Background Angiotensin‐converting enzyme 2 (ACE2) expressions and its modulation are of great interest as being a key receptor for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV2) and the protective arm of the rennin‐angiotensin axis, maintaining cardiovascular homeostasis. However, ACE2 expressions and their modulation in the healthy and disease background are yet to be explored. Method We performed a meta‐analysis, extracting the data for ACE2 expression in human subjects with various diseases, including SARS‐CoV2 infection without or with co‐morbidity. The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines were followed. Out of 203 studies, 39 met the inclusion criteria with SARS‐CoV2 patients without co‐morbidity, SARS‐CoV2 patients with co‐morbidity, cardiovascular (CVD) patients, diabetes patients, kidney disorders patients, pulmonary disease patients, and other viral infections patients. Results Angiotensin‐converting enzyme 2 expression was significantly increased in all diseases. There was an elevated level of ACE2, especially membrane‐bound ACE2, in COVID‐19 patients compared to healthy controls. A statistically significant increase in ACE2 expression was observed in CVD patients and patients with other viral diseases compared to healthy subjects. Moreover, subgroup analysis of ACE2 expression as soluble and membrane‐bound ACE2 revealed a remarkable increase in membrane‐bound ACE2 in CVD patients, patients with viral infection compared to soluble ACE2 and pooled standard mean difference (SMD) with the random‐effects model was 0.37 and 2.23 respectively. Conclusion It was observed that utilizing the ACE2 by SARS‐CoV2 for its entry and its consequence leads to several complications. So there is a need to investigate the underlying mechanism along with novel therapeutic strategies.
The immune system is a complex, intricate organ system with features like flexibility, recognition, discriminating potential between self from non-self, and memory to defeat notorious external and internal threats to human health functioning. Innate immunity is inborn, and acquired immunity develops through secondary education; they are interconnected, interdependent, and execute tasks with bi.directional communications. A deeper understanding of immune biology revealed a remarkable contribution of the immune system in several chronic illnesses, and has taken a central stage in pathophysiology. In essence, the weakened or overactivated immune system leads to these chronic illnesses. Modulation of the immune system is an efficient and valid approach to prevent the underlying pathophysiology of such diseases. A gamut of natural immunomodulators targeted at specific or non-specif immune cells has delineated their potential to achieve the equilibrated and balanced immune system. Preclinical and clinical studies demonstrated the implication of microbiota, nutrients, natural herbs, and micronutrients for immunostasis. The immune system's complexity, its close association with the endocrine and nervous system, target identification, and convenient, reliable tools to assess immune function and modulation are a few limitations that hampered the attainment of immunostasis. Despite these limitations, novel therapies targeted at immunomodulation in chronic diseases are promising and paving the future path to novel therapeutics.
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