Cinnamaldehyde attenuates streptozocin-induced diabetic osteoporosis in a rat model by modulating netrin-1/DCC-UNC5B signal transduction.

Background: Cinnamaldehyde (CMD) is a major functional component of Cinnamomum verum and has shown treatment effects against diverse bone diseases. This study aimed to assess the anti-diabetic osteoporosis (DOP) potential of diabetes mellitus (DM) and to explore the underlying mechanism driving the activity of CMD. Methods: A DOP model was induced via an intraperitoneal injection of streptozocin (STZ) into Sprague-Dawley rats, and then two different doses of CMD were administered to the rats. The effects of CMD on the strength, remodeling activity, and histological structure of the bones were assessed. Changes in the netrin-1 related pathways also were detected to elucidate the mechanism of the anti-DOP activity by CMD. Results: CMD had no significant effect on the body weight or blood glucose level of the model rats. However, the data showed that CMD improved the bone strength and bone remodeling activity as well as attenuating the bone structure destruction in the DOP rats in a dose-dependent manner. The expression of netrin-1, DCC, UNC5B, RANKL, and OPG was suppressed, while the expression of TGF-ß1, cathepsin K, TRAP, and RANK was induced by the STZ injection. CMD administration restored the expression of all of these indicators at both the mRNA and protein levels, indicating that the osteoclast activity was inhibited by CMD. Conclusion: The current study demonstrated that CMD effectively attenuated bone impairments associated with DM in a STZ-induced DOP rat model, and the anti-DOP effects of CMD were associated with the modulation of netrin-1/DCC/UNC5B signal transduction.

Optimal bidding strategy of a wind power producer in Chinese spot market considering green certificate trading.

In China, wind power producers will participate in the spot market as strategic producers. They should submit offering prices and forecasted production to the independent system operator. Intraprovincial and interprovincial green certificate trading, as a mechanism to promote the development of wind power, is advanced in parallel with the spot market. Studying the bidding strategies of wind power producers in the spot market, especially with the introduction of intraprovincial and interprovincial green certificate trading, has great practical significance for the stable operation of wind power producers and the construction of a renewable energy-friendly electricity market. This paper proposes a bi-level stochastic model to simulate the bidding strategy of a wind power producer in the spot market. The upper level problem of the model describes the decision-making process of the wind power producer, and the lower level problems include the clearing process of the spot market and the TGC market, in which the spot market includes the day-ahead market and the balance market, and the TGC market includes the intraprovincial and interprovincial TGC markets. Then, using Karush-Kuhn-Tucker (KKT) conditions, the strong duality theorem, and the big M method, the bi-level model is recast into a mixed integer linear (MIL) model convenient to be solved. Finally, an example is given to analyze the wind power producer's optimal bidding strategy under different electricity market environments and different wind power penetration levels.

Efficacy and Safety of Mulberry Twig Alkaloids Tablet for Treatment of Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Multicenter Clinical Study.

OBJECTIVE: To assess the efficacy and safety of mulberry twig alkaloids (Sangzhi alkaloids, SZ-A) for treatment of type 2 diabetes in a randomized, double-blind, placebo-controlled multicenter clinical trial. METHODS: A total of 200 patients were randomized to receive SZ-A (n=100) or placebo (n=100) for 16 weeks. The data analysis system for electronic data capture clinical trial central randomization system was used for randomization and dispensing of drugs. The primary outcome was the change in glycosylated hemoglobin (HbA1c) level. The secondary outcome included the proportions of cases with HbA1c <7.0% and HbA1c <6.5%, fasting blood glucose (FBG), postprandial blood glucose (PBG), area under curve for the PBG (AUC0-2h), body weight, and body mass index (BMI). Adverse events (AEs), severe adverse events (SAEs), treatment-related adverse events (TAEs), gastrointestinal disorders (GDs), blood pressure, routine blood tests, and liver and kidney function were monitored. RESULTS: Compared with baseline, the change of HbA1c at week 16 was -0.80% (95% CI: -0.98% to -0.62%) and -0.09% (95% CI: -0.27% to 0.09%) in SZ-A group and placebo group, respectively. The proportion of patients with HbA1c <7% and <6.5% was higher in the SZ-A group than in the placebo group (46.8% vs. 21.6% and 29.9% vs. 10.8%). The observed values and changes in FBG, 1 h-PBG, 2 h-PBG, and AUC0-2h differed significantly between groups (P<0.001), but differences were not significant in body weight and BMI (P>0.05). The incidence rates of AEs, TAEs, and GDs differed significantly between groups (P=0.010, P=0.005, and P=0.006, respectively), whereas the incidence rates of SAEs showed no significant differences between groups (P=1.000). CONCLUSION: SZ-A are effective and safe for treatment of type 2 diabetes. The protocol was registered in http://www.chictr.org.cn/showproj.aspx?proj=60117 (ChiCTR2000038550).

Jinmaitong Alleviates Diabetic Neuropathic Pain Through Modulation of NLRP3 Inflammasome and Gasdermin D in Dorsal Root Ganglia of Diabetic Rats.

Jinmaitong (JMT) is a compound prescription of traditional Chinese medicine that has been used to treat diabetic neuropathic pain (DNP) for many years. Here, we investigated the effects of JMT on the activation of NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and pyroptosis in Dorsal root ganglia (DRG) of diabetic rats. Streptozotocin (STZ)-induced diabetic rats were gavaged with JMT (0.88 g/kg/d) or alpha-lipoic acid (ALA, positive control, 0.48 mmol/kg/d) for 12 weeks. Distilled water was administered as a vehicle control to both diabetic and non-affected control rats. Blood glucose levels and body weights were measured. Behavioral changes were tested with mechanical withdrawal threshold (MWT) and tail-flick latency (TFL) tests. Morphological injury associated with DRG was observed with hematoxylin and eosin (H&E) and Nissl's staining. mRNA and protein levels of NLRP3 inflammasome components (NLRP3, ASC, caspase-1), downstream IL-1ß and gasdermin D (GSDMD) were evaluated by immunohistochemistry, quantitative real time-PCR and western blot. The results showed that JMT had no effect on blood glucose levels and body weights, but significantly improved MWT and TFL behavior in diabetic rats, and attenuated morphological damage in the DRG tissues. Importantly, JMT decreased the mRNA and protein levels of components of NLRP3 inflammasome, including NLRP3, ASC and caspase-1. JMT also down-regulated the expression of IL-1ß and GSDMD in the DRG of DNP rats. In addition, ALA treatment did not perform better than JMT. In conclusion, JMT effectively relieved DNP by decreasing NLRP3 inflammasome activation and pyroptosis, providing new evidence supporting JMT as an alternative treatment for DNP.

Efficacy and Safety of Mulberry Twig Alkaloids Tablet for the Treatment of Type 2 Diabetes: A Multicenter, Randomized, Double-Blind, Double-Dummy, and Parallel Controlled Clinical Trial.

OBJECTIVE: This study aimed to evaluate the efficacy and safety of mulberry twig alkaloids (Sangzhi alkaloids [SZ-A]) in the treatment of type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: This was a multicenter, randomized, double-blind, double-dummy, and parallel controlled noninferiority clinical trial that was conducted for 24 weeks. A total of 600 patients were randomly allocated to the SZ-A group (n = 360) or acarbose group (n = 240). The primary efficacy end point was the change of glycosylated hemoglobin (HbA1c) compared with baseline. In addition, adverse events (AEs), severe AEs (SAEs), treatment-related AEs (TAEs), and gastrointestinal disorders (GDs) were monitored. RESULTS: After treatment for 24 weeks, the change in HbA1c was -0.93% (95% CI -1.03 to -0.83) (-10.2 mmol/mol [-11.3 to -9.1]) and -0.87% (-0.99 to -0.76) (-9.5 mmol/mol [-10.8 to -8.3]) in the SZ-A and acarbose groups, respectively, and the least squares mean difference was -0.05% (95% CI -0.18 to 0.07) (-0.5 mmol/mol [-2.0 to 0.8]) between the two groups, with no significant difference on the basis of covariance analysis (P > 0.05). The incidence of TAEs and GDs was significantly lower in the SZ-A group than the acarbose group (P < 0.01), but no differences for AEs or SAEs between the two groups were observed (P > 0.05). CONCLUSIONS: SZ-A exhibited equivalent hypoglycemic effects to acarbose in patients with T2D. Nevertheless, the incidence of TAEs and GDs was lower following SZ-A treatment than acarbose treatment, suggesting good safety.

Discerning drivers and future reduction paths of energy-related CO2 emissions in China: combining EKC with three-layer LMDI.

Recognizing the process and identifying the drivers of energy-related CO2 emissions can provide suggestions for designing carbon emission reduction paths, and then promote the further reduction of carbon emission. In this paper, the carbon emissions in China and its subordinate provinces during 2005-2017 are firstly divided into four stages, named S1, S2, S3, and S4. The results show that China has just entered the S3, and it is impossible to reach the peak of energy-related CO2 emissions with steady economic growth before 2030. Then, three-layer LMDI is utilized to explore the drivers of CO2 emissions, and the impact of urbanization which is separated from the population is considered innovatively. The economic development increases CO2 emissions, while the other drivers have diverse effects, which may be positive or negative, on carbon emissions in different regions. Therefore, four emission reduction paths with provincial characteristics should be followed in the future: (i) three provinces, namely, Ningxia, Shaanxi, and Xinjiang, should optimize multiple basic objectives in parallel; (ii) four provinces, such as Inner Mongolia and Hainan, should optimize the energy structure; (iii) six provinces, such as Jiangxi and Hunan, should optimize the industry structure; and (iv) the other provinces should develop new clean energy according to regional conditions.

How quota allocation affects the unified ETS of China: a simulation with dynamic CGE model.

The national unified carbon trading market has been officially launched at the end of 2017. The carbon emission quotas should be primary concern, which can be allocated in the form of free and paid ways. However, few literatures studied the economic and environmental impacts of quotas allocation. Thus, this paper constructs 7 scenarios and employs a dynamic, recursive computable general equilibrium (CGE) model to simulate carbon trading market, to probe the relationship between quota allocation and carbon price, and the economic and environmental impact of carbon trading scheme (ETS). Empirical results indicate (1) carbon price has an upward trend with time, which reflects a corresponding increase in emission reduction pressure. Specifically, carbon price increases from 12.44-90.57 CNY/t in 2017 to 65.20-523.44 CNY/t in 2030. In addition, whether under carbon intensity criterion (CIC) or carbon emission criterion (CEC), there is a positive relationship between carbon price and free allocation ratio due to the change of the relationship between supply and demand of quota. With a given free allocation ratio, the price formed with CIC grows faster than that with CEC. (2) Compared with the benchmark scenario, the GDP of China decreases in all scenarios. However, a high level of free allocation ratio combined with CIC may prevent GDP dropping too fast. (3) As for industrial output, covered industries in ETS undertake the largest output losses with an average decline by 4.03-13.60%. Similar to GDP variation, a high free allocation ratio combined with CIC is helpful for sustainable development of industry. (4) Carbon trading has a remarkable effect on emission reductions both in covered and uncovered industries of ETS. Free allocation will reduce market efficiency, which implies it should be cut down gradually at the later stages.

A novel optimal-hybrid model for daily air quality index prediction considering air pollutant factors.

Accurate and reliable air quality index (AQI) forecasting is extremely crucial for ecological environment and public health. A novel optimal-hybrid model, which fuses the advantage of secondary decomposition (SD), AI method and optimization algorithm, is developed for AQI forecasting in this paper. In the proposed SD method, wavelet decomposition (WD) is chosen as the primary decomposition technique to generate a high frequency detail sequence WD(D) and a low frequency approximation sequence WD(A). Variational mode decomposition (VMD) improved by sample entropy (SE) is adopted to smooth the WD(D), then long short-term memory (LSTM) neural network with good ability of learning and time series memory is applied to make it easy to be predicted. Least squares support vector machine (LSSVM) with the parameters optimized by the Bat algorithm (BA) considers air pollutant factors including PM2.5, PM10, SO2, CO, NO2 and O3, which is suitable for forecasting WD(A) that retains original information of AQI series. The ultimate forecast result of AQI can be obtained by accumulating the prediction values of each subseries. Notably, the proposed idea not only gives full play to the advantages of conventional SD, but solve the problem that the traditional time series prediction model based on decomposition technology can not consider the influential factors. Additionally, two daily AQI series from December 1, 2016 to December 31, 2018 respectively collected from Beijing and Guilin located in China are utilized as the case studies to verify the proposed model. Comprehensive comparisons with a set of evaluation indices indicate that the proposed optimal-hybrid model comprehensively captures the characteristics of the original AQI series and has high correct rate of forecasting AQI classes.

Humanistic Spirit Contained in Traditional Chinese Medicine should Be Valued.

Medicine is a science studying human's health and diseases as well as the regularity between them. Its research subject is human, who possess natural attribute, psychological attribute and social attribute. Therefore, medicine is bound to possess humanistic attribute. Rooted in Chinese traditional culture, Traditional Chinese Medicine contains abundant humanistic thoughts, for instance, pursuing the unity of human and nature, advocating the vital importance of life, sticking to the virtue of "medicine being humane art", abiding by the principle of "Benevolence prior to interest", complying with the medical rule of "Respecting peers". These are the very concrete reflections of medical humanistic spirit. In this article we aim to explore the humanistic thoughts contained in Traditional Chinese Medicine, and try to inherit and carry forward the spirit to better relieve the tensions between doctors and patients and improve the quality of medical services.

Lentinan inhibits tumor angiogenesis via interferon γ and in a T cell independent manner.

BACKGROUND: Antiangiogenic agents are commonly used in lung and colon cancer treatments, however, rapid development of drug resistance limits their efficacy. METHODS: Lentinan (LNT) is a biologically active compound extracted from Lentinus edodes. The effects of LNT on tumor angiogenesis were evaluated by immunohistochemistry in murine LAP0297 lung and CT26 colorectal tumor models. The impacts of LNT on immune cells and gene expression in tumor tissues were determined by flow cytometry, qPCR, and ELISA. Nude mice and IFNγ blockade were used to investigate the mechanism of LNT affecting on tumor angiogenesis. The data sets were compared using two-tailed student's t tests or ANOVA. RESULTS: We found that LNT inhibited tumor angiogenesis and the growth of lung and colon cancers. LNT treatments elevated the expression of angiostatic factors such as IFNγ and also increased tumor infiltration of IFNγ-expressing T cells and myeloid cells. Interestingly, IFNγ blockade, but not T cell deficiency, reversed the effects of LNT treatments on tumor blood vessels. Moreover, long-lasting LNT administration persistently suppressed tumor angiogenesis and inhibited tumor growth. CONCLUSIONS: LNT inhibits tumor angiogenesis by increasing IFNγ production and in a T cell-independent manner. Our findings suggest that LNT could be developed as a new antiangiogenic agent for long-term treatment of lung and colon cancers.

Combination of quercetin, cinnamaldehyde and hirudin protects rat dorsal root ganglion neurons against high glucose-induced injury through Nrf-2/HO-1 activation and NF-κB inhibition.

OBJECTIVE: To examine the effects of the combination of quercetin (Q), cinnamaldehyde (C) and hirudin (H), a Chinese medicine formula on high glucose (HG)-induced apoptosis of cultured dorsal root ganglion (DRG) neurons. METHODS: DRG neurons exposed to HG (45 mmol/L) for 24 h were employed as an in vitro model of diabetic neuropathy. Cell viability, reactive oxygen species (ROS) level and apoptosis were determined. The expression of nuclear factor of Kappa B (NF-κB), inhibitory kappa Bα(IκBα), phosphorylated IκBα and Nf-E2 related factor 2 (Nrf2) were examined using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot assay. The expression of hemeoxygenase-1 (HO-1), interleukin-6 (IL-6), tumor necrosis factor (TNF-α) and caspase-3 were also examined by RT-PCR and Western blot assay. RESULTS: HG treatment markedly increased DRG neuron apoptosis via increasing intracellular ROS level and activating the NF-κB signaling pathway (P<0.05). Co-treatment with Q, C, H and their combination decreased HG-induced caspase-3 activation and apoptosis (P<0.05 or P<0.01). The expressions of NF-κB, IL-6 and TNF-α were down-regulated, and Nrf2/HO-1 expression was up-regulated (P<0.05 or P<0.01). QCH has better effect in scavenging ROS, activating Nrf-2/HO-1, and down-regulating the NF-κB pathway than other treatment group. CONCLUSIONS: DRG neurons' apoptosis was increased in diabetic conditions, which was reduced by QCH formula treatment. The possible reason could be activating Nrf-2/HO-1 pathway, scavenging ROS, and inhibition of NF-κB activation. The effect of QCH combination was better than each monomer or the combination of the two monomers.

Jinmaitong alleviates the diabetic peripheral neuropathy by inducing autophagy.

OBJECTIVE: To observe the deregulation of autophagy in diabetic peripheral neuropathy (DPN) and investigate whether Jinmaitong ( JMT) alleviates DPN by inducing autophagy. METHODS: DPN models were established by streptozotocin-induced diabetic rats and Schwann cells (SCs) cultured in high glucose medium. The pathological morphology was observed by the improved Bielschowsky's nerve fiber axonal staining and the Luxol fast blue-neutral red myelin staining. The ultrastructure was observed by the transmission electron microscopy. Beclin1 level was detected by immunohistochemistry and Western blot. The proliferation of cultured SCs was detected by methylthiazolyldiphenyl-tetrazolium bromide. RESULTS: Diabetic peripheral nerve tissues demonstrated pathological morphology and reduced autophagic structure, accompanied with down-regulation of Beclin1. JMT apparently alleviated the pathological morphology change and increased the autophagy [in vivo, Beclin1 integral optical density (IOD) value of the control group 86.6±17.7, DM 43.9±8.8, JMT 73.3 ±17.8, P<0.01 or P<0.05, in vitro Beclin1 IOD value of the glucose group 0.47±0.25 vs the control group 0.88±0.29, P<0.05]. Consequently, inhibition of autophagy by 3-methyladenine resulted in a time- and concentration-dependent decrease of the proliferation of SCs (P<0.05, P<0.01). CONCLUSIONS: Down-regulation of autophagy in SCs might contribute to the pathogenesis of DPN. JMT alleviates diabetic peripheral nerve injury at least in part by inducing autophagy.

Acyl ghrelin acts in the brain to control liver function and peripheral glucose homeostasis in male mice.

Recent evidence suggests that peripheral ghrelin regulates glucose metabolism. Here, we designed experiments to examine how central acyl ghrelin infusion affects peripheral glucose metabolism under pair-fed or ad libitum feeding conditions. Mice received intracerebroventricular (icv) infusion of artificial cerebrospinal fluid (aCSF), ghrelin, and allowed to eat ad libitum (icv ghrelin ad lib) or ghrelin and pair-fed to the aCSF group (icv ghrelin pf). Minipumps delivered acyl ghrelin at a dose of 0.25 µg/h at 0.5 µL/h for 7 days. There was no difference in daily blood glucose, insulin, glucagon, triglycerides, or nonesterified fatty acids. Body weight gain and food intake was significantly higher in icv ghrelin ad lib mice. However, both icv ghrelin ad lib and icv ghrelin pf groups exhibited heavier white adipose mass. Icv ghrelin pf mice exhibited better glucose tolerance than aCSF or icv ghrelin ad lib mice during a glucose tolerance test, although both icv ghrelin ad lib and icv ghrelin pf increased insulin release during the glucose tolerance test. Central acyl ghrelin infusion and pair feeding also increased breakdown of liver glycogen and triglyceride, and regulated genes involved in hepatic lipid and glucose metabolism. Icv ghrelin pf mice had an increase in plasma blood glucose during a pyruvate tolerance test relative to icv ghrelin ad lib or aCSF mice. Our results suggest that under conditions of negative energy (icv ghrelin pf), central acyl ghrelin engages a neural circuit that influences hepatic glucose function. Metabolic status affects the ability of central acyl ghrelin to regulate peripheral glucose homeostasis.

Evidence that diet-induced hyperleptinemia, but not hypothalamic gliosis, causes ghrelin resistance in NPY/AgRP neurons of male mice.

High-fat diet (HFD) feeding causes ghrelin resistance in arcuate neuropeptide Y (NPY)/Agouti-related peptide neurons. In the current study, we investigated the time course over which this occurs and the mechanisms responsible for ghrelin resistance. After 3 weeks of HFD feeding, neither peripheral nor central ghrelin increased food intake and or activated NPY neurons as demonstrated by a lack of Fos immunoreactivity or whole-cell patch-clamp electrophysiology. Pair-feeding studies that matched HFD calorie intake with chow calorie intake show that HFD exposure does not cause ghrelin resistance independent of body weight gain. We observed increased plasma leptin in mice fed a HFD for 3 weeks and show that leptin-deficient obese ob/ob mice are still ghrelin sensitive but become ghrelin resistant when central leptin is coadministered. Moreover, ob/ob mice fed a HFD for 3 weeks remain ghrelin sensitive, and the ability of ghrelin to induce action potential firing in NPY neurons was blocked by leptin. We also examined hypothalamic gliosis in mice fed a chow diet or HFD, as well as in ob/ob mice fed a chow diet or HFD and lean controls. HFD-fed mice exhibited increased glial fibrillary acidic protein-positive cells compared with chow-fed mice, suggesting that hypothalamic gliosis may underlie ghrelin resistance. However, we also observed an increase in hypothalamic gliosis in ob/ob mice fed a HFD compared with chow-fed ob/ob and lean control mice. Because ob/ob mice fed a HFD remain ghrelin sensitive, our results suggest that hypothalamic gliosis does not underlie ghrelin resistance. Further, pair-feeding a HFD to match the calorie intake of chow-fed controls did not increase body weight gain or cause central ghrelin resistance; thus, our evidence suggests that diet-induced hyperleptinemia, rather than diet-induced hypothalamic gliosis or HFD exposure, causes ghrelin resistance.

The temporal pattern of cfos activation in hypothalamic, cortical, and brainstem nuclei in response to fasting and refeeding in male mice.

In this study we examined fasted and refed cfos activation in cortical, brainstem, and hypothalamic brain regions associated with appetite regulation. We examined a number of time points during refeeding to gain insight into the temporal pattern of neuronal activation and changes in endocrine parameters associated with fasting and refeeding. In response to refeeding, blood glucose and plasma insulin returned to basal levels within 30 minutes, whereas plasma nonesterified fatty acids and leptin returned to basal levels after 1 and 2 hours, respectively. Within the hypothalamic arcuate nucleus (ARC), fasting increased cfos activation in ∼25% of neuropeptide Y neurons, which was terminated 1 hour after refeeding. Fasting had no effect on cfos activation in pro-opiomelanocortin neurons; however, 1 and 2 hours of refeeding significantly activated ∼20% of ARC pro-opiomelanocortin neurons. Acute refeeding (30, 60, and 120 minutes), but not fasting, increased cfos activation in the nucleus accumbens, the cingulate cortex (but not the insular cortex), the medial and lateral parabrachial nucleus, the nucleus of the solitary tract, the area postrema, the dorsal raphe, and the ventromedial nucleus of the hypothalamus. After 6 hours of refeeding, cfos activity was reduced in the majority of these regions compared with that at earlier time points. Our data indicate that acute refeeding, rather than long-term fasting, activates cortical, brainstem, and hypothalamic neural circuits associated with appetite regulation and reward processing. Although the hypothalamic ARC remains a critical sensory node detecting changes in the metabolic state and feedback during fasting and acute refeeding, our results also reveal the temporal pattern in cfos activation in cortical and brainstem areas implicated in the control of appetite and body weight regulation.

Quercetin protects rat dorsal root ganglion neurons against high glucose-induced injury in vitro through Nrf-2/HO-1 activation and NF-κB inhibition.

AIM: To examine the effects of quercetin, a natural antioxidant, on high glucose (HG)-induced apoptosis of cultured dorsal root ganglion (DRG) neurons of rats. METHODS: DRG neurons exposed to HG (45 mmol/L) for 24 h were employed as an in vitro model of diabetic neuropathy. Cell viability, reactive oxygen species (ROS) level and apoptosis were determined. The expression of NF-кB, IкBα, phosphorylated IкBα and Nrf2 was examined using RT PCR and Western blot assay. The expression of hemeoxygenase-1 (HO-1), IL-6, TNF-α, iNOS, COX-2, and caspase-3 were also examined. RESULTS: HG treatment markedly increased DRG neuron apoptosis via increasing intracellular ROS level and activating the NF-κB signaling pathway. Co-treatment with quercetin (2.5, 5, and 10 mmol/L) dose-dependently decreased HG-induced caspase-3 activation and apoptosis. Quercetin could directly scavenge ROS and significantly increased the expression of Nrf-2 and HO-1 in DRG neurons. Quercetin also dose-dependently inhibited the NF-κB signaling pathway and suppressed the expression of iNOS, COX-2, and proinflammatory cytokines IL-6 and TNF-α. CONCLUSION: Quercetin protects rat DRG neurons against HG-induced injury in vitro through Nrf-2/HO-1 activation and NF-κB inhibition, thus may be beneficial for the treatment of diabetic neuropathy.

Effects of Jinmaitong Capsule () on ciliary neurotrophic factor in sciatic nerves of diabetes mellitus rats.

OBJECTIVE: To study the effects of the Chinese medicine Jinmaitong Capsule (, JMT) on the pathomorphology of sciatic nerves, ciliary neurotrophic factor (CNTF), and the mRNA expressions of CNTF in rats with streptozotocin-induced diabetes mellitus (STZ-DM). METHODS: The animal model was established by one time intraperitoneal injection of streptozotocin. The rats were simply divided by random into 5 groups including model group, low-dose JMT group (JL), medium-dose JMT group (JM), high-dose JMT group (JH) and neurotropin group. For each of the above 5 groups, a group of 10 normal Wistar rats matched in body weight, age and gender were set as normal group. Intragastric administrations were started after the animal model established. The JL group were administered with five times the JMT dose recommended for a human adult; the JM group were administered with ten times the JMT dose recommended for a human adult; the JH group were administered with twenty times the JMT dose recommended for a human adult. The neurotropin group was administered with ten times the neurotropin dose recommended for a human adult. All rats were given intragastric administration for 16 weeks and then killed. In the 4th, 8th, 12th, 16th week, body weight and blood glucose level were detected before and after the intervention. The morphologic changes of the sciatic nerves were observed by optical microscope and transmission electron microscope. The CNTFmRNA expressions were detected by real-time fluorescent quantitative polymerase chain protein, and the CNTF protein expressions were detected by immunohistochemical method. RESULTS: The blood glucose levels of the STZ-DM rats were much higher than normal group (P<0.01), and there was no apparent difference between any treatment groups and the model group (P>0.05). Before and after the intervention in the 4th, 8th, 12th, 16th week, there were no significant differences in the body weight among all the groups (P>0.05). The sciatic nerves of STZ-DM rats might have pathomorphological changes in axons, myelin sheaths, and interstitium. The levels of CNTF and CNTF-mRNA expressions in the STZ-DM rats were both significantly decreased (P<0.01). The sciatic nerves of STZ-DM rats might have pathomorphological changes in axons, myelin sheaths, and interstitium. CONCLUSION: JMT could improve the pathomorphology of sciatic nerves by increasing CNTF's and CNTF-mRNA expressions in sciatic nerve tissues, and promote the repair and regeneration of damaged nerve fibers.

Calorie-restricted weight loss reverses high-fat diet-induced ghrelin resistance, which contributes to rebound weight gain in a ghrelin-dependent manner.

Twelve weeks of high-fat diet feeding causes ghrelin resistance in arcuate neuropeptide Y (NPY)/agouti-related protein (AgRP) neurons. In the current study, we investigated whether diet-induced weight loss could restore NPY/AgRP neuronal responsiveness to ghrelin and whether ghrelin mediates rebound weight gain after calorie-restricted (CR) weight loss. Diet-induced obese (DIO) mice were allocated to one of two dietary interventions until they reached the weight of age-matched lean controls. DIO mice received chow diet ad libitum or chow diet with 40% CR. Chow-fed and high-fat-fed mice served as controls. Both dietary interventions normalized body weight, glucose tolerance, and plasma insulin. We show that diet-induced weight loss with CR increases total plasma ghrelin, restores ghrelin sensitivity, and increases hypothalamic NPY and AgRP mRNA expression. We propose that long-term DIO creates a higher body weight set-point and that weight loss induced by CR, as seen in the high-fat CR group, provokes the brain to protect the new higher set-point. This adaptation to weight loss likely contributes to rebound weight gain by increasing peripheral ghrelin concentrations and restoring the function of ghrelin-responsive neuronal populations in the hypothalamic arcuate nucleus. Indeed, we also show that DIO ghrelin-knockout mice exhibit reduced body weight regain after CR weight loss compared with ghrelin wild-type mice, suggesting ghrelin mediates rebound weight gain after CR weight loss.