Mitochondria-derived peptide is an effective target for treating streptozotocin induced painful diabetic neuropathy through induction of activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator 1alpha -mediated mitochondrial biogenesis.

Painful Diabetic Neuropathy (PDN) is a common diabetes complication that frequently causes severe hyperalgesia and allodynia and presents treatment challenges. Mitochondrial-derived peptide (MOTS-c), a novel mitochondrial-derived peptide, has been shown to regulate glucose metabolism, insulin sensitivity, and inflammatory responses. This study aimed to evaluate the effects of MOTS-c in streptozocin (STZ)-induced PDN model and investigate the putative underlying mechanisms. We found that endogenous MOTS-c levels in plasma and spinal dorsal horn were significantly lower in STZ-treated mice than in control animals. Accordingly, MOTS-c treatment significantly improves STZ-induced weight loss, elevation of blood glucose, mechanical allodynia, and thermal hyperalgesia; however, these effects were blocked by dorsomorphin, an adenosine monophosphate-activated protein kinase (AMPK) inhibitor. In addition, MOTS-c treatment significantly enhanced AMPKα1/2 phosphorylation and PGC-1α expression in the lumbar spinal cord of PDN mice. Mechanistic studies indicated that MOTS-c significantly restored mitochondrial biogenesis, inhibited microglia activation, and decreased the production of pro-inflammatory factors, which contributed to the alleviation of pain. Moreover, MOTS-c decreased STZ-induced pain hypersensitivity in PDN mice by activating AMPK/PGC-1α signaling pathway. This provides the pharmacological and biological evidence for developing mitochondrial peptide-based therapeutic agents for PDN.

Clinical and molecular characteristics of Klebsiella pneumoniae infection in a tertiary general hospital of Wuhan, China.

OBJECTIVES: The aim of this study was to investigate the clinical and molecular characteristics of Klebsiella pneumoniae infection from a tertiary general hospital in Wuhan, China. METHODS: From December 2019 to August 2022, 311 non-duplicate isolates of K. pneumoniae were collected from a tertiary hospital in Wuhan. These comprised 140 carbapenem-resistant K. pneumoniae (CRKP) isolates and 171 carbapenem-susceptible K. pneumoniae (CSKP) isolates. The clinical characteristics of patients with K. pneumoniae infection were retrospectively collected. Polymerase chain reaction (PCR) assays were used to identify the main carbapenem resistance genes, virulence genes and multi-locus sequence typing (MLST) profiles of the isolates, and the Galleria mellonella infection model was used to determine their virulence phenotypes. RESULTS: Independent risk factors for CRKP infection were hypertension, neurological disorders, being admitted to the intensive care unit (ICU) and prior use of antibiotics. Patient with CRKP infection had higher mortality than those with CSKP infection (23.6% vs 14.0%, P < 0.05). One hundred and two sequence types (STs) were identified among the K. pneumoniae isolates, and the most prevalent ST type was ST11 (112/311, 36.0%). All of the ST11 isolates were CRKP. Among the 112 ST11 isolates, 105 (93.8%) harboured the carbapenem resistance gene blaKPC-2 (ST11-KPC-2), and of these isolates, 78 (74.3%, 78/105) contained all of the four virulence genes, namely rmpA, rmpA2, iroN and iucA, suggesting that these genes were widespread among the isolates responsible for K. pneumoniae infections. CONCLUSION: In this study, ST11-KPC-2 was responsible for most of the K. pneumoniae infection cases. Carbapenem resistance rather than the co-occurrence of the virulence genes rmpA, rmpA2, iroN and iucA was associated with K. pneumoniae infection-related mortality during hospitalisation. Furthermore, a high proportion of ST11-KPC-2 isolates carried all of the four virulence genes.

Insufficient compensatory pancreatic ß-cells function might be closely associated with hyperuricemia in U.S. adults: evidence from the National Health and Nutrition Examination Survey.

BACKGROUND: The prevalence of hyperuricemia (HUA) is gradually increasing worldwide. HUA is closely related to diabetes, but the relationship between HUA and pancreatic ß-cells function in the population is unclear. The purpose of this article is to investigate the association between pancreatic ß-cells and HUA. METHODS: This cross-sectional study examined the association between pancreatic ß-cells and HUA in 1999-2004 using data from the National Health and Nutrition Examination Survey (NHANES). Subjects were divided into two groups: HUA and non-HUA. Pancreatic ß-cells function levels were assessed using homeostasis model assessment version 2-%S (HOMA2-%S), homeostasis model assessment version 2-%B (HOMA2-%B) and disposition index (DI). Multivariate logistic regression models and restricted cubic spline models were fitted to assess the association of pancreatic ß-cells function with HUA. RESULTS: The final analysis included 5496 subjects with a mean age of 46.3 years (standard error (SE), 0.4). The weighted means of HOMA2-%B, HOMA2-%S and DI were 118.1 (SE, 1.0), 69.9(SE, 1.1) and 73.9 (SE, 0.7), respectively. After adjustment for major confounders, participants in the highest quartile of HOMA2-%B had a higher risk of HUA (OR = 2.55, 95% CI: 1.89-3.43) compared to participants in the lowest quartile. In contrast, participants in the lowest quartile of HOMA2-%S were significantly more likely to have HUA than that in the highest quartile (OR = 3.87, 95% CI: 2.74-5.45), and similar results were observed in DI (OR = 1.98, 95% CI: 1.32-2.97). Multivariate adjusted restricted cubic spline analysis found evidence of non-linear associations between HOMA2-%B, HOAM2-%S, DI and the prevalence of HUA. CONCLUSION: Our finding illustrated the indicators of inadequate ß-cells compensation might be a new predictor for the presence of HUA in U.S. adults, highlighting a critical role of pancreatic ß-cells function on HUA.

Trends in prevalence of hearing loss in adults in the USA 1999-2018: a cross-sectional study.

BACKGROUND: A better understanding of how the prevalence of hearing loss and its associated factors change over time could help in developing an appropriate program to prevent the development of hearing loss. METHODS: Population-representative cross-sectional data from the United States National Health and Nutrition Examination Survey (NHANES) were used to estimate the trends in the prevalence of hearing loss among adults in the USA over the period 1999-2018. A total of 15,498 adult participants aged 20 years or older had complete audiometric examination data. Logistic regression was employed to evaluate the trend in hearing loss; weighted Rao-Scott χ2 tests and univariate logistic regression analyses were used to examine the association between hearing loss and relevant factors. RESULTS: The overall hearing loss prevalence in 1999-2018 was 19.1% 19.1 (95% CI, 18.0-20.2%). The prevalence of hearing loss decreased in cycles (P for trend < 0.001). For participants aged 20-69 years, the prevalence decreased from 15.6% (95% CI, 12.9-18.4%) in 1999-2000 to 14.9% (95% CI, 13.2- 16.6%) in 2015-2016; for participants aged > 70 years the prevalence decreased from 79.9% (95% CI, 76.1-83.8%) in 2005-2006 to 64.5% (95% CI, 58.8-70.2%) in 2017-2018. Participants with hearing loss were likely to be older, male, non-Hispanic white, and to have not completed high school. Mild hearing loss was more prevalent among those aged 20-79 years; in those aged over 80 years the prevalence of moderate hearing loss exceeded that of mild loss. Among all otologically normal participants, hearing thresholds increased with age across the entire frequency range. CONCLUSIONS: The prevalence of hearing loss in USA adults changed over the period 1999-2018. The trends observed provide valuable insight for making public health plans and allocating resources to hearing care. Further investigation is necessary to monitor hearing loss and its potential risk factors.

Vinculin Identified as a Potential Biomarker in Hand-Arm Vibration Syndrome Based on iTRAQ and LC-MS/MS-Based Proteomic Analysis.

Local vibration can induce vascular injuries, one example is the hand-arm vibration syndrome (HAVS) caused by hand-transmitted vibration (HTV). Little is known about the molecular mechanism of HAVS-induced vascular injuries. Herein, the iTRAQ (isobaric tags for relative and absolute quantitation) followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomics approach was applied to conduct the quantitative proteomic analysis of plasma from specimens with HTV exposure or HAVS diagnosis. Overall, 726 proteins were identified in iTRAQ. 37 proteins upregulated and 43 downregulated in HAVS. Moreover, 37 upregulated and 40 downregulated when comparing severe HAVS and mild HAVS. Among them, Vinculin (VCL) was found to be downregulated in the whole process of HAVS. The concentration of vinculin was further verified by ELISA, and the results suggested that the proteomics data was reliable. Bioinformative analyses were used, and those proteins mainly engaged in specific biological processes like binding, focal adhesion, and integrins. The potential of vinculin application in HAVS diagnosis was validated by the receiver operating characteristic curve.

Rac1/PAK1 signaling contributes to bone cancer pain by Regulation dendritic spine remodeling in rats.

Bone cancer pain (BCP) is severe chronic pain caused by tumor metastasis to the bones, often resulting in significant skeletal remodeling and fractures. Currently, there is no curative treatment. Therefore, insight into the underlying mechanisms could guide the development of mechanism-based therapeutic strategies for BCP. We speculated that Rac1/PAK1 signaling plays a critical role in the development of BCP. Tumor cells implantation (TCI) into the tibial cavity resulted in bone cancer-associated mechanical allodynia. Golgi staining revealed changes in the excitatory synaptic structure of WDR (Wide-dynamic range) neurons in the spinal cord, including increased postsynaptic density (PSD) length and thickness, and width of the cleft. Behavioral and western blotting test revealed that the development and persistence of pain correlated with Rac1/PAK1 signaling activation in primary sensory neurons. Intrathecal injection of NSC23766, a Rac1 inhibitor, reduced the persistence of BCP as well as reversed the remodeling of dendrites. Therefore, we concluded that activation of the Rac1/PAK1 signaling pathway in the spinal cord plays an important role in the development of BCP through remodeling of dendritic spines. Modulation of the Rac1/PAK1 pathway may be a potential strategy for BCP treatment.

Renal nerve stimulation identifies renal innervation and optimizes the strategy for renal denervation in canine.

BACKGROUND: Renal denervation (RDN) was still performed without any intra-procedural method for nerve mapping. Whether renal nerve stimulation (RNS) is an efficient way to identify renal autonomic innervation and optimize the strategy for RDN remain to be worthy for further exploration. METHODS: The characteristics of renal autonomic innervation at the sites with different blood pressure (BP) responses to RNS were explored. Then, dogs anatomically eligible for RDN were randomly assigned into elevated BP response ablation group, reduced BP response ablation group, and RNS-control group. The postoperative outcomes were measured at baseline and after 4 weeks follow-up. RESULTS: The proportion of afferent sensory nerve was higher at elevated BP response sites (ERS) than reduced BP response sites (RRS) and non-response sites (NRS) (P = 0.012 and P = 0.004). Conversely, the proportion of parasympathetic nerve at RRS was the highest (RRS vs. ERS, P = 0.017; RRS vs. NRS, P = 0.023). More importantly, there was a significant correlation between systolic blood pressure changes and the area ratios of afferent sensory and parasympathetic nerve (R = 0.859; P < 0.001). In addition, ablation at BP-elevation sites can result in a significant decrease in BP and plasma norepinephrine (NE) after 4 weeks (P = 0.002; P = 0.008), while ablation at BP-reduction sites can lead to significant increases in BP and plasma NE (P = 0.016; P = 0.033). CONCLUSIONS: RNS is an effective method to identify renal autonomic innervation. It could not only help to identify optimal target sites, but also avoid ablation of sympathetic-inhibitory areas during RDN.

Adsorption of oxytetracycline on subalpine meadow soil from Zoige Plateau, China: Effects of the coexisting Cu2.

Subalpine meadow soil with high moisture and humus content is a unique soil type in the Zoige Plateau. Oxytetracycline and copper are common soil contaminants which interact to form compound pollution. Oxytetracycline's adsorption on natural subalpine meadow soil and its components (humin and the soil without iron and manganese oxides) was studied in the laboratory with and without the presence of Cu2+. The effects of temperature, pH and Cu2+ concentration were documented in batch experiments, allowing deduction of the main sorption mechanisms. The adsorption process had two phases: one rapid, taking place in the first 6 h, and another slower, reaching equilibrium at around 36 h. The adsorption kinetics were pseudo-second-order, and the adsorption isotherm conformed to the Langmuir model at 25 °C. Higher concentrations oxytetracycline increased the adsorption, but higher temperature did not. The presence of Cu2+ had no effect on the equilibrium time, but the amount and rate adsorbed were much greater with Cu2+ concentration increased (except for the soil without iron and manganese oxides). The amounts adsorbed with/without Cu2+ were in the order the humin from subalpine meadow soil (7621 and 7186 µg/g) > the subalpine meadow soil (7298 and 6925 µg/g) > the soil without iron and manganese oxides (7092 and 6862 µg/g), but the difference among those adsorbents was slight. It indicates that humin is a particularly important adsorbent in the subalpine meadow soil. The amount of oxytetracycline adsorbed was greatest at pH 5-9. In addition, Surface complexation through metal bridging was the most important sorption mechanism. Cu2+ and oxytetracycline formed positively-charged complex that was adsorbed and then formed a ternary complex "adsorbent-Cu(II)-oxytetracycline", in which Cu2+ acted as a bridge. These findings provide a good scientific basis for soil remediation, and for assessing environmental health risks.

LncRNA RPPH1 acts as a molecular sponge for miR-122 to regulate Wnt1/ß-catenin signaling in hepatocellular carcinoma.

This study aimed to explore the role of lncRNA RPPH1 in hepatocellular carcinoma. The expression of RPPH1 and miR-122 was determined by Real-time PCR. Cell proliferation and colony formation assays were employed to monitor cell growth in vitro. Wound healing and Transwell assays were applied to detect cell migration and invasion. A dual-luciferase reporter assay was used to verify the interaction between RPPH1 and miR-122. The in vivo function of RPPH1 was illustrated by xenograft tumor models. The results showed that the expression of RPPH1 was markedly upregulated in human HCC specimens and cell lines compared to normal controls. However, the trend of miR-122 was the opposite. RPPH1 facilitates the proliferation, migration, and invasion of HCC cells and synchronously suppresses cell apoptosis. The dual-luciferase assay confirmed the relationship between RPPH1 and miR-122. Rescue experiments showed that RPPH1 acted as a competing endogenous RNA (ceRNA) by sponging miR-122 in HCC cells. Moreover, RPPH1 positively regulated the expression of Wnt1 and its downstream targets through miR-122. Our study demonstrates for the first time that RPPH1 promotes HCC progression via the miR-122/Wnt1/ß-catenin axis, which may represent a valuable therapeutic target for patients with HCC.

Association of coffee consumption with the prevalence of hearing loss in US adults, NHANES 2003-2006.

OBJECTIVE: This study aims to explore the association between coffee consumption and the prevalence of hearing loss in American adults based on a national population-based survey. DESIGN: Cross-sectional analysis of reported audiometric status and coffee intake from the 2003-2006 National Health and Nutrition Examination Survey (NHANES). Multivariate logistic regression, forest plots and restricted cubic spline (RCS) analyses were used to explore the associations and dose-response relationships between coffee consumption frequency and hearing loss. SETTING: The USA. PARTICIPANT: This study included 1894 individuals aged ≥ 20 from the 2003-2006 NHANES. RESULTS: In this study, the prevalence of speech-frequency hearing loss (SFHL) and high-frequency hearing loss (HFHL) among the participants was 35·90 % and 51·54 %, respectively. Compared with those who no consumed coffee, non-Hispanic White who consumed ≥ 4 cups/d had higher prevalence of SFHL (OR: 1·87; 95 % CI: 1·003. 3·47). And a positive trend of coffee consumption frequency with the prevalence of HFHL was found (Ptrend = 0·001). This association of HFHL was similar for participants aged 20-64 (Ptrend = 0·001), non-Hispanic White (Ptrend = 0·002), non-noise exposure participants (Ptrend = 0·03) and noise-exposed participants (Ptrend = 0·003). The forest plots analysis found that the association between 1 cup-increment of daily coffee consumption and the prevalence of HFHL was statistically significant in males. RCS model supported a positive linear association of coffee consumption with SFHL (P for overall association = 0·02, P for nonlinearity = 0·48) and a positive non-linear association of coffee consumption with HFHL (P for overall association = 0·001, P for nonlinearity = 0·001). CONCLUSION: Our findings suggested that coffee consumption was associated with higher prevalence of hearing loss. Further cohort studies in larger population are needed to investigate these findings.

The association of periodontal disease and oral health with hypertension, NHANES 2009-2018.

BACKGROUND: Hypertension is a worldwide public health problem. We sought to explore the interaction of oral health and smoking on hypertension, and periodontal disease and smoking on hypertension. METHODS: We included 21,800 participants aged ≧ 30 years from the National Health and Nutrition Examination Survey (NHANES) 2009-2018. Information of oral health and periodontal disease were self-reported. Blood pressure was taken by trained personnel and/or physicians at mobile testing center. Multiple logistic regression was used to estimate the association between oral health, periodontal disease and the prevalence of hypertension. The effects of oral health and periodontal disease on hypertension under smoking status and age were analyzed by stratified and interaction analysis. RESULTS: A total of 21,800 participants were investigated, including 11,017 (50.54%) in hypertensive group and 10,783 (49.46%) in non-hypertensive group. Compared with the excellent/very good of oral health, the multivariable-adjusted OR of good, fair, and poor were 1.13 (95% CI, 1.02-1.27), 1.30 (95% CI, 1.15-1.47), and 1.48 (95% CI, 1.22-1.79) (p for trend < 0.001) for hypertension, respectively. Compared without periodontal disease group, the multivariable-adjusted OR of periodontal disease for hypertension was 1.21 (95% CI ,1.09-1.35) (p for trend < 0.001). Furthermore, we found the interactions between periodontal disease and smoking, oral health and smoking, periodontal disease and age, oral health and age were p < 0.001. CONCLUSIONS: An association between oral health and periodontal disease with the prevalence of hypertension was identified. There exists interactive effect of periodontal disease and smoking, oral health and smoking, periodontal disease and age, oral health and age on hypertension in American population over 30 years of age and older.

Combined effects of lead and manganese on locomotor activity and microbiota in zebrafish.

Exposure to lead (Pb) and manganese (Mn) during early life influences neurodevelopment and increases the risk of neurodegenerative disorders. However, the level of developmental neurotoxicity due to combined exposure to the two metals remains unclear. Although the microbiota plays an essential part in the development of the nervous system via the gut-brain axis, there is a paucity of information regarding the interactions between exposure to Pb and Mn, the destruction of the microbiome, and neurodevelopmental impacts. To fill in this knowledge gap, we investigated the developmental neurotoxicity and effects on the microbiota of Pb (0.05 mg·L-1) alone and in combination with Mn (0.3 mg·L-1) in zebrafish larvae. Our results revealed that combined exposure precipitated higher malformation rates and lower locomotor activity levels than exposure to either Pb or Mn alone. Additionally, when we separated the combined exposure group from the other groups by applying unsupervised principal coordinates analysis (PCoA) and linear discriminant analysis (LEfSe) of microflora sequencing results, we observed extensive alterations in microbial abundances under combined-exposure conditions. Functional prediction analysis showed that combined exposure contributed to altered amino acid and lipid metabolism, and also that combined exposure to Pb and Mn reflected the greatest number of differentially activated biological pathways compared to the other three groups. ATP-binding cassette G (ABCG) genes and genes related to serotonin signaling and metabolism were altered following combined Pb and Mn exposure and exhibited disparate trends vis-à-vis Pb or Mn exposure alone. According to the results, the combined exposure to Pb and Mn led to more severe effects on both zebrafish locomotor activity and gut microbial composition. We suggest that the microbiota contributes to the combined neurotoxicity by increasing ABCG5 and ABCG8 gene expression.

Water quality assessment and pollution source apportionment using multivariate statistical techniques: a case study of the Laixi River Basin, China.

Identifying potential sources of pollution in tributaries and determining their contribution rates are critical to the treatment of water pollution in main streams. In this paper, we conducted a multivariate statistical analysis on the water quality data of 12 parameters for 3 years (2018-2020) at six sampling sites in the Laixi River to qualitatively identify potential pollution sources and quantitatively calculate the contribution rates to reveal the tributaries' pollution status. Spatio-temporal cluster analysis (CA) divided 12 months into two parts, corresponding to the lightly polluted season (LPS) and highly polluted season (HPS), and six sampling sites were divided into two regions, corresponding to the lightly polluted region (LPR) and highly polluted region (HPR). Principal component analysis (PCA) was used to determine the potential sources of contamination, identifying four and three potential factors in the LPS and HPS, respectively. The absolute principal component score-multiple linear regression (APCS-MLR) receptor model quantitatively analyzed the contribution rates of identified pollution sources, and the importance of the different pollution sources in LPS can be ranked as domestic sewage and industrial wastewater and breeding pollution (33.80%) > soil weathering (29.02%) > agricultural activities (20.95%) > natural influence (13.03%). HPS can be classified as agricultural cultivation (41.23%), domestic sewage and industrial wastewater and animal waste (33.19%), and natural variations (21.43%). Four potential sources were identified in LPR ranked as rural domestic sewage (31.01%) > agricultural pollution (26.82%) > industrial effluents and free-range livestock and poultry pollution (25.13%) > natural influence (14.82%). Three identified latent pollution sources in HPR were municipal sewage and industrial effluents (37.96%) > agricultural nonpoint sources and livestock and poultry wastewater (33.55%) > natural sources (25.23%). Using multivariate statistical tools to identify and quantify potential pollution sources, managers may be able to enhance water quality in tributary watersheds and develop future management plans.

Hybrid Acid/alkali All Covalent Organic Frameworks Battery.

Covalent organic frameworks (COFs), thanks to their adjustable porous structure and abundant build-in functional motifs, have been recently regarded as promising electrode materials for a variety of batteries. There still remain grand opportunities to further utilizing their merits for developing advanced COFs-based batteries. In this paper, we propose a hybrid acid/alkali all-COFs battery by coupling pyrene-4,5,9,10-tetraone based COF cathode with anthraquinone based COF anode. In such a hybrid acid/alkali all-COFs battery, the cathodic COF favorably works in acid with a relatively positive potential, while the anodic COF preferably runs in alkali with a relatively negative potential. It thus can deliver a decently high discharge capacity of 92.97 mAh g-1 with a wide voltage window of 2.0 V, and exhibit high energy density of 74.2 Wh kg-1 along with a considerable cyclic stability over 300 cycles. The development of the proof-of-concept all-COFs battery may drive forward the improvement of newly cost-effective and performance-reliable energy storage devices.

Indoor microbiome, microbial and plant metabolites, chemical compounds, and asthma symptoms in junior high school students: a multicentre association study in Malaysia.

BACKGROUND: Indoor microbial exposure is associated with asthma, but the health effects of indoor metabolites and chemicals have not been comprehensively assessed. METHODS: We collected classroom dust from 24 junior high schools in three geographically distanced areas in Malaysia (Johor Bahru, Terengganu and Penang), and conducted culture-independent high-throughput microbiome and untargeted metabolomics/chemical profiling. RESULTS: 1290 students were surveyed for asthma symptoms (wheeze). In each centre, we found significant variation in the prevalence of wheeze among schools, which could be explained by personal characteristics and air pollutants. Large-scale microbial variations were observed between the three centres; the potential protective bacteria were mainly from phyla Actinobacteria in Johor Bahru, Cyanobacteria in Terengganu and Proteobacteria in Penang. In total, 2633 metabolites and chemicals were characterised. Many metabolites were enriched in low-wheeze schools, including plant secondary metabolites flavonoids/isoflavonoids (isoliquiritigenin, formononetin, astragalin), indole and derivatives (indole, serotonin, 1H-indole-3-carboxaldehyde), and others (biotin, chavicol). A neural network analysis showed that the indole derivatives were co-occurring with the potential protective microbial taxa, including Actinomycetospora, Fischerella and Truepera, suggesting these microorganisms may pose health effects by releasing indole metabolites. A few synthetic chemicals were enriched in high-wheeze schools, including pesticides (2(3H)-benzothiazolethione), fragrances (2-aminobenzoic acid, isovaleric acid), detergents and plastics (phthalic acid), and industrial materials (4,4-sulfonyldiphenol). CONCLUSIONS: This is the first association study between high-throughput indoor chemical profiling and asthma symptoms. The consistent results from the three centres indicate that indoor metabolites/chemicals could be a better indicator than the indoor microbiome for environmental and health assessments, providing new insights for asthma prediction, prevention and control.

MicroRNA-141-3p attenuates oxidative stress-induced hepatic ischemia reperfusion injury via Keap1/Nrf2 pathway.

BACKGROUND: Hepatic ischemia reperfusion injury (IRI) is a major factor affecting the prognosis of liver transplantation through a series of severe cell death and inflammatory responses. However, the potential role of miR-141-3p in hepatic IRI is currently unknown. METHODS: We collected the serum of liver transplantation patients to study the relationship between miR-141-3p and liver injury. A mouse hepatic IRI model was established to measure hepatic dysfunction and cell apoptosis. MiR-141-3p mimic and inhibitor were transfected into hepatocytes to explore the characteristics of hypoxia/reoxygenation (H/R), a classical hepatic IRI in vitro model. RESULTS: We found that miR-141-3p levels were negatively correlated with alanine aminotransferase (ALT)/aspartate aminotransferase (AST) in liver transplantation patients. The results demonstrated that miR-141-3p was decreased in mouse liver tissue after hepatic IRI in mice and in hepatocytes after H/R. Overexpression of miR-141-3p directly decreased Kelch-like ECH-associated protein 1 (Keap1) levels and attenuated cell apoptosis in vivo and in vitro, while inhibition of miR-141-3p facilitated apoptosis. Further experiments revealed that overexpression of miR-141-3p also attenuated oxidative stress-induced damage in hepatocytes under H/R conditions. CONCLUSIONS: Our results indicate that miR-141-3p plays a major role in hepatic IRI through the Keap1 signaling pathway, and the present study suggests that miR-141-3p might have a protective effect on hepatic IRI to some extent.

Jellyfish Collagen Hydrolysate Alleviates Inflammation and Oxidative Stress and Improves Gut Microbe Composition in High-Fat Diet-Fed Mice.

The collagen from jellyfish has many beneficial effects, including antioxidant, anti-inflammatory and immune-modulatory activities. However, whether jellyfish collagen hydrolysate (JCH) has any effects on high-fat diet-induced obesity remains unknown. Consequently, we in the present study orally administrated JCH in high-fat diet-fed mice to explore its effects on body weight gain, inflammatory and oxidative status, and cecum microbe composition. The results showed that oral administration of JCH prevented the body weight gain in high-fat diet-treated mice. Meanwhile, glucose, triglycerides, and total cholesterol level in serum were maintained by JCH administration. Furthermore, JCH administration alleviated oxidative stress by increasing the GSH content and decreasing the level reactive oxygen species in the liver and improved inflammatory response by decreasing the expression of TNF-α, IL-1ß, and IL-8 gene in the liver and ileum. Importantly, JCH administration helps recover the alteration of microbiota composition induced by high-fat diet, and the genus Romboutsia may critically involve in the beneficial effects of JCH administration. In conclusion, our results indicated that JCH could be potentially used for the prevention and treatment of diet-induced obesity.

Local vibration induced vascular pathological structural changes and abnormal levels of vascular damage indicators.

BACKGROUND: The vascular component of the hand-arm-vibration syndrome (HAVS) is often characterized by vibration-induced white fingers (VWF). Active substances secreted by the vascular endothelial cells (VEC) maintain a dynamic balance but damage to the blood vessels may occur when the equilibrium is altered, thus forming an important pathological basis for VWF. This study was aimed at investigating vascular damage indicators as a basis for an early detection of disorders caused by vibration, using the rat tail model. METHODS AND RESULTS: Experiments were conducted using a control group of rats not exposed to vibration while two exposed groups having different exposure durations of 7 and 14 days were randomly formed. Following exposure, the structural changes of tail tissue samples in anesthetized rats were observed. Enzyme-linked immunosorbent assay (ELISA) was used for analyzing four vascular damage indicators myosin regulatory light chain (MLC2), endothelin-1 (ET-1), vinculin (VCL) and 5-hydroxytryptamine (5-HT) in tail blood samples. We found that both vascular smooth muscle and endothelial cells displayed changes in morphology characterized by vacuolization and swelling in the vibration-exposed group. The levels of vascular damage indicators were altered under the vibration. CONCLUSION: The degree of vascular pathology increased with the longer duration exposure. Furthermore, the levels of MLC2, ET-1 and 5-HT in rat plasma were associated with vascular injury caused by local vibration.

The hand-arm vibration syndrome associated with the grinding of handheld workpieces in a subtropical environment.

OBJECTIVES: To study the characteristics and the factors influencing the occurrence of the Hand-Arm Vibration Syndrome (HAVS) for a population grinding handheld workpieces in a subtropical environment. METHODS: A total of 803 workers grinding handheld workpieces formed the exposure group and 464 workers not exposed to hand-transmitted vibration (HTV) were recruited as the non-exposed group within the same factory in a subtropical climate area. The basic personal information and clinical symptoms reported were collected by trained physicians using a questionnaire and representative measurements were made of the HTV exposure levels and dose. RESULTS: The average HTV exposure dose A(8) was measured as 5.3 ± 2.0 m/s2. The proportion of grinders reporting finger blanching was 15.4% while it was 27.5% for finger numbness. Among the non-exposed group, that proportion was 0% and 6.3% respectively. There was a positive association between the vibration exposure duration and the occurrence of finger blanching, finger numbness and finger coldness. Riding a motorcycle to work was also identified as a factor that could contribute to a higher prevalence of finger blanching among the exposed workers, the OR value was found to be 1.75 (1.12, 2.75). CONCLUSIONS: Workers exposed to vibration in a subtropical area can also present evidence of finger blanching in addition to neurological symptoms. The reported rate of HAVS was positively associated with the exposure duration. And the levels of the duration of exposure relative to symptoms of vibration white finger in a subtropical temperate environment exposed to a high-frequency vibration might be deemphasized by the current ISO weighting. Motorcycle transportation to work was identified as a factor that could influence the development of the HAVS among the exposed population of grinders.

Liver kinase B1 attenuates liver ischemia/reperfusion injury via inhibiting the NLRP3 inflammasome.

Liver ischemia/reperfusion injury (IRI), a serious inflammatory response driven by innate immunity, occurs in liver surgeries such as liver resection and liver transplantation, leading to liver dysfunction, liver failure, and even rejection after transplantation. Liver kinase B1 (LKB1) plays a pivotal anti-inflammatory role in IRI. One of the most important factors involved in liver IRI is the aberrant activation of the nucleotide binding oligomerization domain like receptor (NLR) family, pyrin domain-containing 3 (NLRP3) inflammasome in Kupffer cells. However, the mechanisms underlying the effect of LKB1 on the NLRP3 inflammasome in liver IRI remain elusive. In this study, we found that the expression of LKB1 was decreased in liver IRI, while the NLRP3 inflammasome level was increased as shown, as revealed by RT-qPCR and western blot analysis. Furthermore, upregulation of LKB1 abrogated the expression of the NLRP3 inflammasome, which improved liver function and liver pathology in the liver IRI model in vivo. In vitro, overexpression of LKB1 inhibited the activation of NLRP3 inflammasome and nuclear factor-κB, while the inhibitory effect was reversed by silencing the expression of the forkhead box protein O1 in the RAW264.7 macrophage hypoxia/reoxygenation model. In conclusion, our results suggest that LKB1 exerts a protective effect against liver IRI by downregulating the NLRP3 inflammasome.