SARS-CoV-2, the virus that causes COVID-19, is prone to mutations and the generation of genetic variants. Since its first outbreak in 2019, SARS-CoV-2 has continually evolved, resulting in the emergence of several lineages and variants of concern (VOC) that have gained more efficient transmission, severity, and immune evasion properties. The World Health Organization has given these variants names according to the letters of the Greek Alphabet, starting with the Alpha (B.1.1.7) variant, which emerged in 2020, followed by the Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.1.529) variants. This review explores the genetic variation among different VOCs of SARS-CoV-2 and how the emergence of variants made a global impact on the pandemic.
Background/Objectives: Parkinson’s disease (PD) is a rapidly growing neurological disorder in the developed world, affecting millions over the age of 60. The decline in motor functions occurs due to a progressive loss of midbrain dopaminergic neurons, resulting in lowered dopamine levels and impaired muscle function. Studies show defective mitochondrial autophagy (or “mitophagy”) links to PD. Rho-associated coiled-coil containing protein kinases (ROCK) 1 and ROCK2 are serine/threonine kinases, and their inhibition can enhance neuroprotection in PD by promoting mitophagy. Methods: We examine the effects of ROCK inhibitor SR3677, delivered via macrophage-derived small extracellular vesicles (sEVs) to Parkin Q311X(A) PD mouse models. sEVs with SR3677, administered intranasally, increased mitophagy gene expression, reduced inflammatory factors, and elevated dopamine levels in brain tissues. Results: ROCK2 expression decreased, showing the drug’s inhibitory effect. sEV-SR3677 treatment was more effective than treatment with the drug alone, although sham EVs showed lower effects. This suggests that EV-SR3677 not only activates mitochondrial processes but also promotes the degradation of damaged mitochondria through autophagy. Mitochondrial functional assays and oxygen consumption in ex vivo glial cultures revealed that sEV-SR3677 significantly improved mitochondrial respiration compared to that in untreated or SR3677-only treated cells. Conclusion: We demonstrated the efficacy of ROCK2 inhibition on mitochondrial function via sEV-SR3677 in the PD mouse model, necessitating further studies to explore design challenges and mechanisms of sEV-SR3677 as mitochondria-targeted therapy for PD
1 October 2023 in JAIDS Journal of Acquired Immune Deficiency Syndromes
Background: The Miami-CFAR Diversity, Equity & Inclusion Pathway Initiative (Miami CDEIPI) is designed to promote a diverse scientific workforce that reflects the communities at the highest risk of HIV in South Florida. Setting and Methods: The focus of the Miami CDEIPI is to help train the next generation of Underrepresented Minorities (URM) and Black, Indigenous, People of Color (BIPOC) in HIV/AIDS-related research through a team science experience. The Miami CDEIPI objectives are to facilitate the interaction of URM/BIPOC students with the network of CFAR-affiliated investigators and to enable these students to access the cutting-edge technologies at the Miami-CFAR and the Sylvester Comprehensive Cancer Center and other resources at the University of Miami. Results: Five URM/BIPOC students supported by the program in year 1 have been carrying out projects in collaboration with mentors at their parent institution and Miami-CFAR investigators. The students used the state-of-the-art laboratories and core facilities. They began their research with a proposal designed to integrate the cutting-edge technologies now available to them. Their training included participation in Miami-CFAR–sponsored activities such as seminars, an annual conference, and a national HIV workshop. Candidates in the Miami CDEIPI are in the process of developing their research proposals, integrating cutting-edge technologies into their doctoral dissertation research. Their projects are now in the completion phase. Conclusions: The Miami CDEIPI focuses its resources on one of the conspicuous gaps in the career paths of URM/BIPOC researchers—the dearth of leading URM/BIPOC scientists in the field. The Miami CDEIPI provides a professional network that supports the participation of URM/BIPOC trainees in innovative research and career skill training.