Association between dietary protein intake and risk of chronic kidney disease: a systematic review and meta-analysis.

Objective: There is suggestive data indicating a correlation among dietary protein intake and the progression of chronic kidney disease (CKD). Nonetheless, the exact associations between dietary protein intake and the incidence of CKD have remained uncertain. We performed the first meta-analysis to explore the correlation among total protein, plant protein, animal protein intake and CKD risk. Methods: The study conformed the PRISMA statement guidelines. We comprehensively searched PubMed, Web of Science, and Embase until to December 2023. The retrieved studies underwent rigorous evaluation for eligibility, and relevant data were meticulously extracted. The Newcastle-Ottawa Scale (NOS) tool was applied to evaluate the risk of bias. Subsequently, relevant data were extracted and pooled to evaluate the relations among dietary protein intake and CKD incidence. Results: Totally, 6,191 articles were identified, six studies were eligible. A total of 148,051 participants with 8,746 CKD cases were included. All studies had a low overall risk of bias. Higher total, plant and animal protein intake were all correlated with decreased CKD incidence, pooled risk ratios (RRs) and 95% confidence intervals (CIs) were as follows: (RR = 0.82, 95% CI = 0.71-0.94, p = 0.005; I2 = 38%, p = 0.17); (RR = 0.77, 95% CI = 0.61-0.97, p = 0.03; I2 = 77%, p = 0.001); (RR = 0.86, 95% CI = 0.76-0.97, p = 0.02; I2 = 0%, p = 0.59), respectively. For fish and seafood within animal protein: RR = 0.84, 95% CI = 0.74-0.94. Subgroup analysis showed that geographical region, sample size, follow-up time, not assessing protein by food frequency questionnaire, using %energy as the measurement index, not adjusting for several covariates may be the sources of heterogeneity for plant protein. A significant non-linear relation among plant protein and incident CKD was observed by dose-response analysis. Conclusion: The data showed a lower CKD risk significantly associated higher-level dietary total, plant or animal protein (especially for fish and seafood) intake. Further prospective studies demonstrating the correlations of precise sources, intake and duration of dietary protein and incident CKD are warranted.

Elucidating the causal nexus and immune mediation between frailty and chronic kidney disease: integrative multi-omics analysis.

BACKGROUND: Empirical research has consistently documented the concurrent manifestation of frailty and chronic kidney disease (CKD). However, the existence of a reverse causal association or the influence of confounding variables on these correlations remains ambiguous. METHODS: Our analysis of 7,078 participants from National Health and Nutrition Examination Survey(NHANES) (1999-2018) applied weighted logistic regression and Mendelian Randomization (MR) to investigate the correlation between the frailty index (FI) and renal function. The multivariate MR analysis was specifically adjusted for type 2 diabetes and hypertension. Further analysis explored 3282 plasma proteins to link FI to CKD. A two-step network MR highlighted immune cells' mediating roles in the FI-CKD relationship. RESULT: Genetically inferred FI and various renal function markers are significantly correlated, as supported by NHANES analyses. Multivariate MR analysis revealed a direct causal association between the FI and CKD. Additionally, our investigation into plasma proteins identified Tmprss11D and MICB correlated with FI and CKD, respectively. A two-step network MR to reveal 15 immune cell types, notably Central Memory CD4+ T cells and Lymphocytes, as crucial mediators between FI and CKD. CONCLUSION: Our work establishes a causal connection between frailty and CKD, mediated by specific immune cell profiles. These findings highlight the importance of immune mechanisms in the frailty-CKD interplay and suggest that targeting shared risk factors and immune pathways could improve management strategies for these conditions. Our research contributes to a more nuanced understanding of frailty and CKD, offering new avenues for intervention and patient care in an aging population.

Prevalence and trends in overactive bladder among men in the United States, 2005-2020.

The purpose of present study was to examine the current prevalence and recent trends of overactive bladder (OAB) among US adult men and examine the correlations between OAB and several potential risk factors. The study used the nationally representative data between 2005 and 2020 from the National Health and Nutrition Examination Survey in the US. A total of 18,386 participants aged ≥ 20 years were included in the study. We divided the data into three groups: 2005-2008, 2009-2014 and 2015-2020 to investigate the trends in OAB prevalence. The weighted prevalence and corresponding 95% confidence intervals (CI) of OAB were calculated. The differences (95% CI) in prevalence between the surveys were calculated and multivariate-adjusted weighted logistic regression analysis was performed to determine the correlates of OAB. Among all US adult men, the overall prevalence of OAB increased slightly from 11.3% in 2005-2008 to 11.7% in 2009-2014 and significantly increased to 14.5% in 2015-2020 (difference, 3.2% [95% CI (1.9-4.4%)]; P < 0.05). Increases in OAB prevalence especially concentrated on those who were 40-59 years, non-Hispanic White, non-Hispanic Black and those who were overweight and obese. Older age, non-Hispanic Black, lower educational level and family poverty ratio, diabetes, depression, sleep disorder, other chronic comorbidities, less intense recreational activity, poorer health condition and unsafe food were independent risk factors of OAB. The contemporary prevalence of OAB was high, affecting 14.5% US men and the estimated overall prevalence significantly increased from 2005 to 2020. Therefore, future research should be focused to prevent and remedy this growing socioeconomic and individually troublesome malady.

Value of different preoperative bone evaluation methods in predicting intraoperative screw insertion torque-a prospective clinical comparative trial.

BACKGROUND CONTEXT: Establishing good screw-bone structural stability is conducive to reducing the risk of postoperative screw loosening. Screw insertion torque is an objective index for evaluating screw-bone structural stability. Therefore, accurate prediction of screw insertion torque can improve the preoperative evaluation of patients, optimize the surgical plan, and improve the surgical effect. At present, the correlation between different bone assessment methods and screw insertion torque is unclear. PURPOSE: The aim of this study was to evaluate the correlation between different bone assessment methods and screw insertion torque and to optimize the predictive performance of screw insertion torque through mathematical modeling combined with different radiology methods. DESIGN: Prospective cross-sectional study. PATIENT SAMPLES: 77 patients with preoperatively available DXA, CT and MRI data who underwent spinal fixation surgeries between October 2022 and September 2023 and 357 sets of screw data were included in this analysis. OUTCOME MEASURES: Spinal, vertebrae-specific and screw trajectory's BMD were measured preoperatively by different imaging modalities. Intraoperative screw insertion torque was measured using an electronic torque wrench. METHODS: Pearson linear correlation, scatter plots and univariate linear regression were used to evaluate the correlation between different bone evaluation methods and screw insertion torque. Different bone evaluation methods were fitted into the prediction model of screw torque and the related equations were obtained. RESULTS: Screw insertion torque had the strongest positive correlation with the volumetric bone mineral density (vBMD) of the screw trajectory (Pedicle screw insertion torque (PSIT): R = 0.618, p<.001; Terminal screw insertion torque (TSIT): R = 0.735, p<.001). A weak negative correlation was found between the screw insertion torque and level specific vertebral bone quality (VBQ) (PSIT: R = -0.178, p=.001; TSIT: R = -0.147, p=.006). We also found that the PSIT was strongly correlated with the TSIT (R = 0.812, p<.001). CONCLUSIONS: Compared to other bone quality assessment methods, screw trajectory vBMD may be better predict the magnitude of screw insertion torque. In addition, we further optimized preoperative assessments by constructing a mathematical model to better predict screw insertion torque. In conclusion, clinicians should select appropriate preoperative bone quality assessment methods, identify potential low-torque patients, optimize surgical plans, and ultimately improve screw insertion accuracy and reduce postoperative screw loosening rate.

Trends in chlamydia prevalence in the United States, 2005-2016.

In the United States (US), chlamydia is the most frequently reported sexually transmitted infection that is nationally notifiable. We examined trends in chlamydia prevalence in the US in 2011-2016 compared with 2005-2010. Cross-sectional, nationally representative surveys, National Health and Nutrition Examination Surveys (NHANES), were used to compare national chlamydia prevalence estimates from 2011 to 2016 with those from 2005 to 2010, and changes in prevalence since 1999-2004 were also reviewed. Persons aged 18-39 years were included in these analyses. Prevalence of chlamydia was based on results from urine specimens. Results were weighted to represent the U.S. civilian, noninstitutionalized population. The baseline characteristics of the study population were similar in gender, age and race/ethnicity between the two groups (P > 0.05). The overall chlamydia prevalence was 1.88% (95% confidence interval [CI] 1.55-2.22%) in 2011-2016 and 1.57% (95% CI 1.27-1.87%) in 2005-2010, a relative increase of 19.7% (95% CI 0.2-39.2%; P < 0.05) between the two surveys. Increases in chlamydia prevalence was especially concentrated in persons who were male, aged 18 to 29 years, had > high school educational level, never married, age at first sex < 18 years, had 2-5 sexual partners in lifetime and had no past sexually transmitted diagnosis between 2005 and 2016 (P < 0.05). Multivariable logistic regression analysis demonstrated that chlamydia was more prevalent in those aged 18-29 years, being non-Hispanic Blacks, had high school educational level, being widowed/divorced/separated and had > 5 sexual partners. The chlamydia prevalence had an increasing trend from 2005-2010 to 2011-2016. Those with high chlamydia prevalence such as sexually active young adults and Non-Hispanic Black should be screened annually so that infected persons can be diagnosed and they and their sex partners can be treated promptly.

MRI-based Vertebral Bone Quality Score for Osteoporosis Screening Based on Different Osteoporotic Diagnostic Criteria Using DXA and QCT.

In this study, we aim to evaluate the correlation between T score measured by dual X-ray absorptiometry (DXA), volumetric bone mineral density (vBMD) derived from quantitative computed tomography (QCT) and MRI-based vertebral bone quality (VBQ), explore the diagnostic performance of VBQ in osteoporosis and determine the recognition value of VBQ in osteoporotic fracture in a relatively large cohort of elderly patients scheduled to undergo spinal surgery. A total of 260 patients were enrolled in the study. DXA and QCT were used to evaluate osteoporotic status. We calculated the lumbar VBQ score, analyzed the correlation between T score, vBMD and VBQ, and explored whether VBQ was an influential factor of bone quality and fracture by binary logistic regression as well as the diagnostic performance of VBQ in osteoporosis and fracture by ROC curve. VBQ was negatively correlated with vBMD and T score. (r = - 0.487 vs. r = - 0.220). The VBQ score was a risk factor for osteoporosis under the QCT diagnostic criteria (OR = 2.245, 95% CI 1.456-3.460) and osteoporotic fractures (OR = 1.496, 95% CI 1.097-2.040). It exhibited superior discriminant performance for osteoporosis diagnosed by QCT, with a cutoff value of 3.70 and an AUC of 0.7354. Its cutoff value for osteoporotic fractures was 3.72, and its AUC was 0.6717. In a cohort of elderly patients scheduled to undergo spinal surgery, the VBQ score was more strongly associated with vBMD than the T score and could identify patients with osteoporosis and corresponding vertebral compression fracture (VCF).

Assessment of bone density using the 1.5 T or 3.0 T MRI-based vertebral bone quality score in older patients undergoing spine surgery: does field strength matter?

BACKGROUND CONTEXT: Recently published studies have revealed a correlation between MRI-based vertebral bone quality (VBQ) score and bone mineral density (BMD) measured using dual X-ray absorptiometry (DXA) or quantitative computed tomography (QCT). However, no studies have determined if differences in field strength (1.5 vs 3.0 T) could affect the comparability of the VBQ score among different individuals. PURPOSE: To compare the VBQ score obtained from 1.5 T and 3.0 T MRI (VBQ1.5T vs VBQ3.0T) in patients undergoing spine surgery and assess the predictive performance of VBQ for osteoporosis and osteoporotic vertebral fracture (VCF). DESIGN: A nested case‒control study based on an ongoing prospective cohort study of patients undergoing spine surgery. PATIENT SAMPLE: All older patients (men aged >60 years and postmenopausal women) with available DXA, QCT and MR images within 1 month were included. OUTCOME MEASURES: VBQ score, DXA T-score, and QCT derived vBMD. METHODS: The osteoporotic classifications recommended by the World Health Organization and American College of Radiology were used to categorize the DXA T-score and QCT-derived BMD, respectively. For each patient, the VBQ score was calculated using T1-weighted MR images. Correlation analysis between VBQ and DXA/QCT was performed. Receiver operating characteristic (ROC) curve analysis, including determination of the area under the curve (AUC), was performed to assess the predictive performance of VBQ for osteoporosis. RESULTS: A total of 452 patients (98 men aged >60 years and 354 postmenopausal women) were included in the analysis. Across different BMD categories, the correlation coefficients between the VBQ score and BMD ranged from -0.211 to -0.511, and the VBQ1.5T score and QCT BMD demonstrated the strongest correlation. The VBQ score was a significant classifier of osteoporosis detected by either DXA or QCT, with VBQ1.5T showing the highest discriminative power for QCT-osteoporosis (AUC=0.744, 95% CI=0.685-0.803). In ROC analysis, the VBQ1.5T threshold values ranged from 3.705 to 3.835 with a sensitivity between 48% and 55.6% and a specificity between 70.8% and 74.8%, while the VBQ3.0T threshold values ranged from 2.59 to 2.605 with a sensitivity between 57.6% and 67.1% and a specificity between 67.8% and 69.7%. CONCLUSIONS: VBQ1.5T exhibited better discriminability between patients with and without osteoporosis than VBQ3.0T. Considering the non-negligible difference in osteoporosis diagnosis threshold values between the VBQ1.5T and VBQ3.0T scores, it is essential to clearly distinguish the magnetic field strength when assessing the VBQ score.

Quantitative CT screening improved lumbar BMD evaluation in older patients compared to dual-energy X-ray absorptiometry.

BACKGROUND: Robust evidence on whether diagnostic discordance exists between lumbar osteoporosis detected by quantitative computed tomography (QCT) vs. dual-energy X-ray absorptiometry (DXA) is still lacking. In this study involving a relatively large prospective cohort of older men (aged > 60 years) and postmenopausal women, we assessed lumbar QCT-derived volumetric bone mineral density (vBMD) and DXA-derived area BMD and evaluated their predictive performance for prevalent vertebral fracture (VF). METHODS: A total of 501 patients who underwent spinal surgery from September 2020 to September 2022 were enrolled. The criteria recommended by the American College of Radiology and the World Health Organization were used for lumbar osteoporosis diagnosis. The osteoporosis detection rates between QCT and DXA were compared. QCT-vBMD was plotted against the DXA T score, and the line of best fit was calculated based on linear regression. Multivariate logistic regression was used to analyze the associations between risk factors and VF. Receiver operating characteristic curve analysis was performed, and the corresponding area under the curve (AUC) was calculated. RESULTS: QCT screening showed that 60.7% of patients had osteoporosis, whereas DXA screening showed that 50.7% of patients had osteoporosis. Diagnoses were concordant for 325 (64.9%) patients. In all, 205 patients suffered a VF of at least one anatomic level. Of these, 84.4% (173/205) were diagnosed with osteoporosis by QCT, while only 73.2% (150/205) were diagnosed by DXA. Multivariate logistic regression showed that osteoporosis detected by QCT exhibited a stronger relationship with VF than that detected by DXA (unadjusted OR, 6.81 vs. 5.04; adjusted OR, 3.44 vs. 2.66). For discrimination between patients with and without VF, QCT-vBMD (AUC = 0.802) showed better performance than DXA T score (AUC = 0.76). CONCLUSION: In older patients undergoing spinal surgery, QCT-vBMD is more helpful than DXA in terms of osteoporosis detection rate and prediction of patients with prevalent VFs.

Development of Combretastatin A-4 Analogues as Potential Anticancer Agents with Improved Aqueous Solubility.

Combretastatin A-4 (CA-4) is a potent tubulin polymerisation inhibitor. However, the clinical application of CA-4 is limited owing to its low aqueous solubility and the easy conversion of the olefin double bond from the more active cis- to the less active trans-configuration. Several structural modifications were investigated to improve the solubility of CA-4 derivatives. Among the compounds we synthesized, the kinetic solubility assay revealed that the solubility of compounds containing a piperazine ring increased the most, and the solubility of compounds 12a1, 12a2, 15 and 18 was increased 230-2494 times compared with that of the control compound (Z)-3-(4-aminophenyl)-2-(3,4,5-trimethoxyphenyl)acrylonitrile (9a). In addition, these synthesised stilbene nitriles had high anticancer cell (AGS, BEL-7402, MCF-7, and HCT-116) selectivity over L-02 and MCF-10A normal cells while maintaining micromolar activity against cancer cells. The most cytotoxic compound is 9a, and the IC50 value is 20 nM against HCT-116 cancer cells. Preliminary studies indicated that compound 12a1 had excellent plasma stability and moderate binding to rat plasma proteins, suggesting it is a promising lead compound for the development of an anticancer agent.

Discordance in lumbar bone mineral density measurements by quantitative computed tomography and dual-energy X-ray absorptiometry in postmenopausal women: a prospective comparative study.

BACKGROUND CONTEXT: Level-specific lumbar bone mineral density (BMD) evaluation of a single vertebral body can provide useful surgical planning and osteoporosis management information. Previous comparative studies have primarily focused on detecting spinal osteoporosis but not at specific levels. PURPOSE: To compare the detection rate of lumbar osteoporosis between quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA); to explore and analyze the distribution models of QCT-derived BMD and DXA T-score at the specific levels; and to evaluate the diagnostic accuracy of level-specific BMD thresholds for the prediction of osteoporotic vertebral compression fracture (OVCF) in postmenopausal women. STUDY DESIGN/SETTING: A comparative analysis of prospectively collected data comparing QCT-derived BMD with DXA T-score. PATIENT SAMPLE: A total of 296 postmenopausal women who were referred to the spine service of a single academic institution were enrolled. OUTCOME MEASURES: QCT-derived BMD and DXA T-score at specific levels, with or without osteoporotic vertebral compression fracture. METHODS: Postmenopausal women who underwent QCT and DXA within a week of admission from May 2019 to June 2022 were enrolled. The diagnostic criteria for osteoporosis recommended by the World Health Organization and the American College of Radiology were used for lumbar osteoporotic diagnosis. To evaluate differences in lumbar BMD measurements at specific levels, a threshold of T score=-2.5 and QCT-derived BMD = 80 mg/cm3 were used to categorize level-specific lumbar BMD into low and high BMD. Disagreements in BMD categorization between DXA and QCT were classified as a minor or major discordance based on the definition by Woodson. Data between QCT and DXA were visualized in a stacked bar plot and analyzed. Correlations between DXA and QCT at the specific levels were evaluated using Pearson's linear correlation and scatter plots. Curve fitting of BMD distribution, receiver operating characteristic (ROC) and area under the curve (AUC) for each single vertebral level was performed. RESULTS: Of the 296 patients, QCT diagnosed 61.1% as osteoporosis, 30.4% as osteopenia and 8.4% as normal. For those screened with DXA, 54.1% of the patients had osteoporosis, 29.4% had osteopenia and 16.6% had normal BMD. Diagnoses were concordant for 194 (65.5%) patients. Of the other 102 discordant patients, 5 (1.7%) were major and 97 (32.8%) were minor. Significant correlations in level-specific BMD between DXA and QCT were observed (p<.001), with Pearson's correlation coefficients ranging from 0.662 to 0.728. The correlation strength was in the order of L1 > L2 > L3 > L4. The low BMD detection rate for QCT was significantly higher than that for DXA at the L3 and L4 levels (65% vs. 47.9% and 68.1% vs 43.7, respectively, p<.001). Patients with OVCF showed significantly lower QCT-derived BMD (47.2 mg/cm3 vs. 83.2 mg/cm3, p<.001) and T-score (-3.39 vs. -1.98, p<.001) than those without OVCF. Among these patients, 82.8% (101/122) were diagnosed with osteoporosis by QCT measurement, while only 74.6% (91/122) were diagnosed by DXA. For discrimination between patients with and without OVCF, QCT-derived BMD showed better diagnosed performance (AUC range from 0.769 to 0.801) than DXA T-score (AUC range from 0.696 to 0.753). CONCLUSION: QCT provided a more accurate evaluation of lumbar osteoporosis than DXA. The QCT-derived BMD measurements at a specific lumbar level have a high diagnostic performance for OVCF.

A meta-analysis of randomized controlled trials: efficiency and safety of ondansetron in preventing post-anesthesia shivering during cesarean section.

OBJECTIVE: Although ondansetron was considered to prevent post-anesthesia shivering during cesarean section, its efficiency remained controversial. Our review was conducted to estimate the efficiency and safety of ondansetron in preventing post-anesthesia shivering during cesarean section. METHODS: The literature were searched from their inception to October 2020 without restriction of language. All randomized controlled trials investigating the efficacy of ondansetron versus placebo in preventing shivering during cesarean section under neuraxial anesthesia were included. The meta-analysis was conducted using Stata software. RESULTS: Eleven randomized controlled studies with a total of 748 individuals were finally included in our meta-analysis. Our results manifested that intravenous ondansetron compared with intravenous placebo significantly reduced the incidence of post-anesthesia shivering (PAS) (RR 0.53, 95% CI 0.14-0.68). Subgroup analysis according to doses of ondansetron indicated that the efficacy of 4 mg doses of ondansetron (RR 0.37, 95% CI 0.21-0.64) is equivalent to that of 8 mg doses of ondansetron (RR 0.61, 95% CI 0.47-0.81) in preventing PAS. In addition, the intravenous ondansetron led to a lower incidence of hypotension than intravenous placebo (OR 0.47, 95% CI 0.32-0.70). We could not demonstrate differences in the incidence of bradycardia between intravenous ondansetron and intravenous placebo. CONCLUSION: Our results found that intravenous ondansetron was effective in preventing shivering during cesarean section under neuraxial anesthesia, and had an advantage in reducing the incidence of hypotension compared with intravenous placebo.

Moisture-resistant, stretchable NOx gas sensors based on laser-induced graphene for environmental monitoring and breath analysis.

The accurate, continuous analysis of healthcare-relevant gases such as nitrogen oxides (NOx) in a humid environment remains elusive for low-cost, stretchable gas sensing devices. This study presents the design and demonstration of a moisture-resistant, stretchable NOx gas sensor based on laser-induced graphene (LIG). Sandwiched between a soft elastomeric substrate and a moisture-resistant semipermeable encapsulant, the LIG sensing and electrode layer is first optimized by tuning laser processing parameters such as power, image density, and defocus distance. The gas sensor, using a needlelike LIG prepared with optimal laser processing parameters, exhibits a large response of 4.18‰ ppm-1 to NO and 6.66‰ ppm-1 to NO2, an ultralow detection limit of 8.3 ppb to NO and 4.0 ppb to NO2, fast response/recovery, and excellent selectivity. The design of a stretchable serpentine structure in the LIG electrode and strain isolation from the stiff island allows the gas sensor to be stretched by 30%. Combined with a moisture-resistant property against a relative humidity of 90%, the reported gas sensor has further been demonstrated to monitor the personal local environment during different times of the day and analyze human breath samples to classify patients with respiratory diseases from healthy volunteers. Moisture-resistant, stretchable NOx gas sensors can expand the capability of wearable devices to detect biomarkers from humans and exposed environments for early disease diagnostics.

Intrinsically Breathable and Flexible NO2 Gas Sensors Produced by Laser Direct Writing of Self-Assembled Block Copolymers.

The surge in air pollution and respiratory diseases across the globe has spurred significant interest in the development of flexible gas sensors prepared by low-cost and scalable fabrication methods. However, the limited breathability in the commonly used substrate materials reduces the exchange of air and moisture to result in irritation and a low level of comfort. This study presents the design and demonstration of a breathable, flexible, and highly sensitive NO2 gas sensor based on the silver (Ag)-decorated laser-induced graphene (LIG) foam. The scalable laser direct writing transforms the self-assembled block copolymer and resin mixture with different mass ratios into highly porous LIG with varying pore sizes. Decoration of Ag nanoparticles on the porous LIG further increases the specific surface area and conductivity to result in a highly sensitive and selective composite to detect nitrogen oxides. The as-fabricated Ag/LIG gas sensor on a flexible polyethylene substrate exhibits a large response of -12‰, a fast response/recovery of 40/291 s, and a low detection limit of a few parts per billion at room temperature. Integrating the Ag/LIG composite on diverse fabric substrates further results in breathable gas sensors and intelligent clothing, which allows permeation of air and moisture to provide long-term practical use with an improved level of comfort.

The in vitro and in vivo study of a pyrazole derivative, J-1063, as a novel anti-liver fibrosis agent: Synthesis, biological evaluation, and mechanistic analysis.

In the present study, we completed the synthesis of a pyrazole derivative J-1063 and evaluated the kinase inhibitory activity of J-1063 activin receptor-like kinase 5 (ALK5) and p38α mitogen-activated protein (MAP) in the enzymatic assay. We evaluated anti-fibrotic effects of J-1063 on TGF-ß-induced hepatic stellate cells activation and TAA induced mice liver fibrosis. J-1063 showed much prior anti-fibrotic effects than those with LY2157299. Our data revealed that J-1063 exerted anti-fibrotic activity by inhibiting TGF-ßR1 (ALK5), which is likely related to the inhibition of TGF-ß--Smad signaling and NLRP3 inflammasome activation. The results suggest that J-1063 might be potential candidates for further anti-liver fibrosis drug development.

Development and validation of a simple and noninvasive method for salivary uric acid: potential applications for monitoring the salivary uric acid level in healthy volunteers and gout patients

Abstract Serum uric acid (UA) is a traditional biomarker in the clinical diagnosis of gout and hyperuricemia. However, serum treatment and storage are cumbersome, and wounds are susceptible to infection. Therefore, in this study, a simple and noninvasive method was developed to detect the UA in human saliva to monitor the gout. An Inertsil ODS-3 column was used for the analysis under the condition of isocratic elution with the mixed solution phosphate buffer (74 mM, pH=2.2): Methanol=98:2 (v:v) and the UV detection at 284 nm. Using salivary UA data from healthy volunteers (HVs) (n=68) and gout patients (GPs) (n=14), we examined the salivary UA difference in their content. The intra-and inter-day accuracy and precision (RSD %) were less than 2.56%, the limit of detection (LOD) of UA was 5.0 ng/mL, the mean recoveries of the corresponding compounds were 102.48%. Saliva levels of UA in HVs and GPs were 35.26±14.06 µg/mL and 91.96±23.90 µg/mL, respectively. The concentrations of salivary UA in GPs were significantly higher than those in HVs ( p < 0.001). This method was also expected to monitor the hyperuricemia and other metabolic disorders in the future

P2X7 receptor-targeted regulation by tetrahydroxystilbene glucoside in alcoholic hepatosteatosis: A new strategy towards macrophage-hepatocyte crosstalk.

BACKGROUND AND PURPOSE: Regulating macrophage-hepatocyte crosstalk through P2X7 receptors has led to new pharmacological strategies to reverse alcoholic hepatosteatosis. We investigated how tetrahydroxystilbene glucoside (2354glu), isolated from Polygonum multiflorum, modulates macrophage-hepatocyte crosstalk during alcoholic hepatosteatosis. EXPERIMENTAL APPROACH: A model of alcoholic hepatosteatosis was established by giving ethanol intragastrically to C57BL/6 mice. HepG2 cells were incubated in conditioned medium from LPS+ATP-activated THP-1 human macrophages with silenced or overexpressed P2X7 receptors. THP-1 macrophages or mouse peritoneal macrophages were pretreated with 2354glu for 1 hr prior to LPS+ATP stimulation. Western blots, RT-PCR and immunohistochemical analysis were used, along with over-expression and silencing of P2X7 receptors. KEY RESULTS: Knockdown or overexpression of P2X7 receptors in THP-1 macrophages affected release of mature IL-1ß and, subsequently, modulated lipid metabolism in HepG2 cells via the LKB-AMPK pathway. 2354glu ameliorated alcoholic hepatosteatosis in mice by regulating LKB1-AMPK-SREBP1 pathway and its target genes. Suppression of P2X7 receptor activation by 2354glu inhibited IL-1ß release and reduced macrophage and neutrophil infiltration. In macrophages stimulated with LPS+ATP, expression of P2X7 receptors, caspase-1 and NF-κB, release of IL-1ß, calcium influx and PI uptake were reduced by 2354glu. SIRT1-LKB1-AMPK-SREBP1 axis-mediated lipid accumulation in HepG2 cells was reduced when they were cultured with conditioned media from LPS+ATP-activated THP-1 macrophages pretreated with 2354glu. CONCLUSION AND IMPLICATIONS: Modulation of P2X7 receptors in macrophages regulated lipid accumulation in hepatocytes during alcoholic hepatosteatosis. 2354glu might be a promising candidate that targets P2X7 receptors in macrophages interacting with hepatocytes during alcoholic hepatosteatosis.