Circulating mitochondrial DNA promotes M2 polarization of tumor associated macrophages and HCC resistance to sorafenib.

Mitochondrial damage-associated molecular patterns (DAMPs) including mitochondrial DNA (mtDNA), TFAM (transcription factor A, mitochondrial), and ATP, which play crucial roles in the regulation of inflammatory environment in human diseases. However, the role of mitochondrial DAMPs in regulating tumor microenvironment (TME) remains unclear. Herein, we demonstrate that infiltration of M2-type tumor-associated macrophages (TAMs) was correlated with the resistance of hepatocellular carcinoma (HCC) to sorafenib.

TEFM facilitates uterine corpus endometrial carcinoma progression by activating ROS-NFκB pathway.

Background: Mitochondrial transcription elongation factor (TEFM) is a recently discovered factor involved in mitochondrial DNA replication and transcription. Previous studies have reported that abnormal TEFM expression can disrupt the assembly of mitochondrial respiratory chain and thus mitochondrial function. However, the role of TEFM on Uterine corpus endometrial carcinoma (UCEC) progression remains unclear.

Tenofovir disoproxil fumarate mediates neuronal injury by inducing neurotoxicity.

Purpose: Highly active antiretroviral therapy (HAART) is an accepted treatment option for patients with virus infection. Mounting evidence indicated that persistent HAART treatment is implicated with increased morbidity of HIV-associated neurocognitive disorders (HAND) in patients. Tenofovir disoproxil fumarate (TDF), a novel nucleotide reverse transcriptase inhibitor (NRTI), was used in patients with HIV co-infected with HBV.

PRRSV infection activates NLRP3 inflammasome through inducing cytosolic mitochondrial DNA stress.

Porcine reproductive and respiratory syndrome virus (PRRSV) infection causes severe interstitial pneumonia and inflammatory response in piglets and growing pigs. IL-1β is implicated in PRRSV-mediated inflammatory response and the pathogenesis of PRRSV infection. Mitochondria are critical intracellular organelles which is served as signaling platform for antiviral immunity response to participate in immune response of virus infection.

TFAM downregulation promotes autophagy and ESCC survival through mtDNA stress-mediated STING pathway.

The dynamics of mitochondrial biogenesis regulation is critical in maintaining cellular homeostasis for immune regulation and tumor prevention. Here, we report that mitochondrial biogenesis disruption through TFAM reduction significantly impairs mitochondrial function, induces autophagy, and promotes esophageal squamous cell carcinoma (ESCC) growth. We found that TFAM protein reduction promotes mitochondrial DNA (mtDNA) release into the cytosol, induces cytosolic mtDNA stress, subsequently activates the cGAS-STING signaling pathway, thereby stimulating autophagy and ESCC growth.

Increased Drp1 promotes autophagy and ESCC progression by mtDNA stress mediated cGAS-STING pathway.

Background: Mitochondrial dynamics homeostasis is important for cell metabolism, growth, proliferation, and immune responses. The critical GTPase for mitochondrial fission, Drp1 is frequently upregulated in many cancers and is closely implicated in tumorigenesis. However, the mechanism underling Drp1 to influence tumor progression is largely unknown, especially in esophageal squamous cell carcinoma (ESCC).

Ivermectin induces apoptosis of esophageal squamous cell carcinoma via mitochondrial pathway.

Background: Esophageal squamous cell carcinoma (ESCC) is the most predominant primary malignant tumor among worldwide, especially in China. To date, the successful treatment remains a mainly clinical challenge, it is imperative to develop successful therapeutic agents.

Methods: The anti-proliferative effect of ivermectin on ESCC is investigated in cell model and in nude mice model.

Characterization of fragment sizes, copy number aberrations and 4-mer end motifs in cell-free DNA of hepatocellular carcinoma for enhanced liquid biopsy-based cancer detection.

Circulating cell-free DNA (cfDNA) fragmentomics, which encompasses the measurement of cfDNA length and short nucleotide motifs at the ends of cfDNA molecules, is an emerging field for cancer diagnosis. The utilization of cfDNA fragmentomics for the diagnosis of patients with hepatocellular carcinoma (HCC) caused by hepatitis B virus (HBV) is currently limited. In this study, we utilized whole-genome sequencing data of cfDNA in samples from patients with HCC (n = 197) and HBV (n = 187) to analyze the association of fragment size selection (< 150 bp) with tumor fraction (TF), copy number variation (CNV) alterations and the change in the proportion of 4-mer end motifs in HCC and HBV samples.

Long non-coding RNA small nucleolar RNA host gene 7 facilitates the proliferation, migration, and invasion of esophageal cancer cells by regulating microRNA-625.

Background: Esophageal cancer (EC) is a highly aggressive malignant tumor, of which esophageal squamous cell carcinoma (ESCC) constitutes the main subtype. Long non-coding RNA (lncRNA) small nucleolar RNA host gene 7 (SNHG7) has been extensively studied in many tumors and has been confirmed to be an oncogene; however, it has yet to be investigated in an ESCC study. Therefore, this study intended to uncover the role of SNHG7 in ESCC.

Elevated TEFM expression promotes growth and metastasis through activation of ROS/ERK signaling in hepatocellular carcinoma.

TEFM (transcription elongation factor of mitochondria) has been identified as a novel nuclear-encoded transcription elongation factor in the transcription of mitochondrial genome. Our bioinformatics analysis of TCGA data revealed an aberrant over-expression of TEFM in hepatocellular carcinoma (HCC). We analyzed its biological effects and clinical significance in this malignancy.

Machine learning-based genome-wide interrogation of somatic copy number aberrations in circulating tumor DNA for early detection of hepatocellular carcinoma.

Background: DNAs released from tumor cells into blood (circulating tumor DNAs, ctDNAs) carry tumor-specific genomic aberrations, providing a non-invasive means for cancer detection. In this study, we aimed to leverage somatic copy number aberration (SCNA) in ctDNA to develop assays to detect early-stage HCCs.

Methods: We conducted low-depth whole-genome sequencing (WGS) to profile SCNAs in 384 plasma samples of hepatitis B virus (HBV)-related HCC and cancer-free HBV patients, using one discovery and two validation cohorts.

Danshen formula granule and salvianic acid A alleviate ethanol-induced neurotoxicity.

As a direct neurotoxin, ethanol exposure is associated with nerve damage and dysfunction of central nervous system (CNS) and induced obvious neurotoxicity by increasing the reactive oxygen species (ROS) production, activation of endogenous apoptotic as well as necrotic signals, and other molecular mechanisms. The previous studies had demonstrated that natural herbal medicine offers protective effectiveness on ethanol-induced nerve cell damage. Danshen and its extracts have been known to have an antioxidant property and neuroprotective effects.

Long noncoding RNA LINC00662 promotes M2 macrophage polarization and hepatocellular carcinoma progression via activating Wnt/β-catenin signaling.

Tumor-associated macrophages have important roles in hepatocellular carcinoma (HCC) initiation and progression. Long noncoding RNAs (lncRNAs) have also been reported to be involved in HCC. In this study, we explored how lncRNA LINC00662 may influence HCC progression through both tumor cell-dependent and macrophage-dependent mechanisms.

Porcine FcγRIIb mediated PRRSV ADE infection through inhibiting IFN-β by cytoplasmic inhibitory signal transduction.

Antibody-dependent enhancement (ADE) in porcine reproductive and respiratory syndrome virus (PRRSV) infection is a significant obstacle to the development of effective vaccines for controlling PRRS. Our previous results have demonstrated that porcine FcγRIIb (poFcγRIIb) play an important role in mediating ADE of PRRSV infection in vitro. However, the underlying mechanisms involved in poFcγRIIb mediated-ADE are still not clear.

Mitochondrial fission-induced mtDNA stress promotes tumor-associated macrophage infiltration and HCC progression.

Tumor-associated macrophages (TAMs) contribute to hepatocellular carcinoma (HCC) progression. However, the molecular mechanism underlying the infiltration of TAMs into HCC microenvironment is largely unclear. Recent studies have reported that alteration of mitochondrial nucleoid structures induces mitochondrial DNA (mtDNA) release into the cytosol, which is recognized as mtDNA stress, and consequently regulates innate immunity.

Tenofovir disoproxil fumarate induces pheochromocytoma cells apoptosis.

Despite the triumph of highly active antiretroviral therapy (HAART) in anti-HIV infection, more than half of the HIV infection individuals receiving antiretroviral therapy acquire HIV-associated neurocognitive disorder (HAND). Previously researches had reported that the HAART neurotoxicity is implicated in HAND-related morbidity. The molecular mechanism of HAND is not clear.

The attenuation of HIV-1 Tat-induced neurotoxicity by Salvianic acid A and Danshen granule.

The neurotoxicity of HIV-1 Tat protein contributes significantly to the pathogenesis of HAND, and hence the attractive therapeutic strategies focusing on Tat-induced neurotoxicity are warranted. Salvia miltiorrhiza have been known to antioxidant property and neuroprotective effects. The Danshen granule is the pharmaceutical dosage forms of Salvia miltiorrhiza and Salvianic acid A is an essential chemical constituent of Salvia miltiorrhiza.

Protective Effect of Quercetin against Oxidative Stress-Induced Cytotoxicity in Rat Pheochromocytoma (PC-12) Cells.

Oxidative stress has been implicated in the pathogenesis of many kinds of neurodegenerative disorders, particularly Parkinson's disease. Quercetin is a bioflavonoid found ubiquitously in fruits and vegetables, and has antioxidative activity. However, the underlying mechanism of the antioxidative effect of quercetin in neurodegenerative diseases has not been well explored.

The development of a sensitive droplet digital PCR for quantitative detection of porcine reproductive and respiratory syndrome virus.

Porcine reproductive and respiratory syndrome (PRRS) is an infectious disease, resulting in important economic losses in pig farming. Prompt detection of PRRS virus (PRRSV) in the field samples is important for effective PRRS control. Droplet digital PCR (ddPCR) is a novel PCR technology, which offers good precision and direct quantification without using calibration curves.

Development of an immunochromatographic strip for detection of antibodies against porcine reproductive and respiratory syndrome virus.

A simple and rapid immunochromatographic test strip incorporating a colloidal gold-labeled recombinant Nsp7 antigen probe was successfully developed for the detection of anti-porcine reproductive and respiratory syndrome virus (PRRSV) antibodies in swine. Recombinant Nsp7 protein of PRRSV labeled with colloidal gold was dispensed on a conjugate pad for use as the detector. Staphylococcal protein A and purified porcine anti-Nsp7 antibodies were blotted on a nitrocellulose membrane to form test and control lines, respectively.

Alterations of telomere length and mtDNA copy number are associated with overall survival in hepatocellular carcinoma patients treated with transarterial chemoembolization.

Purpose: Increasing evidence suggests that alterations in mitochondrial DNA (mtDNA) copy number (mtDNAcn) and relative telomere length (RTL) may be implicated in the tumorigenesis of several malignancies. Alterations of both RTL and mtDNAcn are generally accepted as independent biomarkers for predicting risk and prognosis in various cancers. The aim of this study was to evaluate the prognostic value of combining leukocyte RTL with mtDNAcn (RTL-mtDNAcn) in hepatocellular carcinoma (HCC).

Effect of thymidylate synthase gene polymorphism on the response to chemotherapy and clinical outcome of non-small cell lung cancer patients.

Genetic polymorphisms of thymidylate synthase (TYMS) gene have been reported to be associated with development or prognosis of several cancers. However, the association between polymorphisms of TYMS gene and clinical outcomes of non-small cell lung cancer (NSCLC) patients are still unknown. In the present study, we investigated the associations between single nucleotide polymorphisms (SNPs) of TYMS gene and response to chemotherapy as well as clinical outcomes in NSCLC patients.

Polymorphisms in genes of the de novo lipogenesis pathway and overall survival of hepatocellular carcinoma patients undergoing transarterial chemoembolization.

Aberrant expression of genes in de novo lipogenesis (DNL) pathway were associated with various cancers, including hepatocellular carcinoma (HCC). Single nucleotide polymorphisms (SNPs) of DNL genes have been reported to be associated with prognosis of some malignancies. However, the effects of SNPs in DNL genes on overall survival of HCC patients receiving transarterial chemoembolization (TACE) treatment are still unknown.

Antibody-dependent enhancement of PRRSV infection down-modulates TNF-α and IFN-β transcription in macrophages.

Porcine reproductive and respiratory syndrome (PRRS) is an infectious disease, resulting in important economic losses in pig farming. Previous studies have shown that Fcγ receptor (FcγR)-mediated entry of infectious PRRSV immune complexes into macrophages plays a pivotal role in the pathogenesis of the disease. This study demonstrates that PRRSV was able to suppress the transcription of key antiviral genes tumor necrosis factor-α (TNF-α) and interferon-β (IFN-β), when infection was via the ADE pathway.