GABA(A) Receptor Activation Drives GABARAP-Nix Mediated Autophagy to Radiation-Sensitize Primary and Brain-Metastatic Lung Adenocarcinoma Tumors.

In non-small cell lung cancer (NSCLC) treatment, radiotherapy responses are not durable and toxicity limits therapy. We find that AM-101, a synthetic benzodiazepine activator of GABA(A) receptor, impairs the viability and clonogenicity of both primary and brain-metastatic NSCLC cells. Employing a human-relevant ex vivo 'chip', AM-101 is as efficacious as docetaxel, a chemotherapeutic used with radiotherapy for advanced-stage NSCLC.

Coordinated Targeting of S6K1/2 and AXL Disrupts Pyrimidine Biosynthesis in PTEN-Deficient Glioblastoma.

Unlabelled: Intrinsic resistance to targeted therapeutics in PTEN-deficient glioblastoma (GBM) is mediated by redundant signaling networks that sustain critical metabolic functions. Here, we demonstrate that coordinated inhibition of the ribosomal protein S6 kinase 1 (S6K1) and the receptor tyrosine kinase AXL using LY-2584702 and BMS-777607 can overcome network redundancy to reduce GBM tumor growth. This combination of S6K1 and AXL inhibition suppressed glucose flux to pyrimidine biosynthesis.

E/e' Ratio and Diastolic Function Between Deep Vein Catheterization and Internal Fistula Treatment in Patients with Chronic Kidney Disease.

Objective: To examine the relationship between diastolic function and the ratio of early diastolic mitral inflow to early diastolic mitral annular velocity (E/e') in patients with chronic renal disease who had deep vein catheterization and internal fistula.

Methods: The clinical data of 50 uremia patients treated at The Affiliated Dongyang Hospital of Wenzhou Medical University from January 2020 to January 2022 were retrospectively analyzed. To assess the differences in E/e' ratio and patients' diastolic function between the two groups, they were split into two teams according to the various therapy modalities: the internal fistula team (n = 42) and the deep vein catheterization team (n = 8).

Comparison of machine learning models based on multi-parametric magnetic resonance imaging and ultrasound videos for the prediction of prostate cancer.

Objective: To establish machine learning (ML) prediction models for prostate cancer (PCa) using transrectal ultrasound videos and multi-parametric magnetic resonance imaging (mpMRI) and compare their diagnostic performance.

Materials And Methods: We systematically collated the data of 383 patients, including 187 with PCa and 196 with benign lesions. Of them, 307 patients (150 with PCa and 157 with benign lesions) were randomly selected to train and validate the ML models, 76 patients were used as test set.

Electric Fields Regulate In Vitro Surface Phosphatidylserine Exposure of Cancer Cells via a Calcium-Dependent Pathway.

Cancer is the second leading cause of death worldwide after heart disease. The current treatment options to fight cancer are limited, and there is a critical need for better treatment strategies. During the last several decades, several electric field (EF)-based approaches for anti-cancer therapies have been introduced, such as electroporation and tumor-treating fields; still, they are far from optimal due to their invasive nature, limited efficacy and significant side effects.

Massive gastrointestinal haemorrhage caused by pancreatic pseudocyst complicated with Dieulafoy's disease in a child: A case report and review of the literature.

Background: Pancreatic pseudocyst (PPC) with massive gastrointestinal bleeding is rare, especially in children. Inadvertent intraoperative examination and damage to the gastric mucosa and malformed blood vessels by the fluid content of PPC can lead to massive bleeding, which may endanger the patient's life.

Case Presentation: Here, we present a case of an 8-year-old boy who was diagnosed with a massive gastrointestinal haemorrhage caused by PPC complicated with Dieulafoy's disease.

Bioinformatics analysis to obtain critical genes regulated in subcutaneous adipose tissue after bariatric surgery.

Bariatric surgery (BS) is a dependable method for managing obesity and metabolic diseases, however, the regulatory processes of lipid metabolism are still not well elucidated. Differentially expressed genes (DEGs) were analysed through three transcriptomic datasets of GSE29409, GSE59034 and GSE72158 from the GEO database regarding subcutaneous adipose tissue (SAT) after BS, and 37 DEGs were identified. The weighted gene co-expression network analysis (WGCNA), last absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine-recursive feature elimination (SVM-RFE) algorithms further screened four key genes involved in the regulation of STMN2, SFRP4, APOE and MXRA5.

Axl Expression in Renal Mesangial Cells Is Regulated by Sp1, Ap1, MZF1, and Ep300, and the IL-6/miR-34a Pathway.

Axl receptor tyrosine kinase expression in the kidney contributes to a variety of inflammatory renal disease by promoting glomerular proliferation. Axl expression in the kidney is negligible in healthy individuals but upregulated under inflammatory conditions. Little is known about Axl transcriptional regulation.

Phosphatidylserine: The Unique Dual-Role Biomarker for Cancer Imaging and Therapy.

Cancer is among the leading causes of death worldwide. In recent years, many cancer-associated biomarkers have been identified that are used for cancer diagnosis, prognosis, screening, and early detection, as well as for predicting and monitoring carcinogenesis and therapeutic effectiveness. Phosphatidylserine (PS) is a negatively charged phospholipid which is predominantly located in the inner leaflet of the cell membrane.

Shp2 suppresses fat accumulation in white adipose tissue by activating Wnt/β-catenin signaling following vertical sleeve gastrectomy in obese rats with type-2 diabetes.

Adipogenesis and fat accumulation are closely associated with the development of obesity. Sleeve gastrectomy (SG) is an effective treatment for obesity and associated metabolic disorders. Leptin is downregulated after SG and Src homology phosphatase 2 (Shp2) has an important role in leptin signaling.

RNA modification writers influence tumor microenvironment in gastric cancer and prospects of targeted drug therapy.

RNA adenosine modifications are crucial for regulating RNA levels. N6-methyladenosine (m6A), N1-methyladenosine (m1A), adenosine-to-inosine RNA editing, and alternative polyadenylation (APA) are four major RNA modification types. We evaluated the altered mRNA expression profiles of 27 RNA modification enzymes and compared the differences in tumor microenvironment (TME) and clinical prognosis between two RNA modification patterns using unsupervised clustering.

Construction of a circRNA-miRNA-mRNA network based on differentially co-expressed circular RNA in gastric cancer tissue and plasma by bioinformatics analysis.

Background: Increasing evidence implicates circular RNAs (circRNAs) have been involved in human cancer progression. However, the mechanism remains unclear. In this study, we identified novel circRNAs related to gastric cancer and constructed a circRNA-miRNA-mRNA network.

The Effects of Antral Preservation and Antral Resection on Body Composition, Glycemic Control and Bone Mineral Density Following Vertical Sleeve Gastrectomy in C57BL/6J Mice with Obesity and Type 2 Diabetes.

Purpose: Sleeve gastrectomy (SG) is the most currently popular operation for obesity and related metabolic disorders. The aim of this study was to compare the effect of antrum preservation SG (AP-SG) and antrum resection SG (AR-SG) on the body composition, glycemic control and bone mineral density (BMD) in mice.

Methods: Sham, AP-SG and AR-SG operation were performed on obese and T2D C57BL/6J mice (8 in each group).

SapC-DOPS as a Novel Therapeutic and Diagnostic Agent for Glioblastoma Therapy and Detection: Alternative to Old Drugs and Agents.

Glioblastoma multiforme (GBM), the most common type of brain cancer, is extremely aggressive and has a dreadful prognosis. GBM comprises 60% of adult brain tumors and the 5 year survival rate of GBM patients is only 4.3%.

Targeting of elevated cell surface phosphatidylserine with saposin C-dioleoylphosphatidylserine nanodrug as individual or combination therapy for pancreatic cancer.

Pancreatic cancer is one of the deadliest of cancers with a five-year survival of roughly 8%. Current therapies are: surgery, radiation and chemotherapy. Surgery is curative only if the cancer is caught very early, which is rare, and the latter two modalities are only marginally effective and have significant side effects.

Autophagy mediated lipid catabolism facilitates glioma progression to overcome bioenergetic crisis.

Background: Activation of mTORC1 plays a significant role in cancer development and progression. However, the metabolic mechanisms to sustain mTORC1 activation of cancer cells within stressed environments are still under-appreciated. We recently revealed high autophagy activity in tumour cells with mTORC1 hyper-activation.

Reuse of Molecules for Glioblastoma Therapy.

Glioblastoma multiforme (GBM) is a highly malignant primary brain tumor. The current standard of care for GBM is the Stupp protocol which includes surgical resection, followed by radiotherapy concomitant with the DNA alkylator temozolomide; however, survival under this treatment regimen is an abysmal 12-18 months. New and emerging treatments include the application of a physical device, non-invasive 'tumor treating fields' (TTFs), including its concomitant use with standard of care; and varied vaccines and immunotherapeutics being trialed.

miR-130a-3p, a Preclinical Therapeutic Target for Crohn's Disease.

Background: Crohn's disease [CD] is a chronic, relapsing and incurable inflammatory disorder. Micro RNAs [miRNAs], which modulate gene expression by binding to mRNAs, may make significant contributions to understanding the complex pathobiology and aetiology of CD. This study aimed to investigate the therapeutic role and mechanism of miR-130a-3p in CD.

A barrier against reactive oxygen species: chitosan/acellular dermal matrix scaffold enhances stem cell retention and improves cutaneous wound healing.

Background: Stem cell therapies have gained great attention for providing novel solutions for treatment of various injuries and diseases due to stem cells' self-renewal, ability to differentiate into various cell types, and favorite paracrine function. Nevertheless, the low retention of transplanted stem cell still limits their clinical applications such as in wound healing in view of an induced harsh microenvironment rich in reactive oxygen species (ROS) during inflammatory reactions.

Methods: Herein, a novel chitosan/acellular dermal matrix (CHS/ADM) stem cell delivery system is developed, which is of great ROS scavenging activity and significantly attenuates inflammatory response.

Biotherapy of Brain Tumors with Phosphatidylserine-Targeted Radioiodinated SapC-DOPS Nanovesicles.

Glioblastoma multiforme (GBM), a common type of brain cancer, has a very poor prognosis. In general, viable GBM cells exhibit elevated phosphatidylserine (PS) on their membrane surface compared to healthy cells. We have developed a drug, saposin C-dioleoylphosphatidylserine (SapC-DOPS), that selectively targets cancer cells by honing in on this surface PS.

Enhanced Efficacy of Combination of Gemcitabine and Phosphatidylserine-Targeted Nanovesicles against Pancreatic Cancer.

Phosphatidylserine (PS) is often externalized in viable pancreatic cancer cells and is therapeutically targetable using PS-selective drugs. One of the first-line treatments for advanced pancreatic cancer disease, gemcitabine (GEM), provides only marginal benefit to patients. We therefore investigated the therapeutic benefits of combining GEM and the PS-targeting drug, saposin C-dioleoylphosphatidylserine (SapC-DOPS), for treating pancreatic ductal adenocarcinoma (PDAC).

Systemic enzyme delivery by blood-brain barrier-penetrating SapC-DOPS nanovesicles for treatment of neuronopathic Gaucher disease.

Background: Enzyme replacement therapy (ERT) can positively affect the visceral manifestations of lysosomal storage diseases (LSDs). However, the exclusion of the intravenous ERT agents from the central nervous system (CNS) prevents direct therapeutic effects.

Methods: Using a neuronopathic Gaucher disease (nGD) mouse model, CNS-ERT was created using a systemic, non-invasive, and CNS-selective delivery system based on nanovesicles of saposin C (SapC) and dioleoylphosphatidylserine (DOPS) to deliver to CNS cells and tissues the corrective, functional acid β-glucosidase (GCase).

SapC-DOPS - a Phosphatidylserine-targeted Nanovesicle for selective Cancer therapy.

Phosphatidylserine (PS) is normally located in the inner leaflet of the membrane bilayer of healthy cells, however it is expressed at high levels on the surface of cancer cells. This has allowed for the development of selective therapeutic agents against cancer cells (without affecting healthy cells). SapC-DOPS is a PS-targeting nanovesicle which effectively targets and kills several cancer types including pancreatic, lung, brain, and pediatric tumors.