Mental health help-seeking in Mexico.

Most people in need of mental health services in Mexico do not seek formal support or professional services to address their mental health needs. Understanding help-seeking behaviors is crucial to addressing underutilized mental health services and to leverage health promotion efforts. Data were collected as part of a larger research project on stigma and help-seeking for mental-health-related concerns in Mexico. A convenience sample of 469 adults residing in Mexico City participated in the study using an experimental vignette methodology assessing stigma toward individuals with mental health conditions, along with characteristics and demographic correlates of help-seeking. All survey measures were administered in Spanish. A structural regression was conducted for the outcome 'openness to professional help seeking for mental health problems' as a latent variable. Compared with males, females were more open to professional help seeking (b = 0.09, p = 0.038), as were people who endorsed higher spirituality (b = 0.01, p = 0.006); while people who experienced self-stigma were less open to professional help-seeking for mental health concerns (b = -0.15, p = 0.005). Self-stigma was a major driver of low service utilization. Contrary to previous studies, spirituality was a significant positive predictor of professional help-seeking. A more nuanced understanding of mental health help-seeking in Mexico can be useful for outreach efforts to increase service utilization both in Mexico and among Latinos in the United States (US). Given historical, geographic, and cultural ties with the US, it is important to understand mental health help-seeking in Mexico, which may relate directly to help-seeking behaviors in many US Latinos who have immigrated to the US. Directions for future research and practice implications are discussed, including a roadmap for health promotion activities.

Kindlin-2 in myoepithelium controls luminal progenitor commitment to alveoli in mouse mammary gland.

Myoepithelium plays an important role in mammary gland development, but less is known about the molecular mechanism underlying how myoepithelium controls acinus differentiation during gestation. Herein, we found that loss of Kindlin-2 in myoepithelial cells impaired mammary morphogenesis, alveologenesis, and lactation. Using five genetically modified mouse lines combined with single-cell RNA sequencing, we found a Kindlin-2-Stat3-Dll1 signaling cascade in myoepithelial cells that inactivates Notch signaling in luminal cells and consequently drives luminal progenitor commitment to alveolar cells identity. Single-cell profiling revealed that Kindlin-2 loss significantly reduces the proportion of matured alveolar cells. Mechanistically, Kindlin-2 depletion in myoepithelial cells promotes Stat3 activation and upregulates Dll1, which activates the Notch pathway in luminal cells and inhibits luminal progenitor differentiation and maturation during gestation. Inhibition of Notch1 with tangeretin allowed luminal progenitors to regain commitment ability in the pregnant mice with Kindlin-2 depletion in myoepithelium. Taken together, we demonstrated that Kindlin-2 is essential to myoepithelium-controlled luminal progenitors to alveoli transition during gestation.

Trastuzumab-induced human cardiomyocyte damage through the Notch2/JAK2/STAT3 pathway.

OBJECTIVE: Trastuzumab is the preferred drug for the treatment of breast cancer. However, research on the cellular mechanisms of trastuzumab's potential cardiotoxicity is insufficient. The purpose of this study was to explore the toxic effects and potential mechanism of action of trastuzumab on cardiomyocytes. METHOD: Human Cardiomyocyte (HCM) viability was assessed using the MTT method. HCM apoptosis was detected using the Hoechst33342/PI Fluorescent staining. The LDH and CK activities of the cell were measured using commercially available LDH and CK assay kits. The expression levels of Notch2, JAK2, STAT3, cleaved caspase 3, bax, and bcl 2 in HCMs were detected using western blotting. RESULTS: The results showed that 250 mg/L trastuzumab induced cardiomyocyte injury and apoptosis, inhibited viability, activated the Notch2 receptor, and inhibited JAK2/STAT3 expression in HCM. Inhibition of Notch2 expression in HCM by targeted siNotch2 transfection reversed the trastuzumab-induced injury and apoptosis, and the expression of JAK2/STAT3 returned to normal levels. CONCLUSIONS: Trastuzumab induces Notch2 expression by inhibiting the JAK2/STAT3 pathway of HCMs, promotes cell apoptosis, and causes cardiomyocyteinjury. Notch2 may be a potential target of trastuzumab-inducedmyocardial injury. This experiment reveals the mechanism of trastuzumab-induced cardiotoxicity, providing a theoretical basis for the application of trastuzumab.

Predictors of Stigma toward Alcohol Misuse in Mexico.

Objective: This study explored factors associated with public stigma toward individuals misusing alcohol in Mexico. Methods: A randomized experimental vignette methodology was used to assess multiple domains of substance use-related stigma and their relationship to the gender of the vignette subject and the sociodemographic characteristics of respondents. Results: Although levels of stigma toward women who were misusing alcohol did not differ significantly from stigma toward men misusing alcohol, stigma levels and type of stigma reported varied with the sociodemographic characteristics of respondents. Education level, gender, self-stigma and openness to seeking mental health services were differentially associated with the three stigma domains. Conclusions: Accordingly, targeted community based stigma reduction efforts are needed to decrease stigma toward those misusing alcohol, and to support treatment initiation, ongoing treatment engagement and long term recovery efforts. Suggestions for future research on the relationship between substance use and stigma are offered.

MTF1 has the potential as a diagnostic and prognostic marker for gastric cancer and is associated with good prognosis.

PURPOSE: Metal Regulatory Transcription Factor 1 (MTF1) can be an essential transcription factor for heavy metal response in cells and can also reduce oxidative and hypoxic stresses in cells. However, the current research on MTF1 in gastric cancer is lacking. METHODS: Bioinformatics techniques were used to perform expression analysis, prognostic analysis, enrichment analysis, tumor microenvironment correlation analysis, immunotherapy Immune cell Proportion Score (IPS) correlation and drug sensitivity correlation analysis of MTF1 in gastric cancer. And qRT-PCR was used to verify MTF1 expression in gastric cancer cells and tissues. RESULTS: MTF1 showed low expression in gastric cancer cells and tissues, and low expression in T3 stage compared with T1 stage. KM prognostic analysis showed that high expression of MTF1 was significantly associated with longer overall survival (OS), FP (first progression) and PPS (post-progression survival) in gastric cancer patients. Cox regression analysis showed that MTF1 was an independent prognostic factor and a protective factor in gastric cancer patients. MTF1 is involved in pathways in cancer, and the high expression of MTF1 is negatively correlated with the half maximal inhibitory concentration (IC50) of common chemotherapeutic drugs. CONCLUSION: MTF1 is relatively lowly expressed in gastric cancer. MTF1 is also an independent prognostic factor for gastric cancer patients and is associated with good prognosis. It has the potential to be a diagnostic and prognostic marker for gastric cancer.

Trastuzumab-induced human cardiomyocyte damage through the Notch2/JAK2/STAT3 pathway

Abstract Objective Trastuzumab is the preferred drug for the treatment of breast cancer. However, research on the cellular mechanisms of trastuzumab's potential cardiotoxicity is insufficient. The purpose of this study was to explore the toxic effects and potential mechanism of action of trastuzumab on cardiomyocytes. Method Human Cardiomyocyte (HCM) viability was assessed using the MTT method. HCM apoptosis was detected using the Hoechst33342/PI Fluorescent staining. The LDH and CK activities of the cell were measured using commercially available LDH and CK assay kits. The expression levels of Notch2, JAK2, STAT3, cleaved caspase 3, bax, and bcl 2 in HCMs were detected using western blotting. Results The results showed that 250 mg/L trastuzumab induced cardiomyocyte injury and apoptosis, inhibited viability, activated the Notch2 receptor, and inhibited JAK2/STAT3 expression in HCM. Inhibition of Notch2 expression in HCM by targeted siNotch2 transfection reversed the trastuzumab-induced injury and apoptosis, and the expression of JAK2/STAT3 returned to normal levels. Conclusions Trastuzumab induces Notch2 expression by inhibiting the JAK2/STAT3 pathway of HCMs, promotes cell apoptosis, and causes cardiomyocyteinjury. Notch2 may be a potential target of trastuzumab-inducedmyocardial injury. This experiment reveals the mechanism of trastuzumab-induced cardiotoxicity, providing a theoretical basis for the application of trastuzumab.