Prime-boost immunization strategies are required to control the global tuberculosis (TB) pandemic, which claims approximately 3 lives every minute. Here, we have generated an immunogenic complex against Mycobacterium tuberculosis ( M.tb ), consisting of promiscuous T cell epitopes ( M.tb peptides) and TLR ligands assembled in liposomes. Interestingly, this complex (peptide–TLR agonist–liposomes; PTL) induced significant activation of CD4 + T cells and IFN-γ production in the PBMCs derived from PPD + healthy individuals as compared with PPD – controls. Furthermore, intranasal delivery of PTL significantly reduced the bacterial burden in the infected mice by inducing M.tb -specific polyfunctional (IFN-γ + IL-17 + TNF-α + IL-2 + ) immune responses and long-lasting central memory responses, thereby reducing the risk of TB recurrence in DOTS-treated infected animals. The transcriptome analysis of peptide-stimulated immune cells unveiled the molecular basis of enhanced protection. Furthermore, PTL immunization significantly boosted the Bacillus Calmette-Guerin–primed (BCG-primed) immune responses against TB. The greatly enhanced efficacy of the BCG-PTL vaccine model in controlling pulmonary TB projects PTL as an adjunct vaccine against TB.
Tuberculosis (TB), is one of the deadliest infectious-diseases of human-civilization. Approximately one-third of global-population is latently-infected with the TB-pathogen Mycobacterium tuberculosis (M.tb). The discovery of anti-TB antibiotics leads to decline in death-rate of TB. However, the evolution of antibiotic-resistant, M.tb-strain, and the resurgence of different immune compromised diseases re-escalated the death-rate of TB. WHO has already cautioned about the chances of pandemic-situation in TB endemic countries unless the discovery of new antitubercular drugs, i.e., the need of the hour. Analysing the pathogenesis of TB it was found that M.tb evades the host by altering the balance of immune-response and affects either by killing the cells or by creating inflammation. In the preantibiotic era, traditional medicines were only therapeutic measures for different infectious-diseases including tuberculosis. The ancient-literatures of India or ample Indian traditional knowledge and ethnomedicinal-practices are evidence for the treatment of TB using different indigenous plants. However, in the light of modern scientific approach, anti-TB effects of those plants and their bioactive-molecules were not established thoroughly. In this review, focus has been given on five bioactive-molecules of different traditionally used Indian ethnomedicinal plants for treatment of TB or TB-like symptom. These compounds are also validated with proper identification and their mode of action with modern scientific approaches. The effectiveness of these molecules for sensitive or drug-resistant TB-pathogen in clinical or preclinical studies were also evaluated. Thus, our specific aim is to highlight such scientifically validated bioactive compounds having anti-mycobacterial and immuno-modulatory activity for future use as medicine or adjunct-therapeutic molecule for TB management.
BACKGROUND Early detection and accurate diagnosis of heart failure remain a huge clinical challenge in patients with acute dyspnoea of various aetiologies. Different biomarkers of left ventricular dysfunction are being studied to differentiate acute cardiogenic from noncardiogenic dyspnoea. Amongst those, Brain Natriuretic Peptide (BNP) is an important biomarker for diagnosing acute stage of cardiac dyspnoea. The aim of this study is to assess the Plasma N-Terminal Pro-Brain Natriuretic Peptide (NT-ProBNP) level in acute dyspnoea of various aetiologies and to establish the diagnostic or prognostic value of plasma NT-ProBNP in acute dyspnoea of cardiac diseases. MATERIALS AND METHODS In our study, we have taken 84 cases of acute dyspnoea. The acute dyspnoea above 15 years of age were included in the study. Whereas dyspnoea due to chest trauma, renal insufficiency (serum creatinine > 2.5 mg/dL), previously known as valvular heart diseases and severe coronary ischaemia identified as > 0.1 MV ST-segment elevation or ST depression on 12-lead ECG were excluded from the study. After taking patient's history, the clinical examination with routine blood test, electrocardiography and chest x-ray were done. In addition, blood sample was collected for NT-ProBNP measurement. RESULTS In our study group, out of 84 cases Male= 55 (65.4%) and Female= 29 (34.6%). Among those cases 40 (47.6%) had acute cardiac dyspnoea, whereas 44 (52.4%) had non-cardiac dyspnoea. The mean + SD NT-ProBNP concentration of cases with acute cardiac dyspnoea was (4539.7 + 4342.9 pg/ mL), which was significantly higher than the cases with non-cardiac dyspnoea (136.6 + 94.7 pg/ mL), (P < 0.00001). On the evaluation of acute heart failure according to NYHA (New York Heart Association classification), 44 (52.4%) had NYHA Class-I symptoms, 3 (7.5%) had NYHA Class-II symptoms, 10 (25%) had Class-III symptoms and 27 (67.5%) had Class-IV symptoms that demonstrate the significant relationship of NT-ProBNP of NYHA symptom severity with analysis using ANOVA (P < 0.00001). The median NT-ProBNP level was 150 pg/ mL (IQR-713 pg/ mL) in patients with left ventricular ejection fraction (LVEF) > 50% and 4580 pg/ mL (IQR-3180 pg/ mL) in those with LVEF < 50% (P < 0.00001). CONCLUSION The serum NT-ProBNP measurement is a useful parameter for diagnosing cardiac causes of dyspnoea and also acute heart failure as per NYHA class. It can be used for early detection and management of acute heart failure.
Corona virus disease 2019 (COVID-19) pandemic is caused by SARS-CoV2 (Severe Acute Respiratory Syndrome Coronavirus-2). It primarily targets lung epithelial cells of human respiratory system. The original strain of coronavirus was first identified at the end of December 2019 and emerged during an outbreak in Wuhan, China. The SARS-CoV-2 infection is mostly seen in the people with weak immune system. There are different ex-situ approaches to prevent the infection of corona virus viz., use of masks, sanitizing body and surfaces and maintaining social distance. But apart from them, in-situ prevention approaches like inclusion of nutrient rich healthy foods and herbs in daily diet helps to protect the body from inside by strengthening immune system. Thus, to strengthen immune system from inside we need to take immunity boosters, apart from normal healthy diet. These immunity boosters are prepared from leaves, roots, stems, flowers, barks and some other parts of medicinal and spice crops. These contain a mixture of proteins and other organic chemicals and carbohydrates, which include alkaloids, flavoids, glycosides, saponins, and terpenes. Kabasura kudineer, Nilavembu kudineer, Immuplus, Echinacea liquid, Immusarc, Septilin and immunity plus are some of the important immunotonics to strengthen and to protect body from infections and safeguard health. In this context we have to supplement our body with these immunity boosters to fight against not only COVID-19 but also other diseases.
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