.05) were observed to be significantly reduced in patients with severe COVID-19 compared with those in the patients in other 2 groups. Our study exhibited a significantly higher IL-6-to-lymphocyte ratio in patients with severe COVID-19 than in those with mild and moderate COVID-19. The calculated neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and ferritin-to-ESR ratio were significantly increased in patients with severe COVID-19. The increase in the IL-4 and IL-6 levels along with CRP and D-dimer levels may envisage a hyperinflammatory environment and immune dysregulation, which contribute to prolonged viral persistence, leading to severe disease. However, the reduced level of IFN-γ can be attributed to a less fatality toll in Bangladesh compared with that in the rest of the world.

Clinical Presentation of COVID-19 and Antibody Responses in Bangladeshi Patients Infected with the Delta or Omicron Variants of SARS-CoV-2.

The clinical presentation of COVID-19 and the specific antibody responses associated with SARS-CoV-2 variants have not been investigated during the emergence of Omicron variants in Bangladesh. The Delta and Omicron variants were identified by post-PCR melting curve analysis of the spike (S) protein receptor binding domain amplicons. Anti-S-protein immunoglobulin-G anti-nucleocapsid (N)-protein immunoglobulin-G and immunoglobulin-A levels were measured by ELISA. The Delta variant was found in 40 out of 40 (100%) SARS-CoV-2 RT-PCR positive COVID-19 patients between 13 September and 23 October 2021 and Omicron variants in 90 out of 90 (100%) RT-PCR positive COVID-19 patients between 9 January and 10 February 2022. The Delta variant associated with hospitalization (74%, 80%, and 40%) and oxygen support (60%, 57%, and 40%) in the no vaccine, dose-1, and dose-2 vaccinated cases, respectively, whereas the Omicron COVID-19 required neither hospitalization nor oxygen support (0%, p < 0.0001). Fever, cough, and breathlessness were found at a significantly higher frequency among the Delta than Omicron variants (p < 0.001). The viral RNA levels of the Delta variant were higher than that of the Omicron variants (Ct median 19.9 versus 23.85; p < 0.02). Anti-spike protein immunoglobulin-G and anti-N-protein immunoglobulin-G within 1 week post onset of Delta variant COVID-19 symptoms indicate prior SARS-CoV-2 infection. The Delta variant and Omicron BA.1 and BA.2 breakthrough infections in the Dhaka region, at 240 days post onset of COVID-19 symptoms, negatively correlated with the time interval between the second vaccine dose and serum sampling. The findings of lower anti-spike protein immunoglobulin-G reactivity after booster vaccination than after the second vaccine dose suggest that the booster vaccine is not necessarily beneficial in young Bangladeshi adults having a history of repeated SARS-CoV-2 infections.

Detection of Anti-Nucleocapsid Antibody in COVID-19 Patients in Bangladesh Is not Correlated with Previous Dengue Infection.

BACKGROUND: The assessment of antibody responses to severe acute respiratory syndrome coronavirus-2 is potentially confounded by exposures to flaviviruses. The aims of the present research were to determine whether anti-dengue antibodies affect the viral load and the detection of anti-coronavirus nucleocapsid (N)-protein antibodies in coronavirus infectious disease 2019 (COVID-19) in Bangladesh. METHODS: Viral RNA was evaluated in swab specimens from 115 COVID-19 patients by real-time reverse transcription polymerase chain reaction (rT-PCR). The anti-N-protein antibodies, anti-dengue virus E-protein antibodies and the dengue non-structural protein-1 were determined in serum from 115 COVID-19 patients, 30 acute dengue fever pre-COVID-19 pandemic and nine normal controls by ELISA. RESULTS: The concentrations of viral RNA in the nasopharyngeal; Ct median (95% CI); 22 (21.9-23.3) was significantly higher than viral RNA concentrations in oropharyngeal swabs; and 29 (27-30.5) p < 0.0001. Viral RNA concentrations were not correlated with-dengue IgG levels. The anti-nucleocapsid antibodies were IgA 27% positive and IgG 35% positive at days 1 to 8 post-onset of COVID-19 symptoms versus IgA 0% and IgG 0% in dengue patients, p < 0.0001. The levels of anti- nucleocapsid IgA or IgG versus the levels of anti-dengue IgM or IgG revealed no significant correlations. CONCLUSIONS: Viral RNA and anti-nucleocapsid antibodies were detected in COVID-19 patients from dengue-endemic regions of Bangladesh, independently of the dengue IgG levels.

Hepatitis E Virus Capsid Antigen (HEV-Ag) - A practical diagnostic biomarker in the HEV outbreak scenario.

BACKGROUND: The increased global incidence of hepatitis E virus (HEV) infections, warrants accurate and affordable diagnostics across different geographical regions. The soluble and highly conserved HEV open reading frame 2 (ORF2) capsid antigen (HEV-Ag) is detectable in self-limited acute enteric hepatitis by HEV-Ag ELISA which is a promising serological assay in settings where HEV-RNA testing is not feasible. Our aim was to assess the HEV-Ag biomarker in an HEV outbreak in a low income country. METHODS: A prospective single center longitudinal study during HEV outbreaks in the Chittagong, Bangladesh region between October 2018 and October 2019 was conducted based on recruitment of acute jaundice cases with clinical signs and symptoms of suspect HEV infections. Acute HEV infection was defined as a positive test result for anti-HEV IgM antibodies. RESULTS: Forty four of the 51 enrolled enteric hepatitis cases (86 %) were confirmed HEV by anti-HEV IgM ELISA at day 0 hospital entry. The anti-HEV-IgM and IgG were positive in all patients and did not reveal significant differences; neither between the time points day 0 and follow-up hospitalization on day 2-6 or day 7-10 nor between RNA-positive (n = 36) versus RNAnegative (n = 8) HEV groups. The HEV-Ag positivity was higher in viral RNA-positive (29/36, 81 %) than the viral RNA-negative (1/8, 12 %) group, p < 0.001 and the HEV-Ag levels positively correlated with viremia, r = 0.77, p < 0.0001. All non-HEV cases; n = 7 tested negative anti-HEV IgM and HEV-Ag and 5 of 7 (71 %) tested anti-HAV IgM positive. CONCLUSIONS: The HEV-Ag ELISA is a reliable and practical diagnostic tool in this acute HEV outbreak.