The coronavirus disease (COVID-19) is caused by a positive-stranded RNA virus called severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), belonging to the Coronaviridae family. This virus originated in Wuhan City, China, and became the cause of a multiwave pandemic that has killed 3.46 million people worldwide as of May 22, 2021. The havoc intensified with the emergence of SARS-CoV-2 variants (B.1.1.7; Alpha, B.1.351; Beta, P.1; Gamma, B.1.617; Delta, B.1.617.2; Delta-plus, B.1.525; Eta, and B.1.429; Epsilon etc.) due to mutations generated during replication. More variants may emerge to cause additional pandemic waves. The most promising approach for combating viruses and their emerging variants lies in prophylactic vaccines. Several vaccine candidates are being developed using various platforms, including nucleic acids, live attenuated virus, inactivated virus, viral vectors, and protein-based subunit vaccines. In this unprecedented time, 12 vaccines against SARS-CoV-2 have been phased in following WHO approval, 184 are in the preclinical stage, and 100 are in the clinical development process. Many of them are directed to elicit neutralizing antibodies against the viral spike protein (S) to inhibit viral entry through the ACE-2 receptor of host cells. Inactivated vaccines, to the contrary, provide a wide range of viral antigens for immune activation. Being an intracellular pathogen, the cytotoxic CD8⁺ T Cell (CTL) response remains crucial for all viruses, including SARS-CoV-2, and needs to be explored in detail. In this review, we try to describe and compare approved vaccines against SARS-CoV-2 that are currently being distributed either after phase III clinical trials or for emergency use. We discuss immune responses induced by various candidate vaccine formulations; their benefits, potential limitations, and effectiveness against variants; future challenges, such as antibody-dependent enhancement (ADE); and vaccine safety issues and their possible resolutions. Most of the current vaccines developed against SARS-CoV-2 are showing either promising or compromised efficacy against new variants. Multiple antigen-based vaccines (multivariant vaccines) should be developed on different platforms to tackle future variants. Alternatively, recombinant BCG, containing SARS-CoV-2 multiple antigens, as a live attenuated vaccine should be explored for long-term protection. Irrespective of their efficacy, all vaccines are efficient in providing protection from disease severity. We must insist on vaccine compliance for all age groups and work on vaccine hesitancy globally to achieve herd immunity and, eventually, to curb this pandemic.

To establish a productive infection in host cells, viruses often use one or multiple host membrane glycoproteins as their receptors. For Influenza A virus (IAV) such a glycoprotein receptor has not been described, to date. Here we show that IAV is using the host membrane glycoprotein CD66c as a receptor for entry into human epithelial lung cells. Neuraminidase (NA), a viral spike protein, binds to CD66c on the cell surface during IAV entry into the host cells. Lung cells overexpressing CD66c showed an increase in virus binding and subsequent entry into the cell. Upon comparison, CD66c demonstrated higher binding capacity than other membrane glycoproteins (EGFR and DC-SIGN) reported earlier to facilitate IAV entry into host cells. siRNA mediated knockdown of CD66c from lung cells inhibited virus binding on cell surface and entry into cells. Blocking CD66c by antibody on the cell surface resulted in decreased virus entry. We found that CD66c is a specific glycoprotein receptor for influenza A virus that did not affect entry of non-IAV RNA virus (Hepatitis C virus). Finally, IAV pre-incubated with recombinant CD66c protein when administered intranasally in mice showed decreased cytopathic effects in mice lungs. This publication is the first to report CD66c (Carcinoembryonic cell adhesion molecule 6 or CEACAM6) as a glycoprotein receptor for Influenza A virus.

Background: Exercise therapy can potentially relieve symptoms and improve functional status of the knee osteoarthritis population. Despite the proved practical benefits, there is no standard, comprehensive physiotherapeutic protocol available targeting the physical and physiological impairment cluster associated with disease. Osteoarthritis is a whole joint disease, affecting joint cartilage, ligaments, menisci and joint associated muscles, from variable pathophysiological processes. Hence, there is a need to develop a physiotherapy protocol to address the multi-structural physical, physiological and functional impairments associated with the disease. Objective: The objective of the present study is to evaluate the efficacy of designed, therapist supervised, patient education, progressive resistance exercises, passive stretching exercises, soft tissue manipulation, muscle energy technique, Maitland mobilization, aerobic exercise, and neuromuscular training physiotherapy protocol on pain, disability, balance, and physical functional performance in knee osteoarthritis patients. Methodology: The preliminary study was conducted on a (n = 60) sample of convenience. The samples were randomly allocated into two study groups, intervention, and control group. The control group was advised on a basic home program. On the other hand, the treatment of the intervention group was designed with a therapist supervised Physiotherapy Protocol. The outcome variables studied were the Visual Analogue Scale, Modified WOMAC Scale, Timed Up and Go Test, Functional Reach Test, 40 m Fast Paced Walk Test, Stair Climb Test, 30 s Chair Stand Test. Results: The results of the study revealed a significant improvement among most of the studied outcome measures in the intervention group, hence the designed supervised physiotherapy protocol was found effective in relieving multiple physiological impairments associated with this whole joint disease.

Traumatic optic neuropathy (TON) has been regarded a vision-threatening condition caused by either ocular or blunt/penetrating head trauma, which is characterized by direct or indirect TON. Injury happens during sports, vehicle accidents and mainly in military war and combat exposure. Earlier, we have demonstrated that remote ischemic post-conditioning (RIC) therapy is protective in TON, and here we report that AMPKα1 activation is crucial. AMPKα1 is the catalytic subunit of the heterotrimeric enzyme AMPK, the master regulator of cellular energetics and metabolism. The α1 isoform predominates in immune cells including macrophages (Mφs). Myeloid-specific AMPKα1 KO mice were generated by crossing AMPKα1^Flox/Flox and LysM^cre to carry out the study. We induced TON in mice by using a controlled impact system. Mice (mixed sex) were randomized in six experimental groups for Sham (mock); Sham (RIC); AMPKα1^F/F (TON); AMPKα1^F/F (TON+RIC); AMPKα1^F/F LysM^Cre (TON); AMPKα1^F/F LysM^Cre (TON+RIC). RIC therapy was given every day (5–7 days following TON). Data were generated by using Western blotting (pAMPKα1, ICAM1, Brn3 and GAP43), immunofluorescence (pAMPKα1, cd11b, TMEM119 and ICAM1), flow cytometry (CD11b, F4/80, CD68, CD206, IL-10 and LY6G), ELISA (TNF-α and IL-10) and transmission electron microscopy (TEM, for demyelination and axonal degeneration), and retinal oxygenation was measured by a Unisense sensor system. First, we observed retinal morphology with funduscopic images and found TON has vascular inflammation. H&E staining data suggested that TON increased retinal inflammation and RIC attenuates retinal ganglion cell death. Immunofluorescence and Western blot data showed increased microglial activation and decreased retinal ganglion cell (RGCs) marker Brn3 and axonal regeneration marker GAP43 expression in the TON [AMPKα1^F/F] vs. Sham group, but TON+RIC [AMPKα1^F/F] attenuated the expression level of these markers. Interestingly, higher microglia activation was observed in the myeloid AMPKα1^F/F KO group following TON, and RIC therapy did not attenuate microglial expression. Flow cytometry, ELISA and retinal tissue oxygen data revealed that RIC therapy significantly reduced the pro-inflammatory signaling markers, increased anti-inflammatory macrophage polarization and improved oxygen level in the TON+RIC [AMPKα1^F/F] group; however, RIC therapy did not reduce inflammatory signaling activation in the myeloid AMPKα1 KO mice. The transmission electron microscopy (TEM) data of the optic nerve showed increased demyelination and axonal degeneration in the TON [AMPKα1^F/F] group, and RIC improved the myelination process in TON [AMPKα1^F/F], but RIC had no significant effect in the AMPKα1 KO mice. The myeloid AMPKα1c deletion attenuated RIC induced anti-inflammatory macrophage polarization, and that suggests a molecular link between RIC and immune activation. Overall, these data suggest that RIC therapy provided protection against inflammation and neurodegeneration via myeloid AMPKα1 activation, but the deletion of myeloid AMPKα1 is not protective in TON. Further investigation of RIC and AMPKα1 signaling is warranted in TON.

Diverse COVID-19 severity levels and a spectrum of clinical manifestations underscore the need to comprehend the underlying genetic mechanisms. Such knowledge is essential for improving disease management and therapeutic approaches. This study aims to explore and uncover pivotal genes and pathways linked to distinct COVID-19 conditions, providing insights into potential therapeutic avenues. Gene expression data from COVID-19 patients across different conditions were analyzed using differential gene expression analysis. Significant genes were subjected to pathway analysis and protein–protein interaction network analysis. Gene ontology was used to identify the functions of these genes. The genes ADAMTS2, PCSK9, and OLAH were upregulated across all disease conditions including SARS-CoV-2 bacterial coinfection, potentially serving as therapeutic targets. The proteins, including RPL and CEACAM, could serve as a potential therapeutic target. The deregulated genes were majorly involved in inflammation, lipid metabolism, and immune regulation. The study's findings reveal significant gene expression differences among COVID-19 disease conditions. These insights guide future research toward targeted therapies and an improved understanding of disease progression and long-term consequences.

The objective of this research is to investigate the pathophysiological progression of HIV from acute infection to chronic immunodeficiency (AIDS) and to understand the host’s immunological responses, which are pivotal for elucidating disease aetiology and optimizing antiretroviral therapy (ART). Additionally, the study aims to explore the role of exosomes (40–130 nm bilipid-layered vesicles released by nearly all cell types) as key mediators of intercellular communication in the context of HIV infection. Recent research has uncovered that cells infected with HIV-1 release exosomes carrying a mix of viral and host components such as proteins, nucleic acids, lipids, and other metabolites. To decipher the plausible role of exosome-derived proteins in HIV disease progression, the exosomes isolated from HIV patient’s serum were subjected to LC–MS/MS analysis to identify exosome-derived human and viral protein sequences. The identified proteins were then investigated, annotated, and explored for protein–protein interaction (PPI) network between HIV and the human host’s proteins. Earlier experimental efforts focused on identifying PPI networks in host cells or only within the virus. The analysis showed that out of twelve exosome-derived host proteins identified from HIV-1 patient’s samples, only five of the proteins were associated with Toll-like receptors (TLR), inflammasome-activation, inhibition of apoptosis, innate immune response modulation, and autophagy pathways. In the TLR pathway, CDH5, ENO1, OGT, TJP1, and TRAF6 exosome-derived host proteins participated in regulation. Notably, CDH5, ENO1, OGT, and TRAF6 were shared among these pathways, BioGRID version 4.4 showed that HIV-1 Gag, Gag-pol, Env, and Nef proteins interact with 196, 162, 158, and 80 human proteins, respectively, associated with different innate immune response pathways. These findings are a step ahead in comprehending the pathophysiology of HIV1 and the innate immune response pathways, providing excellent opportunities to explore further exosome-based biomarkers for theranostic approaches.