Archives of microbiology & immunology最新文献

SARS-CoV-2 infection has led to a range of long-lasting symptoms, collectively referred to as long COVID. Current research highlights the critical role of angiotensin-converting enzyme 2 (ACE2) in regulating gut microbiota diversity, vascular function, and homeostasis within the renin-angiotensin system (RAS). ACE2 is utilized by the SARS-CoV-2 virus to enter host cells, but its downregulation following infection contributes to gut microbiota dysbiosis and RAS disruption. These imbalances have been linked to a range of long COVID symptoms, including joint pain, chest pain, chronic cough, fatigue, brain fog, anxiety, depression, myalgia, peripheral neuropathy, memory difficulties, and impaired attention. This review investigates the dysregulation caused by SARS-CoV-2 infection and the long-term effects it has on various organ systems, including the musculoskeletal, neurological, renal, respiratory, and cardiovascular systems. We explored the bidirectional interactions between the gut microbiota, immune function, and these organ systems, focusing on how microbiota dysregulation contributes to the chronic inflammation and dysfunction observed in long COVID symptoms. Understanding these interactions is key for identifying effective therapeutic strategies and interventional targets aimed at mitigating the impact of long COVID on organ health and improving patient outcomes.

COVID-19 was initially identified as a respiratory system disorder, but it has been reported to interact with and influence the cardiovascular system, in addition to many other body systems. Although COVID-19-associated cardiovascular (CV) complications are common, resulting in high acute phase mortality and a large number of morbidities in the chronic phase, thus severely impacting patients' quality of life and health outcomes, yet clinical, cellular, and molecular biological factors underlying the pathophysiology of cardiovascular complications associated with COVID-19 are poorly understood. This review investigates putative underlying clinical factors as well as cellular and molecular biological mechanisms by which COVID-19 leads to acute CV complications, including state-of-the-art genomic sequencing-based findings, and assessing the long-term CV consequences of COVID-19, aiming to shed light on developing strategies for differential diagnosis, risk prognostic stratification, prevention, and clinical management of CV sequels in COVID-19 patients. We found that the relationship between COVID-19 and CV risk is complex and multifaceted. Intriguingly, in addition to acute COVID-19 detertriuos effects, COVID-19 survivors may experience long-term CV effects as well that may have long-lasting clinical consequences. Here in this article, we provide a detailed account of a large number of genomic alterations, microRNAs, and novel viral as well as host proteins in CVDs associated with COVID-19, which has helped identify some novel drug targets to treat COVID-19-related cardiovascular complications.

Long Covid is one of the most prevalent and puzzling conditions that arose with the Covid pandemic. Covid-19 infection generally resolves within several weeks but some experience new or lingering symptoms. Though there is no formal definition for such lingering symptoms the CDC boadly describes long Covid as persons having a wide range of new, recurring or sustained health issues four or more weeks after first being infected with SARS-CoV2. The WHO defines long Covid as the manifestation of symptoms from a "probable or confirmed" Covid-19 infection that start approximately 3 months after the onset of the acute infection and last for more than 2 months. Numerous studies have looked at the implications of long Covid on various organs. Many specific mechanisms have been proposed for such changes. In this article, we provide an overview of some of the main mechanisms by which long Covid induces end-organ damage proposed in recent research studies. We also review various treatment options, current clinical trials, and other potential therapeutic avenues to control long Covid followed by the information about the effect of vaccination on long Covid. Lastly, we discuss some of the questions and knowledge gaps in the present understanding of long Covid. We believe more studies of the effects long Covid has on quality of life, future health and life expectancy are required to better understand and eventually prevent or treat the disease. We acknowledge the effects of long Covid are not limited to those in this article but as it may affect the health of future offspring and therefore, we deem it important to identify more prognostic and therapeutic targets to control this condition.

There is increasing evidence that the T-cell protein, Lck, is involved in the pathogenesis of chronic lymphocytic leukemia (CLL) as well as other leukemias and lymphomas. We previously discovered that Lck binds to domain 5 of inositol 1,4,5-trisphosphate receptors (IP₃R) to regulate Ca²⁺ homeostasis. Using bioinformatics, we targeted a region within domain 5 of IP₃R-1 predicted to facilitate protein-protein interactions (PPIs). We generated a synthetic 21 amino acid peptide, KKRMDLVLELKNNASKLLLAI, which constitutes a domain 5 sub-domain (D5SD) of IP₃R-1 that specifically binds Lck via its SH2 domain. With the addition of an HIV-TAT sequence to enable cell permeability of D5SD peptide, we observed wide-spread, Ca²⁺-dependent, cell killing of hematological cancer cells when the Lck-IP₃R PPI was disrupted by TAT-D5SD. All cell lines and primary cells were sensitive to D5SD peptide, but malignant T-cells were less sensitive compared with B-cell or myeloid malignancies. Mining of RNA-seq data showed that LCK was expressed in primary diffuse large B-cell lymphoma (DLBCL) as well as acute myeloid leukemia (AML). In fact, LCK shows a similar pattern of expression as many well-characterized AML oncogenes and is part of a protein interactome that includes FLT3-ITD, Notch-1, and Kit. Consistent with these findings, our data suggest that the Lck-IP₃R PPI may protect malignant hematopoietic cells from death. Importantly, TAT-D5SD showed no cytotoxicity in three different non-hematopoietic cell lines; thus its ability to induce cell death appears specific to hematopoietic cells. Together, these data show that a peptide designed to disrupt the Lck-IP₃R PPI has a wide range of pre-clinical activity in leukemia and lymphoma.