VG161 activates systemic antitumor immunity in pancreatic cancer models as a novel oncolytic herpesvirus expressing multiple immunomodulatory transgenes.

The VG161 represents the first recombinant oncolytic herpes simplex virus type 1 carrying multiple synergistic antitumor immuno-modulating factors. Here, we report its antitumor mechanisms and thus provide firm theoretical foundation for the upcoming clinical application in pancreatic cancer. Generally, the VG161-mediated antitumor outcomes were analyzed by a collaboration of techniques, namely the single-cell sequencing, airflow-assisted desorption electrospray ionization-mass spectrometry imaging (AFADSI-MSI) and nanostring techniques. In vitro, the efficacy of VG161 together with immune checkpoint inhibitors (ICIs) has been successfully shown to grant a long-term antitumor effect by altering tumor immunity and remodeling tumor microenvironment (TME) metabolisms. Cellular functional pathways and cell subtypes detected from patient samples before and after the treatment had undergone distinctive changes including upregulated CD8+ T and natural killer cells. More importantly, significant antitumor signals have emerged since the administration of VG161 injection. In conclusion, VG161 can systematically activate acquired and innate immunity in pancreatic models, as well as improve the tumor immune microenvironment, indicative of strong antitumor potential. The more robusting antitumor outcome for VG161 monotherapy or in combination with other therapies on pancreatic cancer is worth of being explored in further clinical trials.

[Identification and preparation of a glycol-protein fraction AN from tea extracts and its in vivo and in vitro anti-hyperglycosemia activity].

The present study compared active ingredients of tea from different sources to select tea type and the fraction of tea extracts for the highest anti-hyperglycemic activity, and to verify anti-hyperglycemic activity of the selected tea extract. Tea extracts were separated and enriched by molecular weight using ultra-filtration technology. The extracts were first screened by α-glucosidase inhibition assay, followed by using a rat inverted intestine sac system to measure the effect on glucose transport. Both alloxan-induced diabetic rat model and high-fat diet combined with streptozotocin-induced rat diabetes mellitus model were used to study the effects of active components on blood glucose, body weight, insulin resistance. The experimental results showed that the different kinds of tea extracts had different inhibitory effects on α-glucosidase, and the inhibitory effect of tea extract E on α-glucosidase was stronger. The effects of different components of tea extract E also varied greatly, of which Fraction AN protein had stronger inhibitory effect on α-glucosidase than other fragments, and Fraction AN protein had a strong inhibitory effect on glucose transport, reduced blood sugar and normalized insulin secretion in diabetic rats. The results suggest that a glycol-protein fraction(AN) from the extracts might be responsible for the anti-hyperglycemic activity of tea polysaccharides. The AN glycol-protein fraction has strong inhibitory effects on both α-glucosidase activity and glucose transport by the small intestine. It also reduced blood glucose level and normalized insulin secretion in diabetic rats, and has a protective effect on diabetic rats.

Renoprotective effect of berberine on type 2 diabetic nephropathy in rats.

Inflammation, fibrosis, and lipid disorder are essential promoters in the pathogenesis of diabetic kidney injury in diabetes mellitus type 2. Berberine (BBR) has been reported to have beneficial effects on diabetic nephropathy, but its action mechanism is still unclear. The present study was designed to elucidate the therapeutic mechanism of BBR in a type 2 diabetic nephropathy rat model induced by a high-fat diet and low-dose streptozotocin injection. The diabetic rats were treated with or without BBR by gavage for 20 weeks and examined by serology, 24-h albuminuria, histology, immunohistochemistry, and molecular analyses. Results showed that treatment with BBR significantly reduced serum levels of blood glucose and lipids, inhibited urinary excretion of albumin, and attenuated renal histological injuries in diabetic rats. Berberine treatment also inhibited renal inflammation, which was associated with inactivation of nuclear factor kappa-light-chain-enhancer of activated B-cell signalling. As a result, the upregulation of pro-inflammatory cytokines (interleukin-1ß, tumour necrosis factor-α) and chemokine (monocyte chemotactic protein-1) was blocked. In addition, BBR treatment also inactivated transforming growth factor-ß/Smad3 signalling and suppressed renal fibrosis, including expression of fibronectin, collagen I, and collagen IV. The present study reveals that BBR is a therapeutic agent for attenuating type 2 diabetic nephropathy by inhibiting nuclear factor kappa-light-chain-enhancer of activated B cell-driven renal inflammation and transforming growth factor-ß/Smad3 signalling pathway.

Vaccines' New Era-RNA Vaccine.

RNA vaccines, including conventional messenger RNA (mRNA) vaccines, circular RNA (circRNA) vaccines, and self-amplifying RNA (saRNA) vaccines, have ushered in a promising future and revolutionized vaccine development. The success of mRNA vaccines in combating the COVID-19 pandemic caused by the SARS-CoV-2 virus that emerged in 2019 has highlighted the potential of RNA vaccines. These vaccines possess several advantages, such as high efficacy, adaptability, simplicity in antigen design, and the ability to induce both humoral and cellular immunity. They also offer rapid and cost-effective manufacturing, flexibility to target emerging or mutant pathogens and a potential approach for clearing immunotolerant microbes by targeting bacterial or parasitic survival mechanisms. The self-adjuvant effect of mRNA-lipid nanoparticle (LNP) formulations or circular RNA further enhances the potential of RNA vaccines. However, some challenges need to be addressed. These include the technology's immaturity, high research expenses, limited duration of antibody response, mRNA instability, low efficiency of circRNA cyclization, and the production of double-stranded RNA as a side product. These factors hinder the widespread adoption and utilization of RNA vaccines, particularly in developing countries. This review provides a comprehensive overview of mRNA, circRNA, and saRNA vaccines for infectious diseases while also discussing their development, current applications, and challenges.

Heterologous boost with mRNA vaccines against SARS-CoV-2 Delta/Omicron variants following an inactivated whole-virus vaccine.

The coronavirus SARS-CoV-2 has mutated quickly and caused significant global damage. This study characterizes two mRNA vaccines ZSVG-02 (Delta) and ZSVG-02-O (Omicron BA.1), and associating heterologous prime-boost strategy following the prime of a most widely administrated inactivated whole-virus vaccine (BBIBP-CorV). The ZSVG-02-O induces neutralizing antibodies that effectively cross-react with Omicron subvariants. In naïve animals, ZSVG-02 or ZSVG-02-O induce humoral responses skewed to the vaccine's targeting strains, but cellular immune responses cross-react to all variants of concern (VOCs) tested. Following heterologous prime-boost regimes, animals present comparable neutralizing antibody levels and superior protection against Delta and Omicron BA.1variants. Single-boost only generated ancestral and omicron dual-responsive antibodies, probably by "recall" and "reshape" the prime immunity. New Omicron-specific antibody populations, however, appeared only following the second boost with ZSVG-02-O. Overall, our results support a heterologous boost with ZSVG-02-O, providing the best protection against current VOCs in inactivated virus vaccine-primed populations.

Transmission of Schistosoma japonicum by humans and domestic animals in the Yangtze River valley, Anhui province, China.

The aim of the present work was to assess the relative contribution to transmission of Schistosoma japonicum by humans and domestic animals in two villages in the Yangtze River valley in Anhui province, China. A cross-sectional survey was conducted to determine the prevalence and intensity of S. japonicum in humans, cattle, water buffaloes, horses, pigs, goats, dogs and cats. Additionally, for each host species the number of individuals and the mean faecal excretion per day was determined. Results showed that both prevalence and intensity of infection varied significantly between species and between the two villages and neither of the variables gave an adequate picture of the potential transmission. Total daily egg excretion was significantly higher in Chenqiao village compared with Guanghui village. Whereas humans were the main contributors to transmission of schistosomiasis in Guanghui village (80.4%), water buffaloes accounted for nearly 90% and goats for more than 5% of the transmission in Chenqiao village. Hence, the present study suggests that schistosomiasis transmission might vary significantly within Chinese farm districts and successful control should rely on prior transmission index determinations on major potential contributors rather than routine data of prevalence and intensity of infection. Further studies should determine the value of adding other transmission variables like egg hatchability and faecal deposition habits.