Evaluation of the immune responses of biological adjuvant bivalent vaccine with three different insertion modes for ND and IBD.

Infectious bursal disease (IBD) is a widespread problem in the poultry industry, and vaccination is the primary preventive method. However, moderately virulent vaccines may damage the bursa, necessitating the development of a safe and effective vaccine. The Newcastle disease virus (NDV) has been explored as a vector for vaccine development. In this study, reverse genetic technology was used to obtain three recombinant viruses, namely, rClone30-VP2L (P/M)-chGM-CSF (NP), rClone30-chGM-CSF (P/M)-VP2L (NP), and rClone30-VP2L-chGM-CSF (P/M). Animal experiments showed that the three biological adjuvant bivalent vaccines effectively increased anti-NDV and anti-infectious bursal disease virus (IBDV) titres, enhancing both humoral and cellular immune responses in chickens without leading to any harm. Amongst the three biological adjuvant bivalent vaccines, the rClone30-chGM-CSF (P/M)-VP2L (NP) group had higher levels of anti-NDV antibodies at 14 days after the first immunization and stimulated a greater humoral immune response in 7-10 days. While, the rClone30-VP2L (P/M)-chGM-CSF (NP) group was the most effective in producing a higher level of IBDV antibody response. In conclusion, these three vaccines can induce immune responses more rapidly and effectively, streamline production processes, be cost-effective, and provide a new avenue for the development of Newcastle disease (ND) and IBD bivalent vaccines.

Oncolytic Newcastle disease virus carrying the IL24 gene exerts antitumor effects by inhibiting tumor growth and vascular sprouting.

The second-leading cause of death, cancer, poses a significant threat to human life. Innovations in cancer therapies are crucial due to limitations in traditional approaches. Newcastle disease virus (NDV), a nonpathogenic oncolytic virus, exhibits multifunctional anticancer properties by selectively infecting, replicating, and eliminating tumor cells. To enhance NDV's antitumor activity, four oncolytic NDV viruses were developed, incorporating IL24 and/or GM-CSF genes at different gene loci using reverse genetics. In vitro experiments revealed that oncolytic NDV virus augmented the antitumor efficacy of the parental virus rClone30, inhibiting tumor cell proliferation, inducing tumor cell fusion, and promoting apoptosis. Moreover, NDV carrying the IL24 gene inhibited microvessel formation in CAM experiments. Evaluation in a mouse model of liver cancer confirmed the therapeutic efficacy of oncolytic NDV viral therapy. Tumors in mice treated with oncolytic NDV virus significantly decreased in size, accompanied by tumor cell detachment and apoptosis evident in pathological sections. Furthermore, oncolytic NDV virus enhanced T cell and dendritic cell production and substantially improved the survival rate of mice with hepatocellular carcinoma, with rClone30-IL24(P/M) demonstrating significant therapeutic effects. This study establishes a basis for utilizing oncolytic NDV virus as an antitumor agent in clinical practice.

Evaluation of prevention and treatment effects of fibroblast growth factor-21 in BLM-induced pulmonary fibrosis.

Pulmonary fibrosis is a progressive and fatal fibrotic lung disease and associated with a high mortality rate. In the study, the prevention and treatment effects of fibroblast growth factor-21 (FGF-21) in bleomycin (BLM)-induced pulmonary fibrosis were investigated in vivo and vitro. In the prevention of pulmonary fibrosis studies, the results showed that interdict of FGF-21 could reduce the related gene and protein expression levels of pulmonary fibrosis. In addition, FGF-21 significantly reduced both the aggregation of inflammatory cells and deposition of collagen in the lung by histopathology. In therapy of pulmonary fibrosis studies, the results indicated that treatment with FGF-21 resulted in an amelioration of the pulmonary fibrosis in mice with reductions of the pathological score, collagen deposition and transforming growth factor (TGF)-ß and α-smooth muscle actin (α-SMA) expressions in the lung tissues at fibrotic stage, and late administration was also able to reduce the degree of pulmonary fibrosis and even better than these in the prevention group. Furthermore, BLM-induced THP-1 macrophage model was verified using FGF-21; the result showed that FGF-21 decreased the related gene expression level of pulmonary fibrosis. FGF-21 may have preventive and therapeutic effects on BLM-induced pulmonary fibrosis via inhibiting myofibroblast differentiation and inflammatory. Thus, FGF-21 represents a potential drug for the prevention and treatment of pulmonary fibrosis.

Development and evaluation of Newcastle disease - avian influenza bivalent vector vaccines in commercial chickens.

Avian influenza (AI) and Newcastle disease (ND) are regarded as the leading viral infectious diseases affecting the global poultry industry. Vaccination is a successful therapeutic intervention to safeguard birds against both ND and AI infections. In this research, ND-AI bivalent vaccines were developed through the incorporation of HA and IRES-GMCSF gene fragments at varying locations of NDV rClone30 vectors. The two constructed vaccines were rClone30-HA-IRES-GMCSF(PM) and rClone30-HA(PM)-IRES-GMCSF(NP). Next, 27-day-old Luhua chickens (the maternal antibody level was reduced to 1.4 log2) were inoculated with the same dose of the vaccines, and humoral and cellular immune responses were assessed at multiple time points. Compared to the commercial vaccine, the levels of anti-NDV antibodies following the administration of the ND-AI vaccines were above the theoretical protection value of 4 log2. The levels of anti-AIV antibodies in the bivalent vaccine group were notably higher than those in the commercial vaccine group. Furthermore, the content of inflammatory factors and transcription levels were significantly increased in chickens administered ND-AI vaccines. The ND-AI vaccines induced stronger proliferative responses of B cells or CD3+, CD8+, and CD4 + T cells. Hematoxylin and eosin staining showed that the tissue damage induced by the two recombinant vaccines was similar to that of commercial vaccines. The outcomes of the study suggest that the two bivalent ND-AI vaccine candidates produced using the reverse genetics approach are both secure and effective. This approach not only enables the multiuse of one vaccine but also provides a new concept for the development of other vaccines against infectious viral diseases.

The efficacy of transitional care services in patients with transient ischemic attack: A retrospective cohort study.

Transient ischemic attack (TIA) carries a particularly high short-term risk of stroke, which is associated with brain dysfunction caused by a regional reduction in blood flow. Transitional care services present benefits in improving ischemic neurological function and decreasing the recurrence in patients with TIA. The purpose of this study was to investigate the effects of transitional care on clinical outcomes in patients hospitalized for TIA. We retrospectively collected data about 1288 patients with TIA from May 2017 to June 2019. Patients were divided into mild (n = 438), moderate (n = 420) and severe group (n = 430) accessed by age, blood pressure, type of TIA, and duration (ABCD2) score. Participants were patients hospitalized due to TIA, assigned to transitional care (n = 643) or usual care (n = 645), and followed up for 24 months. Physical function of patients was evaluated using the 6-minute walk test. We evaluated patient reach, implementation using hospital quality measures, hospital-level sustainability physical function, ischemic neurological score, composite quality indicator score, and recurrence of TIA between transitional care or usual care group. TIA patients in transitional care group had better physical function and quality indicator score, lower ischemic neurological score and recurrence of TIA, and shorter hospital stay than patients in usual care group. Results demonstrated that transitional care significantly improved the patients' satisfaction compared to usual care. Patients in mild, moderate, and severe group presented more benefits than usual care clinical outcomes in patients hospitalized for TIA. Transitional care is associated with better functional status for patients with TIA.

A pilot study of oral S-1 for treating heavily pretreated patients with advanced or recurrent cervical cancer among Chinese population.

This pilot study retrospectively aimed to assess the feasibility effectiveness and safety of oral S-1 in heavily pretreated patients with advanced or recurrent cervical cancer (ARCC) among Chinese population.Thirty patients with ARCC who had undergone one or more lines of chemotherapy received oral S-1 (40-60 mg/m) twice daily for 6 weeks. Outcome measurements included tumor response, time to progression (TTP), overall survival (OS) time, and occurrence of adverse events (AEs).The overall response rate was 43.3%. After a median follow-up of 6 months, the median TTP was 4.4 months and the median OS time was 10.2 months. The most frequent grade 3 or 4 AEs were neutropenia (13.3%) and nausea (16.7%).The results of this study show that oral S-1 is effective and well-tolerated in patients with ARCC who were heavily pretreated among Chinese population.

Delay in oocyte aging in mice by the antioxidant N-acetyl-L-cysteine (NAC).

BACKGROUND: Ovarian aging is associated with declining numbers and quality of oocytes and follicles. Oxidative stress by reactive oxygen species (ROS) contributes to somatic aging in general, and also has been implicated in reproductive aging. Telomere shortening is also involved in aging, and telomeres are particularly susceptible to ROS-induced damage. Previously, we have shown that antioxidant N-acetyl-L-cysteine (NAC) effectively rescues oocytes and embryos from ROS-induced telomere shortening and apoptosis in vitro. Using mice as models, we tested the hypothesis that reducing oxidative stress by NAC might prevent or delay ovarian aging in vivo. METHODS: Initially, young females were treated with NAC in drinking water for 2 months and the quality of fertilized oocytes and early embryo development were evaluated. Next, young mice 1-1½ months old were treated for 1 year with NAC added in drinking water, and their fertility was analyzed starting at 6 months, as indicated by litter size, oocyte number and quality. The ovaries were also examined for telomere activity and length and the expression of selected genes related to aging and DNA damage. RESULTS: Short-term treatment of mice for 2 months with NAC demonstrated that NAC improved the quality of fertilized oocytes and early embryo development. Mice treated with a long-term low concentration (0.1 mM) of NAC had increased litter sizes at the ages of 7-10 months compared with age-matched controls without NAC treatment. NAC also increased the quality of the oocytes from these older mice. Moreover, the expression of sirtuins was increased, telomerase activity was higher and telomere length was longer in the ovaries of mice treated with NAC compared with those of the control group. CONCLUSIONS: These data suggest that appropriate treatment with the antioxidant NAC postpones the process of oocyte aging in mice.