Role of Hypoxia in Mesenchymal Stem Cells from Dental Pulp: Influence, Mechanism and Application.

Mesenchymal stem cells (MSCs) from dental pulp (DP-MSCs), which include dental pulp stem cells (DPSCs) isolated from permanent teeth and stem cells from human exfoliated deciduous teeth (SHED), have emerged as highly promising cell sources for tissue regeneration, due to their high proliferative rate, multi-lineage differentiation capability and non-invasive accessibility. DP-MSCs also exert extensive paracrine effects through the release of extracellular vesicles (EVs) and multiple trophic factors. To be noted, the microenvironment, commonly referred to as the stem cell niche, plays a crucial role in shaping the functionality and therapeutic effects of DP-MSCs, within which hypoxia has garnered considerable attention. Extensive research has demonstrated that hypoxic conditions profoundly impact DP-MSCs. Specifically, hypoxia promotes DP-MSC proliferation, survival, stemness, migration, and pro-angiogenic potential while modulating their multi-lineage differentiation capacity. Furthermore, hypoxia stimulates the paracrine activities of DP-MSCs, leading to an increased production of EVs and soluble factors. Considering these findings, hypoxia preconditioning has emerged as a promising approach to enhance the therapeutic potential of DP-MSCs. In this comprehensive review, we provide a systematic overview of the influence of hypoxia on DP-MSCs, shedding light on the underlying mechanisms involved. Moreover, we also discuss the potential applications of hypoxia-preconditioned DP-MSCs or their secretome in tissue regeneration. Additionally, we delve into the methodologies employed to simulate hypoxic environments. This review aims to promote a comprehensive and systematic understanding of the hypoxia-induced effects on DP-MSCs and facilitate the refinement of regenerative therapeutic strategies based on DP-MSCs.

Hepatocyte Intrinsic Innate Antiviral Immunity against Hepatitis Delta Virus Infection: The Voices of Bona Fide Human Hepatocytes.

The pathogenesis of viral infection is attributed to two folds: intrinsic cell death pathway activation due to the viral cytopathic effect, and immune-mediated extrinsic cellular injuries. The immune system, encompassing both innate and adaptive immunity, therefore acts as a double-edged sword in viral infection. Insufficient potency permits pathogens to establish lifelong persistent infection and its consequences, while excessive activation leads to organ damage beyond its mission to control viral pathogens. The innate immune response serves as the front line of defense against viral infection, which is triggered through the recognition of viral products, referred to as pathogen-associated molecular patterns (PAMPs), by host cell pattern recognition receptors (PRRs). The PRRs-PAMPs interaction results in the induction of interferon-stimulated genes (ISGs) in infected cells, as well as the secretion of interferons (IFNs), to establish a tissue-wide antiviral state in an autocrine and paracrine manner. Cumulative evidence suggests significant variability in the expression patterns of PRRs, the induction potency of ISGs and IFNs, and the IFN response across different cell types and species. Hence, in our understanding of viral hepatitis pathogenesis, insights gained through hepatoma cell lines or murine-based experimental systems are uncertain in precisely recapitulating the innate antiviral response of genuine human hepatocytes. Accordingly, this review article aims to extract and summarize evidence made possible with bona fide human hepatocytes-based study tools, along with their clinical relevance and implications, as well as to identify the remaining gaps in knowledge for future investigations.

Strategies to enhance the ability of nerve guidance conduits to promote directional nerve growth.

Severely damaged peripheral nerves will regenerate incompletely due to lack of directionality in their regeneration, leading to loss of nerve function. To address this problem, various nerve guidance conduits (NGCs) have been developed to provide guidance for nerve repair. However, their clinical application is still limited, mainly because its effect in promoting nerve repair is not as good as autologous nerve transplantation. Therefore, it is necessary to enhance the ability of NGCs to promote directional nerve growth. Strategies include preparing various directional structures on NGCs to provide contact guidance, and loading various substances on them to provide electrical stimulation or neurotrophic factor concentration gradient to provide directional physical or biological signals.

Prognostic factors in patients with thymoma who underwent surgery.

PURPOSE: Thymoma is the most common primary tumor in the anterior mediastinum. The prognostic factors of patients with thymoma still need to be clarified. In this study, we aimed to investigate the prognostic factors of patients with thymoma who received radical resection and establish the nomogram to predict the prognosis of these patients. MATERIALS AND METHODS: Patients who underwent radical resection for thymoma with complete follow-up data between 2005 and 2021 were enrolled. Their clinicopathological characteristics and treatment methods were retrospectively analyzed. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared by the log-rank test. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify the independent prognostic factors. According to the results of the univariate analysis in the Cox regression model, the predictive nomograms were created. RESULTS: A total of 137 patients with thymoma were enrolled. With a median follow-up of 52 months, the 5-year and 10-year PFS rates were 79.5% and 68.1%, respectively. The 5-year and 10-year OS rates were 88.4% and 73.1%, respectively. Smoking status (P = 0.022) and tumor size (P = 0.039) were identified as independent prognostic factors for PFS. Multivariate analysis showed that a high level of neutrophils (P = 0.040) was independently associated with OS. The nomogram showed that the World Health Organization (WHO) histological classification contributed more to the risk of recurrence than other factors. Neutrophil count was the most important predictor of OS in patients with thymoma. CONCLUSION: Smoking status and tumor size are risk factors for PFS in patients with thymoma. A high level of neutrophils is an independent prognostic factor for OS. The nomograms developed in this study accurately predict PFS and OS rates at 5 and 10 years in patients with thymoma based on individual characteristics.

Biomarkers for Bile Acid Malabsorption in Diarrhea-predominant Irritable Bowel Syndrome: A Systematic Review and Meta-analysis.

BACKGROUND AND AIM: A clear relationship of biological indexes between bile acid malabsorption (BAM) and diarrhea-predominant irritable bowel syndrome (IBS-D) has not been well analyzed. This meta-analysis aimed to establish a more convenient method to diagnose BAM in IBS-D patients by comparing the differences in biomarkers between IBS-D patients and healthy people. METHODS: Multiple databases were searched for relevant case-control studies. Indicators used to diagnose BAM included 75 Se-homocholic acid taurine (SeHCAT), 7α-hydroxy-4-cholesten-3-one(C4), fibroblast growth factor-19 and 48-hour fecal bile acid (48FBA). The rate of BAM (SeHCAT) was calculated by using a random-effect model. The levels of C4, FGF19, and 48FBA were compared, and the overall effect size was combined by a fixed effect model. RESULTS: The search strategy identified 10 relevant studies comprising 1034 IBS-D patients and 232 healthy volunteers. The pooled rate of BAM in IBS-D patients was 32% (according to SeHCAT; 95% CI: 24%-40%). The level of C4 in IBS-D patients was significantly higher than that in the control group (2.86 ng/mL; 95% CI: 1.09, 4.63); The level of FGF19 was significantly lower than that in the control group (-33.97 pg/mL; 95% CI: -51.13, -16.82); The level of 48FBA was significantly higher than that in the control group (0.059; 95% CI: 0.41, 0.77). CONCLUSIONS: The results mainly concluded serum C4 and FGF19 levels in IBS-D patients. Most of the studies have different normal cutoff points of serum C4 and FGF19 levels; the performance of each test should be further estimated. By comparing the levels of these biomarkers, BAM in patients with IBS-D could be identified more accurately, which would lead to more effective treatment.

Prognostic microRNAs associated with phosphoserine aminotransferase 1 in gastric cancer as markers of bone metastasis.

This study analyzed PSAT1-targeted miRNAs as a prognostic predictor for gastric cancer. The relationship between the clinical manifestations of gastric cancer in patients and phosphoserine aminotransferase 1 (PSAT1) was analyzed using correlation analysis. PSAT1 was highly expressed in gastric cancer, and its low expression was associated with a poor prognosis. By pan-cancer analysis, PSAT1 could affect the tumor immune microenvironment by immune infiltration analysis. Nine microRNAs targeting PSAT1 and associated with gastric cancer were screened by miRwalk and microRNA expression in TCGA tumor tissues. Six microRNAs were obtained by survival curve analysis, including hsa-miR-1-3p, hsa-miR-139-5p, hsa-miR-145-5p, hsa-miR-195-5p, hsa-miR-218-5p, and hsa-miR-497-5p. Based on the above six microRNAs, a model for bone metastasis prediction in gastric cancer prediction was constructed. An analysis of a decision curve was performed based on the microRNAs obtained to predict bone metastasis from gastric cancer. It had a positive area under the curve (AUC) value of 0.746, and the decision curve analysis (DCA) indicated that it was clinically significant. Dual-luciferase reporter genes indicated that hsa-miR-497-5p and PSAT1 were targeted, and qRT-PCR results confirmed that hsa-miR-497-5p could down-regulate PSAT1 expression. MicroRNAs targeting the regulation of PSAT1 expression can well predict the prognosis of gastric cancer.

Konjac oligosaccharides attenuate DSS-induced ulcerative colitis in mice: mechanistic insights.

This study aims to explore the protective effect of konjac oligosaccharides (KOS) on inflammatory bowel disease in colitis mice. During the experimental period, mice were administered 200 mg kg-1 or 600 mg kg-1 KOS, 200 mg kg-1 sulfasalazine and a combination of KOS and sulfasalazine for 14 days. The mice were then treated with drinking water containing 2.5% DSS for 9 days, while the intervention of KOS and sulfasalazine continued. At the end of the experiment, the phenotype, pathological lesion of the colon, parameters of cytokines and gut microbiota were evaluated. The results showed that mice treated with KOS exhibited alleviated pathological lesion of the colon tissue and significantly increased expression of tight junction proteins (p < 0.05). The level of inflammatory cytokines in the colon tissue of the colitis mice tended to be normal. Moreover, the analysis of the gut microbiota revealed that the structures and composition of the intestinal microorganisms were also regulated by KOS treatment. The possible internal mechanism is that KOS down-regulates the abundance of pro-inflammatory bacteria (Proteobacteria, Campilobacterota and Clostridiaceae) and up-regulates the abundance of anti-inflammatory bacteria (Bifidobacteriaceae and Akkermansiaceae). These findings provide new insights into dietary management for patients with inflammatory bowel disease.

Transcriptome analysis of potential flocculation-related genes in Streptomyces sp. hsn06 with flocculation activity on Chlorella vulgaris biomass.

Chlorella vulgaris is a biomass energy provider with promising potential to help alleviate the energy crisis. Streptomyces sp. hsn06, as an actinomycete, can harvest C. vulgaris biomass safely and efficiently through flocculation activity, and proteins contribute greatly to the flocculation effect. However, potential flocculation protein-related genes are unclear. The mycelia of strain hsn06 after culture with glucose as the sole carbon source exhibited significantly higher flocculation activity as well as higher protein contents than those cultured with starch as the carbon source. To further explore the flocculation mechanism, the mycelia of strain hsn06 with distinct flocculation activities after culture with different carbon sources were examined by transcriptome analysis. We found that 403 genes were differentially up-regulated in mycelia cultured with glucose, compared to those cultured with starch as the carbon source. Five significantly differentially expressed protein-related genes were determined and confirmed by qRT-PCR, which indicated that three of the selected genes were potential flocculation-related genes. These results advance our understanding of potential flocculation-related genes during the harvesting of microalgal biomass.

Omega-3 index and type 2 diabetes: Systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: The relationship between omega-3 index and type 2 diabetes (T2D) is not well established. It is unclear if the change of omega-3 index will affect T2D. Aiming of the present systematic review was to elucidate the correlation between omega-3 index and T2D. METHODS AND STUDY DESIGN: A comprehensive search on PubMed, EMBASE and Web of Science (from 1948 to May 2021) was conducted. The overall effect size (standard mean difference) was combined using a random-effect model. RESULTS: Eight eligible case-control studies were identified, and there were 1,357 patients with T2D and 1,616 non-diabetic controls. The result showed that the omega-3 index was significantly lower in diabetic cases than that in controls (SMD= -1.31; 95% confidence interval (CI): -1.40, -1.22), but with significant heterogeneity (I2 = 99.0%). In subgroup analysis based on race, a negative correlation was found in Asians (SMD = -1.71; 95% CI: -1.82, -1.60), and heterogeneity was substantially decreased (I2=0). CONCLUSIONS: omega-3 index is negatively correlated with T2D, which indicated that increased dietary intake of omega-3 fatty acids might have beneficial on T2D prevention.

Prognostic factor analysis for patient outcome of PD-L1 expression in thoracic oesophageal squamous cell carcinoma.

OBJECTIVES: The purpose of this study was to determine the expression of PD-L1 in oesophageal squamous cell carcinoma (OSCC) and the prognostic factors. METHODS: PD-L1 expression was investigated by immunohistochemical staining of resected specimens from 50 OSCC patients who were randomly selected from 104 patients with complete follow-up data. The relationships among PD-L1 expression, clinicopathological factors and prognosis were assessed by statistical analysis. RESULTS: The expression of PD-L1 was positive in 27 (54%, positive cells' proportion > 25%) and negative in 23 (46%, positive cells proportion ≤25%) of 50 cases, and PD-L1 expression was negative in all pericarcinomatous tissues (P > 0.05). The 5-year survival rate of patients with PD-L1-positive expression was 22.2% (6 of 27), which was less than that of patients with PD-L1-negative expression (47.8%; 11 of 23) (P < 0.05). The results showed significant differences in the depth of tumour invasion, lymph node status, postoperative pathological stage and PD-L1 expression (P < 0.05). Multivariable analysis showed that PD-L1 expression was an independent prognostic factor for survival. CONCLUSIONS: The depth of tumour invasion, lymph node status, postoperative pathological stage and PD-L1 expression are important factors affecting the prognosis of patients with thoracic OSCC; in particular, high PD-L1 expression was a significant independent poor prognostic factor in thoracic OSCC patients.

The effect of sublethal concentrations of benzalkonium chloride on the LuxS/AI-2 quorum sensing system, biofilm formation and motility of Escherichia coli.

Escherichia coli can survive improper disinfection processes, which is a potential source of contamination of food products. Benzalkonium chloride (BC) is a common disinfectant widely used in food industry. Bacterial quorum sensing (QS) plays a major role in food spoilage, biofilm formation and food-related pathogenesis. Understanding QS can help to control the growth of undesirable food-related bacteria. The LuxS/AI-2 QS system of E. coli has been confirmed to regulate many important phenotypes including biofilm formation and motility. In the current study, we aimed to investigate the effect of sublethal concentrations of BC on the LuxS/AI-2 system of E. coli isolates from retail meat samples, as well as bacterial biofilm formation and motility. Our results showed that sublethal concentrations of BC promoted AI-2 production in four test E. coli isolates. The results from microplate assay and confocal laser scanning microscopy (CLSM) analysis indicated that sublethal concentrations of BC enhanced biofilm formation of E. coli. When treated with sublethal concentrations of BC, exopolysaccharides (EPS) production during biofilm development increased significantly and swimming motility of tested isolates was also promoted. The expression levels of luxS, biofilm-associated genes and flagellar motility genes were increased by BC at sublethal concentrations. Our findings underline the importance of proper use of the disinfectant BC in food processing environments to control food contamination by E. coli.

Characteristics of surface water quality and stable isotopes in Bamen Bay watershed, Hainan Province, China.

Bamen Bay is located at the intersection of the Wenjiao River and Wenchang River in Hainan Province (China), where mangroves have been facing a threat of water quality deterioration. Therefore, it is imperative to study the characteristics of the surface water quality on a watershed scale. Water samples were collected three times from 36 monitoring sites from 2015 to 2016. It was found that nitrate was the main inorganic nitrogen form and all the surface water types were alkaline. Meanwhile, aquaculture water had high content of nitrogen, total phosphorus, chlorophyll a (Chl.a), total organic carbon (TOC), and chemical oxygen demand (COD). Significant spatial and temporal variations were found for most parameters. However, stable isotopes of δD and δ18O indicated that river water mainly originated from atmospheric precipitation and experienced strong evaporation. The water chemistry and isotopes of the Bamen Bay, mangroves, and aquaculture water were initially affected by the mixing of fresh water and seawater, followed by evaporation. The river and reservoir water chemistry were mainly controlled by water-rock interactions and cation exchange as deduced from the ionic relationships and Gibbs plots. These interactions involved the dissolution of calcite-, bicarbonate-, carbonate-, and calcium-containing minerals. Oxidized environments (river, reservoir, and Bamen Bay) were conducive for nitrification, while anaerobic conditions (mangrove and aquaculture water) were beneficial to the reduced nitrogen forms.

Learning curve associated with thoraco-laparoscopic esophagectomy for esophageal cancer patients in the prone position.

OBJECTIVE: To observe the surgical index at the different learning stages of thoraco-laparoscopic esophagectomy in the prone position for esophageal cancer and to investigate the learning curve of this surgical procedure. METHODS: Sixty thoraco-laparoscopic esophagectomies in the prone position for esophageal cancer conducted by the same group of surgeons between January 2014 and December 2015 were retrospectively analyzed. The surgeries were divided into 5 groups, A, B, C, D, and E, in chronological order. The duration of surgery, intraoperative blood loss, total number of lymph nodes removed, rate of the intraoperative conversion to open surgery, complication rate, and length of postoperative hospitalization were recorded and analyzed. RESULTS: The general information of the patients did not significantly differ among the 5 groups (P > 0.05). The duration of surgery, intraoperative blood loss, number of lymph node removed, rate of intraoperative conversion to open surgery, and number of injuries to the recurrent laryngeal nerve all significantly differed (P < 0.05). The rates of postoperative pulmonary infection, anastomotic fistula, pneumothorax, and hospitalization did not significantly differ (P > 0.05). CONCLUSION: Thoracic physicians with some endoscopic experience can meet the requirements of the thoraco-laparoscopic esophagectomy in the prone position for esophageal cancer after completing 24-30 surgeries.

Remediation of Crude Oil-Polluted Soil by the Bacterial Rhizosphere Community of Suaeda salsa Revealed by 16S rRNA Genes.

Crude oil pollution of soil is a serious environmental issue, and bioremediation using plants and microorganisms is a natural and sustainable method for its restoration. Pot incubation of a two-factor randomized block (plants with two levels, and crude oil with three levels) was designed to investigate the rhizosphere bacterial community of Suaeda salsa (L.) Pall. Crude oil contamination of soil was studied at different levels: 2 g/kg (low), 4 g/kg (medium), and 6 g/kg (high) levels. In this study, the physicochemical properties of the collected rhizosphere soil were analyzed. Moreover, the soil bacteria were further identified using the 16S rRNA gene. The effects of S. salsa and crude oil and their interaction on the physiochemical properties of the soil and crude oil degradation were found to be significant. Crude oil significantly influenced the diversity and evenness of bacteria, while the effects of S. salsa and interaction with crude oil were not significant. Proteobacteria were found to be dominant at the phylum level. Meanwhile, at the genera level, Saccharibacteria and Alcanivorax increased significantly in the low and medium contamination treatment groups with S. salsa, whereas Saccharibacteria and Desulfuromonas were prevalent in the high contamination treatment group. High crude oil contamination led to a significant decrease in the bacterial diversity in soil, while the effects of S. salsa and its interaction were not significant. Despite the highest abundance of crude oil degradation bacteria, S. salsa reduced crude oil degradation bacteria and increased bacteria related to sulfur, phosphorus, and nitrogen cycling in the low and high contamination group, whereas the opposite effect was observed for the medium contamination treatment group. The abundance of most crude oil degradation bacteria is negatively correlated with crude oil content. Nitrogen cycling bacteria are sensitive to the total nitrogen, total phosphorus, ammonia nitrogen, and nitrate nitrogen, and pH of the soil. Sulfur cycling bacteria are sensitive to aromatic hydrocarbons, saturated hydrocarbons, and asphaltene in soil. This research is helpful for further studying the mechanism of synergistic degradation by S. salsa and bacteria.

Autophagy protects gastric mucosal epithelial cells from ethanol-induced oxidative damage via mTOR signaling pathway.

Alcohol abuse is an important cause of gastric mucosal epithelial cell injury and gastric ulcers. A number of studies have demonstrated that autophagy, an evolutionarily conserved cellular mechanism, has a protective effect on cell survival. However, it is not known whether autophagy can protect gastric mucosal epithelial cells against the toxic effects of ethanol. In the present study, gastric mucosal epithelial cells (GES-1 cells) and Wistar rats were treated with ethanol to detect the adaptive response of autophagy. Our results demonstrated that ethanol exposure induced gastric mucosal epithelial cell damage, which was accompanied by the downregulation of mTOR signaling pathway and activation of autophagy. Suppression of autophagy with pharmacological agents resulted in a significant increase of GES-1 cell apoptosis and gastric mucosa injury, suggesting that autophagy could protect cells from ethanol toxicity. Furthermore, we evaluated the cellular oxidative stress response following ethanol treatment and found that autophagy induced by ethanol inhibited generation of reactive oxygen species and degradation of antioxidant and lipid peroxidation. In conclusion, these findings provide evidence that ethanol can activate autophagy via downregulation of the mTOR signaling pathway, serving as an adaptive mechanism to ameliorate oxidative damage induced by ethanol in gastric mucosal epithelial cells. Therefore, modifying autophagy may provide a therapeutic strategy against alcoholic gastric mucosa injury. Impact statement The effect and mechanism of autophagy on ethanol-induced cell damage remain controversial. In this manuscript, we report the results of our study demonstrating that autophagy can protect gastric mucosal epithelial cells against ethanol toxicity in vitro and in vivo. We have shown that ethanol can activate autophagy via downregulation of the mTOR signaling pathway, serving as an adaptive mechanism to ameliorate ethanol-induced oxidative damage in gastric mucosal epithelial cells. This study brings new and important insights into the mechanism of alcoholic gastric mucosal injury and may provide an avenue for future therapeutic strategies.

[Contamination and Ecological Risk Assessment of Mercury in Hengshuihu Wetland, Hebei Province].

Investigation on the concentrations and the distribution characteristics of total mercury in atmosphere, water surface and soil/ sediments of Hengshuihu wetland was carried out based on a uniform set point sampling method. The geoaccumulation index and potential ecological risk index methods were simultaneously used to assess the mercury pollution in Hengshuihu wetland ecosystem. The results showed that: the total mercury content in Hengshuihu wetland atmosphere ranged from 1.0 to 5.0 ng · m⁻³, with an average of (2.9 ± 0.85) ng · m⁻³; the total mercury content in water surface ranged from 0.010 to 0.57 µg · L⁻¹, with the average value of (0.081 ± 0.053) µg · L⁻¹; the total mercury content in soil/sediment ranged from 0.001 0 to 0.058 mg · kg⁻¹, with an average of (0.027 ± 0.013) mg · kg⁻¹. The distribution features of total mercury in Hengshuihu wetland were as follows: the total mercury concentration in surface water of the shore was significantly higher than that in the center (P < 0.05), but the total mercury concentration of sediments in the center of the lake was significantly higher than that at the shore (P < 0.05); the total mercury in the soil of shore had a consistent trend with that in the atmosphere; high concentrations of total mercury pollution were accompanied by severe human activities. The geoaccumulation index showed that mercury pollution in Hengshuihu wetland was at clean level; potential ecological risk index showed mercury contamination had a low ecological risk in Hengshuihu wetland.

Monoacylglycerol lipase inhibitor JZL184 regulates apoptosis and migration of colorectal cancer cells.

Monoacylglycerol lipase (MAGL) is involved in the degradation of triacylglycerol. Previous studies have demonstrated that MAGL regulates tumor growth and metastasis via fatty acid networks, and is associated with colorectal cancer. JZL184 is a MAGL inhibitor, which in the present study was administered to colorectal cancer cell lines, resulting in decreased tumor proliferation, increased apoptosis and increased tumor cell sensitivity to 5-fluorouracil. B­cell lymphoma 2 (Bcl­2) and Bcl­2­associated X protein (Bax) are key proteins in apoptosis. The expression levels of Bcl­2/Bax were determined in colorectal cancer cell lines following JZL184 administration, and it was observed that the mRNA and protein expression levels of Bcl­2 were decreased, whereas the expression levels of Bax were increased. These results indicated that JZL184 may induce tumor cell apoptosis by regulating the expression of Bcl­2 and Bax. Epithelial-mesenchymal transition (EMT) is closely associated with metastasis. Administration of JZL184 in various malignant colorectal cancer cell lines suppressed migration and altered the expression of EMT markers; E­cadherin was increased, whereas the expression levels of vimentin and zinc finger protein SNAI1 were decreased. These results suggested that JZL184 was able to regulate the EMT process, in order to control the migration of colorectal cancer cells, particularly in tumors with a stronger metastatic capability. Therefore, in colorectal cancer, MAGL may be considered a potential therapeutic target and JZL184 may be a possible therapeutic agent.

Maresin 1 Mitigates Inflammatory Response and Protects Mice from Sepsis.

Sepsis, frequently caused by infection of bacteria, is considered as an uncontrollable systematic inflammation response syndrome (SIRS). Maresin 1 (Mar1) is a new proresolving mediator with potent anti-inflammatory effect in several animal models. However, its effect in sepsis is still not investigated. To address this question, we developed sepsis model in BALB/c mice by cecal ligation and puncture (CLP) with or without Mar1 treatment. Our data showed that Mar1 markedly improved survival rate and decreased the levels of proinflammatory cytokines in CLP mice such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß). Furthermore, Mar1 reduced serum level of lipopolysaccharide (LPS) and enhanced the bacteria clearance in mice sepsis model. Moreover, Mar1 attenuated lung injury and decreased level of alanine transaminase (ALT), aspartate transaminase (AST), creatinine (Cre), and blood urea nitrogen (BUN) in serum in mice after CLP surgery. Treatment with Mar1 inhibited activation of nuclear factor kappa B (NF-κb) pathway. In conclusion, Mar1 exhibited protective effect in sepsis by reducing LPS, bacteria burden in serum, inhibiting inflammation response, and improving vital organ function. The possible mechanism is partly involved in inhibition of NF-κb activation.

Inhibiting enhancer of zeste homolog 2 promotes cellular senescence in gastric cancer cells SGC-7901 by activation of p21 and p16.

Cellular senescence, which can be defined as a stress response preventing the propagation of cells that have accumulated potentially oncogenic alterations, is invariably associated with a permanent cell cycle arrest. Enhancer of zeste homolog 2 (EZH2) as a member of polycomb group proteins and its targets include cell cycle regulatory proteins, which govern cell cycle progression and cellular senescence. In this study, we report that EZH2 depletion promotes the senescent state in human gastric cancer cells SGC-7901. We found that EZH2 functionally suppressed the senescent state in human gastric cancer cells SGC-7901. EZH2 depletion inhibited cell proliferation, arrested cellular cycle, restored features of a cellular senescence phenotype, and promoted doxorubicin-induced senescence. To prove that EZH2 expression contributes substantially to the change of key cell cycle regulators, we showed that p21 and p16 were activated to a certain extent upon EZH2 depletion and activation of p21 was in a p53-independent manner. Taken together, our data suggest that EZH2 depletion promotes the progression of senescence by mediating the activation of tumor suppressor genes p21 and p16, and could serve as a potential epigenetic target for gastric cancer therapy.