PS-MPs promotes the progression of inflammation and fibrosis in diabetic nephropathy through NLRP3/Caspase-1 and TGF-ß1/Smad2/3 signaling pathways.

BACKGROUND: Diabetic nephropathy (DN) is a prevalent chronic microvascular complication of diabetes and the leading cause of end-stage renal disease (ESRD). Understanding the progressive etiology of DN is critical for the development of effective health policies and interventions. Recent research indicated that polystyrene microplastics (PS-MPs) contaminate our diets and accumulate in various organs, including the liver, kidneys, and muscles. METHODS: In this study, ten-week-old db/db mice and db/m mice were fed. Besides, db/db mice were divided into two groups: PS-MPs group (oral administration of 0.5 µm PS-MPs) and an H2O group, and they were fed for three months. A type II diabetes model was established using db/db mice to investigate the effects of PS-MPs on body weight, blood glucose level, renal function, and renal fibrosis. RESULTS: The results demonstrated that PS-MPs significantly exacerbated various biochemical indicators of renal tissue damage, including fasting blood glucose, serum creatinine, blood urea nitrogen, and blood uric acid. Additionally, PS-MPs worsened the pathological alterations and degree of fibrosis in renal tissue. An increased oxidative stress state and elevated levels of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and monocyte chemoattractant protein-1 (MCP-1) were identified. Furthermore, PS-MPs significantly enhanced renal fibrosis by inhibiting the transition from epithelial cells to mesenchymal cells, specifically through the inhibition of the TGF-ß/Smad signaling pathway. The expression levels of NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1, and cleaved Caspase-1, which are inflammasome proteins, were significantly elevated in the PS-MPs group. CONCLUSION: The findings suggested that PS-MPs could aggravate kidney injury and renal fibrosis in db/db mice by promoting NLRP3/Caspase-1 and TGF-ß1/Smads signaling pathways. These findings had implications for elucidating the role of PS-MPs in DN progression, underscoring the necessity for additional research and public health interventions.

The association of blood metals with latent tuberculosis infection among adults and adolescents.

Objective: We aimed to investigate the relationship of metal exposure and latent tuberculosis infection (LTBI) among US adults and adolescents. Methods: Participants from the National Health and Nutrition Examination Surveys (NHANES 2011 ~ 2012) were included. Multiple logistic regression models were used to explore the associations between metal exposure and LTBI. A total of 5,248 adults and 1,860 adolescents were included in the present analysis. Results: For adults, we only found a positive association between total mercury and LTBI (OR: 1.411; 95% CI: 1.164 ~ 1.710) when used as a continuous variable. Compared with Q1, Q4 increased the prevalence of LTBI (2.303; 1.455 ~ 3.644) when used as a quartile. The OR of total mercury and LTBI was higher among females (1.517; 1.009 ~ 2.279), individuals aged 45 ~ 64 (1.457; 1.060 ~ 2.002), and non-Hispanic White individuals (1.773; 1.316 ~ 2.388). A relationship was observed among only participants with obesity (1.553; 1.040 ~ 2.319) or underweight (1.380; 1.076 ~ 1.771), with college or above (1.645; 1.184 ~ 2.286), with PIR > 3.0 (1.701; 1.217 ~ 2.376), reported smoking (1.535; 1.235 ~ 1.907) and drinking (1.464; 1.232 ~ 1.739). For adolescents, blood manganese was positively associated with LTBI. The OR and 95% CIs for each one-unit increase in the log-transformed level of blood manganese with LTBI were 9.954 (1.389 ~ 71.344). Conclusion: Significant associations were observed in girls, aged ≥12 years and in the non-Hispanic white population. In conclusion, total mercury is associated with an increased prevalence of LTBI among adults and positive association between blood manganese and LTBI was observed among adolescents. Further studies should be conducted to verify the results and explore potential biological mechanisms.

Assessment of the albumin-bilirubin score in breast cancer patients with liver metastasis after surgery.

Objective: This study aims to investigate the potential prognostic value of albumin-bilirubin (ALBI) score in breast cancer patients with liver metastasis after surgery. Methods: This was a retrospective study of 178 breast cancer patients with liver metastasis after surgery. ALBI score was calculated by the following formula: (log10 bilirubin × 0.66) - (albumin × 0.085). The optimal cutoff value of ALBI score was assessed by X-tile. The clinical influence of ALBI score on survival outcomes using Kaplan-Meier method, Log-rank test, Cox proportional hazards regression model. The calibration curves, decision curve analysis and time-dependent ROC curve were used to assess the predictive performance of the nomogram's models. Results: The classifications of 178 breast cancer patients with liver metastasis after surgery were as follows: low ALBI score group (＜-3.36) vs. high ALBI score group (≥-3.36). The Cox proportional hazards regression model indicated that ALBI score was a potential predictor. Kaplan-Meier survival curve performed that the median disease free survival (p = 0.0029) and overall survival (p＜0.0001) in low ALBI score group were longer than in high ALBI score group. The ALBI-based nomograms had good predictive performance. Conclusions: The ALBI score has high prognostic ability for survival time in breast cancer with liver metastasis after surgery. These models will be valuable in discriminating patients at high risks of liver metastasis.

Enhancing Anticancer Efficacy of Formononetin Microspheres via Microfluidic Fabrication.

Formononetin is a flavonoid compound with anti-tumor and anti-inflammatory properties. However, its low solubility limits its clinical use. We employed microfluidic technology to prepare formononetin-loaded PLGA-PEGDA microspheres (Degradable polymer PLGA, Crosslinking agent PEGDA), which can encapsulate and release drugs in a controlled manner. We optimized and characterized the microspheres, and evaluated their antitumor effects. The microspheres had uniform size, high drug loading efficiency, high encapsulation efficiency, and stable release for 35 days. They also inhibited the proliferation, migration, and apoptosis. The antitumor mechanism involved the induction of reactive oxygen species and modulation of Bcl-2 family proteins. These findings suggested that formononetin-loaded PLGA-PEGDA microspheres, created using microfluidic technology, could be a novel drug delivery system that can overcome the limitations of formononetin and enhance its antitumor activity.

Performance and effectiveness of hepatocellular carcinoma screening in individuals with HBsAg seropositivity in China: a multicenter prospective study.

Current guidelines recommend hepatocellular carcinoma (HCC) surveillance for at-risk individuals, including individuals with hepatitis B virus infection. However, the performance and survival benefits of annual screening have not been evaluated through multicenter prospective studies in a Chinese population. Between 2017 and 2021, we included 14,426 participants with hepatitis B surface antigen seropositivity in an annual HCC screening study in China using a multicenter prospective design with ultrasonography and serum alpha-fetoprotein. After four rounds of screening and follow-up, the adjusted hazard ratios of death after correction for lead-time and length-time biases for screen-detected cancers at the prevalent and incident rounds were 0.74 (95% confidence interval = 0.60-0.91) and 0.52 (95% confidence interval = 0.40-0.68), respectively. A meta-analysis demonstrated that HCC screening was associated with improved survival after adjusting for lead-time bias. Our findings highlight the 'real-world' feasibility and effectiveness of annual HCC screening in community settings for the early detection of HCC and to improve survival.

Free-standing conductive nickel metal-organic framework nanowires as bifunctional electrodes for wearable pressure sensors and Ni-Zn batteries.

Free-standing metal-organic frameworks (MOFs) with controllable structure and good stability are emerging as promising materials for applications in flexible pressure sensors and energy-storage devices. However, the inherent low electrical conductivity of MOF-based materials requires complex preparation processes that involve high-temperature carbonization. This work presents a simple method to grow conductive nickel MOF nanowire arrays on carbon cloth (Ni-CAT@CC) and use Ni-CAT@CC as the functional electrodes for flexible piezoresistive sensor. The resulting sensor is able to monitor human activity, including elbow bending, knee bending, and wrist bending. Besides, the soft-packaged aqueous Ni-Zn battery is assembled with Ni-CAT@CC, a piece of glass microfiber filters, and Zn foil acting as cathode, separator, and anode, respectively. The Ni-Zn battery can be used as a power source for finger pressure monitoring. This work demonstrates free-standing MOF-based nanowires as bifunctional fabric electrodes for wearable electronics.

Direct Regeneration of NCM Cathode Material with Aluminum Scraps.

Hydrothermal-based direct regeneration of spent Li-ion battery (LIB) cathodes has garnered tremendous attention for its simplicity and scalability. However, it is heavily reliant on manual disassembly to ensure the high purity of degraded cathode powders, and the quality of regenerated materials. In reality, degraded cathodes often contain residual components of the battery, such as binders, current collectors, and graphite particles. Thorough investigation is thus required to understand the effects of these impurities on hydrothermal-based direct regeneration. In this study, we focus on isolating the effects of aluminum (Al) scraps on the direct regeneration process. We found that Al metal can be dissolved during the hydrothermal relithiation process. Even when the cathode material contains up to 15 wt.% Al scraps, no detrimental effects were observed on the recovered structure, chemical composition, and electrochemical performance of the regenerated cathode material. The regenerated NCM cathode can achieve a capacity of 163.68 mAh/g at 0.1 C and exhibited a high-capacity retention of 85.58 % after cycling for 200 cycles at 0.5 C. Therefore, the hydrothermal-based regeneration method is effective in revitalizing degraded cathode materials, even in the presence of notable Al impurity content, showing great potential for industrial applications.

Adipokines in atherosclerosis: unraveling complex roles.

Adipokines are biologically active factors secreted by adipose tissue that act on local and distant tissues through autocrine, paracrine, and endocrine mechanisms. However, adipokines are believed to be involved in an increased risk of atherosclerosis. Classical adipokines include leptin, adiponectin, and ceramide, while newly identified adipokines include visceral adipose tissue-derived serpin, omentin, and asprosin. New evidence suggests that adipokines can play an essential role in atherosclerosis progression and regression. Here, we summarize the complex roles of various adipokines in atherosclerosis lesions. Representative protective adipokines include adiponectin and neuregulin 4; deteriorating adipokines include leptin, resistin, thrombospondin-1, and C1q/tumor necrosis factor-related protein 5; and adipokines with dual protective and deteriorating effects include C1q/tumor necrosis factor-related protein 1 and C1q/tumor necrosis factor-related protein 3; and adipose tissue-derived bioactive materials include sphingosine-1-phosphate, ceramide, and adipose tissue-derived exosomes. However, the role of a newly discovered adipokine, asprosin, in atherosclerosis remains unclear. This article reviews progress in the research on the effects of adipokines in atherosclerosis and how they may be regulated to halt its progression.

LncRNA HOXA11-AS modulates the miR-148b-3p/MLPH axis to promote prostate cancer cell proliferation.

Prostate cancer refers to the epithelial malignant tumor of the prostate. It has a high incidence and mortality rate, seriously endangering the lives of men. In recent years, lncRNAs have become a hot topic for lots of scholars for their regulation functions on assorted cancers. Several lncRNAs have been proven they can take part in the regulation of prostate cancer development. Nevertheless, how HOXA11-AS (homeobox A11 antisense RNA)functioned in prostate cancer is not explained. In our research, the expression of HOXA11-AS in prostate cancer cells was evaluated through qRT-PCR. Colony formation experiments, EdU experiments, Tanswelland TUNEL experiments, as well as caspase-3 detection, were designed to test cell proliferation, migration, invasion and apoptosis. RIP, pull down and luciferase reporter experiments examined the correlations of HOXA11-AS, miR-148b-3p and MLPH. We discovered a high level of HOXA11-AS in prostate cancer cells.HOXA11-AS silence could restrain the mentioned cell malignant behavior. Mechanically, HOXA11-AS could sponge miR-148b-3p to target MLPH. MLPH was positively associated with HOXA11-AS and overexpressed it accelerated the progression of prostate cancer. Taken together, HOXA11-AS elevated MLPH expression by sponging miR-148b-3p and accelerated prostate cancer cell proliferation.

Preparation and cytotoxicity evaluation of folic acid-modified YF8-OA self-assembled lipid prodrug nanoparticles.

This study aimed to improve the use of YF8, a matrine derivative obtained through chemical transformation of matrine extracted from Sophora alopecuroides. YF8 has demonstrated improved cytotoxicity compared to matrine, but its hydrophobic nature hinders its application. To overcome this, the lipid prodrug YF8-OA was synthesized by linking oleic acid (OA) to YF8 through an ester bond. Although YF8-OA could self-assemble into unique nanostructures in water, it was not sufficiently stable. To enhance the stability of YF8-OA lipid prodrug nanoparticles (LPs), we employed the strategy of PEGylation using DSPE-mPEG2000 or DSPE-mPEG2000 conjugated with folic acid (FA). This resulted in the formation of uniform spherical nanoparticles with greatly improved stability and a maximum drug load capacity upto 58.63%. Cytotoxicity was evaluated in A549, HeLa, and HepG2 cell lines. The results showed that in HeLa cells, the IC50 value of YF8-OA/LPs with FA-modified PEGylation was significantly lower than that of YF8-OA/LPs modified by PEGylation alone. However, no significant enhancement was observed in A549 and HepG2 cells. In conclusion, the lipid prodrug YF8-OA can form nanoparticles in aqueous solution to address its poor water solubility. Modification with FA resulted in further enhanced cytotoxicity, providing a potential avenue for exerting the antitumor activity of matrine analogs.

The Associations of Weekend Warrior Activity Patterns With the Visceral Adiposity Index in US Adults: Repeated Cross-sectional Study.

BACKGROUND: According to previous reports, obesity especially visceral fat has become an important public health problem, causing an estimation of 20.5 disability-adjusted life years per 1000 inhabitants. Those who exercised for 1 or 2 days per week and reached the recommended 150 minutes of moderate physical activity (PA) per week have been defined as "weekend warriors" (WWs). Although the benefits of PA in suppressing obesity have been widely studied, the association of WWs with the Visceral Adiposity Index (VAI) and the difference between WW activity and regular PA are yet to be explored. OBJECTIVE: This study aims to explore the association between WW activity and other PA patterns with VAI in US adults. METHODS: The National Health and Nutrition Examination Survey 2007-2016 data set was used, and the analytic sample was limited to adults 20 years and older who had complete information about VAI, PA patterns, and other covariates, including demographic characteristics, behavioral factors, and disease conditions. Participants' characteristics in different PA pattern groups were tested using the Rao and Scott adjusted χ2 test and ANOVA. Univariate and multivariate stepped linear regression models were then used to explore the association between the PA pattern and VAI. Finally, stratified analyses and interaction effects were conducted to investigate whether the association was stable among subgroups. RESULTS: The final sample included 9642 adults 20 years or older, which is representative of 158.1 million noninstitutionalized US adults, with 52.15% (n=5169) being male and 70.8% (n=4443) being non-Hispanic White. Gender, age group, race, education level, income level, marital status, smoking status, alcoholism, VAI, cardiovascular disease, and diabetes were all correlated with the PA pattern, but no relationship between hypertension and PA pattern was observed. After adjusting for demographic covariates, smoking status, alcoholism, cardiovascular disease, diabetes, and hypertension, WW and regularly active adults had a ß of .307 (95% CI -0.611 to -0.003) and .354 (95% CI -0.467 to -0.241), respectively, for reduced VAI when compared with inactive adults, but no significant effect of lowering VAI (ß=-.132, 95% CI -0.282 to 0.018) was observed in insufficiently active adults when compared with inactive adults. Besides, no significant difference was exhibited between WW adults and regularly active adults (ß=.047, 95% CI -0.258 to 0.352), suggesting WW adults had the same benefit of decreasing VAI as regularly active adults. Stratified analyses results exhibited that WW activity was related to reduced VAI in female adults aged 20-44 years who were non-Hispanic Black, other, or multiracial; high school or General Educational Development education; and never married, and the association between PA pattern and VAI remained stable in all demographic subgroups. CONCLUSIONS: Compared with inactive adults, WWs could reduce VAI, and there was no significant difference between WWs and regular active adults in decreasing VAI. Our study provides compelling evidence of the beneficial effect of WW activity on visceral obesity.

Identification of a combined lncRNA prognostic signature and knockdown of lncRNA MANCR to inhibit progression of clear cell renal cell carcinoma by bioinformatics analysis.

Background: Long non-coding RNAs (lncRNAs) have become potential therapeutic targets or promising prognostic biomarkers in cancers. However, individual gene does not show sufficient prognostic value for clear cell renal cell carcinoma (ccRCC). Therefore, this study aims to develop a combined prognostic lncRNA signature to the prognosis of ccRCC. Methods: The transcriptome profiling data for confirmed ccRCC cases were obtained from The Cancer Genome Atlas (TCGA; https://portal.gdc.cancer.gov/). The prognostic significance, survival time and diagnostic effectiveness of the lncRNAs in ccRCC was evaluated using Kaplan-Meier method, the log-rank test and receiver operating characteristic (ROC) curves, respectively. The area under the ROC curve (AUC) of the 4 lncRNAs was also performed. The expression of mitotically-associated lncRNA (MANCR) was measured in ccRCC cells or tissues by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Both Colony formation assays and Cell Counting Kit-8 (CCK-8) assay was conducted to detect the proliferation of both 786-O and SN12C cells. For apoptosis detection, flow cytometry in both 786-O and SN12C cells was performed. For migration of 786-O and SN12C cells detection, wound healing and transwell assays were performed. Results: A total of 1,567 differentially expressed lncRNAs in ccRCC were discerned with 1,340 upregulation and 227 downregulation. Furthermore, a 4-lncRNA signature (FIRRE, MANCR, AC103706.1, and AC018648.1) model was obtained that showed good performance in the prognosis of ccRCC. Gene Ontology (GO) analysis showed that these protein-coding genes (PCGs) were mainly enriched in ATPase activity, catalytic activity, and acting on RNA protein serine/threonine kinase activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that PCGs were mainly involved in endocytosis, oocyte meiosis and spliceosome. In addition, we revealed that MANCR was highly expressed in ccRCC cells and tissues and downregulation of MANCR inhibited cell proliferation and migration. In contrast, apoptosis of 786-O and SN12C cells was promoted with MANCR suppression. Conclusions: A 4-lncRNA prognostic model that presented good performance for prognosis of ccRCC patients was established. Knockdown of MANCR inhibited cell proliferation and migration, and promoted apoptosis of 786-O and SN12C cells, suggesting that a 4-lncRNA signature model might be an essential for ccRCC prognosis.

Prevention of alloimmune rejection using XBP1-deleted bone marrow-derived dendritic cells in heart transplantation.

BACKGROUND: Genetically modified dendritic cells (DCs) modulate the alloimmunity of T lymphocytes by regulating antigen presentation. METHODS: We generated mice with specific deletion of the X-box-binding protein 1 (XBP1) allele in bone marrow cells and cultured bone marrow-derived DCs (Xbp1-/- BMDCs) from these animals. We then tested the phenotype of Xbp1-/- BMDCs, evaluated their capability to activate allogeneic T cells and investigated their mechanistic actions. We developed a mouse model of allogeneic heart transplantation in which recipients received PBS, Xbp1-/- BMDCs, a suboptimal dose of cyclosporine A (CsA), or Xbp1-/- BMDCs combined with a suboptimal dose of CsA to evaluate the effects of Xbp1-/- BMDC transfusion on alloimmunity and on the survival of heart allografts. RESULTS: The deletion of XBP1 in BMDCs exploited the IRE1-dependent decay of TAPBP mRNA to reduce the expression of MHC-I on the cell surface, altered the capability of BMDCs to activate CD8+ T cells, and ultimately suppressed CD8+ T-cell-mediated allogeneic rejection. The adoptive transfer of Xbp1-/- BMDCs inhibited CD8+ T-cell-mediated rejection. In addition, XBP1-deficient BMDCs were weak stimulators of allogeneic CD4+ T cells despite expressing high levels of MHC-II and costimulatory molecules on their cell surface. Moreover, the adoptive transfer of Xbp1-/- BMDCs inhibited the production of circulating donor-specific IgG. The combination of Xbp1-/- BMDCs and CsA treatment significantly prolonged the survival of allografts compared to CsA alone. CONCLUSIONS: The deletion of XBP1 induces immunosuppressive BMDCs, and treatment with these immunosuppressive BMDCs prevents alloimmune rejection and improves the outcomes of heart transplantation. This finding provides a promising therapeutic target in combating transplant rejection and expands knowledge of inducing therapeutic DCs.

A signature based on m6A pattern and tumor microenvironment infiltration in clear cell renal cell carcinoma.

BACKGROUND: RNA N6-methyladenosine (m6A) has been found to have a critical impact on clear cell renal cell carcinoma (ccRCC) by affecting the tumor microenvironment (TME) and immune cell (IC) infiltration and is related to the treatment and survival rate of patients with ccRCC. However, the mechanism of m6A in TME and IC infiltration remained unclear. METHODS: Nonnegative Matrix Factorization (NMF) clustering was performed on 650 ccRCC cases from the Cancer Genome Atlas (TCGA) and the Gene-Expression Omnibus (GEO) datasets. The immune infiltration was generated by the single-sample gene-set enrichment analysis (ssGSEA) algorithm. Survival analyses were performed using the Kaplan-Meier method, and the significance of the differences was determined using the log-rank test. The m6A score was constructed based on the expression of m6A regulators to quantify m6A modification. The package "survminer R" was employed to layer patients' low and high scores groups and predict the immunotherapy response. RESULTS: Three different patterns of m6A modification were established, and significant differences in TME and IC infiltration features were found in these three patterns. Survival analysis demonstrated that m6A cluster A and m6A gene cluster A experienced a longer survival time. Evaluation of m6A modification patterns in individual tumors was initiated by the m6A score. The low m6A score subtype was characterized by increased tumor mutation burden (TMB) and immune infiltration, whereas a high m6A score with a lack of immune cell infiltration showed significantly better overall survival. m6A score was also associated with the expression of programmed cell death protein 1 (PD-L1) and cytotoxic T lymphocyte antigen 4 (CTLA-4). Patients in the high m6A score group had high PD-L1 expression and low CTLA-4 expression. Significant differences in prognosis were identified among types of different TMB and m6A scores, where low TMB and high m6A score had longer survival time. CONCLUSIONS: This research indicated that m6A modification greatly affected TME and IC infiltration. Physicians can develop practical immunotherapy strategies for patients with ccRCC by evaluating m6A-associated genes.

Stepwise Artificial Yarn Muscles with Energy-Free Catch States Driven by Aluminum-Ion Insertion.

Present artificial muscles have been suffering from poor actuation step precision and the need of energy input to maintain actuated states due to weak interactions between guest and host materials or the unstable structural changes. Herein, these challenges are addressed by deploying a mechanism of reversible faradaic insertion and extraction reactions between tetrachloroaluminate ions and collapsed carbon nanotubes. This mechanism allows tetrachloroaluminate ions as a strong but dynamic "locker" to achieve an energy-free high-tension catch state and programmable stepwise actuation in the yarn muscle. When powered off, the muscle nearly 100% maintained any achieved contractile strokes even under loads up to 96,000 times the muscle weight. The actuation mechanism allowed the programmable control of stroke steps down to 1% during reversible actuation. The isometric stress generated by the yarn muscle (14.6 MPa in maximum, 40 times that of skeletal muscles) was also energy freely lockable and step controllable with high precision. Importantly, when fully charged, the muscle stored energy with a high capacity of 102 mAh g-1, allowing the muscle as a battery to power secondary muscles or other devices.

Identification for heavy metals exposure on osteoarthritis among aging people and Machine learning for prediction: A study based on NHANES 2011-2020.

Objective: Heavy metals are present in many environmental pollutants, and have cumulative effects on the human body through water or food, which can lead to several diseases, including osteoarthritis (OA). In this research, we aimed to explore the association between heavy metals and OA. Methods: We extracted 18 variables including age, gender, race, education level, marital status, smoking status, body mass index (BMI), physical activity, diabetes mellitus, hypertension, poverty level index (PLI), Lead (Pb), cadmium (Cd), mercury (Hg), selenium (Se), manganese (Mn), and OA status from National Health and Nutrition Examination Survey (NHANES) 2011-2020 datasets. Results: In the baseline data, the t test and Chi-square test were conducted. For heavy metals, quartile description and limit of detection (LOD) were adopted. To analyze the association between heavy metals and OA among elderly subjects, multivariable logistic regression was conducted and subgroup logistic by gender was also carried out. Furthermore, to make predictions based on heavy metals for OA, we compared eight machine learning algorithms, and XGBoost (AUC of 0.8, accuracy value of 0.773, and kappa value of 0.358) was the best machine learning model for prediction. For interactive use, a shiny application was made (https://alanwu.shinyapps.io/NHANES-OA/). Conclusion: The overall and gender subgroup logistic regressions all showed that Pb and Cd promoted the prevalence of OA while Mn could be a protective factor of OA prevalence among the elderly population of the United States. Furthermore, XGBoost model was trained for OA prediction.

Methyl eugenol attenuates liver ischemia reperfusion injury via activating PI3K/Akt signaling.

BACKGROUND: Liver ischemia reperfusion injury (LIRI) often occurs during liver transplantation, resection, and various circulatory shock procedures, leading to severe metabolic disorders, inflammatory immune responses, oxidative stress injury, and cell apoptosis. Methyl eugenol (ME) is structurally similar to eugenol and has anti-inflammatory and apoptotic pharmacological effects. However, whether ME protects the liver from LIRI damage requires further investigation. METHODS: We established a partially warm LIRI model by subjecting C57BL/6J mice to 60 min of ischemia, followed by reperfusion for 6 h. We also established a hypoxia-reoxygenation injury (H/R) cell model by subjecting AML12 (a mouse liver cell line) cells to 24 h hypoxia, followed by 18 h normoxia. The extent of liver injury was assessed by serum transaminase concentrations, hematoxylin and eosin staining, quantitative real-time PCR, myeloperoxidase activity, and TUNEL analysis. Apoptosis was detected using flow cytometry. The protein levels of p-PI3K, PI3K, p-Akt, Akt, p-Bad, Bad, Bcl-2, Bax, and cleaved caspase-3 were detected by western blotting. LY294002, an inhibitor of PI3K/Akt signaling, was used to elucidate the relationship between ME and PI3K/Akt signaling. RESULTS: ME successfully alleviated LIRI-induced liver injury, inflammatory response, and apoptosis induced, as well as liver cell injury induced by hypoxia reoxygenation. ME is known to activate the PI3K/Akt signaling pathway in hepatocyte injury in vivo and in vitro, and when this signaling pathway is inhibited, the protective effect of ME is abrogated. CONCLUSIONS: The use of ME is a potential therapeutic approach for regulating LIRI by activating PI3K/Akt signaling.

Isolation and Characterization of Anti-Inflammatory Sorbicillinoids from the Mangrove-Derived Fungus Penicillium sp. DM815.

Marine derived fungus has gained increasing ground in the discovery of novel lead compounds with potent biological activities including anti-inflammation. Here, we first report the characterization of one new sorbicillinoid (1) and fourteen known compounds (2-15) from the ethyl acetate (AcOEt) extract of a cultured mangrove derived fungus Penicillium sp. DM815 by UV, IR, HR ESI-Q-TOF MS, and NMR spectra. We then evaluated the anti-inflammatory effects of eleven sorbicillinoids (1-11) using cultured macrophage RAW264.7 cells. The results show that compound 9, and to a lesser degree compound 5, significantly inhibited the Gram-negative bacteria lipopolysaccharide (LPS)-induced upregulation of the inducible nitric oxide synthase (iNOS). Consistently, compounds 5 and 9 significantly reduced the level of nitric oxide (NO), the product of iNOS, induced by LPS. We further show that these two compounds dose-dependently inhibited LPS-triggered iNOS expression and NO production, but had no effect on proliferation of RAW264.7 cells in the presence of LPS. In conclusion, our study identifies novel and known sorbicillinoids as potent anti-inflammatory agents, holding the promise of developing novel anti-inflammation treatment in the future.