Opium dependence is one of the serious and multidimensional problems. Millions of people are opium addicts throughout the world. The aim of this study was to determine the risk factors causing relapse in opium addicts in Internally Displaced People (IDPs). This experiment was conducted in the Drug Detoxification and Health Welfare research center, Bannu, KPK, Pakistan. Sociodemographics characteristics of IDPs were studied in this retrospective crosssectional study. Questionnaire was specifically designed and total 41 relapsed individual’s histories of post treated IDPs were studied. Percentage of factors causing relapse in IDPs included stress in 36.59% individuals, family conflicts 19.51%, friends 12.20%, work load stress 09.76%, body aches 07.31%, sexual satisfaction 09.76% and fun 04.87%. Average time of relapse in IDPs was 6 months. Results revealed that stress was the most notorious factor directing IDPs towards relapse. It is concluded that attention must be paid on the crucial factors of stress to avoid relapse associated with opium dependence such as, family conflicts, personal, occupational and economical status. Conflicts of Interest: Declared None Funding: Drug Detoxification and Health Welfare Research Center, KPK, Pakistan
Urtica dioica L. is widely used as an anti‐inflammatory, antioxidant, antimicrobial, hypocholesterolemic, antiulcer, anti‐colitis, anticancer, hypotensive, immunomodulatory, and hepatoprotective agent. In the present study, the antidiabetic and nephroprotective potentials of U. dioica ethanolic extract was investigated against streptozotocin (STZ) induced diabetic mice. Male mice were divided into six groups: normal control, untreated diabetic, diabetic mice receiving 30, 90 and 270 mg/kg of plant extract (groups UD30, UD90 and UD270, respectively) or 30 mg/kg glibenclamide. At 20 day, the mice killed, dissected, then blood and kidney samples were collected for histological and biochemical parameters analysis. The data was analyzed by one way variance analysis and Duncan’s test using SPSS 21. Different doses of U. dioica (especially UD270) could significantly (p≤0.05) reduce the raised levels of blood glucose, urea, creatinine and volumes and lengths of the proximal and distal convoluted tubules, collecting ducts, vessels and loop of Henle and increase the weight of body and levels of superoxide dismutase (SOD) and catalase (CAT) when compared to the untreated group. The results of the present study showed that under the present experimental conditions, ethanolic extract of U. dioica indicated antidiabetic and nephroprotective abilities against STZ induced kidney damage in mice. Conflicts of Interest: Declared None Funding: None
Valproic acid is widely used as an anti-epileptic globally. Anti-epileptic action is mediated by Gamma Amino Butyric Acid (GABA) receptors. In past and recently, several other clinical outcomes have been proposed by various studies. These under-reported clinical actions apart from anti-epileptic activity are mediated by various intracellular and extracellular pathways. Several mechanisms like Histone deacetylase (HDAC) inhibition, inhibition of inflammatory cytokines, angiogenesis inhibition and many more justifies its possible use in variety of disorders like diabetes mellitus, asthma, cancer, shock, hyperlipidemia, fibrosis etc. Present review throws some light on such under-reported, clinically beneficial effects of Valproic acid in various diseases and disorders. Conflicts of Interest: Declared None Funding: This work was supported by University Grants Commission, New Delhi, India and Department of Pharmaceutical Sciences, Saurashtra University, Rajkot, Gujarat, India.
The goal in studies concerning biomarkers in autoimmune diseases is finding a marker which fluctuates in correlation with the disease’s severity and settles within normal borders after effective treatment. This marker would later be used as an efficient tool in diagnosis and analysis of medicine clout. It seems the most cogent biomarkers are those measurable in serum or plasma. MS is a neurological disease common within the young adult population with a predictable course, often leading to life-immersing disability. The prognosis, however difficult and limited, is currently possible via diagnostic tests (brain MRI) or clinical information (severity and degrees of disability). Many studies have been conducted in an effort to detect an adequate biomarker. It is still often overlooked that a reliable biomarker should both be clinically applicable and functional is prognosis; as this is what could lead to timely treatment. Conflicts of Interest: Declared None Funding: None
Harmine is a harmal-derived alkaloid with antioxidant properties. The morphine produces free radicals and plays a key role in the pathogenesis of kidney disease. This study was designed to evaluate the effects of harmine against morphineinduced damage to the kidneys of rats. In this study, 64 male rats were randomly assigned to 8 groups: saline and morphine treated groups; harmine groups (5, 10, 15 mg/kg) and morphine + harmine treated groups (5, 10, 15 mg/kg). Treatments were administered intraperitoneally daily for 20 days. The weights of the animals and their kidneys, kidney index, glomeruli characteristics, thiobarbituric acid reactive species, antioxidant capacity, kidney function indicators and serum nitrite oxide levels were investigated. Morphine administration significantly improved kidney MDA level, blood urea nitrogen (BUN), creatinine and nitrite oxide levels and decreased glomeruli number and tissue FRAP level compared to the saline group (P < 0.05). The harmine and harmine + morphine treatments at all doses significantly reduced BUN, kidney MDA level, creatinine, glomerular diameter and nitrite oxide levels and increased the glomeruli number and tissue FRAP level compared to the morphine group (p < 0.05). It seems that harmine administration improved kidney injury induced by morphine in rats. Conflicts of Interest: Declared None Funding: Kermanshah University of Medical Sciences
The present study aimed to investigate the role of adenylyl cyclase activator in preventing diabetic nephropathy via antioxidant activity in rats. Biochemical parameters were performed to confirm Streptozotocin induced nephropathy in rats. Male Wistar rats were used in the present study to reduce the effect of estrogen. Rats were subjected to high fat diet (HFD) for two weeks followed by low dose of Streptozotocin (STZ) [35mg/kg, i.p.] to develop experimental diabetic nephropathy in eight weeks. Two weeks treatment with low dose of Forskolin (10mg/kg) reduced the level of diabetic nephropathy markers but results observed were not significant. Whereas, Forskolin intermediate dose (20mg/kg) and high dose (30mg/kg) treated rats significantly attenuated diabetes induced elevated renal function parameters and endogenous antioxidants enzymatic activities. High dose of Forskolin was found to be more effective in attenuating the renal structural and functional abnormalities. Forskolin prevented renal structural and functional abnormalities diabetic rats. In the present study, Glibenclamide (0.6mg/kg) and Atorvastatin (0.5mg/kg) were used as standard drugs. Our results demonstrated synergistic effects, when high dose of Forskolin was co-administered with standard drugs. In conclusion, treatment with adenylyl cyclase activator, Forskolin in diabetic rats reduced the oxidative stress, improved renal functions and enhanced level of endogenous antioxidants. Forskolin prevented renal functional abnormalities due to diabetes mellitus. Forskolin has a potential to prevent diabetic nephropathy, implicating direct renoprotective action in diabetic rats. Conflicts of Interest: Declared None Funding: I.K. Gujral Punjab Technical University Jalandhar (India)
Trastuzumab is a specific monoclonal antibody used for therapeutic of the human epidermal growth factor receptor 2 (HER-2) -positive metastatic breast cancer. But, resistance to trastuzumab is a major obstacle in clinical efficiency. During the past years, several studies have been done to find the mechanisms contributing to trastuzumab resistance. Previous studies have highlighted that bone morphogenic protein (BMP) signaling can indicate a pathway in cancer for sensitizing cells to chemotherapy. Also, it was suggested that Caveolin-1 is essential for the formation of caveolae and endocytic membrane transport and has a critical role in drug resistance and metastasis in cancer. The purpose of this study was to assess the expression of BMP receptor type1A (BMPR1A) and Caveolin-1 genes in compare with trastuzumab-sensitive and resistance BT-474 cells. Trastuzumab-resistant BT474 cells were established by continuous subjection to trastuzumab for six months. Then, an MTT assay was done for determining the resistance. After that, the Expression of BMPR1A and Caveolin-1levels were assessed through real-time PCR. Caveolin-1 expression levels increased significantly (2.4 fold, p<0.05) whereas BMPR1A levels down-regulated significantly (8.26 fold, p<0.05) in BT474-R compared to the parental cells. Our results proposed that BMPR1A and CAV1 regulation take part in BT-474 trastuzumab resistance breast cancer. Therefore, further experiments are required to confirm the role/s of BMPR1A and CAV1 in trastuzumab resistance breast cancer. Conflicts of Interest: Declared None Funding: None
Coriandrum sativum has been used in Iranian traditional medicine as an antiinflammatory, antioxidant, antibacterial, and antifungal agent. The purpose of this study was to evaluate the chemical composition and anti-parasitic property of essential oil of C. sativum leaf on trophozoite of Trichomonas vaginalis. C. sativum was collected from Kermanshah city and essential oil was prepared by the Clevenger device. The essential oil was analyzed by GC/MS. Trophozoite of T. vaginalis was cultured in vitro in CPLM medium and the effect of the essential oil on the survival of T. vaginalis trophozoite was measured by Neobar slide. This study indicated that Linalool (71.2%) was the most constituent found in C. sativum essential oil. Also, the results of anti-parasitic tests demonstrated the concentrations of 0.5, 0.25, 0.125, 0.062, 0.031, 0.015, 0.007, 0.003, and 0.001 g/ml in essential oil and 0.25 g/ml in metronidazole could destroy of T. vaginalis trophozoite completely after 420 minutes incubation. The best results were observed at 0.5 and 0.25 g/ml concentrations of essential oil, because these concentrations were able to destroy trophozoite in 90 minutes. Also, 0.001 g/ml concentration of essential oil had the lower anti-parasitic effect than all concentrations against T. vaginalis trophozoite. The trophozoite survived at DMSO after 600 minutes. MIC and MLC of C. sativum essential oil were 0.015 and 0.031 g/ml concentrations, respectively. In our study, the essential oil of C. sativum leaf in several concentrations destroyed T. vaginalis trophozoite. It appears that C. sativum can be used for the treatment of some T. vaginalis infections as an antibiotic. Conflicts of Interest: Declared None Funding: Razi University, Kermanshah, Iran
Presently drugs that are available to treat the diabetic induced cognitive impairment presents adverse effect on long term used. This study offers evidence that old drugs can be combined and used. Existing and affordable drugs can be repurposed and can benefit patients .The study used a combination of drugs with proven safety for preventing/delaying the development of cognitive impairment in diabetes with a hope to improve the quality of life of diabetic patients. In current study, diabetic rats were treated for eight weeks with combination of gamma linolenic ac-id (30mg/kg,p.o), alpha lipoic acid (30mg/kg,p.o), phloroglucinol (250mg/kg,p.o) l-thyroxine (1mg/kg, s.c) in one group and combination of of gamma linolenic acid (30mg/kg,p.o), alpha lipoic acid (30mg/kg,p.o), allantoin (200mg/kg,p.o), l-thyroxine (1mg/kg,s.c) in other group.The degree of preventative was determined by various parameters like body weight, measurement of neurotransmitter and calculating glycosylated haemoglobin and behavioural studies to check whether the combination therapy has positive impact on diabetic induced cognitive impairment. Conflicts of Interest: Declared None Funding: None
Candida albicans is one of the most common opportunistic fungi which cause oral cavity infections in humans. Most anti-fungal drugs posse side effects and may have an undesirable taste. Ginger is one of the oldest herbal products used in traditional medicine which has known antimicrobial effects and is used in the manufacture of Vi-One mouthwash. The present study was designed to investigate the antifungal effects of Vi-One Mouthwash. In this experimental study, the susceptibility of Candida albicans (PTCC 5027) to Vi-One Ginger mouthwash was evaluated in comparison with nystatin using disk diffusion method. One way analysis of variance (ANOVA) test was employed to evaluate the findings and Pvalues less than 0.05 were considered as significant. The data of the present study showed that the diameter of the inhibition zone in the nystatin group was 8.04 mm while, in the vi-one mouthwash group it was 1.16 mm. The difference between examined groups was significantly different (ANOVA, P-value=0.0001). According to the findings, vi-one ginger mouthwash exhibited a very weak antifungal effect in comparison with nystatin in the laboratory environment. Conflicts of Interest: Declared None Funding: None
Sulfur mustard (SM) is a mutagenic compound that causes oxidative stress, antioxidant depletion even several years after exposure. Melatonin is an alternative medication that has antioxidant peroperties. The aim of this study was to investigate the effect of melatonin treatment on serum levels of several mineral elements, total antioxidant (TAC) and total oxidant status (TOS) in sulfur mustard-exposed patients. Victims with lung and sleep disorders was divided randomly to placebo and melatonin groups. They received melatonin or placebo for 56 days. Blood samples were taken before and after drug usage. The concentrations of serum trace elements (manganese, zinc, copper, and iron) and one other essential element (magnesium) were determined by graphite furnace and flame atomic absorption spectroscopy. TAC and TOS in serum were determined colorimetrically. Results showed that melatonin administration increases the magnesium and TAC concentrations. After the drug usage, placebo and melatonin groups had the highest TOS and TAC contents, respectively. Therefore, melatonin can be considered as a compound suitable for suppression of oxidative stress and helps to decrease oxidative damages induced by mustard gas. Conflicts of Interest: Declared None Funding: None
Trachyspermum copticum is one of the most important Iranian Apiaceae species which is widely distributed in the northern region of Iran. In this study, chemical compounds, anti-tumor and antibacterial activities of T. copticum essential oil were evaluated. The essential oil obtained by Clevenger apparatus and then the chemical composition was analyzed by GC-MS. Antibacterial activity of essential oil was evaluated by well diffusion method. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined by the macrodilution method. An MTT cytotoxicity assay was employed to test effects of the essential oil on each human breast cancer cell lines. The GC-MS spectrums showed 9 major compounds, in which the highest chemical composition was related to thymol (42.16%), -Terpinene (31.49%) and p-cymen (23.29%) compounds. T. copticum essential oil showed good antitumor activity on SKOV3 and MDA-MB-231cell lines (IC50 of 208.13.6μg/ml and IC50 236.16μg/ml, respectively). It also showed good activity against to tested bacteria. The MIC and MBC values of the bacterial strains sensitive to the essential oil were in the ranges of 0.4 to 3.1 mg/ml and 0.4 to 6.25 mg/ml, respectively. Because of the high concentration of phenolic compounds, the essential oil from T. copticum exhibited antimicrobial and antitumor activities, which deserve further research into the chemoprevention and treatment of human ovary and breast cancers as well as infectious diseases. Conflicts of Interest: Declared None Funding: Islamic Azad University, Sari Branch
Design, synthesis, and conjugation of mesoporous silica nanoparticles (MSNs) with biomolecules is a matter of growing interest to enhance selective uptake of contrast agents like gadolinium (Gd3+) by cancer cells. Here, by targeting xc-cystine/glutamate antiporter system in breast cancer cells, conjugation of MSN-Gd3+ with cysteine is used to enhance cancer cellular uptake of Gd3+. Reactions designed to make different covalent bonds between MSNs and cysteine to investigate impact of cysteine conjugation of MSNs-Gd3+ on uptake of Gd3+ by breast cancer cells. Cysteine amino acids were attached to the surface of MSNs via its three functional groups using three different conjugation methods. Therefore, the external surface of MSNs were first modified by three different linkers to create amine, epoxy, and isocyanate groups on the surface of MSNs, then pores loaded with Gd3+ complexes and reacted with toile, epoxy, and amine groups of cysteine, respectively (nanoprobe A, B and C). The nanoprobes were characterized using different techniques, including (scanning electron microscope) SEM, Brunauer–Emmett–Teller BET, dynamic light scattering (DLS) and Fourier Transform Infrared (FTIR). The intracellular uptake of nanoprobes by human dermal fibroblasts (HDF) and human breast adenocarcinoma cells (MCF-7) was investigated using inductively coupled plasma atomic emission spectrometer (ICP-AES). Results demonstrated that accumulation of Gd3+ in cancer cells is highly related to method of cysteine conjugation. The amount of Gd3+ was taken by cancer cells increased 7 folds, when thiol group of cysteine was responsible to make covalent bond with MSNs, in other words when the zwitterionic form of cysteine was on the surface (nanoprobe B). The average intracellular uptake of Gd3+ by cancer cells was 0.5±0.09 pg/cell. On the other hand, uptake of Gd3+ delivered by nanoprobe B into cancer cells was up to 4.7 times higher than normal cells. No appreciable cytotoxicity was seen using HDF and MCF-7 cell lines. This study provides MRI nanoprobes using suitable conjugation of Gd3+ based MSNs with cysteine for next studies about MR imaging of cancer. Conflicts of Interest: Declared None Funding: Iran University of Medical Sciences
Quercetin is one of the major flavonoids finding in many fruits and vegetables. Quercetin has many health promoting advantages such as improvement of allergic, arthritis disorder, and reduction of cancer and cardiovascular risk. The aim of this study was to examine hepatoprotective effects of quercetin on doxorubicin induced toxicity in animal model. Thirty male Wistar rats (200-230 g) were randomly divided in to 5 groups including: Quercetin group was orally treated with 20 mg/kg of quercetin for 14 days. Doxorubicin group was treated with 25 mg/kg of doxorubicin i.p. for 3 days. DoxorubicinQuercetin group (DQ) was orally pretreated of 20 mg/kg quercetin for 14 days with hepatotoxicity induced by i.p. injection of 25 mg/kg doxorubicin (12th, 13th and 14th days). The control and vehicle group were orally received saline (1 mL/kg), and DMSO (1 mL/kg) respectively. Sample of their livers were used to determine the myeloperoxidase (MPO) activity, superoxide dismutase (SOD), malondialdehyde (MDA), GPX, catalase, and histological analysis. The numerical data were evaluated by ANOVA, followed by the Tukey tests. The results show that doxorubicin could produce hepatotoxicity in rat. Also, increased liver enzymatic (ALT, AST, ALP), MPO, MDA (p<0.001), followed infiltration of inflammatory cell, and necrosis of hepatocytes also Pretreatment with quercetin reduces MPO activity (p=0.0034), MDA (p=0.0335) and the elevated liver ALT (0.009), ALP (p=0.0023) and AST activity (0.0074) in rats in DQ group. This study suggests that quercetin have a protective effect on the liver tissue against toxicity induced by doxorubicin. Conflicts of Interest: Declared None Funding: None
For a long period, ethno medicinal plants have been a valuable source of natural products for maintaining human health, especially in the last decade, with more intensive studies for natural therapies. The use of ethno medicinal plant for pharmaceutical purposes has gradually increased in Iran. Gundelia tournefortii has been used as an antibacterial, anti-fungal, antipyretic, anti-inflammatory, and antioxidant agent in Iran. In the recent examination, the testicular protective effect of G. tournefortii aerial parts aqueous extract on diabetic mice has been evaluated. Seventy mice were used and diabetes was induced by administration of 150 mg/kg of alloxan monohydrate intraperitoneally in 60 mature male mice and they were randomly divided into six groups. The treatment groups received glibenclamide 10 mg/kg and 5, 10, 20 and 40 mg/kg of G. tournefortii through gavage for 20 days. Also, one group was considered as the non-diabetic control. At 20 day, the mice were killed, dissected, then blood and testis samples were collected for biochemical and stereological parameters analysis. The data were analyzed by SPSS-21 software. G. tournefortii at all doses (especially GT40) and glibenclamide significantly (p≤0.05) ameliorated the concentrations of fasting blood glucose, testosterone, superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase. Also, multiple doses of G. tournefortii (especially GT40) and glibenclamide increased the weight and volume of the testis, the volumes of the tubule and interstitial tissue, the length and diameter of the tubule, the height of the germinal epithelium, and the number of the Leydig cell compared to the diabetic untreated group. According to the obtained results, G. tournefortii aerial parts aqueous extract can regulate the concentrations of biochemical parameters and inhibit testicular damages in alloxan monohydrate induced diabetic mice. It seems that G. tournefortii can be offered as a testicular protective supplement or drug for prevention, control, and treatment of testicular toxicity in diabetic patients. Conflicts of Interest: Declared None Funding: None
