Safety and immunogenicity of Ad5-nCoV immunization after three-dose priming with inactivated SARS-CoV-2 vaccine in Chinese adults.

Data on the safety and immunity of a heterologous booster (fourth dose) after three-doses of inactivated SARS-CoV-2 vaccine in Chinese adults are limited. We evaluate the safety and immunogenicity of Ad5-nCoV in a randomized, double-blind, parallel-controlled phase 4 clinical trial in Zhejiang, China (NCT05373030). Participants aged 18-80 years (100 per group), administered three doses of inactivated SARS-CoV-2 vaccine ≥6 months earlier, are enrolled and randomized 1:1 into two groups, which are administered intramuscular Ad5-nCoV or inactivated SARS-CoV-2 vaccine (CoronaVac or Covilo). All observed adverse reactions are predictable and manageable. Ad5-nCoV elicits significantly higher RBD-specific IgG levels, with a geometric mean concentration of 2924.0 on day 14 post-booster, 7.8-fold that of the inactivated vaccine. Pseudovirus-neutralizing antibodies to Omicron BA.4/5 show a similar pattern, with geometric mean titers of 228.9 in Ad5-nCoV group and 65.5 in inactivated vaccine group. Ad5-nCoV booster maintains high antibody levels on day 90, with seroconversion of 71.4%, while that of inactivated vaccine is 5.2%, almost pre-booster levels. A fourth Ad5-nCoV vaccination following three-doses of inactivated SARS-CoV-2 vaccine is immunogenic, tolerable, and more efficient than inactivated SARS-CoV-2 vaccine. Ad5-nCoV elicits a stronger humoral response against Omicron BA.4/5 and maintains antibody levels for longer than homologous boosting.

Polyphenol-rich extract of Zhenjiang aromatic vinegar ameliorates high glucose-induced insulin resistance by regulating JNK-IRS-1 and PI3K/Akt signaling pathways.

Zhenjiang aromatic vinegar is a famous traditional fermented cooking ingredient in China, with multiple nutritional and medicinal applications. Zhenjiang aromatic vinegar extract (100-400 µg/mL) is rich in polyphenols increased the glucose uptake and glucose consumption in high glucose-induced insulin resistant HepG2 (IR-HepG2) cells. Zhenjiang aromatic vinegar extract enhanced glycogen synthesis and attenuated gluconeogenesis by regulating key enzymes in IR-HepG2 cells. In addition, Zhenjiang aromatic vinegar extract ameliorated high glucose-induced IR by inhibiting phosphorylated insulin receptor substrate-1 (IRS-1) expression and activating phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway in IR-HepG2 cells. Moreover, Zhenjiang aromatic vinegar extract reduced reactive oxygen species generation and phosphorylated c-Jun NH2 terminal kinase (JNK) expression in IR-HepG2 cells. The attenuation of the high glucose is owned to the PI3K/Akt pathway activation, glycogen synthesis induction and gluconeogenesis suppression in IR-HepG2 cells.

New insight into 20(S)-ginsenoside Rh2 against T-cell acute lymphoblastic leukemia associated with the gut microbiota and the immune system.

T-cell acute lymphoblastic leukemia (T-ALL) is a hematopoietic malignancy associated with unfavorable factors including male gender and over nine years of age. Chemotherapy toxicity continues to present a major challenge. There is a need to develop novel natural agents to improve survival and quality of life in patients with T-ALL. 20(S)-ginsenoside Rh2 (GRh2) exhibits immune regulation and anti-tumor effects in both cellular and murine xenograft models. In the present study, the anti-cancer mechanisms of 20(S)-GRh2 involved in the immune system and intestinal microbiota were investigated in T-ALL mice. We revealed that 20(S)-Rh2 suppressed T-ALL by blocking the PI3K/Akt/mTOR signaling pathway, and enhanced immunity in the spleen by regulating immune factors. In addition, 20(S)-GRh2 altered the composition of the gut microbiota, and promoted intestinal homeostasis by elevating the levels of tight junction proteins, antimicrobial peptides and IgA. 20(S)-GRh2 ameliorated the LPS-induced inflammatory response in the intestine of T-ALL mice. Furthermore, Bacteroidetes, Verrucomicrobia, Akkermansia, Lactobacillus, and Lachnospiraceae_NK4A136_group were positively correlated with anti-tumor immune factors, intestinal barrier-related factors, and the anti-inflammatory response. Conversely, Firmicutes, Proteobacteria, Parabacteroides and Alistipes had the opposite correlation. Collectively, these results suggest that 20(S)-GRh2 is a safe and effective natural product, that shows promise for the prevention and treatment of T-ALL.