Matrix metalloproteinase-8 regulates dendritic cell tolerance in late polymicrobial sepsis via the nuclear factor kappa-B p65/β-catenin pathway.

Background: Tolerogenic dendritic cells (DCs) are associated with poor prognosis of sepsis. Matrix metalloproteinases (MMPs) have been shown to have immunomodulatory effects. However, whether MMPs are involved in the functional reprogramming of DCs is unknown.

Risk model for predicting mortality in patients with necrotizing soft tissue infections in the intensive care unit.

Background: The goal of this study is to look into the factors that lead to death in patients with necrotizing soft tissue infections（NSTIs） in the intensive care unit and create a mortality risk model.

Methods: The clinical data of 106 patients with necrotizing soft tissue infections admitted to intensive care unit(ICU) of the First Affiliated Hospital of Wenzhou Medical University between January 2008 and December 2021 were retrospectively analyzed. Univariate analysis and multivariate analysis were performed to evaluate the risk factors impacting patient mortality.

SUPPLEMENTATION WITH NICOTINAMIDE RIBOSIDE ATTENUATES T CELL EXHAUSTION AND IMPROVES SURVIVAL IN SEPSIS.

T cell exhaustion is the main cause of sepsis-induced immunosuppression and is associated with the poor prognosis. Nicotinamide adenine dinucleotide (NAD + ) is well known for its anti-aging effect, but its role in sepsis-induced T cell exhaustion remains to be elucidated. In the present study, using a classic septic animal model, we found that the levels of NAD + and its downstream molecule, which is sirtuins 1 (SIRT1), in T cells in sepsis were decreased.

Mutual promotion of mitochondrial fission and oxidative stress contributes to mitochondrial-DNA-mediated inflammation and epithelial-mesenchymal transition in paraquat-induced pulmonary fibrosis.

Background: Pulmonary fibrosis (PF) is one of the main causes of death in patients with paraquat (PQ) poisoning. This study aimed to evaluate the relationship between mitochondrial fission and oxidative stress in PQ-induced epithelial-mesenchymal transition (EMT) and PF.

Methods: C57BL/6 mice and MLE-12 cells were exposed to PQ to construct a PF model and .

Vesicle transport related protein Synaptotagmin-1 mediates paraquat transport to antagonize paraquat toxicity.

In this study, A549/PQ cells with moderate resistance to paraquat (PQ) were obtained by treating A549 cells with PQ, their growth rate was slowed down, the accumulation concentration of PQ and the levels of growth inhibition, injury and early apoptosis induced by PQ were significantly lower than those of parental A549 cells. Microarray screening and RT-qPCR detection found that Synaptotagmin-1 (SYT1) expression in drug-resistant cells was significantly increased, and PQ further enhanced its expression. After inhibiting SYT1 expression in A549/PQ cells, cell viability, intracellular PQ concentration and the expression of Bcl-2, SNAP25 and RAB26 were significantly reduced, while the mortality, early apoptosis rate and Bax expression were significantly increased.

CD71 Erythroid Cell Expansion in Adult Sepsis: Potential Causes and Role in Prognosis and Nosocomial Infection Prediction.

Background: Immune suppression contributes to nosocomial infections (NIs) and poor prognosis in sepsis. Recent studies revealed that CD71 erythroid cells had unappreciated immunosuppressive functions. This study aimed to investigate the values of CD71 erythroid cells (CECs) in predicting NIs and prognosis among adult septic patients.

Astaxanthin Ameliorates Blood Pressure in Salt-Induced Prehypertensive Rats Through ROS/MAPK/NF-κB Pathways in the Hypothalamic Paraventricular Nucleus.

Astaxanthin (AST) has a variety of biochemical effects, including anti-inflammatory, antioxidative, and antihypertensive functions. The aim of the present study was to determine whether AST ameliorates blood pressure in salt-induced prehypertensive rats by ROS/MAPK/NF-κB pathways in hypothalamic paraventricular nucleus.To explore the central effects of AST on the development of blood pressure, prehypertensive rats were induced by a high-salt diet (HS, 8% NaCl) and its control groups were treated with normal-salt diet (NS, 0.

Long non-coding RNA ARHGAP5-AS1 inhibits migration of breast cancer cell via stabilizing SMAD7 protein.

Purpose: Tumor metastasis is the main cause of death from breast cancer patients and cell migration plays a critical role in cancer metastasis. Recent studies have shown long non-coding RNAs (lncRNAs) play an essential role in the initiation and progression of cancer. In the present study, the role of an LncRNA, Rho GTPase Activating Protein 5- Antisense 1 (ARHGAP5-AS1) in breast cancer was investigated.

Hypoxia activated long non-coding RNA HABON regulates the growth and proliferation of hepatocarcinoma cells by binding to and antagonizing HIF-1 alpha.

The adaptation of tumour cells to hypoxic microenvironment is one of the most significant characteristics of many malignant tumour diseases including hepatocarcinoma. Recently, long non-coding RNAs (lncRNAs) have been reported to play important roles in the various levels of gene regulation thus functioning in growth and survival of tumour cells. Here, new hypoxia-related lncRNAs in hepatocarcinoma cells were screened and validated by lncRNA chip-array as well as real-time RT-PCR.

Arterial oxygen pressure targets in critically ill patients: Analysis of a large ICU database.

Background: Providing supplemental oxygen is common in the management of critically ill patients, yet the optimal oxygen regimen remains unclear.

Objectives: To explore the optimal range of PaO in critically ill patients.

Methods: This is a retrospective study conducted in the Medical Information Mart for Intensive Care III (MIMIC-III) database.

MiR-133b targets Sox9 to control pathogenesis and metastasis of breast cancer.

The miR-133b, a commonly recognized muscle-specific miRNA, was reported to be deregulated in many kinds of cancers. However, its potential roles in tumorigenesis remain greatly elusive. Herein, we demonstrate that miR-133b is significantly suppressed in human breast cancer specimens, which is reversely correlated to histological grade of the cancer.

Partial Depletion of Regulatory T Cells Enhances Host Inflammatory Response Against Acute Pseudomonas aeruginosa Infection After Sepsis.

Immune dysfunction contributes to secondary infection and worse outcomes in sepsis. Regulatory T cells (Tregs) have been implicated in sepsis-induced immunosuppression. Nevertheless, the role of Tregs in secondary infection after sepsis remains to be determined.

MicroRNA-630 inhibits breast cancer progression by directly targeting BMI1.

MicroRNAs (miRNAs) play critical roles in breast cancer cell biological processes, including proliferation and apoptosis by inhibiting the expression of their target genes. Herein, we reported that miR-630 overexpression initiates apoptosis, blocks cell cycle progression and suppresses cell proliferation in breast cancer cells. Furthermore, BMI1, a member of polycomb group family, was identified as a direct target of miR-630, and there was a negative correlation between the expression levels of BMI1 and miR-630 in human breast cancer samples.

Ethyl pyruvate reverses development of Pseudomonas aeruginosa pneumonia during sepsis-induced immunosuppression.

Sepsis is characterized by an innate immune response and the following immune dysfunction which can increase the emergence of secondary infections. Ethyl pyruvate (EP) has multiple immunoregulation functions in several serious illnesses, such as burn injury, severe sepsis and acute respiratory syndrome. However, little data was shown the effect of EP administration on immunosuppression post-CLP and the following secondary infection.

Growth Arrest-Specific 6 Enhances the Suppressive Function of CD4CD25 Regulatory T Cells Mainly through Axl Receptor.

Growth arrest-specific (Gas) 6 is one of the endogenous ligands of TAM receptors (Tyro3, Axl, and Mertk), and its role as an immune modulator has been recently emphasized. Naturally occurring CD4CD25 regulatory T cells (Tregs) are essential for the active suppression of autoimmunity. The present study was designed to investigate whether Tregs express TAM receptors and the potential role of Gas6-TAM signal in regulating the suppressive function of Tregs.

MicroRNA-494 inhibits breast cancer progression by directly targeting PAK1.

MicroRNA (miRNA) is involved in the progression and metastasis of diverse human cancers, including breast cancer, as strong evidence has been found that miRNAs can act as oncogenes or tumor suppressor genes. Here, we show that miR-494 is decreased in human breast cancer specimens and breast cancer cell lines. Ectopic expression of miR-494 in basal-like breast cancer cell lines MDA-MB-231-LUC-D2H3LN and BT-549 inhibits clonogenic ability and metastasis-relevant traits in vitro.

Design, synthesis and biological evaluation of novel benzo-α-pyrone containing piperazine derivatives as potential BRAF inhibitors.

The increasingly acquired resistance to vemurafenib and side effects of known inhibitors motivate the search for new and more effective anti-melanoma drugs. In this Letter, virtual screening and scaffold growth were combined together to achieve new molecules as BRAF inhibitors. Along with docking simulation, a primary screen in vitro was performed to filter the modifications for the lead compound, which was then substituted, synthesized and evaluated for their inhibitory activity against BRAF and several melanoma cell lines.

Metronidazole containing pyrazole derivatives potently inhibit tyrosyl-tRNA synthetase: design, synthesis, and biological evaluation.

As an important enzyme in bacterial protein biosynthesis, tyrosyl-tRNA synthetase (TyrRS) has been an absorbing therapeutic target for exploring novel antibacterial agents. A series of metronidazole-based antibacterial agents has been synthesized and identified as TyrRS inhibitors with low cytotoxicity and significant antibacterial activity, especially against Gram-negative organisms. Of the compounds obtained, 4f is the most potent agent which inhibited the growth of Pseudomonas aeruginosa ATCC 13525 (MIC = 0.

Design, synthesis and biological evaluation of pyrazolyl-nitroimidazole derivatives as potential EGFR/HER-2 kinase inhibitors.

A series of novel pyrazole-nitroimidazole derivatives had been arranged and evaluated for their EGFR/HER-2 tyrosine kinase inhibitory activity as well as their antiproliferative properties on four kinds of cancer cell lines (MCF-7, Hela, HepG2, B16-F10). The bioassay results showed most of the designed compounds exhibited potential antiproliferation activity, with the IC50 values ranging from 0.13μM to 128.

MiR-630 suppresses breast cancer progression by targeting metadherin.

MicroRNAs have been integrated into tumorigenic programs as either oncogenes or tumor suppressor genes. The miR-630 was reported to be deregulated and involved in tumor progression of several human malignancies. However, its expression regulation shows diversity in different kinds of cancers and its potential roles remain greatly elusive.

Protective Effects of Growth Arrest-Specific Protein 6 (Gas6) on Sepsis-Induced Acute Kidney Injury.

Acute kidney injury (AKI) is a serious complication of sepsis, which has a high mortality rate. Growth arrest-specific protein 6 (Gas6), the protein product of the growth arrest specific gene 6, has been shown to have an anti-apoptotic effect as well as pro-survival capability. Here, we investigated the effects of Gas6 on sepsis-associated AKI in mice subjected to cecal ligation and puncture (CLP).

Sulfonamide derivatives containing dihydropyrazole moieties selectively and potently inhibit MMP-2/MMP-9: Design, synthesis, inhibitory activity and 3D-QSAR analysis.

New series of sulfonamide derivatives containing a dihydropyrazole moieties inhibitors of MMP-2/MMP-9 were discovered using structure-based drug design. Synthesis, antitumor activity, structure-activity relationship and optimization of physicochemical properties were described. In vitro the bioassay results revealed that most target compounds showed potent inhibitory activity in the enzymatic and cellular assays.

Design, synthesis, biological evaluation and molecular modeling of dihydropyrazole sulfonamide derivatives as potential COX-1/COX-2 inhibitors.

Novel dihydropyrazole sulfonamide derivatives (30-56) were designed, synthesized, and evaluated for their biological activities as COX-1 and COX-2 inhibitors. In vitro biological evaluation against three human tumor cell lines revealed that most target compounds showed antiproliferative activities. Among the compounds, compound 48 exhibited the most potent and selective COX-2 inhibitor (COX-2 IC50=0.