Chronic replication stress invokes mitochondria dysfunction via impaired parkin activity.

Replication stress is a major contributor to tumorigenesis because it provides a source of chromosomal rearrangements via recombination events. PARK2, which encodes parkin, a regulator of mitochondrial homeostasis, is located on one of the common fragile sites that are prone to rearrangement by replication stress, indicating that replication stress may potentially impact mitochondrial homeostasis. Here, we show that chronic low-dose replication stress causes a fixed reduction in parkin expression, which is associated with mitochondrial dysfunction, indicated by an increase in mtROS.

[A Case of Scirrhous Gastric Cancer Not Diagnosed by Endoscopy but by Staging Laparoscopy].

A 71-year-old female was referred to our hospital for abdominal distention and anorexia. Gastrointestinal endoscopy revealed wall thickening of the entire circumference. Abdominal CT scan showed diffuse thickening of the stomach, but there was no obvious metastasis.

Nicaraven induces programmed cell death by distinct mechanisms according to the expression levels of Bcl-2 and poly (ADP-ribose) glycohydrolase in cancer cells.

The PARP-1 expression level and poly (ADP-ribosyl)ation activity in cancer markedly affect the therapeutic outcome. Nicaraven, a free radical scavenger has been found to inhibit PARP, but the effect on cancer cells is still unclear. In this study, we investigated the potential role and molecular mechanism of nicaraven on cancer cells.

A disease-driver population within interstitial cells of human calcific aortic valves identified via single-cell and proteomic profiling.

Cellular heterogeneity of aortic valves complicates the mechanistic evaluation of the calcification processes in calcific aortic valve disease (CAVD), and animal disease models are lacking. In this study, we identify a disease-driver population (DDP) within valvular interstitial cells (VICs). Through stepwise single-cell analysis, phenotype-guided omic profiling, and network-based analysis, we characterize the DDP fingerprint as CD44CD29CD59CD73CD45 and discover potential key regulators of human CAVD.

Nicaraven mitigates radiation-induced lung injury by downregulating the NF-κB and TGF-β/Smad pathways to suppress the inflammatory response.

Radiation-induced lung injury (RILI) is commonly observed in patients receiving radiotherapy, and clinical prevention and treatment remain difficult. We investigated the effect and mechanism of nicaraven for mitigating RILI. C57BL/6 N mice (12-week-old) were treated daily with 6 Gy X-ray thoracic radiation for 5 days in sequences (cumulative dose of 30 Gy), and nicaraven (50 mg/kg) or placebo was injected intraperitoneally in 10 min after each radiation exposure.

Nicaraven prevents the fast growth of inflamed tumors by an anti-inflammatory mechanism.

Inflammatory microenvironment is known to accelerate the progression of malignant tumors. We investigated the possible anti-inflammatory effect of nicaraven on slowing tumor growth. Tumor-bearing mice randomly received nicaraven injection (50 mg/kg daily, i.

Mesenchymal stem cell-derived extracellular vesicles as probable triggers of radiation-induced heart disease.

Background: Radiation-induced heart disease has been reported, but the underlying mechanisms remain unclear. Mesenchymal stem cells (MSCs), also residing in the heart, are highly susceptible to radiation. We examined the hypothesis that the altered secretion of extracellular vesicles (EVs) from MSCs is the trigger of radiation-induced heart disease.

Dipyridamole induces the phosphorylation of CREB to promote cancer cell proliferation.

Dipyridamole, a traditional anti-platelet drug, has been reported to inhibit the proliferation of cancer cells. The present study aimed to investigate the possibility of dipyridamole as an adjuvant of chemotherapy by enhancing the cytotoxicity of an anti-cancer drug. The cytotoxicity of colorectal cancer cells (HCT-8), CD133/CD44 stem-like subpopulation of HCT-8 cells and lymphoma cells (U937) to dipyridamole and/or doxorubicin was evaluated using MTT proliferation and colony forming assays.

Enhanced Expression of ABCB1 and Nrf2 in CD133-Positive Cancer Stem Cells Associates with Doxorubicin Resistance.

The precise mechanism about drug resistance of cancer stem cells (CSCs) has not yet been completely understood. Based on the expression of CD44 and CD133, two well-recognized cell surface markers for CSC identification, we tried to separate HCT8 colorectal cancer cells into different subpopulations and then investigated how the expression of CD44 and CD133 associated with doxorubicin (DXR) resistance. Interestingly, DXR resistance was observed in CD44CD133 ( < 0.

Nicaraven Attenuates Postoperative Systemic Inflammatory Responses-Induced Tumor Metastasis.

Background: Inflammation has been demonstrated to promote cancer metastasis. Due to the well-known systemic inflammatory responses (SIR) after major surgery, it is critical to investigate and attenuate SIR-induced tumor metastasis of cancer patients suffering surgical procedures.

Methods: C57BL/6 mice were intravenously injected with Lewis lung cancer cells at 6, 24, and 72 h after the induction of intestinal ischemia/reperfusion (I/R) injury.

Retinoids Repress Human Cardiovascular Cell Calcification With Evidence for Distinct Selective Retinoid Modulator Effects.

Objective: Retinoic acid (RA) is a ligand for nuclear receptors that modulate gene transcription and cell differentiation. Whether RA controls ectopic calcification in humans is unknown. We tested the hypothesis that RA regulates osteogenic differentiation of human arterial smooth muscle cells and aortic valvular interstitial cells that participate in atherosclerosis and heart valve disease, respectively.

Standardization of Human Calcific Aortic Valve Disease Modeling Reveals Passage-Dependent Calcification.

Aortic valvular interstitial cells (VICs) isolated from patients undergoing valve replacement are commonly used as models of calcific aortic valve disease (CAVD). Standardization of VIC calcification, however, has not been implemented, which impairs comparison of results from different studies. We hypothesized that different culture methods impact the calcification phenotype of human VICs.

Immunomodulatory effect of mesenchymal stem cells: Cell origin and cell quality variations.

The immunomodulatory property of mesenchymal stem cells (MSCs) has been previously reported. Still it is unclear if this property can be affected by the cell origin and cell quality. Using primary MSCs expanded from bone marrow (BM-MSCs) and adipose tissue (AD-MSCs) of mice, we investigated whether the immunomodulatory property of MSCs varied with cell origin and cell quality (early- vs.

Spatiotemporal Multi-Omics Mapping Generates a Molecular Atlas of the Aortic Valve and Reveals Networks Driving Disease.

Background: No pharmacological therapy exists for calcific aortic valve disease (CAVD), which confers a dismal prognosis without invasive valve replacement. The search for therapeutics and early diagnostics is challenging because CAVD presents in multiple pathological stages. Moreover, it occurs in the context of a complex, multi-layered tissue architecture; a rich and abundant extracellular matrix phenotype; and a unique, highly plastic, and multipotent resident cell population.

The effect of transient oxygenation on stem cell mobilization and ischemia/reperfusion heart injury.

For general anesthesia, pre-oxygenation is routinely performed prior to intubation. It is well-known that ischemic/hypoxic preconditioning induces stem cell mobilization and protects against ischemia/reperfusion (I/R) injury. In this study, we investigated the effect of transient oxygenation on stem cell mobilization and I/R injury of the heart.

Nicaraven reduces cancer metastasis to irradiated lungs by decreasing CCL8 and macrophage recruitment.

Radiotherapy for cancer patients damages normal tissues, thereby inducing an inflammatory response and promoting cancer metastasis. We investigated whether nicaraven, a compound with radioprotective and anti-inflammatory properties, could attenuate radiation-induced cancer metastasis to the lungs of mice. Nicaraven and amifostine, another commercial radioprotective agent, had limited effects on both the radiosensitivity of Lewis lung carcinoma cells in vitro and radiation-induced tumor growth inhibition in vivo.

Risk factors for difficulty of laparoscopic cholecystectomy in grade II acute cholecystitis according to the Tokyo guidelines 2013.

Background: The Tokyo Guidelines 2013 classifies acute cholecystitis (AC) into three grades and recommends appropriate therapy for each grade. For grade II AC, either early laparoscopic cholecystectomy (LC) or percutaneous transhepatic gallbladder drainage (PTGBD) should be performed. This study aimed to identify the risk factors for difficulty of LC for treating grade II AC.

Surgical strategy for aortic arch reconstruction after the Norwood procedure based on numerical flow analysis.

Objectives: Inefficient aortic flow after the Norwood procedure is known to lead to the deterioration of ventricular function due to an increased cardiac workload. To prevent the progression of aortic arch obstruction, arch reconstruction concomitant with second-stage surgery is recommended. The aim of this study was to determine the indications for reconstruction based on numerical simulation and to reveal the morphology that affects the haemodynamic parameters.

Extreme dilatation of the interposed jejunal pouch after proximal gastrectomy associated with portal venous gas: A case report.

Introduction: The jejunal pouch interposition (JPI) after proximal gastrectomy (PG) was proposed as a reconstructive procedure to provide a gastric reservoir substitute and prevent postgastrectomy syndrome. However, food residue remaining in some of the pouches resulted in the adverse effect of abdominal bloating, thereby body weight loss. Here, we report a rare case with an extreme dilation of the interposed jejunal pouch (JP) 8 years after PG, requiring pouch resection.

Dynamin-Related Protein 1 Inhibition Attenuates Cardiovascular Calcification in the Presence of Oxidative Stress.

Rationale: Mitochondrial changes occur during cell differentiation and cardiovascular disease. DRP1 (dynamin-related protein 1) is a key regulator of mitochondrial fission. We hypothesized that DRP1 plays a role in cardiovascular calcification, a process involving cell differentiation and a major clinical problem with high unmet needs.

Optimal timing of cholecystectomy after percutaneous gallbladder drainage for severe cholecystitis.

Background: The Tokyo guideline for acute cholecystitis recommended percutaneous transhepatic gallbladder drainage followed by cholecystectomy for severe acute cholecystitis, but the optimal timing for the subsequent cholecystectomy remains controversial.

Methods: Sixty-seven patients who underwent either laparoscopic or open cholecystectomy after percutaneous transhepatic gallbladder drainage for severe acute cholecystitis were enrolled and divided into difficult cholecystectomy (group A) and non-difficult cholecystectomy (group B). Patients who had one of these conditions were placed in group A: 1) conversion from laparoscopic to open cholecystectomy; 2) subtotal cholecystectomy and/or mucoclasis; 3) necrotizing cholecystitis or pericholecystic abscess formation; 4) tight adhesions around the gallbladder neck; and 5) unsuccessfully treated using PTGBD.

Enhanced expression of PKM2 associates with the biological properties of cancer stem cells from A549 human lung cancer cells.

Cancer cells express the M2 isoform of glycolytic enzyme pyruvate kinase (PKM2) for favoring the survival under a hypoxic condition. Considering the relative low oxygen microenvironment in stem cell niche, we hypothesized that an enhanced PKM2 expression associates with the biological properties of cancer stem cells. We used A549 human lung cancer cell line and surgical resected lung cancer tissue samples from patients for experiments.

Nicaraven, a Potential Radioprotective Agent, has Very Limited Effects on the Survival of Cancer Cells and the Growth of Established Tumors.

Radiotherapy is one of the major treatment modalities for the management of various cancers, however, it is limited by the severe side effects and complications experienced by some patients. Nicaraven, a chemically synthesized hydroxyl radical-specific scavenger, has been shown to protect normal tissues from radiation-induced injury. We investigated the role of nicaraven in cancer cells and tumor growth.

Correction: Cardiosphere-Derived Cells Facilitate Heart Repair by Modulating M1/M2 Macrophage Polarization and Neutrophil Recruitment.

[This corrects the article DOI: 10.1371/journal.pone.

Dose-dependency and reversibility of radiation-induced injury in cardiac explant-derived cells of mice.

We evaluated the dose-dependency and reversibility of radiation-induced injury in cardiac explant-derived cells (CDCs), a mixed cell population grown from heart tissues. Adult C57BL/6 mice were exposed to 0, 10, 50 and 250 mGy γ-rays for 7 days and atrial tissues were collected for experiments 24 hours after last exposure. The number of CDCs was significantly decreased by daily exposure to over 250 mGy.