Evaluation of parietal pleural adhesion and invasion in subpleural lung cancer: value of B-mode ultrasound and contrast-enhanced ultrasound.

Background: The parietal pleural adhesion/invasion of lung cancer can contribute substantially to poor prognosis and difficulty in surgery. The value of ultrasound in evaluating the parietal pleural adhesion or invasion (pleural adhesion/invasion) of lung cancer remains uncertain. This study investigated the value of B-mode ultrasound and contrast-enhanced ultrasound (CEUS) in diagnosing parietal pleural adhesion/invasion of subpleural lung cancer. Methods: The study animals included 40 male New Zealand white rabbits. A rabbit subpleural lung cancer model was constructed by injecting VX2 tumor tissue under ultrasound guidance. In the 1-3 weeks after subpleural lesion formation, parietal pleural adhesion/invasion of the largest subpleural lesion was evaluated with B-mode ultrasound and CEUS by two sonographers. The parietal pleural adhesion/invasion was also determined using the gold standard method of findings from anatomical and pathological examination. Results: Ultimately, 34 rabbits were subjected to complete ultrasonic evaluation. There were 20 and 14 cases with and without parietal pleural adhesion/invasion, respectively, as confirmed by anatomical and pathological evaluations. The diagnostic sensitivity, specificity, and accuracy of sonographer 1 using B-mode ultrasound were 50.0% [95% confidence interval (CI): 26.0-74.0%], 100%, and 70.6% (95% CI: 54.5-86.7%), respectively; for CEUS, they were 90.0% (95% CI: 75.6-100.0%), 100.0%, and 94.1% (95% CI: 85.8-100.0%), respectively. The diagnostic sensitivity, specificity, and accuracy of sonographer 2 using B-mode ultrasound were 45.0% (95% CI: 21.1-68.9%), 92.9% (95% CI: 77.5-100.0%), and 64.7% (95% CI: 47.8-81.6%), respectively; for CEUS, they were 85.0% (95% CI: 67.9-100.0%), 100.0%, and 91.2% (95% CI: 81.1-100.0%), respectively. The diagnostic accuracy of sonographer 1 was higher with CEUS than with B-mode ultrasound, but not significantly so (94.1% vs. 70.6%; P=0.08). The diagnostic accuracy of sonographer 2 was significantly higher with CEUS than with B-mode ultrasound (91.2% vs. 64.7%; P=0.03). The interrater reliability was higher for CEUS than for B-mode ultrasound (κ=0.941 vs. κ =0.717). Conclusions: Based on an animal model, B-mode ultrasound and CEUS both exhibited good diagnostic efficacy and interrater reliability in evaluating parietal pleural adhesion/invasion of subpleural lung cancer although CEUS outperformed B-mode ultrasound for both measures.

Metabolic Reprogramming in Gliocyte Post-cerebral Ischemia/ Reperfusion: From Pathophysiology to Therapeutic Potential.

Ischemic stroke is a leading cause of disability and death worldwide. However, the clinical efficacy of recanalization therapy as a preferred option is significantly hindered by reperfusion injury. The transformation between different phenotypes of gliocytes is closely associated with cerebral ischemia/ reperfusion injury (CI/RI). Moreover, gliocyte polarization induces metabolic reprogramming, which refers to the shift in gliocyte phenotype and the overall transformation of the metabolic network to compensate for energy demand and building block requirements during CI/RI caused by hypoxia, energy deficiency, and oxidative stress. Within microglia, the pro-inflammatory phenotype exhibits upregulated glycolysis, pentose phosphate pathway, fatty acid synthesis, and glutamine synthesis, whereas the anti-inflammatory phenotype demonstrates enhanced mitochondrial oxidative phosphorylation and fatty acid oxidation. Reactive astrocytes display increased glycolysis but impaired glycogenolysis and reduced glutamate uptake after CI/RI. There is mounting evidence suggesting that manipulation of energy metabolism homeostasis can induce microglial cells and astrocytes to switch from neurotoxic to neuroprotective phenotypes. A comprehensive understanding of underlying mechanisms and manipulation strategies targeting metabolic pathways could potentially enable gliocytes to be reprogrammed toward beneficial functions while opening new therapeutic avenues for CI/RI treatment. This review provides an overview of current insights into metabolic reprogramming mechanisms in microglia and astrocytes within the pathophysiological context of CI/RI, along with potential pharmacological targets. Herein, we emphasize the potential of metabolic reprogramming of gliocytes as a therapeutic target for CI/RI and aim to offer a novel perspective in the treatment of CI/RI.

No-reflow after recanalization in ischemic stroke: From pathomechanisms to therapeutic strategies.

Endovascular reperfusion therapy is the primary strategy for acute ischemic stroke. No-reflow is a common phenomenon, which is defined as the failure of microcirculatory reperfusion despite clot removal by thrombolysis or mechanical embolization. It has been reported that up to 25% of ischemic strokes suffer from no-reflow, which strongly contributes to an increased risk of poor clinical outcomes. No-reflow is associated with functional and structural alterations of cerebrovascular microcirculation, and the injury to the microcirculation seriously hinders the neural functional recovery following macrovascular reperfusion. Accumulated evidence indicates that pathology of no-reflow is linked to adhesion, aggregation, and rolling of blood components along the endothelium, capillary stagnation with neutrophils, astrocytes end-feet, and endothelial cell edema, pericyte contraction, and vasoconstriction. Prevention or treatment strategies aim to alleviate or reverse these pathological changes, including targeted therapies such as cilostazol, adhesion molecule blocking antibodies, peroxisome proliferator-activated receptors (PPARs) activator, adenosine, pericyte regulators, as well as adjunctive therapies, such as extracorporeal counterpulsation, ischemic preconditioning, and alternative or complementary therapies. Herein, we provide an overview of pathomechanisms, predictive factors, diagnosis, and intervention strategies for no-reflow, and attempt to convey a new perspective on the clinical management of no-reflow post-ischemic stroke.

ED-71 ameliorates bone regeneration in type 2 diabetes by reducing ferroptosis in osteoblasts via the HIF1α pathway.

Eldecalcitol (ED-71), a novel active form of vitamin D, shows potential in treating osteoporosis. However, its underlying mechanisms of action remain to be determined. This study aimed to investigate the effect of ED-71 on bone regeneration and to illustrate its mode of action. The in-vitro model was developed using rat primary osteoblasts cultured under high-glucose conditions, and these cells were treated with ED-71. Additionally, an in vivo model of cranial bone defects was established in type 2 diabetic rats, and ED-71 was administered by gavage. The results demonstrated that ED-71 prevented osteoblast cell death, enhanced rat primary osteoblasts' osteogenic capacity, and attenuated the overexpression of hypoxia-inducible factor 1α (HIF1α) induced by high glucose levels. Furthermore, ED-71 increased glutathione peroxidase 4 (GPX4) levels and inhibited ferroptosis in response to hyperglycemic stimulation. Notably, interference with the HIF1α activator and ferroptosis activator Erastin significantly reduced the therapeutic effects of edetate osteolysis. These findings were further tested in vivo experiments. These results suggest that ED-71 activates the HIF1α pathway in vivo and in vitro, effectively relieving the ferroptosis induced by high glucose. Significantly, ED-71 may improve osteogenic disorders caused by diabetes.

A novel teleost microRNA regulates autophagy and NF-κB activation during bacterial infection.

MicroRNAs (miRNAs) are a class of non-coding RNAs with regulatory functions in many cellular processes, including immune defense. In this study, we identified novel-m0089-3p, a novel miRNA with unknown function, in the teleost fish Japanese flounder (Paralichthys olivaceus) and investigated its immune function. Novel-m0089-3p was found to target the autophagy-associated gene ATG7 and negatively regulate ATG7 expression via interaction with the 3' UTR of ATG7. During the infection of the bacterial pathogen Edwardsiella tarda, novel-m0089-3p expression was induced in flounder, which in turn repressed ATG7 expression. Overexpression of novel-m0089-3p or blocking ATG7 expression inhibited autophagy and promoted the intracellular replication of E. tarda. Novel-m0089-3p overexpression, as well as E. tarda infection, activated NF-κB and stimulated the expression of inflammatory cytokines. Together these results revealed an important role of novel-m0089-3p in response to bacterial infection.

Japanese Flounder pol-miR-155 Is Involved in Edwardsiella tarda Infection via ATG3.

MicroRNAs (miRNAs) are small RNA molecules that function in the post-transcriptionally regulation of the expression of diverse genes, including those involved in immune defense. Edwardsiella tarda can infect a broad range of hosts and cause severe disease in aquatic species, including Japanese flounder (Paralichthys olivaceus). In this study, we examined the regulation mechanism of a flounder miRNA, pol-miR-155, during the infection of E. tarda. Pol-miR-155 was identified to target flounder ATG3. Overexpression of pol-miR-155 or knockdown of ATG3 expression suppressed autophagy and promoted the intracellular replication of E. tarda in flounder cells. Overexpression of pol-miR-155 activated the NF-κB signaling pathway and further promoted the expression of downstream immune related genes of interleukin (IL)-6 and IL-8. These results unraveled the regulatory effect of pol-miR-155 in autophagy and in E. tarda infection.

Efficient Bioremediation of Petroleum-Contaminated Soil by Immobilized Bacterial Agent of Gordonia alkanivorans W33.

In this article, we report a method for preparing an immobilized bacterial agent of petroleum-degrading bacteria Gordonia alkanivorans W33 by combining high-density fermentation and bacterial immobilization technology and testing its bioremediation effect on petroleum-contaminated soil. After determining the optimal combination of MgCl2, CaCl2 concentration, and culture time in the fermentation conditions by conducting a response surface analysis, the cell concentration reached 7.48 × 109 CFU/mL by 5 L fed-batch fermentation. The W33-vermiculite-powder-immobilized bacterial agent mixed with sophorolipids and rhamnolipids in a weight ratio of 9:10 was used for the bioremediation of petroleum-contaminated soil. After 45 days of microbial degradation, 56.3% of the petroleum in the soil with 20,000 mg/kg petroleum content was degraded, and the average degradation rate reached 250.2 mg/kg/d.

Maresin1: A multifunctional regulator in inflammatory bone diseases.

Inflammation plays a crucial role in the physical response to danger signals, the elimination of toxic stimuli, and the restoration of homeostasis. However, dysregulated inflammatory responses lead to tissue damage, and chronic inflammation can disrupt osteogenic-osteoclastic homeostasis, ultimately leading to bone loss. Maresin1 (MaR1), a member of the specialized pro-resolving mediators (SPMs) family, has been found to possess significant anti-inflammatory, anti-allergic, pro-hemolytic, pro-healing, and pain-relieving properties. MaR1 is synthesized by macrophages (Mφs) and omega-3 fatty acids, and it may have the potential to promote bone homeostasis and treat inflammatory bone diseases. MaR1 has been found to stimulate osteoblast proliferation through leucine-rich repeat G protein-coupled receptor 6 (LGR6). It also activates Mφ phagocytosis and M2-type polarization, which helps to control the immune system. MaR1 can regulate T cells to exert anti-inflammatory effects and inhibit neutrophil infiltration and recruitment. In addition, MaR1 is involved in antioxidant signaling, including nuclear factor erythroid 2-related factor 2 (NRF2). It has also been found to promote the autophagic behavior of periodontal ligament stem cells, stimulate Mφs against pathogenic bacteria, and regulate tissue regeneration and repair. In summary, this review provides new information and a comprehensive overview of the critical roles of MaR1 in inflammatory bone diseases, indicating its potential as a therapeutic approach for managing skeletal metabolism and inflammatory bone diseases.

The burden of diabetes on the soft tissue seal surrounding the dental implants.

Soft tissue seal around implant prostheses is considered the primary barrier against adverse external stimuli and is a critical factor in maintaining dental implants' stability. Soft tissue seal is formed mainly by the adhesion of epithelial tissue and fibrous connective tissue to the transmembrane portion of the implant. Type 2 diabetes mellitus (T2DM) is one of the risk factors for peri-implant inflammation, and peri-implant disease may be triggered by dysfunction of the soft tissue barrier around dental implants. This is increasingly considered a promising target for disease treatment and management. However, many studies have demonstrated that pathogenic bacterial infestation, gingival immune inflammation, overactive matrix metalloproteinases (MMPs), impaired wound healing processes and excessive oxidative stress may trigger poor peri-implant soft tissue sealing, which may be more severe in the T2DM state. This article reviews the structure of peri-implant soft tissue seal, peri-implant disease and treatment, and moderating mechanisms of impaired soft tissue seal around implants due to T2DM to inform the development of treatment strategies for dental implants in patients with dental defects.

Natural promoters and promoter engineering strategies for metabolic regulation in Saccharomyces cerevisiae.

Sharomyces cerevisiae is currently one of the most important foreign gene expression systems. S. cerevisiae is an excellent host for high-value metabolite cell factories due to its advantages of simplicity, safety, and nontoxicity. A promoter, as one of the basic elements of gene transcription, plays an important role in regulating gene expression and optimizing metabolic pathways. Promoters control the direction and intensity of transcription, and the application of promoters with different intensities and performances will largely determine the effect of gene expression and ultimately affect the experimental results. Due to its significant role, there have been many studies on promoters for decades. While some studies have explored and analyzed new promoters with different functions, more studies have focused on artificially modifying promoters to meet their own scientific needs. Thus, this article reviews current research on promoter engineering techniques and related natural promoters in S. cerevisiae. First, we introduce the basic structure of promoters and the classification of natural promoters. Then, the classification of various promoter strategies is reviewed. Finally, by grouping related articles together using various strategies, this review anticipates the future development direction of promoter engineering.

Hyperlipidemia impacts osteogenesis via lipophagy.

The mechanism of the impact of hyperlipidemia on bone tissue homeostasis is unclear, and the role of lipophagy is yet to be investigated. This study investigated changes in lipophagy and osteogenesis levels under hyperlipemic conditions and explored the effects of lipophagy on bone regeneration. In vivo, femurs of mice with diet-induced moderate hyperlipidemia were ground out with a ball drill to create defects. In vitro, mouse osteoblast cell lines were grown in two different concentrations of the high-fat medium. We found that at hyperphysiological of lipid conditions, activation of lipophagy restored osteoblast function in a way, and similar results were observed in mice with diet-induced hyperlipidemia. Still, at suprahyperphysiological concentrations of lipid culture, the activation of lipophagy further inhibited osteogenesis, and inhibition of autophagy instead promoted osteogenesis to a small extent. These results demonstrate that lipophagy functions differently in diverse high-fat environments, suggesting that cellular and organismal changes in response to high-fat stimuli are dynamic. This may provide new ideas for improving bone dysfunction caused by lipid metabolism disorders.

Influence of the contact area of the sub-antral space with sinus bone and the Schneiderian membrane on osteogenesis in lateral window sinus elevation surgery: a prospective experiment.

BACKGROUND: Osteogenesis of lateral window sinus elevation surgery is the key to placement of the subsequent implant, excessive collapse of the sub-antral space may adversely affect long-term stability of implants. At present, few studies focus on the influence of the contact area of the sub-antral space on osteogenesis. This study evaluated whether the change in the contact area of the sub-antral space with maxillary sinus bone and the Schneiderian membrane can affect osteogenesis. METHODS: Cone beam computed tomography (CBCT) images were collected of patients requiring maxillary sinus floor elevation (residual bone height < 6 mm) for standard-length implant placement before surgery, after surgery, and at 6-month follow-up visits. The postoperative sub-antral space volume (V1) and surface area (S1), and the remaining volume after six months of healing (V2) were measured. Then, the contact area of sub-antral space with maxillary sinus bone (Sbc) and the Schneiderian membrane (Smc), the absorbed volume during healing (Va), and the percentage of remaining volume (V2%) and absorbed volume (Va%) were calculated. The correlation between anatomical parameters was analyzed using multiple linear regression. RESULTS: A total of 62 maxillary sinuses from 56 patients were augmented, of which 57 were considered for the final analysis (5 withdrew due to perforation). Multiple linear regression results demonstrated that Sbc was significantly positively correlated with Va (ß coefficient = 0.141, p < 0.01) without correlation between Smc and Va (ß coefficient = - 0.046, p = 0.470). There was a positive correlation between Sbc and V2% (ß coefficient = 2.269, p < 0.05). CONCLUSIONS: This study confirmed that the size of the Sbc in lateral window sinus elevation surgery affected osteogenesis after six months of healing. Clinicians should assess the sinus contour type preoperatively, then consider whether it is necessary to expand the range of the Schneiderian membrane elevation to avoid excessive collapse of the sub-antral space. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR), ChiCTR2200057924. Registered 22 March 2022-Retrospectively registered.

[Clinical Comparative Analysis of Early-Onset Preeclampsia Combined with HELLP Syndrome].

Objective: To explore the clinical characteristics of early-onset preeclampsia (PE) combined with HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, and to improve the capacity for early diagnosis and treatment. Methods: Pregnant women who received treatment at Women's Hospital, School of Medicine, Zhejiang University between March 2014 and October 2021 were retrospectively enrolled. There were two patient groups, the HELLP group consisting of 70 cases of early-onset PE combined with HELLP syndrome and the control group consisting of 140 cases of early-onset PE without HELLP syndrome. Patients in the two groups were matched by age. The general clinical data, characteristics of pathogenesis, and laboratory findings of the patients were collected and the perinatal outcomes of the two groups were compared and analyzed. Results: 1) There was no significant difference in gravidity, pre-delivery body mass index, years from the last delivery, and family history of diabetes mellitus and hypertension between the two groups. 2) The highest systolic blood pressure, highest diastolic blood pressure during the pregnancy, and the postpartum hospital length-of-stay ( P<0.001) in the HELLP group were higher than those in the control group. The gestational age at the time of the diagnosis of PE ( P=0.001) and the gestational age at delivery ( P<0.001) in the HELLP group were significantly earlier than those in the control group. The difference between the gestational age at the time of blood pressure elevation and that at the time of delivery ( P<0.001), and the gestational age difference between the diagnosis of early-onset PE and delivery ( P=0.027) were lower than those in the control group. The incidences of eclampsia in the HELLP group, pleural effusion, and ascites were higher than those of the control group. 3) Neonates in the HELLP group had a higher probability of being admitted to NICU and developing cyanotic/pale asphyxia ( P<0.001). 4) Before the termination of pregnancy, the HELLP group had higher levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, creatinine, urea, random glucose, lactate dehydrogenase, activated partial thromboplastin time, and the last 24-hour urine protein quantification than those of the control group (all P<0.05), while the platelet (PLT) counts were significantly lower than those of the control group ( P<0.001). 5) There was a significant correlation between PLT counts in the second trimester and the onset of HELLP syndrome ( P=0.006), with the area under the ROC curve reaching 0.746 (95% CI: 0.596-0.897). Conclusion: In comparison with early-onset PE patients without HELLP syndrome, patients with early-onset PE combined with HELLP syndrome are diagnosed for PE at an earlier gestational age, have higher blood pressure, are more prone to serious pregnancy complications, and have longer postpartum hospital length-of-stay and worse neonatal outcomes. Close monitoring of PLT counts of early-onset PE patients in the second trimester may help predict subsequent HELLP syndrome.

Mitochondria-Associated Endoplasmic Reticulum Membranes: Inextricably Linked with Autophagy Process.

Mitochondria-associated membranes (MAMs), physical connection sites between the endoplasmic reticulum (ER) and the outer mitochondrial membrane (OMM), are involved in numerous cellular processes, such as calcium ion transport, lipid metabolism, autophagy, ER stress, mitochondria morphology, and apoptosis. Autophagy is a highly conserved intracellular process in which cellular contents are delivered by double-membrane vesicles, called autophagosomes, to the lysosomes for destruction and recycling. Autophagy, typically triggered by stress, eliminates damaged or redundant protein molecules and organelles to maintain regular cellular activity. Dysfunction of MAMs or autophagy is intimately associated with various diseases, including aging, cardiovascular, infections, cancer, multiple toxic agents, and some genetic disorders. Increasing evidence has shown that MAMs play a significant role in autophagy development and maturation. In our study, we concentrated on two opposing functions of MAMs in autophagy: facilitating the formation of autophagosomes and inhibiting autophagy. We recognized the link between MAMs and autophagy in the occurrence and progression of the diseases and therefore collated and summarized the existing intrinsic molecular mechanisms. Furthermore, we draw attention to several crucial data and open issues in the area that may be helpful for further study.

Maresin1 Suppresses High-Glucose-Induced Ferroptosis in Osteoblasts via NRF2 Activation in Type 2 Diabetic Osteoporosis.

Maresin1 (MaR1) is an endogenous pro-resolving lipid mediator produced from polyunsaturated fatty acids and is believed to have antioxidant and anti-inflammatory properties. The objective of this study was to estimate MaR1's impact on type 2 diabetic osteoporosis (T2DOP) and its pharmacological mode of action. An in vitro high-glucose model of the osteoblast cell line MC3T3-E1 was constructed and stimulated with MaR1. Type 2 diabetic rats were used to establish in vivo models of calvarial defects and were treated in situ with MaR1. The results revealed that, aside from preventing mortality and promoting the osteogenic capacity of MC3T3-E1 cells, MaR1 increased nuclear factor erythroid-2 related factor 2 (NRF2) signaling as well as the activity of glutathione peroxidase 4 (GPX4) and cystine-glutamate antiporter (SLC7A11) and caused the restraint of ferroptosis under hyperglycemic stimulation. However, the therapeutic impact of MaR1 was significantly diminished due to NRF2-siRNA interference and the ferroptosis activator Erastin. Meanwhile, these results were validated through in vivo experiments. These findings imply that MaR1 activated the NRF2 pathway in vivo and in vitro to alleviate high-glucose-induced ferroptosis greatly. More crucially, MaR1 might effectively reduce the risk of T2DOP.

Liquiritigenin Blocks Breast Cancer Progression by Inhibiting Connective Tissue Growth Factor Expression via Up-Regulating miR-383-5p.

The objective of this study was to investigate the effect of liquiritigenin (LQ) on breast cancer (BC) and its mechanism. After BC cell lines and normal mammary epithelial cells were cultured with LQ, CCK-8, and Scratch, Transwell assays and flow cytometry were applied to test the effect of LQ on cell proliferation, migration, invasion, and apoptosis. The effect of LQ on the expression of microRNA-383-5p (miR-383-5p) and connective tissue growth factor (CTGF) was measured by qRT-PCR and Western blotting. Bioinformatics prediction was used to evaluate the binding relationship between miR-383-5p and CTGF, which was verified by dual-luciferase reporter assay. After miR-383-5p and/or CTGF expression was upregulated through cell transfection, the relationship between miR-383-5p and CTGF, as well as their effects on BC, was further assessed. The results showed that LQ can significantly inhibit CTGF expression and the proliferative, migratory, and invasive abilities of BC cells, while facilitating apoptosis of BC cells and miR-383-5p expression. The inhibiting effect of LQ was dose-dependently enhanced in BC cells. Dual-luciferase reporter assay verified that miR-383-5p targeted CTGF. CTGF expression was inversely regulated by miR-383-5p. CTGF upregulation repressed the suppressive effect of miR-385-5p on BC cell development. In conclusion, LQ can inhibit CTGF expression by upregulating miR-383-5p, thereby inhibiting proliferative, migratory, and invasive abilities and promoting apoptosis of BC cells.

Rosuvastatin protects PC12 cells from hypoxia/reoxygenation-induced injury by inhibiting endoplasmic reticulum stress-induced apoptosis.

The endoplasmic reticulum stress (ERS) response serves an important role in cerebral ischemia-reperfusion injury (CIRI). However, to the best of the our knowledge, the effect of rosuvastatin on the ERS response in CIRI has not yet been studied. In the present study, the effect of rosuvastatin on cell damage in CIRI was investigated; furthermore, the effect of rosuvastatin on the ERS response was explored. Firstly, a hypoxia/reoxygenation (H/R)-induced cell damage model was established in PC12 cells. Cell viability was subsequently detected by a Cell Counting Kit-8 assay. A lactate dehydrogenase kit was used to detect cytotoxicity. TUNEL assay was then used to measure the extent of cell apoptosis, and western blotting was used to analyze the expression levels of the apoptosis-associated proteins Bax, Bcl-2, cleaved caspase-3 and cleaved caspase-9. In addition, western blotting was used to detect the expression levels of ERS-associated proteins, including phosphorylated (p)-protein kinase R-like endoplasmic reticulum kinase (PERK), p-eukaryotic initiation factor 2α and other proteins. Treatment with rosuvastatin led to an increased activity of H/R-induced PC12 cells and a decrease in their cytotoxicity. Rosuvastatin also led to an inhibition in apoptosis and ERS in H/R-induced PC12 cells. After administration of the ERS response activator thapsigargin (TG), TG was found to reverse the protective effect of rosuvastatin on injury of H/R-induced PC12 cells. Taken together, these findings have shown that rosuvastatin is able to protect PC12 cells from H/R-induced injury via inhibiting ERS-induced apoptosis, providing a strong theoretical basis for the use of rosuvastatin in the clinical treatment of CIRI.

Research progress in bioremediation of petroleum pollution.

With the enhancement of environmental protection awareness, research on the bioremediation of petroleum hydrocarbon environmental pollution has intensified. Bioremediation has received more attention due to its high efficiency, environmentally friendly by-products, and low cost compared with the commonly used physical and chemical restoration methods. In recent years, bacterium engineered by systems biology strategies have achieved biodegrading of many types of petroleum pollutants. Those successful cases show that systems biology has great potential in strengthening petroleum pollutant degradation bacterium and accelerating bioremediation. Systems biology represented by metabolic engineering, enzyme engineering, omics technology, etc., developed rapidly in the twentieth century. Optimizing the metabolic network of petroleum hydrocarbon degrading bacterium could achieve more concise and precise bioremediation by metabolic engineering strategies; biocatalysts with more stable and excellent catalytic activity could accelerate the process of biodegradation by enzyme engineering; omics technology not only could provide more optional components for constructions of engineered bacterium, but also could obtain the structure and composition of the microbial community in polluted environments. Comprehensive microbial community information lays a certain theoretical foundation for the construction of artificial mixed microbial communities for bioremediation of petroleum pollution. This article reviews the application of systems biology in the enforce of petroleum hydrocarbon degradation bacteria and the construction of a hybrid-microbial degradation system. Then the challenges encountered in the process and the application prospects of bioremediation are discussed. Finally, we provide certain guidance for the bioremediation of petroleum hydrocarbon-polluted environment.

Protective effects and mechanism of coenzyme Q10 and vitamin C on doxorubicin-induced gastric mucosal injury and effects of intestinal flora.

Doxorubicin (Dox) is widely used to the treatment of cancer, however, it could cause damage to gastric mucosa. To investigate the protective effects and related mechanisms of coenzyme Q10 (CoQ10) and vitamin C (VC) on Dox-induced gastric mucosal injury, we presented the survey of the 4 groups of the rats with different conditions. The results showed Dox treatment significantly induced GES-1 apoptosis, but preconditioning in GES-1 cells with VC or CoQ10 significantly inhibited the Dox-induced decrease and other harm effects, including the expression and of IκKß, IκBα, NF-κB/p65 and tumor necrosis factor (TNF-α) in GES-1 cells. Moreover, high-throughput sequencing results showed Dox treatment increased the number of harmful gut microbes, and CoQ10 and VC treatment inhibited this effect. CoQ10 and VC treatment inhibits Dox-induced gastric mucosal injury by inhibiting the activation of the IkKB/IκBα/NF-κB/p65/TNF-α pathway, promoting anti-inflammatory effects of gastric tissue and regulating the composition of the intestinal flora.

Effects of Co-Administration of Icariin and Panax notoginseng Saponins on Intestinal Microbiota and Hippocampal Protein Expression in a Mouse Model of Alzheimer's Disease.

OBJECTIVE: We investigated the effect of icariin (ICA) combined with Panax notoginseng saponins (PNS) on intestinal microbiota and hippocampal protein expression in amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice, a model of Alzheimer's disease (AD). METHODS: Transgenic mice were treated with icariin and PNS. The Morris water maze (MWM) was used to assess spatial memory, and the gut microbiota and differential protein expression in the hippocampus were investigated using high-throughput screening techniques. Differential protein expression was confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. RESULTS: The MWM results showed that the mice treated with the medium dose of ICA+PNS spent significantly more time in the target quadrant compared with the AD group. Bacterial diversity was the lowest in the AD group, with significantly greater diversity in the ICA + PNS treatment group. Three proteins were selected for proteomic analysis, and qRT-PCR and Western blot were used to detect the expression of 2'-5'-oligoadenylate synthetase ubiquitin like 1 (Oasl1), trichoplein keratin filament-binding protein (TCHP), and tumor necrosis factor receptor associated 3-interacting protein 1 (MIPT3). Compared with control mice, MIPT3 expression was increased and Oasl1 and TCHP were reduced in the AD group. These abnormal protein expressions tended to normalization after treatment with medium dose of ICA and PNS. CONCLUSION: Treatment with ICA and PNS ameliorated memory impairment in an AD mouse model. The mechanisms may be related to modulation of the intestinal microbiota and expression of Oasl1, TCHP, and MIPT3.