Sediment pollutant exposures caused hepatotoxicity and disturbed glycogenesis.

Liver metabolic syndrome, which involves impaired hepatic glycogen synthesis, is persistently increased by exposure to environmental pollutants. Most studies have investigated the pathogenesis of liver damage caused by single metal species or pure organics. However, under normal circumstances, the pollutants that we are exposed to are usually chemical mixtures that accumulate over time. Sediments are long-term repositories for environmental pollutants due to their environmental cycles, which make them good samples for evaluating the effect of environmental pollutants on the liver via bioaccumulation. This study aimed to clarify the effects of sediment pollutants on liver damage. Our results indicate that industrial wastewater sediment (downstream) is more cytotoxic than sediments from other zones. Downstream sediment extract (DSE) causes hepatotoxicity, stimulates reactive oxygen species (ROS) generation, triggers mitochondrial dysfunction, induces cell apoptosis, and results in the release of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) proteins. Additionally, to elucidate the underlying mechanism by which sediment pollutants disturb hepatic glycogen synthesis, we investigated the effects of different sediment samples from different pollution situations on glycogen synthesis in liver cell lines. It was found that DSE induced multiple severe impairments in liver cells, and disturbed glycogen synthesis more than under other conditions. These impairments include decreased hepatic glycogen synthesis via inhibition and insulin receptor substrate 1 (IRS-1) /AKT /glycogen synthase kinase3ß (GSK3ß)-mediated glycogen synthase (GYS) inactivation. To our knowledge, this study provides the first detailed evidence of in vitro sediment-accumulated toxicity that interferes with liver glycogen synthesis, leading to hepatic cell damage through apoptosis.

Nuclear accumulation of KPNA2 impacts radioresistance through positive regulation of the PLSCR1-STAT1 loop in lung adenocarcinoma.

Lung adenocarcinoma (ADC) is the predominant histological type of lung cancer, and radiotherapy is one of the current therapeutic strategies for lung cancer treatment. Unfortunately, biological complexity and cancer heterogeneity contribute to radioresistance development. Karyopherin α2 (KPNA2) is a member of the importin α family that mediates the nucleocytoplasmic transport of cargo proteins. KPNA2 overexpression is observed across cancer tissues of diverse origins. However, the role of KPNA2 in lung cancer radioresistance is unclear. Herein, we demonstrated that high expression of KPNA2 is positively correlated with radioresistance and cancer stem cell (CSC) properties in lung ADC cells. Radioresistant cells exhibited nuclear accumulation of KPNA2 and its cargos (OCT4 and c-MYC). Additionally, KPNA2 knockdown regulated CSC-related gene expression in radioresistant cells. Next-generation sequencing and bioinformatic analysis revealed that STAT1 activation and nuclear phospholipid scramblase 1 (PLSCR1) are involved in KPNA2-mediated radioresistance. Endogenous PLSCR1 interacting with KPNA2 and PLSCR1 knockdown suppressed the radioresistance induced by KPNA2 expression. Both STAT1 and PLSCR1 were found to be positively correlated with dysregulated KPNA2 in radioresistant cells and ADC tissues. We further demonstrated a potential positive feedback loop between PLSCR1 and STAT1 in radioresistant cells, and this PLSCR1-STAT1 loop modulates CSC characteristics. In addition, AKT1 knockdown attenuated the nuclear accumulation of KPNA2 in radioresistant lung cancer cells. Our results collectively support a mechanistic understanding of a novel role for KPNA2 in promoting radioresistance in lung ADC cells.

Proteomic and microbial assessments on the effect of Antrodia cinnamomea in C57BL/6 mice.

Antrodia cinnamomea (AC) is a nutraceutical fungus and studies have suggested that AC has the potential to prevent or alleviate diseases. However, little is known about the AC-induced phenotypes on the intestine-liver axis and gut microbial alterations. Here, we performed two-dimensional difference gel electrophoresis (2D-DIGE) and MALDI-Biotyper to elaborate the AC-induced phenotypes on the intestine-liver axis and gut microbial distribution of C57BL/6 mice. The experimental outcomes showed that the hepatic density may increase by elevating hepatic redox regulation, lipid degradation and glycolysis-related proteins and alleviating cholesterol biosynthesis and transport-related proteins in C57BL/6 mice with AC treatment. Moreover, AC facilitates intestinal glycolysis, TCA cycle, redox and cytoskeleton regulation-related proteins, but also reduces intestinal vesicle transport-related proteins in C57BL/6 mice. However, the body weight, GTT, daily food/water intake, and fecal/urine weight were unaffected by AC supplementation in C57BL/6 mice. Notably, the C57BL/6-AC mice had a higher gut microbial abundance of Alistipes shahii (AS) than C57BL/6-Ctrl mice. In summary, the AC treatment affects intestinal permeability by regulating redox and cytoskeleton-related proteins and elevates the gut microbial abundance of AS in C57BL/6 mice that might be associated with increasing hepatic density and metabolism-related proteins of the liver in C57BL/6 mice. Our study provides an insight into the mechanisms of AC-induced phenotypes and a comprehensive assessment of AC's nutraceutical effect in C57BL/6 mice.

Targeting UDP-glucose dehydrogenase inhibits ovarian cancer growth and metastasis.

More than 70% of patients with ovarian cancer are diagnosed in advanced stages. Therefore, it is urgent to identify a promising prognostic marker and understand the mechanism of ovarian cancer metastasis development. By using proteomics approaches, we found that UDP-glucose dehydrogenase (UGDH) was up-regulated in highly metastatic ovarian cancer TOV21G cells, characterized by high invasiveness (TOV21GHI ), in comparison to its parental control. Previous reports demonstrated that UGDH is involved in cell migration, but its specific role in cancer metastasis remains unclear. By performing immunohistochemical staining with tissue microarray, we found overexpression of UGDH in ovarian cancer tissue, but not in normal adjacent tissue. Silencing using RNA interference (RNAi) was utilized to knockdown UGDH, which resulted in a significant decrease in metastatic ability in transwell migration, transwell invasion and wound healing assays. The knockdown of UGDH caused cell cycle arrest in the G0 /G1 phase and induced a massive decrease of tumour formation rate in vivo. Our data showed that UGDH-depletion led to the down-regulation of epithelial-mesenchymal transition (EMT)-related markers as well as MMP2, and inactivation of the ERK/MAPK pathway. In conclusion, we found that the up-regulation of UGDH is related to ovarian cancer metastasis and the deficiency of UGDH leads to the decrease of cell migration, cell invasion, wound healing and cell proliferation ability. Our findings reveal that UGDH can serve as a prognostic marker and that the inhibition of UGDH is a promising strategy for ovarian cancer treatment.

Progesterone receptor membrane component 1 is involved in oral cancer cell metastasis.

Cancer metastasis is a common cause of failure in cancer therapy. However, over 60% of oral cancer patients present with advanced stage disease, and the five-year survival rates of these patients decrease from 72.6% to 20% as the stage becomes more advanced. In order to manage oral cancer, identification of metastasis biomarker and mechanism is critical. In this study, we use a pair of oral squamous cell carcinoma lines, OC3, and invasive OC3-I5 as a model system to examine invasive mechanism and to identify potential therapeutic targets. We used two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF/TOF MS) to examine the global protein expression changes between OC3 and invasive OC3-I5. A proteomic study reveals that invasive properties alter the expression of 101 proteins in OC3-I5 cells comparing to OC3 cells. Further studies have used RNA interference technique to monitor the influence of progesterone receptor membrane component 1 (PGRMC1) protein in invasion and evaluate their potency in regulating invasion and the mechanism it involved. The results demonstrated that expression of epithelial-mesenchymal transition (EMT) markers including Twist, p-Src, Snail1, SIP1, JAM-A, vimentin and vinculin was increased in OC3-I5 compared to OC3 cells, whereas E-cadherin expression was decreased in the OC3-I5 cells. Moreover, in mouse model, PGRMC1 is shown to affect not only migration and invasion but also metastasis in vivo. Taken together, the proteomic approach allows us to identify numerous proteins, including PGRMC1, involved in invasion mechanism. Our results provide useful diagnostic markers and therapeutic candidates for the treatment of oral cancer invasion.

Identification of hyperglycemia-associated microbiota alterations in saliva and gingival sulcus.

Oral microbes are a contributing factor to hyperglycemia by inducing an increase in insulin resistance resulting in uncontrolled blood glucose levels. However, the relationship between the distribution of oral flora and hyperglycemia is still controversial. Combining the power of MALDI-Biotyper with anaerobic bacterial culture, this study explores the correlation between anaerobic bacteria in the oral cavity and blood glucose levels. The results demonstrated that altered blood glucose levels contributed to a varied bacterial distribution in the oral cavity. Specifically, Veillonella spp. and Prevotella spp. were identified in a higher proportion in people with elevated blood glucose levels. Six bacterial species identified in this study (Prevotella melaninogenica, Campylobacter rectus, Streptococcus gordonii, Streptococcus mitis, Streptococcus salivarius, and Veillonella parvula) not only demonstrated a positive association with higher blood glucose levels, but also likely contribute to the development of the condition. The data demonstrated MALDI-TOF MS to be a simpler, faster, and more economical clinical identification tool that provides clarity and depth to the research on blood glucose and oral microbiota.

The Role of Transforming Growth Factor-Beta in Retinal Ganglion Cells with Hyperglycemia and Oxidative Stress.

A characteristic of diabetes mellitus is hyperglycemia, which is considered with an emphasis on the diabetic retinopathy of progressive neurodegenerative disease. Retinal ganglion cells (RGCs) are believed to be important cells affected in the pathogenesis of diabetic retinopathy. Transforming growth factor-beta (TGF-ß) is a neuroprotective protein that helps to withstand various neuronal injuries. To investigate the potential roles and regulatory mechanisms of TGF-ß in hyperglycemia-triggered damage of RGCs in vitro, we established RGCs in 5.5, 25, 50, and 100 mM D-glucose supplemented media and focused on the TGF-ß-related oxidative stress pathway in combination with hydrogen peroxide (H2O2). Functional experiments showed that TGF-ß1/2 protein expression was upregulated in RGCs with hyperglycemia. The knockdown of TGF-ß enhanced the accumulation of reactive oxygen species (ROS), inhibited the cell proliferation rate, and reduced glutathione content in hyperglycemia. Furthermore, the results showed that the TGF-ß-mediated enhancement of antioxidant signaling was correlated with the activation of stress response proteins and the antioxidant pathway, such as aldehyde dehydrogenase 3A1 (ALDH3A1), heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor (Nrf2), and hypoxia-inducible factor (HIF-1α). Summarizing, our results demonstrated that TGF-ß keeps RGCs from hyperglycemia-triggered harm by promoting the activation of the antioxidant pathway, suggesting a potential anti-diabetic therapy for the treatment of diabetic retinopathy.

Proteomic investigating the cooperative lethal effect of EGFR and MDM2 inhibitors on ovarian carcinoma.

With the concept of precision medicine, combining multiple molecular-targeting therapies has brought new approaches to current cancer treatments. Malfunction of the tumor suppressor protein, p53 is a universal hallmark in human cancers. Under normal conditions, p53 is degraded through an ubiquitin-proteosome pathway regulated by its negative regulator, MDM2. In contrast, cellular stress such as DNA damage will activate p53 to carry out DNA repair, cell cycle arrest, and apoptosis. In this study, we focused on ovarian carcinoma with high EGFR and MDM2 overexpression rate. We assessed the effects of combined inhibition by MDM2 (JNJ-26854165) and EGFR (gefitinib) inhibitors on various ovarian cell lines to determine the importance of these two molecular targets on cell proliferation. We then used a proteomic strategy to investigate the relationship between MDM2 and EGFR inhibition to explore the underlying mechanisms of how their combined signaling blockades work together to exert cooperative inhibition. Our results demonstrated that all four cell lines were sensitive to both individual and combined, MDM2 and EGFR inhibition. The proteomic analysis also showed that gefitinib/JNJ-treated CAOV3 cells exhibited downregulation of proteins involved in nucleotide biosynthesis such as nucleoside diphosphate kinase B (NME2). In conclusion, our study showed that the combined treatment with JNJ and gefitinib exerted synergistic inhibition on cell proliferation, thereby suggesting the potential application of combining MDM2 inhibitors with EGFR inhibitors for enhancing efficacy in ovarian cancer treatment.

Proteomic Analysis of Various Rat Ocular Tissues after Ischemia-Reperfusion Injury and Possible Relevance to Acute Glaucoma.

Glaucoma is a group of eye diseases that can cause vision loss and optical nerve damage. To investigate the protein expression alterations in various intraocular tissues (i.e., the cornea, conjunctiva, uvea, retina, and sclera) during ischemia-reperfusion (IR) injury, this study performed a proteomic analysis to qualitatively investigate such alterations resulting from acute glaucoma. The IR injury model combined with the proteomic analysis approach of two-dimensional difference gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used to monitor the protein expression alterations in two groups of specimens (an IR injury group and a control group). The analysis results revealed 221 unique differentially expressed proteins of a total of 1481 proteins in the cornea between the two groups. In addition, 97 of 1206 conjunctival proteins, 90 of 1354 uveal proteins, 61 of 1180 scleral proteins, and 37 of 1204 retinal proteins were differentially expressed. These findings imply that different ocular tissues have different tolerances against IR injury. To sum up, this study utilized the acute glaucoma model combined with 2D-DIGE and MALDI-TOF MS to investigate the IR injury affected protein expression on various ocular tissues, and based on the ratio of protein expression alterations, the alterations in the ocular tissues were in the following order: the cornea, conjunctiva, uvea, sclera, and retina.

Identification of Up- and Down-Regulated Proteins in Pemetrexed-Resistant Human Lung Adenocarcinoma: Flavin Reductase and Calreticulin Play Key Roles in the Development of Pemetrexed-Associated Resistance.

Drug resistance is one of the major causes of cancer chemotherapy failure. In the current study, we used a pair of lung adenocarcinoma cell lines, A549 and the pemetrexed-resistant A549/PEM cells, as a model to monitor resistance-dependent cellular responses and identify potential therapeutic targets. By means of 2D differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), we investigated the global protein expression alterations induced by pemetrexed treatment and resistance. The proteomic result revealed that pemetrexed exposure obviously altered the expression of 81 proteins in the A549 cells, whereas no significant response was observed in the similarly treated A549/PEM cells, hence implying an association between these proteins and the drug-specific response. Moreover, 72 proteins including flavin reductase and calreticulin demonstrated differential expression between the A549 and A549/PEM cells, indicating baseline resistance. Additional tests employed siRNA silencing, protein overexpression, cell viability analysis, and analysis of apoptosis to examine and confirm the potency of flavin reductase and calreticulin proteins in the development of pemetrexed resistance. In summary, by using a proteomic approach, we identified numerous proteins, including flavin reductase and calreticulin, involved in pemetrexed drug resistance-developing mechanisms. Our results provide useful diagnostic markers and therapeutic candidates for pemetrexed-resistant lung cancer treatment.

[Effect of acupoint massage dominant early comprehensive intervention on the prognosis of premature infants with brain injury].

OBJECTIVE: To explore the effect of acupoint massage dominant early comprehensive intervention on the prognosis of premature infants with brain injury. METHODS: Totally 210 premature infants with brain injury were assigned to the intervention group (112 cases) and the control group (98 cases). All patients received routine therapy (medicinal + routine care instructions). Patients in the intervention group additionally received acupoint massage. Those with abnormal early motion received physical sports treatment. Those with upper limbs dysfunction or with fine movement disorders received occupational therapy. Premature infants' development quotient (DQ) was performed at corrected age of 6 and 12 months by using neuropsychological development examination table for 0 - 6 years old children. The incidence of cerebral palsy was statistically calculated. RESULTS: At corrected age of 6 months, DQ of gross motor, fine motor, language three functional areas was higher in the intervention group than in the control group with significant difference (P < 0.05). At corrected age of 12 months, DQ of gross motor, fine motor, language, social and adaptive capacities was higher in the intervention group than in the control groupwith significant difference (P < 0.05). The incidence of cerebral palsy was 4.46% (5/112) in the intervention group and 12.24% (12/98) in the control group (P < 0.05). CONCLUSION: Acupoint massage dominant early comprehensive intervention could obviously improve the intelligence development level and lower the incidence of cerebral palsy in premature infants with brain injury.

Lactobacillus rhamnosus 069 and Lactobacillus brevis 031: Unraveling Strain-Specific Pathways for Modulating Lipid Metabolism and Attenuating High-Fat-Diet-Induced Obesity in Mice.

Obesity is a global health crisis, marked by excessive fat in tissues that function as immune organs, linked to microbiota dysregulation and adipose inflammation. Investigating the effects of Lactobacillus rhamnosus SG069 (LR069) and Lactobacillus brevis SG031 (LB031) on obesity and lipid metabolism, this research highlights adipose tissue's critical immune-metabolic role and the probiotics' potential against diet-induced obesity. Mice fed a high-fat diet were treated with either LR069 or LB031 for 12 weeks. Administration of LB031 boosted lipid metabolism, indicated by higher AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation, and increased the M2/M1 macrophage ratio, indicating LB031's anti-inflammatory effect. Meanwhile, LR069 administration not only led to significant weight loss by enhancing lipolysis which evidenced by increased phosphorylation of hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) but also elevated Akkermansia and fecal acetic acid levels, showing the gut microbiota's pivotal role in its antiobesity effects. LR069 and LB031 exhibit distinct effects on lipid metabolism and obesity, underscoring their potential for precise interventions. This research elucidates the unique impacts of these strains on metabolic health and highlights the intricate relationship between gut microbiota and obesity, advancing our knowledge of probiotics' therapeutic potential.

Efficacy and Mechanism of the Action of Live and Heat-Killed Bacillus coagulans BC198 as Potential Probiotic in Ameliorating Dextran Sulfate Sodium-Induced Colitis in Mice.

Inflammatory bowel disease alters the gut microbiota, causes defects in mucosal barrier function, and leads to dysregulation of the immune response to microbial stimulation. This study investigated and compared the efficacy of a candidate probiotic strain, Bacillus coagulans BC198, and its heat-killed form in treating dextran sulfate sodium-induced colitis. Both live and heat-killed B. coagulans BC198 increased gut barrier-associated protein expression, reduced neutrophil and M1 macrophage infiltration of colon tissue, and corrected gut microbial dysbiosis induced by colitis. However, only live B. coagulans BC198 could alleviate the general symptoms of colitis, prevent colon shortening, and suppress inflammation and tissue damage. At the molecular level, live B. coagulans BC198 was able to inhibit Th17 cells while promoting Treg cells in mice with colitis, reduce pro-inflammatory MCP-1 production, and increase anti-inflammatory IL-10 expression in the colonic mucosa. The live form of B. coagulans BC198 functioned more effectively than the heat-killed form in ameliorating colitis by enhancing the anti-inflammatory response and promoting Treg cell accumulation in the colon.

Links between oral microbiome and insulin resistance: Involvement of MAP kinase signaling pathway.

Oral dysbiosis contributes to periodontitis and has implications for systemic diseases. Diabetes mellitus is a common metabolic disorder characterized by impaired glucose regulation. AMP-activated protein kinase (AMPK) plays a vital role in regulating glucose uptake and glycogenesis in the liver. This study aimed to investigate the association between periodontal bacteria and diabetes mellitus. A clinical trial was conducted to explore the association between oral bacteria and hyperglycemia. Additionally, we elucidated the molecular mechanisms by which periodontal bacteria cause insulin resistance. In the clinical trial, we discovered significant alterations in the expression levels of Fusobacterium nucleatum (Fn) and Tannerella forsythia (Tf) in patients with diabetes compared with healthy controls. Furthermore, Fn and Tf levels positively correlated with fasting blood glucose and glycated hemoglobin (HbA1C) levels. Moreover, we explored and elucidated the molecular mechanism by which Fusobacterium nucleatum culture filtrate (FNCF) induces cytokine release via the Toll-like receptor 2 (TLR2) signaling pathway in human gingival epithelial Smulow-Glickman (S-G) cells. This study investigated the effects of cytokines on insulin resistance pathways in liver cells. The use of an extracellular signal-regulated kinase (ERK) inhibitor (U0126) demonstrated that FNCF regulates the insulin receptor substrate 1 and protein kinase B (IRS1/AKT) signaling pathway, which affects key proteins involved in hepatic glycogen synthesis, including glycogen synthase kinase-3 beta (GSK3ß) and glycogen synthase (GS), ultimately leading to insulin resistance. These findings suggest that ERK plays a crucial role in hepatocyte insulin resistance.

Fecal Protein Analysis of Dusp6 Knockout C57BL/6J Mice by Metaproteomics.

The research of obesity and gut microbiota has been carried out for years, yet the study process was in a slow pace for several challenges to conquer. As a complex status of disorder, the contributing factors refer to gut microbiota about obesity were controversial in a wide range. In terms of proteomics, 2D-DIGE technology is a powerful method for this study to identify fecal proteins from lean microbiota in Dusp6 knockout C57BL/6J mice, exploring the protein markers of the ability resisting to diet-induced obesity (DIO) transferred to the host mice after fecal microbiota transplantation. The results showed that the fecal microbiota expressed 289 proteins differentially with 23 proteins identified, which were considered to be the reasons to assist the microbiota exhibiting distinct behavior. By means of proteomics technology, we had found that differentially expressed proteins of lean microbiota determined the lean microbial behavior might be able to resist leaky gut. To sum up our study, the proteomics strategies offered as a tool to demonstrate and analyze the features of lean microbiota, providing new speculations in the behavior about the gut microbiota reacting to DIO.

Metabolic Dysfunction-Associated Fatty Liver Disease Increases the Risk of Gastroesophageal Reflux Symptoms.

OBJECTIVE: The present study aimed to explore the relationship between metabolic dysfunction-associated fatty liver disease (MAFLD) and gastroesophageal reflux symptoms (GERS). METHODS: The present study was a cross-sectional observational study. The study population was 3002 subjects from a single hospital who underwent a health checkup from September 1, 2019, to December 31, 2020. The diagnosis of MAFLD was based on the diagnosis of fatty liver in the subject by ultrasound or computed tomography (CT) and the presence of one of the following conditions: overweight or obesity (body mass index [BMI] ≥ 23), type 2 diabetes mellitus, and metabolic abnormalities. The subjects were divided into the GERS group (n = 305) and the non-GERS group (n = 2697) based on the presence or absence of GERS, based on the GerdQ score. RESULTS: The prevalence of MAFLD was significantly higher in the GERS group than in the non-GERS group (p = 0.001). In the univariate analysis of risk factors for GERS, MAFLD was identified as a risk factor for GERS (OR 1.5; 95% CI 1.176-1.913; p = 0.001). With adjustment of confounding factors such as BMI, waist circumference, lipid levels, and blood pressure, the correlation between MAFLD and GERS was attenuated but still significant (OR 1.408; 95% CI 1.085-1.826; p = 0.010). CONCLUSION: MAFLD might be an independent risk factor for GERS.

Identification of Core Genes of Toll-like Receptor Pathway from Lymantria dispar and Induced Expression upon Immune Stimulant.

The gypsy moth, Lymantria dispar, is a polyphagous forest pest worldwide. The baculovirus, Lymantria dispar multiple nucleopolyhedrovirus (LdMNPV) is a natural pathogen of L. dispar. The Toll-like receptors (TLR) pathway plays a crucial role in both innate and adaptive immunity in animals. However, The TLR pathway and its underlying immune mechanism against baculovirus in L. dispar have not been explored. In this study, eleven TLRs and five downstream TLR pathway components were identified and characterized from L. dispar. Structural analysis indicated that intracellular Toll/interleukin-1 receptor (TIR) domains of LdTLRs and LdMyD88 contained three conserved motifs, and the 3D structures of TIR domains of LdTLRs possessed similar patterns in components arrangement and spatial conformation. The TLR proteins of L. dispar were placed into five monophyletic groups based on the phylogenetic analysis. LdTLR1, 2, 5, 6, 7, 8 and all identified downstream TLR pathway factors were highly induced upon LdMNPV infection, indicating that the TLR pathway of L. dispar was activated and might play a role in the immune response to LdMNPV infection. Collectively, these results help elucidate the crucial role of the TLR pathway in the immune response of L. dispar against LdMNPV, and offer a foundation for further understanding of innate immunity of the pest.

Characterization of TGF-ß by Induced Oxidative Stress in Human Trabecular Meshwork Cells.

Oxidative stress generated by reactive oxygen species (ROS) plays a critical role in the pathomechanism of glaucoma, which is a multifactorial blinding disease that may cause irreversible damage within human trabecular meshwork cells (HTMCs). It is known that the transforming growth factor-ß (TGF-ß) signaling pathway is an important component of oxidative stress-induced damage related to extracellular matrix (ECM) fibrosis and activates cell antioxidative mechanisms. To elucidate the dual potential roles and regulatory mechanisms of TGF-ß in effects on HTMCs, we established an in vitro oxidative model using hydrogen peroxide (H2O2) and further focused on TGF-ß-related oxidative stress pathways and the related signal transduction. Via a series of cell functional qualitative analyses to detect related protein level alterations and cell fibrosis status, we illustrated the role of TGF-ß1 and TGF-ß2 in oxidative stress-induced injury by shTGF-ß1 and shTGF-ß2 knockdown or added recombinant human TGF-ß1 protein (rhTGF-ß1). The results of protein level showed that p38 MAPK, TGF-ß, and its related SMAD family were activated after H2O2 stimulation. Cell functional assays showed that HTMCs with H2O2 exposure duration had a more irregular actin architecture compared to normal TM cells. Data with rhTGF-ß1 (1 ng/mL) pretreatment reduced the cell apoptosis rate and amount of reactive oxygen species (ROS), while it also enhanced survival. Furthermore, TGF-ß1 and TGF-ß2 in terms of antioxidant signaling were related to the activation of collagen I and laminin, which are fibrosis-response proteins. Succinctly, our study demonstrated that low concentrations of TGF-ß1 (1 ng/mL) preserves HTMCs from free radical-mediated injury by p-p38 MAPK level and p-AKT signaling balance, presenting a signaling transduction mechanism of TGF-ß1 in HTMC oxidative stress-related therapies.

The distribution of cultivable oral anaerobic microbiota identified by MALDI-TOF MS in healthy subjects and in patients with periodontal disease.

In this study, we aimed to identify the cultivatable oral anaerobic bacterial distribution in oral cavity by MALDI-TOF Biotyper. The bacterial distribution of three groups, including subjects with/without periodontal disease, two clusters of age (60 years as the cutoff), and before/after treatment, were investigated in this study. There were 38 participants recruited in this study, involving 18 subjects with moderate to severe periodontal-infected patients and 20 healthy controls. Total number of 126 bacterial species were identified by MALDI-TOF MS. The relative abundance of Streptococcus gordonii and Streptococcus intermedius in periodontal patients is higher than healthy controls indicating potential biomarkers for periodontal disease. Participants with periodontal disease were subdivided in to two clusters of age (60 years as the cutoff), 11 and 7 participants were age <60 years and>60 years, respectively. Meanwhile, the incidence of Streptococcus pneumoniae and Streptococcus oralis infection were higher in the subjects above 60 years old than below. Moreover, the bacterial distribution between pre-treatment and post-treatment was similar indicating that basic treatment without the ability to redistribute the microbiota. In summary, the cultivable oral anaerobic bacteria were identified by MALDI-TOF MS and the bacterial distribution shifting was shown to be associated with the progress of periodontal disease to aging and basic treatment. This study provided information for diagnosis and treatment guidelines for oral healthcare.

TGF-ß1 signaling protects retinal ganglion cells from oxidative stress via modulation of the HO-1/Nrf2 pathway.

Oxidative stress provides a major contribution to the pathogenesis of glaucoma and may induce retinal ganglion cell (RGC) damage. Transforming growth factor ß (TGF-ß) has appeared as a neuroprotective protein in various indignities. However, the TGF-ß mechanism of protective effects against oxidative stress damage in RGCs still undetermined. In our research, we investigated the regulatory mechanisms and potential effects of TGF-ß1 & TGF-ß2 in hydrogen peroxide (H2O2)-stimulated oxidative stress of RGCs in vitro. By a series of cell functional qualitative analysis, such as MTT cell viability assay, wound healing ability assay, apoptosis assay, intracellular ROS detection, immunoblot analysis, intracellular GSH content, and high-resolution respirometry, we illustrated the cell state in oxidative stress-induced injury. Results of protein expression showed that TGF-ß1 & TGF-ß2 was upregulated in RGCs after H2O2 stimulation. Cell functional assays resulted that knockdown of TGF-ß1 & TGF-ß2 reduced survival rate whereas enhanced apoptosis and accumulation of reactive oxygen species (ROS). Especially TGF-ß1 upregulation promoted the protein expression of aldehyde dehydrogenase 3A1 (ALDH3A1) and increased the activity of antioxidant and neuroprotection pathways. Additionally, TGF-ß1 & TGF-ß2 on antioxidant signaling was related to activation of heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor (Nrf2), which are stress-response proteins. ROS accumulation followed by the accumulation of hypoxia-inducible factor (HIF-1α) caused mitochondrial damage and led to neurodegeneration. In summary, our results demonstrated that TGF-ß1 preserves RGCs from free radicals-mediated injury by upregulating the activation of Nrf2 expression and HO-1 signaling balance HIF-1α upregulation, implying a prospective role of TGF-ß1 in retinal neuroprotection-related therapies.