An RFC4/Notch1 signaling feedback loop promotes NSCLC metastasis and stemness.

Notch signaling represents a key mechanism mediating cancer metastasis and stemness. To understand how Notch signaling is overactivated to couple tumor metastasis and self-renewal in NSCLC cells, we performed the current study and showed that RFC4, a DNA replication factor amplified in more than 40% of NSCLC tissues, directly binds to the Notch1 intracellular domain (NICD1) to competitively abrogate CDK8/FBXW7-mediated degradation of NICD1. Moreover, RFC4 is a functional transcriptional target gene of Notch1 signaling, forming a positive feedback loop between high RFC4 and NICD1 levels and sustained overactivation of Notch signaling, which not only leads to NSCLC tumorigenicity and metastasis but also confers NSCLC cell resistance to treatment with the clinically tested drug DAPT against NICD1 synthesis.

Storage Time of Cryopreserved Embryos and Pregnancy Outcomes: A Dose-Response Meta-Analysis.

Cryopreservation techniques have become an essential part of assisted reproduction technology. Embryos may be cryopreserved for several years before transfer, and the safety of long-term cryopreservation needs to be considered. This dose-response meta-analysis was conducted to evaluate whether there were dose-response relationships between the storage time of cryopreserved embryos and pregnancy outcomes such as survival rate, implantation rate, miscarriage rate, clinical pregnancy rate, and congenital malformation rate.

Impaired neurogenesis in the hippocampus of an adult VPS35 mutant mouse model of Parkinson's disease through interaction with APP.

Vacuolar protein sorting protein 35 (VPS35) is a core component of the retromer complex involved in regulating protein trafficking and retrieval. Recently, a missense mutation, Asp620Asn (D620N), in VPS35 (PARK17) has been identified as a pathogenic mutation for late-onset autosomal dominant Parkinson's disease (PD). Although PD is characterized by a range of motor symptoms associated with loss of dopaminergic neurons in the substantial nigra, non-motor symptoms such as impaired hippocampal neurogenesis were observed in both PD patients and animal models of PD caused by multiple PD-linked pathogenic genes such as alpha-synuclein and leucine-rich repeat kinase 2 (LRRK2).

Research on the Potential Mechanism of Gentiopicroside Against Gastric Cancer Based on Network Pharmacology.

Background: Gastric cancer was still one of the commonly diagnosed cancer types and the third-most common cause of cancer-related death in the world. Gentiopicroside, which is extracted from the , is commonly used in both traditional treatment and modern clinical care; therefore, its anticancer effects have been attracted more attention. However, the systematic analysis of action mechanism of Gentiopicroside on gastric cancer (GC) has not yet been carried out.

Small Molecule Epigenetic Modulators in Pure Chemical Cell Fate Conversion.

Although innovative technologies for somatic cell reprogramming and transdifferentiation provide new strategies for the research of translational medicine, including disease modeling, drug screening, artificial organ development, and cell therapy, recipient safety remains a concern due to the use of exogenous transcription factors during induction. To resolve this problem, new induction approaches containing clinically applicable small molecules have been explored. Small molecule epigenetic modulators such as DNA methylation writer inhibitors, histone methylation writer inhibitors, histone acylation reader inhibitors, and histone acetylation eraser inhibitors could overcome epigenetic barriers during cell fate conversion.

xCT: A Critical Molecule That Links Cancer Metabolism to Redox Signaling.

System x cystine/glutamate antiporter, composed of a light-chain subunit (xCT, SLC7A11) and a heavy-chain subunit (CD98hc, SLC3A2), is mainly responsible for the cellular uptake of cystine in exchange for intracellular glutamate. In recent years, the xCT molecule has been found to play an important role in tumor growth, progression, metastasis, and multidrug resistance in various types of cancer. Interestingly, xCT also exhibits an essential function in regulating tumor-associated ferroptosis.

Amyloid precursor protein intracellular domain-dependent regulation of FOXO3a inhibits adult hippocampal neurogenesis.

The amyloid precursor protein (APP) intracellular domain (AICD) is a metabolic by-product of APP produced through sequential proteolytic cleavage by α-, β-, and γ-secretases. The interaction between AICD and Fe65 has been reported to impair adult neurogenesis in vivo. However, the exact role of AICD in mediating neural stem cell fate remains unclear.

Epidemiologic and clinical characteristics of 42 deaths caused by SARS-CoV-2 infection in Wuhan, China: A retrospective study.

This study described the epidemiologic and clinical characteristics of patients who died from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and pointed out the potential risk factors associated with fatal outcomes. Retrospective data from 42 death cases due to SARS-CoV-2 infection at Tongji Hospital Affiliated to Huazhong University of Science and Technology, Wuhan, China was analyzed. Demographics, clinical detection, laboratory findings, and treatments of the deceased were collected and analyzed.

Individualized cumulative cisplatin dose for locoregionally-advanced nasopharyngeal carcinoma patients receiving induction chemotherapy and concurrent chemoradiotherapy.

Objectives: To screen subgroup potentially benefiting from cumulative cisplatin dose (CCD) ≥ 200 mg/m during concurrent chemoradiotherapy (CCRT) of patients with locoregionally-advanced nasopharyngeal carcinoma (LA-NPC) receiving induction chemotherapy (IC) and CCRT.

Materials And Methods: In total, 2 063 patients with non-disseminated LA-NPC diagnosed from 2009 to 2015 receiving IC plus CCRT were enrolled. Patients were restaged based on proposed stage groupings and risk groupings was established.

Mean platelet volume/platelet count ratio predicts long-term mortality in patients with infective endocarditis.

We aimed to examine the association between baseline mean platelet volume/platelet count ratio (MPR) and all-cause mortality in patients with infective endocarditis (IE). This study analyzed 218 consecutive patients with IE and divided them into four groups based on MPR quartiles. We used Kaplan-Meier survival curves to determine the cumulative survival and Cox proportional hazards models to investigate the association between MPR and all-cause mortality after hospital discharge.

8‑Gingerol regulates colorectal cancer cell proliferation and migration through the EGFR/STAT/ERK pathway.

8‑Gingerol, which is extracted from ginger (Zingiber officinale Roscoe), has been shown to possess antioxidant and anti‑inflammatory properties. However, the antitumor effect of 8‑gingerol has not been fully elucidated. The aim of the present study was to investigate the therapeutic potential of 8‑gingerol against colorectal cancer (CRC).

DACT1 Involvement in the Cytoskeletal Arrangement of Cardiomyocytes in Atrial Fibrillation by Regulating Cx43.

Objective: To determine the role of the dishevelled binding antagonist of beta catenin 1 (DACT1) in the cytoskeletal arrangement of cardiomyocytes in atrial fibrillation (AF).

Methods: The DACT1 expression and its associations with the degree of fibrosis and β-catenin in valvular disease patients were analyzed by immunohistochemistry and Masson's staining. DACT1 was overexpressed in the atrial myocyte cell line (HL-1) and the cardiac cell line (H9C2) by adenoviral vectors.

Thioesterase PPT1 balances viral resistance and efficient T cell crosspriming in dendritic cells.

Conventional type 1 dendritic cells (cDC1s) are inherently resistant to many viruses but, paradoxically, possess fewer acidic phagosomes that enable antigen retention and cross-presentation. We report that palmitoyl-protein thioesterase 1 (PPT1), which catabolizes lipid-modified proteins in neurons, is highly expressed in cDC1s. PPT1-deficient DCs are more susceptible to vesicular stomatitis virus (VSV) infection, and mice with PPT1 deficiency in cDC1s show impaired response to VSV.

Clinicopathological characteristics and health care for Tibetan women with breast cancer: a cross-sectional survey.

Background: The healthcare system (HCS) improved in Tibet Autonomous Region (TAR), China. The present study aimed to investigate whether these improvements might alter the clinicopathological characteristics of a Tibetan female with breast cancer (BC) in TAR.

Methods: This was a single-center cross-sectional study conducted at TAR People's Hospital.

[Effects of different administration methods of hydrocortisone on blood glucose in patients with septic shock: a Meta-analysis].

Objective: To systematically evaluate the effect of different administration methods of hydrocortisone on blood glucose in patients with septic shock.

Methods: The Cochrane Library, PubMed, Web of Science, Embase, CNKI, CBM, Wanfang, and VIP databases were searched from foundation to December 31st, 2017 for the randomized controlled trials (RCTs) about hydrocortisone on blood glucose of different drug-deliver ways in patients with septic shock. In addition, the citation retrievals were performed by the literature references.

Soluble (pro)renin receptor as a potential therapy for diabetes insipidus.

The antidiuretic hormone vasopressin (VP) is produced by the hypothalamus and is stored and secreted from the posterior pituitary. VP acts via VP type 2 receptors (V2Rs) on the basolateral membrane of principal cells of the collecting duct (CD) to regulate fluid permeability. The VP-evoked endocrine pathway is essential in determining urine concentrating capability.

Role of (pro)renin receptor in albumin overload-induced nephropathy in rats.

Proteinuria is not only a common feature of chronic kidney diseases (CKD) but also an independent risk factor promoting CKD progression to end-stage renal failure. However, the underlying molecular mechanisms for protein overload-induced renal injury remain elusive. The present study examined the role of (pro)renin receptor (PRR) in pathogenesis of albumin overload (AO)-induced nephropathy and activation of the intrarenal renin-angiotensin system (RAS) in rats.

Platelet-rich Plasma Protects HUVECs against oX-LDL-induced Injury.

Unlabelled: Platelet-rich plasma (PRP) contains a variety of cytokines, some of which ameliorate oX-LDL (oxidized low-density lipoprotein)-induced endothelial cell (EC) injury. Therefore, we hypothesized that PRP might alleviate oX-LDL-induced injury.

Methodology: Human umbilical vein endothelial cells (HUVECs) were divided into four groups: a PPP (platelet-poor plasma) group, an oX-LDL group, an oX-LDL+PRP group and a PRP group.

CK1α suppresses lung tumour growth by stabilizing PTEN and inducing autophagy.

The contribution of autophagy to cancer development remains controversial, largely owing to the fact that autophagy can be tumour suppressive or oncogenic in different biological contexts. Here, we show that in non-small-cell lung cancer (NSCLC), casein kinase 1 alpha 1 (CK1α) suppresses tumour growth by functioning as an autophagy inducer to activate an autophagy-regulating, tumour-suppressive PTEN/AKT/FOXO3a/Atg7 axis. Specifically, CK1α bound the C-terminal tail of PTEN and enhanced both PTEN stability and activity by competitively antagonizing NEDD4-1-induced PTEN polyubiquitination and abrogating PTEN phosphorylation, thereby inhibiting AKT activity and activating FOXO3a-induced transcription of Atg7.

A novel antigenic cathepsin B protease induces protective immunity in Trichinella-infected mice.

Trichinellosis is a foodborne disease that remains a public health hazard and an economic problem in food safety. Vaccines against the parasite can be an effective way to control this disease; however, commercial vaccines against Trichinella infection are not yet available. Trichinella cathepsin B proteins appear to be promising targets for vaccine development.

The soluble (Pro) renin receptor does not influence lithium-induced diabetes insipidus but does provoke beiging of white adipose tissue in mice.

Earlier we reported that the recombinant soluble (pro) renin receptor sPRR-His upregulates renal aquoporin-2 (AQP2) expression, and attenuates polyuria associated with nephrogenic diabetes insipidus (NDI) induced by vasopressin type 2 receptor (V2R) antagonism. Patients that receive lithium therapy develop polyuria associated NDI that might be secondary to downregulation of renal AQP2. We hypothesized that sPRR-His attenuates indices of NDI associated with lithium treatment.

Decorin gene upregulation mediated by an adeno-associated virus vector increases intratumoral uptake of nab-paclitaxel in neuroblastoma via inhibition of stabilin-1.

The availability of effective medication for the treatment of refractory or recurrent neuroblastoma remains limited. This study sought to investigate the effects of increased decorin (DCN) expression on the intratumoral uptake of nab-paclitaxel as a potential novel approach to NB. Correlation between the clinical characteristics of neuroblastoma and the expression of DCN, secreted protein acidic and rich in cysteine (SPARC) and stabilin-1 was evaluated.

Simultaneous overactivation of Wnt/β-catenin and TGFβ signalling by miR-128-3p confers chemoresistance-associated metastasis in NSCLC.

Cancer chemoresistance and metastasis are tightly associated features. However, whether they share common molecular mechanisms and thus can be targeted with one common strategy remain unclear in non-small cell lung cancer (NSCLC). Here, we report that high levels of microRNA-128-3p (miR-128-3p) is key to concomitant development of chemoresistance and metastasis in residual NSCLC cells having survived repeated chemotherapy and correlates with chemoresistance, aggressiveness and poor prognosis in NSCLC patients.

Suberoylanilide hydroxamic acid sensitizes neuroblastoma to paclitaxel by inhibiting thioredoxin-related protein 14-mediated autophagy.

Paclitaxel is not as effective for neuroblastoma as most of the front-line chemotherapeutics due to drug resistance. This study explored the regulatory mechanism of paclitaxel-associated autophagy and potential solutions to paclitaxel resistance in neuroblastoma. The formation of autophagic vesicles was detected by scanning transmission electron microscopy and flow cytometry.

Real role of β-blockers in regression of left ventricular mass in hypertension patients: Bayesian network meta-analysis.

Background: Left ventricular hypertrophy (LVH) is commonly present in patients with hypertension (HT). According to the expert consensus document from American, angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blockers (ARBs) were recommended as 1st-line therapeutic drugs. However, none noticed the different efficacy between fat-soluble and selective β1-receptor blockers (FS-β-B) and other β-blockers on regression of LVH before.