Silibinin sensitizes chemo-resistant breast cancer cells to chemotherapy

Context: Multiple drug resistance is the major obstacle to conventional chemotherapy. Silibinin, a nontoxic naturally occurring compound, has anticancer activity and can increase the cytotoxic effects of chemotherapy in various cancer models.

Objective: To evaluate the effects of silibinin on enhancing the sensitivity of chemo-resistant human breast cell lines to doxorubicin (DOX) and paclitaxel (PAC).

Materials and methods: The cells were treated with silibinin (at 50 to 600?μM concentrations) and/or chemo drugs for 24 and 48?h, then cell viability and changes in oncogenic proteins were determined by MTT assay and Western blotting/RT-PCR, respectively. Flow cytometry was used to study apoptosis in the cells receiving different treatments. The antitumorigenic effects of silibinin (at 200 to 400?μM concentration) were evaluated by mammosphere assay.

Results: Silibinin exerted significant growth inhibitory effects with IC₅₀ ranging from 200 to 570?μM in different cell lines. Treatment of DOX-resistant MDA-MB-435 cells with silibinin at 200?μM reduced DOX IC₅₀ from 71 to 10?μg/mL and significantly suppressed the key oncogenic pathways including STAT3, AKT, and ERK in these cells. Interestingly treatment of DOX-resistant MDA-MB-435 cells with silibinin at 400?μM concentration for 48?h induced a 50% decrease in the numbers of colonies as compared with DMSO-treated cells. Treatment of PAC-resistant MCF-7 cells with silibinin at 400?μM concentration generated synergistic effects when it was used in combination with PAC at 250?nM concentration (CI?=?0.81).

Conclusion: Silibinin sensitizes chemo-resistant cells to chemotherapeutic agents and can be useful in treating breast cancers.     

Relaxant effect of Curcuma longa on rat tracheal smooth muscle and its possible mechanisms

Context: Turmeric is a spice obtained from the root of Curcuma longa L. (Zingiberaceae) with anti-aging, anticancer, anti-Alzheimer’s disease, antioxidant and other medicinal properties.

Objective: The relaxant effect of C. longa on rat tracheal smooth muscle and its possible mechanisms were investigated in this study.

Materials and methods: The relaxant effects of four cumulative concentrations of hydro-ethanol extract of C. longa (6.25, 12.5, 25, 50?mg/mL) were studied on tracheal smooth muscle precontracted by methacholine or KCl in non-incubated or incubated with different substances including propranolol, diltiazem, L-NAME, glibenclamide, atropine, chlorpheniramine, indomethacin and papaverine. The duration of the study was 84?days.

Results: In non-incubated tracheal smooth muscle, the extract of C. longa showed significant concentration-dependent relaxant effects (p?C. longa and theophylline in both methacholine and KCl-induced contraction conditions. In tissues incubated with propranolol, diltiazem, L-NAME and glibenclamide on methacholine-induced contraction and in tissues incubated with atropine, chlorpheniramine, indomethacin and papaverine on KCl-induced contraction, the extract also showed significant concentration-dependent relaxant effects (p?50 values of C. longa between non-incubated (16.22?±?0.62) and incubated tissues (atropine: 13.03?±?0.55, chlorpheniramine: 12.94?±?0.68, indomethacin: 14.80?±?0.57 and papaverine: 16.16?±?1.42) were not significantly different.

Conclusions: Tracheal smooth muscle relaxant effects of C. longa, were comparable to those of theophylline, which could be due to the presence of methylxanthines or its possible interaction with non-adrenergic non-cholinergic nervous system.     

Treatment of Visceral Pain Associated with Irritable Bowel Syndrome using Acupuncture: Mechanism of Action

Irritable bowel syndrome (IBS) is a relatively common condition characterized by abdominal pain, among other symptoms, that significantly impacts the quality of life of IBS patients. Therapeutic treatment of IBS results in limited success, and the focus is placed on relieving patients of some of the symptoms, visceral pain in particular. Acupuncture is commonly used as a treatment modality of choice. However, the debate on whether acupuncture can be effectively used for this purpose is ongoing. In this work, we critically review the available literature to establish a potential mechanism of action in treating visceral pain in IBS using acupuncture. The sources used are Google Scholar, EBSCO, Cochrane Library and PubMed as well as Chinese database sources. The keywords used in the literature search are “acupuncture,” “IBS,” “Irritable Bowel Syndrome,” and “visceral pain.” We find that the literature strongly indicates that acupuncture, by stimulating points located on the dermatomes proximal to the spinal level of the area where the sympathetic outflow of the particular gut area affected by the pain is, can interfere with the efferent signal that transports information about the noxious stimuli and interrupt the “connectivity” between the gut and brain, and as a final result, reduce or stop IBS pain. Our findings justify that clinical trials are conducted to test the utility of acupuncture in treating abdominal visceral pain in IBS.     

The expression of GAS5, THRIL,and RMRP lncRNAs is increased in T cells of patients with rheumatoid arthritis

Clinical Rheumatology - Long non-coding RNAs (lncRNAs) comprise a large and diverse group of non-coding RNAs (ncRNAs) with important regulatory roles in various biological processes, including the...     

Intraspecific variation within Phlebotomus sergenti Parrot (1917) (Diptera: Psychodidae) based on mtDNA sequences in Islamic Republic of Iran

An intraspecific study on the morphological and molecular characteristics of Phlebotomus sergenti s.l., the main vector of Leishmania tropica, was performed on 28 Iranian populations from 11 provinces and a few samples from Greece, Morocco, Lebanon, Turkey, Pakistan, and Syria. Three morphotypes were identified as A, B and C, with some intermediate forms in the samples under investigation. Based on the number of setae and the width of basal lobe of coxite, differences between A and B morphotypes were highly significant. Excluding one unusual haplotype, sequence analysis of approximately 439 bp of mtDNA (a fragment of cytochrome B gene, tRNA for serine gene, and a fragment of NADH1 gene) revealed a 6-7% genetic distance within the Iranian populations and among the specimens of other countries. Neighbor-Joining (NJ) analysis confirmed the existence of three main groups within our samples. Although there was no consistency between morphotypes and genotypes, but an interrelationship was found between morphometry and morphotypes. Morphotype A, which was considered as P. sergenti sergenti, was the most prevalent in collection sites. Morphotype B, which was identified as Phlebotomus sergenti similis, is the first record of this subspecies in Iran, and was found to be sympatric with other morphotypes. Morphotype C had an elongated style in comparison with P. sergenti sergenti. Molecular database showed three main genetic structures. This is the first combined morphological and molecular studies on P. sergenti s.l. in Iran.     

Pharmacological effects of Zataria multiflora Boiss L. and its constituents focus on their anti‐inflammatory,antioxidant, and immunomodulatory effects

Zataria multiflora Boiss (Z. multiflora) belongs to the Lamiaceae family is used traditionally for culinary and medicinal purposes. Different pharmacological effects have been described for the plant including; bronchodilation, vasodilation, and effect on lung inflammation. The plant is also used as a remedy against cough in the traditional medicine. In this article, ‘pharmacological effects of Z. multiflora and its constituents focusing on their anti‐inflammatory, antioxidant, and immunomodulatory properties were reviewed’ by searching various databases until ‘June’ 2016. The anti‐inflammatory effects of the plant such as decreased total white blood cell, neutrophils, and eosinophils counts were demonstrated. The sprotective effects of Z. multiflora on serum levels of phospholipase A2 and total protein were showed. In addition, constituents of the plant, such as flavonoids and carvacrol, also showed anti‐inflammatory effects. Z. multiflora also reduced oxidative stress by scavenging free radicals and can be used in the therapy of oxidative damage. Decreased level of malondialdehyde and protective effects of Z. multiflora on serum levels of nitric oxide were also shown. Improvement of the serum levels of IgE, reduction in pro‐inflammatory cytokine (IL‐4, TGF‐β, and IL‐17), and increased anti‐inflammatory cytokines (IFN‐γ and FOXP3) were shown for Z. multiflora and its constituents, carvacrol and thymol. These results indicated that carvacrol and thymol could be used for treatment of inflammatory diseases as new anti‐inflammatory agents. Therefore, Z. multiflora showed anti‐inflammatory, antioxidant, and immunomodulatory effects which could be used for treatment of inflammatory and immune dysregulation diseases or disorders associated with increased oxidative stress.     

Energy dispersive x-ray analysis of corrosion products in nondiscolored dentin and a dye-extraction study of Class 2 composite restorations following amalgam removal

Objective: To evaluate the effect of corrosion products on the microleakage of composite placed adjacent to nondiscolored dentin after amalgam removal. Method and Materials: Sixty Class 2 cavities were prepared on extracted premolars, which were divided into four equal groups according to the manner in which they were restored: group 1, light-cured packable composite (Elite LS) to establish a microleakage baseline; group 2, a high-copper amalgam (World Work) previously stored in 37°C normal saline for 6 months to create amalgam corrosion products; group 3, identical to group 2, but the amalgam was later replaced with composite, leaving the cavity walls intact; and group 4, identical to group 3 except the cavity walls were extended 0.5 mm after amalgam removal prior to insertion of the composite. Groups 1, 3, and 4 were kept in a 37°C normal saline for 1 week. Ten specimens from each of these three groups were randomly selected for dye-extraction testing, while dentin elemental microanalysis of five specimens from all four experimental groups was also conducted. Data were analyzed using ANOVA and the Tukey tests (α = .05). Results: Corrosion products were not detected in group 4, and no statistically significant difference (P > .05) in microleakage was found between this group and group 1. The highest dye absorbance was associated with group 3 (P < .05). Conclusion: After amalgam removal, a 0.5-mm extension of the cavity walls could improve the dentinal marginal seal to replicate that of an initial composite restoration. (Quintessence Int 2012;43:325?332).