Integrated analysis of microbiome and host transcriptome unveils correlations between lung microbiota and host immunity in bronchoalveolar lavage fluid of pneumocystis pneumonia patients.

Objective: The lung microbiota of patients with pulmonary diseases is disrupted and impacts the immunity. The microbiological and immune landscape of the lungs in patients with pneumocystis pneumonia (PCP) remains poorly understood.

Methods: Multi-omics analysis and machine learning were performed on bronchoalveolar lavage fluid to explore interaction between the lung microbiota and host immunity in PCP.

Ubiquitin-proteasome system-mediated ubiquitination modification patterns and characterization of tumor microenvironment infiltration, stemness and cellular senescence in low-grade glioma.

The Ubiquitin-proteasome system (UPS) performs a crucial role in immune activation and tumorigenesis. Nevertheless, the comprehensive role of the ubiquitin-proteasome system in the low-grade glioma (LGG) tumor microenvironment (TME) remains unknown. Ubiquitination modification patterns in LGG patients and corresponding characteristics of tumor immune traits, CSC stemness, and cellular senescence were evaluated via a comprehensive analysis of 20 ubiquitination modification regulators.

Integrative Analysis of Transcriptome and Metabolome to Illuminate the Protective Effects of Didymin against Acute Hepatic Injury.

Based on the multiomics analysis, this study is aimed at investigating the underlying mechanism of didymin against acute liver injury (ALI). The mice were administrated with didymin for 2 weeks, followed by injection with lipopolysaccharide (LPS) plus D-galactosamine (D-Gal) to induce ALI. The pathological examination revealed that didymin significantly ameliorated LPS/D-Gal-induced hepatic damage.

Diagnostic, Prognostic, and Immunological Roles of FABP4 in Pancancer: A Bioinformatics Analysis.

Background: Fatty acid binding protein 4 (FABP4) is mainly involved in the regulation of systemic metabolism through various lipid signaling pathways. Metabolic reprogramming is one of the important factors in the development and progression of cancer. It has been recently reported that FABP4 is closely related to the development of cancer and may be involved in tumor invasion and metastasis.

Reactive Oxygen Species-Responsive Nanococktail With Self-Amplificated Drug Release for Efficient Co-Delivery of Paclitaxel/Cucurbitacin B and Synergistic Treatment of Gastric Cancer.

Application of drug combinations is a powerful strategy for the therapy of advanced gastric cancer. However, the clinical use of such combinations is greatly limited by the occurrence of severe systemic toxicity. Although polymeric-prodrug-based nanococktails can significantly reduce toxicity of drugs, they have been shown to have low intracellular drug release.

Isovitexin protects against acute liver injury by targeting PTEN, PI3K and BiP via modification of m6A.

Isovitexin (IVT) has been shown to have a potential therapeutic effect on acute liver injury (ALI), but its underlying mechanisms especially the targets remain unclear, which was investigated in the present study. Briefly, the targets of IVT were predicted by bioinformatics and then were verified by multiple examinations using molecular docking, cellular thermal shift assay (CETSA), and Lipopolysaccharide/D-Galactosamine (LPS/D-GalN)-induced ALI animal model. The bioinformatic analysis predicted that the target genes of IVT against ALI were enriched into the PI3K/Akt and ERS-related pathways, in which, molecular docking and CETSA examination verified that the binding sites of IVT likely were PTEN, PI3K and BiP.

POU2F2-IL-31 Autoregulatory Circuit Converts Hepatocytes into the Origin Cells of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) originates from fully differentiated hepatocytes, but the decisive events for converting hepatocytes to the cells of origin for HCC are still unclear. Liver cancer stem cells (LCSCs) cause HCC but are not bona fide cells of origin. Here, the expressions of POU2F2 and IL-31 are identified in macroscopically normal livers of diethylnitrosamine-challenged mice.

Didymin ameliorates dexamethasone-induced non-alcoholic fatty liver disease by inhibiting TLR4/NF-κB and PI3K/Akt pathways in C57BL/6J mice.

The present study aimed to investigate the protective effects and mechanisms of Didymin from Mentha spicata on non-alcoholic fatty liver disease (NAFLD) induced by dexamethasone and high-fat diet (DEX/HFD) in C57BL/6J mice. Briefly, mice were acclimated for 5 days and then subjected to DEX/HFD from days 5 to 28; meanwhile, the animals were treated with Didymin or Silibinin from days 12 to 28. Key indicators of NAFLD were then detected, including the pathological changes of liver tissues, serum biochemical indicators, inflammation, oxidative stress, apoptosis and lipid metabolism.

Asiatic acid ameliorates acute hepatic injury by reducing endoplasmic reticulum stress and triggering hepatocyte autophagy.

Endoplasmic reticulum stress (ERS), mutual crosstalk between autophagy and apoptosis-related signaling pathway, plays an important role in the process of acute liver injury (ALI). The present study was to investigate the effects and underlying mechanisms of Asiatic acid from Potentilla chinensis (AAPC) on ALI. The model of ALI in mice was induced by administration with Lipopolysaccharide/D-Galactosamine (LPS/D-GalN).

The inhibition of IL-2/IL-2R gives rise to CD8 T cell and lymphocyte decrease through JAK1-STAT5 in critical patients with COVID-19 pneumonia.

Although most patients with COVID-19 pneumonia have a good prognosis, some patients develop to severe or critical illness, and the mortality of critical cases is up to 61.5%. However, specific molecular information about immune response in critical patients with COVID-19 is poorly understood.

Downregulated Gene Expression Spectrum and Immune Responses Changed During the Disease Progression in Patients With COVID-19.

Background: The World Health Organization characterizes novel coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as a pandemic. Here, we investigated the clinical, cytokine levels; T-cell proportion; and related gene expression occurring in patients with COVID-19 on admission and after initial treatment.

Methods: Eleven patients diagnosed with COVID-19 with similar initial treatment regimens were enrolled in the hospital.

Activation of EGFR-KLF4 positive feedback loop results in acquired resistance to sorafenib in hepatocellular carcinoma.

Sorafenib is the standard first-line systemic chemotherapeutic drugs for advanced hepatocellular carcinoma (HCC), but acquired resistance to sorafenib is frequently observed in clinical practice. In this study, we first produced three sorafenib resistance (SR) HCC cell lines by using two human HCC cell lines (Hep3B and Huh7) and a human primary HCC cell line. We identified that epidermal growth factor receptor (EGFR) and Kruppel-like factor 4 (KLF4) are dramatically increased in the three SR HCC cell lines.

AZD3759 induces apoptosis in hepatoma cells by activating a p53-SMAD4 positive feedback loop.

AZD3759 is a tyrosine kinase inhibitor and has an encouraging future in treating brain metastases of non-small cell lung cancer. Here, we determined that AZD3759 suppressed the viability of HepG2 cells, a hepatoma cell line, and induced their apoptosis, suggesting a new therapeutic potential of AZD3759 in hepatocellular carcinoma (HCC) treatment. Furthermore, we found that the activation of p53-SMAD family member 4 (SMAD4) positive feedback loop was involved in the induction of bulks of apoptosis in HepG2 cells in response to AZD3759 treatment.

Mitochondrial DNA mutations accumulated in HIV-1-infected children who have an excellent virological response when exposed to long-term antiretroviral therapy.

Objectives: There is growing concern about mitochondrial DNA (mtDNA) mutations with long-term NRTI exposure in HIV-1 infected children.

Methods: Twenty-four HIV-1 infected children who started ART more than 2 years earlier who had an excellent virological response and had not changed their regimen were enrolled retrospectively. Their corresponding PBMCs in 2009 (T1), 2010 (T2) and 2013 (T3) were included.

Asiatic acid from Potentilla chinensis alleviates non-alcoholic fatty liver by regulating endoplasmic reticulum stress and lipid metabolism.

Endoplasmic reticulum stress (ERS) is induced by accumulation of misfolded proteins, playing a pivotal role during the processes of non-alcoholic fatty liver disease (NAFLD). The present study was to investigate the effect of Asiatic acid from Potentilla chinensis (AAPC) on liver cell lipid metabolism, exploring the underlying mechanism of AAPC against NAFLD. In vivo, the animal NAFLD model was induced by feeding rats with high fat diet (HFD) for 18 weeks, and meanwhile the rats were treated with AAPC from weeks 8 to 18; In vitro experiment, the effect of AAPC on dyslipidemia induced by oleic acid (OA) in hepatic cells (HepG2) was evaluated.

The molecular mechanism and clinical significance of LDHA in HER2-mediated progression of gastric cancer.

Objective: The use of human epidermal growth factor receptor-2 (HER2) as a biomarker for gastric cancer (GC) has greatly helped some patients receive benefit from HER2-targeted therapy. However, the correlation between HER2 and other biochemical markers is unclear. The aim of this study was to examine the relationship between HER2 and lactate dehydrogenase A (LDHA) in GC tissues and GC cells.

DNA damage regulated autophagy modulator 1 recovers the function of apoptosis-stimulating of p53 protein 2 on inducing apoptotic cell death in Huh7.5 cells.

Overexpression of apoptosis-stimulating of p53 protein 2 (ASPP2) can induce apoptotic cell death in hepatoma cells, which contributes to a killing effect of ASPP2 on treating hepatocellular carcinoma (HCC). In the present study, ASPP2 overexpression failed to induce apoptotic cell death in the HCC Huh7.5 cell line, but promoted autophagy development by inhibiting AKT/mTOR pathway.

Overexpression of apoptosis-inducing factor mitochondrion-associated 1 (AIFM1) induces apoptosis by promoting the transcription of caspase3 and DRAM in hepatoma cells.

Full-length apoptosis-inducing factor mitochondrion-associated 1 (AIFM1) (∼67 kDa) induces apoptosis in a caspase-independent manner when it is cleaved at its N-terminus to produce truncated AIFM1 (∼57 kDa). Here, we produced recombinant adenovirus AIFM1 (rAd-AIFM1) encoding full-length AIFM1 to detect whether full-length AIFM1 suppresses cell growth and induces apoptosis of hepatoma cell lines (HepG2 and Hep3B). Hepatocellular carcinoma (HCC) is one of the most difficult cancers to treat worldwide.

Differential effects of reticulophagy and mitophagy on nonalcoholic fatty liver disease.

Autophagy affects the pathological progression of non-alcoholic fatty liver disease (NAFLD); however, the precise role of autophagy in NAFLD remains unclear. In this study, we want to identify the role of autophagy including reticulophagy and mitophagy in NAFLD pathogenesis. When HepG2 cells were treated with 400 μM oleic acid (OA), increased reticulophagy was induced 8 h after treatment, which correlated with an anti-apoptotic response as shown by the activation of the PI3K/AKT pathway, an increase in BCL-2 expression, and the downregulation of OA-induced lipotoxicity.

ASPP2 Inhibits the Profibrotic Effects of Transforming Growth Factor-β1 in Hepatic Stellate Cells by Reducing Autophagy.

Background: Apoptosis-stimulating protein of p53-2 (ASPP2) is a damage-inducible P53-binding protein that enhances damage-induced apoptosis. Fibrosis is a wound-healing response, and hepatic stellate cells (HSCs) are key players in liver fibrogenesis. However, little is known about the relationship between ASPP2 and hepatic fibrosis.

The Δ133p53 Isoform Reduces Wtp53-induced Stimulation of DNA Pol γ Activity in the Presence and Absence of D4T.

Unlabelled: The mitochondrial toxicity of nucleoside reverse transcriptase inhibitors (NRTIs) is due to the inhibition of mitochondrial DNA (mtDNA) polymerase γ (pol γ). Previous studies have shown that wild type p53 (wtp53) can interact with pol γ and mtDNA to enhance mitochondrial DNA base excision repair (mtBER) activity and increase the accuracy of DNA synthesis. The N-terminal transactivation domain and central specific DNA-binding domain of p53 play critical roles in the stimulation of BER.

Amphiregulin impairs apoptosis-stimulating protein 2 of p53 overexpression-induced apoptosis in hepatoma cells.

Overexpression of apoptosis-stimulating protein 2 of p53 (ASPP2) induces apoptotic cell death in hepatoma cells (e.g. HepG2 cells) by enhancing the transactivation activity of p53, but long-term ASPP2 overexpression fails to induce more apoptosis since activation of the epidermal growth factor/epidermal growth factor receptor/SOS1 pathway impairs the pro-apoptotic role of ASPP2.

RNA methyltransferase NSUN2 promotes stress-induced HUVEC senescence.

The tRNA methyltransferase NSUN2 delays replicative senescence by regulating the translation of CDK1 and CDKN1B mRNAs. However, whether NSUN2 influences premature cellular senescence remains untested. Here we show that NSUN2 methylates SHC mRNA in vitro and in cells, thereby enhancing the translation of the three SHC proteins, p66SHC, p52SHC, and p46SHC.