Antialcohol and Hepatoprotective Effects of Tamarind Shell Extract on Ethanol-Induced Damage to HepG2 Cells and Animal Models.

Alcohol liver disease (ALD) is one of the leading outcomes of acute and chronic liver injury. Accumulative evidence has confirmed that oxidative stress is involved in the development of ALD. In this study, we used chick embryos to establish ALD model to study the hepatoprotective effects of tamarind shell exttract (TSE). Chick embryos received 25% ethanol (75 µL) and TSE (250, 500, 750 µg/egg/75 µL) from embryonic development day (EDD) 5.5. Both ethanol and TSE were administrated every two days until EDD15. Ethanol-exposed zebrafish and HepG2 cell model were also employed. The results suggested that TSE effectively reversed the pathological changes, liver dysfunction and ethanol-metabolic enzyme disorder in ethanol-treated chick embryo liver, zebrafish and HepG2 cells. TSE suppressed the excessive reactive oxygen species (ROS) in zebrafish and HepG2 cells, as well as rebuilt the irrupted mitochondrial membrane potential. Meanwhile, the declined antioxidative activity of glutathione peroxidase (GPx) and superoxide dismutase (SOD), together with the content of total glutathione (T-GSH) were recovered by TSE. Moreover, TSE upregulated nuclear factor erythroid 2-related factor 2 (NRF2) and heme oxyense-1 (HO-1) expression in protein and mRNA level. All the phenomena suggested that TSE attenuated ALD through activating NRF2 to repress the oxidative stress induced by ethanol.

Insufficiency of Mrpl40 disrupts testicular structure and semen parameters in a murine model.

Approximately 31% of patients with 22q11.2 deletion syndrome (22q11.2DS) have genitourinary system disorders and 6% of them have undescended testes. Haploinsufficiency of genes on chromosome 22q11.2 might contribute to the risk of 22q11.2DS. In this study, we used mice with single-allele deletion in mitochondrial ribosomal protein L40 (Mrpl40 +/- ) as models to investigate the function of Mrpl40 in testes and spermatozoa development. The penetrance of cryptorchidism in Mrpl40 +/- mice was found to be higher than that in wild-type (WT) counterparts. Although the weight of testes was not significantly different between the WT and Mrpl40 +/- mice, the structure of seminiferous tubules and mitochondrial morphology was altered in the Mrpl40 +/- mice. Moreover, the concentration and motility of spermatozoa were significantly decreased in the Mrpl40 +/- mice. In addition, data-independent acquisition mass spectrometry indicated that the expression of genes associated with male infertility was altered in Mrpl40 +/- testes. Our study demonstrated the important role of Mrpl40 in testicular structure and spermatozoa motility and count. These findings suggest that Mrpl40 is potentially a novel therapeutic target for cryptorchidism and decreased motility and count of spermatozoa.

Tripeptide Leu-Pro-Phe from Corn Protein Hydrolysates Attenuates Hyperglycemia-Induced Neural Tube Defect in Chicken Embryos.

Neural tube defect (NTD) is the most common and severe embryopathy causing embryonic malformation and even death associated with gestational diabetes mellitus (GDM). Leu-Pro-Phe (LPF) is an antioxidative tripeptide isolated from hydrolysates of corn protein. However, the biological activity of LPF in vivo and in vitro remains unclear. This study is aimed at investigating the protective effects of tripeptide LPF against NTD in the high glucose exposure condition and delineate the underlying biological mechanism. We found that LPF alleviated NTD in the high glucose-exposed chicken embryo model. In addition, DF-1 chicken embryo fibroblast was loaded with high glucose for induction of oxidative stress and abnormal O-GlcNAcylation in vitro. LPF significantly decreased accumulation of reactive oxygen species and content of malondialdehyde in DF-1 cells but increased the ratio of reduced glutathione and oxidized glutathione in chick embryo. Oxygen radical absorbance capacity results showed that LPF itself had good free radical scavenging capacity and could enhance antioxidant activity of the cell content. Mechanistic studies suggested that the resistance of LPF to oxidative damage may be related to promotion of NRF2 expression and nuclear translocation. LPF alleviated the overall O-GlcNAcylation level of cellular proteins under high glucose conditions and restored the level of Pax3 protein. Collectively, our findings indicate that LPF peptide could act as a nutritional supplement for the protection of development of embryonic neural tube affected by GDM.

Cyclo(-Phe-Phe) alleviates chick embryo liver injury via activating the Nrf2 pathway.

Excessive reactive oxygen species (ROS) accumulation is involved in the pathogenesis of liver fibrosis and damage, specifically in the developing embryo that is extremely sensitive to oxidative stress. Herein, a liver injury model in chick embryo was established by using 2,2-azobis (2-amidinopropane) dihydrochloride (AAPH), which was used to investigate the effect of cyclo(-Phe-Phe) (CPP), a natural dipeptide found in foods and beverages. The results showed that CPP significantly alleviated AAPH-induced liver pathological damage, hepatic dysfunction and inhibited the excessive production of ROS in both chick embryo liver and HepG2 cells. Additionally, CPP increased the antioxidative activity of glutathione peroxidase (GPx) and superoxide dismutase (SOD), as well as elevated the level of glutathione (GSH), suggesting that CPP combating liver injury probably depends on its antioxidant capability. Mechanistically, CPP upregulated the mRNA and protein expression of heme oxyense-1 (HO-1) and NADPH quinone oxidoreductase 1 (NQO1) in vivo and in vitro, along with promoting the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) while inhibiting its degradation through binding with Kelch-like ECH-associated protein 1 (Keap1). In conclusion, this study proposes a potential peptide drug for the treatment of hepatic damage induced by oxidative stress and also unravels its mechanism of action.

The Impact of Traditional Chinese Medicine on Mitophagy in Disease Models.

Mitophagy plays an important role in maintaining mitochondrial quality and cell homeostasis through the degradation of damaged, aged, and dysfunctional mitochondria and misfolded proteins. Many human diseases, particularly neurodegenerative diseases, are related to disorders of mitochondrial phagocytosis. Exploring the regulatory mechanisms of mitophagy is of great significance for revealing the molecular mechanisms underlying the related diseases. Herein, we summarize the major mechanisms of mitophagy, the relationship of mitophagy with human diseases, and the role of traditional Chinese medicine (TCM) in mitophagy. These discussions enhance our knowledge of mitophagy and its potential therapeutic targets using TCM.

Inhibitory effects of baicalein against herpes simplex virus type 1.

Herpes simplex virus type 1 (HSV-1) is a ubiquitous and widespread human pathogen, which gives rise to a range of diseases, including cold sores, corneal blindness, and encephalitis. Currently, the use of nucleoside analogs, such as acyclovir and penciclovir, in treating HSV-1 infection often presents limitation due to their side effects and low efficacy for drug-resistance strains. Therefore, new anti-herpetic drugs and strategies should be urgently developed. Here, we reported that baicalein, a naturally derived compound widely used in Asian countries, strongly inhibited HSV-1 replication in several models. Baicalein was effective against the replication of both HSV-1/F and HSV-1/Blue (an acyclovir-resistant strain) in vitro. In the ocular inoculation mice model, baicalein markedly reduced in vivo HSV-1/F replication, receded inflammatory storm and attenuated histological changes in the cornea. Consistently, baicalein was found to reduce the mortality of mice, viral loads both in nose and trigeminal ganglia in HSV-1 intranasal infection model. Moreover, an ex vivo HSV-1-EGFP infection model established in isolated murine epidermal sheets confirmed that baicalein suppressed HSV-1 replication. Further investigations unraveled that dual mechanisms, inactivating viral particles and inhibiting IκB kinase beta (IKK-ß) phosphorylation, were involved in the anti-HSV-1 effect of baicalein. Collectively, our findings identified baicalein as a promising therapy candidate against the infection of HSV-1, especially acyclovir-resistant strain.

Environmental tobacco smoke and cancer risk, a prospective cohort study in a Chinese population.

Few prospective cohort studies have investigated associations between environmental tobacco smoke (ETS) and other cancer sites, in addition to lung cancer. We assessed these associations in a population-based prospective cohort study started from 2008 to 2011 with average of 9.1 years of follow-up, in Minhang district, Shanghai, China. The study included a total of 23,415 participants (8388 men, 15,027 women) and 205,515 person-years. Epidemiological data were collected by a standardized questionnaire including ETS exposure. Newly diagnosed patients with primary cancers and deaths were identified by record linkage system with the Shanghai Cancer Registry and Shanghai Vital Statistics. Hazard ratios (HRs) and their 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models, adjusting for potential confounders. During the study period, a total of 1462 patients with diagnoses of primary cancers were identified. Among all participants and non-smokers, ETS was associated with an increased risk of all smoking-related cancers (all: adjusted HR: 1.23, 95% CI: 1.05-1.43 and non-smokers: 1.24, 1.02-1.49), lung cancer (1.29, 0.98-1.71 and 1.27, 0.91-1.77), and stomach cancer (1.86, 1.21-2.85 and 1.75, 1.05-2.91), respectively. Furthermore, associations for lung and stomach cancers were the strongest among non-smoking females. The joint effects of both ETS and active smoking were strongest for all cancers, all smoking-related cancers, lung cancer, and stomach cancer. No clear interactions were observed. These results suggest that ETS exposure may increase the risk of smoking-related cancers in a Chinese population. Further studies on the relationship between ETS exposure and specific cancer sites are warranted to replicate our findings.

Theacrine, a purine alkaloid from kucha, protects against Parkinson's disease through SIRT3 activation.

BACKGROUND: Oxidative damage of dopaminergic neurons is the fundamental causes of Parkinson's disease (PD) that has no standard cure at present. Theacrine, a purine alkaloid from Chinese tea Kucha, has been speculated to benefit the neurodegeneration in PD, through similar actions to its chemical analogue caffeine, albeit excluding side effects. Theacrine has nowadays gained a lot of interest for its multiple benefits, while the investigations are weak and insufficient. HYPOTHESIS/PURPOSE: It is well-known that tea has a wide range of functions, especially in the prevention and treatment of neurodegenerative diseases. Theacrine is an active monomer compound in Camellia assamica var. kucha Hung T. Chang & H.S.Wang (Kucha), which appears to be effective and safe in PD therapy. The aim of this study is to examine its actions in diverse PD models and explore the mechanisms. STUDY DESIGN: For determination of theacrine's effects, we employed diverse oxidative damage-associated PD models, including 6-OHDA-treated rats, MPTP-treated mice/zebrafish and MPP+-treated SH-SY5Y cells, and using caffeine, selegiline and depranyl as positve control. For investigation and verification of the mechanisms, we utilized approaches testing mitochondrial function-related parameters and enzyme activity as well as applied gene knockdown and overexpression. METHODS: We employed behavioral tests including spontaneous activity, pole, swimming, rotarod and gait, immunohistochemistry, HPLC, flow cytometry, immunohistochemistry, Western blot, gene knockdown by siRNA and overexpression by plasmid in this study. RESULTS: Theacrine is demonstrated to retrieve the loss of dopaminergic neurons and the damages of behavioral performance in multiple animal models of PD (6-OHDA-treated rats and in MPTP-treated mice and zebrafish). The followed data of MPP+-treated SH-SY5Y cells indicate that theacrine relieves apoptosis resulted from oxidative damage and mitochondrial dysfunction. Further investigations illustrate that theacrine activates SIRT3 directly. It is of advantage to prevent apoptosis through SIRT3-mediated SOD2 deacetylation that reduces ROS accumulation and restores mitochondrial function. This concept is elaborated by 3TYP that inhibits SIRT3 enzyme activity and knockdown/overexpression of SIRT3 gene, demonstrating a crucial role of SIRT3 in theacrine-benefited dopaminergic neurons. CONCLUSION: Theacrine prevents apoptosis of dopaminergic neurons through directly activating SIRT3 which deacetylating SOD2 and restoring mitochondrial functions.

New insights into the effects of caffeine on adult hippocampal neurogenesis in stressed mice: Inhibition of CORT-induced microglia activation.

Chronic stress-evoked depression has been implied to associate with the decline of adult hippocampal neurogenesis. Caffeine has been known to combat stress-evoked depression. Herein, we aim to investigate whether the protective effect of caffeine on depression is related with improving adult hippocampus neurogenesis and explore the mechanisms. Mouse chronic water immersion restraint stress (CWIRS) model, corticosterone (CORT)-established cell stress model, a coculture system containing CORT-treated BV-2 cells and hippocampal neural stem cells (NSCs) were utilized. Results showed that CWIRS caused obvious depressive-like disorders, abnormal 5-HT signaling, and elevated-plasma CORT levels. Notably, microglia activation-evoked brain inflammation and inhibited neurogenesis were also observed in the hippocampus of stressed mice. In comparison, intragastric administration of caffeine (10 and 20 mg/kg, 28 days) significantly reverted CWIRS-induced depressive behaviors, neurogenesis recession and microglia activation in the hippocampus. Further evidences from both in vivo and in vitro mechanistic experiments demonstrated that caffeine treatment significantly suppressed microglia activation via the A2AR/MEK/ERK/NF-κB signaling pathway. The results suggested that CORT-induced microglia activation contributes to stress-mediated neurogenesis recession. The antidepression effect of caffeine was associated with unlocking microglia activation-induced neurogenesis inhibition.

Multifunctional HNT@Fe3O4@PPy@DOX Nanoplatform for Effective Chemo-Photothermal Combination Therapy of Breast Cancer with MR Imaging.

Multifunctional nanoparticles for imaging and treatment in cancer are getting more and more attention recently. Herein, halloysite nanotubes (HNTs), natural clay nanotubes, are designed as multifunctional nanoplatform for targeted delivering photothermal therapy agents and chemotherapeutic drugs. Fe3O4 was anchored on the outer surfaces of HNTs and then doxorubicin (DOX) was loaded on the nanotubes. Afterward, a layer of polypyrrole (PPy), as photothermal agent, was wrapped on the tubes. The nanoplatform of HNT@Fe3O4@PPy@DOX can be guided to tumor tissue by an external magnetic field, and then performs chemo-photothermal combined therapy by 808 nm laser irradiation. HNT@Fe3O4@PPy@DOX shows the ability of T2-weighted magnetic resonance imaging, which could be considered as a promising application in magnetic targeting tumor therapy. In vitro and in vivo experiments demonstrate that HNTs nanoplatform has good biocompatibility and produces a strong antitumor effect trigged by near-infrared laser irradiation. The novel chemo-photothermal therapy nanoplatform based on HNTs may be developed as a multifunctional nanoparticle for imaging and therapy in breast cancer.

Piperazine-Derived α1D/1A Antagonist 1- Benzyl-N- (3-(4- (2-Methoxyphenyl) Piperazine-1-yl) Propyl) -1H- Indole-2- Carboxamide Induces Apoptosis in Benign Prostatic Hyperplasia Independently of α1-Adrenoceptor Blocking.

Previous studies have indicated that α1D/1A antagonist naftopidil (NAF) suppresses prostate growth by decreasing cell proliferation without affecting apoptosis and prostate volume in benign prostatic hyperplasia (BPH). A NAF-derived α1D/1A antagonist 1- benzyl-N-(3-(4-(2-methoxyphenyl) piperazine-1-yl) propyl)-1H-indole-2- carboxamide (HJZ-12) has been reported from our laboratory, which exhibits high subtype-selectivity to both α1D- and α1A- AR (47.9- and 19.1- fold, respectively) with respect to a1B-AR in vitro. However, no further study was conducted. In the present study, a pharmacological evaluation of HJZ-12 in BPH was performed on an estrogen/androgen-induced rat BPH model and human BPH-1 cell line. In vivo, HJZ-12 exhibited better performance than NAF in preventing the progression of rat prostatic hyperplasia by not only decreasing prostate weight and proliferation (similar to NAF) but also, shrinking prostate volume and inducing prostate apoptosis (different from NAF). In vitro, HJZ-12 exhibited significant cell viability inhibition and apoptotic induction in BPH-1 cell line, without presenting cell anti-proliferation properties. Intriguingly, the role of HJZ-12 on cell viability and apoptosis was an α1-independent action. Furthermore, RNA-Seq analysis was applied to screen out six anti-apoptotic genes (Bcl-3, B-lymphoma Mo-MLV insertion region 1 [Bmi-1], ITGA2, FGFR3, RRS1, and SGK1). Amongst them, Bmi-1 was involved in the apoptotic induction of HJZ-12 in BPH-1. Overall, HJZ-12 played a remarkable role in preventing the progression of prostatic hyperplasia through α1-independent apoptotic induction, indicating that it will be a multi-target effective candidate for BPH treatment.

Comparison of chemical constitution and bioactivity among different parts of Lonicera japonica Thunb.

BACKGROUND: Lonicera japonica Thunb is a common herb in East Asia. The flower buds are usually regarded as the traditional medicinal part, while leaves and stems are considered less valuable and receive little attention. This study compared the chemical constituents and anti-inflammatory effects of the different tissues in L. japonica Thunb for the first time. RESULTS: Thirty compounds were identified by ultra-performance liquid chromatography-photodiode detector-quadrupole / time of flight-mass spectrometry (UPLC-PDA-Q/TOF-MS/MS) analysis. Hydroxycinnamic acids, flavonoids, and iridoids were identified as the major components. The flower buds (FLJ), leaves (LLJ), and stems (SLJ) of L. japonica Thunb showed strong similarities in chemical components. The LLJ contained higher levels of hydroxycinnamic acids and flavonoids than the FLJ and SLJ. Furthermore, FLJ, LLJ, and SLJ exhibited potent anti-inflammatory activity in croton oil-induced ear edema and carrageenan-induced paw edema assays in mice. Moreover, FLJ, LLJ, and SLJ showed a cytoprotective effect on lipopolysaccharide- (LPS-) stimulated RAW 264.7 macrophages. Lipopolysaccharide-induced increases in nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) were suppressed by treatments of FLJ, LLJ, and SLJ, respectively. The LLJ possessed a stronger anti-inflammatory effect than the FLJ. CONCLUSION: Leaves and stems of L. japonica Thunb have chemical components and anti-inflammatory properties similar to flower buds, and may become alternative or supplementary sources of flower buds. © 2019 Society of Chemical Industry.

[Cloning and expression analysis of LncRNA-RgAGT2 responding to consecutive monoculture in Rehmannia glutinosa].

The consecutive monoculture obstacle is a major problem in the field of Rehmannia glutinosa( R. glutinosa),has severely declined the yield and quality of R. glutinosa. Here,using hi TAIL-PCR and RACE techniques,we have cloned the full-length transcript( 1 573 bp) of Unigene 29334＿All screened by DGE as a consecutive monoculture obstacle response gene of R. glutinosa. Based on ORF Finder prediction,all ORFs detected in the full-length transcript were less than 300 nt,which suggested that the above transcript was confirmed to be a long non-coding RNA( LncRNA). With alignment in R. glutinosa transcriptome,this LncRNA was partially homologous to alanine glyoxylate transaminase 2 gene( Rg AGT2),which was named LncRNA-RgATG2. To further explore the function of LncRNA-RgAGT2,we have examined expression patterns of LncRNA-RgAGT2 and Rg AGT2 at five critical development stages( seedling,elongation,pre-expanding,mid-expanding,late-expanding) in the first and second year replanting of R. glutinosa,respectively. The results indicated that LncRNA-RgAGT2,as a potential regulator,is possible to play a vital role in Rg AGT2 expression regulation. Meanwhile,LncRNA-RgAGT2 has presented significant variation in all development stages of R. glutinosa,which could be used as a " diagnostic label" to assess consecutive monoculture obstacle. This study,for the first time,showed that LncRNA was responsible for the response and regulation of consecutive monoculture obstacle,which would be a powerful supplement to reveal the molecular mechanisms of consecutive monoculture obstacle of R. glutinosa.

Curative effect of minimally invasive surgery on palmar and foot hyperhidrosis and its influence on serum-related cytokines and immunoglobulins.

The curative effect of minimally invasive surgery on palmar and foot hyperhidrosis and its influence on serum-related cytokines and immunoglobulins were investigated. Seventy-six patients with palmar and foot hyperhidrosis admitted to Yunnan University Hospital from August 2014 to July 2016 were selected and randomly divided into control group (n=38) and observation group (n=38) using a random number table. Patients in control group received drug therapy, while those in observation group underwent laparoscopic thoracic-4 sympathetic chain combined with thoracic-3 branch amputation. The therapeutic effects of patients in the two groups were compared. The levels of serum C-reactive protein (CRP), interleukin-6 (IL-6), IL-10 and tumor necrosis factor-α (TNF-α) of patients in the two groups were measured by enzyme-linked immunosorbent assay (ELISA) before treatment and at one week after treatment. The levels of immunoglobulin G (IgG), IgA and IgM were detected by immunoturbidimetry. The quality of life (QOL) in patients was evaluated by quality-of-life index (iQOL) before and after treatment. The total effective rate in the observation group was significantly higher than that in the control group (P<0.05). The serum levels of CRP, IL-6, IL-10 and TNF-α of patients in the two groups were higher at one week after treatment than those before treatment (P<0.05), and there were no significant differences between the two groups (P>0.05). At one week after treatment, IgG, IgM and IgA levels of patients in the two groups were remarkably increased (P<0.05), and there were no significant differences between the two groups (P>0.05). After treatment, the iQQL scores of patients in the two groups were significantly decreased, and iQQL score in observation group was decreased more significantly compared with that in control group (P<0.05). Compared with drug therapy, minimally invasive surgery is more effective in the treatment of palmar and foot hyperhidrosis with smaller trauma and inflammatory reaction, and it has less influence on serum immunoglobulin levels, which is conducive to the rehabilitation of patients.

Correlation between survivin polymorphism and acute leukemia of children.

The correlation between the variations in the polymorphic sites of survivin, rs9904341C/G and rs8073069C/G, and the pathogenesis of acute leukemia, as well as the guiding significance in clinical practice were investigated. We enrolled a total of 182 children with acute leukemia and 200 healthy children as the subjects. In accordance with the case-control method, the polymerase chain reaction was carried out for genetic typing of the two polymorphic sites, rs9904341C/G and rs8073069C/G. In the case group and the healthy group, the frequencies of C and G alleles in rs9904341C/G of survivin were 59.3 and 41.7%, and 46.7 and 50.3%, respectively, and the pairwise comparison showed statistically significant differences (P=0.008). Additionally, the frequencies of genotypes, C/C, C/G and G/G, were 38.5 and 41.7%; 19.8 and 26.5%; 16.5 and 27.0% in the case group and the healthy group, respectively, and the differences in comparisons showed statistical significance (P=0.033). The genotype frequency of C/C in the case group was 38.5%, significantly higher than that in the healthy group (26.5%). Compared with C/C, the risk coefficient of leukemia in patients with genotypes of C/G or G/G was significantly decreased. In the case group and the healthy group, the frequencies of C and G alleles in rs8073069C/G of survivin were 30.5 and 69.5%; 27.7 and 72.3%, respectively, and the pairwise comparison showed no statistically significant differences (P=0.404). Additionally, the frequencies of genotypes, C/C, C/G and G/G, were 11 and 39.0%; 50.0 and 9.0%; 37.5 and 53.5% in the case group and the healthy group, respectively, and the differences in comparisons showed no statistical significance (P=0.62). Compared with the genotype of C/C, we found that the risk of leukemia was not affected in patients with genotypes of C/G and G/G. In conclusion, the SNP of rs9904341C/G in survivin may be correlated with the risk of acute leukemia, and compared with C/C genotype, patients with C/G or G/G may have a decreased risk of acute leukemia. In survivin, rs8073069C/G may have no correlation with the risk of acute leukemia.

A comparative analysis of chemical compositions in Camellia sinensis var. puanensis Kurihara, a novel Chinese tea, by HPLC and UFLC-Q-TOF-MS/MS.

Camellia sinensis var. puanensis Kurihara (Puan tea) is a kind of ancient tea plant newly found in Jiangxipo and the surrounding areas of Puan County (Guizhou, China). People there always believe that drinking Puan tea is beneficial to the promotion of health and prevention of diseases. However, detailed information on its compositions has not been reported. Therefore, in this study, the varieties and contents of purine alkaloids and polyphenols in Puan tea were identified and determined by HPLC and UFLC-Q-TOF-MS/MS. Our results showed that theacrine, but not caffeine, was the dominated purine alkaloid detected in Puan tea. Meanwhile, Puan tea contained B-type procyanidin dimer, trimer and dimer monogallate, which were not detected in Camellia sinensis, Camellia ptilophylla and Camellia assamica var. kucha. The obtained results could support the local uses of Puan tea in health and nutrition and contribute to the research of tea variety.

Prediction and evaluation of the lipase inhibitory activities of tea polyphenols with 3D-QSAR models.

The extraordinary hypolipidemic effects of polyphenolic compounds from tea have been confirmed in our previous study. To gain compounds with more potent activities, using the conformations of the most active compound revealed by molecular docking, a 3D-QSAR pancreatic lipase inhibitor model with good predictive ability was established and validated by CoMFA and CoMISA methods. With good statistical significance in CoMFA (r2cv = 0.622, r2 = 0.956, F = 261.463, SEE = 0.096) and CoMISA (r2cv = 0.631, r2 = 0.932, F = 75.408, SEE = 0.212) model, we summarized the structure-activity relationship between polyphenolic compounds and pancreatic lipase inhibitory activities and find the bulky substituents in R2, R4 and R5, hydrophilic substituents in R1 and electron withdrawing groups in R2 are the key factors to enhance the lipase inhibitory activities. Under the guidance of the 3D-QSAR results, (2R,3R,2'R,3'R)-desgalloyloolongtheanin-3,3'-O-digallate (DOTD), a potent lipase inhibitor with an IC50 of 0.08 µg/ml, was obtained from EGCG oxidative polymerization catalyzed by crude polyphenol oxidase. Furthermore, DOTD was found to inhibit lipid absorption in olive oil-loaded rats, which was related with inhibiting the activities of lipase in the intestinal mucosa and contents.

Cancer incidence in patients with type 2 diabetes mellitus: a population-based cohort study in Shanghai.

BACKGROUND: Type 2 diabetes mellitus (T2DM) has been suggested to increase the risk of cancers. The aim of this study was to investigate the risk of common cancers in Chinese patients with T2DM. METHODS: A population-based retrospective cohort study including 36,379 T2DM patients was conducted in Minhang District of Shanghai, China, during 2004 to 2010. All T2DM patients were enrolled from the standardized management system based on local electronic information system. Newly-diagnosed cancer cases were identified by record-linkage with the Shanghai Cancer Registry. Standardized incidence ratios (SIR) and 95% confidence interval (CI) were used to estimate the risk of cancers among T2DM patients. RESULTS: Overall crude incidence rate (CIR) of cancers was 955.21 per 105 person-years in men and 829.57 per 105 person-years in women. Increased risk of cancer was found in both gender, with an SIR being 1.28 (95% CI = 1.17-1.38) in men and 1.44 (95% CI =1.32-1.55) in women. Increased risk of colon (SIR = 1.97; 95% CI = 1.49 to 2.46), rectum (1.72; 1.23 to 2.21), prostate (2.87; 2.19 to 3.56), and bladder cancers (1.98, 1.28 to 2.68) were observed in men and elevated risk of colon (1.67; 1.25 to 2.08), breast (1.66; 1.38 to 1.95), and corpus uteri cancers (2.87; 2.03 to 3.71) were observed in women. CONCLUSIONS: Our results indicate that Chinese patients with T2DM may have an increased risk of some cancers, and the increase may vary by sub-sites of cancers.

Theacrine, a purine alkaloid obtained from Camellia assamica var. kucha, attenuates restraint stress-provoked liver damage in mice.

Theacrine (1,3,7,9-tetramethyluric acid), a purine alkaloid, has proven to be beneficial in maintaining several brain functions and is being studied for potential medicinal uses in recent years. In this study, we isolated theacrine from Camellia assamica var. kucha and investigated its protective effects on liver damage induced by restraint stress in mice. Results showed that 18 h of restraint stress could induce liver damage, with an obvious increase in levels of plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST). This finding was further confirmed by hepatic pathological examination, which showed inflammatory cell infiltration and focal necrosis of hepatocytes. However, oral administration of theacrine (10, 20, 30 mg/kg for 7 consecutive days) was found to decrease plasma ALT and AST levels, reduce hepatic mRNA levels of inflammatory mediators (IL-1ß, TNF-α, IL-6, and IFN-γ), and reverse the histologic damages in stressed mice. Simultaneously, theacrine also significantly decreased the content of malondialdehyde and increased oxygen radical absorbance capacity (ORAC) level in the plasma and liver of stressed mice. These results suggested that the protective effects of theacrine on stress-induced liver damage might be correlated with its antioxidative activity. The antioxidative capacity of theacrine was further evaluated by in vitro ORAC and cellular antioxidant activity assay. The results suggested that the antioxidative capacity of theacrine was not due to the direct action on free radical clearance. Moreover, the elevated activities and gene expressions of superoxide dismutase, catalase, and glutathione peroxidase, as well as the reduced activity of xanthine oxidase by theacrine treatment in stressed mice suggested that the antioxidative activity might be due to the strengthening of the antioxidant system in vivo. On the basis of the above results, theacrine is possibly a good candidate for protecting against or treating lifestyle diseases and might contribute to the study of natural products.

[Research of heavy metals determination in cereals by inductively coupled plasma mass spectrometry].

The present paper established the determination method of heavy metals such as As, Pb, Hg and Cd in cereals by inductively coupled plasma mass spectrometry (ICP-MS) with microwave digestion. The pretreatment conditions were improved and the instrument operating parameters were optimized. 72Ge, 115In and 209Bi were selected as the internal standard elements to overcome the matrix effects and instrument fluctuations effectively. Interference correction equations were used to eliminate the interference of polyatomic ions. Satisfactory linearity of standard curves was obtained with elemental correlation coefficients over 0.9999. The detection limits were in the range of 0.0006-0.016 mg x L(-1), the recoveries of samples were 90%-110%, and the RSD was within 5%. The accuracy of the method was evaluated with national standard reference materials and the interference test was experimented using standard solution. Studies have shown that the method is suitable for rapid determination of heavy metals As, Pb, Hg and Cd in cereals with wide linear range, good precision and high accuracy.