Mesenchymal stromal cells (MSCs) are a versatile platform for regenerative medicine and gene delivery because they combine multipotency, immunoregulatory activity, and injury-directed trafficking. Translation is nevertheless limited by donor- and tissue-dependent heterogeneity, variable biodistribution, and engineering-related risks. This review evaluates genetically modified MSCs as medicinal products rather than as a general MSC class. We compare self-inactivating lentiviral (SIN-LV) transduction, which provides efficient and durable expression and has limited early clinical experience, with targeted genome editing, which can define the integration locus and copy number but remains constrained by variable precise knock-in efficiency, off-target and double-strand-break-associated effects, manufacturing cost, and the absence of long-term clinical safety data. We integrate preclinical and clinical evidence with GMP-compatible manufacturing, potency testing, genomic surveillance, and release criteria. Particular attention is given to safe-harbor integration and B2M/CIITA-based hypoimmunogenic designs as strategies to reduce engineering-related batch variability and HLA-dependent donor variability. Together, these developments support a transition from empirically optimized MSC preparations toward molecularly defined cellular medicines with predefined genotype, expression, potency, and safety attributes.

This study is the first to report the genotypic distribution of the PPARG Pro12Ala polymorphism among Uzbek athletes. The human peroxisome proliferator-activated receptor gamma (PPARγ) is involved in lipid storage, glucose homeostasis and adipocyte differentiation. Pro-allele contributes to the development of high physical performance in sports where you need extra physical stamina, and Ala-allele - in sports based on strength and speed. An analysis of the distribution frequency of genotypes of the PPARG gene, based on the general model of inheritance, in the group of athletes involved in Boxing and Football, was statistically significant compared to the control (p =0.006; p =0,000006). These results suggest that the presence of PPARG Ala allele, which increases the sensitivity of muscle tissue to insulin, and thus enhances its anabolic effect on skeletal muscle, predisposes the development and display of speed-power qualities. In addition, we studied frequencies of Pro/Ala genotypes in Uzbek population in comparison with Russian, Ukrainian, Italian, Bosnian and Herzegovinian, and Ethiopian samples. In conclusion, the present data seem to suggest that some selective factors such as climate could have influenced the present distribution of the Ala allele. Keywords: Peroxisome proliferator-activated receptor gamma (PPARG), polymorphism, human genetics, genetic predisposition to sport

(1) Background: Hemorrhagic fever with renal syndrome (HFRS) remains a prevalent zoonosis in Eurasia. Orthohantavirus puumalaense (PUUV), carried by bank voles (Myodes glareolus), is the principal zoonotic pathogen of HFRS in this region. Despite ongoing efforts to develop effective drugs and vaccines against PUUV, this challenge remains. (2) Aim: In this study, we aimed to express a large quantity of the PUUV recombinant N (rN) protein using E. coli. We also sought to develop a protocol for extracting the rN protein from pellets, solubilizing, and refolding it to restore its native form. This protocol is crucial for producing a large quantity of rN protein to develop vaccines and diagnostic tools for HFRS. (3) Methods; PUUV S segment open reading frame (ORF) coding for N protein was synthesized and cloned into the plasmid vector pET-28 (A+). The ORF was transformed, expressed and induced in BL21(DE3) pLysS E. coli strain. Subsequently, rN protein was purified using immobilized metal affinity and ion chromatography. Immune reactivity of rN protein was tested by employing in house and commercial VektoHanta-IgG kit ELISA methods (both in vitro and in vivo). (4) Results: The best conditions for scaling up the expression of the PUUV rN protein were an incubation temperature of 20 °C during a 20 h incubation period, followed by induction with 0.5 mM IPTG. The most significant protein yield was achieved when the pellets were incubated in denaturing buffer with 8M urea. The highest yield of refolded proteins was attained using non-denaturing buffer (50 mM Tris-HCl) supplemented with arginine. A final 50 μL of PUUV rN protein solution with a concentration of 7 mg/mL was recovered from 1 L of culture. The rN protein elicited an antibody response in vivo and reacted with serum taken from patients with HFRS by ELISA in vitro. (5) Conclusion: Therefore, the orthohantavirus N protein’s ability to elicit immune response in vivo suggests that it can be used to develop vaccines against PUUV after conducting in vitro and in vivo studies to ascertain neutralising antibodies.

The coronavirus disease 2019 (COVID-19) pandemic remains a significant public health threat globally with significant socio-economic impacts. People living with human immunodeficiency virus (HIV) (PLWH) have a high risk of severe outcomes of COVID-19 due to immunosuppression. Clinical manifestation of COVID-19 in HIV patients largely remains unclear. We carried out a pilot study to investigate the clinical laboratory data and circulating cytokines in PLWH infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in Tatarstan, Russia. Serum samples were collected from three groups: PLWH with COVID-19 (PLWH/COVID-19), COVID-19-only, and uninfected controls. We found an increased risk of severe COVID-19 in PLWH/COVID-19 patients compared to COVID-19-only. Four fatal cases were in PLWH/COVID-19, while there was no fatality in COVID-19-only. Pro-inflammatory cytokines, such as IL-5, IL-6, IL-9, and IL-15, were elevated in PLWH/COVID-19 compered to COVID-19-only. These preliminary findings highlight the potential for more severe COVID-19 in PLWH/COVID-19 where pro-inflammatory cytokines could play pathogenic role.