C-C chemokine hepatocellular carcinoma motif ligand 5-deficiency promotes hepatocellular carcinoma progression by affecting B cell recruitment.

Objective: To evaluate the expression of C-C motif chemokine ligand 5 (CCL5) in hepatocellular carcinoma (HCC) and to explore its role in regulating the immune microenvironment and the related mechanism in tumor immunity.

Methods: The mRNA expression level of CCL5 in HCC and adjacent non-cancerous tissues was measured by quantitative polymerase chain reaction and the protein expression was examined by immunohistochemistry. Serum CCL5 expression was measured by an enzyme-linked immunosorbent assay (ELISA).

A conserved residue in the P2X4 receptor has a nonconserved function in ATP recognition.

Highly conserved amino acids are generally anticipated to have similar functions across a protein superfamily, including that of the P2X ion channels, which are gated by extracellular ATP. However, whether and how these functions are conserved becomes less clear when neighboring amino acids are not conserved. Here, we investigate one such case, focused on the highly conserved residue from P2X4, E118 (rat P2X4 numbering, rP2X4), a P2X subtype associated with human neuropathic pain.

DJ-1 Deficiency in Hepatocytes Improves Liver Ischemia-Reperfusion Injury by Enhancing Mitophagy.

Background & Aims: DJ-1 is universally expressed in various tissues and organs and is involved in the physiological processes in various liver diseases. However, the role of DJ-1 in liver ischemia-reperfusion (I/R) injury is largely unknown.

Methods: In this study, we first examined the DJ-1 expression changes in the liver tissues of mice and clinical donor after hepatic I/R by both quantitative polymerase chain reaction and Western blotting assays.

Systematic elucidation of the mechanism of Jingyin granule in the treatment of Novel Coronavirus (COVID-19) Pneumonia via Network Pharmacology.

Jingyin granule is one of the widely used traditional Chinese medicine mixture composed of multiple herbs in the treatment of respiratory system diseases. The mechanism of its therapeutic effects has still been obscure. The aim of this study is to use the network pharmacology approach for identification of the main active ingredients of Jingyin granule against COVID-19 targets and to explore their therapeutic mechanism.

Comprehensive genomic analysis of microenvironment phenotypes in ovarian cancer.

Background: Ovarian cancer is one of the leading causes of cancer-related death in women. The incidence of ovarian cancer is insidious, and the recurrence rate is high. The survival rate of ovarian cancer has not significantly improved over the past decade.

Non-metabolic role of UCK2 links EGFR-AKT pathway activation to metastasis enhancement in hepatocellular carcinoma.

Up-regulation of Uridine-cytidine kinase 2 (UCK2), a rate-limiting enzyme of the pyrimidine salvage pathway, has been suggested in HCC, but the detailed molecular mechanisms and therapic role of UCK2 remain elusive. Bioinformatic analyses revealed that UCK2 might be a key up-regulated metabolic gene in HCCs. The expressional pattern and prognostic value of UCK2 were further examined in a large number of clinical samples.

Bioinformatic Analysis to Identify a Multi-mRNA Signature for the Prediction of Metastasis in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) with metastasis indicates worse prognosis for patients. However, the current methods are insufficient to accurately predict HCC metastasis at early stage. Based on the expression profiles of three Gene Expression Omnibus datasets, the differentially expressed genes associated with HCC metastasis were screened by online analytical tool GEO2R and weighted gene co-expression network analysis.

Comprehensive analysis of circular RNAs from steatotic livers after ischemia and reperfusion injury by next-generation RNA sequencing.

Global organ shortage has led to the acceptance of steatotic livers for transplantation, taking the risk of graft dysfunction associated with the higher sensitivity of steatotic livers to ischemia and reperfusion injury (IRI). Data about circular RNAs (circRNAs) in steatotic livers following IRI are practically nonexistent. In our study, a high-fat diet-fed mouse model of hepatic steatosis was generated, and RNA sequencing was performed both on IRI and on sham liver tissues of these mice to screen for circRNAs with significant differential expression.

Pros and Cons: High Proportion of Stromal Component Indicates Better Prognosis in Patients With Pancreatic Ductal Adenocarcinoma-A Research Based on the Evaluation of Whole-Mount Histological Slides.

The study aimed to investigate the potential of tumor-stroma ratio (TSR) on digitalized whole-mount histopathology to predict prognosis in patients with pancreatic ductal adenocarcinoma (PDAC). The effectiveness were evaluated through internal validation. Data were retrospectively collected from consecutive patients who underwent primary pancreatic resection from December 2016 to August 2017 (developing cohort) and from September 2017 to April 2018 (validation cohort).

Effects of Electroacupuncture on Ovarian Expression of the Androgen Receptor and Connexin 43 in Rats with Letrozole-Induced Polycystic Ovaries.

Background: Polycystic ovarian syndrome (PCOS) occurs in women of reproductive age and is often characterized by reproductive and endocrine dysfunction. Androgens play a major role in PCOS, and previous studies reported abnormal expression of Connexin 43 (Cx43) in animal models of PCOS, suggesting an association of Cx43 with PCOS pathogenesis. Experimental and clinical evidence indicated that acupuncture may be a safe and effective approach for treating reproductive and endocrine disorders in women with PCOS.

CUX1, A Controversial Player in Tumor Development.

CUX1 belongs to the homeodomain transcription factor family and is evolutionarily and functionally conserved from to humans. In addition to the involvement in various physiological events including tissue development, cell proliferation, differentiation and migration, and DNA damage response, CUX1 has been implicated in tumorigenesis. Interestingly, has been recently recognized as a haploinsufficient tumor suppressor, which is paradoxically overexpressed in tumor cells.

Effects of edaravone on postoperative cognitive function in elderly patients undergoing hip joint replacement surgery: A randomized controlled trial.

Background: Postoperative cognitive dysfunction (POCD) is a complication of central nervous system in patients after surgery. Edaravone as a brain-protective agent may have protective effect on postoperative cognitive function. The study was designed to explore the effects of edaravone on postoperative cognitive function in elderly patients undergoing hip joint replacement surgery and potential mechanism.

Blocking GSDMD processing in innate immune cells but not in hepatocytes protects hepatic ischemia-reperfusion injury.

Pyroptosis, a proinflammatory form of programmed cell death, plays important roles in the pathogenesis of many diseases. Inflammasome activation, which has been shown in hepatic ischemia-reperfusion injury (IRI), is demonstrated to be closely associated with pyroptosis, indicating that pyroptosis may occur and perform functions in hepatic IRI. However, there is no direct evidence showing the function of pyroptosis in hepatic IRI.

Herbal Therapy for the Treatment of Acetaminophen-Associated Liver Injury: Recent Advances and Future Perspectives.

Acetaminophen (APAP) overdose is the leading cause of drug-induced liver injury worldwide, and mitochondrial oxidative stress is considered the major event responsible for APAP-associated liver injury (ALI). Despite the identification of N-acetyl cysteine, a reactive oxygen species scavenger that is regarded as an effective clinical treatment, therapeutic effectiveness remains limited due to rapid disease progression and diagnosis at a late phase, which leads to the need to explore various therapeutic approaches. Since the early 1990s, a number of natural products and herbs have been found to have hepatoprotective effects against APAP-induced hepatotoxicity in terms of acute liver failure prevention and therapeutic amelioration of ALI.

Correction: IRE1 promotes neurodegeneration through autophagy-dependent neuron death in the Drosophila model of Parkinson's disease.

Since online publication of this article, the authors noticed that some of the fly stocks were mislabelled in the methods and in Supplementary Figure 5. The corrected methods text is provided below.

Deficiency in the anti-apoptotic protein DJ-1 promotes intestinal epithelial cell apoptosis and aggravates inflammatory bowel disease via p53.

Parkinson disease autosomal recessive, early onset 7 (PARK7 or DJ-1) is involved in multiple physiological processes and exerts anti-apoptotic effects on multiple cell types. Increased intestinal epithelial cell (IEC) apoptosis and excessive activation of the p53 signaling pathway is a hallmark of inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD). However, whether DJ-1 plays a role in colitis is unclear.

Prognostic values of a novel multi-mRNA signature for predicting relapse of cholangiocarcinoma.

Cholangiocarcinoma (CCA) is an epithelial cancer and has high death and recurrence rates, current methods cannot satisfy the need for predicting cancer relapse effectively. So, we aimed at conducting a multi-mRNA signature to improve the relapse prediction of CCA. We analyzed mRNA expression profiling in large CCA cohorts from the Gene Expression Omnibus (GEO) database (GSE76297, GSE32879, GSE26566, GSE31370, and GSE45001) and The Cancer Genome Atlas (TCGA) database.

Correction to: DNMT3A reads and connects histone H3K36me2 to DNA methylation.

The author would like to add the below information in this correction. A similar study from Chao Lu group was published online on 5 September 2019 in Nature, entitled "The histone mark H3K36me2 recruits DNMT3A and shapes the intergenic DNA methylation landscape" (Weinberg et al., 2019).

Altered allostery of the left flipper domain underlies the weak ATP response of rat P2X5 receptors.

Although the extracellular ATP-gated cation channel purinergic receptor P2X5 is widely expressed in heart, skeletal muscle, and immune and nervous systems in mammals, little is known about its functions and channel-gating activities. This lack of knowledge is due to P2X5's weak ATP responses in several mammalian species, such as humans, rats, and mice. WT human P2X5 (hP2X5) does not respond to ATP, whereas a full-length variant, hP2X5 (hP2X5-FL), containing exon 10 encoding the second hP2X5 transmembrane domain (TM2), does.

IRE1 promotes neurodegeneration through autophagy-dependent neuron death in the Drosophila model of Parkinson's disease.

Abnormal aggregation of misfolded pathological proteins in neurons is a prominent feature of neurodegenerative disorders including Parkinson's disease (PD). Perturbations of proteostasis at the endoplasmic reticulum (ER) triggers ER stress, activating the unfolded protein response (UPR). Chronic ER stress is thought to underlie the death of neurons during the neurodegenerative progression, but the precise mechanism by which the UPR pathways regulate neuronal cell fate remains incompletely understood.

CCL5 deficiency promotes liver repair by improving inflammation resolution and liver regeneration through M2 macrophage polarization.

Despite the diverse etiologies of drug-induced liver injury (DILI), innate immunity activation is a common feature involved in DILI progression. However, the involvement of innate immunity regulation in inflammation resolution and liver regeneration in DILI remains obscure. Herein, we identified the chemokine CCL5 as a central mediator of innate immunity regulation in the pathogenesis of DILI.

Metabolic modulation of acetaminophen-induced hepatotoxicity by osteopontin.

Induction of osteopontin (OPN), a well-known pro-inflammatory molecule, has been observed in acetaminophen (APAP)-induced hepatotoxicity. However, the precise cell source for OPN induction and its role during APAP-induced hepatotoxicity has not been fully explored. By employing a hepatotoxic mouse model induced by APAP overdose, we demonstrate that both serum and hepatic OPN levels were significantly elevated in response to APAP treatment.

A dose-finding study for hemoporfin in photodynamic therapy for port-wine stain: A multicenter randomized double-blind phase IIb trial.

Background/purpose: Previous studies have shown that hemoporfin-mediated photodynamic therapy (PDT) was a treatment for port-wine stain (PWS). Our current study aimed to identify optimal hemoporfin dose.

Methods: A prospective, multicenter, double-blind, randomized clinical trial was conducted.