Effect of prolactin on cytotoxicity and oxidative stress in ovine ovarian granulosa cells.

Background: Prolactin (PRL) has been reported to be associated with oxidative stress, which is an important contributor leading to cell apoptosis. However, little is known about the mechanisms underlying the effects of PRL on cytotoxicity and oxidative stress in ovine ovarian granulosa cells (GCs). Methods: Ovine ovarian GCs were treated with 0, 4, 20, 100 and 500 ng/mL of PRL. Then, the cytotoxicity, cell viability, malondialdehyde (MDA), reactive oxygen species (ROS), superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) of GCs were detected. Additionally, 500 ng/mL PRL was chosen as the high PRL concentration (HPC) due to its high cytotoxicity and oxidative stress. Proteomic and metabonomic were performed to examine the overall difference in proteins and metabolic pathways between C (control: 0 ng/mL PRL) and P groups (500 ng/mL PRL). Results: The results indicated that GCs treated with 4 ng/mL PRL significantly decreased (P < 0.05) the cytotoxicity, ROS and MDA, increased (P < 0.05) the cell viability, SOD and T-AOC, and the GCs treated with 500 ng/mL PRL showed the opposite trend (P < 0.05). Supplementation with 500 ng/mL PRL significantly increased the proteins of MT-ND1, MAPK12, UBA52 and BCL2L1, which were enriched in ROS and mitophagy pathways. Pathway enrichment analysis showed that the pentose phosphate pathway was significantly enriched in the P group. Conclusion: A low concentration of PRL inhibited cytotoxicity and oxidative stress. HPC induced oxidative stress in ovine ovarian GCs via the pentose phosphate pathway by modulating the associated proteins MT-ND1 in ROS pathway and UBA52, MAPK12 and BCL2L1 in mitophagy pathway, resulting in cytotoxicity.

Phylogenomic discovery of deleterious mutations facilitates hybrid potato breeding.

Hybrid potato breeding will transform the crop from a clonally propagated tetraploid to a seed-reproducing diploid. Historical accumulation of deleterious mutations in potato genomes has hindered the development of elite inbred lines and hybrids. Utilizing a whole-genome phylogeny of 92 Solanaceae and its sister clade species, we employ an evolutionary strategy to identify deleterious mutations. The deep phylogeny reveals the genome-wide landscape of highly constrained sites, comprising ∼2.4% of the genome. Based on a diploid potato diversity panel, we infer 367,499 deleterious variants, of which 50% occur at non-coding and 15% at synonymous sites. Counterintuitively, diploid lines with relatively high homozygous deleterious burden can be better starting material for inbred-line development, despite showing less vigorous growth. Inclusion of inferred deleterious mutations increases genomic-prediction accuracy for yield by 24.7%. Our study generates insights into the genome-wide incidence and properties of deleterious mutations and their far-reaching consequences for breeding.

Super-pangenome analyses highlight genomic diversity and structural variation across wild and cultivated tomato species.

Effective utilization of wild relatives is key to overcoming challenges in genetic improvement of cultivated tomato, which has a narrow genetic basis; however, current efforts to decipher high-quality genomes for tomato wild species are insufficient. Here, we report chromosome-scale tomato genomes from nine wild species and two cultivated accessions, representative of Solanum section Lycopersicon, the tomato clade. Together with two previously released genomes, we elucidate the phylogeny of Lycopersicon and construct a section-wide gene repertoire. We reveal the landscape of structural variants and provide entry to the genomic diversity among tomato wild relatives, enabling the discovery of a wild tomato gene with the potential to increase yields of modern cultivated tomatoes. Construction of a graph-based genome enables structural-variant-based genome-wide association studies, identifying numerous signals associated with tomato flavor-related traits and fruit metabolites. The tomato super-pangenome resources will expedite biological studies and breeding of this globally important crop.

The multi-omics basis of potato heterosis.

Heterosis is a fundamental biological phenomenon characterized by the superior performance of hybrids over their parents. Although tremendous progress has been reported in seed crops, the molecular mechanisms underlying heterosis in clonally propagated crops are largely unknown. Potato (Solanum tuberosum L.) is the most important tuber crop and an ongoing revolution is transforming potato from a clonally propagated tetraploid crop into a seed-propagated diploid hybrid potato. In our previous study, we developed the first generation of highly homozygous inbred lines of potato and hybrids with strong heterosis. Here, we integrated transcriptome, metabolome, and DNA methylation data to explore the genetic and molecular basis of potato heterosis at three developmental stages. We found that the initial establishment of heterosis in diploid potato was mainly due to dominant complementation. Flower color, male fertility, and starch and sucrose metabolism showed obvious gene dominant complementation in hybrids, and hybrids devoted more energy to primary metabolism for rapid growth. In addition, we identified ~2 700 allele-specific expression genes at each stage, which likely function in potato heterosis and might be regulated by CHH allele-specific methylation level. Our multi-omics analysis provides insight into heterosis in potato and facilitates the exploitation of heterosis in potato breeding.

Safety and efficacy of TURP vs. laser prostatectomy for the treatment of benign prostatic hyperplasia in multi-morbid and elderly individuals aged ≥ 75.

PURPOSE: To compare the safety and durability of transurethral resection of the prostate (TURP) and Laser prostatectomy (LP) among multi-morbid and elderly patients. METHODS: Using data retrieved from the New York State Department of Health Statewide Planning and Research Cooperative System and the California Office of Statewide Health Planning and Development, we selected cohorts of 1) multi-morbid (Charlson comorbidity index ≥ 3) and 2) elderly (aged ≥ 75) patients with benign prostatic hyperplasia who underwent laser coagulation, vaporization, enucleation, or TURP between January 2005 and December 2016. We assessed the post-operative incidence of hospital readmission and ER visit at 30 days and 90 days, complications at 90 days, and reoperation and the development of urethral stricture at 6 months or longer. RESULTS: We found 12,815 and 29,806 patients in the multi-morbid and elderly cohort, respectively. Compared to LP, TURP was associated with lower odds of 90-day hospital readmission and ER visit in the multi-morbid cohort (OR 0.92, 95% CI 0.85-1.00) and higher odds in the elderly cohort (OR 1.07, 95% CI 1.01-1.14). The multi-morbid cohort showed lower odds of urinary tract infections (Ref: LP, OR 0.83, 95% CI 0.73-0.93). The elderly cohort showed higher odds of experiencing hematuria (OR 1.28, 95% CI 1.03-1.59) post TURP. TURP was associated with a 19% (95% CI 0.66-1.00) and 20% (95% CI 0.71-0.91) reduced hazard of reoperation at 6 months or longer for multi-morbid and elderly cohorts, respectively. CONCLUSION: Compared to LP, TURP was associated with higher complication rates for the multi-morbid and elderly cohorts overall but a lower hazard of reoperation, supporting its durability.

Effects of a 16-week Tai Chi intervention on cutaneous sensitivity and proprioception among older adults with and without sensory loss.

This study investigated the effects of a 16-week Tai Chi (TC) intervention on cutaneous sensitivity and proprioception among older adults with and without sensory loss. Thirty-six older adults were divided into sensory loss and control groups, and they underwent a 16-week TC intervention. Significant interactions were detected in heel cutaneous sensitivity (p = 0.046, F = 4.419) and knee flexion (p = 0.043, F = 4.580), extension (p = 0.027, F = 5.529) and ankle plantar-flexion proprioception (p = 0.037, F = 4.860). The post hoc test indicated that in the sensory loss group, heel cutaneous sensitivity threshold (p = 0.034) and knee flexion (p = 0.004), extension (p = 0.002) and ankle plantar-flexion (p = 0.023) proprioception threshold decreased at week 17, whereas in the control group, knee flexion (p = 0.029) proprioception threshold decreased at week 17. TC intervention improved cutaneous sensitivity at more sites and proprioception in more joints among the older adults with sensory loss. TC intervention is a good option for older adults to exercise, and it is more effective among older adults with sensory loss.

Effects of air-abrasion pressure on mechanical and bonding properties of translucent zirconia.

OBJECTIVES: The purpose of this in vitro study was to investigate the effects of different air-abrasion pressures on flexural strength and shear bond strength of a translucent zirconia. MATERIALS AND METHODS: The translucent zirconia surface was treated with 50 µm abrasive alumina particles at different pressure: 0.1 MPa; 0.2 MPa; 0.3 MPa; 0.4 MPa; 0.5 MPa; untreated specimens were used as control group (n = 33). For each group, three-point bending test was used to evaluate the flexural strength, and surface characterizations were analyzed. Following adhesive bonding and water storage for 24 h, specimens were subdivided into groups baseline and aged (5000 thermocycles). Then, shear bond strength was measured and failure mode was recorded. Statistical analysis was performed with one-way ANOVA and Tukey test (α = 0.05). RESULTS: Increasing air-abrasion pressure (0.3 MPa, 0.4 MPa, and 0.5 MPa) decreased the flexural strength. Higher air-abrasion pressure resulted in rougher zirconia surfaces and caused more microcracks. The highest shear bond strength was obtained for zirconia surfaces abraded at 0.2 MPa (15.88 ± 2.70 MPa) and 0.3 MPa (14.32 ± 1.12 MPa). Aging did not decrease the strength for all groups except control group (p < 0.001). CONCLUSIONS: Air-abrasion with 50 µm abrasive alumina particles at 0.2 MPa could achieve good strength for translucent zirconia ceramics while maintaining adequate and durable bonding with resin cement. CLINICAL RELEVANCE: A total of 0.2 MPa is recommended for air-abrasion procedure applied before a dental restoration fabricated with translucent zirconia is bonded to resin cement.

Effectiveness of Huai Qi Huang Granules on Juvenile Collagen-induced Arthritis and Its Influence on Pyroptosis Pathway in Synovial Tissue.

Huai Qi Huang (HQH) exerts great effects in clinic, such as anti-inflammation, immune-regulation, anti-cancer, and so on. However, the mechanism by which HQH protects juvenile idiopathic arthritis (JIA) is obscure. Thus, we explored deeply the protective mechanisms in juvenile collagen-induced arthritis (CIA) rat model. Pyroptosis is Gasdermin D (GSDMD)-dependent programmed cell death, involved in many diseases, such as sepsis. We investigated whether GSDMD-induced pyroptosis take part in mechanisms of juvenile CIA arthritis. Juvenile Wistar rats (3-4 weeks) were injected intradermally with fully emulsified bovine type II collagen and complete Freund's adjuvant to establish CIA rat models. Later, the CIA rats received oral administration of HQH (4.16 g/kg) once a day from the day 21 of modeling, with the treatment lasting for 28 days. Varieties of indicators were measured for evaluation of anti-inflammation effect of HQH, including hind paw swelling, arthritis scores, micro CT, and histopathological changes and the level of pro-inflammatory cytokines in the serum, including tumor necrosis factor alpha (TNF-±) and interleukin-18 (IL-18). The expression of GSDMD and caspase-1 in the joint synovial tissues was detected. The results demonstrated that the expression of the pyroptotic protein GSDMD and its upstream caspase-1 was significantly increased in the synovial tissues of CIA rats. The treatment of HQH ameliorated the symptoms in CIA rats, reduced levels of pro-inflammatory cytokines and hind paw swelling, down-regulated the expression of GDSMD and caspase-1. GSDMD-induced pyroptosis participated in the pathogenesis of CIA rats. The study supported that HQH can effectively improve joints inflammation of juvenile collagen-induced arthritis rats by inhibiting pyroptosis pathway in the joint synovial tissues.

Effects of mindfulness-based interventions on quality of life of women with breast cancer: a systematic review.

Aim: The systematic review assessed the effect of mindfulness-based interventions on the quality of life among women with breast cancer. Methods: PubMed, Cochrane library, EMBASE, Web of Science and CINAHL databases were searched for studies published. Our review assessed the effect of mindfulness-based interventions (Mindfulness-Based Stress Reduction [MBSR] intervention and Mindfulness-Based Cognitive Therapy [MBCT]) on quality of life for women with breast cancer. Two authors independently assessed the quality of all included studies using the Downs and Black Quality Index. Results: The search finally identified 15 studies. The MBSR intervention showed a significant effect between groups. The MBCT intervention also showed good effect on quality of life. Adverse events were inadequately reported. Conclusion: The MBSR intervention on quality of life among women with breast cancer was effective and safe. The effect of MBCT intervention on quality of life still needs more research.

The effectiveness of acupuncture therapy in patients with post-stroke depression: An updated meta-analysis of randomized controlled trials.

BACKGROUND: To assess the effectiveness of acupuncture in patients with post-stroke depression (PSD). METHODS: The Cochrane Library, CINAHL, EMBASE, PubMed, SCOPUS, Web of Science, and 4 Chinese databases were electronically searched for articles published between January 1, 2010 and May 31, 2018. Randomized controlled trials (RCTs) investigating the effects of acupuncture on PSD were included. The quality of all included trials was assessed according to guidelines published by the Cochrane Collaboration. RESULTS: Seven trials compared the effectiveness of acupuncture therapy with that of control in alleviating the symptoms of PSD. Pooled analysis demonstrated that patients in the acupuncture intervention group experienced a significantly higher treatment effect than controls (RR 1.16 [95% CI 1.08-1.24]; P < .0001), with low study heterogeneity (I = 4%). Based on intervention methods, further analysis revealed a statistically significant difference in effectiveness between the acupuncture alone and medicine groups (RR 1.25 [95% CI 1.11 1.41]; Z = 3.78; P = .0002). There was no statistically significant difference in efficacy between the acupuncture combined with medicine and medicine groups (RR 1.07 [95% CI 0.98-1.17]; P = .11). CONCLUSIONS: This meta-analysis provides evidence supporting the viewpoint that acupuncture is an effective and safe treatment for PSD. Subgroup analyses further revealed that acupuncture alone resulted in better outcomes than drug therapy in improving depressive symptoms. Further high-quality RCTs are needed to systematically evaluate the effectiveness of acupuncture for PSD and develop standardized acupuncture protocols.

Effects of acupuncture on breast cancer-related lymphoedema: a systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: Breast cancer-related lymphoedema (BCRL) is a common complication after breast cancer treatment. We investigated whether acupuncture could be used to manage limb oedema in women after breast cancer surgery. METHODS: The Cochrane Library, PubMed, Embase, Web of Science, CINAHL, and four Chinese databases were electronically searched for papers published through November 2017. Randomised controlled trials (RCTs) of acupuncture for BCRL were included. RESULTS: In total, six RCTs with 318 patients were identified. The main analysis revealed a positive overall effect of acupuncture intervention on pre/post-treatment differences in the diameter of the elbow joint, reductions in upper limb lymphoedema and effectiveness index based on arm measurement data in patients with breast cancer. Two studies evaluating the outcome of acupuncture on the diameter of the elbow joint found a significant reduction in diameter between the acupuncture and control groups (weighted mean difference (WMD) 6 cm, 95% CI 5.11 to 6.89 cm; P<0.001). The same two studies investigated the effect of acupuncture on upper limb lymphoedema reduction and found a significant difference between the acupuncture and control groups (risk ratio 1.4, 95% CI 1.17 to 1.67; P<0.001). Two other studies used the effectiveness index to assess the arm and found a significant difference between the acupuncture and control groups (WMD 23.34, 95% CI 10.74 to 35.94; P<0.001). The fifth study used bioelectrical impedance spectroscopy to assess lymphoedema at several points on the arm before and after acupuncture; this study also reported a significant reduction in lymphoedema. The sixth study reported no significant difference in bioimpedance between the groups. CONCLUSIONS: The present meta-analysis and systematic review suggests that acupuncture is effective at reducing BCRL in patients after breast cancer treatment.

Chang-wei-qing, a Chinese herbal formula, ameliorates colitis-associated tumour development via inhibiting NF-κB and STAT3 signalling pathway.

CONTEXT: Chang-wei-qing (CWQ) is a Chinese herbal recipe with clinical efficacy. However, the molecular mechanism underlying its recognized therapeutic benefits against colorectal cancer is still elusive. OBJECTIVE: To investigate the potential beneficial effects of CWQ in drug-induced colitis-associated cancer (CAC) model and its mechanistic involvements in this disease. MATERIALS AND METHODS: Colitis-associated cancer model was induced by azoxymethane (AOM) and dextran sulphate sodium (DSS). CWQ was administrated by gavage. Colon length and tumour size were determined after resection. The colitis was systematically scored. The microbiota and population of Faecalibacterium prausnitzii (F. prausnitzii) Hauduroy & Duncan was analysed by quantitative polymerase chain reaction (PCR). ß-Glucuronidase, d-lactose and endotoxin were determined with commercially available kits. Pro-inflammatory cytokines were analysed in the colon tissues. Relative protein expressions were determined by Western blotting. RESULTS: High concentration CWQ significantly restored the colon length, decreased tumour number and size (1.7 ± 0.6 vs. 2.8 ± 0.4 mm, p < 0.01) and reduced colitis score (11.8 ± 2.1 vs. 18.2 ± 2.3, p < 0.01). CWQ also suppressed expansion of F. prausnitzii population (0.029 ± 0.015% vs. 0.052 ± 0.019%, p < 0.01). CWQ greatly inhibited the activity of ß-glucuronidase and leakage of d-lactose and endotoxin. Meanwhile, the pro-inflammatory cytokines were remarkably decreased in CAC mice in response to CWQ treatment. We further demonstrated that CWQ inhibited both NF-κB and STAT3 signalling. CONCLUSIONS: We for the first time demonstrated the antitumour properties of CWQ in vivo via inhibiting NF-κB and STAT3 signalling.

Selenium Antagonizes the Lead-Induced Apoptosis of Chicken Splenic Lymphocytes In Vitro by Activating the PI3K/Akt Pathway.

Lead (Pb) pollution has become one of the most serious global ecological problems. In animals, Pb ingestion induces apoptosis in many tissues. However, the mechanisms by which Pb induces apoptosis in chicken splenic lymphocytes in vitro via the PI3K/Akt pathway and the antagonistic effect of selenium (Se) on Pb remain unclear. Therefore, we established the in vitro Se-Pb interaction model in chicken splenic lymphocytes and examined the frequency of apoptotic cells using acridine orange/ethidium bromide (AO/EB) staining and the TdT-mediated dUTP nick end labeling assay and detected the activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT), as well as the levels of malondialdehyde (MDA) and reactive oxygen species (ROS). The expression of PI3K/Akt pathway-related genes was also examined by qRT-PCR and western blotting. MDA and ROS levels were markedly increased, whereas the activities of GPx, SOD, and CAT were significantly decreased; the levels of the PI3K, Akt, and Bcl-2 messenger RNAs (mRNAs) and proteins were decreased; and the levels of the p53, Bax, cytochrome c (Cyt-c), caspase 3, and caspase 9 mRNAs and proteins were increased in the Pb group. In addition, the frequency of apoptotic cells was also significantly increased by the Pb treatment. However, Se supplementation during Pb exposure observably attenuated Pb-induced apoptosis; increased the levels of the PI3K, Akt, and Bcl-2 mRNAs and proteins; and decrease the levels of the p53, Bax, Cyt-c, caspase 3, and caspase 9 mRNAs and proteins in the chicken spleen. In conclusion, Pb exposure causes oxidative stress, inhibits the PI3K/Akt pathway, and subsequently induces apoptosis in chicken splenic lymphocytes in vitro, and these effects are partially attenuated by Se supplementation. To the best of our knowledge, this study is the first to reveal the antagonistic effect of Se on Pb-induced apoptosis of chicken splenic lymphocytes in vitro via the activation of the PI3K/Akt pathway.

What is the impact of n-3 PUFAs on inflammation markers in Type 2 diabetic mellitus populations?: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: To explore the possible role of n-3 polyunsaturated fatty acids (PUFAs) in lowering inflammation markers in individuals with type 2 diabetes mellitus. METHODS: PubMed, CNKI and Cochrane databases were searched until December 30, 2015; references from papers or reviews were also retrieved and screened. Screening was performed by two independent researchers, and randomized controlled trials reporting the specific n-3 PUFA type, dose, frequency, and duration of treatment, as well as the baseline and follow-up concentrations of inflammation markers, including interleukin 2 (IL-2), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) and C-reactive protein (CRP), were selected for final analysis. Data analysis was performed using RevMan 5.2 software. RESULTS: Eight studies involving 955 participants were included; all reported CRP. Only one included study reported IL-2 or IL-6 while two studies reported TNF-α. N-3 PUFAs significantly reduced CRP concentration compared with control [SMD 95 % CI, 1.90 (0.64, 3.16), Z = 2.96, P = 0.003, random effect model]. CONCLUSIONS: N-3 PUFAs decrease CRP concentration in type-2 diabetes mellitus. However, larger and rigorously designed RCTs are required to confirm this finding and extend it into other inflammatory biomarkers.

Effects of temperature on the quality of black garlic.

BACKGROUND: Black garlic is a type of garlic product that is generally produced by heating raw garlic at high temperature with controlled humidity for more than 30 days. Black garlic has appeared on the market for many years. It is crucial to investigate the characteristics of quality formation of black garlic during processing at various temperatures. RESULTS: In this study, fresh garlic was processed to black garlic at temperatures of 60, 70, 80 and 90 °C. Moisture, amino acid nitrogen and allicin contents decreased gradually during thermal processing of various temperatures. Reducing sugar, 5-hydroxymethylfurfural, total phenols, total acids contents and browning increased. The changing rate of quality indicators and flavour of black garlic varied at different temperatures. Browning intensity reached about 74 when black garlic aged. The sensory score was significantly higher in black garlic aged at 70 °C (39.95 ± 0.31) compared with that at other temperatures, suggesting that 70 °C might facilitate formation of good quality and flavour of black garlic during processing. CONCLUSION: Temperature had a remarkable impact on the quality and flavour of black garlic. © 2015 Society of Chemical Industry.

[Fe-ZSM-5 catalysts with different silica-alumina ratios for N2O, catalytic decomposition].

The Fe-ZSM-5 catalysts were prepared with H-ZSM-5 of different Si/Al ratios by wet ion exchange and chemical vapor deposition. Then the catalysts were investigated by XRD, BET, TEM, UV-vis and NH3-TPD technologies to analyze the iron states in Fe-ZSM-5 zeolites. The results showed that after H-ZSM-5 zeolites were prepared by chemical vapor deposition and heating wet ion exchange, the nano Fe2 O3 particles were uniformly dispersed with the sizes of 8 nm in the Fe-ZSM-5-25 (Si/A1-25). Moreover, there were more oligonuclear Fe3+ Oy clusters in the Fe-ZSM-5-25 catalysts than in Fe-ZSM-5-300 (Si/Al-300). The results of catalytic performance on N2O decomposition showed that Fe-ZSM-5-25 catalysts had higher catalytic activities than Fe-ZSM-5-300 catalysts. The Fe-ZSM-5 catalysts prepared by chemical vapor deposition achieved the best catalytic activity in N2O decomposition among the catalysts prepared by the three methods. Moreover, the presence of O2 only slightly reduced N2O conversion, while NO promoted the N2O decomposition. Finally, after reaction for more than 100 h, Fe-ZSM-5 catalyst showed no obvious deactivation under simulated emission conditions.

Chemoprevention of 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster cheek pouch carcinogenesis by a 5-lipoxygenase inhibitor, garcinol.

Our previous studies have shown that aberrant arachidonic acid metabolism, especially the 5-lipoxygenase (5-Lox) pathway, is involved in oral carcinogenesis and can be targeted for cancer prevention. To develop potent topical agents for oral cancer chemoprevention, 5 known 5-Lox inhibitors from dietary and synthetic sources (Zileuton, ABT-761, licofelone, curcumin, and garcinol) were evaluated in silico for their potential efficacy. Garcinol, a polyisoprenylated benzophenone from the fruit rind of Garcinia spp., was found to be a promising agent based on the calculation of a theoretical activity index. Computer modeling showed that garcinol well fit the active site of 5-Lox, and potentially inhibited enzyme activity through interactions between the phenolic hydroxyl groups and the non-heme catalytic iron. In a short-term study on 7,12-dimethylbenz[a]anthracene (DMBA)-treated hamster cheek pouch, topical garcinol suppressed leukotriene B4 (LTB4) biosynthesis and inhibited inflammation and cell proliferation in the oral epithelium. In a long-term carcinogenesis study, topical garcinol significantly reduced the size of visible tumors, the number of cancer lesions, cell proliferation, and LTB4 biosynthesis. These results demonstrated that topical application of a 5-Lox inhibitor, garcinol, had chemopreventive effect on DMBA-induced hamster cheek pouch carcinogenesis.

Inhibitory effects of Zengshengping fractions on DMBA-induced buccal pouch carcinogenesis in hamsters.

BACKGROUND: Zengshengping (ZSP) tablets had inhibitory effects on oral precancerous lesions by reducing the incidence of oral cancer. However, the severe liver toxicity caused by systemic administration of ZSP limits the long-term use of this anti-cancer drug. The purpose of this study was to evaluate the tumor inhibitory effects due to the topical application of extracts from ZSP, a Chinese herbal drug, on 7, 12-dimethlbenz(a)anthracene (DMBA) induced oral tumors in hamsters. The study also investigated the anti-cancer mechanisms of the ZSP extracts on oral carcinogenesis. METHODS: DMBA (0.5%) was applied topically to the buccal pouches of Syrian golden hamsters (6 - 8 weeks old) three times per week for six weeks in order to induce the development of oral tumors. Different fractions of ZSP were either applied topically to the oral tumor lesions or fed orally at varying dosages to animals with oral tumors for 18 weeks. Tumor volume was measured by histopathological examination. Tumor cell proliferation was evaluated by counting BrdU labeled cells and by Western blotting for mitogen-activated protein kinase (MAPK) protein levels. The protein levels of apoptosis marker Caspase-3 and regulator Bcl-2 protein were also measured by Western blotting. RESULTS: Topical application of DMBA to the left pouch of hamsters induced oral tumor formation. Animals treated with DMBA showed a loss in body weight while animals treated with ZSP maintained normal body weights. Both the ZSP n-butanol fraction and water fraction significantly reduced tumor volume by 32.6% (P < 0.01) and 22.9% (P < 0.01) respectively. Topical application of ZSP also markedly decreased the BrdU-positive cell numbers in oral tumor lesions and reduced the expression level of MAPK. In addition, ZSP promoted tumor cell apoptosis by increasing Caspase-3 expression but decreasing Bcl-2 protein production. CONCLUSION: The n-butanol and water fractions of ZSP are effective at inhibiting tumor cell proliferation and stimulating apoptosis in oral cancer suggesting that these fractions have chemopreventive effects on DMBA induced oral carcinogenesis.

[Effects of hydrogen sulfide on myocardial mitochondrial injury during acute myocardial ischemia in rats].

OBJECTIVE: To investigate the effect of hydrogen sulfide (H2S) on mitochondrial function in acute myocardial ischemia in rats. METHODS: Acute myocardial ischemia models were established by ligating the left anterior descending coronary artery (LADC) of rats. Fourty-eight male SD rats were randomly divided into 6 groups (n = 8): sham operation group, ischemia group, ischemia + sodium hydrosulfide (NaHS) low, middle and high dose groups and ischemia + DL-proparglycine(PPG) group. The ultrastructures of myocardial mitochondria were observed with electron microscope. The content of H2S in plasma and the activity of cystathionine-gamma-lyase (CSE) in myocardial tissue of rats were respectively detected. The swelling and activity of myocardial mitochondria were determined. The activities of ATPase, GSH-Px, SOD and the content of malondial-dehyde (MDA) in myocardial mitochondria of rats were also measured. RESULTS: Compared with those of the sham operation group, the content of H2S in plasma, the activity of CSE in myocardial tissue and the activity of myocardium mitochondria were significantly decreased. The activities of ATPase, SOD, GSH-Px in myocardial mitochondria were significantly decreased, The content of malondial dehyde(MDA) in myocardial mitochondria and the swelling of mitochondria were distinctly increased in the ischemia group (P < 0.01). Compared with those of the ischemia group, the content of H2S in plasma and the activity of CSE in myocardial tissue were increased, and the activities of mitochondria, ATPase, SOD, and GSH-Px in myocardial mitochondria were significantly increased in ischemia + NaHS low, middle and high-dose groups; the swelling of mitochondria and the content of MDA in myocardial mitochondria were significantly decreased in ischemia + NaHS middle and high-dose groups (P < 0.05 or P < 0.01). The administration of PPG could partially reduce the myocardial protection of hydrogen sulfide (P < 0.05 or P < 0.01). CONCLUSION: It could be concluded that the administration of hydrogen sulfide could enhance the activities of mitochondrial ATPase, SOD, GSH-Px, decrease the level of mitochondrial lipid peroxidation, and play a protective effect against acute myocardial ischemia.

[Chemopreventive effect of boswellic acid and curcumin on 7,12-dimethyl benzanthracene-induced hamster cheek pouch carcinogenesis].

OBJECTIVE: To evaluate the chemopreventive effects of boswellic acid and curcumin on 7,12-dimethyl benzanthracene(DMBA)-induced oral carcinogenesis in the hamster cheek pouch model. METHODS: Male Syrian golden hamsters (6 - 8 weeks old, 80 - 130 g in weight) were randomly divided into seven groups, with group A serving as the untreated negative control. The left cheek pouch of the remaining hamsters was topically treated with 0.5% DMBA in mineral oil three times a week for 6 weeks. They were then randomized to six groups with group B serving as a positive control and receiving no further treatment. Groups C-G were treated topically with 5, 10 mg/L boswellic acid, 5, 10 µmol/L curcumin, or the combination of 5 mg/L boswellic acid and 5 µmol/L curcumin three times per week for 18 weeks. The animals were injected with bromodeoxyuridine intraperitoneally at 50 mg/kg 2 h prior to killing. At the 25 th week all the hamsters were sacrificed and cheek pouch tissue was harvested. One half of the tissue was snap frozen in liquid nitrogen for analysis of arachidonic acid metabolites, and the other half was fixed in 10% phosphate-buffered saline(PBS)-buffered formalin for histopathological examination. RESULTS: Six-weeks of DMBA followed by 18-weeks of topical application of boswellic acid and curcumin, both boswellic acid (5, 10 mg/L) and curcumin (5, 10 µmol/L) significantly inhibited the incidence from 93.8% to 73.9% (P > 0.05), numbers from 2.19 ± 0.98 to 1.13 ± 0.81 (P < 0.01) and size of visible tumors. Microscopically the incidence of squamous cell carcinoma and BrdU index were also significantly suppressed by boswellic acid and curcumin. CONCLUSIONS: Both boswellic acid and curcumin were effective in preventing oral carcinogenesis in DMBA-induced hamster cheek pouch model.