Cytotoxicity of curcumin against CD44± prostate cancer cells: Roles of miR-383 and miR-708.

Objective: Cancer stem cells (CSCs) remaining in the tumor tissues after applying treatments may cause recurrence or metastasis of prostate cancer (PC). Curcumin has the promising potential to target CSCs. Here, we aim to evaluate the cytotoxic effects of curcumin on the expression of miR-383-5p and miR-708-5p and their target genes in CD44+ CSCs and CD44- non-CSCs isolated from the PC3 prostate cancer cell line. Materials and Methods: We used MTT assay to determine the optimal cytotoxic dose of curcumin on CD44± PC cells. Then, we assessed nuclear morphological changes using DAPi staining. We used Annexin V-FITC/PI to quantify apoptotic cell death. qRT-PCR was also used to detect miRNA and gene expression levels after curcumin treatment. Results: Curcumin significantly enhanced the apoptosis in both CD44- and CD44+ PC cells in a dose-dependent manner (p < 0.05). The cytotoxicity of curcumin against CD44- cells (IC50 40.30±2.32 µM) was found to be greater than that against CD44+ cells (IC50 83.31±2.91 µM). Also, curcumin promoted miR-383-5p and miR-708-5p overexpression while downregulating their target genes LDHA, PRDX3, and RAP1B, LSD1, respectively. Conclusion: Our findings indicate that curcumin, by promoting the expression of tumor suppressors, miR-383-5p and miR-708-5p, and inhibiting their target genes, induced its cytotoxicity against CD44± PC cells. We trust that curcumin could be established as a promising adjuvant therapy to current PC treatment options following more research in clinical settings.

Protective effect of saponin on sperm DNA fragmentation of mice treated with cyclophosphamide.

Cyclophosphamide (CP) is a common chemotherapy drug with the testicular damage. The aim of this study was to investigate the effect of saponin (SP) on the toxicity of CP in the male reproductive system. Following an experimental pilot study for determining SP dose, 40 male mice (32 ± 3 g) were divided into five groups (n = 8): control, sham (normal saline 0.2 ml/day), CP (15 mg/kg/week, intraperitoneally), SP (2.5 mg/kg/day, intraperitoneally) and saponin group with cyclophosphamide (SP + CP). After treatment, the left testes were removed for the measurement of malonedialdehyde (MDA) and total antioxidant capacity (TAC) levels, and sperm DNA fragmentation was assessed by SDFA kit. In the CP group, a significant decrease in motility, viability, count, normal morphology and DNA fragmentation of spermatozoa and TAC was observed, while in MDA level, a significant increase was observed compared with the control group (p < 0.05). Attenuated sperm parameters in CP group improved significantly in SP + CP group (p < 0.05). According to the findings of this study, SP was able to alter the reproductive toxicity of CP in NMRI mice and increase the antioxidant capacity of the testis.

Protection of CCl4-induced hepatic and renal damage by linalool.

The aim of the current study is to determine the protective and therapeutic effects of linalool against carbon tetrachloride (CCl4)-induced hepatoxicity and nephrotoxicity. Six-week-old male Wistar rats were divided into five groups: Control group (a regular diet); CCl4 group (1 ml/kg dissolved in olive oil, intraperitoneally at 14th day); pretreatment group (25 mg/kg linalool daily + CCl4 14thday); post-treatment group (25 mg/kg linalool 2, 6, 24, and 48 h after the injection of CCl4 at 14th day); and linalool group (25 mg/kg linalool daily, orally). All animals were sacrificed, tissue and blood samples were collected to analysis. Administration of CCl4 resulted in a marked increase in hepatic (aspartate aminotransferase, alanine transaminase, and alkaline phosphatase) and renal (blood urea nitrogen and creatinine) markers. Also, CCl4 resulted in pathological damages, a significant increase in the concentration of malondialdehyde , tumor necrosis factor-alpha, and Interleukin 6 , expression of nuclear factor kappa-light-chain-enhancer of activated B cells and a significant decrease in the levels of serum total protein, serum albumin, and antioxidants. However, in pretreatment and post treatment groups, linalool significantly inhibited CCl4- induced hepatic and nephric damages. These results demonstrate that linalool has protective and therapeutic effects in an in vitro model of CCL4-induced hepatic and nephric damage, proposing linalool as a potential therapeutic agent against chemical and drug induced hepatotoxicity and nephrotoxicity.

Treatment of cartilage defects by Low-intensity pulsed ultrasound in a sheep model.

Aim of this study was to evaluate effects of Low-intensity pulsed ultrasound on repair of articular cartilage defects. Low-intensity pulsed ultrasound (Lipus) can induce the differentiation and activation of chondrocytes. This study was designed to evaluate the effect of Lipus on articular cartilage defects in a sheep. Eight sheep were divided in to two groups. The animals received bilateraly, articular cartilage defects 4 mm in diameter and 2 mm in deep on the patellar groove and experimental groups were treated with intensity 200 mW/cm2, 20 min/day with low-intensity pulsed ultrasound for 2 month. Then both knee joints underwent surgery for remove of formed tissue sample from defects.The samples were evaluated by Quantitative real-time polymerase chain reaction (qRT-PCR), Safranin-o staining, Immunofluorescence Staining and Morphological characterization. The best and worst sample per group according to Macroscopic and micriscopic scoring were icentified. The results showed that the operated groups with-Lipus-treatment and without-Lipus treatment had considered statistically significant. Gross photography revealed that the defects in experimental groups were filled with proliferative tissue, while in control groups, a thin layer of proliferative tissue was formed in defects. qRT-PCR results showed the expression of coll2, sox9, aggrecan and Osteocalcin in experimental groups. Intense safranin-O staining show the formation cartilage tissue in ultrasound treated group, while loose safranin-o-staining were observed at the control groups. Immunofluorescence staining showed the type 2 Collagen protein expression. We suggest that low-intensity pulsed ultrasound provide the mechanistic basis force for articular cartilage repair and effective treatment modality for improving of articular cartilage defects.

The protective effect of cinnamon and ginger hydro-alcoholic extract on carbon tetrachloride-induced testicular damage in rats.

Sexual dysfunction of men is one of the most serious problems in human society. This study aimed to evaluate the protective effect of cinnamon and ginger extract on testicular damages induced by carbon tetrachloride (CCl4). Thirty-six male Wistar rats were randomly divided into 6 groups (n = 6): 1. Normal control; 2. Carbon tetrachloride (CCl4); 3. CCl4 + Cinnamon; 4. CCl4 + Ginger; 5. CCl4 + Cinnamon and Ginger; and 6. Cinnamon + Ginger. CCl4 (1 ml/kg) was injected intraperitoneally on the 14th day, and cinnamon (50 mg/kg, orally) and ginger (250 mg/kg, orally) were administered daily for 14 days. Fifty hours after the CCl4 injection, the testicles and epididymis were separated and examined as to histological alterations and oxidative stress markers. CCl4 significantly increased malondialdehyde level and decreased total antioxidant capacity when compared to the normal control group (p < .05). In addition, degenerative alterations in the testicular and epididymal tissue were observed in CCl4 group. The pre-treatment with ginger and cinnamon extract significantly improved these parameters when compared to the CCl4 group (p < .05). The results of this study indicated that co-treatment of ginger and cinnamon reduces the damages induced by CCl4 in testicular tissue by increasing antioxidant capacity and reducing lipid peroxidation.

A variation of Musculocutaneous nerve without piercing the coracobrachialis muscle while communicating to the median nerve: A case report and literature review.

INTRODUCTION: Anatomical variations of the peripheral nervous system may have not any clinical signs and symptoms. One of these variations belongs to the Musculocutaneous nerve. However, a good knowledge of nerve pathways and their variations is very important for surgeons in post-traumatic evaluations, exploratory interventions, and/or administration of neuromuscular blocks in axillary region in order to surgical therapies. PRESENTATION OF CASE: This report describes a case of variation of the musculocutaneous nerve which was observed in an old Iranian male cadaver during routine educational dissection (Fig. 1). DISCUSSION AND CONCLUSION: Anatomically, in the axilla region, the Musculocutaneous nerve is originated of the lateral cord of brachial plexus, then, by piercing the coracobrachialis muscle arrives enters to anterior compartment of the arm. But, in the present report, we observed that the Musculocutaneous nerve without piercing the coracobrachialis muscle has arrived in the left arm, then communicated to the Median nerve. To exploratory interventions of the arms for peripheral nerve repair and surgical therapies, a good knowledge of nerve pathways helps to surgeons for preventing possible mistakes during surgery.