APT imaging of hepatocellular carcinoma signals an effective therapeutic response in advance of tumor shrinkage.

The aim of this study was to assess the utility of weighted amide proton transfer (APT) MRI in three different rodent models of hepatocellular carcinoma (HCC). APT MRI was evaluated in models of diethylnitrosamine (DEN) induced HCC, N1S1 syngeneic orthotopic xenograft and human HepG2 ectopic xenograft. All models of HCC showed a higher APT signal over the surrounding normal tissues.

Cooperation of Wnt/β-catenin and Dll1-mediated Notch pathway in Lgr5-positive intestinal stem cells regulates the mucosal injury and repair in DSS-induced colitis mice model.

Background: Lgr5-positive cells located in the basal layer of crypts have self-regenerative and proliferative differentiation potentials of intestinal stem cells (ISCs), maintaining a balance of regeneration-repair in mucosal epithelium. However, the mechanisms of mucosal repair that are regulated by ISCs in ulcerative colitis (UC) remain unclear.

Method: Colon tissues from patients with UC were collected to test β-catenin and Notch1 expression by using Western blot and quantitative real-time polymerase chain reaction (PCR).

Facile prepared microfluidic chip for multiplexed digital RT-qPCR test.

The chip-based digital polymerase chain reaction (PCR) is an indispensable technique for amplifying and quantifying nucleic acids, which has been widely employed in molecular diagnostics at both fundamental and clinical levels. However, the previous designs have yet to achieve widespread application due to limitations in complex chip fabrication, pretreatment procedures, special surface properties, and low throughput. This study presents a facile digital microfluidic chip driven by centrifugal force for digital PCR analysis.

LAMB3 Promotes Intestinal Inflammation Through SERPINA3 and Is Directly Transcriptionally Regulated by P65 in Inflammatory Bowel Disease.

Background: Various extracellular matrix (ECM) reshaping events are involved in inflammatory bowel disease (IBD). LAMB3 is a vital subunit of laminin-332, an important ECM component. Data on the biological function of LAMB3 in intestinal inflammation are lacking.

The Effects of a Blood-Brain Barrier Penetrating Erythropoietin in a Mouse Model of Tauopathy.

Erythropoietin (EPO), a hematopoietic neurotrophin, is a potential therapeutic for Alzheimer's disease (AD) but has limited blood-brain barrier (BBB) permeability. EPO fused to a chimeric transferrin receptor monoclonal antibody (cTfRMAb) enters the brain via TfR-mediated transcytosis across the BBB. We previously showed that cTfRMAb-EPO is protective in a mouse model of amyloidosis, but its effects on tauopathy are not known.

Genetic compensation response could exist in colorectal cancer: UPF3A upregulates the oncogenic homologue gene SRSF3 expression corresponding to SRSF6 to promote colorectal cancer metastasis.

Background: Genetic compensation response (GCR) is a mechanism that maintains the robustness of functional genes, which has been recently identified. Whether GCR exists in tumors and its effects on tumor progression remains unknown.

Methods: Whole exome sequencing was performed to identify premature termination codon (PTC) gene mutations in colorectal cancer (CRC) tissues.

Efficacy and Safety of a Brain-Penetrant Biologic TNF-α Inhibitor in Aged APP/PS1 Mice.

Tumor necrosis factor alpha (TNF-α) plays a vital role in Alzheimer's disease (AD) pathology, and TNF-α inhibitors (TNFIs) modulate AD pathology. We fused the TNF-α receptor (TNFR), a biologic TNFI that sequesters TNF-α, to a transferrin receptor antibody (TfRMAb) to deliver the TNFI into the brain across the blood-brain barrier (BBB). TfRMAb-TNFR was protective in 6-month-old transgenic APP/PS1 mice in our previous work.

Full- versus Sub-Regional Quantification of Amyloid-Beta Load on Mouse Brain Sections.

Extracellular accumulation of amyloid-beta (Aβ) plaques is one of the major pathological hallmarks of Alzheimer's disease (AD), and is the target of the only FDA-approved disease-modifying treatment for AD. Accordingly, the use of transgenic mouse models that overexpress the amyloid precursor protein and thereby accumulate cerebral Aβ plaques are widely used to model human AD in mice. Therefore, immunoassays, including enzyme-linked immunosorbent assay (ELISA) and immunostaining, commonly measure the Aβ load in brain tissues derived from AD transgenic mice.

Comparative studies between the murine immortalized brain endothelial cell line (bEnd.3) and induced pluripotent stem cell-derived human brain endothelial cells for paracellular transport.

Brain microvascular endothelial cells, forming the anatomical site of the blood-brain barrier (BBB), are widely used as in vitro complements to in vivo BBB studies. Among the immortalized cells used as in vitro BBB models, the murine-derived bEnd.3 cells offer culturing consistency and low cost and are well characterized for functional and transport assays, but result in low transendothelial electrical resistance (TEER).

Biologic TNF-α inhibitors reduce microgliosis, neuronal loss, and tau phosphorylation in a transgenic mouse model of tauopathy.

Background: Tumor necrosis factor-α (TNF-α) plays a central role in Alzheimer's disease (AD) pathology, making biologic TNF-α inhibitors (TNFIs), including etanercept, viable therapeutics for AD. The protective effects of biologic TNFIs on AD hallmark pathology (Aβ deposition and tau pathology) have been demonstrated. However, the effects of biologic TNFIs on Aβ-independent tau pathology have not been reported.

Cut-off value of ulcerative colitis endoscopic index of severity (UCEIS) score for predicting the need for pouch construction in ulcerative colitis: results of a multicenter study with long-term follow-up.

Background: Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) was the first choice for the surgical treatment of the ulcerative colitis (UC) patients. The data on the predictive value of the ulcerative colitis endoscopic index of severity (UCEIS) for the need for IPAA in UC patients is scarce. We aimed to establish the UCEIS cut-off value to further analyse whether the UCEIS cut-off was suitable for predicting the need for IPAA in UC patients.

Increased expression of yes-associated protein/YAP and transcriptional coactivator with PDZ-binding motif/TAZ activates intestinal fibroblasts to promote intestinal obstruction in Crohn's disease.

Background: Intestinal obstruction caused by intestinal fibrosis is a common and serious complication of Crohn's disease (CD). Intestinal fibroblasts, the main effector cells mediating gastrointestinal fibrosis, are activated during chronic inflammation. However, the mechanism of fibroblast activation in CD has not been well elucidated.

Acute and Chronic Dosing of a High-Affinity Rat/Mouse Chimeric Transferrin Receptor Antibody in Mice.

Non-invasive brain delivery of neurotherapeutics is challenging due to the blood-brain barrier. The revived interest in transferrin receptor antibodies (TfRMAbs) as brain drug-delivery vectors has revealed the effect of dosing regimen, valency, and affinity on brain uptake, TfR expression, and Fc-effector function side effects. These studies have primarily used monovalent TfRMAbs with a human constant region following acute intravenous dosing in mice.

LAMB3 promotes tumour progression through the AKT-FOXO3/4 axis and is transcriptionally regulated by the BRD2/acetylated ELK4 complex in colorectal cancer.

Aberrant expression of laminin-332 promotes tumour growth and metastasis in multiple cancers. However, the dysregulated expression and mechanism of action of LAMB3, which encodes the β3 subunit of laminin-332, and the mechanism underlying dysregulated LAMB3 expression in CRC remain obscure. Here, we show that LAMB3 is overexpressed in CRC and that this overexpression is correlated with tumour metastasis and poor prognosis.

Clinical outcomes and risk factors of secondary extraintestinal manifestation in ulcerative colitis: results of a multicenter and long-term follow-up retrospective study.

Background: Extraintestinal manifestations (EIM) are common in ulcerative colitis (UC). In Shanghai, China, data on the incidence rate and risk factors of EIM in UC patients remain scarce.

Methods: The study population consisted of UC patients who were identified from a prospectively maintained, institutional review board-approved database at our institutes from June 1986 to December 2018.

effects of N-acetylcysteine alone and combined with tigecycline on planktonic cells and biofilms of .

Background: (), as a common opportunistic pathogen, has strong ability to form biofilms, which has led to drug resistance and chronic infections. The combination of N-acetylcysteine (NAC) and tigecycline (TGC) was demonstrated to synergistically inhibit biofilm-associated bacterial infections, including methicillin-resistant and The purpose of this study is to investigate the effect of NAC and TGC on planktonic cells and biofilms of

Methods: Minimum inhibitory concentrations (MICs) of NAC were determined by broth microdilution method. Biofilm susceptibility was assessed by crystal violet stain.

Restoration of KLF4 Inhibits Invasion and Metastases of Lung Adenocarcinoma through Suppressing MMP2.

Background: KLF4 is a zin-finger transcription factor that plays roles in differentiation, development, and proliferation. Recent studies show that KLF4 is involved in tumorigenesis and somatic cells reprogramming. Metastasis is the primary cause of death in patients with lung cancer, and its biological mechanisms are poorly understood.

Low-density lipoprotein docosahexaenoic acid nanoparticles induce ferroptotic cell death in hepatocellular carcinoma.

Unlabelled: Low-density lipoprotein nanoparticles reconstituted with the natural omega-3 fatty acid, docosahexaenoic acid (LDL-DHA), have been reported to selectively kill hepatoma cells and reduce the growth of orthotopic liver tumors in the rat. To date, little is known about the cell death pathways by which LDL-DHA nanoparticles kill tumor cells. Here we show that the LDL-DHA nanoparticles are cytotoxic to both rat hepatoma and human hepatocellular carcinoma (HCC) cell lines.

TP53 mutation is associated with a poor clinical outcome for non-small cell lung cancer: Evidence from a meta-analysis.

A number of studies have examined the association between tumor protein 53 (TP53) mutations and the clinical outcome in patients with non-small-cell lung cancer (NSCLC), although these have yielded conflicting results. In the present study, electronic databases updated to September 2015 were searched to find relevant studies. A meta-analysis was performed on the eligible studies, which quantitatively evaluated the association between the TP53 mutations and the survival of patients with NSCLC.

PTEN expression is associated with the outcome of lung cancer: evidence from a meta-analysis.

Introduction: Various studies examined the relationship between the expression of phosphatase and tensin homolog (PTEN) with the clinical outcome in patients with lung cancer, but yielded conflicting results.

Evidence Acquisition: Electronic databases updated to January 2016 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between the expression of PTEN and clinical outcomes of patients with lung cancer.

[Development and assessment of a chemiluminescence assay kit for detecting anti-HEV IgG].

Objective: To develop an anti-hepatitis E virus (anti-HEV) IgG chemiluminescence assay kit and assess its clinical application.

Methods: The HEV recombinant antigen was used as coating antigen, horseradish peroxidase (HRP)-conjugated monoclonal anti-human IgG as the secondary antibody, and the luminol chemiluminescent reaction system as a substrate. The sensitivity, specificity, precision and other technical indicators of the kit were evaluated using the HEV national reference product, and a contrast experiment was conducted on 1012 serum samples by the kit developed in this research and a commercialized anti-HEV IgG chemiluminescence assay kit.

Label-free photoelectrochemical immunosensor for neutrophil gelatinase-associated lipocalin based on the use of nanobodies.

Acute renal failure (ARF) represents a very important and potentially devastating disorder in clinical nephrology. Neutrophil gelatinase-associated lipocalin (NGAL) is an early biomarker for ARF in a wide range of different disease processes, which is frequently detected in clinical diagnosis. Herein, we present a label-free and sensitive photoelectrochemical (PEC) immunosensor for NGAL by utilizing a biotinylated anti-NGAL Nanobody (Nb) orientedly immobilized to streptavidin-coated cobalt 2,9,16,23-tetraaminophthalocyanine (CoPc)-sensitized TiO2 electrode.