Notes

Differential osteogenic potential associated with human adipose-derived stem cells co-cultured along with human being osteoblasts upon polymeric microfiber scaffolds.
Dysregulated androgen receptor (AR) plays a crucial role in prostate cancer (PCa) development, though further factors involved in its regulation remain to be identified. Recently, paradoxical results were reported on the implication of the MEN1 gene in PCa. To dissect its role in prostate luminal cells, we generated a mouse model with inducible Men1 disruption in Nkx3.1-deficient mice in which mouse prostatic intraepithelial neoplasia (mPIN) occur. Prostate glands from mutant and control mice were analyzed pathologically and molecularly; cellular and molecular analyses were carried out in PCa cell lines after MEN1 knockdown (KD) by siRNA. Double-mutant mice developed accelerated mPIN and later displayed microinvasive adenocarcinoma. Markedly, early-stage lesions exhibited a decreased expression of AR and its target genes, accompanied by reduced CK18 and E-cadherin expression, suggesting a shift from a luminal to a dedifferentiated epithelial phenotype. Intriguingly, over 60% of menin-deficient cells expressed CD44 at a later stage. Furthermore, MEN1 KD led to the increase in CD44 expression in PC3 cells re-expressing AR. Menin bound to the proximal AR promoter and regulated AR transcription via the H3K4me3 histone mark. Interestingly, the cell proliferation of AR-dependent cells (LNCaP, 22Rv1, and VCaP), but not of AR-independent cells (DU145, PC3), responded strongly to MEN1 silencing. Finally, menin expression was found reduced in some human PCa. These findings highlight the regulation of the AR promoter by menin and the crosstalk between menin and the AR pathway. Our data could be useful for better understanding the increasingly reported AR-negative/NE-negative subtype of PCa and the mechanisms underlying its development.Cancer cell expression of PD-L1 leads to T cells exhaustion by transducing co-inhibitory signal, and further understanding the regulation of PD-L1 in cancer cells may provide additional therapeutic strategies. Here by drug repurposing screen, we identified amlodipine as a potent inhibitor of PD-L1 expression in cancer cells. Further survey of calcium-associated pathways revealed calpain-dependent stabilization of the PD-L1 protein. Intracellular calcium delivered an operational signal to calpain-dependent Beclin-1 cleavage, blocking autophagic degradation of PD-L1 accumulated on recycling endosome (RE). Blocking calcium flux by amlodipine depleted PD-L1 expression and increased CD8+ T-cell infiltration in tumor tissues but not in myocardium, causing dose-dependent tumor suppression in vivo. Rescuing PD-L1 expression eliminated the effects of amlodipine, suggesting the PD-L1-dependent effect of amlodipine. These results reveal a calcium-dependent mechanism controlling PD-L1 degradation, and highlight calcium flux blockade as a potential strategy for combinatorial immunotherapy.Colorectal tumors are hierarchically organized and governed by populations of self-renewing cancer stem cells, representing one of the deadliest types of cancers worldwide. Emergence of cancer stemness phenotype depends on epigenetic reprogramming, associated with profound transcriptional changes. As described for pluripotent reprogramming, epigenetic modifiers play a key role in cancer stem cells by establishing embryonic stem-like transcriptional programs, thus impacting the balance between self-renewal and differentiation. We identified overexpression of histone methyltransferase G9a as a risk factor for colorectal cancer, associated with shorter relapse-free survival. Moreover, using human transformed pluripotent cells as a surrogate model for cancer stem cells, we observed that G9a activity is essential for the maintenance of embryonic-like transcriptional signature promoting self-renewal, tumorigenicity, and undifferentiated state. Such a role was also applicable to colorectal cancer, where inhibitors of G9a histone methyltransferase function induced intestinal differentiation while restricting tumor-initiating activity in patient-derived colorectal tumor samples. Finally, by integrating transcriptome profiling with G9a/H3K9me2 loci co-occupancy, we identified the canonical Wnt pathway, epithelial-to-mesenchyme transition, and extracellular matrix organization as potential targets of such a chromatin regulation mechanism in colorectal cancer stem cells. Selleck Lonidamine Overall, our findings provide novel insights on the role of G9a as a driver of cancer stem cell phenotype, promoting self-renewal, tumorigenicity, and undifferentiated state.
Cross-sectional study.

To describe the socio-demographics, injury characteristics, prevalence of shoulder and neck symptoms, weekly participation in leisure time physical activity (LTPA) and quality of life (QoL) of individuals with spinal cord injury in Denmark (SCI).

Nation-wide community survey, Denmark.

Individuals with SCI for >2 years were included from three SCI rehabilitation departments. Questionnaire data regarding socio-demographic details, SCI injury characteristics, medical history, shoulder and neck symptoms, LTPA and QoL were collected.

Of 2454 potential participants, 1517 (62%) responded to the survey (mean age = 56.2, SD 16.1, 37% female, 42% tetraplegia, 23% complete SCI, mean time since injury = 16.9, SD 13.5). link2 75% used some form of assistive mobility device. Responders and non-responders showed no sex or injury type/severity differences. Shoulder and neck symptoms within the past 3 months were reported by 63 and 67% respectively, with 51% reporting shoulder symptoms within theudies using data from this cohort will investigate patterns and associations between shoulder/neck symptoms, use of assistive mobility devices, LTPA and QoL.
The effect of dietary cholesterol consumption on health effects and serum lipids remains controversial. This study aimed to examine the association of dietary cholesterol trajectories over 14 years in China with the risk of cardio-metabolic diseases and all-cause mortality and serum lipids.

This study used weighted longitudinal data of 8952 adults from the China Health and Nutrition Survey, and subgroup analyses included 5466 adults who provided blood samples. Latent class trajectory modelling was performed to examine cholesterol trajectories. Cox regression models and general linear regressions were performed to examine the association between trajectories and outcomes.

Compared to the participants with persistently low dietary cholesterol intake, participants with gradually increasing cholesterol intake throughout adulthood were more likely to have hypertension (HR = 1.14, 95% CI 1.03, 1.28) and to die due to all causes (HR = 2.19, 95% CI 1.57, 3.05). Moreover, participants with persistently high cholesterol intake were more likely to die due to all causes (HR = 2.26, 95% CI 1.47, 3.47). The total cholesterol (TC)HDL-cholesterol (HDL-C) ratio and apolipoprotein B (ApoB) in these two groups were also significantly elevated compared to the group with persistently low dietary cholesterol intake (all P < 0.05). An association between trajectories of cholesterol and the incidence of diabetes was also observed; however, such an association became non significant after additional adjustment for other nutrients, food consumption and social environment.

Gradually increasing or persistently high cholesterol consumption throughout adulthood was significantly associated with an increased risk of hypertension and all-cause mortality with elevated serum lipids.
Gradually increasing or persistently high cholesterol consumption throughout adulthood was significantly associated with an increased risk of hypertension and all-cause mortality with elevated serum lipids.
Nutrition is associated with frailty, functional impairments, and mortality in elderly people. Only a few studies focused on oldest-old hospitalized patients with worse health and more comorbidities compared with the general older adults in China.

This study aimed to investigate the nutritional risk, malnutrition, and nutritional support status of oldest-old hospitalized patients (≥80 years of age) in China, and to provide a basis for implementing an effective nutritional intervention.

This study involved 358 oldest-old patients of Peking Union Medical College Hospital in China. The Nutrition Risk Screening 2002 scale was used to assess nutritional risk. Malnutrition was defined as body mass index (BMI) < 18.5 kg/m
; or unwanted weight loss >10% at any time, or unwanted weight loss >5% in recent 3 months and BMI < 22 kg/m
. Logistic regression analysis was used to identify factors associated with nutritional risk.

The overall frequency of nutritional risk and malnutrition was 50.3% (180/358) and 36.0% (129/358), respectively. Also, 134 (37.3%) patients received nutritional support; the ratio of parenteral nutrition (PN) to enteral nutrition (EN) was 1.351. Further, 106 (58.9%) patients with nutritional risk received nutritional support. The number of chronic diseases and age were protective factors, and activities of daily living (ADL) were risk factors.

The overall frequencies of nutritional risk and malnutrition of oldest-old hospitalized patients were high, and the rates of EN and PN were low. Nutritional risk was associated with the number of chronic diseases, age, and ADL.
The overall frequencies of nutritional risk and malnutrition of oldest-old hospitalized patients were high, and the rates of EN and PN were low. Nutritional risk was associated with the number of chronic diseases, age, and ADL.Triple-negative breast cancer (TNBC) is an aggressive cancer, and rapidly progresses following relapse in advanced stage. This cancer is usually associated with worse overall survival, so the carcinogenesis of TNBC needs to be further explored to find more effective therapies. In this study, we intended to identify the roles of YY1-mediated long non-coding RNA Kcnq1ot1 in TNBC. First, the paired samples of tumor tissues and adjacent tissues were collected to determine YY1, lncRNA Kcnq1ot1, and PTEN expression using RT-qPCR and Western blot analysis followed by analysis of the relationship between them and patient survival. The results revealed that YY1 and lncRNA Kcnq1ot1 were upregulated in TNBC tissues, and high expression of YY1 and lncRNA Kcnq1ot1 was associated with poor patient survival. Then, ChIP and MSP assays were employed to explore interactions between YY1, lncRNA Kcnq1ot1, and PTEN gene. We obtained that YY1 upregulated lncRNA Kcnq1ot1, which mediated PTEN methylation via DNMT1, thus decreasing PTEN expression. link3 Afterward, TNBC cells were examined for their viability using functional assays with the results displaying that overexpression of YY1 facilitated TNBC cell proliferation, invasion, and migration. Mechanistically, upregulated YY1 repressed tumor growth by inhibiting PTEN via upregulation of lncRNA Kcnq1ot1. Mouse models were also constructed, and the above effects of YY1, lncRNA Kcnq1ot1, and PTEN on TNBC were also established in vivo. Taken together, this study demonstrates that the silencing of YY1 exerted tumor-suppressive effects on TNBC by modulating lncRNA Kcnq1ot1/DNMT1/PTEN pathway, in support of further investigation into anti-tumor therapy for TNBC.
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