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Patients with advanced salivary gland mucoepidermoid carcinoma (MEC) are treated with surgery and radiotherapy, as current systemic therapies are largely ineffective. As such, current treatment frequently leads to poor long-term survival due to locoregional recurrence or metastases. We have shown that salivary gland cancer stem cells (CSCs) are resistant to platinum-based chemotherapy and drive tumor progression. The purpose of this study was to investigate the effect of therapeutic inhibition of mTOR (mechanistic target of rapamycin) on resistance of CSCs to cisplatin, a prototypic platinum-based chemotherapeutic agent. Viability assays determined the effect of several inhibitors of PI3k/mTOR signaling (e.g., temsirolimus, BKM120, AZD8055, PF4708671) and/or cisplatin on survival of human MEC cells. The impact of mTOR inhibitors and/or cisplatin on MEC stemness was examined with salisphere assays, flow cytometry for ALDH/CD44 (CSC markers for MEC), and Western blots for Bmi-1 expression (marker of stem cell self-renewal). Salivary gland MEC patient-derived xenografts were used to examine the effect of cisplatin and/or temsirolimus on CSCs in vivo. We observed that cisplatin induced mTOR and S6K1 phosphorylation, increased the number and size of MEC salispheres, and induced Bmi-1 expression and the fraction of CSCs in MEC models in vitro. Cisplatin also increased the fraction of CSCs in vivo. In contrast, mTOR inhibition (e.g., temsirolimus) blocked cisplatin-induced Bmi-1 expression and salisphere formation in vitro. Remarkably, temsirolimus slowed down tumor growth and decreased the fraction of CSCs (P less then 0.05) even in presence of cisplatin in a short-term in vivo experiment. Collectively, these results demonstrate that therapeutic inhibition of mTOR ablates cytotoxic-resistant CSCs, and they suggest that a combination of an mTOR inhibitor and platinum-based chemotherapy might be beneficial to patients with salivary gland mucoepidermoid carcinoma.Researchers have expanded the aggressor-victim dyad by showing that bystanders play pivotal roles in the process of cyberbullying. Bystanders' responses entail moral engagement and are guided by personal and social norms. Most research on normative influences on bystanders' responses to cyberbullying has focused on personal or social norms but has ignored how they jointly affect bystanders' responses. Inspiring by the modified Theory of Planned Behavior, a cross-sectional study of Chinese high-school students (N = 333) examined how cyberbullying-related personal and social norms affect adolescent bystanders' responses to cyberbullying. We collected information on personal norms, social norms, and bystanders' responses to cyberbullying. Boys reported stronger intentions than girls to reinforce the bully, but intentions to help the victim were equivalent among boys and girls. Regression analysis revealed that pro-cyberbullying personal and social norms combined could negatively predict intentions to help the victim. However, personal and social norms interacted to influence behavioral intentions to reinforce the bully. Specifically, when pro-cyberbullying social norms were at a high level, a higher level of pro-cyberbullying personal norms was correlated with higher intentions to reinforce the bully. Conversely, when pro-cyberbullying social norms were at a low level, the effect of personal norms disappeared. The findings contribute to understanding the process by which adolescents adapt themselves to norms and provide guidance for educational advice on intervening in cyberbullying.This study aimed to compare the performance of MilliSect dissection and manual dissection. Twenty-five formalin-fixed paraffin-embedded (FFPE) breast cancer tissue blocks were selected for comparison. Specific areas of interest (AOIs) in invasive carcinoma on tissue sections were transferred to dissection slides by manual macrodissection or the MilliSect instrument. The comparison criteria were 1) the time required for dissection; 2) RNA concentration and purity; 3) RNA quantity of 5 housekeeping genes (by RT-qPCR); and 4) ER, PR, HER2, Ki-67 and recurrence score (RS) values (by the 21-gene assay). Then, tumor-adjacent tissues, including fibrocollagenous and epithelial tissues, from the same selected tissue blocks of 8 of 25 patients were scraped using the mesodissection method, and their RS values were assessed to evaluate the influence of tumor-adjacent tissues on the target AOIs. Ultimately, 4 AOIs of invasive ductal carcinoma (IDC) from 1 tissue block of another 4 patients with lymph node (LN) metastases ion.We previously reported that sputum induction was more sensitive than throat swabs for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in two convalescent coronavirus disease 2019 (COVID-19) patients; however, the value and safety of induced sputum testing require further study. We conducted a prospective multi-center cross-sectional study to compare induced sputum to throat swabs for SARS-CoV-2 detection. Confirmed COVID-19 patients from six hospitals in six cities across China who received one or more negative RT-PCR result for SARS-CoV-2 were enrolled, and paired specimens (induced sputum and throat swabs; 56 cases) were assayed. In three paired samples, both the induced sputum and throat swabs were positive for SARS-CoV-2. The positive rate for induced sputum was significantly higher than for throat swabs both overall (28.6% vs 5.4%, respectively; p less then 0.01). Patients were divided according to time span from onset of illness to sample collection into the more-than-30-day (n = 26) and less-than-30-day (n = 30) groups. The positive rate for induced sputum was also significantly higher than for throat swabs in the less-than-30-day group (53.3% vs 10.0%, respectively; p less then 0.001). For the more-than-30-day group, all paired samples were negative for SARS-CoV-2. Blood oxygen saturation, respiratory rate, and heart rate remained stable during sputum induction and no staff were infected. Because induced sputum is more reliable and has a lower false-negative rate than throat swabs, we believe induced sputum is more useful for the confirmation of COVID-19 and is safer as a criterion for release from quarantine.

Colorectal cancer (CRC) is one of the most common digestive malignant tumors globally. Focally amplified lncRNA on chromosome 1 (FALEC) is a novel lncRNA that has been reported to be involved in many biological processes during carcinogenesis. https://www.selleckchem.com/products/acss2-inhibitor.html However, its role in CRC remains poorly understood.

Gene expression at mRNA or protein level was measured by qRT-PCR or western blot, respectively. In vitro experiments including EdU, colony formation, flow cytometry, wound-healing and transwell assays, as well as in vivo xenograft experiment, were utilized to determine the functional role of FALEC in CRC. Relevant mechanical assays were performed to investigate the underlying molecular mechanism.

FALEC was aberrantly up-regulated in CRC. FALEC knockdown could impair CRC cell proliferation, migration and invasion, whereas facilitate cell apoptosis. MiR-2116-3p was revealed to be sponged by FALEC. PIWIL1 was identified as the target of miR-2116-3p. Mechanically, FALEC restored the expression of PIWIL1 via absorbing miR-2116-3p. MiR-2116-3p inhibition and PIWIL1 enrichment could counteract the anti-tumor impact induced by silenced FALEC on the oncogenic behaviors of CRC cells.

Our study revealed that FALEC promoted CRC progression via restoring the expression of miR-2116-3p-targeted PIWIL1, suggesting the potential application of targeting FALEC in the treatment of CRC.

Our study revealed that FALEC promoted CRC progression via restoring the expression of miR-2116-3p-targeted PIWIL1, suggesting the potential application of targeting FALEC in the treatment of CRC.Our study aimed to identify differentially methylated CpGs/regions and their enriched genomic pathways associated with underlying chronic musculoskeletal pain in older individuals. We recruited cognitively healthy older adults with (n = 20) and without (n = 9) self-reported musculoskeletal pain and collected DNA from peripheral blood that was analyzed using MethylationEPIC arrays. We identified 31,739 hypermethylated CpG and 10,811 hypomethylated CpG probes (ps ≤ 0.05). All CpG probes were clustered into 5966 regions, among which 600 regions were differentially methylated at p ≤ 0.05 level, including 294 hypermethylated regions and 306 hypomethylated regions (differentially methylated regions). Ingenuity pathway enrichment analysis revealed that the pain-related differentially methylated regions were enriched across multiple pathways. The top 10 canonical pathways were linked to cellular signaling processes related to immune responses (i.e. antigen presentation, programed cell death 1 receptor/PD-1 ligand 1, interleukin-4, OX40 signaling, T cell exhaustion, and apoptosis) and gamma-aminobutyric acid receptor signaling. Further, Weighted Gene Correlation Network Analysis revealed a comethylation network module in the pain group that was not preserved in the control group, where the hub gene was the cyclic adenosine monophosphate-dependent transcription factor ATF-2. Our preliminary findings provide new epigenetic insights into the role of aberrant immune signaling in musculoskeletal pain in older adults while further supporting involvement of dysfunctional GABAergic signaling mechanisms in chronic pain. Our findings need to be urgently replicated in larger cohorts as they may serve as a basis for developing and targeting future interventions.The immunodeficiency observed in HIV-1-infected patients is mainly due to uninfected bystander CD4+ T lymphocyte cell death. The viral envelope glycoproteins (Env), expressed at the surface of infected cells, play a key role in this process. Env triggers macroautophagy/autophagy, a process necessary for subsequent apoptosis, and the production of reactive oxygen species (ROS) in bystander CD4+ T cells. Here, we demonstrate that Env-induced oxidative stress is responsible for their death by apoptosis. Moreover, we report that peroxisomes, organelles involved in the control of oxidative stress, are targeted by Env-mediated autophagy. Indeed, we observe a selective autophagy-dependent decrease in the expression of peroxisomal proteins, CAT and PEX14, upon Env exposure; the downregulation of either BECN1 or SQSTM1/p62 restores their expression levels. Fluorescence studies allowed us to conclude that Env-mediated autophagy degrades these entire organelles and specifically the mature ones. Together, our results on Env-induced pexophagy provide new clues on HIV-1-induced immunodeficiency. Abbreviations Ab antibodies; AF auranofin; AP anti-proteases; ART antiretroviral therapy; BafA1 bafilomycin A1; BECN1 beclin 1; CAT catalase; CD4 CD4 molecule; CXCR4 C-X-C motif chemokine receptor 4; DHR123 dihydrorhodamine 123; Env HIV-1 envelope glycoproteins; GAPDH glyceraldehyde-3-phosphate dehydrogenase; GFP green fluorescent protein; GFP-SKL GFP-serine-lysine-leucine; HEK human embryonic kidney; HIV-1 type 1 human immunodeficiency virus; HTRF homogeneous time resolved fluorescence; MAP1LC3/LC3 microtubule associated protein 1 light chain 3; NAC N-acetyl-cysteine; PARP poly(ADP-ribose) polymerase; PEX peroxin; ROS reactive oxygen species; siRNA small interfering ribonucleic acid; SQSTM1/p62 sequestosome 1.