Exploration of the photothermal role of curcumin-loaded targeted carbon nanotubes as a potential therapy for melanoma cancer.

In this research, the hydrophilic structure of multi-walled carbon nanotubes (MWCNTs) was modified by synthesizing polycitric acid (PCA) and attaching folic acid (FA) to create MWCNT-PCA-FA. This modified nanocomplex was utilized as a carrier for the lipophilic compound curcumin (Cur). Characterization techniques including TGA, TEM, and UV-visible spectrophotometry were used to analyze the nanocomplex. The mechanism of cancer cell death induced by MWCNT-PCA-FA was studied extensively using the MTT assay, colony formation analysis, cell cycle assessment via flow cytometry, and apoptosis studies. Furthermore, we assessed the antitumor efficacy of these targeted nanocomplexes following exposure to laser radiation. The results showed that the nanocomposites and free Cur had significant toxicity on melanoma cancer cells (B16F10 cells) while having minimal impact on normal cells (NHDF cells). This selectivity for cancerous cells demonstrates the potential of these compounds as therapeutic agents. Furthermore, MWCNT-PCA-FA/Cur showed superior cytotoxicity compared to free Cur alone. Colony formation studies confirmed these results. The researchers found that MWCNT-FA-PCA/Cur effectively induced programmed cell death. In photothermal analysis, MWCNT-PCA-FA/Cur combined with laser treatment achieved the highest mortality rate. These promising results suggest that this multifunctional therapeutic nanoplatform holds the potential for combination cancer therapies that utilize various established therapeutic methods.

Sex Differences in Immune Cell Infiltration and Hematuria in SCI-Induced Hemorrhagic Cystitis.

Rats manifest a condition called hemorrhagic cystitis after spinal cord injury (SCI). The mechanism of this condition is unknown, but it is more severe in male rats than in female rats. We assessed the role of sex regarding hemorrhagic cystitis and pathological chronic changes in the bladder. We analyzed the urine of male and female Sprague-Dawley and Fischer 344 rats after experimental spinal cord contusion, including unstained microscopic inspections of the urine, differential white blood cell counts colored by the Wright stain, and total leukocyte counts using fluorescent nuclear stains. We examined bladder histological changes in acute and chronic phases of SCI, using principal component analysis (PCA) and clustered heatmaps of Pearson correlation coefficients to interpret how measured variables correlated with each other. Male rats showed a distinct pattern of macroscopic hematuria after spinal cord injury. They had higher numbers of red blood cells with significantly more leukocytes and neutrophils than female rats, particularly hypersegmented neutrophils. The histological examination of the bladders revealed a distinct line of apoptotic umbrella cells and disrupted bladder vessels early after SCI and progressive pathological changes in multiple bladder layers in the chronic phase. Multivariate analyses indicated immune cell infiltration in the bladder, especially hypersegmented neutrophils, that correlated with red blood cell counts in male rats. Our study highlights a hitherto unreported sex difference of hematuria and pathological changes in males and females' bladders after SCI, suggesting an important role of immune cell infiltration, especially neutrophils, in SCI-induced hemorrhagic cystitis.

Effects of Scrophularia oxysepala Methanolic Extract on Early Stages of Dimethylhydrazine-Induced Colon Carcinoma in Rats: Apoptosis Pathway Approach.

Purpose: Colorectal cancer is one of the most prevalent cancers, worldwide. The present study aimed to examine the effects of Scrophularia oxysepala (SO) methanolic extract on 1,2-dimethylhydrazine (DMH) induced colon cancer model in the Wistar rats. Methods: The animals administered DMH (40 mg/kg/S.C.) biweekly for 2 weeks to induce aberrant crypt foci (ACF). Other groups of animals were given the SO extract (50, 100 and 200 mg/kg/orally once/day) either before or after the DMH treatments. In the end, all animals were killed and at necropsy, the colon samples examined. The ACF, aberrant crypt (AC), crypt multiplicity (CM), caspase 3 protein and apoptosis measurement were performed. Results: The SO extract significantly (P<0.001) decreased the number of AC, ACF, and CM in all pre- and post-treated groups and caused significant increases in caspase 3 and apoptosis as compared to the DMH group. However, post-treated animals showed significantly more effective than pre-treatment groups. Methanolic extract of SO showed a chemopreventive potential, by effectively reducing the number of AC, ACF, and CM and increasing caspase 3 protein and apoptosis. Conclusion: One of the possible mechanisms might be involved in the induction of apoptosis through the caspase 3 mediated pathway.

Protective effect of black mulberry (Morus nigra L) fruit hydroalcoholic extract against testosterone-induced benign prostatic hyperplasia in rats / Efecto protector del extracto hidroalcohólico de las moras (Morus nigra L) en la hiperplasia prostática benigna no inducida por testosterona, en ratas

BACKGROUND: Finding new agents for prevention and/or treatment of benign prostatic hyperplasia (BPH) especially from natural sources is a demanding field. OBJECTIVES: This study aimed to evaluate the effect of black mulberry (BM) (Morus nigra) fruit hydroalcoholic extract on the establishment of BPH in rats. MATERIALS AND METHODS: Forty-nine adult male rats were randomly assigned into 7 equal groups: I: Sham control (SC), a sham surgery was performed. II: positive control (PC), rats were castrated and received testosterone propionate, at 10mg/kg/day S.C. for BPH induction. III: comparative control (CC), BPH was induced and the rats received finasteride at 5mg/kg/day P.O. IV-VII: (T1-T4): BPH was induced and the rats received BM extract at 25, 50, 100 and 200mg/kg/day P.O. for 4 consecutive weeks. RESULTS: Finasteride and/or BM extract especially at the two higher dosages, significantly affected prostate weight, prostatic index, percent of inhibition, serum and prostatic levels of dihydrotestosterone (DHT), serum prostate-specific antigen (PSA), antioxidant parameters of prostatic tissue as well as histopathological and histomorphometric parameters (epithelial thickness and acinar area) of prostate. CONCLUSIONS: BM extract has protective effects against experimentally-induced BPH in rats with regard to histopathological and biochemical parameters which may be related to its antioxidant as well as DHT reducing properties in prostatic tissue

ANTECEDENTES: El hallazgo de nuevos agentes para prevenir y/o tratar la hiperplasia prostática benigna (HBP), procedentes especialmente de fuentes naturales, es un campo exigente. OBJETIVOS: El objetivo de este estudio fue evaluar el efecto del extracto hidroalcohólico de las moras (Morus nigra) sobre el establecimiento de HBP en ratas. MATERIALES Y MÉTODOS: Se asignaron aleatoriamente 49 ratas adultas macho en 7 grupos iguales: I: grupo control (GC), en el que se practicó cirugía de control; II: control positivo (CP), en el que se castró a las ratas y se les administró propionato de testosterona, a una dosis de 10mg/kg/día sc para inducción de BPH. III: control comparativo (CC), en el que se indujo BPH y se administró a las ratas finasterida a una dosis de 5mg/kg/día po; IV-VII: (T1-T4), en el que se indujo BPH y se administró a las ratas extracto de moras a una dosis de 25, 50, 100 y 200mg/kg/día po durante 4 días consecutivos. RESULTADOS: La finasterida y/o el extracto de moras, especialmente en 2 dosis elevadas, afectaron significativamente al peso prostático, al índice prostático, al porcentaje de inhibición, a los niveles séricos y prostáticos de dihidrotestosterona (DHT), al antígeno prostático específico sérico (PSA), a los parámetros antioxidantes del tejido prostático, así como a los parámetros histopatológicos e histomorfométricos (espesor epitelial y área acinar) de la próstata. CONCLUSIONES: El extracto de mora tiene efectos protectores frente a HPB experimentalmente inducido en ratas, con respecto a sus parámetros histopatológicos y bioquímicos, y que pueden guardar relación con sus propiedades antioxidantes y reductoras de DHT en el tejido prostático

Protective effect of black mulberry (Morus nigra L.) fruit hydroalcoholic extract against testosterone-induced benign prostatic hyperplasia in rats.

BACKGROUND: Finding new agents for prevention and/or treatment of benign prostatic hyperplasia (BPH) especially from natural sources is a demanding field. OBJECTIVES: This study aimed to evaluate the effect of black mulberry (BM) (Morus nigra) fruit hydroalcoholic extract on the establishment of BPH in rats. MATERIALS AND METHODS: Forty-nine adult male rats were randomly assigned into 7 equal groups: I: Sham control (SC), a sham surgery was performed. II: positive control (PC), rats were castrated and received testosterone propionate, at 10mg/kg/day S.C. for BPH induction. III: comparative control (CC), BPH was induced and the rats received finasteride at 5mg/kg/day P.O. IV-VII: (T1-T4): BPH was induced and the rats received BM extract at 25, 50, 100 and 200mg/kg/day P.O. for 4 consecutive weeks. RESULTS: Finasteride and/or BM extract especially at the two higher dosages, significantly affected prostate weight, prostatic index, percent of inhibition, serum and prostatic levels of dihydrotestosterone (DHT), serum prostate-specific antigen (PSA), antioxidant parameters of prostatic tissue as well as histopathological and histomorphometric parameters (epithelial thickness and acinar area) of prostate. CONCLUSIONS: BM extract has protective effects against experimentally-induced BPH in rats with regard to histopathological and biochemical parameters which may be related to its antioxidant as well as DHT reducing properties in prostatic tissue.

Green synthesis of gold nanoparticles by using Ferula persica Willd. gum essential oil: production, characterization and in vitro anti-cancer effects.

OBJECTIVES: Synthesizing and characterization of gold nanoparticles (Au NPs) by Ferula persica gum essential oil and investigating in vitro anti-cancer effects. METHODS: Characterization of NPs was performed. Cytotoxicity and apoptosis were determined on cancerous CT26 and non-cancerous Vero cells using MTT assay and acridine orange/ethidium bromide (AO/EB) staining, respectively. Clonogenic assay was also performed. KEY FINDINGS: The absorption peak in UV-visible spectroscopy was at 530 nm. In TEM image, Au NPs were spherical in shape with average size of 37.05 nm (78.6 nm in DLS analysis). Comparison of the FTIR spectrum of the Au NPs with the essential oil revealed the presence of compounds responsible for reducing and capping the gold ions. XRD pattern showed metal crystal structure. Au NPs exerted dose-dependent cytotoxicity with IC50 values of 0.0024 and 0.0307 mg/ml against CT26 and Vero cell lines, respectively. Au NPs induced apoptosis on both cell lines with statistically more intense effect on CT26 cells (P < 0.0001). Colony formation of CT26 and Vero cells was also inhibited in comparison to untreated cells (P < 0.05). CONCLUSIONS: Ferula persica gum can be successfully used for green production of Au NPs. Au NPs show in vitro anti-cancer activity including cytotoxic, apoptotic and antiproliferative effects.

Immunomodulatory effects of Calcitriol in acute spinal cord injury in rats.

Pharmacological therapy options for spinal cord injury (SCI) in acute phase have so far been limited, thus we focused on Calcitriol, FDA-approved biologically active form of vitamin D whose neuroprotective effects are increasingly recognized, to ameliorating damage following acute SCI in rats. Calcitriol (1 µg/kg) treatment for 7 consecutive days after SCI was compared SCI control and Sham control rat groups. Calcitriol-treated group had significantly improved outcome in standard functional recovery evaluation test (BBB) 12 weeks after SCI compared to SCI control, which was confirmed by increased ventral horn motor neurons in Calcitriol-treated group. In addition, proliferation test performed on lymphocytes from spleen and lymph nodes one week after SCI showed that calcitriol injection has a significant regulatory effect on Division Index (DI) in response to MBP stimulation compared to control SCI groups, which was associated with significant reduction in IFN-γ and IL-17A secretion and leukocyte infiltration into injury site. Along with confirmation of immunoregulatory aspects of Calcitriol treatment against myelin antigens in SCI, this study has shown that reducing the extent of progressive tissue loss by Calcitriol therapy in acute phase, could result in better recovery after SCI.

Implications of immunotherapy with high-dose glatiramer acetate in acute phase of spinal cord injury in rats.

Objective: Recently, many researches with different viewpoints have focused on application of immunotherapy agents in treatment of spinal cord injury (SCI) according to neuroprotective results in some neurodegenerative disease. Glatiramer acetate (GA) is the most commonly used drug for Multiple sclerosis (MS) patients that exerts an immunomodulatory effect against Myelin basic protein (MBP) antigen. Materials and methods: High-dose (2mg/kg) treatment of GA for 28 consecutive days after SCI was compared with its low-dose (0.5 mg/kg) treatment, SCI control and Sham control rat groups. Results: High-dose GA group had significantly worsened outcome in standard functional recovery evaluation test (BBB) 12 weeks after SCI compared to SCI control and low-dose GA groups, which was confirmed by augmented spinal cavity volume and reduced ventral horn motor neurons in high-dose GA group; however, there was no significant difference between low-dose GA and control SCI group. In addition, proliferation test performed on lymphocytes from spleen and lymph nodes one week after SCI showed that high-dose GA injection has more significant effect on Division Index (DI) in response to MBP stimulation compared to low-dose GA and control SCI groups, which was associated with significant increase in IFN-γ, IL-4, and IL-17A secretion. Conclusion: Along with confirmation of deleterious aspects of autoimmunity resulting from autoreactive lymphocytes against myelin antigens in SCI, this study has shown that high-dose immunotherapy using GA, especially in acute phase after SCI, overwhelms any neuroprotective effect of adoptive immune system.

Antibacterial effects of gold nanoparticles functionalized with the extracted peptide from Vespa orientalis wasp venom.

The development of novel antimicrobial strategies is necessary because of the escalation of multidrug-resistant pathogens. Recently, antimicrobial peptides and their combination with nanoparticles were regarded as a promising tool to target drug-resistant pathogens. Herein, we evaluated antimicrobial efficacy of a peptide extracted from Vespa orientalis wasp venom and also its conjugation with gold nanoparticles. Nanoparticle conjugation measurement was done by evaluating the absorbance changes of the surface plasmon resonance band of gold nanoparticles at 555 nm. A significant increase in the antibacterial activity against gram negative and positive bacteria was obtained when the extracted peptide conjugated with gold nanoparticles. Finally, the results show that this new peptide-AuNps has the high practical potential for antibacterial activity and may provide an alternative therapy for bacterial infection.

Oxidative stress in opium users after using lead-adulterated opium: The role of genetic polymorphism.

Use of lead-adulterated opium has become one of the major sources of lead poisoning in Iran. This study was designed to assess clinical effects and oxidative stress and its association with GSTM1, GSTT1, NQO1, and ALAD genes polymorphisms and blood lead level (BLL) in lead-adulterated opium users. The oxidative stress status in 192 opium users with lead poisoning symptoms measured and compared with 102 healthy individuals. Gluthatione S-transferase (GST)-M1 and -T1 genes deletion, NQO1 rs1800566, and δ-aminolevulinic acid dehydratase (ALAD) rs1800435 polymorphisms were determined using PCR and PCR-RFLP. The relation between the polymorphisms, BLL, and oxidative stress parameters were analysed using multivariate linear regressions. The common symptoms of lead toxicity were gastrointestinal and neurologic complications. Oxidative stress was significantly higher in opium addicts and lipid peroxidation significantly correlated with BLL. There was significant association between ALAD rs1800435 and BLL, and the BLL was significantly lower in the patients with ALAD 1-2 genotype. Use of lead-adulterated opium causes high frequency of lead toxicity symptoms, hematological and biochemical abnormalities, and oxidative stress which are associated with BLL. Route of opioid use and the polymorphism of rs1800435 in ALAD gene are the major determinants of BLL in lead-adulterated opium users.

Cell growth inhibition and apoptosis in breast cancer cells induced by anti-FZD7 scFvs: involvement of bioinformatics-based design of novel epitopes.

BACKGROUND: FZD7 has a critical role as a surface receptor of Wnt/ß-catenin signaling in cancer cells. Suppressing Wnt signaling through blocking FZD7 is shown to decrease cell viability, metastasis and invasion. Bioinformatic methods have been a powerful tool in epitope designing studies. Small size, high affinity and human origin of scFv antibodies have provided unique advantages for these recombinant antibodies. METHODS: Two epitopes from extracellular domain of FZD7 were designed using bioinformatic methods. Specific anti-FZD7 scFvs were selected against these epitopes through panning process. The specificity of the scFvs was assessed by phage ELISA and the ability to bind to FZD7 expressing cell line (MDA-MB-231) was determined by flowcytometry. Antiproliferative and apoptotic effects of the scFvs were evaluated by MTT and Annexin V/PI assays. The effects of selected scFvs on expression level of Surivin, c-Myc and Dvl genes were also evaluated by real-time PCR. RESULTS: Results demonstrated selection of two specific scFvs (scFv-I and scFv-II) with frequencies of 35 and 20%. Both antibodies bound to the corresponding peptides and cell surface receptors as shown by phage ELISA and flowcytometry, respectively. The scFvs inhibited cell growth of MDA-MB-231 cells significantly as compared to untreated cells. Growth inhibition of 58.6 and 53.1% were detected for scFv-I and scFv-II, respectively. No significant growth inhibition was detected for SKBR-3 negative control cells. The scFvs induced apoptotic effects in the MDA-MB-231 treated cells after 48 h, which were 81.6 and 74.9% for scFv-I and scFv-II, respectively. Downregulation of Surivin, c-Myc and Dvl genes were also shown after 48h treatment of cells with either of scFvs (59.3-93.8%). ScFv-I showed significant higher antiproliferative and apoptotic effects than scFv-II. CONCLUSIONS: Bioinformatic methods could effectively select potential epitopes of FZD7 protein and suggest that epitope designing by bioinformatic methods could contribute to the selection of key antigens for cancer immunotherapy. The selected scFvs, especially scFv-I, with high antiproliferative and apoptotic effects could be considered as effective agents for immunotherapy of cancers expressing FZD7 receptor including triple negative breast cancer.

Evaluation of 'green' synthesis and biological activity of gold nanoparticles using Tragopogon dubius leaf extract as an antibacterial agent.

Currently, the use of 'green' synthesised nanoparticles with environmentally friendly properties is considered a novel therapeutic approach in medicine. Here, the authors evaluated gold nanoparticles (AuNPs) conjugated with Tragopogon dubius leaf extract and their antibacterial activity in vitro and in vivo. Colour changes from yellow to dark brown and a peak at 560 nm on ultraviolet-visible spectroscopy confirmed the formation of nanoparticles. Additionally, transmission electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy analyses were performed to determine particle sizes and functional groups involved in gold reduction. Moreover, using standard micro-dilution and disc-diffusion assays against Klebsiella pneumoniae, Bacillus cereus, Escherichia coli, and Staphylococcus aureus, the antimicrobial properties of synthesised AuNPs were investigated. To confirm antibacterial activity, synthesised AuNPs were applied in a rat model on burn wounds infected with S. aureus, and the nanoparticles were as effective as tetracycline in bacterial reduction and wound healing. In conclusion, the synthesis of AuNPs with aqueous T. dubius extract was rapid, simple, and inexpensive, and the synthesised nanoparticles had significant antibacterial activity in vitro and in vivo.

Evaluating the effect of adding Fish oil to Fingolimod on TNF-α, IL1ß, IL6, and IFN-γ in patients with relapsing-remitting multiple sclerosis: A double-blind randomized placebo-controlled trial.

OBJECTIVES: Fish oil is claimed to improve outcome in multiple sclerosis (MS) through anti-inflammatory and antioxidant effects by reducing cytokines including TNF-α, IFN-γ, IL6, and IL-1ß. We aimed to evaluate the efficacy of adding fish oil to Fingolimod on these serum cytokines. PATIENTS AND METHODS: This double-blind randomized trial was conducted during April 2015 to September 2016 in Isfahan, Iran. Patients with diagnosis of relapsing remitting MS, aged 18-45years old and expanded disability status scale (EDSS) ≤5 were enrolled in the study. The experimental group received 1g/day of fish oil. Serum levels of TNF-α, IFN-γ, IL6, and IL-1ß were measured before intervention, 6 months, and 12 months after intervention as the primary outcome. Also, EDSS was evaluated before and at the end of study. RESULTS: 50 patients were recruited initially and nine of them left the study. We found no difference between serum levels of TNF-α, IFN-γ, IL6, and IL-1ß at three time-points between two groups (P-value >0.05). Also, there was no statistically significant difference in the mean EDSS between the experimental group and the control group after 12 months of intervention (P-value=0.08). CONCLUSIONS: Administration of fish oil did not lower the serum levels of TNF-α, IL1ß, IL6, and IFN-γ compared to placebo. Similarly, it did not improve the disability in patients.

Anti-photoaging potential of propolis extract in UVB-irradiated human dermal fibroblasts through increasing the expression of FOXO3A and NGF genes.

Propolis is a resinous compound that has been widely used in folk medicine. Different biological activities and therapeutic applications of propolis have been studied before. However, the effects of propolis on longevity-associated genes expression in the prevention of skin photoaging still remained unclear. Therefore in this study the protective effects of propolis on the expressions of two longevity-associated genes, FOXO3A and NGF genes, against UVB-induced photoaging in human dermal fibroblasts (HDF) were investigated. Propolis extract demonstrated a concentration-dependent free radical scavenging activity that was determined by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) assay. Also, Folin-Ciocalteu method was used to measure the total phenolic content of the extract. The viability of HDF cells was decreased gradually with increasing UVB radiation doses and 248mJ/cm2 was selected as the sub-cytotoxic dose. Pre-treatment with propolis extract increased the viability of UVB-irradiated human dermal fibroblasts and decreased the number of ß-galactosidase positive cells as senescent cells among them. It also increased the expression of FOXO3A and NGF genes in irradiated and non-irradiated cells. Consequently, these findings suggest that propolis extract has anti-photoaging potential and this property, in addition to its strong antioxidant activity, may be due to its effects on upregulation of longevity-associated genes.

The Effect of Snail1 Gene Silencing by siRNA in Metastatic Breast Cancer Cell Lines.

BACKGROUND: Breast cancer is the most common diagnosed cancer among women in the world. Snail1 plays a role in the development of the invasive phenotypes of cancer, neural cell differentiation, cell division and apoptosis in tumor cells. Traces of snail1 in metastasis of breast cancer to bone are observed. The aim of this study was to investigate the effect of specific snail1 siRNAs on the proliferation, migration, induction of apoptosis and cell cycle arrest of MDA-MB-468 cells. METHODS: In 2015, this experimental study was performed on the MDA-MB-468 cell lines in Immunology Research Center, Tabriz University of Medical Sciences. After the design and construction of siRNA, transfection was performed with transfection reagent. The expression levels of mRNA and protein were measured by qRT-PCR and western blot analysis, respectively. The survival of cells was determined by using MTT assay cells, apoptosis using Tunel assay, Cell migration using scratch assay, Cell cycle analysis by Propidium Iodide (PI) DNA staining method using flow cytometry on the MDA-MB-468. RESULTS: Transfection with siRNA significantly suppressed the expression of snail1 gene in dose-dependent manner after 48 h (P<0.0001). Surprisingly, treatment with snail1 siRNA arrested cell cycle in S phases (P<0.0001). Moreover, siRNA transfection had effects on breast adenocarcinoma cells and inhibited the migration (P<0.0001), proliferation (P<0.0001) and induced apoptosis (P<0.0016). CONCLUSION: The snail1 can be considered as a potent adjuvant in breast cancer therapy.

Apoptosis and Caspase 3 Pathway Role on Anti-Proliferative Effects of Scrophulariaoxy Sepala Methanolic Extract on Caco-2 Cells.

Colorectal cancer is one the most important malignancies worldwide and finding new treatment option for this cancer is of high priority. Natural compounds are common source of drugs for treatment of various diseases including cancers. The aim of this study was to investigate the effects of Scrophularia oxysepala extract on Caco-2 cells and explore the possible role of caspase 3 pathway in inducing cell death in this cancer cells in compare with chemotherapy agents of cisplatin and capecitabine. The methanolic extract of Scrophularia oxysepala (SO) was prepared by drench method. The IC50 of extract, cisplatin and capecitabine on Caco-2 cells were determined by MTT assay. The effect of SO extract on caspase 3 expression and inducing apoptosis were determined using TUNEL assay and caspase 3 ELISA methods, respectively. The IC50 of SO extract, cisplatin and capecitabine were 300, 195 and 80 µg/ml, respectively. Analysis for apoptosis revealed that SO methanolic extract increased apoptosis significantly (P<0.001) compared with control group. The effect of high doses of SO extract on apoptosis induction were comparable to cisplatin but significantly were higher than capecitabine. Only high doses of SO methanolic extract showed significant effects (P<0.05) on increasing caspase 3 compared to control group. The methanolic extract of SO showed inhibitory effect on Caco-2 cells and induced apoptosis in a dose-dependent manner comparable to cisplatin and higher than capecitabine 2 commonly used chemotherapeutic agent for various cancers.

Therapeutic effects of oral dimethyl fumarate on stroke induced by middle cerebral artery occlusion: An animal experimental study.

BACKGROUND: Dimethyl fumarate (DMF) has immune-modulatory and neuro-protective characteristics that can be used for treatment of acute ischemic stroke. OBJECTIVE: To investigate the therapeutic effects of DMF on histological and functional recovery of rats after transient middle cerebral artery (MCA) occlusion. METHODS: 22 Sprague-Dawley male rats weighing 275-300 g were randomized into three groups by block randomization. In the sham group (n = 7), the neck was opened, but neither MCA was occluded, nor any drug was administered.The control group (n = 7) was treated with vehicle (methocel) by gavage for 14 days after MCA occlusion. In the DMF-treated group (n = 8), treatment was performed with 15 mg/kg body weight dimethyl fumarate twice a day for 14 days after MCA occlusion. Transient occlusion of the right MCA was performed by intraluminal thread method in the DMF-treated and the control group. Neurological deficit score (NDS), pole test, and adhesive removal test were performed before the surgery, and on post-operative Days 0, 3, 5, 7, 10, and 14. After the final behaviour test, the animals' brains were perfused and removed. Brains were frozen and sectioned serially and coronally using a cryostat. Infract volume and brain volume were estimated by stereology. RESULTS: The percentage of infarct volume was significantly lower in DMF-treated animals (5.76%) than in the control group (22.39%) (P < 0.0001). Regarding behavioural tests, the DMF-treated group showed better function in NDS on Days 7 (P = 0.041) and 10 (P = 0.046), but not in pole and adhesive removal tests. There was no significant correlation between behavioural tests and histological results. CONCLUSION: Dimethyl fumarate could be beneficial as a potential neuroprotective agent in the treatment of stroke.

Boswellic Acid Improves Cognitive Function in a Rat Model Through Its Antioxidant Activity: - Neuroprotective effect of Boswellic acid.

OBJECTIVES: Boswellic acid (BA), a compound isolated from the gum-resin of Boswellia carterii, is a pentacyclic terpenoid that is active against many inflammatory diseases, including cancer, arthritis, chronic colitis, ulcerative colitis, Crohn's disease, and memory impairment, but the mechanism is poorly understood. This study investigated the effects of boswellic acid on spatial learning and memory impairment induced by trimethyltin (TMT) in Wistar rats. METHODS: Forty male Wistar rats were randomly divided into 5 groups: Normal group, TMT-administrated rats (8.0 mg/kg, Intraperitoneally, i.p.) and TMT + BA (40, 80 and 160 mg/kg, i.p.)-administrated rats. BA was used daily for 21 days. To evaluate the cognitive improving of BA, we performed the Morris water maze test. Moreover, to investigate the neuroprotective effect of BA, we determined the acetylcholinesterase (AchE) activity, the malondialdehyde (MDA) level as a marker of lipid peroxidation, and the glutathione (GSH) content in the cerebral cortex. RESULTS: Treatment with TMT impaired learning and memory, and treatment with BA at a dose of 160 mg/kg produced a significant improvement in learning and memory abilities in the water maze tasks. Consistent with behavioral data, the activity of AChE was significantly increased in the TMT-injected rats compared to the control group (P < 0.01) whereas all groups treated with BA presented a more significant inhibitory effect against AChE than the TMT-injected animals. In addition, TMT reduced the GSH content and increased the MDA level in the cerebral cortex as compared to the control group) P < 0.01). On the other hand, treatment with BA at 160 mg/kg slightly increased the GSH content and reduced the MDA level in comparison to the TMT-administered group (P < 0.01). CONCLUSION: The above results suggest that the effect of BA in improving the cognitive function may be mediated through its antioxidant activity.

Therapeutic effects of bach1 siRNA on human breast adenocarcinoma cell line.

BACKGROUND: Despite the great improvements in clinical and therapeutic techniques in recent years, many advanced breast cancer patients still died of the postoperative recurrence and metastasis of disease. Bach1 plays a role in the development of the invasive phenotypes of cancer, cell division and apoptosis in tumor cells. The aim of this study was to investigate the effect of specific bach1 siRNAs, on the proliferation, migration, invasive, induction of apoptosis, cell cycle arrest and alter EMT related miRNA of MDA-MB-468 cells (breast cancer). METHODS: siRNA transfection was performed with transfection reagent. The expression levels of Bach1 mRNA and protein were measured by qRT-PCR and western blot analysis, respectively. The survival of cells was determined using MTT assay cells, apoptosis using Tunel assay, Cell migration using scratch assay and Cell cycle analysis by Propidium Iodide (PI) DNA staining method by using flow cytometry on the MDA-MB-468. The expression levels of MMP-9 and CXCR4 were measured by qRT-PCR. RESULTS: Transfection with siRNA significantly suppressed the expression of bach1 gene in dose dependent manner after 48h (p<0.0001). Surprisingly, treatment with bach1 siRNA arrest cell cycle in S phases (p<0.0001). Moreover siRNA transfection had effects on breast adenocarcinoma cells and inhibits the migration (p<0.0001), proliferation (p<0.0001), cell cycle arrest (p=0.03) and induces apoptosis (p<0.0001) and reduces the expression of miR-21 (P=0.0014). CONCLUSION: Our results suggest that the bach1 can be considered as a potent adjuvant in breast cancer therapy.

Expression of HCA2 Receptors in Femoral Epiphysis and Metaphysis of Rats with Dexamethasone-Induced Osteoporosis.

The present study describes the changes in expression of hydroxy- carboxylic acid receptor 2 (HCA2 receptor) in femoral epiphysis and metaphysis of rats with glucocorticoid-induced osteoporosis (GIO). 16 growing male Sprauge dawley rats were randomly divided into two equal groups consisting of normal control and rats that were rendered osteoporotic by receiving 0.1 mg/kg/day dexamethasone subcutaneously. After 4 weeks, all rats were sacrificed and immediately right and left femoral bones were removed for RT-qPCR and histological examination, respectively. Immunohistochemical parameters using a primary rabbit polyclonal GPR109A antibody in hematoxylin and eosin- counter stained slides were determined. HCA2 receptor expression was evaluated using RT- qPCR. Qualitative and histomorphometric evaluation of slides revealed the establishment of glucocorticoid- induced osteoporosis (GIO) in rats treated with dexamethasone. In immunohistochemical study, dexamethasone administration appreciably reduced receptor density in all evaluated cell types and in total slides as compared to control. mRNA level of HCA2 receptor gene was reduced in dexamethasone- treated group. GIO may be associated with down regulation of HCA2 receptors in proximal femoral bone of rats at mRNA as well as protein level in no- cell type-specific manner, although reduction in protein expression needs to be further confirmed by western blotting.