Select amino acids recover cytokine-altered ENaC function in human bronchial epithelial cells.

The airway epithelium plays a pivotal role in regulating mucosal immunity and inflammation. Epithelial barrier function, homeostasis of luminal fluid, and mucociliary clearance are major components of mucosal defense mechanisms. The epithelial sodium channel (ENaC) is one of the key players in controlling airway fluid volume and composition, and characteristic cytokines cause ENaC and barrier dysfunctions following pulmonary infections or allergic reactions.

Assessing safety and efficacy of a novel glucose-free amino acid oral rehydration solution for watery diarrhea management in children: a randomized, controlled, phase III trial.

Background: Diarrhoeal disease poses a significant global health challenge, especially in children under three years old. Despite the effectiveness of oral rehydration therapy (ORT), its adoption remains low. Glucose-based ORS (GORS) is the standard, but novel formulations like glucose-free amino acid-based VS002A have emerged as potential alternatives.

Clinicopathological and Molecular Characteristics of Early-Onset Stage III Colon Adenocarcinoma: An Analysis of the ACCENT Database.

Background: Colon cancer (CC) incidence in young adults (age 20-49 years), termed early-onset CC (EO-CC), is increasing.

Methods: Individual patient data on 35 713 subjects with stage III colon cancer from 25 randomized studies in the Adjuvant Colon Cancer ENdpoint database were pooled. The distributions of demographics, clinicopathological features, biomarker status, and outcome data were summarized by age group.

Acute Kidney Injury-Induced Systemic Inflammation and Risk of Kidney Cancer Formation.

In this issue of , Zhou and colleagues investigate the role of acute kidney injury (AKI) and AKI-associated systemic inflammation in the development of kidney cancer. They demonstrate a positive association between the formation of clear-cell renal cell carcinoma and AKI induced by ischemia-reperfusion injury in genetically modified mice. In parallel with the emergence of kidney tumors, mice with ischemic injury develop systemic inflammation associated with tissue infiltration by neutrophils and fibroblasts and upregulated expression of several inflammatory factors, with CXCL1 displaying the highest levels of upregulation.

Microsatellite Instability in Patients With Stage III Colon Cancer Receiving Fluoropyrimidine With or Without Oxaliplatin: An ACCENT Pooled Analysis of 12 Adjuvant Trials.

Purpose: In patients with stage III colon cancer (CC) whose tumors demonstrate microsatellite instability (MSI), the efficacy of adjuvant fluoropyrimidine (FP) with or without oxaliplatin has not been clearly demonstrated and the prognostic value of MSI remains uncertain.

Materials And Methods: Individual patient data from the ACCENT database were used to evaluate the effect of FP with or without oxaliplatin on disease-free survival (DFS) and overall survival (OS) among patients with MSI stage III CC and the prognostic value of MSI in patients treated with FP plus oxaliplatin, by stratified Cox models adjusted for demographic and clinicopathological factors.

Results: MSI status was available for 5,457 patients (609 MSI, 11.

The role of asparagine synthetase on nutrient metabolism in pancreatic disease.

The pancreas avidly takes up and synthesizes the amino acid asparagine (Asn), in part, to maintain an active translational machinery that requires incorporation of the amino acid. The de novo synthesis of Asn in the pancreas occurs through the enzyme asparagine synthetase (ASNS). The pancreas has the highest expression of ASNS of any organ, and it can further upregulate ASNS expression in the setting of amino acid depletion.

Aptamer-Directed Protein-Specific Multiple Modifications of Membrane Glycoproteins on Living Cells.

Understanding how a cell membrane protein functions on living cells remains a challenge for cell biology. Specific placement of functional molecules on specific proteins in their native environment would allow comprehensive study of proteins' dynamic functions. Existing methods cannot facilely achieve multiple modifications on specific membrane proteins.

Site-Directed Mutagenesis Improves the Transduction Efficiency of Capsid Library-Derived Recombinant AAV Vectors.

Recombinant adeno-associated virus (rAAV) vectors selected from capsid libraries present enormous advantages in high selectivity of tissue tropism and their potential use in human gene therapy applications. For example, rAAV-LK03, was used in a gene therapy trial for hemophilia A (ClinicalTrials.gov: NCT03003533).

An Amino Acid-Based Oral Rehydration Solution Regulates Radiation-Induced Intestinal Barrier Disruption in Mice.

Background: Radiotherapy inadvertently affects gastrointestinal (GI) epithelial cells, causing intestinal barrier disruption and increased permeability.

Objective: We examined the effect of amino acid-based oral rehydration solution (AA-ORS) on radiation-induced changes of intestinal barrier function and epithelial tight junctions (TJs) in a randomized experimental study using a total-body irradiation (TBI) mouse model.

Methods: Eight-week-old male Swiss mice received a single-dose TBI (0, 1, 3, or 5 Gy), and subsequent gastric gavage with AA-ORS (threonine, valine, serine, tyrosine, and aspartic acid) or saline for 2 or 6 d.

DNA-Capped Silver Nanoflakes as Fluorescent Nanosensor for Highly Sensitive Imaging of Endogenous HS in Cell Division Cycles.

Biochemical sensing is essential toward gaining a full understanding of various physiological and pathological events. The in vivo level of hydrogen sulfide (HS), the third endogenous gaseous transmitter, is closely related to its biological functions at different phases of the cell division cycle. Here we report a facile strategy for HS sensing in live cells at different phases of cell division by developing a fluorescent nanosensor with double-strand DNA (dsDNA)-stabilized silver nanoflakes (AgNF@dsDNA).

3D halos assembled from FeO/Au NPs with enhanced catalytic and optical properties.

3D structures assembled from multiple components have attracted increasing research interest based on their enriched functionalities and broadened applications. Here, we report a bottom-up strategy to fabricate 3D halos through the co-assembly of FeO and Au nanoparticles (NPs). Typically, FeO NPs assemble into a 3D core (size around 500 nm) with simultaneous growth of Au NPs on the 3D surface during the assembly process.

Aptamer Selection for Detecting Molecular Target Using Cell-SELEX (Systematic Evolution of Ligands by Exponential Enrichment) Technology.

Cell-SELEX is a live cell-based in vitro selection method that generates functional oligonucleotides, or aptamers. Often referenced as the chemist's antibody, aptamers bind to select targets with high affinity and can be utilized in a number of applications, including biomedicine, bioimaging, and biosensing. Here we describe the cell-SELEX technique and discuss this methodology's unique merit(s)-namely the ability to isolate highly selective aptamer panels with no prior knowledge of cellular signatures.

Construction of a Multiple-Aptamer-Based DNA Logic Device on Live Cell Membranes via Associative Toehold Activation for Accurate Cancer Cell Identification.

The ability to accurately identify and isolate cells is the cornerstone of precise disease diagnosis and therapies. A single-step cell identification method based on logic analysis of multiple surface markers will have unique advantages because of its accuracy and efficacy. Herein, using multiple DNA aptamers for cancer biomarker recognition and associative toehold activation for signal integration and amplification as two molecular keys, we have successfully operated a cell-surface device that can perform AND Boolean logic analysis of multiple biomarkers and precisely label the target cell subtype in large populations of similar cells via the presence or absence of different biomarkers.

Interaction-Transferable Graphene-Isolated Superstable AuCo Nanocrystal-Enabled Direct Cyanide Capture.

Noble metals with strong plasmons have been widely used as enhancement substrates for molecule identification. However, cyanide, a toxic and important signaling molecule with a corrosive nature to noble metals, makes direct recognition challenging. Herein a novel superstable magnetic graphene-isolated AuCo nanocrystal (MACG) has been designed.

Free-standing 2D nanorafts by assembly of 1D nanorods for biomolecule sensing.

Novel materials from self-assembled nanocrystals hold great promise for applications ranging from inorganic catalysis to bio-imaging. However, because of the inherent anisotropic properties, it is challenging to assemble one-dimensional (1D) nanorods into higher-order structures (e.g.

Lenalidomide and Prednisone in Low and Intermediate-1 IPSS Risk, Non-Del(5q) Patients With Myelodysplastic Syndromes: Phase 2 Clinical Trial.

Purpose: To test the hypothesis that combination treatment with lenalidomide and prednisone will yield a higher erythroid response rate in patients with non-del(5q) lower-risk myelodysplastic syndromes compared to the historical clinical trial data with lenalidomide monotherapy, which reported a 26% transfusion independence rate.

Patients And Methods: The study enrolled 25 patients with lower-risk myelodysplastic syndromes by the International Prognostic Scoring System who were transfusion dependent or who had symptomatic anemia and prior erythroid stimulating agent failure or low chance of response. The planned dose of lenalidomide was 10 mg per day.

Visible Light-Driven Self-Powered Device Based on a Straddling Nano-Heterojunction and Bio-Application for the Quantitation of Exosomal RNA.

This paper reports the design and fabrication of a self-powered biosensing device based on TiO nanosilks (NSs)@MoS quantum dots (QDs) and demonstrates a bioapplication for the quantitative detection of exosomal RNA ( Homo sapiens HOXA distal transcript antisense RNA, HOTTIP). This self-powered device features enhanced power output compared to TiO NSs alone. This is attributed to the formation of a heterojunction structure with suitable band offset derived from the hybridization between TiO NSs and MoS QDs, i.

Facile approach to prepare HSA-templated MnO nanosheets as oxidase mimic for colorimetric detection of glutathione.

In this work, a simple, rapid, and highly sensitive colorimetric assay for the determination of glutathione (GSH) was developed. It employs human serum albumin (HSA)-templated MnO nanosheets as an artificial oxidase. HSA-templated MnO nanosheets can oxidize 3,3',5,5'-tetramethylbenzidine (TMB) to a blue oxTMB product with a significant increase in absorbance at 652 nm in the absence of HO.

The adaptive regulation of thiamine pyrophosphokinase-1 facilitates malignant growth during supplemental thiamine conditions.

Supplemental levels of vitamin B1 (thiamine) have been implicated in tumor progression. Tumor cells adaptively up-regulate thiamine transport during hypoxic stress. Upon uptake, thiamine pyrophosphokinase-1 (TPK1) facilitates the rapid phosphorylation of thiamine into thiamine pyrophosphate (TPP).

Induction of early growth response gene 1 (EGR1) by endoplasmic reticulum stress is mediated by the extracellular regulated kinase (ERK) arm of the MAPK pathways.

Endoplasmic reticulum (ER) stress activates three principal signaling pathways, collectively known as the unfolded protein response, leading to translational and transcriptional control mechanisms that dictate the cell's response as adaptive or apoptotic. The present study illustrates that for HepG2 human hepatocellular carcinoma cells the signaling pathways triggered by ER stress extend beyond the three principal pathways to include mitogen-activated protein kinase (MAPK) signaling, leading to activation of transcription from the early growth response 1 (EGR1) gene. Analysis provided evidence for a SRC-RAS-RAF-MEK-ERK cascade mechanism that leads to enhanced phosphorylation of the transcription factor ELK1.

Construction of self-powered cytosensing device based on ZnO nanodisks@g-CN quantum dots and application in the detection of CCRF-CEM cells.

We herein report a self-powered and renewable cytosensing device based on ZnO nanodisks(NDs)@g-CN quantum dots. The device features enhanced photoelectrochemical (PEC) activity compared to ZnO NDs or g-CN QDs alone. The enhanced PEC ability is attributed to the synergistic effect of the high visible light sensitivity of g-CN QDs and the staggered band alignment heterojunction structure with suitable band offset, which affords higher photoelectron transfer and separation efficiency.

Preservation of swallowing function with de-intensified chemoradiation therapy for HPV-associated oropharyngeal squamous cell carcinoma.

Purpose: This study aimed to compare the swallowing function in patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma treated with de-intensified chemoradiation therapy (6 weeks, 60 Gy) versus those receiving standard-of-care chemoradiation therapy (7 weeks, 70 Gy).

Methods And Materials: A retrospective review was conducted of 78 patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma with modified barium swallow studies pretreatment and 6 to 8 weeks posttreatment. The swallowing function was objectively scored for penetration, aspiration, and pharyngeal residue.

Targeting CD26 suppresses proliferation of malignant mesothelioma cell via downmodulation of ubiquitin-specific protease 22.

Malignant pleural mesothelioma (MPM) is an aggressive malignancy arising from mesothelial lining of pleura. It is associated with a poor prognosis, partly due to the lack of a precise understanding of the molecular mechanisms associated with its malignant behavior. In the present study, we expanded on our previous studies on cell cycle control of MPM cells by targeting CD26 molecule with humanized anti-CD26 monoclonal antibody (HuCD26mAb), focusing particularly on ubiquitin-specific protease 22 (USP22).