Prevalence and risk evaluation of cardiovascular disease in the newly diagnosed prostate cancer population in China: A nationwide, multi-center, population-based cross-sectional study.

BACKGROUND: Cardiovascular disease (CVD) has emerged as the leading cause of death from prostate cancer (PCa) in recent decades, bringing a great disease burden worldwide. Men with preexisting CVD have an increased risk for major adverse cardiovascular events when treated with androgen deprivation therapy (ADT). The present study was aimed to explore the prevalence and risk evaluation of CVD among people with newly diagnosed PCa in China. METHODS: Clinical data of newly diagnosed PCa patients were retrospectively collected from 34 centers in China from 2010 to 2022 through convenience sampling. CVD was defined as myocardial infarction, arrhythmia, heart failure, stroke, ischemic heart disease, and others. CVD risk was estimated by calculating Framingham risk scores (FRS). Patients were accordingly divided into low-, medium-, and high-risk groups. χ2 or Fisher's exact test was used for comparison of categorical variables. RESULTS: A total of 4253 patients were enrolled in the present study. A total of 27.0% (1147/4253) of patients had comorbid PCa and CVD, and 7.2% (307/4253) had two or more CVDs. The enrolled population was distributed in six regions of China, and approximately 71.0% (3019/4253) of patients lived in urban areas. With imaging and pathological evaluation, most PCa patients were diagnosed at an advanced stage, with 20.5% (871/4253) locally progressing and 20.5% (871/4253) showing metastasis. Most of them initiated prostatectomy (46.6%, 1983/4253) or regimens involving ADT therapy (45.7%, 1944/4253) for prostate cancer. In the present PCa cohort, 43.1% (1832/4253) of patients had hypertension, and half of them had poorly controlled blood pressure. With FRS stratification, as expected, a higher risk of CVD was related to aging and metabolic disturbance. However, we also found that patients with treatment involving ADT presented an originally higher risk of CVD than those without ADT. This was in accordance with clinical practice, i.e., aged patients or patients at advanced oncological stages were inclined to accept systematic integrative therapy instead of surgery. Among patients who underwent medical castration, only 4.0% (45/1118) received GnRH antagonists, in stark contrast to the grim situation of CVD prevalence and risk. CONCLUSIONS: Prostate cancer patients in China are diagnosed at an advanced stage. A heavy CVD burden was present at the initiation of treatment. Patients who accepted ADT-related therapy showed an original higher risk of CVD, but the awareness of cardiovascular protection was far from sufficient.

Clinical efficacy of comprehensive therapy based on traditional Chinese medicine patterns on patients with pneumoconiosis: a pilot double-blind, randomized, and placebo-controlled study.

Effective therapy options for pneumoconiosis are lacking. Traditional Chinese medicine (TCM) presents a favorable prospect in the treatment of pneumoconiosis. A pilot study on TCM syndrome differentiation can evaluate the clinical efficacy and safety of TCM and lay a foundation for further clinical research. A double-blind, randomized, and placebo-controlled trial was conducted for 24 weeks, in which 96 patients with pneumoconiosis were randomly divided into the control and treatment groups. Symptomatic treatment was conducted for the two groups. The treatment group was treated with TCM syndrome differentiation, and the control group was treated with placebo. The primary outcomes were the six-minute walking distance (6MWD) and the St. George Respiratory Questionnaire (SGRQ) score. The secondary outcomes were the modified British Medical Research Council Dyspnea Scale (mMRC), Chronic Obstructive Pulmonary Disease Assessment Test (CAT), Hospital Anxiety and Depression Scale (HADS), and pulmonary function. Only 83 patients from the 96 patients with pneumoconiosis finished the study. For the primary outcome, compared with the control groups, the treatment group showed a significantly increased 6MWD (407.90 m vs. 499.51 m; 95% confidence interval (CI) 47.25 to 135.97; P < 0.001) and improved SGRQ total score (44.48 vs. 25.67; 95% CI -27.87 to -9.74; P < 0.001). The treatment group also significantly improved compared with the control group on mMRC score (1.4 vs. 0.74; 95% CI -1.08 to -0.23; P =0.003), CAT score (18.40 vs. 14.65; 95% CI -7.07 to -0.43; P =0.027), and the total symptom score (7.90 vs. 5.14; 95% CI -4.40 to -1.12; P < 0.001). No serious adverse events occurred. This study showed that TCM syndrome differentiation and treatment had a favorable impact on the exercise endurance and quality of life of patients with pneumoconiosis.

Xanthophylls Modulate Palmitoylation of Mammalian ß-Carotene Oxygenase 2.

An extensive body of work has documented the antioxidant role of xanthophylls (lutein and zeaxanthin) in human health and specifically how they provide photoprotection in human vision. More recently, evidence is emerging for the transcriptional regulation of antioxidant response by lutein/lutein cleavage products, similar to the role of ß-carotene cleavage products in the modulation of retinoic acid receptors. Supplementation with xanthophylls also provides additional benefits for the prevention of age-related macular degeneration (AMD) and attenuation of Alzheimer's disease symptoms. Mammalian ß-carotene oxygenase 2 (BCO2) asymmetrically cleaves xanthophylls as well as ß-carotene in vitro. We recently demonstrated that mouse BCO2 (mBCO2) is a functionally palmitoylated enzyme and that it loses palmitoylation when cells are treated with ß-carotene. The mouse enzyme is the easiest model to study mammalian BCO2 because it has only one isoform, unlike human BCO2 with several major isoforms with various properties. Here, we used the same acyl-RAC methodology and confocal microscopy to elucidate palmitoylation and localization status of mBCO2 in the presence of xanthophylls. We created large unilamellar vesicle-based nanocarriers for the successful delivery of xanthophylls into cells. We demonstrate here that, upon treatment with low micromolar concentration of lutein (0.15 µM), mBCO2 is depalmitoylated and shows partial nuclear localization (38.00 ± 0.04%), while treatment with zeaxanthin (0.45 µM) and violaxanthin (0.6 µM) induces depalmitoylation and protein translocation from mitochondria to a lesser degree (20.00 ± 0.01% and 35.00 ± 0.02%, respectively). Such a difference in the behavior of mBCO2 toward various xanthophylls and its translocation into the nucleus in the presence of various xanthophylls suggests a possible mechanism for transport of lutein/lutein cleavage products to the nucleus to affect transcriptional regulation.

Preparation of smooth and macroporous hydrogel via hand-held blender for wound healing applications: in vitro and in vivo evaluations.

Wound dressings play an indispensable role in wound healing. However, traditional wound dressings have several disadvantages, such as poor mechanical properties and small pore diameters, which do not allow sufficient gas exchange. To overcome these shortcomings, this paper reports a polyvinyl alcohol (PVA)-based hydrogel physically crosslinked at -20 °C and containing polyethylene glycol (PEG) and nanohydroxyapatite (HAP). The physical and chemical properties of the hydrogels formed by different stirring methods (stirring with a glass rod or a hand-held homogenizer) were compared. The average roughness of Gel 1 (prepared using a hand-held homogenizer) is 112.6 nm, which is much lower than the average surface roughness of Gel 2 (1222 nm, prepared using a glass rod). Moreover, the hydrogel made by the unconventional mixing method (with a homogenizer) showed better performance, including a more interconnected open-pore microstructure and better mechanical properties. Finally, a full-thickness skin defect test was performed. The experimental results demonstrated that the hydrogel has considerable potential for applications in wound dressings.

The Antioxidant Polysaccharide from Semiaquilegia adoxoides (DC.) Makino Adjusts the Immune Response of Mice Infected by Bacteria.

Semiaquilegia adoxoides (DC.) Makino is a herbal medicine and it is recorded that its water extract can be used to treat acute diseases caused by bacterial infections. In order to understand the polysaccharide of Semiaquilegia adoxoides (DC.) Makino (SMP), FT-IR and HPLC methods were performed to determine the basic chemical structure and monosaccharide compositions of SMP. The antioxidant capacity of SMP was analyzed by monitoring both the scavenging rate of DPPH and ABTS free radical. To investigate the effects of SMP on the acute bacterial disease, minimum inhibitory concentrations (MICs) of SMP on E. coli or S. aureus were detected; meanwhile, mice were administrated with SMP for 7 days and then infected with E. coli or S. aureus, and the parameters were measured at the 9th day. Results showed that SMP was a furanose which was mainly composed of glucose (60.3%) and had certain antioxidant activities. Both MIC values of SMP on E. coli and S. aureus were 250 ml/mL, which means that SMP has no direct antibacterial effects. The mice experiments revealed that SMP had potential effects on immunomodulatory by reducing WBC and the expression of serum IL-1, IL-6, and TNF-α and increasing IgM of E. coli or S. aureus infected mice. These findings supported the effect of Semiaquilegia adoxoides (DC.) Makino in folk use with scientific evidence.

[Effect of traditional Chinese medicine syndrome differentiation and standard bundle therapy in patients with septic shock].

OBJECTIVE: To evaluate an effective and feasible quantitative evaluation table of traditional Chinese medicine (TCM) syndrome differentiation, and to observe the effect of combination of TCM syndrome differentiation and standard bundle therapy in patients with septic shock. METHODS: A prospective randomized controlled trial was conducted. The septic shock patients with acute deficiency syndrome admitted to department of critical care medicine of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from January 1st, 2016 to December 31st, 2017 were enrolled. The patients were randomly divided into control group and Shenfu group. The patients in both groups received early application of standardized bundle therapy; those in Shenfu group received 60 mL Shenfu injection infusion in addition for 7 days. The TCM syndrome score was evaluated by classification and scoring method of TCM symptoms. The circulation and tissue perfusion, severity of disease, organ function, inflammation response, adjuvant treatment and 28-day mortality were compared between the two groups. RESULTS: A total of 50 patients with septic shock were enrolled in the analysis, 25 in control group and 25 in Shenfu group. The markedly effective rate of TCM symptoms score in Shenfu group was significantly higher than that in control group [60.0% (15/25) vs. 16.0% (4/25), P < 0.01]. There was no significant difference in all parameters before treatment between the two groups. After treatment, the observation indexes of both groups were improved. Compared with control group, the mean arterial pressure (MAP) in Shenfu group increased more significantly [mmHg (1 mmHg = 0.133 kPa): 13.0 (2.5, 28.5) vs. 6.0 (0, 13.5)], the lactate (Lac) and procalcitonin (PCT) decreased more significantly [Lac (mmol/L): 0.8 (0.1, 3.7) vs. 0.5 (-0.6, 1.7), PCT (µg/L): 2.0 (0.7, 32.3) vs. 0 (-1.8, 3.8)], activated partial thromboplastin time (APTT) was shortened more significantly [s: 8.5 (0, 12.9) vs. 0 (-7.2, 10.0)], and interleukins (IL-2 receptor and IL-6) levels decreased more significantly [IL-2 receptor (ng/L): 1 031.0 (533.0, 1 840.0) vs. 525.5 (186.0, 1 166.8), IL-6 (ng/L): 153.1 (21.4, 406.8) vs. 35.1 (16.3, 110.1)] with significant differences (all P < 0.05). There was no significant difference in the use time of vasoactive drugs, duration of mechanical ventilation, severity of the disease or 28-day mortality between the two groups. However, the use time of vasoactive drugs in Shenfu group was shorter than that in control group (days: 5.48±4.81 vs. 8.28±7.83), and the 28-day mortality was decreased [8.0% (2/25) vs. 20.0% (5/25)]. CONCLUSIONS: TCM syndrome score is helpful to evaluate the effect of TCM syndrome differentiation and treatment, and it is effective and feasible in clinical application. Septic shock patients treated with TCM syndrome differentiation and treatment combined with standard bundle therapy were significantly improved in circulation, tissue perfusion, coagulation function and inflammation reaction.

Nerve Growth Factor Levels are Associated with Overactive Bladder Symptoms and Long-Term Treatment Outcome after Transurethral Resection of the Prostate in Patients with Benign Prostatic Hyperplasia.

PURPOSE: We investigated changes in urinary nerve growth factor in patients with benign prostatic hyperplasia after transurethral prostate resection. We also assessed the association between nerve growth factor and changes of overactive bladder symptoms and long-term treatment outcomes after surgery. MATERIALS AND METHODS: This was a prospective study of 178 patients at Peking University People's Hospital with benign prostatic hyperplasia between January 2011 and January 2013. Urinary nerve growth factor levels were determined preoperatively using a commercial enzyme-linked immunosorbent assay kit. We also determined prostate volume, I-PSS (International Prostate Symptom Score), quality of life, OABSS (Overactive Bladder Symptom Score), ultrasound estimated post-void residual urine and urodynamics before surgery. Urinary nerve growth factor levels, I-PSS and OABSS were assessed again 1 year after transurethral prostate resection. RESULTS: Urinary nerve growth factor/creatinine levels differed between patients with moderate and severe lower urinary tract symptoms (mean ± SD 10.513 ± 4.255 vs 12.334 ± 4.048 pg/µmol, p = 0.002). There was no significant difference between patients with grades III/IV and V/VI bladder outlet obstruction (mean 11.285 ± 4.069 vs 11.781 ± 4.437 pg/µmol, p = 0.354). However, differences were significant for urinary nerve growth factor/creatinine levels in patients without overactive bladder, and mild, moderate and severe overactive bladder (mean 8.132 ± 3.489, 10.128 ± 3.817, 13.232 ± 3.290 and 14.029 ± 3.820 pg/µmol, respectively, p <0.001). One year after transurethral prostate resection we noted a decrease vs baseline in mean urinary nerve growth factor/creatinine (8.978 ± 4.022 pg/µmol, p <0.001), and I-PSS and OABSS (10.2 ± 5.4 and 4.3 ± 3.7, respectively, each p <0.001). Compared with the good outcome group, the fair/poor group had higher mean baseline urinary nerve growth factor/creatinine (12.319 ± 4.017 vs 11.015 ± 4.298 pg/µmol, p = 0.045), higher mean 1-year urinary nerve growth factor/creatinine (10.847 ± 4.267 vs 7.850 ± 3.419 pg/µmol, p <0.001) and a lesser mean postoperative change in urinary nerve growth factor/creatinine (1.472 ± 4.928 vs 3.165 ± 4.863 pg/µmol, p = 0.031). CONCLUSIONS: Nerve growth factor was associated with overactive bladder symptoms in patients with benign prostatic hyperplasia as well as with the assessment of successful long-term treatment outcome of bladder outlet obstruction with symptoms of overactive bladder.

Synthesis and Characterization of an Antioxidative Galactomannan⁻Iron(III) Complex from Sesbania Seed.

Galactomannan, a water-soluble polymer in the cell wall of leguminous plants, has been proven to possess anticancer and antioxidative activity. In this work, galactomannan with different molecular weights (GM-40 and GM-65) was obtained from Sesbania seeds and synthesized into galactomannan⁻iron(III) complexes, which are termed as GM-40-Fe and GM-65-Fe, respectively. These galactomannan⁻iron(III) complexes are intended to function as organic iron supplements to treat iron deficiency with the added benefit of antioxidative activity. The prepared galactomannan⁻iron(III) complexes were characterized for chemical composition, morphology, antioxidant capacity, and bioavailability in vitro. The results showed that galactomannan⁻iron(III) complexes could be produced with iron contents as high as 65.4 mg/g. Antioxidant assays indicated that both GM-40-Fe and GM-65-Fe exhibited antioxidant activities for scavenging radicals in vitro. The iron release/bioavailability assays showed that the iron was easily released into artificial gastric and intestinal juices, resulting in iron release rates of 88⁻94% over 300 min. These results suggest that galactomannan⁻iron(III) complexes synthesized from Sesbania seed polysaccharides are capable of being administered as organic iron supplements to patients with iron deficiency.

Black Phosphorus Nanosheets as a Neuroprotective Nanomedicine for Neurodegenerative Disorder Therapy.

Transition-metal dyshomeostasis is recognized as a critical pathogenic factor at the onset and progression of neurodegenerative disorder (ND). Excess transition-metal ions such as Cu2+ can catalyze the generation of cytotoxic reactive oxygen species and thereafter induce neuronal cell apoptosis. Exploring new chelating agents, which are not only capable of capturing excess redox-active metal, but can also cross the blood-brain barrier (BBB), are highly desired for ND therapy. Herein, it is demonstrated that 2D black phosphorus (BP) nanosheets can capture Cu2+ efficiently and selectively to protect neuronal cells from Cu2+ -induced neurotoxicity. Moreover, both in vitro and in vivo studies show that the BBB permeability of BP nanosheets is significantly improved under near-infrared laser irradiation due to their strong photothermal effect, which overcomes the drawback of conventional chelating agents. Furthermore, the excellent biocompatibility and stability guarantee the biosafety of BP in future clinical applications. Therefore, these features make BP nanosheets have the great potential to work as an efficient neuroprotective nanodrug for ND therapy.

Dusuqing granules (DSQ) suppress inflammation in Klebsiella pneumonia rat via NF-κB/MAPK signaling.

BACKGROUND: Dusuqing granules (DSQ) have been used in the treatment of bacterial pneumonia clinically, with remarkable benefits. This study was initiated to explore the effects of DSQ on pulmonary inflammation by regulating nuclear factor (NF)-κB/mitogen-activated protein kinase (MAPK) signaling in bacterial pneumonia rats. METHODS: Rat model was duplicated with Klebsiella pneumonia by a one-time intratracheal injection. Rats were randomized into control, model, DSQ and levofloxacin (LVX) groups. After administrated with appropriate medicines for 7 days, lung tissues were harvested and prepared for pathological analysis, and interleukin (IL)-1, IL-6, monocyte chemotactic protein (MCP)-1and macrophage inflammatory protein (MIP)-2 detections. NF-κB mRNA was measured by real-time qPCR, and the phosphorylation and total proteins of P38MAPK, JNK46/54, ERK42/44 were determined by Western blotting. RESULTS: Marked pathological impairments were observed in model rats, whereas were improved in DSQ group. The cytokines levels, NF-κB mRNA expression and the phosphorylation of P38MAPK, JNK46/54 and ERK42/44 proteins were significantly higher in model group, and were significantly depressed in DSQ group. CONCLUSION: The protective effects of DSQ on Klebsiella pneumonia might be attributed to its inactivative effects of NF-κB/ MAPK pathway.

Asparagus cochinchinensis Extract Alleviates Metal Ion-Induced Gut Injury in Drosophila: An In Silico Analysis of Potential Active Constituents.

Metal ions and sulfate are components of atmospheric pollutants that have diverse ways of entering the human body. We used Drosophila as a model to investigate the effect of Asparagus cochinchinensis (A. cochinchinensis) extracts on the gut and characterized gut homeostasis following the ingestion of metal ions (copper, zinc, and aluminum). In this study, we found that the aqueous A. cochinchinensis extract increased the survival rate, decreased epithelial cell death, and attenuated metal ion-induced gut morphological changes in flies following chronic exposure to metal ions. In addition, we screened out, by network pharmacology, six natural products (NPs) that could serve as putative active components of A. cochinchinensis that prevented gut injury. Altogether, the results of our study provide evidence that A. cochinchinensis might be an effective phytomedicine for the treatment of metal ion-induced gut injury.

Epigallocatechin gallate promotes the development of mouse 2-cell embryos in vitro by regulating mitochondrial activity and expression of genes related to p53 signalling pathway.

Preliminary studies have found that the epigallocatechin gallate (EGCG) at proper concentration could promote development of pre-implantation mouse embryos in vitro. However, the underlying mechanisms have not been well understood. In this study, we collected 1-cell embryos from Kunming (KM) mice, cultured them in M16 medium or M16 medium supplemented with 10 µg/mL EGCG and investigated the effects of EGCG on mitochondrial activity and reactive oxygen species (ROS) level of 2-cell embryos. Furthermore, we explored expression differences of genes related to p53 signalling pathway in 2-cell embryos using a PCR array. The results showed that ROS level and mitochondrial membrane potential were significantly lower in embryos cultured in the EGCG group than in the M16 group (p < 0.05), while the adenosine triphosphate content was slightly lower than in the M16 group (p > 0.05). PCR array test results showed that 18 genes were differentially expressed, among which eight genes involving cell growth, cell cycle regulation and mRNA transcription were up-regulated and 10 genes involving apoptosis, cell cycle arrest and DNA repair were down-regulated in the EGCG groups. It is concluded that EGCG could promote the development of 1-cell embryos in vitro possibly due to its ability to scavenge ROS and regulate mitochondrial activity. In addition, EGCG could influence expression of genes related to p53 signalling pathway in 2-cell embryos and promote cell cycle progression.

Omega-3 PUFA supplementation and the response to evoked endotoxemia in healthy volunteers.

SCOPE: Fish oil-derived n-3 PUFA may improve cardiometabolic health through modulation of innate immunity. However, findings in clinical studies are conflicting. We hypothesized that n-3 PUFA supplementation would dose-dependently reduce the systemic inflammatory response to experimental endotoxemia in healthy humans. METHODS AND RESULTS: The Fenofibrate and omega-3 Fatty Acid Modulation of Endotoxemia (FFAME) study was an 8-wk randomized double-blind trial of placebo or n-3 PUFA supplementation (Lovaza 465 mg eicosapentaenoic acid (EPA) + 375 mg docosahexaenoic acid (DHA)) at "low" (1/day, 900 mg) or "high" (4/day, 3600 mg) dose in healthy individuals (N = 60; age 18-45; BMI 18-30; 43% female; 65% European-, 20% African-, 15% Asian-ancestry) before a low-dose endotoxin challenge (LPS 0.6 ng/kg intravenous bolus). The endotoxemia-induced temperature increase was significantly reduced with high-dose (p = 0.03) but not low-dose EPA + DHA compared to placebo. Although there was no statistically significant impact of EPA + DHA on individual inflammatory responses (tumor necrosis factor-α (TNF-α), IL-6, monocyte chemotactic protein (MCP-1), IL-1 receptor agonist (IL-1RA), IL-10, C-reactive protein (CRP), serum amyloid A (SAA)), there was a pattern of lower responses across all biomarkers with high-dose (nine of nine observed), but not low-dose EPA + DHA. CONCLUSION: EPA + DHA at 3600 mg/day, but not 900 mg/day, reduced fever and had a pattern of attenuated LPS induction of plasma inflammatory markers during endotoxemia. Clinically and nutritionally relevant long-chain n-3 PUFA regimens may have specific, dose-dependent, anti-inflammatory actions.

Development of a novel niosomal system for oral delivery of Ginkgo biloba extract.

BACKGROUND: The aim of this study was to develop an optimal niosomal system to deliver Ginkgo biloba extract (GbE) with improved oral bioavailability and to replace the conventional GbE tablets. METHODS: In this study, the film dispersion-homogenization method was used to prepare GbE niosomes. The resulting GbE niosome suspension was freeze-dried or spray-dried to improve the stability of the niosomes. GbE-loaded niosomes were formulated and characterized in terms of their morphology, particle size, zeta potential, entrapment efficiency, and angle of repose, and differential scanning calorimetry analysis was performed. In vitro release and in vivo distribution studies were also carried out. RESULTS: The particle size of the optimal delivery system prepared with Tween 80, Span 80, and cholesterol was about 141 nm. There was a significant difference (P < 0.05) in drug entrapment efficiency between the spray-drying method (about 77.5%) and the freeze-drying method (about 50.1%). The stability study revealed no significant change in drug entrapment efficiency for the GbE niosomes at 4°C and 25°C after 3 months. The in vitro release study suggested that GbE niosomes can prolong the release of flavonoid glycosides in phosphate-buffered solution (pH 6.8) for up to 48 hours. The in vivo distribution study showed that the flavonoid glycoside content in the heart, lung, kidney, brain, and blood of rats treated with the GbE niosome carrier system was greater than in the rats treated with the oral GbE tablet (P < 0.01). No flavonoid glycosides were detected in the brain tissue of rats given the oral GbE tablets, but they were detected in the brain tissue of rats given the GbE niosomes. CONCLUSION: Niosomes are a promising oral system for delivery of GbE to the brain.

Palmitoleate induces hepatic steatosis but suppresses liver inflammatory response in mice.

The interaction between fat deposition and inflammation during obesity contributes to the development of non-alcoholic fatty liver disease (NAFLD). The present study examined the effects of palmitoleate, a monounsaturated fatty acid (16:1n7), on liver metabolic and inflammatory responses, and investigated the mechanisms by which palmitoleate increases hepatocyte fatty acid synthase (FAS) expression. Male wild-type C57BL/6J mice were supplemented with palmitoleate and subjected to the assays to analyze hepatic steatosis and liver inflammatory response. Additionally, mouse primary hepatocytes were treated with palmitoleate and used to analyze fat deposition, the inflammatory response, and sterol regulatory element-binding protein 1c (SREBP1c) activation. Compared with controls, palmitoleate supplementation increased the circulating levels of palmitoleate and improved systemic insulin sensitivity. Locally, hepatic fat deposition and SREBP1c and FAS expression were significantly increased in palmitoleate-supplemented mice. These pro-lipogenic events were accompanied by improvement of liver insulin signaling. In addition, palmitoleate supplementation reduced the numbers of macrophages/Kupffer cells in livers of the treated mice. Consistently, supplementation of palmitoleate decreased the phosphorylation of nuclear factor kappa B (NF-κB, p65) and the expression of proinflammatory cytokines. These results were recapitulated in primary mouse hepatocytes. In terms of regulating FAS expression, treatment of palmitoleate increased the transcription activity of SREBP1c and enhanced the binding of SREBP1c to FAS promoter. Palmitoleate also decreased the phosphorylation of NF-κB p65 and the expression of proinflammatory cytokines in cultured macrophages. Together, these results suggest that palmitoleate acts through dissociating liver inflammatory response from hepatic steatosis to play a unique role in NAFLD.

Synthesis and biological evaluation of oleanolic acid derivatives as inhibitors of protein tyrosine phosphatase 1B.

Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator in the process of insulin signaling and a promising drug target for diabetes and obesity. Derivatives of oleanolic acid were synthesized and evaluated as PTP1B inhibitors. Several derivatives exhibited moderate to good inhibitory activities against PTP1B, with 25f displaying the most promising inhibition (IC(50) = 3.12 µM). Structure-activity relationship analyses of these derivatives demonstrated that the integrity of the A ring and 12-ene moieties was important in the retention of PTP1B enzyme inhibitory activities. In addition, hydrophilic and acidic groups as well as the distance between the oleanene and acid moieties were associated with PTP1B inhibitory activities. Possible binding modes of 25f were explored by molecular docking simulations.

[Preventive effects of emodin on cerebral ischemia injury and expression of the inflammatory factors in rats with cerebral ischemia].

OBJECTIVE: To assess emodin antagonism to cerebral ischemia injury, and to discuss the mechanism of emodin inhibiting the inflammatory cascade reaction from the levels and expressions of cytokines. METHOD: Rats were divided into sham-operated group, model group, Ligustrazine group and emodin groups (low, middle, high dosage). After focal cerebral ischemic model of cerebral middle artery occlusion was duplicated with nylon thread, we took the speciments after ischemia 6 hours, observed the changes of the evaluating score of neural symptoms, brain water ratio and cerebral infarction area, determined the levels of TNF-alpha, IL-beta and TGF-beta in rats brain tissue by radioimmunoassay, detected the expressions of TNF-alpha and VCAM-1 by immunohistochemistry, and measured VCAM-1-mRNA expression by in-situ hybridization. RESULT: Compared with sham-operated group, the evaluating score of neural symptoms, brain water ratio and cerebral infarction area of rats in model group were higher (P < 0.01) , the levels of TNF-alpha and IL-1beta of rats brain tissue in model group increased, while the level of TGF-beta was lower, and the expressions of TNF-alpha and VCAM-1 increased (P < 0.01). The evaluating score of neural symptoms, brain water ratio and cerebral infarction area improved obviously in every emodin group, especially in emodin low dosage group. Levels of TNF-alpha, IL-1beta and the expressions of TNF-alpha and ICAM-1 in emodin low dosage group and Ligustrazine group were lower, while the level of TGF-beta was higher. Compared with Ligustrazine group, the changes aboved are more significant in emodin low dosage group (P < 0.01). CONCLUSION: The increase of inflammatory cascade reaction mediated by various cytokines such as TNF, IL-1beta, ICAM-1 and the decrease of TGF protection are the important mechanism of cerebral ischemia injury. The mechanism of emodin antagonism to cerebral ischemia injury may be implemented by inhibiting inflammatory cascade reaction and increasing the brain protective factors, such as TGF.