Pancreatic ductal adenocarcinoma (PDA) is an aggressive type of malignant tumor with a poor prognosis and high mortality. Aberrant activation of hedgehog signaling plays a crucial role in the maintenance and progression of PDA. Here, we report that the dietary bioflavonoid quercetin has therapeutic potential for PDA by targeting sonic hedgehog (SHH) signaling. The effects of quercetin on the proliferation

Mitochondria are double membrane–bound cellular work-horses constantly functioning to regulate vital aspects of cellular metabolism, bioenergetics, proliferation and death. Biogenesis, homeostasis and regulated turnover of mitochondria are stringently regulated to meet the bioenergetic requirements. Diverse external and internal stimuli including oxidative stress, diseases, xenobiotics and even age

In the original publication the grant number is incorrectly published.

Drug toxicity and efficacy are difficult to predict partly because they are both poorly defined, which I aim to remedy here from a transcriptomic perspective. There are two major categories of drugs: (1) restorative drugs aiming to restore an abnormal cell, tissue, or organ to normal function (e.g., restoring normal membrane function of epithelial cells in cystic fibrosis), and (2) disruptive drugs

Spinal cord injury (SCI) is a devastating neurological trauma that causes losses of motor and sensory function. Sestrin2, also known as hypoxia inducible gene 95, is emerging as a critical determinant of cell homeostasis in response to cellular stress. However, the role of sestrin2 in the neuronal response to endoplasmic reticulum (ER) stress and the potential mechanism remain undefined. In this study

Atrazine (ATZ), a commonly used pesticide linked to endocrine disruption, cancer, and altered neurochemistry, frequently contaminates water sources at levels above the US Environmental Protection Agency’s 3 parts per billion (ppb; μg/L) maximum contaminant level. Adult male zebrafish behavior, brain transcriptome, brain methylation status, and neuropathology were examined to test the hypothesis that

Gene modification and editing using mitochondrial DNA (mtDNA) is a promising option to conventional therapy for mitochondrial dysfunction which can result in a wide range of diseases and failure of organ and tissue functions. RNA-free DddA-derived cytosine base editors have been a promising method due to its high target specificity and high product purity in human mtDNA. However, mtDNA editing is still

Ziram, a zinc dithiocarbamate is widely used worldwide as a fungicide in agriculture. In order to investigate ziram-induced changes in macrophage functions and polarization, human monocytes-derived macrophages in culture were treated with ziram at 0.01–10 μmol.L−1 for 4–24 h. To characterize zinc involvement in these changes, we also determined the effects of disulfiram alone (dithiocarbamate without

CD8+T cells play an important role in controlling infections and tumorigenesis in vivo. naïve CD8+T cells exponentially expand and exert effector functions in response to TCR ligation. After antigen clearance, most effector CD8+T cells (Teff) experience activation-induced cell death, only a small portion becomes long-lived memory T cells (Tmem). The cell-intrinsic mechanisms driving the differentiation

Bisphenol A (BPA) is an endocrine-disrupting chemical (EDC) associated with non-alcoholic fatty liver disease (NAFLD). The effects of gestational BPA exposure on hepatic lipid accumulation in offspring are not fully understood. Here, we investigate the sex-dependent effects of gestational BPA exposure on hepatic lipid and glucose metabolism in the offspring of mice to reveal the mechanisms underlying

Non-alcoholic steatohepatitis (NASH) is a highly prevalent, chronic liver disease characterized by hepatic lipid accumulation, inflammation, and concomitant fibrosis. Up to date, no anti-NASH drugs have been approved. In this study, we reproduced key NASH characteristics in vitro by exposing primary human hepatocytes (PHH), human skin stem cell-derived hepatic cells (hSKP-HPC), HepaRG and HepG2 cell

Aflatoxin B1 (AFB1) is widely distributed in nature and is confirmed to be the most toxic of all the aflatoxins, whose predominant metabolism site is the liver. As a well-studied and vital mode of epigenetic modifications, aberrant methylation of the promoters in eukaryotic cells may cause the silence of essential genes, affecting their related transcriptional pathways and ultimately leading to the

Smoke inhalation injury is the leading cause of death in firefighters and victims. Inhaled hot air and toxic smoke are the predominant hazards to the respiratory epithelium. We aimed to analyze the effects of thermal stress and smoke aldehyde on the permeability of the airway epithelial barrier. Transepithelial resistance (RTE) and short-circuit current (ISC) of mouse tracheal epithelial monolayers

The embryonic stem cell test (EST) represents the only validated and accepted in vitro system for the detection and classification of compounds according to their developmental and reproductive teratogenic potency. The widespread implementation of the EST, however, in particular for routine application in pharmaceutical development, has not been achieved so far. Several drawbacks still limit the high-throughput

Cisplatin-based therapy is a widely used chemotherapeutic regimen for non-small cell lung cancer (NSCLC); however, drug resistance limits its efficacy. Acetyl-11-keto-β-boswellic acid (AKBA), a bioactive compound from frankincense, has been shown to exert anti-cancer effects. The aim of this study is to explore the potential of AKBA in combination with cisplatin as a new regimen for NSCLC. CCK8 assay

Background Methylsulfonylmethane (MSM) is a commonly used diet supplement believed to decrease the inflammation in joints and fastens recovery in osteoarthritis, gastric mucosal injury, or obesity-related disorders. It was also suggested that MSM might play a beneficial role in cancer treatment. Purpose So far, the MSM might have a potentially beneficial effect in endometrial cancer (EC) treatment

Steatosis is a liver lesion reported with numerous pharmaceuticals. Prior studies showed that severe impairment of mitochondrial fatty acid oxidation (mtFAO) constantly leads to lipid accretion in liver. However, much less is known about the mechanism(s) of drug-induced steatosis in the absence of severe mitochondrial dysfunction, although previous studies suggested the involvement of mild-to-moderate

The exosome of MSCs derived from human umbilical cord blood (HUCB-MSC) has been reported to have cardioprotective effects on mouse models of acute myocardial infarction (AMI) and cardiomyocyte hypoxia injury, but the exact mechanisms involved require further investigation. This paper aimed to study the role of HUCB-MSC-exosomes in inhibiting ferroptosis to attenuate myocardial injury. Compared with

Transient receptor potential vanilloid 3 (TRPV3) is highly expressed in skin keratinocytes where it forms Ca2+-permeable nonselective cation channels to regulate various cutaneous functions. TRPV3 expression is upregulated in many skin disorders. Here, we examined how TRPV3 affects keratinocyte proliferation and investigated the underlying mechanism. Topical application of TRPV3 agonist, carvacrol

Mesenchymal stem cells (MSC) are promising candidates for use as a biological therapeutic. Since locally injected MSC disappear within a few weeks, we hypothesize that efficacy of MSC can be enhanced by prolonging their presence. Previously, encapsulation in alginate was suggested as a suitable approach for this purpose. We found no differences between the two alginate types, alginate high in mannuronic

Uncoupling protein 1 (UCP1) has been implicated in ameliorating metabolic related disorders, of which most symptoms are risk factors for breast cancer. Here, we found that UCP1 was obviously downregulated in basal-like breast cancer (BLBC) and was positively correlated with improved survival. However, the underlying regulatory mechanisms remain largely unknown. Our studies showed that UCP1 inhibited

Mitochondrial DNA (mtDNA) plays an important role in regulating mitochondrial homeostasis, transcription, cell metabolism, and drug sensitivity. Patterns and regulations of mtDNA methylation vary among cell types, species, functions, and diseases. High-resolution mtDNA methylation maps of human and animal mitochondrial genomes addressed that the light (L)-strand non-CpG methylation of mtDNA varied

The application of silver nanoparticles (AgNPs) in consumer products has been increasing rapidly over the past decades. Therefore, in vitro models capable of accurately predicting the toxicity of AgNPs are much needed. Hepatocyte-like cells (HLCs) derived from human induced pluripotent stem cells (iPSCs) represent an attractive alternative in vitro hepatotoxicity model. Yet, the use of iPSC-derived

Recepteur d'origine nantais (RON) has been implicated in cell proliferation, metastasis, and chemoresistance of various human malignancies. The short-form RON (sf-RON) encoded by RON transcripts was overexpressed in gastric cancer tissues, but its regulatory functions remain illustrated. Here, we found that sf-RON promoted gastric cancer cell proliferation by enhancing glucose metabolism. Furthermore

Sirtuin 6 (Sirt6) is important for maintaining kidney homeostasis and function. Cd exposure increases the risk of developing kidney diseases. However, the role of Sirt6 in kidney disease mechanisms is unclear. Here, we evaluated the role of Sirt6 in Cd-induced kidney toxicity. After Cd exposure, p62/sequestosome-1 (SQSTM1), an autophagy substrate, accumulated in mouse kidney mesangial cells in monomeric

Substituting small molecule drugs with abundant and easily affordable ions may have positive effects on the way countless disease treatments are approached. The interest in strontium cation in bone therapies soared in the wake of the success of strontium ranelate in the treatment of osteoporosis. A new method for producing thin strontium-containing hydroxyapatite (Sr-HA, Ca9Sr(PO4)6(OH)2) films as

Owing to the excellent antibacterial and antiviral activity, silver nanoparticles have a widespread use in the food and pharmaceutical industries. With the increase in the production and use of the related products, the potential hazard of silver nanoparticles has aroused public attention. The main purpose of this study is to explore the toxicity of silver nanoparticles and induction of lung inflammation

Lung cancer is a heterogeneous and complex disease with the highest incidence and mortality rate. The present study aims at defining the lung cancer phenome specificity of lipidomic profiles, screening target lipid-dependent transcriptional alternations, identifying target lipid-associated target genes, and exploring molecular mechanisms. Lung cancer-specific and lung cancer subtype-specific target

Background Chronic obstructive pulmonary disease (COPD) is a global health problem. Currently, there is a lack of knowledge about the pathobiology of this disease and available therapies are ineffective. Cigarette smoking is the leading cause of COPD; however, not all smokers develop COPD. Exacerbations of COPD caused by microbes are common and detrimental. Approximately 20–50% of patient exacerbations

A percentage of colorectal cancer (CRC) patients display low sensitivity to radiotherapy, which affects its therapeutic effect. Cancer cells DNA double-strand breaks (DSBs) repair capacity is crucial for radiosensitivity, but the roles of long noncoding RNAs (lncRNAs) in this process are largely uncharacterized. This study aims to explore whether lnc-RI regulates CRC cell growth and radiosensitivity

The mutation rates of tumor suppressor protein p53 gene (TP53) are high in lung adenocarcinoma and promote the development of acquired drug resistance. The present study evaluated the p53-dependent role in lung cancer cell sensitivity to PI3K-specific inhibitors, PI3K-associated inhibitors, PI3K-non-related inhibitors, and protein-based stimuli using designed p53 mutation. We found that the deletion

Pro-apoptotic peptides have attracted much attention as promising anticancer agents due to their high activity. However, poor cellular uptake of the peptides is often associated with limited therapeutic application. Cell-penetrating homing peptides (CPHPs) were found to increase cell internalization as well as anticancer efficacy of the peptide conjugates. In this study, we developed a novel recombinant

Large animal models have been widely used to facilitate the translation of mesenchymal stem cells (MSC) from the laboratory to patient. MSC, with their multi-potent capacity, have been proposed to have therapeutic benefits in a number of pathological conditions. Laboratory studies allow the investigation of cellular and molecular interactions, while small animal models allow initial ‘proof of concept’

Colorectal cancer (CRC) liver metastasis (CLM) is the leading death cause of CRC patients, but there is no satisfied approach to treat CLM. Gut microbiota plays a pivotal role in CRC initiation and development. Targeting dysbiosis of the gut microbiota might open up new opportunities for CLM treatment. Here, we investigated the efficacy of sodium butyrate (NaB), a major product of gut microbial fermentation

Diethylstilbestrol (DES) is a synthetic estrogen and proven human teratogen and carcinogen reported to act via the estrogen receptor α (ERα). Since the endogenous ERα ligand 17β-estradiol (E2) does not show these adverse effects to a similar extent, we hypothesized that DES’ interaction with the ERα differs from that of E2. The current study aimed to investigate possible differences between DES and

Recent findings suggest a functional interaction of the drug resistance enzyme glutathione S-transferase P (GSTP) with the transcription factor Nrf2, a master regulator of the adaptive stress response to cellular electrophiles. The effect of this interaction on the metabolism and redox of cellular thiols was investigated in this study during the exposure to alkylating Se-compounds in murine embryonic

Single-cell biomedicine, a new merging discipline of cell biology and medicine to improve the life quality of patients, gains high priority in cell biology and toxicology. Single-cell nuclear elements are specially focused and headlined to understand regulatory mechanisms by which transcriptional factors, DNA elements, and genome organization interact with each other and contribute to the developmental

Androgen deprivation therapy (ADT) via surgical or chemical castration frequently fails to halt lethal castration-resistant prostate cancer (CRPC), which is induced by multiple mechanisms involving constitutive androgen receptor (AR) splice variants, AR mutation, and/or de novo androgen synthesis. The AR N-terminal domain (NTD) possesses most transcriptional activity and is proposed as a potential

Mitochondrial fission factor (Mff) has been demonstrated to play a role in the activation of mitochondrial cleavage and mitochondrial death, denoting its role in the regulation of mitochondrial quality control. Recent evidence suggested that the mRNA translation of Mff is under the negative regulation by the RNA-binding protein Pumilio2 (Pum2). This study was designed to examine the role of Pum2 and

Taxol has been widely used as a first-line chemotherapeutic agent for the treatment of advanced nasopharyngeal carcinoma (NPC). However, acquired drug resistance has caused great difficulties in clinical treatment. Pyroptosis is a newly discovered programmed cell death pathway, and Caspase-1 and gasdermin D (GSDMD) play key roles in driving canonical pyroptosis. Increasing evidence suggests that pyroptosis

Unfortunately, there are some tiny errors in the data for Fig. 1a-c and Fig. 2a-e in the published online paper. Please see the correct relative data in Tables 3 and 4 given in the next page. These errors does not interfere the results and conclusions of authors study.

Protein neddylation, a process of conjugating neural precursor cell expressed, developmentally downregulated 8 (NEDD8) to substrates, plays a tumor-promoting role in lung carcinogenesis. Our previous study showed MLN4924, an inhibitor of NEDD8 activating enzyme (E1), significantly inhibits the growth of multiple cancer cells. However, resistance can develop to MLN4924 by mutation. Therefore, it is

ObjectivesLncRNAs (long noncoding RNAs) have been reported to critically regulate colorectal cancer (CRC). We prospectively investigated effects and mechanisms of lncRNA LINC00858 on regulation of CRC progression. MethodsExpression of LINC00858 and its target were analyzed by quantitative real-time polymerase chain reaction and in situ hybridization. MTT and bromodeoxyuridine/5-bromo-2′-deoxyuridine

Hydroquinone (HQ), a major metabolic product of benzene, causes acute myeloid leukemia (AML) elicited by benzene exposure. Past studies found that continuous exposure of human AML U937 cells to HQ selectively produces malignant U937/HQ cells in which FOXP3 upregulation modulates malignant progression. Other studies revealed that AMPK promotes TET2 activity on DNA demethylation and that TET2 activity

Hematopoietic stem cells (HSCs) produce new blood cells everyday throughout life, which is maintained by the self-renewal and differentiation ability of HSCs. This is not controlled by the HSCs alone, but rather by the complex and exquisite microenvironment surrounding the HSCs, which is called the bone marrow niche and consists of various bone marrow cells, growth factors, and cytokines. It is essential

Unfortunately, the author names in the author group section were incorrectly captured in the published online paper.

Particulate matter (PM) is an environmental pollutant closely associated with human airway inflammation. However, the molecular mechanisms of PM-related airway inflammation remains to be fully elucidated. It is known that COX-2/PGE2 play key roles in the pathogenesis of airway inflammation. Filaggrin is a transmembrane protein contributing to tight junction barrier function. As such, Filaggrin prevents

Para-cresyl sulfate (P-CS), a major uremic toxin derived from the metabolites of tyrosine and phenylalanine through liver, existed in the blood of patients with chronic kidney disease (CKD). CKD increases the malignancy in bladder cancers; however, effects of P-CS on bladder cancers are not fully understood. P-CS is conjugated with BSA physiologically, and this study aims to investigate the effects

Animal and clinical studies have shown that mesenchymal stem cells (MSCs) play an important role in cartilage repair. The therapeutic effect of mesenchymal stem cells based therapies has been increasingly demonstrated to exosome-mediated paracrine secretion. Here, we investigated the cellular processes and mechanism of exosomes produced by conventional 2D culture (2D-Exos) and exosomes produced from

Like the organism they constitute, the cells also die in different ways. The death can be predetermined, programmed, and cleanly executed, as in the case of apoptosis, or it can be traumatic, inflammatory, and sudden as many types of necrosis exemplify. Nevertheless, there are a number of cell deaths—some of them bearing a resemblance to apoptosis and/or necrosis, and many, distinct from each—that

Inflammation reaction mediated by NLRP3 inflammasome and Nrf2-related oxidative stress are vital participants in the development of diabetic nephropathy (DN) and closely associated to kidney fibrosis. Nrf2, a known antioxidative transcription factor, has been reported to activate NLRP3 inflammasome through its downstream factors (HO-1, NQO1, etc.) recently. AB38b is a newly synthesized biphenyl diester

Glioblastoma (GBM) is the most aggressive type of glioma. Temozolomide (TMZ) is currently the drug of choice used for post-operative chemotherapy of GBM. However, the presence of intrinsic and acquired resistance hinders the success of chemotherapy. To understand the TMZ resistant mechanisms in glioma, we investigated the alterations in cellular signaling pathways by performing transcriptome analysis