Network toxicology and molecular docking for the toxicity analysis of food contaminants: A case of Aflatoxin B1.

The present study aims to promote network toxicology and molecular docking strategies for the efficient evaluation of the toxicity of food contaminants. With the example of liver injury induced by the food contaminant Aflatoxin B1(AFB1), this study effectively investigated the putative toxicity of food contaminants and the potentially molecular mechanisms. The study found that AFB1 regulates multiple signalling pathways by modulating core targets such as AKT1, BCL2, TNF, CASP3, SRC and EGFR. These pathways encompass Pathways in cancer, PI3K-Akt signalling pathway, Endocrine resistance, Lipid and atherosclerosis, Apoptosis and other pathways, subsequently impacting immunotoxicity, inflammatory responses, apoptosis, cytogenetic mutations, and ultimately leading to liver injury. We provide a theoretical basis for understanding the molecular mechanisms of AFB1 hepatotoxicity and for the prevention and treatment of cancers caused by the food contaminant AFB1. Furthermore, our network toxicology and molecular docking methods also provide an effective method for the rapid evaluation of the toxicity of food contaminants, which effectively solves the cost and ethical problems associated with the use of experimental animals.

Observation of the efficacy of elongated needle therapy in treating patients with â ¢B prostatitis of stagnant dampness-heat syndrome. / 芒针治疗湿热瘀阻证⠢Båž‹å‰åˆ—è ºç‚Žæ‚£è€ çš„ç–—æ•ˆè§‚å¯Ÿ.

OBJECTIVES: To observe the clinical efficacy in patients with ⅢB prostatitis of stagnant dampness-heat syndrome treated with elongated needle therapy. METHODS: A total of 90 patients with ⅢB prostatitis of stagnant dampness-heat syndrome were selected and randomly divided into a treatment group(45 cases, 2 dropped out) and a control group(45 cases, 1 dropped out) using a random number table method. The control group was treated with oral administration of Qianlie Shutong Capsule, 3 capsules per dose, 3 times a day for a total of 4 weeks. The treatment group received elongated needle therapy at Qihai(CV6), Zhongji(CV3), bilateral Zhibian(BL54) and Shuidao(ST28), with one treatment per day for 4 weeks. Before and after treatment, the traditional Chinese medicine syndrome score, National Institutes of Health Chronic Prostatitis Symptom Index(NIH-CPSI) score were compared between the two groups, and the clinical efficacy was compared after treatment. RESULTS: Compared with that before treatment, the control group showed significant decrease in traditional Chinese medicine syndrome score, testicular pain, urinary frequency, unending remnants of urine, scrotal wetness, yellowish urine, urinary symptoms, and quality of life scores after treatment(P<0.05)；the treatment group showed significant decrease in traditional Chinese medicine syndrome score, and perineal pain, groin pain, pelvic pain, testicular pain, scrotal wetness, yellowish urine scores, NIH-CPSI total score, pain symptoms, urinary symptoms, and quality of life scores after treatment(P<0.05). After treatment, the treatment group showed significantly lower traditional Chinese medicine syndrome score, and perineal pain, groin pain, pelvic pain, testicular pain scores, NIH-CPSI total score, pain symptoms, and quality of life scores than those of the control group(P<0.05). The effective rate in the treatment group (63.64%, 28/43) was significantly higher than that in the control group (88.37%, 38/44, P<0.05). CONCLUSIONS: Elongated needle therapy can significantly improve the traditional Chinese medicine syndrome score, NIH-CPSI total score, and pain symptom scores in patients with ⅢB prostatitis of stagnant dampness-heat syndrome. It can significantly improve the cure rate in these patients and is particularly effective in relieving pain.

[Dumai moxibustion combined with low-dose tadalafil for erectile dysfunction: Evaluation of therapeutic effect].

OBJECTIVE: To investigate the clinical effect of dumai (governor meridian) moxibustion combined with low-dose tadalafil in the treatment of ED with decline of vital gate fire. METHODS: We enrolled in this study 130 ED patients with decline of vital gate fire who met the inclusion criteria and equally randomized them into a control and an experimental group, the former treated with low-dose tadalafil tablets at 5 mg once a day while the latter by dumai moxibustion once a week in addition, all for 4 weeks. Of the total number of subjects, 62 in the control group and 63 in the experimental group completed the experiment. We recorded the scores on IIEF-5, Erection Quality Scale (EQS), Erection Hardness Scale (EHS), TCM symptoms and Treatment Satisfaction Scale (TSS) as well as the penile hemodynamic parameters peak systolic velocity (PSV), end diastolic velocity (EDV) and resistance index (RI) before and after treatment and compared them between the two groups. RESULTS: The total response rate was significantly higher in the experimental group than in the control (87.30% vs 66.13%, P < 0.05). IIEF-5, EQS, EHS and TSS scores, PSV and RI were markedly increased while TCM symptoms and EDV remarkably decreased in both groups after treatment (P < 0.05), even more significantly in the experimental than in the control group (P < 0.05). CONCLUSION: Dumai moxibustion combined with low-dose tadalafil can improve erectile function, increase penile blood flow velocity and alleviate clinical symptoms in ED patients with decline of vital gate fire, with definite clinical effect and safety.

[Corrigendum] Fully human VEGFR2 monoclonal antibody BC001 attenuates tumor angiogenesis and inhibits tumor growth.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that, for the scratch wound assay experiments shown in Fig. 1 on p. 2413, the panels showing the '0 h' experiments for the respective incubations with VEGF or BC001 were apparently identical. The authors were able to re­examine their original data files, and realized that this figure had been inadverently assembled incorrectly. The revised version of Fig. 1, containing the correct data for the '0 h / BC001' panel, is shown below. Note that the revisions made to this figure do not affect the overall conclusions reported in the paper. The authors are grateful to the Editor of International Journal of Oncology for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [International Journal of Oncology 45: 2411­2420, 2014; DOI: 10.3892/ijo.2014.2690].

Molecular Mechanism Pathways of Natural Compounds for the Treatment of Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, and its incidence continues to increase each year. Yet, there is still no definitive drug that can stop its development. This review focuses mainly on lipotoxicity, oxidative stress, inflammation, and intestinal flora dysbiosis to understand NAFLD's pathogenesis. In this review, we used NCBI's PubMed database for retrieval, integrating in vivo and in vitro experiments to reveal the therapeutic effects of natural compounds on NAFLD. We also reviewed the mechanisms by which the results of these experiments suggest that these compounds can protect the liver from damage by modulating inflammation, reducing oxidative stress, decreasing insulin resistance and lipid accumulation in the liver, and interacting with the intestinal microflora. The natural compounds discussed in these papers target a variety of pathways, such as the AMPK pathway and the TGF-ß pathway, and have significant therapeutic effects. This review aims to provide new possible therapeutic lead compounds and references for the development of novel medications and the clinical treatment of NAFLD. It offers fresh perspectives on the development of natural compounds in preventing and treating NAFLD.

Allergen desensitization reduces the severity of relapsed alopecia areata in dust-mite allergic patients.

Atopy may be a facilitating factor in some alopecia areata (AA) patients with early disease onset and more severe/extensive AA. The underlying immune mechanisms are unknown, but allergen responses may support a pro-inflammatory environment that indirectly promotes AA. To investigate the long-term effect of allergen immunotherapy (AIT) against house dust mite (HDM) allergy on disease severity and prognosis for AA patients. An observational comparative effectiveness study was conducted on 69 AA patients with HDM allergy. 34 patients received conventional/traditional AA treatment (TrAA) plus AIT (AIT-TrAA), and 35 patients received TrAA alone. Serum total immunoglobulin E (tIgE), HDM specific IgE (sIgE), HDM specific IgG4 (sIgG4) and cytokines (IL-4, IL-5, IL-10, IL-12, IL-13, IL-33, IFNγ) were quantified in these patients, together with 58 non-allergic AA patients and 40 healthy controls. At the end of the 3-year desensitization course, the AIT-TrAA group presented with lower SALT scores than the TrAA group, especially in non-alopecia totalis/universalis (AT/U) patients and pre-adolescent AT/U patients (age ≤ 14). In patients with elevated tIgE levels before AIT, a decrease in tIgE was correlated to reduced extent of AA on completion of the AIT course. After desensitization, elevation of IL-5 and decrease of IL-33 were observed in HDM allergic-AA patients. Desensitization to HDM in allergic AA patients reduces the severity of relapse-related hair loss over the 3-year AIT treatment course, possibly via opposing Th2 dominance. This adjunctive treatment may help reduce disease severity and curtail the disease process in allergic patients with AA.

A glucose-blue light AND gate-controlled chemi-optogenetic cell-implanted therapy for treating type-1 diabetes in mice.

Exogenous insulin therapy is the mainstay treatment for Type-1 diabetes (T1D) caused by insulin deficiency. A fine-tuned insulin supply system is important to maintain the glucose homeostasis. In this study, we present a designed cell system that produces insulin under an AND gate control, which is triggered only in the presence of both high glucose and blue light illumination. The glucose-sensitive GIP promoter induces the expression of GI-Gal4 protein, which forms a complex with LOV-VP16 in the presence of blue light. The GI-Gal4:LOV-VP16 complex then promotes the expression of UAS-promoter-driven insulin. We transfected these components into HEK293T cells, and demonstrated the insulin was secreted under the AND gate control. Furthermore, we showed the capacity of the engineered cells to improve the blood glucose homeostasis through implantation subcutaneously into Type-1 diabetes mice.

[Governor vessel moxibustion combined with wenyang yiqi qiwei decoction for erectile dysfunction with spleen-kidney deficiency and its effect on testosterone and vascular endothelial function].

OBJECTIVE: To observe the therapeutic effect of governor vessel moxibustion combined with wenyang yiqi qiwei decoction on erectile dysfunction (ED) with spleen-kidney deficiency and to explore the possible mechanism. METHODS: A total of 130 ED patients with spleen-kidney deficiency were randomized into an observation group (65 cases, 2 cases dropped off) and a control group (65 cases, 3 cases dropped off). The control group was given wenyang yiqi qiwei decoction orally, one dose daily. On the basis of the treatment in the control group, governor vessel moxibustion was applied from Dazhui (GV 14) to Yaoshu (GV 2) in the observation group, 110 min a time, once a day. The treatment of 4 weeks was required in both groups. Before and after treatment, 5-question international index of erectile function (IIEF-5) score, erection quality scale (EQS) score, erectile hardness assessment (EHS) score, TCM syndrome score, serum testosterone (T) level and vascular endothelial function indexes (prostaglandin I2 [PGI2], endothelin-1 [ET-1] and nitric oxide [NO] levels) were observed respectively, and the clinical efficacy was evaluated in both groups. RESULTS: After treatment, the scores of IIEF-5, EQS, EHS and serum levels of T, PGI2, NO were increased compared before treatment (P<0.01), the TCM syndrome scores and serum ET-1 levels were decreased compared before treatment (P<0.01) in the two groups; the scores of IIEF-5, EQS, EHS and serum levels of T, PGI2, NO in the observation group were higher than those in the control group (P<0.01, P<0.05), the TCM syndrome score and serum ET-1 level were lower than those in the control group (P<0.01, P<0.05). The total effective rate was 88.9% (56/63) in the observation group, which was superior to 74.2% (46/62) in the control group (P<0.05). CONCLUSION: Governor vessel moxibustion combined with wenyang yiqi qiwei decoction can improve the erectile function and increase the erection hardness and quality in ED patients with spleen-kidney deficiency, its mechanism may relate to improving serum T level and vascular endothelial function.

[Research Progress in Niacinamide in the Prevention and Treatment of Mouth and Systemic Diseases].

Nicotinamide (NAM) is the amide form of niacin and one of the precursors of nicotinamide adenine dinucleotide (NAD +). NAM can be used as a dietary supplement or clinical therapeutic drug to replenish NAD + levels in the human body and participate in key bodily functions such as cellular metabolism and DNA repair. NAM has the advantage of low cost, wide availability, and sound biosafety. It also has multiple biological functions, including antibacterial effect, anti-inflammatory effect, and modulation of cellular immunity, producing significant ameliorative effects on skin and neurodegenerative diseases. However, most studies on NAM are still at the laboratory stage. Herein we reviewed the role and mechanism of NAM in the prevention and treatment of oral and systemic diseases, explored its potential as clinical therapeutic medication, provided some basis and references for the clinical application of nicotinamide in the prevention and treatment of various diseases, and discussed its prospects for future research and application.

Governor vessel moxibustion combined with wenyang yiqi qiwei decoction for erectile dysfunction with spleen-kidney deficiency and its effect on testosterone and vascular endothelial function / 中国针灸

OBJECTIVE@#To observe the therapeutic effect of governor vessel moxibustion combined with wenyang yiqi qiwei decoction on erectile dysfunction (ED) with spleen-kidney deficiency and to explore the possible mechanism.@*METHODS@#A total of 130 ED patients with spleen-kidney deficiency were randomized into an observation group (65 cases, 2 cases dropped off) and a control group (65 cases, 3 cases dropped off). The control group was given wenyang yiqi qiwei decoction orally, one dose daily. On the basis of the treatment in the control group, governor vessel moxibustion was applied from Dazhui (GV 14) to Yaoshu (GV 2) in the observation group, 110 min a time, once a day. The treatment of 4 weeks was required in both groups. Before and after treatment, 5-question international index of erectile function (IIEF-5) score, erection quality scale (EQS) score, erectile hardness assessment (EHS) score, TCM syndrome score, serum testosterone (T) level and vascular endothelial function indexes (prostaglandin I2 [PGI2], endothelin-1 [ET-1] and nitric oxide [NO] levels) were observed respectively, and the clinical efficacy was evaluated in both groups.@*RESULTS@#After treatment, the scores of IIEF-5, EQS, EHS and serum levels of T, PGI2, NO were increased compared before treatment (P<0.01), the TCM syndrome scores and serum ET-1 levels were decreased compared before treatment (P<0.01) in the two groups; the scores of IIEF-5, EQS, EHS and serum levels of T, PGI2, NO in the observation group were higher than those in the control group (P<0.01, P<0.05), the TCM syndrome score and serum ET-1 level were lower than those in the control group (P<0.01, P<0.05). The total effective rate was 88.9% (56/63) in the observation group, which was superior to 74.2% (46/62) in the control group (P<0.05).@*CONCLUSION@#Governor vessel moxibustion combined with wenyang yiqi qiwei decoction can improve the erectile function and increase the erection hardness and quality in ED patients with spleen-kidney deficiency, its mechanism may relate to improving serum T level and vascular endothelial function.

[To evaluate the efficacy of Yishen Tongluo decoction combined with low-dose tadalafil in the treatment of diabetic erectile dysfunction with kidney deficiency and blood stasis syndrome].

OBJECTIVE: To observe the clinical efficacy of the combined treatment of Yishen Tongluo formula and low-dose tadalafil in diabetic erectile dysfunction. METHODS: A total of 80 patients with diabetic erectile dysfunction were randomly divided into two groups. The control group given tadalafil treatment, observation group in the control group given Yishen Tongluo Formula on the basis of treatment. The treatment period was 8 weeks. Erectile function were observed before and after treatment in the two groups patients-5 international questionnaire (IIEF - 5) score, erection quality scale (EQS) score, erectile hardness (EHS) score, TCM syndrome integral, content of serum homocysteine (HCY), endothelial function index ï¼»serum levels of prostaglandin I2 (PGI2)ï¼½ and endothelin (ET) content, a The changes of nitrogen oxide (NO), glucose and lipid metabolism indexes ï¼»triglyceride (TC), total cholesterol (TG)ï¼½ and oxidative stress related factors ï¼»total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-Px)ï¼½ were evaluated, and the clinical efficacy of the two groups was evaluated. RESULTS: In terms of overall efficacy rate, the observation group (79.4%) outperformed that of the control (48.7%, P< 0.01).After treatment, the IIEF-5 score, EQS score, EHS score, and serum levels of PGI2, NO, T-AOC and GSH-Px were higher than those before treatment in the two groups (P< 0.05). The TCM syndrome score and serum HCY, ET-1, TC and TG were lower than those before treatment (P< 0.05), and the comparison group's consequence was comparatively worse than the group under observation (P< 0.01). CONCLUSIONS: Yishen Tongluo Formula can dramatically enhance the erectile dysfunction andimprovement of glucose-lipid metabolism when adopted in together with low-dose tadalafil.

[The causal relationship between gut microbiota and male reproductive and sexual health].

OBJECTIVE: The purpose of this study was to use the MR method to explore the causal relationship between 211 gut microbiota and male reproductive and sexual health. METHODS: The MiBioGen alliance published genome-wide association study (GWAS) related genetic variation data was used as instrumental variables (IVs) for gut microbiota, and the Finngen biobank GWAS related genetic variation data was used as IVs for male infertility, abnormal sperm, sexual dysfunction, erectile dysfunction, and testicular dysfunction. The inverse variance-weighted (IVW) method was used as the MR analysis method, the results were evaluated according to the odds ratio and 95% confidence interval of the effect measures, and data sensitivity analysis was performed. RESULTS: The results showed that 6 types of gut microbiota were related to male infertility, 12 types were related to abnormal sperm, 5 types were related to sexual dysfunction, 4 types were related to erectile dysfunction, and 4 types were related to testicular dysfunction. And there was no abnormality in the data sensitivity analysis. CONCLUSION: The intestinal microbiota is closely related to male reproductive and sexual health.

[Research progress on the mechanism of ferroptosis in septic cardiomyopathy].

Sepsis is a serious complication of infection, and its further development may lead to multi-organ dysfunction syndrome. Sepsis cardiomyopathy is a common complication of sepsis and has been directly linked to high mortality. Although the pathogenesis of septic cardiomyopathy is not fully understood, in-depth study of the pathogenesis of septic cardiomyopathy and the identification of its potential therapeutic targets may reduce mortality in patients with sepsis. Ferroptosis is an iron-dependent mode of cell death that has been shown to be involved in the pathophysiological mechanisms of many diseases. Some related studies have reported that ferroptosis may be a potential mechanism of septic cardiomyopathy. This review provides new insights into the mechanisms of mitochondrial dysfunction, lipid peroxidation, xc-system, glutathione peroxidase 4 (GPX4), iron metabolism and the role of ferroptosiswith septic cardiomyopathy for further research and treatment of septic cardiomyopathy.

Molecular Mechanistic Pathways Targeted by Natural Compounds in the Prevention and Treatment of Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is one of the most common complications of diabetes, and its prevalence is still growing rapidly. However, the efficient therapies for this kidney disease are still limited. The pathogenesis of DKD involves glucotoxicity, lipotoxicity, inflammation, oxidative stress, and renal fibrosis. Glucotoxicity and lipotoxicity can cause oxidative stress, which can lead to inflammation and aggravate renal fibrosis. In this review, we have focused on in vitro and in vivo experiments to investigate the mechanistic pathways by which natural compounds exert their effects against the progression of DKD. The accumulated and collected data revealed that some natural compounds could regulate inflammation, oxidative stress, renal fibrosis, and activate autophagy, thereby protecting the kidney. The main pathways targeted by these reviewed compounds include the Nrf2 signaling pathway, NF-κB signaling pathway, TGF-ß signaling pathway, NLRP3 inflammasome, autophagy, glycolipid metabolism and ER stress. This review presented an updated overview of the potential benefits of these natural compounds for the prevention and treatment of DKD progression, aimed to provide new potential therapeutic lead compounds and references for the innovative drug development and clinical treatment of DKD.

Synthesis and antidepressant activity of novel 1-(1-benzoylpiperidin-4-yl) methanamine derivatives selectively targeting SSRI/5-HT1A.

A series of novel 1-(1-benzoylpiperidin-4-yl) methanamine derivatives were synthesized and evaluated for the serotonin reuptake inhibitory abilities and binding affinities to the 5-HT1A receptor. The metabolic stabilities of these compounds were measured in vitro using human or mouse liver microsomes and the antidepressant activities were explored In vivo using the forced swimming test (FST) and tail suspension test (TST) in mice. The results indicated that the compound 12a exhibited strongest serotonin reuptake inhibition (IC50 = 8.2 nM) and marked 5-HT1A receptor affinity (Ki = 0.069 nM), which were significantly superior to lead compounds Ⅰ and Ⅱ. Meanwhile, compound 12a showed good metabolic stability in vitro and exhibited potential antidepressant-like effects in the FST and TST in mice.

In vivo antiviral effect of plant essential oils against avian infectious bronchitis virus.

BACKGROUND: Infectious bronchitis virus (IBV) leads to huge economic losses in the poultry industry worldwide. The high levels of mutations of IBV render vaccines partially protective. Therefore, it is urgent to explore an effective antiviral drug or agent. The present study aimed to investigate the in vivo anti-IBV activity of a mixture of plant essential oils (PEO) of cinnamaldehyde (CA) and glycerol monolaurate (GML), designated as Jin-Jing-Zi. RESULTS: The antiviral effects were evaluated by clinical signs, viral loads, immune organ indices, antibody levels, and cytokine levels. The infection rates in the PEO-M (middle dose) and PEO-H (high dose) groups were significantly lower than those in the prevention, positive drug, and PEO-L (low dose) groups. The cure rates in the PEO-M and PEO-H groups were significantly higher than those in the prevention, positive drug, and PEO-L groups, and the PEO-M group had the highest cure rate of 92.31%. The symptom scores and IBV mRNA expression levels were significantly reduced in the PEO-M group. PEO significantly improved the immune organ indices and IBV-specific antibody titers of infected chickens. The anti-inflammatory factor levels of IL-4 and IFN-γ in the PEO-M group maintained high concentrations for a long time. The IL-6 levels in the PEO-M group were lower than those in prevention, positive drug, and PEO-L groups. CONCLUSION: The PEO had remarkable inhibition against IBV and the PEO acts by inhibiting virus multiplication and promoting immune function, suggesting that the PEO has great potential as a novel anti-IBV agent for inhibiting IBV infection.

[Effects of Yishen Tongluo Prescription on the PI3K-Akt-MTOR pathway and the protein and mRNA expressions of CatSper-1 and HSPA2 in the testis tissue of oligoasthenospermia rats].

OBJECTIVE: To study the effect of Yishen Tongluo Prescription (YTP) on the testis tissue of the male rats with oligoasthenospermia (OAS) and its action mechanism based on the PI3K-AKT-mTOR pathway. METHODS: We randomly divided 48 SPF male SD rats into 8 groups: normal control, OAS model control, L-carnitine (LC), high-dose YTP, low-dose YTP, Omipalisib inhibitor (OI), OI + high-dose YTP, and OI + low-dose YTP, with 6 rats in each group. We established a model of OAS in the latter 7 groups by intragastric administration of tripterygium wilfordii polyside, followed by intervention with corresponding drugs. After treatment, we obtained semen parameters from the rats, observed pathological changes in the testis tissue by HE staining, and determined the expressions of the PI3K-AKT-mTOR signaling pathway-related proteins and mRNA by Western blot and real-time fluorescence quantitative PCR (qRT-PCR). RESULTS: Sperm concentration and total sperm motility were significantly improved in the LC and YTP groups compared with those in the OAS model control group (P < 0.001). HE staining showed irregularly arranged spermatogenic cells and narrowed lumina and widened gaps of seminiferous tubules in the OAS model controls, as well as similar pathological changes in the LC, YTP and OI + YTP groups. Significant up-regulation was observed in the protein expressions of p-Akt, CatSper-1 and HSPA2 in the LC group (P < 0.05), those of p-Akt, mTOR, catsper-1 and HSP2 in the low-dose YTP group (P < 0.05) and that of PI3K in the high-dose YTP group (P < 0.05) compared with those in the model controls. There were no statistically significant differences in the expressions of PI3K, mTOR and catsper-1 between the OI and model control groups (P > 0.05), nor in those of PI3K, p-Akt, mTOR, CatSper-1 and HSPA2 between the OI + YTP and the former two groups (P > 0.05). The mRNA expressions of PI3K, mTOR, CatSper-1 and HSPA2 were remarkably higher in the LC and YTP groups than in the model control (P< 0.05), with those of catsper-1 and PI3K even more significantly up-regulated in the high-dose than in the low-dose YTP group (P< 0.001; P< 0.05). Statistically significant differences were not observed in the mRNA expressions of PI3K, mTOR, CatSper-1 and HSPA2 between the model control and OI groups (P > 0.05), nor in those of PI3K, mTOR, catsper-1 and HSPA2 between the model control and OI + YTP groups (P > 0.05). CONCLUSION: Yishen Tongluo Prescription can improve sperm quality and pathological changes of the testis tissue in rats with Tripterygium glycoside-induced OAS, which might be attributed to its ability of up-regulating the expressions of the PI3K Akt mTOR pathway-related proteins and mRNA in the testis tissue.

[Clinical and mechanism research on functional erectile dysfunction treated with moxibustion and qiangshen shugan qiwei decoction].

OBJECTIVE: To observe the clinical therapeutic effect on functional erectile dysfunction (FED) of kidney deficiency and liver stagnation treated by Baixiao moxibustion and qiangshen shugan qiwei decoction. METHODS: A total of 120 patients with FED were randomized into an observation group (60 cases, 2 cases dropped off) and a control group (60 cases, 4 cases dropped off). In the control group, the patients were treated with oral qiangshen shugan qiwei decoction (Radix Rehmanniae Praeparata, Rhizoma Dioscoreae, Rhizoma Curculiginis, Herba Epimedii, etc.), one dose daily. In the observation group, on the base of the treatment as the control group, Baixiao moxibustion was exerted along the distribution of governor vessel on the back, 30 min each time, once a week. The treatment duration was 4 weeks in the two groups. Before and after treatment, the scores of international index of erectile function-5 (IIEF5), erectile hardness scale (EHS), erectile dysfunction inventory of treatment satisfaction (EDITS) and TCM symptoms were observed in the patients of the two groups. Before and after treatment, the levels of serum sex hormones (testosterone [T], luteinizing hormone [LH], estradiol [E2], prolactin [PRL]) and the expressions of relevant proteins (matrix metalloproteinase-3 [MMP-3], matrix metalloproteinase-9 [MMP-9] and vascular endothelial growth factor [VEGF]) were determined in the patients of the two groups separately. The penile vascular function (peak systolic velocity [PSV], end-diastolic velocity [EDV], resistance index [RI]) was compared before and after treatment. Besides, the clinical therapeutic effect was evaluated. RESULTS: After treatment, the scores of IIEF5, EHS and EDITS were all increased as compared with the values before treatment (P<0.05), and the scores of TCM symptoms were reduced as compared with the values before treatment in the patients of the two groups (P<0.05). After treatment, the scores of IIEF5, EHS and EDITS in the observation group were higher than those in the control group (P<0.05), and the score of TCM symptoms was lower than the control group (P<0.05). After treatment, the levels of T and LH in serum of the two groups and the expressions of serum MMP-3 and MMP-9 in the observation group were all increased as compared with those before treatment (P<0.05), the levels of E2 and PRL in the observation group and VEGF expressions in the two groups were all reduced as compared with those before treatment (P<0.05). The levels of serum T and LH and the expressions of MMP-3 and MMP-9 in the observation groups were all higher than those in the control group (P<0.05), and the levels of E2 and PRL and VEGF expression were lower than the control group (P<0.05). After treatment, PSV was increased and EDV was reduced as compared with those before treatment in the patients of the two groups (P<0.05), RI in the observation group was reduced as compared with that before treatment (P<0.05). After treatment, PSV in the observation group was higher and EDV and RI were lower than the control group (P<0.05). The total effective rate was 87.9% (51/58) in the observation group, higher than 76.8% (43/56) in the control group (P<0.05). CONCLUSION: The combined therapy of Baixiao moxibustion and qiangshen shugan qiwei decoction effectively increases erectile function, erectile hardness and treatment satisfaction in the patients with functional erectile dysfunction of kidney deficiency and liver stagnation, as well as improves penile vascular function. The effect mechanism of this therapy may be related to the regulation of serum sex hormones and relevant proteins.

Identification of differentially methylated genes as diagnostic and prognostic biomarkers of breast cancer.

BACKGROUND: Aberrant DNA methylation is significantly associated with breast cancer. METHODS: In this study, we aimed to determine novel methylation biomarkers using a bioinformatics analysis approach that could have clinical value for breast cancer diagnosis and prognosis. Firstly, differentially methylated DNA patterns were detected in breast cancer samples by comparing publicly available datasets (GSE72245 and GSE88883). Methylation levels in 7 selected methylation biomarkers were also estimated using the online tool UALCAN. Next, we evaluated the diagnostic value of these selected biomarkers in two independent cohorts, as well as in two mixed cohorts, through ROC curve analysis. Finally, prognostic value of the selected methylation biomarkers was evaluated breast cancer by the Kaplan-Meier plot analysis. RESULTS: In this study, a total of 23 significant differentially methylated sites, corresponding to 9 different genes, were identified in breast cancer datasets. Among the 9 identified genes, ADCY4, CPXM1, DNM3, GNG4, MAST1, mir129-2, PRDM14, and ZNF177 were hypermethylated. Importantly, individual value of each selected methylation gene was greater than 0.9, whereas predictive value for all genes combined was 0.9998. We also found the AUC for the combined signature of 7 genes (ADCY4, CPXM1, DNM3, GNG4, MAST1, PRDM14, ZNF177) was 0.9998 [95% CI 0.9994-1], and the AUC for the combined signature of 3 genes (MAST1, PRDM14, and ZNF177) was 0.9991 [95% CI 0.9976-1]. Results from additional validation analyses showed that MAST1, PRDM14, and ZNF177 had high sensitivity, specificity, and accuracy for breast cancer diagnosis. Lastly, patient survival analysis revealed that high expression of ADCY4, CPXM1, DNM3, PRDM14, PRKCB, and ZNF177 were significantly associated with better overall survival. CONCLUSIONS: Methylation pattern of MAST1, PRDM14, and ZNF177 may represent new diagnostic biomarkers for breast cancer, while methylation of ADCY4, CPXM1, DNM3, PRDM14, PRKCB, and ZNF177 may hold prognostic potential for breast cancer.

[Expression and clinical significance of HIST1H2BH in head and neck squamous cell carcinoma].

PURPOSE: The purpose of this study was to investigate the expression of HIST1H2BH in head and neck squamous cell carcinoma (HNSCC) and to analyze its clinical significance. METHODS: The expression of HIST1H2BH in different tumors and HNSCC were analyzed based on the Oncomine and GEPIA database, and its relationship with clinicopathological parameters and prognostic value of HNSCC patients were also analyzed. The expression of HIST1H2BH in clinical specimens were detected by immunohistochemical staining. The variation of HIST1H2BH in HNSCC and its relationship with prognosis were analyzed based on the cBioPortal database. The interaction proteins and molecular mechanism of HIST1H2BH were preliminarily predicted using the String database. SPSS 24.0 software package was used for statistical analysis of the data. RESULTS: Analysis of Oncomine database and GEPIA database showed that HIST1H2BH was highly expressed in variety of tumors, and was significantly highly expressed in HNSCC. The expression level of HIST1H2BH was closely related to the pathological stage and prognosis of HNSCC patients, the prognosis of patients with high HIST1H2BH expression was poor. Immunohistochemical results of clinical specimens showed that the expression of HIST1H2BH in the cancerous tissue of HNSCC patients was significantly higher than that in the adjacent tissues. cBioPortal database analysis showed that the variation rate of HIST1H2BH in HNSCC patients was not high, but it was related to the disease-free survival rate. String database analysis showed that there were many genes associated with HIST1H2BH, and the signal pathways involved in biological processes were also complex. CONCLUSIONS: The expression of HIST1H2BH is elevated in HNSCC tissues, and its high expression is associated with poor prognosis. HIST1H2BH could be served as a marker for diagnosis and prognosis of HNSCC.