Transglutaminase 2 serves as a pathogenic hub gene of KRAS mutant colon cancer based on integrated analysis.

BACKGROUND: Colon cancer is acknowledged as one of the most common malignancies worldwide, ranking third in United States regarding incidence and mortality. Notably, approximately 40% of colon cancer cases harbor oncogenic KRAS mutations, resulting in the continuous activation of epidermal growth factor receptor signaling. AIM: To investigate the key pathogenic genes in KRAS mutant colon cancer holds considerable importance. METHODS: Weighted gene co-expression network analysis, in combination with additional bioinformatics analysis, were conducted to screen the key factors driving the progression of KRAS mutant colon cancer. Meanwhile, various in vitro experiments were also conducted to explore the biological function of transglutaminase 2 (TGM2). RESULTS: Integrated analysis demonstrated that TGM2 acted as an independent prognostic factor for progression-free survival. Immunohistochemical analysis on tissue microarrays revealed that TGM2 was associated with an elevated probability of perineural invasion in patients with KRAS mutant colon cancer. Additionally, biological roles of the key gene TGM2 was also assessed, suggesting that the downregulation of TGM2 attenuated the proliferation, invasion, and migration of the KRAS mutant colon cancer cell line. CONCLUSION: This study underscores the potential significance of TGM2 in the progression of KRAS mutant colon cancer. This insight not only offers a theoretical foundation for therapeutic approaches but also highlights the need for additional clinical trials and fundamental research to support our preliminary findings.

Blood Lipid Metabolic Profiles and Causal Links to Site-Specific Cancer Risks: A Mendelian Randomization Study.

Observational and Mendelian randomization (MR) studies have established links between dyslipidemia and select cancer susceptibilities. However, there is a lack of comprehensive exploration of causal relationships spanning diverse cancer types. Here, we conducted a two-sample MR analysis to elucidate the causative connections between 9 blood lipid metabolic profiles (namely, adiponectin, leptin, lipoprotein A, apolipoprotein A1, apolipoprotein B, cholesterol, triglycerides, LDL-cholesterol, and HDL-cholesterol) and 21 site-specific cancer risks. Our findings reveal genetically predicted adiponectin levels to be associated with a reduced ovarian cancer risk, while genetically determined leptin increases bladder cancer risk but decreases prostate cancer risk. Lipoprotein A elevates risk of prostate cancer while diminishing risk of endometrial cancer, while apolipoprotein A1 heightens risks of breast and cervical cancers. Furthermore, elevated levels of cholesterol are positively correlated with kidney cancer, and triglycerides demonstrate a positive association with non-melanoma skin cancer but a negative association with breast cancer. Protective effects of genetically predicted LDL-cholesterol on endometrial cancer and adverse effects of HDL-cholesterol on breast cancer are also observed. Our study conclusively establishes that blood lipid metabolic profiles exert causal effects on cancer susceptibility, providing more robust evidence for cancer prevention and prompting contemplation regarding the future health of the human populace.

The impact of human capital on green economic efficiency: evidence from 280 prefectural cities in China.

Balancing economic growth with resources and the environment to achieve sustainable development is a key issue in the development of all countries, and researchers are trying to find feasible development paths. The aim of this study is to examine the impact of human capital levels on green economic efficiency (GEE) and the underlying mechanisms in 280 prefecture-level cities in China and covering the 2003-2019 period. In addition, we calculate GEE including undesired outputs based on a super-efficiency slack-based measure (SBM) model, and we construct panel regression and moderating effect models for empirical studies. The results of the baseline regression study show that the improvement in the human capital level contributes to the GEE of prefecture-level cities. Among the control variables, the economic development level, foreign direct investment (FDI), city size, and the science and technology innovation (STI) level positively affect GEE, while industrialization and environmental regulation negatively affect GEE. The study results concerning the mechanism of action indicate that industrial structure upgrading plays a positive moderating role. That is, industrial structure upgrading can strengthen the effect of human capital on GEE, which is further clarified. This study suggests that government policies must favor the cultivation of high-level human capital, especially in the environmental protection industry, and that talent support strategies should be differentiated between regions to promote industrial structure upgrading and human capital matching through green technology development. Modern human capital theory reveals the important role of human capital in improving economic efficiency and provides new ideas for achieving sustainable development. This paper explores the role of human capital in improving the GEE based on the human capital perspective, which is important for research on the pathways to achieve sustainable development.

The effectiveness of creatine treatment for Parkinson's disease: an updated meta-analysis of randomized controlled trials.

BACKGROUND: The effectiveness of creatine in treating Parkinson's disease (PD) has not been conclusively determined. Therefore, we performed a meta-analysis to address this issue. METHODS: The Cochrane Central Register of Controlled Trials, PUBMED, EMBASE, and other databases were searched, and outcomes measured by the Total Unified Parkinson's Disease Rating Scale (UPDRS) and the Schwab & England Scale were analyzed. RESULTS: Five randomized controlled trials (RCTs) were selected, and 1339 participants were included in the analysis. There were no significant differences between the control and treatment groups in the total, mental, activities of daily living (ADL), or motor UPDRS scores, but an improvement in Schwab & England Scale scores was observed. CONCLUSIONS: Creatine has no observed benefit in PD patients, although more correlated studies are still needed.

[In vitro anti-tumor effect of cytotoxic T lymphocyte activated by antigen- loaded dendritic cells from peripheral blood mononuclear cells treated with calcium ionophore A23187 and GM-CSF].

OBJECTIVE: To evaluate the effect of calcium ionophore (CI) A23187 and human recombinant granulocyte/macrophage colony stimulating factor (rhGM-CSF) on the cultivation of dendritic cell (DC) from healthy human peripheral blood mononuclear cell (PBMC) and to evaluate the in vitro effect of DC stimulated by K562 cell lysate on inducing specific cytotoxic T lymphocyte (CTL) against K562 cell. METHODS: Human PBMCs isolated from healthy subjects were separated into two groups. In Group A, the cells were cultured with additional rhGM-CSF, recombinant human interleukin 4 and recombinant human tumor necrosis factor-α only as control group. In Group B, the cells were cultured in the presence of rhGM-CSF and CI A23187. The cells in both groups were pre-incubated with K562 cell lysate at 37°C for 30 min. The cells were harvested after a 4-day cultivation. Morphology of DC was continuously observed under inverted microscope. The surface antigens of induced cells were analyzed by flow cytometry (FCM). Then the proliferation of allogeneic T cell and the specific cytotoxicity of T cell primed with DC were examined by colorimetry. Also, the nonspecific inhibition of DC loaded K562 cell lysate against K562 cell was detected. RESULTS: Typical morphological features of DC could be observed in both groups. The expressions of CD83, CD1a, CD86 and CD40 were stronger in Group B than those in control group (45.2% ± 1.8%, 31.5% ± 3.9%, 40.1% ± 7.8%, 36.4% ± 6.3% vs 16.9% ± 1.3%, 20.4% ± 3.4%, 26.5% ± 2.2%, 22.3% ± 3.0%) (all P < 0.05). The expression of CD14 was weaker in Group B than that in control group (5.7% ± 0.8% vs 19.0% ± 1.6%) (P < 0.05). As compared with the control group, DC in Group B loaded with K562 lysate could evidently stimulate the proliferation of allogeneic T cell (P < 0.05, exclusion of effector-to-target ratio of 1:40) and inhibit the growth of K562 cell (P < 0.05). In addition, both groups of DC-stimulated CTL had specific cytotoxicity against K562 cell. At the effector-to-target ratios of 10:1 and 40:1, the DC-stimulated CTL of Group B had stronger cytotoxicity against K562 cell (both P < 0.05). CONCLUSION: In combination with rhGM-CSF, CI A23187 induces PBMC into DC in a more effective way. DC loaded with K562 lysate can stimulate CTL and maintain high immunocompetence with specific cytotoxicity against K562 cell.

[Study on the strategy of Japanese encephalitis immunization using live attenuated vaccine combined with inactivated vaccine].

OBJECTIVE: Using the advantages of Japanese encephalitis live attenuated and inactivated vaccine, to reduce the rate of immunization reaction and to increase the effect, we conducted a study on the strategy of immunization in Japanese encephalitis using live attenuated vaccine combined with inactivated vaccine. METHODS: Observing the safety and immune effects of different groups. RESULTS: Data on side effect showed that the rate of moderate and severe systematic reactions of the group who were inoculated with combined vaccine was 0.73%, with local reaction 1.46% while the combined rate of moderate and severe systematic reaction of the group who were inoculated with inactivated vaccine was 2.8%. Under the detection of serum neutralizing antibody, the GMT rose from 1:1.05 - 1:3.35 before vaccination to 1:47.34 - 1:101.30 after vaccination in the different groups. Neutralizing antibody was detected in 97.67% of the combined group. There was a significant difference by comparing neutralizing antibody seroconversion rate of the combined group with the inactivated group (chi(2) = 3.89, P < 0.05), but no significant difference with attenuated group (chi(2) = 0.74, P > 0.05). CONCLUSION: Results showed that in children who previously had been immunized with two doses of inactivated vaccine, the booster administration of live attenuated vaccine was both effective and safe.