Triptolide-induced cuproptosis is a novel antitumor strategy for the treatment of cervical cancer.

BACKGROUND: Cuproptosis is a unique copper-dependent form of cell death that is highly correlated with the metabolic state of cells. Triptolide exerts pharmacological activity by altering the regulation of metal ions. Cuproptosis is poorly understood in cancer, so in this study, we explored whether triptolide could induce cuproptosis in cervical cancer cells. METHODS: The human cervical cancer cell lines HeLa and SiHa, which primarily rely on oxidative phosphorylation, were treated with triptolide. Cell viability, proliferation and migration, copper levels and cuproptosis-related protein levels were evaluated in these cell lines. The copper ion chelator tetrathiomolybdate (TTM) was administered to determine whether it could reverse the cuproptosis induced by triptolide. In addition, a nude mouse cervical cancer xenograft model was established to determine the effects of triptolide on cuproptosis in isolated tumor tissues. RESULTS: The copper concentration increased with triptolide treatment. The levels of cuproptosis -related proteins, such as FDX1, LIAS, and DLAT, in the HeLa and SiHa cell lines decreased with triptolide treatment. XIAP, the target of triptolide, played a role in cuproptosis by regulating COMMD1. The level of copper exporters (ATP7A/B) decreased, but the level of the copper importer (CTR1) did not change with triptolide treatment. Furthermore, triptolide inhibited cervical cancer growth and induced cuproptosis in vivo. CONCLUSIONS: In summary, we report a new antitumor mechanism by which triptolide disrupted intracellular copper homeostasis and induced cuproptosis in cervical cancer by regulating the XIAP/COMMD1/ATP7A/B axis.

Three-dimensional printed cast assisted screw fixation of calcaneal fractures: a prospective study.

BACKGROUND: Treatment of displaced intra-articular calcaneal fractures (DIACFs) with percutaneous screw fixation remains defective in some aspects. A novel three-dimensional (3D) printed cast was devised to assist screw placement. This study assessed the radiological and functional outcomes of 3D-printed cast assisted screw fixation for patients with DIACFs. METHODS: Patients with unilateral Sanders type II or III DIACFs admitted to a single-centre hospital underwent either 3D-printed cast assisted screw fixation (3D group) or minimally invasive plate fixation (control group) from September 2020 to November 2022. All patients were assessed at one, two, three, and six months of follow-up. Comparison between groups was conducted in operative duration, fluoroscopic times, radiographic measurements of the calcaneus, and the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Score. RESULTS: A total of 32 patients were enrolled (19 in the 3D group versus 13 in the control group). Significant differences were detected between the 3D group and control group in operative duration (53.63±8.95 min, 95.08±8.31 min, P <0.001), fluoroscopic times (7.37±1.21, 16.85±1.57, P <0.001). At a follow-up of six months, the 3D group showed better restoration than the control group in calcaneal width, height, Bohler angle, and AOFAS Ankle-Hindfoot scores (all P <0.001). No significant differences were shown in calcaneal length and Gissane angle (P >0.05). No wound-related complications occurred in either group. CONCLUSION: The 3D-printed cast assisted screw fixation has shown superiority over minimally invasive plate fixation in the operative duration, fluoroscopic exposure, morphological restoration of the calcaneus, and functional outcomes in the treatment of DIACFs.

The alteration of serum bile acid profile among traumatic brain injury patients: a small-scale prospective study.

Traumatic brain injury is one of the major causes of morbidity and mortality worldwide. With the development of bile acids as a potential treatment, to identify the influence of traumatic brain injury on bile acid metabolism shows growing importance. This present study did a preliminary exploration of the bile acid profile alteration among traumatic brain injury patients. In total, 14 patients and 7 healthy volunteers were enrolled. The bile acid profile of the blood samples were detected by an Ultra-performance Liquid Chromatography Mass Spectrometer/Mass Spectrometer system. It was found that 6 bile acids were statistically decreased in traumatic brain injury patients comparing with healthy volunteers: glycocholic acid (median level 44.4 ng/ml vs 98.7 ng/ml, p = 0.003), taurocholic acid (median level 10.9 ng/ml vs 19.5 ng/ml, p = 0.006), glycoursodeoxycholic acid (median level 17.4 ng/ml vs 71.4 ng/ml, p = 0.001), ursodeoxycholic acid (median level <1 ng/ml vs 32.4 ng/ml, p = 0.002), taurochenodeoxycholic acid (median level <1 ng/ml vs 53.6 ng/ml, p = 0.003) and glycochenodeoxycholic acid (GCDCA, median level 160 ng/ml vs 364 ng/ml, p<0.001). In conclusion, traumatic brain injury events are able to induce bile acid metabolism alteration in plasma and might cause reduction in glycocholic, taurocholic, glycoursodeoxycholic, ursodeoxycholic, taurochenodeoxycholic and glycochenodeoxycholic acid levels.

Increased CD4+ T cell count is associated with lower anal human papillomavirus prevalence among HIV-positive male cohort in Taizhou, China: a cross-sectional study.

OBJECTIVES: This study aims to investigate the association between CD4+ T cell count and combined antiretroviral therapy (cART) with the prevalence of anal human papillomavirus (HPV) infection among HIV-positive male cohort in China. METHODS: A survey was conducted in men from a HIV cohort in Taizhou, China between 2016 and 2019. A face-to-face questionnaire interview was administered, and an anal-canal swab was collected for HPV genotyping. RESULTS: A total of 766 HIV-positive men were recruited. The HPV prevalence was lower among those with increased CD4+ T cell count than those with decreased or unchanged (46.5 vs. 56.6%, p = 0.033) from baseline. In multivariable models, having the current CD4+ T cell count of 350-499 cells/µL (aOR 0.28, 95% CI 0.13-0.64), and of ≥ 500 cells/µL (aOR 0.26, 95% CI 0.11-0.60) were associated with lower prevalence of any type HPV infection compared with those with < 200 cells/µL. Having taken NVP + 3TC + AZT was inversely associated with any high-risk (HR)-HPV (aOR 0.47, 95% CI 0.25-0.90) and any low-risk (LR)-HPV infection (aOR 0.40, 95% CI 0.18-0.88), compared with those taking EFV + 3TC + TDF. CONCLUSIONS: Increased CD4+ T cell count at follow-up was significantly associated with lower prevalence of anal HPV infection. Inverse associations between NVP + 3TC + AZT and HR-HPV or LR-HPV infecton were observed.

The Peripheral Immune System and Traumatic Brain Injury: Insight into the role of T-helper cells.

Emerging evidence suggests that immune-inflammatory processes are key elements in the physiopathological events associated with traumatic brain injury (TBI). TBI is followed by T-cell-specific immunological changes involving several subsets of T-helper cells and the cytokines they produce; these processes can have opposite effects depending on the disease course and cytokine concentrations. Efforts are underway to identify the T-helper cells and cytokine profiles associated with prognosis. These predictors may eventually serve as effective treatment targets to decrease morbidity and mortality and to improve the management of TBI patients. Here, we review the immunological response to TBI, the possible molecular mechanisms of this response, and therapeutic strategies to address it.

Visible Light-Driven Azidation/Difunctionalization of Vinyl Arenes with Azidobenziodoxole under Copper Catalysis.

Visible light-driven azidation of vinyl arenes with azidobenziodoxole as the azidating agent was investigated in acetonitrile by using Cu(I)(phenanthroline)2 complex [Cu(dap)2]PF6 as photocatalyst. The reactions generated three types of difunctionalization products, which correspond to reaction patterns of amido-azidation, benzoyloxy-azidation, and diazidation. The electronic nature of the aryl group attached to the olefin moiety was found to play a crucial role in determining the reaction consequence: when the aryl group was electron-rich, the reactions afforded benzoyloxy-azidation products exclusively; for highly electron-deficient vinyl arenes, by contrast, diazidation products were generated in moderate yields. When the aryl group was moderately electron-rich or electron-deficient, on the other hand, a three-component reaction involving acetonitrile as well as azidobenziodoxole took place to give predominantly amido-azidation products. A plausible mechanism is proposed based on the mechanistic studies to rationalize these results. The reactions of electronically less biased vinyl arenes probably proceed via a redox catalysis pathway, while the electron-rich alkenes are believed to be converted through a radical chain process. The present reactions may be of synthetic usefulness as they provide a new means for the amido-azidation of vinyl arenes.

Peripheral Blood miR-937 May Serve as a Biomarker for Metabolic Disorders by Targeting AMPKα.

BACKGROUND: The current study mainly evaluated whether peripheral blood miR-937 could be a biomarker to differentiate patients with metabolic disorders and healthy controls. METHODS: The peripheral blood was collected with patients with hyperglycemia, hyperlipidemia and healthy control. The relative peripheral blood miR-937 level in patients with metabolic disorders and healthy individuals were evaluated by real-time PCR. Receiver operating characteristic curve (ROC) analysis and Spearman's correlation coefficient were applied to evaluate whether miR-937 could be a potential biomarker for metabolic disorders. Dual luciferase reporter assay was performed to identify the possible target genes of miR-937. RESULTS: First, miR-937 was significantly increased (8.02 ± 8.27) in the peripheral blood of hyperglycemia patients. The level of miR-937 of patients with hyperlipidemia (13.7 ± 14.72) was also enhanced obviously compared with healthy controls (1 ± 1.35). ROC analysis showed that the peripheral blood levels of miR-937 could screen patients with hyperglycemia or hyperlipidemia from healthy controls. Furthermore, peripheral blood miR-937 level posi-tively correlated with serum glucose level (r = 0.556, p < 0.01) as well as total serum TG/TC levels (r = 0.455, p < 0.01). Dual luciferase reporter assay indicated that miR-937 suppressed the relative luciferase activity of pmir-GLO-AMPKα-3'UTR. CONCLUSIONS: The upregulation of circulating miR-937 level may cause a metabolism disorder by suppressing the expression of AMPKα. miR-937 could be a potential biomarker to differentiate patients with metabolism syndrome from healthy controls.

Diagnostic Value of Serum MiR-587 in Patients with Metabolic Syndrome.

BACKGROUND: The current study aims to explore the changes of serum miR-587 level in patients with metabolic syndrome (MS) and analyze its clinical diagnostic value. METHODS: The serum levels of miR-587 in 50 patients with hyperglycemia, 50 patients with hyperlipidemia, and 50 healthy controls were detected by RT-qPCR. The diagnostic value of serum miR-587 was detected by ROC analy-sis and correlation analysis in MS. Dual luciferase reporter assay was carried out to determine the possible target gene of miR-587. RESULTS: The results of RT-qPCR showed that the relative content of serum miR-587 in patients with hyperglyce-mia and hyperlipidemia was 0.45 ± 0.30, 0.41 ± 0.30, compared with 1 ± 0.87 in healthy people. The area under ROC curve (AUC) of serum miR-587 in hyperglycemic patients was 0.830 (95% CI = 0.716 - 0.863, p < 0.001), with the sensitivity of 68.6% and specificity of 89.3%. The AUC of serum miR-587 in hyperlipidemia patients was 0.790 (95% CI = 0.759 - 0.851, p < 0.001), with the sensitivity of 78% and specificity of 89.7%. Correlation analysis showed that serum miR-587 level was negatively correlated with fasting blood glucose (FBG) (r = -0.291, p < 0.05), and negatively correlated with total cholesterol (TC) (r = -0.243, p < 0.01). Furthermore, dual luciferase reporter assay showed that PTEN was the target gene of miR-587. CONCLUSIONS: In summary the decreased expression of miR-587 in serum is a potential diagnostic marker and in-dependent risk factor in patients with MS.

Inhibition of Poly(ADP-Ribose) Polymerase Increased Lipid Accumulation Through SREBP1 Modulation.

BACKGROUND/AIMS: Excess energy intake leads to metabolic dysfunction, accompanied by oxidative stress and poly(ADP-ribose) polymerase (PARP) activation. METHODS: To determine the role of PARP activation in the incidence of metabolic dysfunction, PJ34, the PARP inhibitor, was administered to the oleic acid-treated hepatoma cells and high-fat diet-fed mice. The expression of genes was detected by quantitative real-time PCR and western blotting. Lipid droplets in the cells and tissues were stained with Oil Red O. RESULTS: PJ34 treatment aggravated oleic acid-induced lipid accumulation in hepatoma cells and induced SREBP1 expression by modulating the modification of transcription factor specificity protein 1 (Sp1). The high-fat diet-mice exhibited hyperglycemia, insulin resistance and lipid accumulation after 3 months of feeding. Although the serum level of lipid was not altered after PJ34 treatment, the expression level of lipogenic gene was up-regulated and the lipid accumulation was increased in the liver tissues of high-fat diet + PJ34-treated mice. In the high-fat diet + PJ34-treated mice, the insulin sensitivity was slightly changed and the levels of blood glucose and serum insulin were decreased compared with the mice fed with a high-fat diet alone. CONCLUSION: Taken together, PARP inhibition up-regulated the expression level of lipogenic gene and significantly induced lipid accumulation in the liver, which might worsen lipid metabolism disorders. These data will guide future research into the application of PARP inhibitors in the management of metabolic diseases.

Metformin-Induced Changes of the Coding Transcriptome and Non-Coding RNAs in the Livers of Non-Alcoholic Fatty Liver Disease Mice.

BACKGROUND/AIMS: Recent studies have suggested that changes in non-coding mRNA play a key role in the progression of non-alcoholic fatty liver disease (NAFLD). Metformin is now recommended and effective for the treatment of NAFLD. We hope the current analyses of the non-coding mRNA transcriptome will provide a better presentation of the potential roles of mRNAs and long non-coding RNAs (lncRNAs) that underlie NAFLD and metformin intervention. METHODS: The present study mainly analysed changes in the coding transcriptome and non-coding RNAs after the application of a five-week metformin intervention. Liver samples from three groups of mice were harvested for transcriptome profiling, which covered mRNA, lncRNA, microRNA (miRNA) and circular RNA (circRNA), using a microarray technique. RESULTS: A systematic alleviation of high-fat diet (HFD)-induced transcriptome alterations by metformin was observed. The metformin treatment largely reversed the correlations with diabetes-related pathways. Our analysis also suggested interaction networks between differentially expressed lncRNAs and known hepatic disease genes and interactions between circRNA and their disease-related miRNA partners. Eight HFD-responsive lncRNAs and three metformin-responsive lncRNAs were noted due to their widespread associations with disease genes. Moreover, seven miRNAs that interacted with multiple differentially expressed circRNAs were highlighted because they were likely to be associated with metabolic or liver diseases. CONCLUSIONS: The present study identified novel changes in the coding transcriptome and non-coding RNAs in the livers of NAFLD mice after metformin treatment that might shed light on the underlying mechanism by which metformin impedes the progression of NAFLD.

Adipose-specific deletion of Kif5b exacerbates obesity and insulin resistance in a mouse model of diet-induced obesity.

Recent studies have shown that KIF5B (conventional kinesin heavy chain) mediates glucose transporter type 4 translocation and adiponectin secretion in 3T3-L1 adipocytes, suggesting an involvement of KIF5B in the homeostasis of metabolism. However, the in vivo physiologic function of KIF5B in adipose tissue remains to be determined. In this study, adipose-specific Kif5b knockout (F-K5bKO) mice were generated using the Cre-LoxP strategy. F-K5bKO mice had similar body weights to controls fed on a standard chow diet. However, F-K5bKO mice had hyperlipidemia and significant glucose intolerance and insulin resistance. Deletion of Kif5b aggravated the deleterious impact of a high-fat diet (HFD) on body weight gain, hepatosteatosis, glucose tolerance, and systematic insulin sensitivity. These changes were accompanied by impaired insulin signaling, decreased secretion of adiponectin, and increased serum levels of leptin and proinflammatory adipokines. F-K5bKO mice fed on an HFD exhibited lower energy expenditure and thermogenic dysfunction as a result of whitening of brown adipose due to decreased mitochondria biogenesis and down-regulation of key thermogenic gene expression. In conclusion, selective deletion of Kif5b in adipose tissue exacerbates HFD-induced obesity and its associated metabolic disorders, partly through a decrease in energy expenditure, dysregulation of adipokine secretion, and insulin signaling.-Cui, J., Pang, J., Lin, Y.-J., Gong, H., Wang, Z.-H., Li, Y.-X., Li, J., Wang, Z., Jiang, P., Dai, D.-P., Li, J., Cai, J.-P., Huang, J.-D., Zhang, T.-M. Adipose-specific deletion of Kif5b exacerbates obesity and insulin resistance in a mouse model of diet-induced obesity.

Peripheral Blood miR-139 May Serve as a Biomarker for Metabolic Disorders by Targeting FoxO1 and FoxP1.

BACKGROUND: The current study mainly evaluated whether peripheral blood miR-139 could be used as a biomarker to screen patients with metabolic disorders. METHODS: The peripheral blood was collected with patients with hyperglycemia and high triglycerides (TG) combined with high total cholesterol (TC) as well as healthy control. Real time PCR was carried out to determine the relative peripheral blood miR-139 level in patients with metabolic disorders and healthy individuals. Receiver operating characteristic curve (ROC) analysis and Spearman's correlation coefficient were carried out to evaluate the possible application of miR-139 as a potential biomarker for metabolic disorders. Dual luciferase reporter assay was performed to identify the possible target genes of miR-139. RESULTS: First, miR-139 was highly upregulated (19.9 ± 12.67) in the peripheral blood of hyperglycemia patients. Meanwhile, compared with healthy controls (1 ± 0.66), the level of miR-139 was much higher (50.28 ± 26.26) in the peripheral blood of high TG combined with TC patients. ROC analysis showed that the peripheral blood levels of miR-139 may be used to differentiate subjects with hyperglycemia or high TG and TC from healthy controls. Furthermore, peripheral blood miR-139 level positively correlated with serum glucose level (r = 0.592, p < 0.001) as well as total serum TG/TC levels (r = 0.423, p < 0.001). Dual luciferase reporter assay indicated that miR-139 significantly suppressed the relative luciferase activity of pmirGLO-FoxO1-3'UTR or pmirGLO-FoxP1-3'UTR. CONCLUSIONS: In summary, enhanced circulating miR-139 level may be a potential biomarker for patients with metabolic disorders via suppressing the expression of FoxO1 and FoxP1.

Associations of nicotinamide N-methyltransferase gene single nucleotide polymorphisms with sport performance and relative maximal oxygen uptake.

To observe the associations between single nucleotide polymorphisms (SNPs) of nicotinamide N-methyltransferase (NNMT) gene and sport performance and to analyse genotype associations of the associated SNPs with sport performance and relative maximal oxygen uptake ([Formula: see text]). Participants were selected from 685 Chinese Han male college students. The completion times of a 1000-m run and a 50-m run were used to reflect sport performance, respectively. Nineteen tagSNPs were genotyped with Polymerase chain reaction-ligase detection reaction. Relative [Formula: see text] was directly determined with a cardiopulmonary function analyser. A significant association was found between rs2256292 and 1000-m run performance, but no significant association was found between any tagSNPs and 50-m run performance. The genotype associations of rs2256292 with 1000-m run performance and with relative [Formula: see text] were both significant under the recessive model (CC vs. CG + GG). No tagSNP in NNMT is significantly associated with 50-m run performance but rs2256292 is significantly associated with 1000-m run performance. The genotype associations of rs2256292 with sport performance are significant under recessive model, and a higher relative [Formula: see text] may be the physiological reason for minor homozygote CC carriers being of the better 1000-m runners.

Conventional kinesin KIF5B mediates adiponectin secretion in 3T3-L1 adipocytes.

Insulin stimulates adiponectin secretion and glucose transporter type 4 (GLUT4) translocation in adipocyte to regulate metabolism homeostasis. Similar to GLUT4 translocation, intracellular trafficking and release of adiponectin in adipocytes relies on the trans-Golgi network and endosomal system. Recent studies show that the heavy chain of conventional kinesin (KIF5B) mediates GLUT4 translocation in murine 3T3-L1 adipocytes, however, the motor machinery involved in mediating intracellular trafficking and release of adiponectin is unknown. Here, we examined the role of KIF5B in the regulation of adiponectin secretion. The KIF5B level was up-regulated during 3T3-L1 adipogenesis. This increase in cytosolic KIF5B was synchronized with the induction of adiponectin. Endogenous KIF5B and adiponectin were partially colocalized at the peri-nuclear and cytosolic regions. In addition, adiponectin-containing vesicles were co-immunoprecipitated with KIF5B. Knockdown of KIF5B resulted in a marked inhibition of adiponectin secretion and overexpression of KIF5B enhanced adiponectin release, whereas leptin secretion was not affected by changes in KIF5B expression. These data suggest that the secretion of adiponectin, but not leptin, is dependent on functional KIF5B.

Incidence, clearance, and factors associated with anal human papilloma virus infection among men with HIV.

OBJECTIVES: This study aims to estimate the incidence and persistence/clearance of anal human papilloma virus (HPV) infection and related factors among men with HIV in Taizhou, China. DESIGN: A prospective cohort study. METHODS: Men with HIV were recruited and followed up from 2016 to 2021. Questionnaire surveys were used to collect social-demographic and behavioral characteristics, and anal swabs were collected for HPV Genotyping. RESULTS: A total of 675 men with HIV were recruited and followed up. After an average follow-up time of 1.75 years, HPV39 (3.8/100 person-years), HPV52 (3.6/100 person-years), HPV51 (3.1/100 person-years), HPV58 (2.5/100 person-years) and HPV16 (2.4 cases/100 person-years) in the high-risk types showed the highest incidence rate. In marriage with woman [adjusted hazard ratio (aHR) = 0.44, 95% confidence interval (CI) 0.20-0.99] showed an inverse association with HPV incidence, while bisexuality or undetermined sexual orientation (aHR = 2.62, 95% CI 1.08-6.36) showed a positive association. For those infected at baseline, the top three high-risk HPV with the lowest clearance density were HPV52 (32.2/100 person-years), HPV58 (38.1/100 person-years), and HPV16 (43.5/100 person-years). Daily consumption of 1-28 g alcohol (aHR = 0.62, 95% CI 0.41-0.95) showed an inverse association with HPV clearance, while illicit drug use (aHR = 3.24, 95% CI 1.59-6.59) showed a positive association. CONCLUSION: Anal HPV infection and clearance were both active in men with HIV in China. Marriage status and sexuality were associated with the incidence of HPV infection, while substance use including alcohol and illicit drug were associated with HPV clearance. More studies are needed to explore the risk factors of HPV persistence.

Bortezomid enhances the efficacy of lidamycin against human multiple myeloma cells.

The proteasome inhibitor bortezomib has been applied successfully to treat multiple myeloma (MM). Its synergistic effects with other anticancer drugs have been studied widely. In the present study, it was found that lidamycin (LDM), a member of the enediyne antibiotic family, showed much more potent cytotoxicity than bortezomib to MM cell lines: U266 and SKO-007. Here, we investigated the potential synergy of bortezomib and LDM on MM cells. The results showed that cotreatment of bortezomib and LDM synergistically induced cytotoxicity and apoptosis in MM cell lines, followed by enhanced caspase-3 cleavage and degradation of poly-ADP-ribose polymerase together with the decreased nuclear factor-κB protein. These two drugs synergistically induced apoptosis, which was associated with enhanced activation of two mitogen-activated protein kinases: p38 mitogen-activated protein kinase and c-Jun NH(2)-terminal kinase. Moreover, bortezomib plus LDM synergistically induced apoptosis was also associated with downregulation of extracellular signal-regulated kinase, and induction of endoplasmic reticulum stress response. Overall, our results indicate that the combined regimen of bortezomib and LDM might be a potential therapeutic remedy for the treatment of MM.

Rhein lysinate increases the median survival time of SAMP10 mice: protective role in the kidney.

AIM: To investigate the protective effects of rhein lysinate (RHL), a major bioactive constituent of the rhizome of rhubarb (Rheum palmatum Linn or Rheum tanguticum Maxim), against kidney impairment in senescence-prone inbred strain 10 (SAMP10) mice. METHODS: SAMP10 mice were orally administered RHL (25 or 50 mg/kg) daily until 50% of the mice died. Senescence-resistant inbred strain 1 (SAMR1) mice administered no drug were taken as control. The kidneys were harvested after animal death, and examined morphologically and with immunochemical assays. The levels of MAD, SOD and GSH-px in the kidneys were measured with a photometric method. The expression of inflammatory factors and related proteins in the kidneys was analyzed using Western blotting. RESULTS: Treatment of SAMP10 mice with RHL had no effect on the body weight or phenotype. However, RHL significantly prolonged the median survival time of SAMP10 mice by approximately 25%, as compared to untreated SAMP10 mice. Compared SAMR1 mice, SAMP10 mice had a significantly lower level of SOD in the kidneys, but had no significant difference in the MDA or GSH-px levels. Treatment of SAMP10 mice with RHL significantly reduced the MAD level, and increased the SOD and GSH-px levels in the kidneys. Glomerulonephritis was observed in SAMP10 mice but not in SAMR1 mice. RHL decreased the incidence of glomerulonephritis, and significantly decreased the levels of TNF-α, IL-6, NF-κB, collagen types I and III in the kidneys. CONCLUSION: Accelerated senescence is associated with glomerulonephritis in SAMP10 mice, and RHL prolongs their median survival time by reducing the severity of glomerulonephritis.

Astragalus polysaccharides suppress ICAM-1 and VCAM-1 expression in TNF-α-treated human vascular endothelial cells by blocking NF-κB activation.

AIM: To investigate the effects Astragalus polysaccharides (APS) on tumor necrosis factor (TNF)-α-induced inflammatory reactions in human umbilical vein endothelial cells (HUVECs) and to elucidate the underlying mechanisms. METHODS: HUVECs were treated with TNF-α for 24 h. The amounts of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were determined with Western blotting. HUVEC viability and apoptosis were detected using cell viability assay and Hoechst staining, respectively. Reactive oxygen species (ROS) production was measured by DHE staining. Monocyte and HUVEC adhesion assay was used to detect endothelial cell adhesive function. NF-κB activation was detected with immunofluorescence. RESULTS: TNF-α (1-80 ng/mL) caused dose- and time-dependent increases of ICAM-1 and VCAM-1 expression in HUVECs, accompanied by significant augmentation of IκB phosphorylation and NF-κB translocation into the nuclei. Pretreatment with APS (10 and 50 µg/mL) significantly attenuated TNFα-induced upregulation of ICAM-1 VCAM-1 and NF-κB translocation. Moreover, APS significantly reduced apoptosis, ROS generation and adhesion function damage in TNF-α-treated HUVECs. CONCLUSION: APS suppresses TNFα-induced adhesion molecule expression by blocking NF-κB signaling and inhibiting ROS generation in HUVECs. The results suggest that APS may be used to treat and prevent endothelial cell injury-related diseases.

Rhein lysinate decreases the generation of ß-amyloid in the brain tissues of Alzheimer's disease model mice by inhibiting inflammatory response and oxidative stress.

The protective effect of rhein lysinate (RHL) on Alzheimer's disease (AD) was explored in senescence-accelerated mouse prone-8 (SAMP8) mice. SAMP8 mice without treatment were used as the AD-positive control, and senescence-accelerated-resistant mice were used as the AD-negative control. In this study, 4-month-old male SAMP8 mice were orally administered 25 and 50 mg/kg RHL in drinking water for 6 months. The results of brain tissue enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and Western blot were demonstrated that compared with SAMP8 group, ß-amyloid1-40 and ß-amyloid1-42 were reduced; the levels of tumor necrosis factor-α and interleukin 6 of brain tissues were also significantly decreased; however, the level of sirtuin 1 (SIRT1) was increased in the RHL-treated group. Compared with SAMP8 group, the ROS levels and malondialdehyde levels were decreased; however, superoxide dismutase and glutathione peroxidase levels were increased in the brain tissues of SAMP8 25 and 50 mg/kg RHL-treated groups. In conclusion, the reduction of Aß induced by RHL was related to the increase of SIRT1 and the inhibition of the inflammatory response and oxidative stress in SAMP8 mice. It might be a promising biological therapeutic drug for AD.