Chitosan-coated PLGA microemulsion loaded with tannic acid against Escherichia coli in vitro and in vivo.

The overuse of antibiotics has resulted in a surge of drug-resistant bacteria, making the pursuit of natural antimicrobials an urgent and significant trend. Encapsulation and nanoparticulation are effective ways to enhance the antibacterial properties of natural drugs. In this study, we encapsulated tannic acid (TA) with chitosan (CS) and poly (lactide-co-glycolide) (PLGA) using the emulsion-solvent evaporation method to enhance the antimicrobial effect of TA. We prepared a bilayer membrane spherical nanoemulsion of TA-PLGA-CS (TPC) with uniform size of 559.87 ± 1.16 nm, and zeta potential of 59.53 ± 1.07 mV. TPC could be stably stored for 90 days at 4°C without affecting the properties of the emulsion, and the minimum bactericidal concentration against four strains of Escherichia coli (E. coli) remained unchanged for 60 d. The results indicated that TPC enhanced the inhibitory effect of TA against E. coli. Scanning electron microscope images revealed that TPC treatment caused damage to the bacterial cell membrane. In addition, in vivo experiments indicated that TPC exhibited a superior therapeutic effect on artificial colibacillosis in chickens infested with Avian pathogenic Escherichia coli, as evidenced by the changes in body weight and a reduction bacterial load in heart. Furthermore, TPC reversed the down-regulation of catalase, glutathione peroxidase1 (GPX1), and GPX7 gene expression levels in intestinal tissues. Compared to the model group, TPC treatment elevated serum glutathione peroxidase activities and lowered myeloperoxidase and lactate dehydrogenase levels, offering antioxidant protection that was slightly better than that of doxycycline hydrochlorid group. In summary, we prepared a novel TA antimicrobial preparation with significant antioxidant potential and inhibitory effect against E. coli both in vitro and in vivo.

Comparison, optimization and antioxidant activity of ultrasound-assisted natural deep eutectic solvents extraction and traditional method: A greener route for extraction of flavonoid from Moringa oleifera Lam. leaves.

To develop an environmentally sustainable and efficient extraction method for flavonoids from Moringa oleifera Lam. (M. oleifera) leaves, natural deep eutectic solvents (NADES) with ultrasound-assisted extraction was utilized in this study. After optimization of extraction parameters of NADES, including ultrasonic power, ultrasonic time, and liquid-solid ratio, the extraction yield of ultrasound-assisted NADES (UAN) composed of betaine and urea (Bet-Urea) reached 54.69 ± 0.19 mg RE/g DW, which made a 1.7-fold increase compared to traditional ultrasound-assisted traditional solvent (UATS). UPLC-Q Exactive/MS analysis revealed that M. oleifera leaves flavonoids (MOLF) was mainly composed of Quercetin 3-ß-D-glucoside, Rutin, Kaempferol-3-O-glucoside, Vitexin and Quercetin. Furthermore, the COSMO-RS model was employed to verify the optimal compatibility of solubility and activity coefficient between Bet-Urea and the five primary flavonoids in MOLF. In vitro antioxidant assays verified that MOLF extracted by UAN exhibited superior antioxidant activity compared to MOLF extracted by UATS. Overall, the devised process not only augmented the extraction yield of MOLF but also effectively preserved the bioactive compounds, thus promoting the utilization of green extraction solvents in the food industry.

Association of weight-adjusted waist index with all-cause mortality among non-Asian individuals: a national population-based cohort study.

INTRODUCTION: The Weight-Adjusted Waist Index (WWI) is a new indicator of obesity that is associated with all-cause mortality in Asian populations. Our study aimed to investigate the linear and non-linear associations between WWI and all-cause mortality in non-Asian populations in the United States, and whether WWI was superior to traditional obesity indicators as a predictor of all-cause mortality. METHODS: We conducted a cohort study using data from the 2011-2018 National Health and Nutrition Examination Survey (NHANES), involving 18,592 participants. We utilized Cox proportional hazard models to assess the association between WWI, BMI, WC, and the risk of all-cause mortality, and performed subgroup analyses and interaction tests. We also employed a receiver operating characteristics (ROC) curve study to evaluate the effectiveness of WWI, BMI, and WC in predicting all-cause mortality. RESULTS: After adjusting for confounders, WWI, BMI, and WC were positively associated with all-cause mortality. The performance of WWI, BMI, and WC in predicting all-cause mortality yielded AUCs of 0.697, 0.524, and 0.562, respectively. The data also revealed a U-shaped relationship between WWI and all-cause mortality. Race and cancer modified the relationship between WWI and all-cause mortality, with the relationship being negatively correlated in African Americans and cancer patients. CONCLUSIONS: In non-Asian populations in the United States, there is a U-shaped relationship between WWI and all-cause mortality, and WWI outperforms BMI and WC as a predictor of all-cause mortality. These findings may contribute to a better understanding and prediction of the relationship between obesity and mortality, and provide support for effective obesity management strategies.

Laponite/lactoferrin hydrogel loaded with eugenol for methicillin-resistant Staphylococcus aureus-infected chronic skin wound healing.

Severe bacterial infections can give rise to protracted wound healing processes, thereby posing a significant risk to a patient's well-being. Consequently, the development of a versatile hydrogel dressing possessing robust bioactivity becomes imperative, as it holds the potential to expedite wound healing and yield enhanced clinical therapeutic outcomes. In this context, the present study involves the formulation of an injectable multifunctional hydrogel utilizing laponite (LAP) and lactoferrin (LF) as foundational components and loaded with eugenol (EG). This hydrogel is fabricated employing a straightforward one-pot mixing approach that leverages the principle of electrostatic interaction. The resulting LAP/LF/EG2% composite hydrogel can be conveniently injected to address irregular wound geometries effectively. Once administered, the hydrogel continually releases lactoferrin and eugenol, mitigating unwarranted oxidative stress and eradicating bacterial infections. This orchestrated action culminates in the acceleration of wound healing specifically in the context of MRSA-infected wounds. Importantly, the LAP/LF/EG2% hydrogel exhibits commendable qualities including exceptional injectability, potent antioxidant attributes, and proficient hemostatic functionality. Furthermore, the hydrogel composition notably encourages cellular migration while maintaining favorable cytocompatibility. Additionally, the hydrogel manifests noteworthy bactericidal efficacy against the formidable multidrug-resistant MRSA bacterium. Most significantly, this hydrogel formulation distinctly expedites the healing of MRSA-infected wounds by promptly inducing hemostasis, curbing bacterial proliferation, and fostering angiogenesis, collagen deposition, and re-epithelialization processes. As such, the innovative hydrogel material introduced in this investigation emerges as a promising dressing for the facilitation of bacterial-infected wound healing and consequent tissue regeneration.

Eugenol Possesses Colitis Protective Effects: Impacts on the TLR4/MyD88/NF-[Formula: see text]B Pathway, Intestinal Epithelial Barrier, and Macrophage Polarization.

Eugenol (EU) has been shown to ameliorate experimental colitis due to its anti-oxidant and anti-inflammatory bioactivities. In this study, DSS-induced acute colitis was established and applied to clarify the regulation efficacy of EU on intestinal barrier impairment and macrophage polarization imbalance along with the inflammatory response. Besides, the adjusting effect of EU on macrophages was further investigated in vitro. The results confirmed that EU intervention alleviated DSS-induced colitis through methods such as restraining weight loss and colonic shortening and decreasing DAI scores. Microscopic observation manifested that EU maintained the intestinal barrier integrity in line with the mucus barrier and tight junction protection. Furthermore, EU intervention significantly suppressed the activation of TLR4/MyD88/NF-[Formula: see text]B signaling pathways and pro-inflammatory cytokines gene expressions, while enhancing the expressions of anti-inflammatory cytokines. Simultaneously, WB and FCM analyses of the CD86 and CD206 showed that EU could regulate the DSS-induced macrophage polarization imbalance. Overall, our data further elucidated the mechanism of EU's defensive effect on experimental colitis, which is relevant to the protective efficacy of intestinal barriers, inhibition of oxidative stress and excessive inflammatory response, and reprogramming of macrophage polarization. Hence, this study may facilitate a better understanding of the protective action of the EU against UC.

Mucosal immune responses and protective efficacy elicited by oral administration AMP-ZnONPs-adjuvanted inactivated H9N2 virus in chickens.

The avian influenza virus is infected through the mucosal route, thus mucosal barrier defense is very important. While the inactivated H9N2 vaccine cannot achieve sufficient mucosal immunity, adjuvants are needed to induce mucosal and systemic immunity to prevent poultry from H9N2 influenza virus infection. Our previous study found that polysaccharide from Atractylodes macrocephala Koidz binding with zinc oxide nanoparticles (AMP-ZnONPs) had immune-enhancing effects in vitro. This study aimed to evaluate the mucosal immune responses of oral whole-inactivated H9N2 virus (WIV)+AMP-ZnONPs and its impact on the animal challenge protection, and the corresponding changes of pulmonary metabolomics after the second immunization. The results showed that compared to the WIV, the combined treatment of WIV and AMP-ZnONPs significantly enhanced the HI titer, IgG and specific sIgA levels, the number of goblet cells and intestinal epithelial lymphocytes (iIELs) as well as the expression of J-chain, polymeric immunoglobulin receptor (pIgR), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α) and transforming growth factor-ß (TGF-ß). In viral attack experiments, WIV combing with AMP-ZnONPs effectively reduced lung damage and viral titers in throat swabs. Interestingly, significant changes of both the IgA intestinal immune network and PPAR pathway could also be found in the WIV+AMP-ZnONPs group compared to the non-infected group. Taken together, these findings suggest that AMP-ZnONPs can serve as a potential mucosal vaccine adjuvant, thereby avoiding adverse stress and corresponding costs caused by vaccine injection.

Association between cardiovascular health and abdominal aortic calcification: Analyses of NHANES 2013-2014.

BACKGROUND: Abdominal aortic calcification (AAC) is closely connected to cardiovascular disease. We aimed to measure the association between cardiovascular health (CVH) levels, assessed by the Life's Essential 8 (LE8) score, and AAC within a nationally representative sample of the US. METHODS: The National Health and Nutrition Examination Survey 2013-2014 participants were chosen for this cross-sectional investigation. LE8 scores, ranging from 0 to 100, were calculated according to the criteria outlined by the American Heart Association. AAC was evaluated using a semi-quantitative scoring system known as AAC-24. Weighted linear regression, multivariate logistic regression, and restricted cubic spline models were used to investigate the correlations. Subgroup analysis and interaction tests were conducted to assess this association's robustness across different population groups. RESULTS: Increased CVH levels were associated with diminished AAC scores and a reduced prevalence of severe AAC. In the partially adjusted model, each unit increase in LE8 score was associated with a 2% decrease in severe AAC prevalence [OR 0.98; 95% CI 0.96, 0.99]. Participants in the high CVH level group experienced a 72% reduced prevalence of severe AAC compared to those in the low CVH level group in model 2 [OR 0.28; 95% CI 0.12, 0.63]. This inverse association was notably more prominent in adults aged 60 years and above. CONCLUSIONS: CVH exhibited a robust negative correlation with AAC. Promoting optimal CVH levels may favor averting AAC within the general population.

Polysaccharide from Atractylodes macrocephala Koidz Binding with Zinc Oxide Nanoparticles as a Novel Mucosal Immune Adjuvant for H9N2 Inactivated Vaccine.

H9N2 avian influenza poses a significant public health risk, necessitating effective vaccines for mass immunization. Oral inactivated vaccines offer advantages like the ease of administration, but their efficacy often requires enhancement through mucosal adjuvants. In a previous study, we established a novel complex of polysaccharide from Atractylodes macrocephala Koidz binding with zinc oxide nanoparticles (AMP-ZnONPs) and preliminarily demonstrated its immune-enhancing function. This work aimed to evaluate the efficacy of AMP-ZnONPs as adjuvants in an oral H9N2-inactivated vaccine and the vaccine's impact on intestinal mucosal immunity. In this study, mice were orally vaccinated on days 0 and 14 after adapting to the environment. AMP-ZnONPs significantly improved HI titers, the levels of specific IgG, IgG1 and IgG2a in serum and sIgA in intestinal lavage fluid; increased the number of B-1 and B-2 cells and dendritic cell populations; and enhanced the mRNA expression of intestinal homing factors and immune-related cytokines. Interestingly, AMP-ZnONPs were more likely to affect B-1 cells than B-2 cells. AMP-ZnONPs showed mucosal immune enhancement that was comparable to positive control (cholera toxin, CT), but not to the side effect of weight loss caused by CT. Compared to the whole-inactivated H9N2 virus (WIV) group, the WIV + AMP-ZnONP and WIV + CT groups exhibited opposite shifts in gut microbial abundance. AMP-ZnONPs serve as an effective and safe mucosal adjuvant for oral WIV, improving cellular, humoral and mucosal immunity and microbiota in the gastrointestinal tract, avoiding the related undesired effects of CT.

RBCK1 overexpression is associated with immune cell infiltration and poor prognosis in hepatocellular carcinoma.

RBCK1 is an important E3 ubiquitin ligase, which plays an important role in many major diseases. However, the function and mechanism of RBCK1 in pan-cancer and its association with immune cell infiltration have not been reported. The purpose of this study is to find out the expression of RBCK1 in cancer, and to explore the relationship between RBCK1 and the prognosis of patients. Our results show that the expression of RBCK1 is up-regulated in a variety of malignant tumors, and is closely related to the prognosis of patients. Further studies have shown that RBCK1 regulates protein expression in the nucleus and plays an important role in ribosome and valine, leucine, and isoleucine degradation. Genetic variation analysis showed that RBCK1 was mainly involved in missense mutations in multiple tumors, and mutated patients showed poor prognoses. Further studies showed that RBCK1 may be interacted with proteins such as RNRPB, MCRS1, TRIB3, MKKS and ARPC3. Through protein interaction analysis, we found 43 proteins interacting with RBCK1 in liver cancer. We also analyzed immune cell infiltration and found that RBCK1 expression was positively correlated with T cells and macrophages, while it was negatively correlated with neutrophils, NK cells, and DCs in liver cancer. Finally, we confirmed experimentally that RBCK1 can significantly inhibit the apoptosis and invasion of HCC. Therefore, we speculate that RBCK1 plays an important regulatory role in the occurrence and development of HCC.

Associations of cereal fiber intake with rheumatoid arthritis mediated by dietary inflammatory index: insights from NHANES 2011-2020.

Rheumatoid Arthritis (RA) is an increasingly prevalent inflammatory disorder worldwide. Its complex etiology has recently brought dietary factors, particularly fiber intake, into focus as potential influencers. Our study investigates the intricate relationship between various sources of dietary fiber and RA, emphasizing the mediating role of the Dietary Inflammatory Index (DII). Leveraging data from the National Health and Nutrition Examination Survey spanning 2011 to 2020. We meticulously assessed dietary fiber intake through dual 24 h dietary recall interviews, while RA diagnoses were established based on comprehensive medical surveys. The relationships between fiber intake, RA prevalence, and DII mediation were analyzed using sophisticated multivariate logistic regression and mediation analysis. Among our study cohort, 7% were diagnosed with RA. We observed a notable inverse correlation between increased total fiber intake, particularly 5 g/day increments, and the incidence of RA, with cereal fiber intake emerging as the primary mitigating factor. Intriguingly, the DII played a significant role in mediating this association, especially regarding cereal fiber. Our findings reveal a significant association between higher cereal fiber consumption and a reduced prevalence of RA. Additionally, the DII stands out as a pivotal mediator in this relationship, highlighting dietary management's critical role in preventing and managing RA.

Chitosan-coated artesunate protects against ulcerative colitis via STAT6-mediated macrophage M2 polarization and intestinal barrier protection.

Oral delivery of chitosan-coated artesunate (CPA) has been proven to be effective at preventing ulcerative colitis (UC) in mice. However, the anti-inflammatory mechanism is not fully understood. STAT6 is a key transcription factor that promotes anti-inflammatory effects by inducing M2 and Th2 dominant phenotypes, therefore we hypothesized STAT6 might play a key role in the process. To prove it, a STAT6 gene knockout macrophage cell line (STAT6-/- RAW264.7, by CRISPR/Cas9 method), and its corresponding Caco-2/RAW264.7 co-culture system combined with the STAT6 inhibitor (AS1517499, AS) in a mouse UC model were established and studied. The results showed that CPA remarkably suppressed the activation of TLR-4/NF-κB pathway and the mRNA levels of proinflammatory cytokines, while increased the IL-10 levels in RAW264.7. This effect of CPA contributed to the protection of the ZO-1 in Caco-2 which was disrupted upon the stimulation to macrophages. Simultaneously, CPA reduced the expression of CD86 but increase the expression of CD206 and p-STAT6 in LPS-stimulated RAW264.7 cells. However, above alterations were not obvious as in STAT6-/- RAW264.7 and its co-culture system, suggesting STAT6 plays a key role. Furthermore, CPA treatment significantly inhibited TLR-4/NF-κB activation, intestinal macrophage M1 polarization and mucosal barrier injury induced by DSS while promoted STAT6 phosphorylation in the UC mouse model, but this effect was also prominently counteracted by AS. Therefore, our data indicate that STAT6 is a major regulator in the balance of M1/M2 polarization, intestinal barrier integrity and then anti-colitis effects of CPA. These findings broaden our understanding of how CPA fights against UC and imply an alternative treatment strategy for UC via this pathway.

The inhibition effect of caffeic acid on NOX/ROS-dependent macrophages M1-like polarization contributes to relieve the LPS-induced mice mastitis.

The mammary gland is an adipose tissue containing not only adipocytes but also epithelial, endothelial, and immune cells. Epithelial cells and macrophages, as the integral components of the immune system, are on the front line of defense against infection. Our preliminary work proved that caffeic acid (CA) can effectively inhibit the inflammatory cascade of bovine mammary epithelial cells (BMEC) induced by lipopolysaccharide (LPS) and maintain cellular integrity and viability. Here, we investigated the therapeutic effect of CA on LPS-induced mice mastitis and explored its regulatory mechanism on macrophage inflammatory response induced by LPS in vitro. Firstly, the mice mastitis model was established by intramammary injection with 10 µg LPS, after which different CA doses (5, 10, 15 mg/kg) were administered. Then, the pathological section, myeloperoxidase (MPO) activity, proinflammatory factors and chemokines releasement, and redox state of mammary tissues were assessed, confirming CA's effectiveness on mice mastitis. In vitro, we validated the therapeutic relevance of CA in relieving LPS-induced RAW264.7 inflammatory and oxidative stress responses. Moreover, we further provided evidence that CA significantly reduced LPS-induced reactive oxygen species (ROS) generation via NADPH oxidase (NOX), which improved the imbalance relationship between nuclear factor kappa-B (NF-κB) and NF-E2 p45-related factor 2 (Nrf2) and led to a marked weakening of M1 polarization. The NOX-ROS signal inhibited by CA weakened the oxidative burst and neutrophil chemotaxis of macrophages, thus alleviating the immune cascade in mammary gland tissue and reducing the LPS-induced inflammatory damage. Collectively, CA would be a potential candidate or antibacterial synergist for curbing mastitis.

Associations between apolipoprotein B and bone mineral density: a population-based study.

BACKGROUND: Lipids are critical in bone metabolism, and several studies have highlighted their importance. This study aimed to investigate the relationship between apolipoprotein B (apo B) and bone mineral density (BMD) at different skeletal sites (lumbar spine, femoral neck, and total femur) and to compare the influence of apo B with other traditional lipid markers. METHODS: The study included participants from the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2016 who had complete data for apo B and BMD at the three skeletal sites. We used weighted multivariate regression analysis, subgroup analysis, and interaction tests to examine associations. Restricted cubic spline (RCS) was used to examine the non-linear relationship. RESULTS: A total of 4,258 adults were included in the study. Multivariate linear regression analysis showed that the relationship between apo B and BMD varied by skeletal site: a negative association was found with lumbar spine BMD [ß = -0.054, 95%CI: (-0.073, -0.035)]. In contrast, a positive association was found with femoral neck BMD [ß = 0.031, 95%CI: (0.011, 0.051)] and no significant association between apo B and total femur BMD. CONCLUSIONS: Our findings suggest that apo B is associated with BMD in a site-specific manner.

Therapeutic effect of a self-made herbal formula on a multi-drug resistant Eimeria tenella isolate infection in broiler chickens.

In-feed prophylactic chemotherapy is widely considered the mainstay of avian coccidiosis control, while serious drug resistance strictly restricts its application. Confronted with the urgent need for an alternative strategy, a traditional Chinese medicine formula (TCMF) was developed. Meanwhile, its potential to iron out complicated clinical coccidiosis was scrutinized in vivo with a field-isolated multi-drug resistant Eimeria tenella (E. tenella) isolate. Birds were inoculated with 5 × 104 sporulated oocysts and administrated with TCMF supplementation in water from 72 h post-infection to the end of the experiment, diclazuril (DIC) was set as a positive control. As a result, TCMF intervention reduced oocyst shedding, cecal lesion and mortality, and enhanced body weight gain. According to the above, anticoccidial index (ACI) was calculated and TCMF exerted a moderate anticoccidial activity. Besides, macroscopic, histopathological, and ultrastructural observations revealed the safeguarding effects of TCMF on E. tenella-induced cecal injury. Following, TCMF treatment presented an obvious inhibition effect on E. tenella caused oxidative stress and inflammatory response. Moreover, TCMF supplementation restored the cecal flora abundance and diversity, reduced the colonization of harmful bacteria, and increased the probiotics abundance. In conclusion, TCMF exhibited a moderate anticoccidial effect along with alleviating E. tenella-induced cecal injury, redox imbalance, and inflammatory response which may be associated with the microflora modulatory effect.

Candidate Marker Genes for Diagnosis of Osteoarthritis and Prediction of Their Regulatory Mechanisms.

We have screened candidate marker genes for the diagnosis of osteoarthritis and predicted their regulatory mechanisms. Six expression chips of tissue samples and one expression chip of peripheral blood mononuclear cell (PMBC) samples were obtained from the GEO database. Differential analysis, GSEA, and WGCNA were performed on the integra-ted tissue sample data with batch correction. Can-didate genes were obtained from the intersection of the genes significantly related to osteoarthritis in the WGCNA and the differentially expressed genes. ROC analysis was performed on the candidate genes in the tissue and PMBC samples. Genes with AUC values greater than 0.6 were retained as final candidates, and their upstream regulatory miRNAs were predicted. A total of 106 genes with differential expression were found in osteoarthritis tissue samples, which were mainly enriched in cell cycle and p53 signalling pathways. WGCNA selected a gene module significantly correlated with the occurrence of osteoarthritis. Fourteen candidate genes were obtained from the intersection of the genes in the module and the differentially expressed genes. ROC analysis showed that among these 14 candidate genes, only ADM, CX3CR1 and GADD45A had AUC values greater than 0.6 in both tissue and PMBC samples. The AUC values of the gene set of these three genes were greater than 0.7. Multiple miRNAs were predicted to be regulators of these three genes. ADM, CX3CR1 and GADD45A have potential as diagnostic marker genes for osteoarthritis and may be regulated by multiple miRNAs.

Association between urine caffeine metabolites and bone mineral density: A population-based study.

The association between coffee intake and bone mineral density (BMD) remains a subject of debate in epidemiological research. Furthermore, the potential relationship between BMD and urine caffeine or caffeine metabolites has not yet been explored. Therefore, the present study aimed to investigate the possible association between BMD and urine caffeine and its metabolites in U.S. adults. We employed multivariate linear and logistic regression models to analyze the relationship between urine caffeine and caffeine metabolites and lumbar BMD using data from the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2014. Additionally, fitted smoothing curves and generalized additive models were used. After adjusting for several factors, we found no significant association between urine caffeine and its metabolites and BMD. However, subgroup analyses stratified by gender and ethnicity showed that the relationship between urine caffeine and its metabolites and lumbar BMD remained consistent. Our investigation revealed that the inflection points for the U-shaped relationship between urinary theophylline and paraxanthine and BMD were observed at levels of 0.006 mmol/L for theophylline and 0.052 mmol/L for paraxanthine. In this cross-sectional study, we found no significant correlation between urine caffeine and its metabolites and BMD. However, more research is required to confirm our findings, as well as to investigate the underlying mechanisms.

Long non-coding HOXA-AS3 contributes to osteosarcoma progression through the miR-1286/TEAD1 axis.

Long non-coding RNA (lncRNA) HOXA cluster antisense RNA 3 (HOXA-AS3) regulates the progression of several types of human malignancy. However, the role and potential mechanism of HOXA-AS3 in osteosarcoma (OS) remain unknown. In this study, upregulation of HOXA-AS3 was observed in OS tissues and cell lines and associated with poor clinical outcomes. Silencing of HOXA-AS3 significantly inhibited the proliferation, migration and invasion of OS cells in vitro and suppressed the tumorigenesis of OS cells in vivo. Furthermore, knockdown of HOXA-AS3 inhibited the proliferation and migration of human umbilical vein endothelial cells (HUVECs) and epithelial-to-mesenchymal transition (EMT) in OS. Further investigation of this mechanism revealed that HOXA-AS3 could directly upregulate the expression of TEAD1 via its competing endogenous RNA (ceRNA) activity on miR-1286. This study clarified the oncogenic roles of the HOXA-AS3/miR-1286/TEAD1 axis in OS progression, suggesting a novel therapeutic target for OS.

Threshold effects and inflection points of flavonoid intake in dietary anti-inflammatory effects: Evidence from the NHANES.

Flavonoids have been shown to be beneficial in a variety of inflammatory and metabolic diseases because of their anti-inflammatory and antioxidant properties. However, previous epidemiological studies have only demonstrated a negative correlation between flavonoid intake on inflammatory markers, and the optimal intake of dietary flavonoids and subclasses in terms of dietary anti-inflammatory efficacy remains undetermined. This study was based on 3 cycles (2007-2010, 2017-2018) of the National Health and Nutrition Examination Survey and the corresponding expanded flavonoid database. Weighted multiple linear regression was used to assess linear relationships between flavonoid intake and Dietary inflammation index (DII). Smoothed curve fit and a generalized additive model were used to investigate the nonlinear relationships and threshold effects, the 2-tailed linear regression model was used to find potential inflection points. A total of 12,724 adults were included in the study. After adjusting for potential confounders, flavonoid intake was significantly associated with DII, with the strongest negative association effect for flavonols (-0.40 [-0.45, -0.35]). In subgroup analyses stratified by sex, race, age, body mass index, education levels, and diabetes, flavonol intake maintained a significant negative linear correlation with DII. In addition, we found significant nonlinear relationships (L-shaped relationships) and threshold effects between total flavonoids, flavan-3-ols, and flavanols and DII, with inflection points of 437.65 mg/days, 157.79 mg/days, and 46.36 mg/days, respectively. Our results suggest a threshold for the dietary anti-inflammatory capacity of flavonoid intake in U.S. adults.

Paeonol accelerates skin wound healing by regulating macrophage polarization and inflammation in diabetic rats.

Diabetic ulcer is usually seen in people with uncontrolled blood sugar. Reportedly, many factors such as impaired glucose metabolism, and macrovascular and microvascular diseases caused angiogenesis disorders and delayed the healing of diabetic ulcers, thus affecting the body's metabolism, nutrition, and immune function. This study aimed to explore the effect of paeonol on skin wound healing in diabetic rats and the related mechanism. A rat model of diabetic ulcer was established. High glucose-treated mouse skin fibroblasts were co-cultured with M1 or M2-polarized macrophages treated with or without paeonol. H&E and Masson staining were used to reveal inflammatory cell infiltration and collagen deposition, respectively. Immunohistochemistry visualized the expression of Ki67, CD31, and vascular endothelial growth factor (VEGF). Western blot was used to detect interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-4, IL-10, CD31, VEGFA, and collagen I/III. The expression of iNOS and arginase 1 was revealed by immunofluorescence staining. Paeonol treatment augmented collagen deposition and the expression of Ki67, CD31, VEGF, and macrophage M2 polarization markers (IL-4 and IL-10) and reduced wound area, inflammatory cell infiltration, and macrophage M1 polarization markers (IL-1ß and TNF-α) in the ulcerated area. In vitro, paeonol treatment promoted M2-polarization and repressed M1-polarization in macrophages, thereby improving the repair of cell damage induced by high glucose. Paeonol accelerates the healing of diabetic ulcers by promoting M2 macrophage polarization and inhibiting M1 macrophage polarization.

Associations between weight-adjusted waist index and bone mineral density: results of a nationwide survey.

BACKGROUND: The weight-adjusted waist circumference index (WWI) is a novel obesity indicator that offers improved accuracy in assessing both muscle and fat mass compared to traditional measures. This study aimed to investigate the association between WWI and bone mineral density (BMD) in adults. METHODS: Weighted multivariate logistic regression, subgroup analysis, interaction tests and restricted cubic spline (RCS) curves were used to explore the relationship between WWI and BMD based on data from the National Health and Nutrition Examination Survey (NHANES). RESULTS: This study had 40,568 individuals in total. At all four measurement sites, we detected a negative linear correlation between WWI and BMD. Even when quartile factors for WWI were created, this unfavorable connection maintained. In comparison to those in the lowest quartile, those in the highest percentile of WWI showed declines in lumbar BMD of 0.08 g/cm2 and femoral neck BMD of 0.03 g/cm2, respectively. This adverse correlation, nevertheless, differed among several categories. CONCLUSIONS: Our findings suggest an adverse correlation between WWI and BMD among US adults. Employing WWI as a tool for osteoporosis prevention in the general population may enhance interventions.