Analyzing microbial community and volatile compound profiles in the fermentation of cigar tobacco leaves.

Variations in industrial fermentation techniques have a significant impact on the fermentation of cigar tobacco leaves (CTLs), consequently influencing the aromatic attributes of the resulting cigars. The entire fermentation process of CTLs can be categorized into three distinct phases: phase 1 (CTLs prior to moisture regain), phase 2 (CTLs post-moisture regain and pile fermentation), and phase 3 (CTLs after fermentation and drying). These phases were determined based on the dynamic changes in microbial community diversity. During phase 2, there was a rapid increase in moisture and total acid content, which facilitated the proliferation of Aerococcus, a bacterial genus capable of utilizing reducing sugars, malic acid, and citric acid present in tobacco leaves. In contrast, fungal microorganisms exhibited a relatively stable response to changes in moisture and total acid, with Aspergillus, Alternaria, and Cladosporium being the dominant fungal groups throughout the fermentation stages. Bacterial genera were found to be more closely associated with variations in volatile compounds during fermentation compared to fungal microorganisms. This association ultimately resulted in higher levels of aroma components in CTLs, thereby improving the overall quality of the cigars. These findings reinforce the significance of industrial fermentation in shaping CTL quality and provide valuable insights for future efforts in the artificial regulation of secondary fermentation in CTLs. KEY POINTS: • Industrial fermentation processes impact CTLs microbial communities. • Moisture and total acid content influence microbial community succession in fermentation. • Bacterial microorganisms strongly influence CTLs' aldehyde and ketone flavors over fungi.

Correlation study on microbial communities and volatile flavor compounds in cigar tobacco leaves of diverse origins.

To elucidate the significant influence of microorganisms on geographically dependent flavor formation by analyzing microbial communities and volatile flavor compounds (VFCs) in cigar tobacco leaves (CTLs) obtained from China, Dominica, and Indonesia. Microbiome analysis revealed that the predominant bacteria in CTLs were Staphylococcus, Aerococcus, Pseudomonas, and Lactobacillus, while the predominant fungi were Aspergillus, Wallemia, and Sampaiozyma. The microbial communities of CTLs from different origins differed to some extent, and the diversity and abundance of bacteria were greater than fungi. Metabolomic analysis revealed that 64 VFCs were identified, mainly ketones, of which 23 VFCs could be utilized to identify the geographical origins of CTLs. Sixteen VFCs with OAV greater than 1, including cedrol, phenylacetaldehyde, damascone, beta-damascone, and beta-ionone, play important roles in shaping the flavor profile of CTLs from different origins. Combined with the correlation analysis, bacterial microorganisms were more closely related to key VFCs and favored a positive correlation. Bacillus, Vibrio, and Sphingomonas were the main flavor-related bacteria. The study demonstrated that the predominant microorganisms were essential for the formation of key flavor qualities in CTLs, which provided a theoretical reference for flavor control of CTLs by microbial technology. KEY POINTS: • It is the high OAV VFCs that determine the flavor profile of CTLs. • The methylerythritol phosphate (MEP) pathway and the carotenoid synthesis pathway are key metabolic pathways for the formation of VFCs in CTLs. • Microbial interactions influence tobacco flavor, with bacterial microorganisms contributing more to the flavor formation of CTLs.

Warfarin compared with non-vitamin K antagonist oral anticoagulants in subjects with liver disease and atrial fibrillation: A meta-analysis.

INTRODUCTION: Many concerns were raised about the outcome of non-vitamin K antagonist oral anticoagulants compared with warfarin in subjects with atrial fibrillation and liver disease. However, the reported relationship between their efficacy and safety was variable. This meta-analysis was performed to evaluate this relationship. METHODS: A systematic literature search up to July 2020 was performed and six studies included 50 074 subjects with atrial fibrillation and liver disease at the baseline with 32 229 non-vitamin K antagonist oral anticoagulant consumers and 18 920 warfarin consumers. They were reporting relationships between non-vitamin K antagonist oral anticoagulants and warfarin in subjects with atrial fibrillation and liver disease. Odds ratio (OR) with 95% confidence intervals (CIs) was calculated to evaluate the prognostic role of the efficacy and safety of non-vitamin K antagonist oral anticoagulants compared with warfarin in subjects with atrial fibrillation and liver disease subjects using the dichotomous method with a random or fixed-effect model. RESULTS: Non-vitamin K antagonist oral anticoagulants consumption was significantly related to lower all-cause mortality in subjects with atrial fibrillation and liver disease (OR, 0.90; 95% CI, 0.81-0.99, P = .03); lower intracranial haemorrhage (OR, 0.67; 95% CI, 0.55- 0.82, P < .001) and low stroke and system embolism (OR, 0.76; 95% CI, 0.68-0.86, P < .001) compared with warfarin consumption. However, non-vitamin K antagonist oral anticoagulants consumption was not significantly related to lower major bleeding in subjects with atrial fibrillation and liver disease (OR, 0.73; 95% CI, 0.52-1.02, P = .06); and gastrointestinal bleeding (OR, 0.93; 95% CI, 0.58-1.49, P = .77) compared with warfarin consumption. CONCLUSIONS: Based on this meta-analysis, non-vitamin K antagonist oral anticoagulant consumption may have an independent lower risk relationship with all-cause mortality, intracranial haemorrhage, and stroke and system embolism compared with warfarin consumption in subjects with atrial fibrillation and liver disease. This relationship forces us to recommend non-vitamin K antagonist oral anticoagulant use in subjects with atrial fibrillation and liver disease for better outcomes and to avoid any possible complications. Further studies are required.

Protective Effect of Hesperidin Against Sepsis-Induced Lung Injury by Inducing the Heat-Stable Protein 70 (Hsp70)/Toll-Like Receptor 4 (TLR4)/ Myeloid Differentiation Primary Response 88 (MyD88) Pathway.

BACKGROUND Sepsis-induced lung injury is associated with high mortality. The present investigation evaluated the protective effect of hesperidin against sepsis-induced lung injury and also postulates the possible mechanism of its action. MATERIAL AND METHODS Lung injury was induced by sepsis in all animals, in which sepsis was produced by cecal ligation and puncture (CLP). Animals were treated with hesperidin 10 and 20 mg/kg i.v. 30 min after the surgery. Oxygenation index and lung injury score were determined and levels of pro-inflammatory mediators and markers of oxidative stress were also estimated in the lung tissues. Moreover, expression of caspase-3, B-cell lymphoma (Bcl-2), Toll-like receptor 4 (TLR4), heat-stable protein 70 (Hsp70) and myeloid differentiation primary response 88 (MyD88) protein was estimated by Western blot assay and immunofluorescence assay. RESULTS Hesperidin attenuated the partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio and lung injury score in CLP-induced lung injury mice. There was a significant (p<0.01) decrease in the level of pro-inflammatory mediators in the lung tissue of CLP-induced lung injury mice. Moreover, markers of oxidative stress were attenuated in the hesperidin-treated group. Treatment with hesperidin attenuated the expression of caspase-3, Bcl-2, TLR4, Hsp70, and MyD88 protein in the lung tissue of CLP-induced lung injury mice. CONCLUSIONS Hesperidin protects against lung injury by attenuating the Hsp70/TLR4/MyD88 pathway in CLP-induced lung injury mice.

Factors affecting the work competency and stability of family doctors in Shanghai: a tracking study.

BACKGROUND: Family doctors can fulfill the gatekeeper duty to protect the residents' health, which depends on their work competency and stability. The study aimed to identify factors influencing work competency and stability among Shanghai family doctors. METHODS: This study was a 2-year follow-up survey (2013/2016). A representative sample of 146 family doctors in Shanghai community health service centers was interviewed in 2013. The tracked sample (n = 142) was resurveyed in 2016. A 50-item questionnaire organized into four parts, i.e., general demographic characteristics, working conditions, cognition about family doctor services, and job satisfaction was issued to all family doctors. Models for factors influencing family doctors' work competency and stability were then established. The collected data were analyzed using ordinal regression methods and descriptive, factor, and multiple-factor analyses. RESULTS: The family doctors' work competency model showed demographic characteristics (education level and job title), family doctors' team, family doctors' training, grasp of specific content regarding the family doctor system, and whether the family doctors' ability was played and demonstrated were statistically significant at different levels (P < 0.05). The analysis of family doctors' work stability showed that work competency (whether it was possible to provide residents with all contents specified in the contract service package, employment form, and support satisfaction) and work cognition (whether the daily work was meaningful and had value) had a significant impact on work stability (P < 0.05). CONCLUSION: Family doctors' job satisfaction is a key factor affecting their work stability. Family doctors' competency can also affect their job stability, and their work cognition may play a role in work competency and stability. This study provides evidence for strengthening the stability of the family doctor teams in Shanghai.

A preliminary effect analysis of family doctor and medical insurance payment coordination reform in Changning District of Shanghai, China.

BACKGROUND: Changning District of Shanghai pioneered in implementing Family Doctor and Medical Insurance Payment Coordination Reform. The survey aimed to assess the effect of the reform to provide a decision-making basis for ensuring the "gatekeeper" role of the family doctor. METHODS: A cross-sectional survey was conducted using a self-designed questionnaire in Changning District of Shanghai during January and February in 2014. Multi-stage random cluster was applied and 3040 residents were selected. Comparisons were made with statistically test between the contracted and non-contracted residents in four policy targeted dimensions, doctor-visiting behavior, health management and status, medical cost control and satisfaction. RESULTS: Compared with the non-contracted residents, the contracted residents (72.9%) presented a higher prevalence rate of chronic diseases (32.6%), a higher proportion (51.9%) in first-contact in the community health service center and a higher proportion to refer to specialists as well (P < 0.001).The result showed that the average annual medical expense were significantly higher than non-contracted residents (P < 0.001), however, the difference disappeared after age, medical insurance and other socio-demographic variables were controlled. In terms of self-management of non-communicable diseases and complication prevention, the blood pressure control rate and blood glucose control rate for the contracted group were also higher than the counterparts, reaching up to 85.6 and 72.7% respectively. CONCLUSION: The preliminary analysis indicated that the contracted residents performed better in orderly doctor visiting behavior, health management behavior, health status and satisfaction. Follow up survey is necessary to further analyze the policy effect.

The effect of family doctor-contracted services on noncommunicable disease self-management in Shanghai, China.

BACKGROUND: Noncommunicable diseases (NCDs) are a major threat to population health worldwide. In Shanghai, China, a new pattern of NCD management-self-management-has been developed in community health service centres (CHSCs). OBJECTIVE: To clarify how contracting with CHSC-based family doctors (FDs) influences the engagement in and effectiveness of self-management behaviour among NCD patients. METHOD: We conducted two waves of a questionnaire survey (in 2013 and 2016) to collect data on patients with NCDs. Separate logistic regression models and longitudinal analysis were performed to examine the effect of contracting with an FD on NCD self-management and the effectiveness of this self-management. RESULTS: Nearly all contracted patients (80.79%) had implemented NCD self-management, while only 55.57% of non-contracted patients did so. The self-management effectiveness rate was also higher among contracted patients than among non-contracted ones (86.66% vs. 54.79%). In the population-averaged models, contracted patients had 2.25 and 2.91 times greater odds of implementing self-management and reporting that the self-management was effective, respectively, after controlling for all related variables. Additionally, awareness of FD-contracted services, satisfaction with CHSCs, and experiencing first contact at CHSCs had positive impacts on the implementation and effectiveness of self-management. CONCLUSIONS: FDs were important for ensuring that NCD patients engaged in self-management behaviour, the most common form of which was focus group. Participation in NCD focus groups may be key for attaining the effects of self-management, including improved health knowledge, greater health awareness, more frequent engagement in health behaviour, and, most importantly, greater practice of self-monitoring. Self-management might help to achieve greater NCD control.

Exosomes from MiR-126-Overexpressing Adscs Are Therapeutic in Relieving Acute Myocardial Ischaemic Injury.

BACKGROUND/AIMS: Recent studies have indicated that exosomes play an important role in adipose-derived stem cell (ADSC) transplant-mediated ischaemic heart disease therapy. However, the treatment effect is not obvious. The aim of this study is to investigate whether ADSC-derived exosomes enriched with microRNA (miR)-126 have a more protective effect on acute myocardial infarction (AMI). METHODS: Exosomes were characterized by transmission electron microscopy, and the exosome particles were further examined using nanoparticle tracking analyses. A rat model of myocardial infarction and in vitro model of hypoxia-induced H9c2 myocardial cell injury were established to study the protective mechanism of exosomes from miR-126-overexpressing ADSCs. RESULTS: The in vitro results showed that exosomes derived from miR-126-overexpressing ADSCs decreased H9c2 myocardial cell injury by reducing inflammation factor expression during hypoxia induction. The miR-126-enriched exosomes also decreased the expression of fibrosis-related proteins of H9c2 cells under hypoxic conditions. Matrigel® and Transwell® assays showed that miR-126-enriched exosomes significantly promoted microvascular generation and migration, respectively. In vivo studies confirmed that exosomes derived from ADSCs significantly decreased the myocardial injury area of infarction, especially after miR-126-enriched exosome treatment. Cardiac fibrosis and inflammatory cytokine expression were also decreased after treatment with miR-126-enriched exosomes. However, blood vessel formation was promoted in the infarction region of AMI rats. CONCLUSIONS: The results suggested that the expression of miR-126-enhanced ADSC-derived exosomes prevented myocardial damage by protecting myocardial cells from apoptosis, inflammation, fibrosis, and increased angiogenesis.

Prionic Acid: An Effective Sex Attractant for an Important Pest of Sugarcane, Dorysthenes granulosus (Coleoptera: Cerambycidae: Prioninae).

Male Dorysthenes granulosus (Thomson, 1860) (Coleoptera: Cerambycidae: Prioninae) were caught in traps baited with racemic 3,5-dimethyldodecanoic acid (prionic acid) during field screening trials in China that tested known cerambycid pheromones. This species is an important pest of sugarcane (Saccharum officinarum L.). In follow-up dose-response trials, plastic sachets loaded with 1 or 0.1 mg of prionic acid were equally attractive to male beetles, whereas lower doses were no better than controls. Two commercial prionic acid lures also were attractive, suggesting that traps baited with prionic acid can be rapidly incorporated into integrated pest management programs targeting this major pest. It is likely that this compound is a major component of the female-produced sex pheromone of D. granulosus because this species is in the same subfamily as Prionus californicus Motschulsky, 1845, the species from which prionic acid was originally identified.

Integrated characterization of filler tobacco leaves: HS-SPME-GC-MS, E-nose, and microbiome analysis across different origins.

This study delves into the aroma characteristics and microbial composition of filler tobacco leaves (FTLs) sourced from six distinct cigar-growing regions within Yunnan, China, following standardized fermentation. An integrated approach using gas chromatography-mass spectrometry (GC-MS), electronic nose (E-nose), and microbiome analysis was employed for comprehensive profiling. Results derived from Linear Discriminant Analysis (LDA) using E-nose data confirmed the presence of notable variability in flavor substance profiles among the FTLs from six regions. Additionally, GC-MS was used to discern disparities in volatile organic compound (VOC) distribution across FTLs from these regions, identifying 92, 81, 79, 58, 69, and 92 VOCs within each respective sample set. Significantly, 24 VOCs emerged as pivotal determinants contributing to the heterogeneity of flavor profiles among FTLs from diverse origins, as indicated by Variable Importance for the Projection (VIP) analysis. Furthermore, distinctions in free amino acid content and chemical constituents were observed across FTLs. Of noteworthy significance, solanone, isophorone, durene, (-)-alpha-terpineol, and 2,3'-bipyridine exhibited the strongest correlations with microbiome data, with fungal microorganisms exerting a more pronounced influence on metabolites, as elucidated through two-way orthogonal partial least-squares (O2PLS) modeling. These findings provide a theoretical and technical basis for accurately evaluating the synchronization of FTLs in aromas and fermentation processes, and they will enhance the quality of fermented FTLs and foster the growth of the domestic cigar tobacco industry ultimately.

Effects of mesencephalic astrocyte-derived neurotrophic factor on sepsis-associated acute kidney injury.

BACKGROUND: To determine the protective role of mesencephalic astrocyte-derived neurotrophic factor (MANF) in regulating sepsis-associated acute kidney injury (S-AKI). METHODS: A total of 96 mice were randomly divided into the control group, control+MANF group, S-AKI group, and S-AKI+MANF group. The S-AKI model was established by injecting lipopolysaccharide (LPS) at 10 mg/kg intraperitoneally. MANF (200 µg/kg) was administered to the control+MANF and S-AKI+MANF groups. An equal dose of normal saline was administered daily intraperitoneally in the control and S-AKI groups. Serum and kidney tissue samples were obtained for biochemical analysis. Western blotting was used to detect the protein expression of MANF in the kidney, and enzyme-linked immunosorbent assay (ELISA) was used to determine expression of MANF in the serum, pro-inflammatory cytokines (tumor necrosis factor-α [TNF-α] and interleukin-6 [IL-6]). Serum creatinine (SCr), and blood urea nitrogen (BUN) were examined using an automatic biochemical analyzer. In addition, the kidney tissue was observed for pathological changes by hematoxylin-eosin staining. The comparison between two groups was performed by unpaired Student's t-test, and statistics among multiple groups were carried out using Tukey's post hoc test following one-way analysis of variance (ANOVA). A P-value <0.05 was considered statistically significant. RESULTS: At the early stage of S-AKI, MANF in the kidney tissue was up-regulated, but with the development of the disease, it was down-regulated. Renal function was worsened in the S-AKI group, and TNF-α and IL-6 were elevated. The administration of MANF significantly alleviated the elevated levels of SCr and BUN and inhibited the expression of TNF-α and IL-6 in the kidney. The pathological changes were more extensive in the S-AKI group than in the S-AKI+MANF group. CONCLUSION: MANF treatment may significantly alleviate renal injury, reduce the inflammatory response, and alleviate or reverse kidney tissue damage. MANF may have a protective effect on S-AKI, suggesting a potential treatment for S-AKI.

Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) Alleviates Sepsis-Induced Cardiomyopathy by Inhibiting Pyroptosis.

Background: Sepsis-induced cardiomyopathy (SIC) is a common complication of sepsis accompanied by high prevalence and mortality in sepsis patients. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a neurotrophic factor, and it exerts critical functions in various diseases, including heart diseases, while its effect on SIC remains elusive. Hence, we aimed to investigate the action of MANF on SIC. Methods: This study was under the guidance of Gongli Hospital, Shanghai, China from January 2021 to December 2021. H9c2 cells and mice were induced by LPS to establish SIC in vitro and in vivo models. qRT-PCR and Western blot were used to determine gene and protein expressions. The levels of MANF, Interleukin-1ß (IL-1ß), Interleukin 18 (IL-18), creatine kinase-MB (CK-MB), and cardiac troponin I (cTn I) were detected using ELISA assay. Cell pyroptosis determination was performed by flow cytometry. The DCFDA assay kit was used to determine ROS production. Results: In SIC in vitro model, LPS induced cell pyroptosis (P<0.001) and ROS accumulation (P<0.001). Besides, MANF was decreased in LPS-induced H9c2 cells (P<0.001) and SIC patients (P<0.001). In addition, overexpression of MANF ameliorated SIC-induced injury in H9C2 cells (P<0.001). Furthermore, inhibition of NLRP3 rescued the function of MANF on SIC-induced injury in H9C2 cells (P<0.001). Moreover, enforced MANF suppressed the SIC-induced injury in vivo model (P<0.001). Conclusion: MANF was down-regulated in SIC. Overexpressed MANF ameliorated the SIC injury by inhibiting NLRP3-mediated pyroptosis.

Effects of Fermented Green Tea Waste Extract Gels on Oxidative Damage in Short-Term Passive Smoking Mice.

Passive smoking is extensively studied because of its harmfulness to human health. In this study, the effects of fermented green tea waste extract gels (GTEG) on oxidative damage in mice exposed to short-term cigarette smoke (CS) were investigated. The GTEG is prepared from green tea waste extract and microbial transglutaminase (MTGase). The lung injury model of mice was established through passive smoking for 5 days. The experimental results revealed the following findings. (1) The GTEG induced by MTGase has obvious gel properties; (2) GTEG has strong biological activity and antioxidant properties in vitro; (3) The passive smoking model was established successfully; specifically, the lung tissue of the model mice exhibited inflammatory symptoms, oxidative stress response appeared in their bodies, and their inflammatory indicators increased; (4) Compared with the passive smoking model group, the mice, which were exposed to CS and received GTEG treatment, exhibited increased food intake and body weight; increased total superoxide dismutase and glutathione peroxidase activity in serum; significant decreases (p < 0.05) in the content levels of the inflammatory factors malondialdehyde, interleukin (IL)-6, and tumor necrosis factor α (TNF-α); and inhibited expression of IL-6, IL-33, TNF-α, and IL-1ß inflammatory genes. The results indicated that taking GTEG can relieve the oxidative stress injury of mice caused by short-term CS and has antioxidant properties.

[Detection of inorganic elements in parasitic plants and their hosts].

Parasitic plants are destructive agricultural pests. Today, parasitic plants have been recognized as serious pests causing considerable economic damage on crop and woods in China. Parasites are among the most destructive weeds known, and more and more people begin to pay more attention to the relationship between parasitic plant and host. Two cistanches and their hosts were analyzed and characterized by ICP-AES. The contents of K, P, Na, Ca, Mg, Fe, B, Cu, Zn, Al and Mn in Tamarix chinensis, Haloxylon ammodendron, Cistanche deserticola and Cistanche tubulosa were determined. The results showed that the spectra of main elements of the two cistanches and their hosts are similar, but the content of each element is different. The content of K, P, N and Ca is higher than other element, The content of K and P in Cistanche deserticola and Cistanche tubulosa is higher than the content of theirs hosts. The present study provides a new scientific foundation for further study and general application of parasitic plant.

Cangrelor ameliorates CLP-induced pulmonary injury in sepsis by inhibiting GPR17.

BACKGROUND: Sepsis is a common complication of severe wound injury and infection, with a very high mortality rate. The P2Y12 receptor inhibitor, cangrelor, is an antagonist anti-platelet drug. METHODS: In our study, we investigated the protective mechanisms of cangrelor in CLP-induced pulmonary injury in sepsis, using C57BL/6 mouse models. RESULTS: TdT-mediated dUTP Nick-End Labeling (TUNEL) and Masson staining showed that apoptosis and fibrosis in lungs were alleviated by cangrelor treatment. Cangrelor significantly promoted surface expression of CD40L on platelets and inhibited CLP-induced neutrophils in Bronchoalveolar lavage fluid (BALF) (p < 0.001). We also found that cangrelor decreased the inflammatory response in the CLP mouse model and inhibited the expression of inflammatory cytokines, IL-1ß (p < 0.01), IL-6 (p < 0.05), and TNF-α (p < 0.001). Western blotting and RT-PCR showed that cangrelor inhibited the increased levels of G-protein-coupled receptor 17 (GPR17) induced by CLP (p < 0.001). CONCLUSION: Our study indicated that cangrelor repressed the levels of GPR17, followed by a decrease in the inflammatory response and a rise of neutrophils in BALF, potentially reversing CLP-mediated pulmonary injury during sepsis.

Polydatin Alleviates Septic Myocardial Injury by Promoting SIRT6-Mediated Autophagy.

Sepsis is a life-threatening condition. Polydatin (PD), a small natural compound from Polygonum cuspidatum, possesses antioxidant and anti-inflammatory properties. However, the protective mechanism of PD on sepsis-induced acute myocardial damage is still unclear. The aim of this study was to investigate the effect and mechanism of action of PD on lipopolysaccharide (LPS)-induced H9c2 cells and in a rat model of sepsis, and explored the role of PD-upregulated sirtuin (SIRT)6. LPS-induced H9c2 cells were used to simulate sepsis. Cecal ligation and puncture (CLP)-induced sepsis in rats were used to verify the protective effect of PD. ELISA, western blotting, immunofluorescence, immunohistochemistry, and flow cytometry were used to study the protective mechanism of PD against septic myocardial injury. PD pretreatment suppressed LPS-induced H9c2 cell apoptosis by promotion of SIRT6-mediated autophagy. Downregulation of SIRT6 or inhibition of autophagy reversed the protective effect of PD on LPS-induced apoptosis. PD pretreatment also suppressed LPS-induced inflammatory factor expression. CLP-induced sepsis in rats showed that PD pretreatment decreased CLP-induced myocardial apoptosis and serum tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6 expression. 3-Methyladenine (autophagy inhibitor) pretreatment prevented the protective effect of PD on septic cardiomyopathy. SIRT6 expression was increased with PD treatment, which confirmed that PD attenuates septic cardiomyopathy by promotion of SIRT6-mediated autophagy. All these results indicate that PD has potential therapeutic effects that alleviate septic myocardial injury by promotion of SIRT6-mediated autophagy.

The Heat Shock Protein 70 Plays a Protective Role in Sepsis by Maintenance of the Endothelial Permeability.

Sepsis is a severe system inflammatory response syndrome in response to infection. The vascular endothelium cells play a key role in sepsis-induced organ dysfunction. The heat shock protein 70 (HSP70) has been reported to play an anti-inflammatory role and protect from sepsis. The present study is aimed at finding the function of HSP70 against sepsis in vascular endothelium cells. Lipopolysaccharide (LPS) and HSP70 agonist and inhibitor were used to treat HUVEC. Cell permeability was measured by transepithelial electrical resistance (TEER) assay and FITC-Dextrans. Cell junction protein levels were measured by western blot. Mice were subjected to cecal ligation and puncture (CLP) to establish a sepsis model and were observed for survival. After LPS incubation, HSP70 expression was decreased in HUVEC. LPS induced the inhibition of cell viability and the increases of IL-1ß, IL-6, and TNF-α. Furthermore, cell permeability was increased and cell junction proteins (E-cadherin, occludin, and ZO-1) were downregulated after treatment with LPS. However, HSP70 could reverse these effects induced by LPS in HUVEC. In addition, LPS-induced elevated phosphorylation of p38 can be blocked by HSP70. On the other hand, we found that inhibition of HSP70 had similar effects as LPS and these effects could be alleviated by the inhibitor of p38. Subsequently, HSP70 was also found to increase survival of sepsis mice in vivo. In conclusion, HSP70 plays a protective role in sepsis by maintenance of the endothelial permeability via regulating p38 signaling.

Polydatin protects against acute myocardial infarction-induced cardiac damage by activation of Nrf2/HO-1 signaling.

Polydatin is a traditional Chinese medicine that provides myocardial protection after acute myocardial infarction (AMI). The study aim was to investigate the myocardial protection polydatin in H9c2 myocardial cells cultured in a hypoxic atmosphere and in a rat AMI model induced by ligating the left anterior descending coronary artery and treated with polydatin 100 mg/kg/day for 30 days. The involvement of Nrf2 in mediating the effects of polydatin was investigated in H9c2 cells following Nrf2 knockdown by transfection of siRNA. Polydatin suppressed hypoxia-induced H9c2 cell apoptosis and reactive oxygen species (ROS) generation by promoting Nrf2/HO-1 signaling. Nrf2 knockdown reversed the protective effects of polydatin against hypoxia-induced myocardial cell injury. The in vivo results were consistent with polydatin suppression of apoptosis and ROS generation in myocardial tissue by promotion of Nrf2/HO-1 signaling. In conclusion, polydatin effectively inhibited hypoxia- and AMI-induced myocardial damage by promotion of Nrf2/HO-1 signaling.