A novel bacterium-like particles platform displaying antigens by new anchoring proteins induces efficacious immune responses.

Bacterium-like particles (BLP) are the peptidoglycan skeleton particles of lactic acid bacteria, which have high safety, mucosal delivery efficiency, and adjuvant effect. It has been widely used in recent years in the development of vaccines. Existing anchoring proteins for BLP surfaces are few in number, so screening and characterization of new anchoring proteins are necessary. In this research, we created the OACD (C-terminal domain of Escherichia coli outer membrane protein A) to serve as an anchoring protein on the surface of BLP produced by the immunomodulatory bacteria Levilactobacillus brevis 23017. We used red fluorescent protein (RFP) to demonstrate the novel surface display system's effectiveness, stability, and ability to be adapted to a wide range of lactic acid bacteria. Furthermore, this study employed this surface display method to develop a novel vaccine (called COB17) by using the multi-epitope antigen of Clostridium perfringens as the model antigen. The vaccine can induce more than 50% protection rate against C. perfringens type A challenge in mice immunized with a single dose and has been tested through three routes. The vaccine yields protection rates of 75% for subcutaneous, 50% for intranasal, and 75% for oral immunization. Additionally, it elicits a strong mucosal immune response, markedly increasing levels of specific IgG, high-affinity IgG, specific IgA, and SIgA antibodies. Additionally, we used protein anchors (PA) and OACD simultaneous to show several antigens on the BLP surface. The discovery of novel BLP anchoring proteins may expand the possibilities for creating mucosal immunity subunit vaccines. Additionally, it may work in concert with PA to provide concepts for the creation of multivalent or multiple vaccines that may be used in clinical practice to treat complex illnesses.

Lactobacilli-derived adjuvants combined with immunoinformatics-driven multi-epitope antigens based approach protects against Clostridium perfringens in a mouse model.

Clostridium perfringens is ubiquitously distributed and capable of secreting toxins, posing a significant threat to animal health. Infections caused by Clostridium perfringens, such as Necrotic Enteritis (NE), result in substantial economic losses to the livestock industry annually. However, there is no effective commercial vaccine available. Hence, we set out to propose an effective approach for multi-epitope subunit vaccine construction utilizing biomolecules. We utilized immunoinformatics to design a novel multi-epitope antigen against C. perfringens (CPMEA). Furthermore, we innovated novel bacterium-like particles (BLPs) through thermal acid treatment of various Lactobacillus strains and selected BLP23017 among them. Then, we detailed the structure of CPMEA and BLPs and utilized them to prepare a multi-epitope vaccine. Here, we showed that our vaccine provided full protection against C. perfringens infection after a single dose in a mouse model. Additionally, BLP23017 notably augmented the secretion of secretory immunoglobulin A (sIgA) and enhanced antibody production. We conclude that our vaccine possess safety and high efficacy, making it an excellent candidate for preventing C. perfringens infection. Moreover, we demonstrate our approach to vaccine construction and the preparation of BLP23017 with distinct advantages may contribute to the prevention of a wider array of diseases and the novel vaccine development.

Lysinibacillus capsici 38,328 isolated from agricultural soils as a promising probiotic candidate for intestinal health.

There is an increasing interest in the use of spore-forming Bacillus spp. as probiotic ingredients on the market. However, probiotics Bacillus species are insufficient, and more safe Bacillus species were required. In the study, traditional fermented foods and soil samples were collected from more than ten provinces in China, and 506 Bacillus were selected from 109 samples. Using the optimized procedure, we screened nine strains, which successfully passed the acid, alkali, bile salt, and trypsin resistance test. Drug sensitivity test results showed that three Bacillus out of the nine isolates exhibited antibiotic sensitivity to more than 29 antibiotics. The three strains sensitive to antibiotics were identified by 16S ribosomal RNA, recA, and gyrB gene analysis, two isolates (38,327 and 38,328) belong to the species Lysinibacillus capsici and one isolate (37,326) belong to Bacillus halotolerans. Moreover, the three strains were confirmed safe through animal experiments. Finally, L. capsici 38,327 and 38,328 showed protections in the Salmonella typhimurium infection mouse model, which slowed down weight loss, reduced bacterial load, and improved antioxidant capacity. Altogether, our data demonstrated that selected L. capsici strains can be used as novel probiotics for intestinal health.

The mechanism of myocardial fibrosis is ameliorated by myocardial infarction-associated transcript through the PI3K/Akt signaling pathway to relieve heart failure.

OBJECTIVE: This study aimed to investigate the role of long noncoding RNA (LncRNA) myocardial infarction-associated transcript (MIAT) in a heart failure (HF) model in vivo and in vitro by regulating the PI3K/Akt signaling pathway. METHODS: We established HF models in vivo and in vitro and evaluated the collagen content of these models and other factors. RESULTS: We found that when LncRNA MIAT was silenced, vascular endothelial growth factor, phosphorylated protein kinase B (Akt), and phosphorylated phosphoinositide 3-kinase (PI3K) mRNA and protein levels were significantly downregulated, which suggested that MIAT activated the PI3K/Akt signaling pathway. Akt and PI3K expression was not significantly changed. We also found that when LncRNA MIAT was silenced, collagen expression was significantly downregulated. This finding suggested that MIAT promoted myocardial fibrosis during the development of HF. The levels of inflammatory factors were also significantly reduced with silencing of LncRNA MIAT. This finding suggested that MIAT promoted the expression of inflammatory factors in myocardial fibrosis by activating the PI3K/Akt signaling pathway. CONCLUSION: This study indicates that silencing LncRNA MIAT may improve myocardial fibrosis and alleviate HF through the PI3K/Akt signaling pathway, which may be helpful for patients with HF to obtain a better therapeutic effect.

Smoking, barriers to quitting, and smoking-related knowledge, attitudes, and patient practices among male physicians in China.

INTRODUCTION: Successful interventions to reduce the high rate of smoking among male physicians in China might contribute to reduction in tobacco use in the country overall. Better characterization of smoking, barriers to quitting, and smoking-related knowledge, attitudes, and patient practices in this physician population will help plan such interventions and provide baseline data to evaluate their effectiveness. METHODS: A self-administered survey of smoking-related knowledge, attitudes, behaviors, and patient practices was conducted among health care professionals in 2 large teaching hospitals in China. RESULTS: Of 103 male physicians, those who smoked (n = 51) had a more limited knowledge of smoking-related disease and were less likely to advise patients to quit smoking compared with nonsmoking physicians (n = 52). More than one-fourth (29%) of nonsmoking physicians accepted gift cigarettes, and these physicians were less likely to ask their patients about their smoking status than those who did not accept gift cigarettes. Seventy-five percent of smokers reported that their hospitals did not help them quit, and only 19% reported receiving training in how to help their patients quit. CONCLUSION: High rates of smoking, gifting of cigarettes, limited support for physician quitting, and limited training on cessation approaches may compromise the ability of male physicians in China to effectively treat their patients who smoke.

[Expression of chemokine-like factor 2(CKLF2) mRNA in rat myocardium with hypertrophy].

OBJECTIVE: To investigate the expression of CKLF2 mRNA in the rat myocardium with hypertrophy. METHODS: Rat abdominal aorta was constricted by operation to make myocardium hypertrophy in the hypertrophy group and the control group was subjected to the sham-operation. The CKLF2 mRNA expressions were tested by competitive polymerase chain reaction (CPCR). RESULTS: Compared to the control-group, the expression of CKLF2 mRNA of hypertrophy-group significantly increased on the 17th day after operation, and decreased to the control level on the 45th day. CONCLUSION: The expression of rCKLF2 mRNA in rat myocardium with hypertrophy significantly increased in early days of hypertrophy.