p16 flow cytometry of exfoliated cervical cells: Its role in quantitative pathology and clinical diagnosis of squamous intraepithelial lesions.

Background: P16 is a surrogate signature compensating for the specificity and/or sensitivity deficiencies of the human papillomavirus (HPV) DNA and Papanicolaou smear (Pap) co-test for detecting high-grade cervical squamous intraepithelial lesions or worse (HSIL+). However, traditional p16INK4A immunostaining is labour intensive and skill demanding, and subjective biases cannot be avoided. Herein, we created a high-throughput, quantitative diagnostic device, p16INK4A flow cytometry (FCM) and assessed its performances in cervical cancer screening and prevention.

Therapeutic effect and mechanism of combination therapy with ursolic acid and insulin on diabetic nephropathy in a type I diabetic rat model.

This work aims to investigate the therapeutic effect of ursolic acid (UA) plus insulin (In) on diabetic nephropathy (DN) in streptozotocin (STZ)-induced T1DM rats. The experimental groups and operational details are as follows: A total of thirty-two SD rats were divided into four groups: the DN model group (DN, = 8), DN + In treatment group (DN + In, = 8), DN + In + UA administration group (DN + In + UA, = 8), and negative control group (control, = 8). After 8 weeks, changes in renal function indices and pathological damage were assessed.

hTERT promoter methylation promotes small cell lung cancer progression and radiotherapy resistance.

Small cell lung cancer (SCLC) has been a devastating actuality in clinic and the molecular mechanisms underlying this disease remain unclear. The epigenetic alterations located in the promoter region of human telomerase reverse transcriptase (hTERT) have been demonstrated as one of the most prevalent non-coding genomic modifications in multiple cancers. However, alteration of hTERT promoter methylation in SCLC and the subsequently induced change in tumor cell behavior remains unclear.

Landscape of RAS Variations in 17,993 Pan-cancer Patients Identified by Next-generation Sequencing.

RAS family genes (HRAS, KRAS and NRAS) were frequently observed in several tumors. The expression of constitutively active RAS proteins mediated by RAS variations promote the development of tumors. KRAS is an important prognostic and drug resistance biomarker.

MicroRNA-221 promotes breast cancer resistance to adriamycin via modulation of PTEN/Akt/mTOR signaling.

As a prevalent tumor among women, breast cancer is still an incurable disease due to drug resistance. In this study, we report microRNA-221 to have a significant effect on breast cancer resistance to adriamycin. The microRNA-221 is elevated in tumor tissue compared with nearby nontumor samples, as well as in breast cancer cell line with adriamycin resistance (MCF-7/ADR) compared to its parental line (MCF-7) and the normal breast epithelial cell line (MCF-10A).

TWIST1 Alleviates Hypoxia-induced Damage of Trophoblast Cells by inhibiting mitochondrial apoptosis pathway.

Preeclampsia (PE), especially severe and early-onset preeclampsia is one of the major causes of maternal and neonatal morbidity and mortality. However, the exact mechanism is not fully understood. In this study, we first demonstrated that the expression of TWIST1 was decreased in the placental tissues of patients with early-onset severe preeclampsia, compared with non-severe early onset preeclampsia.

Downregulations of circulating miR-31 and miR-21 are associated with preeclampsia.

MicroRNAs (miRNAs/miRs) are highly stable in circulating, which suppress target gene expression by base-pairing to the 3'-untranslated region. We compared the expressions of 3 circulating miRs (miR-31, miR-21, and miR-16), which are related to the control of cell apoptosis, invasion, angiogenesis and immune tolerance in non-pregnancy (n = 10), 20-34 gestational weeks normal pregnancy (20-34 GW NP, n = 20), early onset preeclampsia (EOPE, n = 20), 34-41 gestational weeks normal pregnancy (34-41 GW NP, n = 20) and late onset preeclampsia (LOPE, n = 20). Using quantitative RT-PCR, we found the levels of miR-31, miR-21 and miR-16 changed throughout different stages of pregnancy with the non-pregnancy as the calibrator.

MiR-204 suppresses cell proliferation and promotes apoptosis in ovarian granulosa cells via targeting TPT1 in polycystic ovary syndrome.

MicroRNA (miR)-204 is known to be associated with several different diseases. Polycystic ovary syndrome (PCOS) has the highest incidence rate among the endocrine disorders in females between the ages of 18 and 44. We aimed to illustrate the miR-204 function in PCOS.

CCL20 Promotes Ovarian Cancer Chemotherapy Resistance by Regulating ABCB1 Expression.

Ovarian cancer (OC) is one of prevalent tumors and this study aimed to explore CCL20's effects on doxorubicin resistance of OC and related mechanisms. Doxorubicin-resistant SKOV3 DR cells were established from SKOV3 cells via 6-month continuous exposure to gradient concentrations of doxorubicin. Quantitative PCR and Western blot assay showed that SKOV3 DR cells had higher level of CCL20 than SKOV3 cells, and doxorubicin upregulated CCL20 expression in SKOV3 cells.

Correction to: CDK5 Regulates PD-L1 Expression and Cell Maturation in Dendritic Cells of CRSwNP.

The article CDK5 Regulates PD-L1 Expression and Cell Maturation in Dendritic Cells of CRSwNP, written by C. C. Liu, H.

Genistein Inhibited Estradiol-Induced Vascular Endothelial Cell Injury by Downregulating the FAK/Focal Adhesion Pathway.

Background/aims: In this study, we aimed to investigate the effects of genistein on the focal adhesion signaling pathway through its regulation of FAK. Genistein ultimately restored and alleviated estradiol-induced vascular endothelial injury.

Methods: Microarray analysis was used to select differentially expressed genes.

CDK5 Regulates PD-L1 Expression and Cell Maturation in Dendritic Cells of CRSwNP.

The maturation of dendritic cells is critical for chronic rhinosinusitis with nasal polyps (CRSwNPs), especially eosinophilic chronic rhinosinusitis with nasal polyps (EosCRSwNPs), but the regulation mechanism of dendritic cells (DCs) maturation is still unclear. We identified nasal mucosa of 20 patients with EosCRSwNP, 16 non-EosCRSwNP patients, and inferior turbinate of 14 patients with nasal septum deviation after surgery. The expression of cyclin-dependent kinase 5 (CDK5) and programmed cell death 1 ligand 1 (PD-L1) were detected by immunofluorescent, real-time quantitative PCR, and Western blot in EosCRSwNP.

Potent Activity of the Bromodomain Inhibitor OTX015 in Multiple Myeloma.

Several studies demonstrate that the bromodomain inhibitor OTX015 has an antitumor activity in cancers. However, translation of these data to molecules suitable for clinical development has yet to be accomplished in multiple myeloma (MM). Here, we identified genes and biologic processes that substantiated the antimyeloma activity of OTX015 with global transcriptomics.

The Drug Combination of SB202190 and SP600125 Significantly Inhibit the Growth and Metastasis of Olaparib-resistant Ovarian Cancer Cell.

Background & Objective: Many targeted ovarian cancer patients are resistant to olaparib treatment. Here we seek to understand the underlying molecular events and search for potential combinational therapeutics to surmount the intrinsic olaparib resistance in human ovarian cancer.

Methods: The cytotoxicity was determined by the MTT assay and cell viability was measured using Cell Counting Kit-8 (CCK-8).

Triptolide antagonized the cisplatin resistance in human ovarian cancer cell line A2780/CP70 via hsa-mir-6751.

Aim: We aimed to investigate the effect of triptolide on cisplatin resistance in ovarian cancer cell lines.

Methods: The apoptosis of ovarian cancer cell lines A2780 and A2780/CP70 was determined by flow cytometry. Protein expression levels of  Hexokinase 2 (HK2) were detected by western blot.

Protective effect of KLF15 on vascular endothelial dysfunction induced by TNF‑α.

Atherosclerosis (AS) is a cardiovascular disease with a relatively high incidence rate. Krüppel‑like factor 15 (KLF15) has a role in numerous pathological processes, including nephropathy, abnormal glucose metabolism and myocardial injury. The aim of the present study was to investigate the function of KLF15 in vascular endothelial dysfunction.

scAAV9-VEGF-165 inhibits neuroinflammatory responses and invasion of macrophages into the peripheral nervous system of ALS transgenic mice.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that leads to paralysis and death within 3-5 years. Although the vast majority of studies have focused on vulnerable neurons, growing evidence has shown that non-neuronal cells contribute to the pathogenesis and disease progression. Here, we showed that intrathecal injection of scAAV9-VEGF at 60 days of age significantly reduced the number of microglia and inhibited the neuroinflammatory response in the CNS.

miR-146a promotes cell migration and invasion in melanoma by directly targeting SMAD4.

Previous studies have explored the functions of microRNA (miR)-146a in different types of cancer through mediating different targets. However, the roles of miR-146a in malignant melanoma (MM) cell migration and invasion remain largely elusive. In the present study, the potential molecular function of miR-146a in MM was investigated.

Systemic administration of scAAV9-IGF1 extends survival in SOD1 ALS mice via inhibiting p38 MAPK and the JNK-mediated apoptosis pathway.

Amyotrophic lateral sclerosis (ALS) is closely associated with a reduction of neurotrophic factors in the central nervous system (CNS). Insulin-like growth factor 1 (IGF1)-encoding vectors delivered via intramuscular and intraparenchymal spinal cord injections have conferred therapeutic benefits in ALS model mice, although the development of a noninvasive delivery route is still needed. Intravenous administration of adeno-associated virus (AAV) vectors has been used to induce expression of neurotrophic genes in the lumbar spinal cords of adult mice.

Endometriosis induces gut microbiota alterations in mice.

Study Question: What happens to the gut microbiota during development of murine endometriosis?

Summary Answer: Mice with the persistence of endometrial lesions for 42 days develop a distinct composition of gut microbiota.

What Is Known Already: Disorders in the immune system play fundamental roles in changing the intestinal microbiota. No study has used high-throughput DNA sequencing to show how endometriosis changes the gut microbiota, although endometriosis is accompanied by abnormal cytokine expression and immune cell dysfunction.

Emodin Enhances the Chemosensitivity of Endometrial Cancer by Inhibiting ROS-Mediated Cisplatin-resistance.

Background: Endometrial cancer is a common cause of death in gynecological malignancies. Cisplatin is a clinically chemotherapeutic agent. However, drug-resistance is the primary cause of treatment failure.

Down-regulation of TGF-β RII expression is correlated with tumor growth and invasion in non-functioning pituitary adenomas.

The two types of TGF-β receptors play a crucial role in TGF-β signaling. It has been reported that TGF-β signaling activity may be associated with the development and invasion of NFPAs. However, the role of TGF-β receptor signaling in NFPAs has not been fully explored.

Dietary epigallocatechin 3-gallate supplement improves maternal and neonatal treatment outcome of gestational diabetes mellitus: a double-blind randomised controlled trial.

Background: Gestational diabetes mellitus (GDM) is an increasing prevalent health risk in pregnant women. Epigallocatechin 3-gallate (EGCG) is known to benefit the insulin secretory machinery. We aimed to investigate the effect of daily dietary EGCG supplementation on both the maternal and neonatal treatment outcomes in GDM-affected pregnancies.