Ardabil University of Medical Sciences

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    Targeting immune checkpoints: Building better therapeutic puzzle in pancreatic cancer combination therapy

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    Pancreatic cancer is related to a very weak diagnosis; the close parallel between disease incidence and mortality rates from pancreatic cancer reflects the fatal nature of this disease. Although early detection procedures are growing, they are not applicable yet for pancreatic cancer. The majority of cancer patients suffer from advanced disease, in which surgery has no potential effect. Based on the growing evidence, it is predicated that cancer immunotherapy alone or in combination will probably be an essential section of different cancer treatment methods. There are different kinds of immune processes, including various antitumour and tumour-promoting leukocytes. Moreover, tumour cells utilise numerous approaches to overwhelm the immune response. Use of antibody in the therapeutic protocols is proving significant success and is probably a key element of cancer treatment. This method is directed against numerous negative immunologic regulators and immune checkpoints. In the present review, the clinical outlines of immune checkpoint inhibition are discussed in pancreatic cancer

    Prevention of Gestational Diabetes Mellitus (GDM) and Probiotics: Mechanism of Action: A Review

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    Background: Gestational Diabetes Mellitus (GDM) is a health problem that is increasing around the world. Introduction: Prevention of GDM, rather than treatment, could have several benefits in terms of both health and economic cost. Even a slight reduction in maternal glucose in non-diabetic women, particularly in women at high risk for GDM, may have significant benefits for pregnancy results and the future health of off-springs. Probiotics are a relatively new intervention, which are assessed by mothers' metabolism, and can reduce blood sugar levels, prevent gestational diabetes and reduce the maternal and fetal complications resulting from it. The aim of this study was to review the studies on the prevention of gestational diabetes and assess the potential beneficial effects of probiotics on gestational diabetes and their possible mechanism of action. Methods: Articles compiled through clinical trials indexed in PubMed, Science Direct, Cochran, and Medlib between 2000 and 2017, with the keywords probiotics, prevention, and gestational diabetes mellitus were selected. Results: Considering the potential of probiotics in the modulation of gut microbiota, naturalization increases intestinal permeability, regulation of pro-inflammatory mediators' secretion and thereby controlling local and systemic inflammation results in decreasing intestinal permeability, enhancing the immune system. It likely has the ability to prevent or control diabetes during pregnancy although confirmatory studies are still needed. Conclusion: Experimental and clinical evidence support the supposition that the modulation of the gut microbiota via probiotic microorganisms could be effective in the prevention of gestational diabetes mellitus

    The role of curcumin/curcuminoids during gastric cancer chemotherapy: a systematic review of non-clinical study

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    Aims: Chemotherapy is an effective therapeutic modality which is commonly used for battling various cancers. However, several side effects induced by chemotherapeutic drugs would limit their clinical use. The present systematic review aims to evaluate the role of curcumin/curcuminoids co-administration during gastric cancer chemotherapy. Methods: This systematic review was done according to PRISMA guidelines and a full systematic search in the electronic databases up to May 2020 using search terms in the titles and abstracts for the identification of relevant literature. 279 articles were found in electronic databases and 175 articles screened by title and abstract. Finally, 13 articles were included in this systematic review according to our inclusion and exclusion criteria. Key findings: The findings indicated that gastric cancer chemotherapy induces cytotoxicity effects in various ways including a decrease of cell viability, colony formation, metastasis, tumor growth, and weight, as well as elevation of apoptosis pathway, oxidative stress pathway compared to the control group. Co-administration of curcumin/curcuminoids with chemotherapy synergistically increased the effects of anti-cancer chemotherapy compared to the group solo treated with chemotherapeutic agents. Also, in chemoresistance gastric cancer cells, co-administration of curcumin reduced chemoresistance mainly through the reduction of NF-κB activation and elevation of apoptosis. Significance: According to the findings, the use of curcumin/curcuminoids during gastric cancer chemotherapy has chemosensitizing effects, and also it can reduce chemoresistance in gastric cancer

    Anxiolytic and Antidepressant Effects of Aqueous Extract of Stachys lavandulifolia Vahl. in Mice

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    Background: Stachys lavandulifolia Vahl. is a widely used plant in Iranian traditional medicine. It has long been used as an anxiolytic herb. The aim of this work was to investigate the anxiolytic and antidepressant properties of aqueous extract of aerial parts of Stachys lavandulifolia Vahl. in mice. Materials and Methods: For evaluation of anxiolytic and antidepressant effects of the plant, different doses (500, 1000, 1200, and 1400 mg/kg) of the extract were used in the mouse models of elevated plus maze (EPM) and forced swimming test (FST), respectively. The possible anxiolytic mechanism of the extract was determined by using pentylenetetrazol (PTZ) (10 mg/kg), propranolol (0.2 mg/kg), and atropine (0.5 mg/ kg). Sedative effect of the extract was evaluated by ketamine sleeping time test, and rotarod was used to determine the effects of the extract on motor function. Statistical analysis was performed using one-way analysis of variance (ANOVA). Results: The results showed that the percentage of time spent and number of entries is significantly increased (P < 0.05) with doses of 1000 and 1200 mg/kg of the extract. PTZ but not propranolol or atropine reversed the effects of the extract (1000 mg/kg) on EPM. Neither doses of the extract could decrease the immobility of the mice in FST (P >0.05). Motor coordination was impaired (all doses) by the plant. Conclusion: This study confirms the anxiolytic properties of aqueous extract of S. lavandulifolia and suggests that its effects are mediated through GABAA receptors. The extract does not have sedative properties but the results are indicative of a coordination impairing potential of the extract

    Synthesis and characterization of trypsin enzyme-conjugated rituximab monoclonal antibody

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    Introduction: Each year many people die from cancer and it force governments and people high costs. Blood cancer is one of the most common cancers. Although there been a lot of progress in treating blood cancers but it is problematic because of different types of blood cancer and resistant to treatment. In recent year’s chemotherapy been a choice treatment but because of high numbers of adverse effects and low selectivity scientists look for new treatments .There been many studies to find new drugs and we probably going to have better choices of treatment in near future. In this study we tried to enhance rituximab antibody by conjugating it to trypsin enzyme. Methods and materials In first step, we activated rituximab monoclonal antibody using DSP linker. Then we added same molar ratio of trypsin enzyme to rituximab. Then we put it in refrigerator for 24 hours. Finally, we used TEM and DLS to confirm final product. Results In first step, we confirmed the conjugation of trypsin to rituximab using DLS and TEM then we confirmed using cell culture. Conclusion Our studies showed that we can conjugate trypsin to a mAb using a DSP. In future studies, we will study the effect of conjugate at cellular studie

    A Review on the Relation between Sepsis and Vitamin D Level among Neonatal Intensive Care Unit Infants

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    Background Neonatal sepsis is a critical condition caused by a generalized bacterial infection in the first month of life. The present study aimed to investigate the relationship between serum vitamin D levels and neonatal sepsis. Materials and Methods: A search of online databases (Medline, Cochrane Library, Web of Science, EMBASE-Ovid, and Scopus) were carried out for randomized control trials and non-randomized prospective or retrospective clinical studies published in English till April 2020. Two reviewers selected the studies. Results: In the first study, the level of 25-hydroxyvitamin D [25(OH)D] in the cord-blood sample of infants in the Early-Onset Neonatal Sepsis (EONS) group was significantly lower compared to the control group. 25(OH)D level (19 ng/ml) in the control group were significantly higher compared to the 25(OH) level (8.6 ng/ml) in the sepsis group. In the third study, the serum 25(OH) level showed a significant decrease in the affected neonates (6.4 nmol/L) compared to healthy neonates (42.5 nmol/L). In the fourth study, the sepsis and control group had a significant difference in the level of 25(OH)D (69±7.5ng/ml and 35±19ng/ml). According to the fifth study, the serum 25(OH)D level was insufficient in the case group and sufficient in the control group (p<0.0001). In the sixth study, the odds of very-early-onset neonatal sepsis among the neonates who had the serum 25-hydroxyvitamin D deficiency were lower compared to the odds among neonates who did not have serum 25-hydroxyvitamin D deficiency. Conclusion The level of 25-hydroxyvitamin D in the blood sample of infants in the sepsis group was significantly lower compared to the control group; further studies required to confirm the results by considering more confounders

    Combating with ageism in care settings: A qualitative study

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    This study was conducted to collect and explore the experiences of hospital caregivers about strategies to deal with ageism in care settings. This qualitative research used conventional content analysis. Twelve nurses and physicians in Tehran hospitals were selected by purposeful sampling method and entered the study after data saturation. The study data were collected using in-depth and semi-structured interviews with open-ended questions. The interviews were recorded and then transcribed verbatim. The obtained data were analyzed with Hsieh and Shannon approach. After analyses of the interviews, 640 primary codes were extracted, which resulted in the emergence of two main categories of “caregiving is worthwhile” with four subcategories (Not considering caregiving a useless task, Not considering more valuable dead older people over alive ones, Not considering caregiving costly, Motivation for caregiving) and “caregiving is sensitive “with three subcategories (Being sensitive to the health of older people, Supervising and follow up, Education and culture-building). According to the study results, caregivers believed that the valuation of caregiving and being sensitive to caregiving were the most important strategies to deal with ageism in care settings. Therefore, health care decision-makers and authorities can reduce the likelihood of discrimination in the care provided to the elderlies by proper policy-making to promote caregivers’ attitudes towards the worthwhileness and sensitiveness of caregiving

    Illicit Drug Use and the Associated Factors Among University Students: A Report in the Southwest of Iran

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    Background: Illicit drug use is a major public health concern among university students. Objectives: The present study aimed to determine the prevalence of illicit drug use and the associated factors in a population of Iranian university students. Methods: This cross-sectional study was conducted in Bushehr, located in the Northwest of Iran in 2017. The participants were selected randomly and included 977 university students. Anonymous, structured questionnaires were completed by the students. The self-administered questionnaire consisted of data on illicit drug use, smoking habits, sexual behaviors, alcohol consumption, physical fights, religious beliefs, parental support, and illicit drug use by the family members and friends. Data analysis was performed using chi-square and logistic regression analysis. Results: The prevalence of illicit drug use during the lifetime, past year, past month, and daily/almost daily was estimated at 4%, 3.3%, 2.4%, and 0.9%, respectively. The lifetime prevalence of cannabis, amphetamine-type stimulants, opium, and heroin was 1.3%, 1.5%, 1.5%, and 0.1%, respectively. After adjustment for other factors, male gender (OR = 4.06), working along with education (OR = 2.33), smoking habits (OR = 4.00), physical fights (OR = 4.04), and illicit drug use by friends (OR = 2.71) were associated with illicit drug use. Conclusions: According to the results, the prevalence of illicit drug use was relatively low, albeit significant, among the students in Bushehr. Among the determined factors associated with this issue, illicit drug use was strongly correlated with drug use by friends. Our findings could be used for the planning and evaluation of interventions based on the related risk factors

    Evaluation of antibiotic prescription pattern for prophylaxis of surgical site infection in the surgical wards of Fatemi hospital in Ardabil, During the Second 6 month of 1398

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    Introduction: Surgical site infection (SSI) is one of the major surgical problem. Antibiotic prophylaxis recommendation which provided by international guidelines such as American Society of Health-System Pharmacists(ASHP) and the Society for Healthcare Epidemiology of America (SHEA), offer an effective way for reducing postoperative infections. Prevention of SSI can effectively reduce the incidence of postoperative infections, Length of hospital stay, adverse drug reactions, microbial resistance, and ultimately the cost of the patient and the health system. Present work evaluate the pathern of antibiotic application for SSI prophylaxis and its compliance with ASHP guideline, in the surgical section of Fatemi hospital , Ardabil,Iran. Methods: This prospective cross-sectional study was performed on patients who underwent surgery in orthopedic, neurosurgery, ENT and general surgery wards during the second half of 2016 in Ardabil Fatemi Hospital.Demographics data and data regarding antibiotic prophylaxis eg. rout of administration, antibiotic type, dosing, frequency of administration, time of administration and duration of antibiotic prophylaxis, recorded and analyzed using SPSS 21. Results: Out of 200 patients studied, antibiotic prescribing indications, appropriate antibiotic selection, time of first dose administration,proper dosing, duration of antibiotic prophylaxis, time intervals between two administrations are 89.4% _78.8% _62.7% _32.9% _53.4%_49.6% of the cases, respectively was in accordance with guideline recomendastion. Conclusion:In accordance with the previous studies, our result show mismatch between guideline recomendation and clinical practice for antibiotic prophylaxis in surgical ward patients, which necessitate revising and updating hospital protocol for antibiotic prophylaxis

    Persian Gulf Snail Crude Venom (Conus textile): A Potential Source of Anti-Cancer Therapeutic Agents for Glioblastoma through Mitochondrial-Mediated Apoptosis

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    Background: Research on animal toxins have shown toxicity potential on cancerous cell and tissues in the cultures. Conotoxins obtained from marine cone snails show the highest toxicity potential, so that several human deaths have been attributed to this species of snail. These toxins have proven to be valuable agents to inhibit enzymes, channels and proteins, in the nervous systems of humans. Methods: We have studied the effects of Conus textile crude venom on U87MG human glioma cells and their mitochondria as main inducers of apoptosis and human embryonic kidney 293 cells (HEK293) as non-cancerous normal control cells. Cellular toxicity assessments including MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and measurement of caspase-3 activation as well as mitochondrial toxicity assays including measurement of the activity of succinate dehydrogenase (SDH) enzyme, mitochondrial swelling, reactive oxygen species (ROS) production, collapse of mitochondrial membrane potential (MMP) and cytochrome c release were performed in U87MG human glioma cells and HEK293 cells (as non-cancerous normal cells). Results: The results illustrated the significant cytotoxic effect of Conus textile crude venom on U87MG human glioma cells, that inhibits 50% (IC50=10µg/mL) of the cell growth after 12 h of exposure. Viability measurement showed which the Conus textile crude venom is selectively cytotoxic to U87MG human glioma cells, and induced activation of caspase-3 and induction of cell apoptosis via through mitochondrial signaling. Conus textile crude venom also selectively increased mitochondria swelling, ROS formation, cytochrome c release and MMP decrease in cancerous mitochondria but not normal mitochondria. Conclusion; Based on the obtained results from this investigation, it is concluded that the Conus textile crude venom contains promising natural compounds to fight U87MG human glioma cells through activation of apoptosis intrinsic pathways

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