Unveiling molecular mechanisms of pigment synthesis in gardenia (Gardenia jasminoides) fruits through integrative transcriptomics and metabolomics analysis.

This study conducted a combined transcriptomics and metabolomics analysis in premature and mature developmental stages of Gardenia jasminoides Ellis fruits to identify the molecular mechanisms of pigment synthesis. The transcriptomics data produced high-quality clean data amounting to 46.98 gigabytes, exhibiting a mapping ratio of 86.36% to 91.43%. Transcriptomics analysis successfully identified about 3,914 differentially expressed genes which are associated with pivotal biological processes, including photosynthesis, chlorophyll, biosynthetic processes, and protein-chromophore linkage pathways. Functional diversity was clarified by the Clusters of Orthologous Groups (COG) classification, which focused mainly on pigment synthesis functions. Pathways analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) revealed critical pathways affecting pigment development. Metabolomics studies were carried out utilizing Ultra Performance Liquid Chromatography and mass spectrometry (UPLC-MS). About 480 metabolites were detected via metabolomics investigation, the majority of that were significantly involved in pigment synthesis. Cluster and pathway analyses revealed the importance of pathways such as plant secondary metabolite biosynthesis, biosynthesis of phenylpropanoids and plant hormone signal transduction in pigment synthesis. Current research advances our comprehension of the underlying mechanisms at the molecular level governing pigment synthesis in gardenia fruits, furnishing valuable insights for subsequent investigations.

Dankasterone A induces prostate cancer cell death by inducing oxidative stress.

Oxidative stress plays a dual role in tumor survival, either promoting tumor development or killing tumor cells under different conditions. Dankasterone A is a secondary metabolite derived from the fungus Talaromyces purpurogenu. It showed good potential in a screen for anti-prostate cancer compounds. In this study, MTT results showed dankasterone A was cytotoxic to prostate cancer cells, with an IC50 of 5.10 µM for PC-3 cells and 3.41 µM for 22Rv1 cells. Further studies, plate cloning assays and real-time cell analysis monitoring showed that dankasterone A significantly inhibited clonal colony formation and cell migration in 22Rv1 and PC-3 cells. In addition, flow cytometry results showed that dankasterone A induced apoptosis in prostate cancer cells while having no impact on cell cycle distribution. At the molecular level, Protein microarray experiments and western blot assays revealed that dankasterone A specifically and dramatically upregulated HO-1 protein expression; and the results of cell fluorescence staining showed that dankasterone A induced overexpression of reactive oxygen species in 22Rv1 and PC-3 cells. Taken together, dankasterone A induced prostate cancer cells to undergo intense oxidative stress, which resulted in the production of large amounts of HO-1 and the release of large amounts of reactive oxygen species, leading to apoptosis of prostate cancer cells, ultimately resulting in the inhibition of both cell proliferation and migration. We also validated the anti-prostate cancer effects of dankasterone A in vivo in a zebrafish xenograft tumor model. In conclusion, dankasterone A has the potential to be developed as an anti-prostate cancer drug.

Detection of Ningnanmycin Using Fluorescence Spectroscopy Combined with BP Neural Network.

BACKGROUND: Ningnanmycin is a new antibiotic pesticide with good bactericidal and antiviral efficacy, which is widely used in the control of fruit and vegetable diseases, and the excessive pesticide residues pose a serious threat to the environment and human health. METHODS: In this study, we used fluorescence spectrometer to scan the three-dimensional spectrum of ningnanmycin samples. We used a BP neural network to complete the regression analysis of content prediction based on the fluorescence spectra. After that, the prediction performance of the BP neural network was compared with the exponential fitting method. RESULTS: The results of the BP neural network modeling based on the obtained samples showed that the mean square error of the prediction results of the test set is less than 10-4, the R-square is greater than 0.99, the average recovery is 99.11%, and the model performance of the BP neural network is better than exponential fitting. CONCLUSION: Studies have shown that fluorescence spectroscopy combined with BP neural network can effectively predict the concentration of ningnanmycin.

Detection of Dihydrocoumarin in Coconut Juice via Photoelectric Detection System Based on Ultraviolet Absorption Spectrometry.

Based on ultraviolet absorption spectroscopy technology combined with stoichiometry, a portable photoelectric detection system with wireless transmission was designed with the advantages of simple operation, low cost, and quick response to realize the non-destructive detection of dihydrocoumarin content in coconut juice. Through the detection of a sample solution, the light intensity through the solution is measured and converted into absorbance. Particle swarm optimization (PSO) is applied to optimize support vector regression (SVR) to establish a corresponding concentration prediction model. At the same time, in order to solve the shortcomings of the conventional portable photoelectric detection equipment in data storage, data transmission, and other aspects, based on the optimal PSO-SVR model, we used Python language to develop a friendly graphical user interface (GUI), integrating data collection, storage, analysis, and prediction modeling in one, greatly simplifying the operation process. The experimental results show that, compared with the traditional methods, the system achieves the purpose of rapid and non-destructive detection and has a small gap compared with the detection results of the ultraviolet spectrophotometer. It provides a good method for the determination of dihydrocoumarin in coconut juice.

Analysis of regulating activities of 5'-epiequisetin on proliferation, apoptosis, and migration of prostate cancer cells in vitro and in vivo.

Advanced prostate cancer has a poor prognosis, and it is urgent to develop new effective drugs. 5'-Epiequisetin is a tetramic acid derivative which was isolated from a marine sponge-derived fungus Fusarium equiseti in our previous study. In this study, 5'-epiequisetin showed cytotoxicity against four prostate cancer cell lines, namely, LNCaP, 22Rv1, DU145, and PC-3 cells, with the lowest IC50 value of 4.43 ± 0.24 µM in PC-3 cells. Further studies showed that it could dramatically regulate the clonal colony formation, apoptosis, and migration of PC-3 cells. In addition, flow cytometry data showed that 5'-epiequisetin could block the cell cycle at the G1 phase. Proteome profiler array and Western blot revealed that 5'-epiequisetin could regulate the expression of proteins responsible for cell proliferation, apoptosis, and migration. 5'-Epiequisetin regulated the expression of PI3K, Akt, phosphorylated Akt, and proteins which control the cell cycle. Meanwhile, 5'-epiequisetin upregulated expression of DR5 and cleave-caspase 3, which play important roles in the process of apoptosis. Moreover, when DR5 was silenced by small interfering RNA, the proportion of apoptotic cells induced by 5'-epiequisetin remarkably declined. In addition, 5'-epiequisetin downregulated the expression of survivin which plays a key role in the process of survival and apoptosis. 5'-Epiequisetin also impacted beta-catenin and cadherins, which were associated with cell migration. In addition, 5'-Epiequisetin significantly inhibited the progression of prostate cancer in mice, accompanied by regulating the protein expression of DR5, caspase 8, survivin, and cadherins in vivo. Taken together, these findings indicated that 5'-epiequisetin showed an anti-prostate cancer effect by inducing apoptosis and inhibiting cell proliferation and migration both in vitro and in vivo, suggesting a promising lead compound for the pharmacotherapy of prostate cancer.

Insights into Aptamer-Drug Delivery Systems against Prostate Cancer.

Prostate cancer is a common cancer in elderly males. Significant progress has been made in the drug therapies for prostate cancer in recent years. However, side effects are still problems that have not been overcome by the currently used anti-prostate cancer drugs. Novel technologies can be applied to reduce or even eliminate the side effects of drugs. An aptamer may be a sequence of nucleic acids or peptides that can specifically recognize proteins or cells. Taking advantage of this feature, scientists have designed aptamer-drug delivery systems for the development of anti-prostate cancer agents. Theoretically, these aptamer-drug delivery systems can specifically recognize prostate cancer cells and then induce cell death without attacking normal cells. We collected the relevant literature in this field and found that at least nine compounds have been prepared as aptamer-drug delivery systems to evaluate their precise anti-prostate cancer effects. However, the currently studied aptamer-drug delivery systems have not yet entered the market due to defects. Here, we analyze the published data, summarize the characteristics of these delivery systems, and propose ways to promote their application, thus promoting the development of the aptamer-drug delivery systems against prostate cancer.

Pollen typhae total flavone suppresses A7r5 cell proliferation promoted by insulin involving the MEK1/2-ERK1/2 cascades.

Pollen typhae, a traditional medicine in China, performs an anti-diabetic function and has anti-atherosclerosis effects involving suppression of vascular smooth muscle cell proliferation. However, the potential mechanisms keep to be revealed. The present study intended to investigate the influences of Pollen typhae extract named Pollen typhae total flavone (PTF) on A7r5 cell proliferation promoted by insulin and to uncover the underlying mechanisms. Proliferation and viability were evaluated by CCK-8 method. Western blotting was adopted to analyze the protein expression. Insulin promoted A7r5 cell proliferation, while PTF suppressed insulin-promoted proliferation in a concentration-dependent fashion. Although PTF did not change c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38MAPK) or MAPK kinase 1/2 (MEK1/2) protein expression and failed to affect the phosphorylation of JNK and p38MAPK, PTF remarkably inhibited extracellular signal-regulated kinase 1 and 2 (ERK1/2) protein expression and reduced ERK1/2 and MEK1/2 phosphorylation in A7r5 cells stimulated by insulin. Insulin-induced proliferation of A7r5 cells was abolished by inhibiting ERK1/2, which was in line with PTF. These findings indicate that PTF suppresses insulin-promoted proliferation of A7r5 cells involving the MEK1/2-ERK1/2 cascades, providing new insight into the potential uses of PTF for treatment of diabetic atherosclerosis.

Palmitic acid impairs INS-1 cells and alters the global gene expression profile.

Chronic elevated free fatty acids (FFAs) impair pancreatic ß cells, but the mechanisms remain elusive. In this study, palmitic acid (PA) impaired viability and glucose-stimulated insulin secretion of INS-1 cells. Microarray analysis showed that PA markedly altered the expression of 277 probe sets of genes with 232 upregulated and 45 downregulated (fold change ≥ 2.0 or ≤ -2.0; P < 0.05). Gene Ontology analysis displayed a series of the biological process of the differentially expressed genes, such as intrinsic apoptotic signaling pathway in response to endoplasmic reticulum (ER) stress and oxidative stress, inflammatory response, positive regulation of macroautophagy, regulation of insulin secretion, cell proliferation and cycle, fatty acid metabolic process, glucose metabolic process and so on. Kyoto Encyclopedia of Genes and Genomes analysis demonstrated molecular pathways with which the differentially expressed genes associated, including NOD-like receptor, NF-κB and PI3K-Akt signaling pathways, apoptosis, adipocytokine signaling pathway, ferroptosis, protein processing in ER, fatty acid biosynthesis and cell cycle. Moreover, PA promoted protein expression of CHOP, cleaved caspase-3, microtubule-associated proteins light chain 3 (LC3)-II, NOD-like receptor pyrin domain containing 3 (NLRP3), cleaved IL-1ß and Lcn2, increased reactive oxygen species, apoptosis and the ratio of LC3-II/I, and reduced p62 protein expression, intracellular glutathione peroxidase and catalase levels, suggesting activation of ER stress, oxidative stress, autophagy and NLRP3 inflammasome. The results indicate the impaired role of PA and the global gene expression profile of INS-1 cells following PA intervention, providing new insights into the mechanisms involving the damage of pancreatic ß cells by FFAs.

Analysis of pesticide residues by a support vector machine combined with fluorescence spectroscopy.

Pesticide residues enter a lake through the water cycle, causing harm to the water environment and human health. It is necessary to select highly sensitive fluorescence spectroscopy to detect pesticides (bifenthrin, prochloraz, and cyromazine), and a support vector machine (SVM) is used to analyze the concentration of pesticides. In addition, this paper adopts K-fold cross validation and a grid search to optimize the SVM algorithm. The performance evaluation index and running time prove the reliability of the results of this experiment. They show that fluorescence spectroscopy combined with SVM is efficient in predicting pesticide residue content.

Effects of insulin on the proliferation and global gene expression profile of A7r5 cells.

Insulin contributes to atherosclerosis, but the potential mechanisms are kept unclear. In this study, insulin promoted proliferation of A7r5 cells. Microarray analysis indicated that insulin significantly changed 812 probe sets of genes, including 405 upregulated and 407 downregulated ones (fold change ≥ 1.5 or ≤ - 1.5; p < 0.05). Gene ontology analysis showed that the differentially expressed genes were involved in a number of processes, including the regulation of cell proliferation/migration/cycle, apoptotic process, oxidative stress, inflammatory response, mitogen-activated protein kinase (MAPK) activity, lipid metabolic process and extracellular matrix organization. Moreover, Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that the genes were involved in biosynthesis of amino acids, fatty acid metabolism, glycolysis/gluconeogenesis, metabolic pathways, regulation of autophagy, cell cycle and apoptosis, as well as the PI3K-Akt, MAPK, mTOR and NF-κB signaling pathways. Additionally, insulin enhanced phosphorylation of MAPK kinase 1/2 and Akt, suggesting activation of the MAPK and PI3K-Akt signaling pathways. Inhibition of ERK1/2 reduced insulin-induced proliferation. This study revealed the proliferative effects of insulin and displayed global gene expression profile of A7r5 cells stimulated by insulin, suggesting new insight into the molecular pathogenesis of insulin promoting atherosclerosis.

Protective role of Pollen Typhae total flavone against the palmitic acid-induced impairment of glucose-stimulated insulin secretion involving GPR40 signaling in INS-1 cells.

Prolonged elevated levels of free fatty acids (FFAs) contribute to the impairment of insulin secretion function of pancreatic ß cells, a hallmark of type 2 diabetes, which is partly attributed to the dysfunction of G-protein-coupled receptor 40 (GPR40) signaling. Pollen Typhae total flavone (PTF), an extract from a Chinese herbal medicine named Pollen Typhae, has been reported to effectively treat type 2 diabetes, but the underlying mechanisms remain to be fully elucidated. In the present study, palmitic acid (PA), a saturated fatty acid, severely impaired glucose-stimulated insulin secretion (GSIS) in a time-dependent manner in INS-1 cells, and PTF treatment prevented the impairment in a dose-dependent manner. Moreover, PTF improved insulin secretion function in rats presenting with type 2 diabetes induced by a high-fat diet and low-dose streptozotocin. Furthermore, PA exposure for 24 h decreased the protein expression of GPR40, phospholipase C (PLC)ß1, PLCß3, and protein kinase C (PKC), and inhibited the activity of PLC and PKC stimulated by GW9508, a GPR40 agonist. In addition, PTF enhanced the protein expression of GPR40 and to a certain extent strengthened the protein expression of PKC, increased cellular levels of triphosphoinositide (IP3) and diacylglycerol (DAG), and promoted GW9508-stimulated activity of PLC and PKC reduced by PA in INS-1 cells, which were blocked by PLC inhibitor U-73122 and PKC inhibitor staurosporine, respectively. Additionally, the improvement in PA-induced impairment of GSIS by PTF in INS-1 cells was restrained by U-73122, staurosporine, and calcium channel inhibitor nifedipine, respectively. The results indicate that PTF exerts a protective role against PA-induced impairment of GSIS involving GPR40 signaling in INS-1 cells.

ANTI-DIABETIC EFFECTS OF ZHUODUQING FORMULA, A CHINESE HERBAL DECOCTION, ON A RAT MODEL OF TYPE 2 DIABETES.

BACKGROUND: Zhuoduqing formula (ZDQ) is a Chinese herbal decoction and used to treat type 2 diabetes in clinical practice, but the potential evidence needs to be provided. MATERIALS AND METHODS: Type 2 diabetic model rats were induced by feeding high fat diet (HFD) and intraperitoneal injection of streptozotocin (STZ). The model rats were given ZDQ for 4 weeks. Insulin sensitivity was evaluated by homeostasis model assessment of basal insulin resistance (HOMA-IR) and intraperitoneal glucose tolerance test (IPGTT). Blood insulin and tumour necrosis factor-α (TNF-α) levels as well as SOCS-3 levels in skeletal muscles were analyzed by ELISA. RESULTS: ZDQ significantly decreased fasting blood glucose, ameliorated HOMA-IR and IPGTT, and reduced triglyceride and total cholesterol in type 2 diabetic rats. Moreover, ZDQ remarkably lowered blood TNF-α levels and inhibited SOCS-3 levels in skeletal muscles. CONCLUSION: The results display that ZDQ performs anti-diabetic functions in type 2 diabetic rats induced by feeding HFD and intraperitoneal injection of STZ. Abbreviations: ZDQ, zhuoduqing formula; ROS, rosiglitazone; HOMA-IR, homeostasis model assessment of basal insulin resistance; IPGTT, intraperitoneal glucose tolerance test; HFD, high fat diet; SOCS-3, suppressor of cytokine signaling-3; TNF-α, tumour necrosis factor-α.

Electroacupuncture relieves labour pain and influences the spinal dynorphin/κ-opioid receptor system in rats.

BACKGROUND: The dynorphin (DYN)/κ-opioid receptor (KOR) system plays a key role in the control of labour pain. Our previous clinical study reported that electroacupuncture (EA) provided intrapartum analgesia, but the underlying mechanisms of action have not been fully elucidated. AIMS: To observe the effect of EA on labour pain and to explore the underlying mechanisms of action in a rat model. METHODS: Copulation-confirmed pregnant rats (n=120) were given castor oil to induce labour. Rats remained untreated (control group, n=20) or received either meperidine (an opioid that is commonly used to treat labour pain, n=20) or EA at SP6, LI4, SP6+LI4 or SP10 (four groups, n=20 each). Labour pain was evaluated by the warm water tail-flick test. Serum DYN values were measured by ELISA. Protein and mRNA expression of prodynorphin (PDYN, the precursor protein of DYN) and KOR were analysed by Western blotting and real-time PCR, respectively. RESULTS: EA treatment at all acupuncture point combinations studied significantly relieved labour pain and increased serum DYN concentrations, to a degree similar to that achieved with meperidine. EA notably enhanced protein expression of KOR and PDYN and mRNA expression in the lumbar spinal cord but not in the cerebral cortex. The size of effect varied by EA group in the order: SP6>LI4>SP6+LI4>SP10 for all parameters measured, indicating differential effects relating to acupuncture point selection/combination. CONCLUSIONS: The present study indicates that EA relieves labour pain, at least in part, by regulation of the spinal DYN/KOR system in a rat model.

Global Gene Expression Profile of the Hippocampus in a Rat Model of Vascular Dementia.

Vascular dementia (VD) has been one of the most serious public health problems worldwide. It is well known that cerebral hypoperfusion is the key pathophysiological basis of VD, but it remains unclear how global genes in hippocampus respond to cerebral ischemia-reperfusion. In this study, we aimed to reveal the global gene expression profile in the hippocampus of VD using a rat model. VD was induced by repeated occlusion of common carotid arteries followed by reperfusion. The rats with VD were characterized by deficit of memory and cognitive function and by the histopathological changes in the hippocampus, such as a reduction in the number and the size of neurons accompanied by an increase in intercellular space. Microarray analysis of global genes displayed up-regulation of 7 probesets with genes with fold change more than 1.5 (P < 0.05) and down-regulation of 13 probesets with genes with fold change less than 0.667 (P < 0.05) in the hippocampus. Gene Ontology (GO) and pathway analysis showed that the up-regulated genes are mainly involved in oxygen binding and transport, autoimmune response and inflammation, and that the down-regulated genes are related to glucose metabolism, autoimmune response and inflammation, and other biological process, related to memory and cognitive function. Thus, the abnormally expressed genes are closely related to oxygen transport, glucose metabolism, and autoimmune response. The current findings display global gene expression profile of the hippocampus in a rat model of VD, providing new insights into the molecular pathogenesis of VD.

Pollen Typhae total flavone improves insulin resistance in high-fat diet and low-dose streptozotocin-induced type 2 diabetic rats.

Pollen Typhae total flavone (PTF), the extract from Pollen Typhae, is reported to enhance glucose uptake in C2C12 myotubes in vitro, but the convincing evidence is lacking in vivo. In this study, PTF ameliorated insulin resistance and dyslipidemia, but failed to significantly increase body weight in type 2 diabetic rats induced by high-fat diet and low-dose streptozotocin.

Suppressors of cytokine signaling (SOCS) and type 2 diabetes.

The suppressors of cytokine signaling (SOCS) proteins are originally identified as negative regulators of cytokine-activated Janus kinase/signal transducers and activators of transcription signaling pathway, but increasing evidence reveals that SOCS proteins play an important role in the development of type 2 diabetes involving regulation of the insulin signaling and pancreatic ß-cell function, and that SOCS are promising to be the targets for the treatment of type 2 diabetes. In this review, we focus on the emerging role for SOCS and the potential drugs targeting SOCS for type 2 diabetes.

Effects of Chinese herbal medicine Yiqi Huaju Qingli Formula in metabolic syndrome patients with microalbuminuria: a randomized placebo-controlled trial.

BACKGROUND: Microalbuminuria (MAU) is a key component of metabolic syndrome (MetS) and is an early sign of diabetic nephropathy as well. Although routine Western medicine treatments are given to MetS patients to control high blood pressure, hyperglycemia and dyslipidemia, some patients still experience progressive renal lesions and it is necessary to modify and improve the treatment strategy for MetS patients. OBJECTIVE: To investigate the efficacy of Yiqi Huaju Qingli Herb Formula, a compound traditional Chinese herbal medicine, in MetS patients with MAU when it is combined with routine Western medicine treatment. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: Sixty patients with MetS were randomized into the Chinese herbal formula group (CHF, Yiqi Huaju Qingli formula treatment in combination with Western medicine) and control group (placebo in combination with Western medicine). All treatments were administered for 12 weeks. MAIN OUTCOME MEASURES: Urinary microalbumin (MA), urinary albumin-to-creatinine ratio (UACR), 24-hour total urine protein (24-hTP), body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2-hPPG), glycosylated hemoglobin (HbA1c), homeostasis model assessment for insulin resistance (HOMA-IR), blood lipid profile and blood pressure were observed. RESULTS: Compared with the control group, CHF treatment significantly decreased BMI (P<0.05), WC (P<0.01) and WHR (P<0.01). Both groups had significant decreases in FPG, 2-hPPG, HbA1c, HOMA-IR, MA, and UACR, with CHF treatment showing better effects on these parameters compared with the control treatment (P<0.05). Both treatments significantly reduced the levels of total cholesterol, low-density lipoprotein cholesterol and triacylglycerol (TAG), and a greater reduction in TAG was observed with CHF treatment (P<0.05). The level of high-density lipoprotein cholesterol did not change in the control group after treatment (P>0.05), whereas it significantly increased with CHF treatment (P<0.01). Compared with before the treatment, significant decreases in systolic blood pressure, diastolic blood pressure and mean arterial blood pressure were observed in both groups (P<0.01). However, there was no significant difference between the two groups (P>0.05). CONCLUSION: Combined treatment of Yiqi Huaju Qingli Formula and Western medicine significantly alleviated MAU, which may correlate with the improvement of insulin sensitivity and glucose and lipid metabolism. TRIAL REGISTRATION IDENTIFIER: This trial was registered in the Chinese Clinical Trial Registry with the identifier ChiCTR-TRC-11001633.

Effects of Chinese herbal medicine Yiqi Huaju Formula on hypertensive patients with metabolic syndrome: a randomized, placebo-controlled trial.

BACKGROUND: Patients with hypertension coupled with metabolic syndrome (MetS) are among the high risk population in cardiovascular and cerebrovascular diseases. To reduce the prevalence of cardiovascular and cerebrovascular diseases, it is essential to appropriately control blood pressure together with other cardiovascular risk factors. OBJECTIVE: The current study was designed to investigate the therapeutic effects on blood pressure, blood pressure variability and other cardiovascular risk factors by giving Yiqi Huaju Formula, a compound traditional Chinese herbal medicine, in addition to routine treatment to hypertensive patients coupled with MetS. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A total of 43 patients with hypertension coupled with MetS were recruited into this study. The enrolled patients were randomly divided into the Chinese herbal formula group (anti-hypertensive drugs plus Yiqi Huaju Formula, CHF) and the control group (anti-hypertensive drugs plus placebo). The CHF group enrolled 22 patients while the control group received 21 cases. Treatments were given for 12 weeks in both groups. MAIN OUTCOME MEASURES: Parameters examined include 24-hour ambulatory blood pressure monitoring, body mass index, waist circumference, waist-to-hip ratio, homeostatic model assessment for insulin resistance (HOMA-IR), fasting glycosylated hemoglobin (HbA1c), fasting plasma glucose, 2-hour postprandial plasma glucose (PPG), fasting plasma insulin, serum lipid, etc. RESULTS: Compared with the control group, the CHF group had significant improvement (P<0.01) in anthropometric parameters, FPG, HOMA-IR, blood pressure amplitude, blood pressure variability and blood pressure load. CONCLUSION: This study showed that integrated traditional Chinese and Western medicine treatment can achieve better results in controlling blood pressure as well as other cardiovascular risk factors. The mechanism of controlling of blood pressure may be associated with the improvement of insulin sensitivity due to the Yiqi Huaju intervention. TRIAL REGISTRATION IDENTIFIER: ChiCTR-TRC-11001633.

GPR40: a therapeutic target for mediating insulin secretion (review).

G-protein-coupled receptor 40 (GPR40), known as free fatty acid receptor 1, is mainly expressed in pancreatic ß-cells and activated by medium- and long-chain fatty acids. Increasing evidence indicates that the activation of GPR40 in cells causes insulin secretion, and GPR40 has become an attractive therapeutic target for type 2 diabetes. Recently, certain novel GPR40 agonists have been identified that regulate glucose-stimulated insulin secretion, leading to the development of new drugs for the treatment of type 2 diabetes. In this review, we focus on progress in the physiological role of GPR40 and potential drugs targeting GPR40 over the past decade.

Hexavalent chromium induces energy metabolism disturbance and p53-dependent cell cycle arrest via reactive oxygen species in L-02 hepatocytes.

Hexavalent chromium [Cr(VI)] has become a non-negligible pollutant in the world. Cr(VI) exposure leads to severe damage to the liver, but the mechanisms involved in Cr(VI)-mediated toxicity in the liver are unclear. The present study aimed to explore whether Cr(VI) induces energy metabolism disturbance and cell cycle arrest in human L-02 hepatocytes. We showed that Cr(VI) inhibited state 3 respiration, respiratory control rate (RCR), and subsequently induced energy metabolism disturbance with decreased ATP production. Interestingly, cell cycle analysis by flow cytometry and protein expression analysis by western blotting revealed that low dose of Cr(VI) (4 uM) exposure induced S phase cell cycle arrest with decreased mediator of replication checkpoint 1 (Mrc1) and cyclin-dependent kinase 2 (CDK2), while higher doses of Cr(VI) (16, 32 uM) exposure resulted in G2/M phase arrest with decreased budding uninhibited by benzimidazoles-related 1 (BubR1) and cell division cycle 25 (CDC25). Mechanism study revealed that Cr(VI) decreased the activities of mitochondrial respiratory chain complex (MRCC) I and II, thus leading to ROS accumulation. Moreover, inhibiting ROS production by antioxidant N-acetyl-L-cysteine (NAC) rescued Cr(VI)-induced ATP depletion and cell cycle arrest. ROS-mediated p53 activation was found to involve in Cr(VI)-induced cell cycle arrest, and p53 inhibitor Pifithrin-α (PFT-α) rescued Cr(VI)-induced reduction of check point proteins Mrc1 and BubR1, thus inhibiting cell cycle arrest. In summary, the present study provides experimental evidence that Cr(VI) leads to energy metabolism disturbance and p53-dependent cell cycle arrest via ROS in L-02 hepatocytes.