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1.
Besides using for hair removal, depilatory agents have been considered to be used as a penetration enhancer for transepidermal drug delivery. To examine the effect in hair follicles (HFs), two commercially available depilatory creams were tested on the dorsal skin of mice to monitor the effect deep into the skin structure. Fifteen male BALB/c mice were used in this study. Depilatory creams were applied to the dorsal skin of the same animal using shaved and untouched treatments as controls to minimize individual differences. Skin samples were collected at three days, one week and two weeks (n = 5 for each) after the treatment, and subjected for hematoxylin-eosin staining, and immunohistochemical analysis for proinflammatory cytokines. The morphological examination showed an increase in the thickness of epidermal layer of the depilatory cream-treated skin at early time points and in the subcutis at two weeks. Depilatory cream promoted entry of anagen phase and increased the number of hair follicles in the subcutis at one and two weeks. Immunohistochemistry showed elevated percentages of dermal fibroblasts expressing interleukin-6, tumor necrosis factor-α, and tumor necrosis factor-β. Shaving process increased the thickness of epidermis and dermis as depilatory creams did, but did neither induce the expression of proinflammatory cytokines in the dermal fibroblasts nor the number of HFs. The results suggested that the commercially available depilatory creams caused a transient minor inflammatory response of the skin and increased the levels of cytokines that might subsequently affect hair growth. 相似文献
2.
ContextRosmarinic acid (RA) dose-dependently ameliorates acetaminophen (APAP) induced hepatotoxicity in rats. However, whether RA hepatoprotective effect is by regulating RACK1 and its downstream signals is still unclear. ObjectiveThis study explores the RA protective effect on APAP-induced ALI and its mechanism. Materials and methodsSixty Kunming mice 6–8 weeks old were randomly separated into six groups ( n = 10) and pre-treated with normal saline, ammonium glycyrrhetate (AG) or RA (10, 20 or 40 mg/kg i.p./day) for two consecutive weeks. Then, APAP (300 mg/kg, i.g.) was administrated to induce ALI, except for the control. Serum alanine/aspartate aminotransferases (ALT and AST), malondialdehyde (MDA), superoxide dismutase (SOD) and histopathology were used to authenticate RA effect. The liver RACK1 and TNF-α were measured by western blot. ResultsCompared with the APAP group, different dosages RA significantly decreased ALT (52.09 ± 7.98, 55.13 ± 10.19, 65.08 ± 27.61 U/L, p < 0.05), AST (114.78 ± 19.87, 115.29 ± 31.91, 101.78 ± 21.85 U/L, p < 0.05), MDA (2.37 ± 0.87, 2.13 ± 0.87, 1.86 ± 0.39 nmol/mg, p < 0.01) and increased SOD (306.178 ± 90.80, 459.21 ± 58.54, 444.01 ± 78.09 U/mg, p < 0.05). With increasing doses of RA, RACK1 and TNF-α expression decreased. Moreover, the RACK1 and TNF-α levels were positively correlated with MDA ( r = 0.8453 and r = 0.9391, p < 0.01). Discussion and conclusionsOur findings support RA as a hepatoprotective agent to improve APAP-induced ALI and the antioxidant effect mediated through RACK1/TNF-α pathway. 相似文献
3.
Murine macrophage-derived tumor necrosis factor alpha (TNF-α) gene expression has been shown to be dramatically induced by bacterial lipopolysaccharide, and to be dependent upon nuclear factor-κB (NF-κB) binding sites in its promoter for the lipopolysaccharide induction. Murine J774.1 macrophage cells were found to predominately express the adenosine A 3 receptor RNA relative to adenosine A 1 receptor or adenosine A 2 receptor RNA. Adenosine receptor agonists, in a dose-dependent manner characteristic of the adenosine A 3 receptor, blocked the endotoxin induction of the TNF-α gene and TNF-α protein expression in the J774.1 macrophage cell line. The adenosine A 3 receptor antagonist BW-1433 dose-dependently reversed this adenosine inhibitory effect on TNF-α gene expression. Thus, the binding of adenosine receptor agonists to the adenosine A 3 receptor interrupts the endotoxin CD14 receptor signal transduction pathway and blocks induction of cytokine TNF-α, revealing a novel cross-talk between the murine adenosine A 3 receptor and the endotoxin CD14 receptor in J774.1 macrophages. 相似文献
4.
目的: 系统评价中药组方联合美沙拉嗪或柳氮磺吡啶治疗溃疡性结肠炎患者的疗效及安全性。 方法: 在PubMed、Web of Science、中国知网、万方、维普数据库以"中药"、"溃疡性结肠炎"等为检索词,检索并筛选相关文献,以临床有效率及不良反应为结局指标,采用Revman 5.4进行Meta分析。 结果: 本次研究共检索文献2 124篇,最终纳入117篇;Meta分析发现,美沙拉嗪联合中药组方口服(OR=3.49,95% CI[2.75,4.43])或灌肠(OR=4.42,95% CI[3.56,5.48])治疗均能提高临床有效率,且并未增加不良反应的发生风险(OR=0.55,95% CI[0.28,1.06];OR=0.39,95% CI[0.26,0.58]);柳氮磺吡啶联合中药组方口服(OR=5.95,95% CI[3.76,9.40])或灌肠(OR=3.75,95% CI[2.80,5.01])治疗同样可提高临床有效率,不良反应的风险并未因中药组方的使用而增加(OR=0.33,95% CI[0.05,2.07];OR=0.27,95% CI[0.01,5.66])。 结论: 在美沙拉嗪/柳氮磺吡啶的基础上联合中药组方口服或灌肠治疗能有效提高溃疡性结肠炎的治愈率,且并未增加不良反应的发生风险,但中药组方联合治疗溃疡性结肠炎仍需高质量的研究。 相似文献
5.
Background: Psoriasis vulgaris is a chronic skin condition affecting patients’ quality of life. Long-term use of conventional therapy increases risk of unwanted side effects. Compound glycyrrhizin in conjunction with conventional therapy has been used in clinical practice, but the evidence for such practice has not been evaluated systematically. Objective: This review aims to evaluate the efficacy and safety of compound glycyrrhizin in combination with conventional therapy for psoriasis vulgaris. Methods: PubMed, Excerpta Medica dataBASE (Embase), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Central Register of Controlled Trials, Allied and Complementary Medicine Database (AMED), CiNii, Chinese Biomedical Literature, China National Knowledge Infrastructure, Chinese Scientific Journals Full Text Database and Wanfang Data were searched from their respective inceptions to July 2015. Randomized controlled trials comparing compound glycyrrhizin plus conventional therapy to conventional therapy alone for psoriasis vulgaris were included. Data analysis was performed using Review Manager 5.3. Results: Eleven randomized controlled trials were included in this review. Meta-analysis of the 11 randomized controlled trials indicated that the addition of compound glycyrrhizin increased the number of patients achieving Psoriasis Area and Severity Index (PASI) 60 (RR: 1.30 [1.21, 1.40], I2 = 6%), when compared with conventional therapy alone. Comparable numbers of patients experienced adverse events in the two groups. Conclusions: Compound glycyrrhizin in conjunction with conventional therapy enhances clinical response, and compound glycyrrhizin as add-on therapy does not appear to pose any additional risk in the treatment of psoriasis vulgaris. However, the findings should be interpreted with caution of methodological flaws in the included studies. PROSPERO registration number: CRD42015027763. 相似文献
6.
ABSTRACTBackground: Lorcaserin is a novel, selective 5-hydroxytryptamine 2C serotonin receptor agonist, approved for the treatment of obesity. Several phase 3 randomized controlled trials (RCTs) trials have shown a significant reduction in body weight with lorcaserin. Research design and methods: We systematically searched the database of PubMed, Embase, The Cochrane Library and ClinicalTrials.gov up to 31 July 2019 and retrieved all the studies conducted with lorcaserin for ≥1 year that have explicitly reported the efficacy and safety outcomes versus placebo. Subsequently, we studied the effect of lorcaserin on weight reduction, FDA-defined valvulopathy, depression and suicidal risks in RCTs. Results: The meta-analysis of four RCTs (N = 16,856) demonstrated a significant decrease in body weight (mean ? ?3.076 Kg; 95% CI, ?3.49 to ?2.66; P < 0.00001), compared to placebo. No significant difference in FDA-defined valvulopathy (RR 1.20; 95% CI, 0.89 to 1.63; P = 0.24), depression (RR 1.07; 95% CI, 0.80 to 1.43; P = 0.67) or suicidal risk (RR 1.43; 95% CI, 0.96 to 2.15; P = 0.08) has been observed with lorcaserin compared to placebo. Conclusions: Lorcaserin reduces body weight modestly, with no obvious serious adverse side effects. The common adverse events noted with lorcaserin include nausea, dizziness, and transient headache. 相似文献
7.
Multiple sclerosis (MS) is a complex inflammatory, degenerative, and demyelinating disease of the central nervous system. Although treatments exist, MS cannot be cured by available drugs, which primarily target neuroinflammation. Thus, it is feasible that a well concerted polypharmacological approach able to act at multiple points within the intricate network of inflammation, neurodegeneration, and demyelination/remyelination pathways would succeed where other drugs have failed. Starting from reported beneficial effects of α-linolenic acid (ALA) and valproic acid (VPA) in MS, and by applying a rational strategy, we developed a small set of codrugs obtained by conjugating VPA and ALA through proper linkers. A cellular profiling identified 1 as a polypharmacological tool able not only to modulate microglia polarization, but also to counteract neurodegeneration and demyelination and induce oligodendrocyte precursor cell differentiation, by acting on multiple biochemical and epigenetic pathways. 相似文献
8.
The tumor necrosis factor-α (TNF-α)-inducing protein (tipα) gene family, comprising Helicobacter pylori membrane protein 1 (hp-mp1) and tipα, has been identified as a tumor promoter, contributing to H. pylori carcinogenicity. Tipα is a unique H. pylori protein with no similarity to other pathogenicity factors, CagA, VacA, and urease. American H. pylori strains cause human gastric cancer, whereas African strains cause gastritis. The presence of Tipα in American and Euro-Asian strains suggests its involvement in human gastric cancer development. Tipα secreted from H. pylori stimulates gastric cancer development by inducing TNF-α, an endogenous tumor promoter, through its interaction with nucleolin, a Tipα receptor. This review covers the following topics: tumor-promoting activity of the Tipα family members HP-MP1 and Tipα, the mechanism underlying this activity of Tipα via binding to the cell-surface receptor, nucleolin, the crystal structure of rdel-Tipα and N-terminal truncated rTipα, inhibition of Tipα-associated gastric carcinogenesis by tumor suppressor B-cell translocation gene 2 ( BTG2/TIS21), and new strategies to prevent and treat gastric cancer. Thus, Tipα contributes to the carcinogenicity of H. pylori by a mechanism that differs from those of CagA and VacA. 相似文献
9.
11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity is implicated as a moderator of the progression of multiple diseases and disorders in medicine and is actively subject to investigation as a therapeutic target. Here we summarize the mechanisms of the enzyme and detail the novel agents under investigation. Such agents modulate peripheral cortisol and cortisone levels in hypertension, type 2 diabetes, metabolic disorders, and Alzheimer’s disease models, but there is mixed evidence for transduction into symptom management. There is inchoate evidence that 11β-HSD1 modulators may be useful pharmacotherapies for clinical improvement in psychiatry and neurology; however, more research is required. 相似文献
10.
Overactivation of Wnt/β-catenin pathway due to dysfunction of retinoid-related orphan receptor α (RORα) is related to cancer development and progression. Diallyl disulfide (DADS), an active component of garlic, has been reported in our previous study for upregulation of RORα expression in gastric cancer (GC) cells. It remains to be elucidated the role and mechanism of RORα in DADS against GC. This study revealed that DADS treatment resulted in reduced expression levels of Wnt1, β-catenin, TCF-4, intranuclear β-catenin and p-β-catenin in GC cells, concomitant with the compromised expression of β-catenin target genes (Axin, c-Jun, and c-Myc). RORα overexpression augmented DADS-induced downregulation of Wnt1/β-catenin pathway, G2/M phase arrest, and cell growth inhibition in vitro and in vivo. Contrarily, knockdown of RORα attenuated these effects of DADS. Interestingly, DADS induced an increase in the binding of RORα to β-catenin, which may lead to reduction of β-catenin phosphorylation and nuclear translocation. This interplay modulated by DADS may affect β-catenin target gene expression for that the opposite results were observed in DADS-treated RORα knockdown and overexpression cells. DADS caused a decrease in vimentin, snail and MMP-9, as well as an increase in E-cadherin and TIMP3 expression, which restricted epithelial–mesenchymal transition (EMT), migration, and invasion. The aforementioned effects of DADS were weakened simultaneously when the suppression of DADS on the Wnt1/β-catenin pathway was resisted by knockdown of RORα. In contrast, overexpression of RORα enhanced the effects of DADS. Therefore, RORα-mediated downregulation of Wnt1/β-catenin pathway could undertake an important role in anticancer activity of DADS against GC cell proliferation, EMT, migration, and invasion. 相似文献
12.
In this work, series of pH-responsive hydrogels (FMA1–FMA9) were synthesized, characterized, and evaluated as potential carrier for oral delivery of an antiviral drug, acyclovir (ACV). Different proportions of β-cyclodextrin (β-CD), chitosan (CS), methacrylic acid (MAA) and N′ N′-methylenebis-acrylamide (MBA) were used to fabricate hydrogels via free radical polymerization technique. Fourier transform infrared spectroscopy confirmed fabrication of new polymeric network, with successful incorporation of ACV. Scanning electron microscopy (SEM) indicated presence of slightly porous structure. Thermal analysis indicated enhanced thermal stability of polymeric network. Swelling studies were carried out at 37 °C in simulated gastric and intestinal fluids. The drug release data was found best fit to zero-order kinetics. The preliminary investigation of developed hydrogels showed a pH-dependent swelling behavior and drug release pattern. Acute oral toxicity study indicated no significant changes in behavioral, clinical, or histopathological parameters of Wistar rats. Pharmacokinetic study indicated that developed hydrogels caused a significant increase in oral bioavailability of ACV in rabbit plasma as compared to oral suspension when both were administered at a single oral dose of 20 mg kg −1 bodyweight. Hence, developed hydrogel formulation could be used as potential candidate for controlled drug delivery of an antiviral drug acyclovir. 相似文献
13.
We report the discovery of two compounds, TKD150 and TKD152, that promote the aggregation of α-synuclein (aSN) using a real-time quaking-induced conversion (RT-QuIC) assay to detect abnormal aSN. By utilizing a Pd-catalyzed C–H arylation of benzoxazole with iodoarenes and implementing a planar conformation to the design, we successfully identified TKD150 and TKD152 as proaggregators for aSN. In comparison to a previously reported proaggregator, PA86, the two identified compounds were able to promote aggregation of aSN at twice the rate. Application of TKD150 and TKD152 to the RT-QuIC assay will shorten the inherent lag time and may allow wider use of this assay in clinical settings for the diagnosis of α-synucleinopathy-related diseases. 相似文献
14.
Given the application of αB-VxXXIVA-conotoxin (αB-CTX) in analgesics and cancer chemotherapeutics, and its threat to humans, it is urgent to develop a rapid, effective and accurate method for the analysis and detection of αB-CTX in real shellfish and medicine drug samples. In the present study, two different immunochromatographic strips were established for αB-CTX detection, based on the monoclonal antibody 5E4 against αB-CTX, and the visual limits of detection (vLOD) for the colloidal gold nanoparticles-based strip (AuNPs-based strip) and nanoflowers-based strip (AuNFs-based strip) were 4 μg/mL and 1.5 μg/mL, respectively. The developed AuNPs-/AuNFs-based strips have good specificity and accuracy, and the detection results were analyzed in less than 10 min, without using an instrument. In view of the excellent repeatability and usability, the established methods could be applied to detect and analyze the content of αB-CTX in real samples. 相似文献
15.
目的:比较使用肾素-血管紧张素(renin-angiotensin,RAS)阻滞剂与钙通道阻滞剂(calcium channel blockers,CCBs)长期治疗高血压合并糖尿病患者的疗效和安全性。方法:通过检索PubMed、Cochrane Central Register of Controlled Trials、万方数据库,收集公开发表的关于RAS阻滞剂与CCBs长期治疗高血压合并糖尿病的疗效和安全性的随机对照试验(randomized controlled trial,RCT)。根据改良版的Jadad量表对符合纳入标准的研究进行质量评价,采用Stata 12.0软件进行Meta分析。结果:共纳入12 RCTs,包括14 564人。Meta分析显示:在长期治疗过程中,RAS阻滞剂治疗组和CCBs治疗组的全因死亡率、心血管事件死亡率以及心血管事件、心肌梗死、心绞痛的发生率均没有明显差异。与CCBs相比,RAS阻滞剂可显著降低终末期肾病[RR=0.82,95% CI(0.68,0.92), P=0.031]和心衰[RR=0.77,95% CI(0.68,0.86), P<0.001]的发生率,但会增加卒中的发生风险[RR=1.15,95% CI(1.00,1.33), P=0.046]。RAS阻滞剂治疗后更易发生干咳[RR=2.1,95% CI(1.00,4.41), P=0.046],CCBs治疗过程中更易出现水肿[RR=0.48,95% CI(0.25,0.94), P=0.032]。结论:在高血压合并糖尿病患者的长期治疗中,RAS阻滞剂治疗发生卒中的风险大于CCBs,CCBs长期治疗发生心衰的风险明显大于RAS阻滞剂。RAS阻滞剂能延缓肾脏疾病的进展。 相似文献
16.
α-Ketoacids (KAs) are widely used in chronic kidney disease (CKD), but their efficacy is not clear. Therefore, we conducted a systematic review of the benefits of KAs. Two reviewers independently searched MEDLINE, EMBASE, the Cochrane library (http://www.cochrane.org), CNKI, and Wan Fang databases from inception to May 31, 2016 for randomized controlled trials (RCTs) comparing KAs plus low protein diet (LPD) with LPD only on CKD patients. Statistical analyses were performed using both a random effects model and a fixed effects model with Rev Man 5.3, followed by sensitivity analysis. We identified 21 randomized controlled trials that enrolled a total of 1448 patients. 726 had received LPD plus KAs and 722 had received only LPD. Compared with simply using of LPD, combining with KAs could decrease serum creatinine (95% CI, 0.46–0.96; P<0.00001), serum cholesterol (95% CI, 0.24–0.77; P = 0.02), serum LDL cholesterol (95% CI, 0.12–0.54; P = 0.31), and serum triglyceride (95% CI, 0.28–0.83; P = 0.02) while increasing serum HDL cholesterol (95% CI, -1.73–0.07; P<0.00001). Likewise, a decrease in P 3– (95% CI, 0.90–1.26; P<0.00001) and PTH (95% CI, 0.70–1.21; P = 0.007) were observed. No hypercalcemia and other ARD or toxicity was reported, which indicated the safety of KAs. Nevertheless, the studies were pooled with considerable heterogeneity. In patients with CKD, there was low-quality evidence suggesting that KAs may perform an additive effect on the improvement of renal function, lipid profile, as well as the correction of calcium-phosphate metabolism disorders. On account of the considerable heterogeneity of the meta-analysis and the costly price and adherence of KAs administration, KAs’ roles in the management of mild or moderate CKD patients may need more RCTs of large scale and high quality to confirm. 相似文献
17.
Psychostimulant dependence is characterized by dopamine deficit, which could be reversed with indirect dopamine agonists (IDAs). A systematic review and meta-analysis of randomized, parallel-group, placebo-controlled clinical trials assessing the efficacy of IDAs in psychostimulant-dependent individuals were conducted. The study outcomes were psychostimulant abstinence, assessed by means of urinalysis, and retention in treatment. Risk of bias was determined using a Cochrane Collaboration instrument. Twenty-nine studies fulfilled the inclusion criteria, involving 2,467 participants. Compared with placebo, IDAs increased psychostimulant abstinence (standardized mean difference = 0.20; 95% confidence interval, 0.06-0.35; p = .005) but did not increase retention in treatment. Efficacy was larger in comorbid heroin-dependent individuals and was positively related with treatment length. No study was considered fully free of bias. IDAs appear to be efficacious for reducing psychostimulant use but did not improve retention. Efforts should be undertaken to reduce the risk of bias of clinical trials with psychostimulant-dependent individuals. 相似文献
19.
It has been well established that neurogenic inflammation is one of the major pathological processes underlying inflammatory pain, but there are few effective anti‐inflammatory drugs to alleviate such pain. The present study shows that minocycline, a widely used glial activation inhibitor, is effective in reducing neurogenic inflammation. Patch‐clamp recordings showed that small sized dorsal root ganglion (DRG) neurons were dramatically excited following intradermal capsaicin injection in the rat hind paw, evidenced by decreased rheobase and membrane threshold. Pretreatment with minocycline (30 mg/kg for 1 day, intraperitoneal injection) blocked the increased neuronal excitability. Western blot and immunostaining of DRG revealed the activation of satellite glial cells (SGCs) following capsaicin injection. The up‐regulation of glial fibrillary acidic protein (GFAP) was significantly inhibited by minocycline pre‐administration. Measurement of tumor necrosis factor α (TNF‐ α) and its receptor, TNF‐ α receptor 1 (TNFR1), showed that minocycline mainly blocked the up‐regulation of TNF‐ α in SGCs and TNFR1s in neurons following capsaicin injection. The pivotal role of TNF‐ α in neurogenic inflammation was further supported by the findings that incubation DRG with TNF‐ α mimicked the increased excitability of DRG neurons induced by capsaicin injection, and that TNF‐ α application enhanced cutaneous vasodilation in the hind paws induced by antidromic electrical stimulation of dorsal roots. Based on these results, we propose that minocycline is a potential therapeutic drug that can reduce neuronal excitability and neurogenic inflammation by working on SGCs to inhibit the expression of TNF‐ α. 相似文献
20.
Approximately one-third of humankind is chronically exposed to the carcinogenic aflatoxin M 1 contained in milk. As β-cyclodextrin is frequently used in the food industry, its effect on aflatoxin M 1 concentration was investigated during cholesterol removal from milk due to the similarity among the physicochemical properties of aflatoxin M 1 and cholesterol. Moreover, the elimination of cholesterol using β-cyclodextrin has been successfully applied in many studies without any substantial effect on the quality of the treated milk. Therefore, milk samples were spiked with aflatoxin M 1 within the range from 0.20 to 2.00 µg/kg, and cholesterol removal was carried out by 2.0% ( w/w) β-cyclodextrin addition, as this concentration is enough for the sufficient removal of cholesterol. It was found that the mean cholesterol concentration decreased by 92.3%, while the aflatoxin M 1 concentration decreased to 0.53 ± 0.04 µg/kg, i.e., by 39.1% after treatment (n = 2). This mitigation procedure itself is easy and inexpensive and thus is fully applicable with a high potential for complete decontamination of aflatoxin M 1 milk. This method will therefore considerably improve the food safety issues associated with aflatoxin M 1 presence in milk and dairy products. 相似文献
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