Evaluation of protective immunity induced by a DNA vaccine encoding SAG2 and SRS2 against Toxoplasma gondii infection in mice.

Toxoplasma gondii is an important protozoan pathogen, which can cause severe diseases in the newborns and immunocompromised individuals. Developing an effective vaccine against Toxoplasma infection is a critically important global health priority. Immunofluorescence staining analysis revealed that TgSAG2 and TgSRS2 are membrane associated and displayed on the surface of the parasite. Immunizations with pBud-SAG2, pBud-SRS2 and pBud-SAG2-SRS2 DNA vaccines significantly increased the production of specific IgG antibodies. Immunization with pBud-SAG2-SRS2 elicited cellular immune response with higher concentrations of IFN-γ and IL-4 compared to the control group. Antigen-specific lymphocyte proliferations in the pBud-SRS2 and pBud-SAG2-SRS2 groups were significantly higher compared to that in the control group. Furthermore, 30 % of mice immunized with pBud-SAG2-SRS2 survived after the challenge infection with virulent T. gondii RH tachyzoites. This study revealed that immunization with pBud-SAG2-SRS2 induced potent immune responses, and has the potential as a promising vaccine candidate for the control of T. gondii infection.

Electrochemical aerobic Wacker-type oxygenation of triaryl substituted alkenes to 1,2,2-triarylethanones.

An effective synthetic approach for various 1,2,2-triarylethanones from triaryl substituted alkenes has been developed via an electrochemical Wacker-type oxygenation with O2 as the sole oxygen source. It presents the first instance of the Wacker-type oxidation expanding its substrate scope to trisubstituted alkenes. The approach is transition-metal-free, compatible with various functional groups, and can be carried out under mild conditions resulting in satisfactory yields. Mechanistic experiments suggest the CO bond formation occurs through reactions between cationic carbon species and the superoxide radical, which involves the 1,2-shift of the electron-rich substituent.

VNP20009-Abvec-Igκ-MIIP suppresses ovarian cancer progression by modulating Ras/MEK/ERK signaling pathway.

Ovarian cancer poses a significant threat to women's health, with conventional treatment methods encountering numerous limitations, and the emerging engineered bacterial anti-tumor strategies offer newfound hope for ovarian cancer treatment. In this study, we constructed the VNP20009-Abvec-Igκ-MIIP (VM) engineered strain and conducted initial assessments of its in vitro growth performance and the expression capability of migration/invasion inhibitory protein (MIIP). Subsequently, ID8 ovarian cancer cells and mouse cancer models were conducted to investigate the impact of VM on ovarian cancer. Our results revealed that the VM strain demonstrated superior growth performance, successfully invaded ID8 ovarian cancer cells, and expressed MIIP, consequently suppressing cell proliferation and migration. Moreover, VM specifically targeted tumor sites and expressed MIIP which further reduced the tumor volume of ovarian cancer mice (p < 0.01), via the downregulation of epidermal growth factor receptor (EGFR), Ras, p-MEK, and p-ERK. The downregulation of the PI3K/AKT signaling pathway and the decrease in Bcl-2/Bax levels also indicated VM's apoptotic potency on ovarian cancer cells. In summary, our research demonstrated that VM exhibits promising anti-tumor effects both in vitro and in vivo, underscoring its potential for clinical treatment of ovarian cancer. KEY POINTS: • This study has constructed an engineered strain of Salmonella typhimurium capable of expressing anticancer proteins • The engineered bacteria can target and colonize tumor sites in vivo • VM can inhibit the proliferation, migration, and invasion of ovarian cancer cells.

Effects of the CRYAB gene on stem cell-like properties of colorectal cancer and its mechanism.

Aims: Alpha B-crystallin (CRYAB), a known molecular chaperone, is involved in the occurrence and development of various tumor types. However, the function of CRYAB in colorectal cancer stem cells (CSCs) remains unknown. This study aimed to elucidate the role and possible regulatory mechanisms of CRYAB in the cancer stem cell-like phenotype of colorectal cancer (CRC). Subjects and Methods: The expression of CRYAB in patients with CRC and lymph node metastasis at various stages and its relationship with overall survival were detected using the TCGA database. In this study, CRC-CSCs were enriched from HCT116 and Caco2 cells with serum-free suspension culture. The CRYAB gene, stemness-related genes, and mesenchymal markers were detected via quantitative real-time PCR (qRT-PCR) in CRC cells. Then, CRYAB-HCT116S and CRYAB-Caco2S cell lines were established by lentivirus-mediated overexpression of CRYAB. Self-renewal ability and stemness features were measured by the sphere formation assay and flow cytometry. The tumorigenesis capacity in vivo was inspected in nude mice. The functions of CRYAB on CSC proliferation, migration, and invasion were examined using colony formation and the transwell assay. Finally, the Wnt/ß-catenin pathway-related mRNAs and proteins were detected via qRT-PCR and western blotting. Results: The expression of CRYAB in CRC is related to the clinical phase and prognosis, except with lymphoid metastasis. CRYAB expression was elevated in CSCs. Upregulation of CRYAB enhanced the expression of CSC-related genes and mesenchymal markers. The capacity to form colonospheres, tumorigenesis, cell proliferation, and metastasis were significantly advanced in CRYAB-overexpressed cells. Moreover, CRYAB dramatically suppressed ß-catenin degradation and downregulated the expression of p-GSK-3ß. Conclusions: CRYAB maintains CSC formation via the Wnt/ß-catenin pathway in CRCs, which may, therefore, function as vital molecular targets for CRC therapeutic strategies.

Nuclear receptor estrogen-related receptor gamma suppresses colorectal cancer aggressiveness by regulating Wnt/ß-catenin signaling.

Colorectal cancer (CRC) is the predominant cause of cancer-related death worldwide, because of the lack of effective therapeutic targets. Estrogen-related receptor gamma (ESRRG), which belongs to the family of nuclear receptors, functions as an important element regulating gene transcription. In our report, we identified ESRRG as a potential tumor suppressor. The decreased level of ESRRG was initially observed in CRC and was highly associated with a poor prognosis. ESRRG overexpression abrogated cell growth and metastasis in vitro and in vivo. Mechanistically, ESRRG repressed the epithelial-to-mesenchymal transition process and antagonized Wnt signaling by regulating ß-catenin degradation. In addition, significant ESRRG hypermethylation was found in CRC and inversely correlated with its expression. Consistently, the expression of ESRRG was induced after treatment with DNA demethylating agent 5-aza-2'-deoxycytidine. Taken together, these findings define a tumor-suppressive role of ESRRG in CRC, providing a potential novel therapeutic approach for this cancer.

Sex Estimation of Typical Adult Vertebrae Morphology in Central China Based on CT Technique / 法医学杂志

Objective The morphological data of the second thoracic vertebra and the third lumbar vertebra were measured by computerized tomography （CT）. The sex differences were analyzed and the discrimination equation was obtained. Methods The data of 274 adults （203 cases from experimental group and 69 cases from validation group） from central China were collected. Four linear data （maximum transverse length of vertebral body, maximum longitudinal length of vertebral body, maximum transverse length of vertebral foramen, maximum longitudinal length of vertebral foramen）, one angle data （angle between spinous processes） and two area （vertebral foramen area, total cross-sectional area of vertebral body） data of the second thoracic vertebra and the third lumbar vertebra were collected, respectively. Then three ratios ［maximum transverse length/　maximum longitudinal length of vertebral body, maximum transverse length/ maximum longitudinal length of vertebral foramen, vertebral foramen area/ （total cross-sectional area of vertebral body-vertebral foramen area）］ and one angle （angle between spinous processes） were obtained. The discriminant equation was established for sexual discriminant analysis. Results The morphology of the second thoracic vertebra and the third lumbar vertebra was related with gender. Four single index discriminant formulae and eleven multi-index discriminant formulae were established. The 69 validation group samples were substituted into the formula for testing, and the maximum discriminant accuracy rate of the single-index discriminant formula was 75%. The maximum discriminant accuracy rate of multi-index discriminant formula was 83%. Conclusion It is feasible to conduct individual sex analysis by the morphological indexes of second thoracic vertebra and the third lumbar vertebra. The indexes have important application values in practice.