Extracellular Vesicle Inhibitors Enhance Cholix-Induced Cell Death via Regulation of the JNK-Dependent Pathway.

is an important foodborne pathogen. Cholix cytotoxin (Cholix), produced by , is a novel eukaryotic elongation factor 2 (eEF2) adenosine diphosphate ribosyltransferase that causes host cell death by inhibiting protein synthesis. However, the role of Cholix in the infectious diseases caused by remains unclear.

Clinical Trial Validation of Automated Segmentation and Scoring of Pulmonary Cysts in Thoracic CT Scans.

In cystic lung diseases such as lymphangioleiomyomatosis (LAM), a CT-based cyst score that measures the percentage of the lung volume occupied by cysts is a common index of the cyst burden in the lungs. Although the current semi-automatic measurement of the cyst score is well established, it is susceptible to human operator variabilities. We recently developed a fully automatic method incorporating adaptive features in place of manual adjustments.

Unsupervised Exercise in Interstitial Lung Disease: A Delphi Study to Develop a Consensus Preparticipation Screening Tool for Lymphangioleiomyomatosis.

Background: Little research is available to provide practical guidance to health care providers for exercise preparticipation screening and referral of patients with interstitial lung diseases (ILDs), including lymphangioleiomyomatosis (LAM), to participate in remote, unsupervised exercise programs.

Research Question: What exercise preparticipation screening steps are essential to determine whether a patient with LAM is medically appropriate to participate in a remote, unsupervised exercise program?

Study Design And Methods: Sixteen experts in LAM and ILD participated in a two-round modified Delphi study, ranking their level of agreement for 10 statements related to unsupervised exercise training in LAM, with an a priori definition of consensus. Additionally, 60 patients with LAM completed a survey of the perceived risks and benefits of remote exercise training in LAM.

Glycoprotein non-metastatic melanoma protein B promotes tumor growth and is a biomarker for lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a rare, progressive cystic lung disease affecting almost exclusively female-sexed individuals. The cysts represent regions of lung destruction caused by smooth muscle tumors containing mutations in one of the two tuberous sclerosis (TSC) genes. mTORC1 inhibition slows but does not stop LAM advancement.

Synthetic Circular RNA for microRNA-1269a Suppresses Tumor Progression in Oral Squamous Cell Carcinoma.

microRNAs (miRs) function in cancer progression as post-transcriptional regulators. We previously reported that endogenous circular RNAs (circRNAs) function as efficient miR sponges and could act as novel gene regulators in oral squamous cell carcinoma (OSCC). In this study, we carried out cellular and luciferase reporter assays to examine competitive inhibition of miR-1269a, which is upregulated expression in several cancers, by circRNA-1269a, a synthetic circRNA that contains miR-1269a binding sequences.

Ultra-low dose chest CT with silver filter and deep learning reconstruction significantly reduces radiation dose and retains quantitative information in the investigation and monitoring of lymphangioleiomyomatosis (LAM).

Purpose: Frequent CT scans to quantify lung involvement in cystic lung disease increases radiation exposure. Beam shaping energy filters can optimize imaging properties at lower radiation dosages. The aim of this study is to investigate whether use of SilverBeam filter and deep learning reconstruction algorithm allows for reduced radiation dose chest CT scanning in patients with lymphangioleiomyomatosis (LAM).

Automated Segmentation and Measurements of Pulmonary Cysts in Lymphangioleiomyomatosis across Multiple CT Scanner Platforms over a Period of Two Decades.

(1) Background: Lymphangioleiomyomatosis is a genetic disease that affects mostly women of childbearing age. In the lungs, it manifests as the progressive formation of air-filled cysts and is associated with a decline in lung function. With a median survival of 29 years after the onset of symptoms, computed-tomographic monitoring of cystic changes in the lungs is a key part of the management of the disease.

Unexpected sirolimus-stimulated airway hyperreactivity in lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a multisystem disease affecting primarily women, characterised in the lung by proliferation of LAM cells, abnormal smooth muscle-like cells with dysfunctional tuberous sclerosis complex genes. This dysfunction results in activation of mechanistic target of rapamycin (mTOR), leading to LAM cell proliferation. Sirolimus (rapamycin) is the only United States Food and Drug Administration-approved treatment for pulmonary LAM, resulting in decreased LAM cell growth/size and stabilised lung function [1].

Cell survival pathways targeted in rare lung disease affecting women.

Novel drug targets are identified in lymphangioleiomyomatosis (LAM), a rare disease in women. These targets focus on uterine transcription factors necessary for LAM cell survival.

Comprehensive genetic and phenotype analysis of 95 individuals with mosaic tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is a neurogenetic disorder due to loss-of-function TSC1 or TSC2 variants, characterized by tumors affecting multiple organs, including skin, brain, heart, lung, and kidney. Mosaicism for TSC1 or TSC2 variants occurs in 10%-15% of individuals diagnosed with TSC. Here, we report comprehensive characterization of TSC mosaicism by using massively parallel sequencing (MPS) of 330 TSC samples from a variety of tissues and fluids from a cohort of 95 individuals with mosaic TSC.

Diagnosis of Mosaic Tuberous Sclerosis Complex Using Next-Generation Sequencing of Subtle or Unusual Cutaneous Findings.

Skin findings can be critical to determining whether a patient with lymphangioleiomyomatosis (LAM), a progressive pulmonary disease that predominantly affects adult women, has sporadic LAM or LAM in association with tuberous sclerosis complex (TSC). Three individuals with LAM underwent evaluation for TSC-associated mucocutaneous and internal findings. We used our previously published algorithm to confirm the clinical suspicion for mosaicism and guide the selection of tissue specimens and genetic workup.

Mono-ADP-ribosyltransferase 1 ( )-deficiency decreases tumorigenesis, increases inflammation, decreases cardiac contractility, and reduces survival.

Arginine-specific mono-ADP-ribosylation is a reversible post-translational modification; arginine-specific, cholera toxin-like mono-ADP-ribosyltransferases (ARTCs) transfer ADP-ribose from NAD to arginine, followed by cleavage of ADP-ribose-(arginine)protein bond by ADP-ribosylarginine hydrolase 1 (ARH1), generating unmodified (arginine)protein. ARTC1 has been shown to enhance tumorigenicity as does deficiency. In this study, -KO and -double-KO mice showed decreased spontaneous tumorigenesis and increased age-dependent, multi-organ inflammation with upregulation of pro-inflammatory cytokine TNF- .

A PARP inhibitor, rucaparib, improves cardiac dysfunction in ( ) deficiency.

Aims: Patients with ( ) deficiency exhibit stress-induced childhood-onset neurodegeneration with ataxia and seizures (CONDSIAS). ARH3 degrades protein-linked poly(ADP- ribose) (PAR) synthesized by poly(ADP-ribose)polymerase (PARP)-1 during oxidative stress, leading to cleavage of the ADP-ribose linked to protein. deficiency leads to excess accumulation of PAR, resulting in PAR-dependent cell death or parthanatos.

Macrodomain Mac1 of SARS-CoV-2 Nonstructural Protein 3 Hydrolyzes Diverse ADP-ribosylated Substrates.

Unlabelled: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for a global pandemic that resulted in more than 6-million deaths worldwide. The virus encodes several non-structural proteins (Nsps) that contain elements capable of disrupting cellular processes. Among these Nsp proteins, Nsp3 contains macrodomains, e.

( ) deficiency results in cardiac dysfunction, tumorigenesis, inflammation, and decreased survival.

ADP-ribosylation is a reversible reaction with ADP-ribosyltransferases catalyzing the forward reaction and ADP-ribose-acceptor hydrolases (ARHs) hydrolyzing the ADP-ribose acceptor bond. ARH2 is a member of the 39-kDa ARH family (ARH1-3), which is expressed in heart and skeletal muscle. ARH2 failed to exhibit any in vitro enzymatic activity.

An Enzyme-Linked Immunosorbent Assay to Quantify Poly (ADP-Ribose) Level In Vivo.

PolyADP-ribosylation is a posttranslational modification of proteins that results from enzymatic synthesis of poly(ADP-ribose) with NAD as the substrate. A unique characteristic of polyADP-ribosylation is that the poly(ADP-ribose) chain can have 200 or more ADP-ribose residues in branched patterns, and the presence and variety of these chains can have substantive effects on protein function. To understand how polyADP-ribosylation affects biological processes, it is important to know the physiological level of poly(ADP-ribose) in cells.

ARH Family of ADP-Ribose-Acceptor Hydrolases.

The ARH family of ADP-ribose-acceptor hydrolases consists of three 39-kDa members (ARH1-3), with similarities in amino acid sequence. ARH1 was identified based on its ability to cleave ADP-ribosyl-arginine synthesized by cholera toxin. Mammalian ADP-ribosyltransferases (ARTCs) mimicked the toxin reaction, with ARTC1 catalyzing the synthesis of ADP-ribosyl-arginine.