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This work presents a comprehensive synthesis method for the development of a new hyperbranched unsaturated polyester resin (HUPR). The resin is synthesized by modifying dehydrated castor oil fatty acid (DCOFA) with methyl methacrylate (MMA) and styrene, dicyclopentadiene-maleate (DCPD-M), and trimethylol propane diallyl ether (TMPDE). The synthesis process involves the radical addition reaction of DCOFA with MMA and styrene, followed by the addition of DCPD-M and TMPDE to form a HUPR. The resulting resin exhibits enhanced properties, making it a promising candidate for car body putty in the polymer industry.

Hyperbranched polyester polyols have emerged as a promising candidate for polyurethane coatings due to their unique structure and properties. In this context, this paper aims to synthesize a new hyperbranched polyester polyol and evaluate its potential as a polyol for polyurethane coating applications. In this study, the synthesis of hyperbranched polyester polyol involves the reaction between a multifunctional alcohol and a multifunctional carboxylic acid or anhydride. It is further modified by incorporating 2-hydroxyethyl methacrylate and styrene. The properties of the polyester polyol were characterized using various analytical techniques, including FTIR, NMR, SEM and TGA. This paper also provides a discussion on the potential applications of the synthesized hyperbranched polyester polyol in several industries such as automotive, aerospace and construction.

ABSTRACTPharmaceutical waste disposal is a significant problem for the global healthcare system. It poses a threat to water safety, which is already a challenge as 1 out of 3 people still lack access to safe drinking water. We conducted a thorough literature review of relevant articles published between 2000 and 2023. Our review scrutinized 107 studies, each of which applied pre-set inclusion and exclusion criteria to ensure high-quality research. The focus of our interest was on the health risks posed by pharmaceutical compounds in waste. We also evaluated recycling methods and proposed practical measures for proper education and the implementation of strict legislation to address this issue. Pharmaceutical compounds have been found in water resources worldwide. These compounds can have negative effects on multiple organs and it’s important to remove them from water resources. However, water quality varies globally due to limitations in accessibility and budget for water purification and recycling efforts. Comprehensive studies are needed to identify drinking water’s most common pharmaceutical residues and develop effective removal strategies. Proper disposal of pharmaceuticals is crucial to protect water resources and ensure clean drinking water. This requires raising awareness, educating the public population, implementing strict regulations, and collaborating among stakeholders.

Higher utilization of existing resources and facilities in order to increase efficiency and profitability is always one of the basic challenges for parallel processing systems and environments, and this challenge becomes more complicated when the system resources are heterogeneous. One way to achieve high efficiency and profitability of heterogeneous parallel systems is to schedule tasks optimally. In this paper, an extended tabu search-based scheduling algorithm (ESTS) is presented to improve the profitability of heterogeneous parallel systems, which can achieve suitable solutions in a short computational time. To evaluate the efficiency of the proposed solution, due to the lack of a suitable criterion to evaluate this problem, the obtained results are compared with both the results of an extended scheduling based on a genetic algorithm (ESGA) with a large number of chromosomes and a high number of generations, as well as an extended scheduling based on a simulated annealing algorithm (ESSA) with a linear temperature reduction. The benchmark files of different sizes were tested under the same conditions, and the comparison of results shows the superiority of the proposed solution in terms of profitability and computational time.

It has been brought to the attention of the Editorial Office that Figure 1 in the original publication [...]

Background & Aim: Today, ageing is a challenge for health and care systems, and one of its main consequences is an increase in the readmission rates. Therefore, in all countries, efforts are being made to reduce the readmission rate. The Readiness for Hospital Discharge Scale was designed to understand patients' readiness levels for discharge. This study was conducted to translate and evaluate the psychometric properties of the Readiness for Hospital Discharge Scale. Methods & Materials: In this methodological study, a convenience sample of 500 elderly patients admitted to hospitals affiliated with Mashhad University of Medical Sciences was selected in 2020-2021. The instrument was translated using the forward-backwards method. The psychometric properties of the final version of the instrument were assessed by employing exploratory and confirmatory factor analysis (validity) and Cronbach's alpha and the Guttman's split-half coefficient (reliability). Results: In the factor analysis, all items had a factor loading above 0.3 and, all of them were retained. The goodness of fit indices confirmed the model and a good fit of the model. The Cronbach's alpha coefficient for the whole scale and the Guttman's split-half coefficient were 0.92 and 0.86, respectively. Conclusion: The results of our study supported the four-dimensional structure of this instrument and indicated that this instrument has adequate validity and reliability. Therefore, nurses and doctors can use this tool as a suitable method to measure the elderly patients' readiness for discharge and to achieve a safe transfer from the hospital to home.

Abstract Considering the progressive prevalence and co-occurrence of type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD), as well as the current evidence suggesting the elevated levels of basal metabolic rate (BMR) among these individuals, the present study aimed to identify factors determining hypermetabolism in such subjects. This cross sectional study was conducted in 30 to 53-year-old individuals with concurrent T2DM and NAFLD (controlled attenuation parameter score ≥ 260 dB/m). Resting energy expenditure (REE) was determined by an indirect calorimetry device. Hypermetabolism was defined as an elevated measured REE > 110% of the predicted REE. The multivariate logistic regression test was used for detecting factors associated with hypermetabolism. Between September, 2017, and March, 2018, a total of 95 eligible participants (64.40% male) with both T2DM and NAFLD were included, while 32.63% of them were classified as hypermetabolic. Overall, the mean recruitment age ± standard deviation and median (interquartile range) body mass index were 44.69 ± 5.47 years and 30.20 (27.80–33.30) kg/m2, respectively. Demographic, anthropometric and biochemical variables did not vary significantly across two groups except for total body water, low-density lipoprotein cholesterol and dipeptidyl peptidase 4 (DPP-4) inhibitors (p

In this study, we first identified the existing knowledge about temporal management of pesticide consumption. Then the growers view and performance in this regard was estimated. Comparing growers’ knowledge with experts’ idea, the pistachio producers score related to temporal management of pests control was calculated. Pistachio producers of Anar and Rafsanjan areas in Kerman province, Iran were considered as our study population. Using stratified random sampling method, a sample of 100 growers were selected. Pearson correlation, analysis of variance and regression were used to investigate the socioeconomic factors affecting growers’ knowledge and the effect of this knowledge on growers’ performance. The results showed that in the field of temporal management of pesticide use, growers’ knowledge is low. Investigating the factors affecting growers’ knowledge level showed that research, education and extension activities have had the significant effect on increasing knowledge of inputs temporal management. The results also showed that knowledge of temporal management pest control did not increase land use productivity (pistachio yield) but enhanced pesticide productivity. The amount of pesticide usage decreased by 0.477 l/ha/year, with increasing of each score to pest control knowledge. In other words, with increasing knowledge of pest control, not only the costs of spraying will be reduced, but it will also have environmental benefits. In short, current conditions are not suitable for precision agriculture application in Iranian pistachio orchards, but with increasing knowledge of growers, these conditions will be created.

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This experiment was conducted to evaluate the effects of changing feed form in commercial laying pullets at their 9-14 weeks of age. In the first eight weeks of rearing, the birds were fed four basal diets, including two feed forms (mash;M vs. pellet;P) and two levels of sunflower hulls (SH) inclusion (0 vs. 4%); then, they were assigned to 11 treatments with eight replicates of 9 birds each. The experimental groups consisted of the mash diet during 0-8 and 9-14 weeks (control); mash from 0-8 week and pellet +SH from 9-14 weeks (M-PSH); and so on MSH-MSH; MSH-PSH; P-P; P-M; P-MSH; P-PSH; PSH-PSH; PSH-MSH; and M-MSH. During the whole period, average daily feed intake (ADFI) in the birds fed with pellet or mash and then fed with the pellet containing SH (P-PSH and M-PSH) was higher than with the other treatments (P < 0.05). Average daily weight gain (ADG) was affected by dietary fiber and feed form, whereas it was found lower in the PSH–MSH treatment birds and greater for the birds in MSH-PSH treatment than others (P < 0.05). Further, FCR improved in the birds fed the mash diet with and without fiber from during 1-14 weeks (P < 0.05). Feeding pellet diet without fiber during 1-14 weeks resulted in lower gizzard weight and deeper crypt than the other groups (P < 0.05). In addition, the greater and lower villus surface area belonged to the birds fed MSH-MSHP-P diets during 1-14 weeks, respectively. The greatest tibiotarsal index was related to the group fed the pellet or mash without fiber during 0-14 weeks (P < 0.05). In conclusion, considering the costs for pellet production, it seems that feeding pellets just during the first eight weeks of age could lead to better performance in commercial situations. Moreover, dietary inclusion of SH improved the function of gizzard.

Background: As a medical dilemma, gastric cancer will have 7.3 million new cases in 2040. Despite the disease’s high economic and global burden, conventional chemotherapy regimens containing cisplatin have insufficient effectiveness and act non-specifically, leading to several adverse drug reactions To address these issues, the biological efficacy of the cisplatin-resveratrol combination was tested.Methods: To find IC50, gastric adenocarcinoma cells (AGS) were exposed to different concentrations of resveratrol and cisplatin. Anti-cancer and anti-metastatic effects of 100 M resveratrol with concentrations of cisplatin (25, 50, and 100 g/ml) were studied by assessing ß-galactosidase and telomerase activities, senescence and migration gene expression, reactive oxygen species (ROS) level, and cell cycle arrest.Results: Co-administration of cisplatin and resveratrol increased ß-galactosidase activity, ROS level as a key marker of oxidative stress, p53, p38, p16, p21, and MMP-2 gene expression, and induced G0/G1 cell cycle arrest. Additionally, telomerase activity, pro-inflammatory gene expression, and cell invasion were suppressed. The best results were achieved with 100 g/ml cisplatin co-administered with resveratrol.Conclusion: The current study proved the synergistic effect of the cisplatin-resveratrol combination on suppressing metastasis and inducing apoptosis and cell senescence through targeting P38/P53 and P16/P21 pathways. Such promising results warrant translation to animal models and the clinic. This may lead to cost-effective, available, and accessible treatment regimens with targeted action and the fewest ADRs.

BackgroundDiabetes-induced reproductive complications can lead to subfertility and infertility, raising the need to protect reproductive organs. There are limited medications used to improve reproductive health in diabetic patients. Melatonin, mainly produced by the pineal gland, may improve diabetes-associated reproductive complications through various mechanisms and may be a preferred candidate to protect the reproductive system. The present review aims to elucidate the underlying mechanisms of melatonin’s effect on the reproductive system adversely affected by diabetes mellitus (DM).MethodsA comprehensive systematic literature electronic search was done using the PRISMA guidelines. Web of Science, PubMed, Embase, and Scopus were searched for publications up to June 2022. Search terms were selected based on the study purpose and were explored in titles and abstracts. After screening, out of a total of 169 articles, 14 pertinent articles were included based on our inclusion and exclusion criteria.ResultsThe results of studies using rats and mice suggest that DM adversely affects reproductive tissues, including testes and epididymis, prostate, corpus cavernosum, and ovary leading to alterations in histological and biochemical parameters compared to the normal groups. Treatment with melatonin improves oxidative stress, blocks apoptosis induced by endoplasmic reticulum stress and caspase activation, reduces pro-inflammation cytokines, and enhances steroidogenesis.ConclusionMelatonin exerted a protective action on the impaired reproductive system in in-vivo and in-vitro models of DM. The topic has to be followed up in human pregnancy cases that will need more time to be collected and approved.

Aluminum phosphide (AlP) poisoning can be highly fatal due to its severe toxicity to the heart. Based on the evidence, edaravone (EDA) has protective effects on various pathological conditions of the heart. This research aimed to examine the potential protective effects of EDA on AlP-induced cardiotoxicity in rats. The rats were divided into six groups, including almond oil (control), normal saline, AlP (LD50), and AlP + EDA (20, 30, and 45 mg/kg). Thirty minutes following AlP poisoning, the electrocardiographic (ECG), blood pressure (BP), and heart rate (HR) parameters were examined for 180 min. The EDA was injected 60 min following the AlP poisoning intraperitoneally. Also, 24 h after poisoning, echocardiography was carried out to evaluate the ejection fraction (EF), stroke volume (SV), and cardiac output (CO). The biochemical and molecular parameters, such as the activities of the mitochondrial complexes, reactive oxygen species (ROS), apoptosis and necrosis, and troponin I and lactate levels, were also examined after 12 and 24 h in the heart tissue. According to the results, AlP-induced ECG abnormalities, decrease in blood pressure, heart rate, SV, EF%, and CO were significantly improved with EDA at doses of 30 and 45 mg/kg. Likewise, EDA significantly improved complex I and IV activity, apoptosis and necrosis, ROS, troponin I, and lactate levels following AlP-poisoning (p < 0.05). Also, the mean survival time was increased following EDA treatment, which can be attributed to the EDA’s protective effects against diverse underlying mechanisms of phosphine-induced cardiac toxicity. These findings suggest that EDA, by ameliorating heart function and modulating mitochondrial activity, might relieve AlP-induced cardiotoxicity. Nonetheless, additional investigations are required to examine any potential clinical advantages of EDA in this toxicity.

Root-knot nematodes, Meloidogyne species are among the most critical plant-parasitic nematodes attacking okra Abelmoschus esculentus (L.) Moench in tropical and subtropical regions. In the present study, the effects of various levels of zinc and iron on okra infected with M. javanica were investigated under greenhouse conditions in a completely randomized factorial design with five replications. Four-leaf stage seedlings of the susceptible okra, cv. Clemson Spineless were inoculated with 8000 eggs of M. javanica per pot. Five days later, the soil of each pot was treated with a combination of iron or zinc (0, 1, 3, and 6 mg∙kg-1 soil) from nano chelated iron and zinc fertilizer sources. Sixty days after inoculation, plants were harvested, and okra growth indices and nematode population indices were determined. Results showed that vegetative indices increased in most cases compared to non-treated plants. Fruit fresh weight of inoculated plants treated with iron at the rate of 1 mg∙kg-1 soil + zinc at the rate of 3 mg∙kg-1 soil from nano chelated iron and zinc fertilizer sources increased by 205%, compared to inoculated control plants. Combined application of iron at the rate of 6 mg∙kg-1 soil + zinc at the rate of 6 mg∙kg-1 soil from nano chelated iron and zinc fertilizer sources reduced the number of eggs, galls, and egg masses per root system and the reproductive factor (224, 415, 455 and 231%, respectively) compared to non-treated plants.

Background and objectives: Inflammatory bowel disease (IBD) is a recurrent chronic inflammatory disease of the gastrointestinal tract. In Iranian traditional medicine, the oleo-gum-resin of the genus Pistacia is recommended for treatment of various diseases including gastrointestinal disorders. The present study investigated the therapeutic action of a combination of Pistacia atlantica subspecies kurdica oleo-gum-resin and honey in acetic acid-induced colitis in rats. Methods: Pistacia atlantica oleo-gum-resin was mixed with honey. The mixture was suspended in distilled water. Following induction of colitis with 4% acetic acid in all animals, except in sham group,themixture was orally administered for two consecutive days at the concentrations of 100, 200, 400 mg/kg. Other groups included the control, sham and a standard group (dexamethasone). Microscopic and histopathologic examinations were conducted in inflamed colonic tissue. The inflammatory biomarkers of colitis including interleukin 6 (IL-6), tumor necrosis factor (TNF-α), and myeloperoxidase (MPO) and the gene expression level of toll like receptor-4 (TLR-4) were assessed. Results: Pistacia atlantica oleo-gum-resin+ honey induced significant progress in macroscopic and microscopic scores. Colonic levels of MPO, IL-6, and TNF-α significantly declined in rats treated with the mixture; while significant decrease in mucosal gene expression of TLR-4 and significant improvement of colitis were observed. Pistacia atlantica oleo-gum-resin (400 mg/kg) + honey (400 mg/kg)reduced inflammation of the bowel and colonic ulcer severity shown by downregulation of inflammation cytokines, reduction of neutrophil infiltration, and suppression of TLR-4 expression. Conclusion: The combination might be a promising supplement for treatment of inflammatory disorders.

The required capital and liquidity for agricultural production are always a limiting factor in Iranian agriculture. Since, income is a combination of production and product price, one of the major problems of the country's pistachio industry is the high yield fluctuations and high price fluctuations. In the present study, the mean and yield fluctuations of four pistachio commercial cultivars (Kaleh-Ghoochi, Ahmad-Aghaei, Akbari, and Owhadi) were evaluated in the Anar and Rafsanjan orchards in Kerman province. The information used in this study was collected through a questionnaire from farmers. The orchards were selected by multi-stage random method. From the total number of villages in the two regions, some sites were selected based on random. Then, some farmers were selected randomly. By referring to the selected farmers, an orchard was selected from each cultivar. The number of studied orchards was 100 forms in each cultivar. To measure the yield per hectare, the amount of actual product that had achieved in the last six years. Finally, the mean and yield fluctuations of 4 pistachio commercial cultivars were analyzed. The results showed that the studied cultivars had a significant difference in the yield, profit net and coefficient variation at a probability level of 5%. The results indicated that the Ahmad-Aghaei cultivar was the best in average yield (1758.7 kg ha-1) and net profit per hectare (292530201 Rials ha-1) and then Akbari cultivar. However, performance fluctuations in the Owhadi cultivar (53.06%) was lower than the other three cultivars. Base on the results, the Kaleh-Ghoochi cultivar was minimum in average yield (1073.6 kg ha-1) and production fluctuations (73.14%) than the others. Therefore, if the aim is to minimize the income fluctuations of pistachio farmers, depending on the region, one of Ahmad-Aghaei or Akbari cultivars should be planted. It can be concluded that among commercial cultivars, prioritization and justification for planting and propagation were Ahmad-Aghaei, Akbari, Owhadi and Kaleh-Ghoochi, respectively.

Background: Althaea officinalis L., Lavandula angustifolia Mill. and Rosa x damascena Herrm. are used to treat excision or burn lesions in traditional medicine. Objective: To evaluate the healing effect of a polyherbal ointment containing L. angustifolia, R. x damascena, and A. officinalis combination on wounds caused by third grade skin cut. Methods: To evaluate the wound healing effect of this polyherbal formulation, an ointment containing the extract of A. officinalis, the essential oil of R. x damascena (2 % essence) and the essential oil of L. officinalis (2 % essence) in an eucerin base (20:20:10:50) was prepared. The formulation was examined using excision wound test for 14 days and the percentage of healing effect in each group was calculated. Formalin induced rat hind paw edema method was used for determination of anti-inflammatory activities of the same formulation. Results: The percentage of recovery in the polyherbal formulation group was significantly higher than the other groups. Histological studies also confirmed these results. Herbal formulation treated group showed significant improvement in terms of re-epithelialization, angiogenesis, collagen deposition, and reducing inflammation. The percentage of wound healing was 99.07 ± 0.34, 99.22 ± 0.35, 98.45 ± 0.733, 98.75 ± 0.88 and 63.72 ± 5.64, for the polyherbal formulation, L. angustifolia, R. damascena, A. officinalis extracts, and the placebo group, respectively. Conclusion: This polyherbal formulation could act as a wound healing agent, possibly due to the suppression of inflammatory mediators. The presence of phenolic compounds might be a reason behind the therapeutic effect of these plants.

Botulinum toxin type-A (BoNT/A) application, especially neurological disorders, has been spread nowadays while it may cause side effects. The current study aimed to assess the BoNT/A dose-dependent effect on induction of aging in the Drosophila melanogaster model. The third instar larvae of Drosophila melanogaster were exposed to ¼ LC50, ½ LC50, and LC50 of BoNT/A in the Drosophila diet for 48 h while H2O2 1% was used as a positive control. After the exposure time, some larvae were collected for molecular study, including gene expression analysis, comet assay, oxidative stress markers, and the phenotype changes. BoNT/A induced dose-dependent cytotoxicity, elevated reactive oxygen species (ROS) levels, and superoxide dismutase (SOD) enzyme activity. In addition, it caused DNA damage and activated caspase-3 and -9, and reduced the body size of the fly, especially in high doses. In line with the purpose of the study, aging markers, including β-galactosidase (β-gal), p16, p21, p38, and p53, were up-regulated by BoNT/A low dose. BoNT/A activates the aging pathway in the low dose, and increasing the dose induces toxicity, including oxidative stress, DNA damage, and apoptosis.

In this research, a simple, label-free, and ultra-sensitive fluorescent platform based on a metal–organic framework (MOF) has been developed to detect melamine in milk powder. This fluorescence sensor was fabricated from sensitized terbium (Tb)@NH2-MIL-253 (Al) MOF using a hydrothermal method that involved combining the green emission of Tb (λem = 545 nm) with the blue emission of NH2-MIL-253(Al) MOF (λem = 430 nm) under a single excitation wavelength (λex = 335 nm). The fluorescence sensor was then used under optimized conditions (pH = 9.0; sensor concentration = 30 mg/L; response time = 30 s) to quantify melamine in milk powder. The accuracy, sensitivity, and reproducibility of this sensor were established compared to the high-performance liquid chromatography (HPLC) method. The linear range and lower limit of detection (LLOD, computed with 3σ/S) of the sensor were between 40–396.45 nM (equal to 25 µg/kg–0.25 mg/kg) and 40 nM (equal to 25 µg/kg), respectively, which is much less than the maximum residual level (MRL) for the detection of melamine in infant formula (1 mg/kg) and other foods/feeds (2.5 mg/kg). Additionally, the results had good agreement with the HPLC outcomes, suggesting that the NH2-MIL-253(Al) MOF sensing probe has great precision and repeatability. To conclude, the new fluorescence sensor developed in this study can accurately and sensitively detect melamine in food samples, which may be useful for screening for adulteration of milk powders and other foods.

Abstract Background COVID-19 has caused great concern for patients with underlying medical conditions. We aimed to determine the prognosis of patients with current or previous cancer with either a PCR-confirmed COVID-19 infection or a probable diagnosis according to chest CT scan. Methods We conducted a case control study in a referral hospital on confirmed COVID-19 adult patients with and without a history of cancer from February25th to April21st, 2020. Patients were matched according to age, gender, and underlying diseases including ischemic heart disease (IHD), diabetes mellitus (DM), and hypertension (HTN). Demographic features, clinical data, comorbidities, symptoms, vital signs, laboratory findings, and chest computed tomography (CT) images have been extracted from patients’ medical records. Multivariable logistic regression was used to estimate odd ratios and 95% confidence intervals of each factor of interest with outcomes. Results Fifty-three confirmed COVID-19 patients with history of cancer were recruited and compared with 106 non-cancerous COVID-19 patients as controls. Male to female ratio was 1.33 and 45% were older than 65. Dyspnea and fever were the most common presenting symptoms in our population with 57.86 and 52.83% respectively. Moreover, dyspnea was significantly associated with an increased rate of mortality in the cancer subgroup (p = 0.013). Twenty-six patients (49%) survived among the cancer group while 89 patients (84%) survived in control (p = 0.000). in cancer group, patients with hematologic cancer had 63% mortality while patients with solid tumors had 37%. multivariate analysis model for survival prediction showed that history of cancer, impaired consciousness level, tachypnea, tachycardia, leukocytosis and thrombocytopenia were associated with an increased risk of death. Conclusion In our study, cancer increased the mortality rate and hospital stay of COVID-19 patients and this effect remains significant after adjustment of confounders. Compared to solid tumors, hematologic malignancies have been associated with worse consequences and higher mortality rate. Clinical and para-clinical indicators were not appropriate to predict death in these patients.

Insecticides are commonly used pesticides in the world. Chronic exposure to insecticides has adverse effects on various human body organs. In this study, hematological findings were assessed in workers in an insecticide manufacturing plant. Hematological parameters and clinical symptoms were recorded in 99 workers exposed to insecticides and 107 workers not exposed to them in a cross-sectional study. Assessment of the hematological results showed a higher prevalence of thrombocytosis in the exposed group than the non-exposed group (P < 0.05). Mean white blood cell (WBC) and platelet counts, anisocytosis of red blood cells (RBCs), and neutrophils to lymphocytes ratio (NLR) were significantly higher in the exposed group compared to the non-exposed group (P < 0.05). Prevalence rates of headache, itchy skin, cough, and sleep disorders were higher in the exposed group than in the non-exposed group (P < 0.05). Chronic exposure to insecticides can alter hematological parameters in the normal range. Occupational exposure to insecticides may increase WBCs, platelet count, NLR, and red cell distribution width (RDW). It can also cause thrombocytosis. Complete blood count (CBC), as an inexpensive and accessible tool, can help monitor workers' health status exposed to insecticides properly.

Objective Metformin has a potent inhibitory activity against inflammation and oxidative stress, which inevitably occur in sepsis-associated encephalopathy (SAE). The precise mechanisms underlying neuroprotective effects of metformin in SAE, are still unclear. In the present work, the protective effect of metformin on SAE using cecal ligation and puncture (CLP) model of sepsis, was assessed. Materials And Methods In this experimental study, CLP procedure was performed in Wistar rats and 50 mg/kg metformin was administered immediately. Specific markers of sepsis severity, inflammation, blood brain barrier (BBB) dysfunction, and brain injury, were investigated. Specific assay kits and real-time polymerase chain reaction (RT-PCR) were used. Histopathological assessment was also carried out. Results Treatment with metformin decreased murine sepsis score (MSS), lactate, platelet lymphocyte ratio (PLR), and high mobility group box (HMGB1) levels. The expression levels of claudin 3 (Cldn3) and claudin 5 (Cldn5) were increased following treatment with metformin. Metformin decreased the expression of S100b, neuron specific enolase (Nse), and glial fibrillary acidic protein (Gfap). Conclusion Our study suggests that metformin may inhibit inflammation and increase tight junction protein expressions which may improve BBB function and attenuate CLP-induced brain injury. Hence, the potential beneficial effects of metformin in sepsis, should be considered in future.

Sulfur-containing pollutants lead to reduced quality of end products and environmental problems. Mercaptans are one of those sulfur pollutants which not only are smelly and toxic but also have high corrosive property. Mercaptan catalytic oxidation is the most important method of oil production refining from mercaptan. Thus, cognition of the reaction kinetics and interrogation of effects of various factors on the process are of the most requirements of mercaptan removing units. Due to the inadequate efforts made on reaction kinetics determination of catalytic oxidation of light mercaptans available in liquefied petroleum gas (LPG), this study was done in this regards. First, rate-determining step (RDS) of reactions was determined by analyzing the experimental data obtained from the Merox unit. The experiments were carried out on a cobaltphthalocyanine liquid catalyst in a packed reactor. In order to better understand the process, design, and optimization, the kinetics were defined with respect to the limiting reaction. By investigating the effective parameters of the kinetics, it was determined that the mercaptide ion (RS-) confines the oxidation reaction rate and has the first order in the rate equation. Finally, optimal values were proposed for each of the parameters.

Background: Obesity as a developing global challenge can be characterized by increase in adipocyte number and size arising from adipogenesis. Control of adipogenesis, as a potential strategy, can prevent and manage obesity. So far, the effectiveness of herbal medicine and active ingredients therapies for obesity and metabolic syndrome treatment has been investigated. In this study, a novel combination of berberine, catechin, and capsaicin was developed, and their effect on 3T3-L1 adipocytes was investigated. Methods: The effect of active ingredient on the cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Adipocytes were treated with various concentrations of berberine (3 and 6.25 μM), catechin (6.25 and 12.5 μM), and capsaicin (6.25 and 12.5 μM) alone and in combination. Results: All active ingredients did not affect the cell viability by MTT assay at different concentrations. The dual and triple combinations of three active ingredients showed excellent potential as anti-obese without any toxicity. The inhibitory effect of berberine, catechin, and capsaicin on the differentiation of 3T3-L1 preadipocytes was found to be dose-dependent. These results indicate that catechin in both doses may have a stronger effect than the two other active ingredients on the intracellular lipid accumulation. Also, the triple combination of the aforementioned ingredients showed better responses than their dual combination. Conclusion: This work is the first report to simultaneously investigate these three active ingredients in a single, dual, and triple formats. The berberine, catechin, and capsaicin co-treatment inhibits the adipogenesis during the differentiation process. This compound can be a prospective therapy for obesity and relevant diseases such as dyslipidemia.

Abstract The COVID-19 pandemic has become the leading societal concern. The pandemic has shown that the public health concern is not only a medical problem, but also affects society as a whole; so, it has also become the leading scientific concern. We discuss in this treatise the importance of bringing the world’s scientists together to find effective solutions for controlling the pandemic. By applying novel research frameworks, interdisciplinary collaboration promises to manage the pandemic’s consequences and prevent recurrences of similar pandemics.

Background: Ethnomedicinal plants are of interest for treatment of various wound types. Objective: This study aimed to evaluate burn wound healing potential of the hydro-alcoholic extract of the flowers of Lilium candidum L. in rats. Methods: DPPH free radical scavenging power, total flavonoids, and the phenolic content of the extract were evaluated. Following burn wound induction, 30 Wistar rats were divided into 5 groups; silver sulfadiazine cream 1% (reference standard), eucerin (control), and 5%, 10% and 20% ointments of L. candidum flowers extract (treatment groups). Wound contraction and the percentage of wound healing were measured every day until 14th day and the histological changes were evaluated. Results: DPPH assay of L. candidum extract indicated high antioxidant activity. Total phenolic content of L. candidum extract was equal to 157 mg gallic acid equivalent/g; while total flavonoid was measured as 32.4 mg quercetin equivalent/g dried extract. The mean of wound area was significantly different in three 5%, 10% and 20% extract-treated rats in comparison with the control. Although, 20% ointment of L. candidum flowers extract demonstrated the best wound healing improvement, even better than silver sulfadiazine. Histopathological analysis confirmed the wound healing activity of L. candidum and promoting tissue repair, especially for the ointment containing 20% extract. Conclusion: Regarding the high content of phenolic compounds and flavonoids, besides potent antioxidant properties of the flowers of L. candidum, the use of its ointments led to significant decrease of burn wound area, suggesting that these extract ointments can treat burn wounds and improve the healing processes.

Abstract Effects of Pseudomonas fluorescens L. (jimsonweed) (Pf) isolate and the two plant extracts, Datura stramonium and Myrtus communis, were investigated on hatching and juvenile (J2s) mortality of Meloidogyne javanica (Tylenchida: Heteroderidae) under laboratory conditions. After determining the values of LC30, LC50, and LC70 of each extract, four leaf stage seedlings of tomato were treated by 20 ml of Pf suspension at a concentration of 108 CFU/ml, using a soil drenching method. After 1 week, the tested plants were inoculated by 4000 eggs and (J2s) of M. javanica and simultaneously were treated by 100 ml of the selected concentrations of D. stramonium (1.1, 1.4, and 1.8%) and M. communis (1.8, 3 and 5.2%), as soil drench. Results showed that a combination of Pf and the leaf extract, D. stramonium at the rate of 1.8% or M. communis at the rate of 5.2%, respectively, reduced the number of eggs per root system and the reproduction factor by 68 and 45%, the number of galls by 64 and 33%, and the number of egg masses by 65 and 43%, than the control. In conclusion, combination of Pf and D. stramonium at the rate of 1.8% or M. communis at the rate of 5.2% can significantly reduce the damage of M. javanica on tomato, under greenhouse conditions.

Crohn's disease (CD) is an inflammatory disease of the gastrointestinal tract (GIT) and can affect several parts of the digestive system. There is a relationship between impaired mucosal barrier in the GIT of inflammatory bowel disease patients and the role of bacteria such as Mycobacterium avium in CD. Apart from different therapeutic approaches for treating CD, development of a vaccine is a novel modality. In the present article, most available therapeutic opportunities in the last decade, especially the possibility of vaccines against CD, are reviewed. According to the search, availability of a new generation of vaccines against CD is expected specially tolerogenic ex vivo-derived DC-based vaccines. Regarding different locations of the challenge and the variety of clinical manifests of CD and also the type of resident antigen-presenting cells and their traffic in different parts of GIT, the results of immunotherapy with DC-based vaccines may vary case by case.

Background: Parkin-mediated mitophagy is the dominant mitophagy pathway of neural cells. Its restoration will result in prevention of cognitive decline, including Alzheimer's disease (AD). The role of this mitophagy pathway in neurodegenerative diseases has drawn attention in recent years. The two main pathological proteins in AD, amyloid β (Aβ) and human Tau (hTau), interfere with mitochondrial dynamics through several pathways. However, taking into consideration the specific interactions between Aβ/hTau and Parkin, special focus is required on this mitophagy pathway and AD. In this review, these interactions are fully discussed, and an overview of the neuroprotective drugs that enhance Parkin-mediated mitophagy is presented.Methods: This systematic review was performed according to PRISMA guidelines, and a comprehensive literature search was done in the electronic databases up to September 2020, using search terms in the titles and abstracts to identify relevant studies. One hundred eighty-six articles were found, and 113 articles were screened by title and abstract. Finally, 25 articles were included in this systematic review according to our inclusion and exclusion criteria.Results: Accumulation of Aβ and hTau affects mitophagy, including Parkin-mediated. Tau seems to prevent Parkin translocation directly. A Parkin level in the cell appears to be of importance in determining the damage caused by Aβ and hTau and in the future therapeutic approaches. Parkin controls the PINK1 level via the presenillins, suggesting that mutations in presenillins affect Parkin mitophagy.Significance: Parkin mitophagy is a process affected by several AD pathological events multidimensionally.

Despite advances in sepsis management, it remains a major intensive-care-unit (ICU) concern. From new prospective, positive effects of metformin, such as anti-oxidant and anti-inflammatory properties are considered potentially beneficial properties for management of septic patients. This article reviewed the potential ameliorative effects of metformin in sepsis-induced organ failure. Information were retrieved from PubMed, Scopus, Embase, and Google Scholar. Multi-organ damage, oxidative stress, inflammatory cytokine stimulation, and altered circulation are hallmarks of sepsis. Metformin exerts its effect via adenosine monophosphate-activated protein kinase (AMPK) activation. It improves sepsis-induced organ failure by inhibiting the production of reactive oxygen species (ROS) and pro-inflammatory cytokines, preventing the activation of transcription factors related to inflammation, decreasing neutrophil accumulation/infiltration, and also maintaining mitochondrial membrane potential. Studies reported the safety of metformin therapeutic doses, with no evidence of lactic acidosis, in septic patients.

Background and objective: Trachyspermum ammi (T. ammi) has been used for the treatment of various digestive disorders with considerable therapeutic effects such as anticholinergic and anti-oxidant activities.This study aimed to evaluate the efficacy of the hydro-alcoholic extract of the fruits of T. ammi in an experimental model of irritable bowel syndrome (IBS). Methods: The rats were classified into seven groups, including sham (no stress), control (saline recipients), loperamide and fluoxetine (10 mg/kg/day) (positive controls), and the plant groups at the doses of 150, 250 and 500 mg/kg/day for 5 days under restrictive stress, 2 days before receiving the treatment. All medicines were given as gavage. The effect of the plant extract on gastric emptying and the transit of the small intestine was evaluated. The levels of the inflammatory and oxidative related biomarkers, tumor necrosis factor alpha (TNF-α) and lipid peroxidation (LPO), also the myeloperoxidase (MPO) activity were measured. Results: The gastric emptying and the transit of the small intestine were significantly reduced in all T. ammi treated groups, and no significant difference was observed at the dose of 500 mg/kg/day compared with the loperamide group. The levels of TNF-α and MPO activities decreased in the treatment groups compared with the control, and the LPO level was decreased at the concentrations of 250 and 500 mg/kg/day compared to the control. The antioxidant levels significantly increased in the rats treated with T. ammi at the doses of 250 and 500 mg/kg/day. Conclusions: The severity of stress-induced IBS was reduced in a dose-dependent manner by the hydro-alcoholic extract of the fruits of T. ammi, confirming the effectiveness of this plant in the management of IBS.

Objective(s): Diabetes is a metabolic disease with an increasing prevalence for which finding new and efficient therapeutic approaches has always been a challenge. Preserving integrity and functionality of pancreatic β-cells as the only source of insulin in the body is such a case. To achieve this goal different cellular targets have been proposed among which pancreatic estrogen receptors have gotten much attention. In this work, we evaluated the integrity and function of islets of Langerhans under the influence of factors known to intervene with estrogen receptors. Cadmium, a toxic heavy metal, has been recently shown to interact with estrogen receptors but its toxicity in the pancreatic islets regarding this mechanism remains unclear. Materials and Methods: Isolated islets of Langerhans from the pancreas of rats were grouped and treated with cadmium chloride and also cadmium chloride plus β-estradiol. After 24 hr incubation, parameters of cellular viability, oxidative stress, apoptosis, and insulin secretion were measured. Results: The results indicated that cadmium reduced viability of the islets along with an increase in the formation of reactive oxygen species and apoptosis markers, and β-estradiol, in turn, was able to alleviate these disturbances to some extent, implicating the protective role of β-estradiol against pancreatic toxicity of cadmium. Conclusion: It can be concluded that modification of estrogen receptors in the endocrine pancreas and especially β-cells may be a promising target to find a new therapeutic strategy for diabetes and even uncovering mechanisms of environmental toxicants that have been known as risk factors of diabetes.

Background: Cystic ovarian disease (COD) is one of the common reproductive disorders which affecting the fertility of dairy cattle induces heavy financial burdens on herds owners. Various insecticides, fungicides and herbicides, collectively known as pesticides are frequently used in the agricultural systems of different countries. Given the fact that pesticides are known to have endocrine disrupting properties, exposure to these compounds may play a role in the development of COD. Materials and Methods: The plasma concentrations of a complete profile of common pesticides including organophosphorus, organochlorine, and carbamate and pyrethroid compounds in the plasma of cattle with COD compared to healthy controls was examined. Moreover, plasma concentrations of inflammatory cytokines as well as oxidative stress parameters were investigated. Results: No significant amounts of any of the pesticides investigated were detectable in the plasma of neither the healthy nor cystic cows. The plasma indices of total antioxidant capacity (TAC), thiol, lipid peroxidation (LPO), and reactive oxygen species (ROS) did not show any significant differences between the affected and the control groups. Tumor necrosis factors alpha (TNF-α), progesterone, lymphocyte, neutrophil, fibrinogen and MCHC had significantly higher amounts in the plasma of COD cows. Conclusion: Findings of the present study do not support the notion that exposure to the studied pesticides is a contributing factor in the development of follicular cysts in dairy cattle. In addition, TNF-α might be affected as a factor in the pathogenesis of COD by an independent pathway of pesticides effect.

Tragopogon graminifolius DC. is a perennial plant from the family Asteraceae which grows in West parts of Iran. Several biological activities like antimicrobial, antioxidant and anti-inflammatory effects are reported for the plant. The aim of this study was to assess the wound healing activity of standardized extract from T. graminifolius (TG) aerial parts. Topical standardized TG extract with 5% and 10% concentrations in eucerine base was assessed for its healing properties on second degree burn in rats during a 14-day period. Biomarkers of oxidative damage including total antioxidant power, lipid peroxidation and total thiol molecules of the skin tissue samples were also evaluated. Results showed that 10%TG had the best efficacy with 80 ± 3% wound closure and tissue repair in comparison to negative control (p

Chlorpyrifos (CPF) is an organophosphorus (OP) pesticide, resulting in various health complications as the result of ingestion, inhalation, or skin absorption, and leads to DNA damage and increased oxidative stress. Metformin, derived from Galega officinalis, is reported to have anti-inflammatory and anti-apoptotic properties; thus, this study aimed to investigate the beneficial role of metformin in neurotoxicity induced by sub-acute exposure to CPF in Wistar rats. In this study, animals were divided into nine groups and were treated with different combinations of metformin and CPF. Following the 28 days of CPF and metformin administration, brain tissues were separated. The levels of inflammatory biomarkers such as tumor necrosis factor alpha (TNFα) and interleukin 1β (IL-1β), as well as the expression of 5HT1 and 5HT2 genes, were analyzed. Moreover, the levels of malondialdehyde (MDA), reactive oxygen species (ROS), and the ADP/ATP ratio, in addition to the activity of acetylcholinesterase (AChE) and superoxide dismutase (SOD), were tested through in vitro experiments. This study demonstrated the potential role of metformin in alleviating the mentioned biomarkers, which can be altered negatively as a result of CPF toxicity. Moreover, metformin showed protective potential in modulating inflammation, as well as oxidative stress, the expression of genes, and histological analysis, in a concentration-dependent manner.

Acrylamide is a toxic chemical substance produced when starch-rich foods are fried at high temperatures. Asthma is a chronic and complicated respiratory disease, of which genetic and environmental factors are the main triggers. Orally-received components may have an effect on asthma pathophysiology. The aim of this study was to investigate the role of AA as a stimulus in asthma. BALB/c mice were allocated into four groups as follows: two OVA-sensitized asthmatic groups, including one treated with AA by gavage feeding and one non-treated (asthma group), and two healthy (non-asthmatic) groups, one treated with AA by gavage feeding and one non-treated (negative control group). Airway hyperresponsiveness, cell count, cytokine levels in BAL fluid, lung histopathology, IgE levels, and oxidative stress indices including plasma level of MDA, pulmonary antioxidant enzymes (SOD and CAT) levels, HP content, and collagen fiber accumulation in lung tissue were measured. We found that the group of mice treated with both OVA and AA (asthmatic and AA-treated mice) experienced higher levels of asthma-associated biomarkers, including higher enhanced pause (Penh value), eosinophilic inflammation, mucus hyper secretion, goblet cell hyperplasia, total and OVA-specific IgE levels, IL-4, IL-5, and IL-13 levels than the group sensitized only with OVA (asthmatic mice). The OVA-AA-treated mice also experienced worsened levels of oxidative stress indicators. Healthy (non-asthmatic) mice that only received AA were in similar conditions to healthy untreated mice (negative control group). The OVA-AA-treated group showed more severe allergic asthma symptoms in comparison to the group only sensitized with OVA. Therefore, food/water contaminated with AA can act as a stimulant of allergic asthma and exacerbate the bronchial inflammatory responses.

Polycystic ovary syndrome (PCOS) is an endocrine-gynecology disorder affecting many women of childbearing age. Although a part of the involved mechanism in PCOS occurrence is discovered, the exact etiology and pathophysiology are not comprehensively understood yet. We searched PubMed for PCOS pathogenesis and management in this article and ClinicalTrials.gov for information on repurposed medications. All responsible factors behind PCOS were thoroughly evaluated. Furthermore, the complete information on PCOS commonly prescribed and repurposed medications is summarized through tables. Epigenetics, environmental toxicants, stress, diet as external factors, insulin resistance, hyperandrogenism, inflammation, oxidative stress, and obesity as internal factors were investigated. Lifestyle modifications and complementary and alternative medicines are preferred first-line therapy in many cases. Medications, including 3-hydroxy-3-methyl-3-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors, thiazolidinediones, sodium-glucose cotransporter-2 inhibitors, dipeptidyl peptidase-4 inhibitors, glucose-like peptide-1 receptor agonists, mucolytic agents, and some supplements have supporting data for being repurposed in PCOS. Since there are few completed clinical trials with a low population and mostly without results on PCOS repurposed medications, it would be helpful to do further research and run well-designed clinical trials on this subject. Moreover, understanding more about PCOS would be beneficial to find new medications implying the effect via the novel discovered routes.

Bisphenol A (BPA) as a pervasive endocrine-disrupting compound (EDC) has been shown to cause multiple detrimental effects including cardiovascular disorders, pregnancy complications, obesity, glucose metabolism disorders, and reproductive toxicity even at a concentration as low as tolerable daily intake (TDI) (4 μg/kg/day). In the present study, a novel ultra-sensitive, electrochemical aptasensor was designed using a screen-printed carbon electrode (SPCE) modified by gold nanoparticles (Au NPs) conjugated to thiolated aptamers for accurate determination of BPA in biological, industrial and environmental samples. To characterize the electrochemical properties of the aptasensor, cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were implemented. Detection of BPA was also performed through differential pulse voltammetry (DPV) in [Fe(CN)6]3–/4– electrolyte solution. Under optimum condition, the present electrochemical aptasensor demonstrated an outstanding linear response in the concentration range of 1 pM to 10 nM with a remarkably low limit of detection of 0.113 pM. Due to the superb affinity between anti-BPA aptamers and BPA molecules, the designed aptasensor did not show any significant interaction with other analytes in real samples. Also, fabricated biosensor remained perfectly stable in long-term storage. The analytical results of the fabricated aptasensor are well compatible with those obtained by the ELISA method, indicating the trustworthiness and reasonable accuracy of the application of aptasensor in real samples. Overall, the proposed aptasensor would be a credible and economical method of precise, reproducible, and highly selective detection of minimum levels of BPA in food containers and clinical samples. This would be a promising strategy to enhance the safety of food products and reduce the risk of BPA daily exposure.

Purpose: The current project aimed to design a simple, highly sensitive, and economical label-free electrochemical aptasensor for determination of prostate-specific antigen (PSA), as the gold standard biomarker for prostate cancer diagnosis. The aptasensor was set up using a screen-printed carbon electrode (SPCE) modified by gold nanoparticles (Au NPs) conjugated to thiolated aptamers. Methods: Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were implemented for electrochemical (EC) characterization of the aptasensor. The determination of PSA was also performed through differential pulse voltammetry (DPV) in [Fe (CN) 6]3-/4- electrolyte solution. Results: The present aptasensor was shown an outstanding linear response in the concentration range of 1 pg/mL - 200 ng/mL with a remarkably lower limit of detection of 0.077 pg/mL. The optimum concentration for PSA separation and the optimum incubation time for antigen-aptamer binding were determined by observing and electing the highest electrochemical responses in a specified time or concentration. Conclusion: According to the results of the specificity tests, the designed aptasensor did not show any significant interactions with other analytes in real samples. Clinical functionality of the aptasensor was appraised in serum samples of healthy individuals and patients examining the PSA level through the fabricated aptasensor and the reference methods. Both methods are comparable in sensitivity. The present fabricated PSA aptasensor with substantial characteristics of ultra-sensitivity and cost-effectiveness can be conventionally built and used for the routine check-up of the men for prostate problems.

Metabolic syndrome includes a series of metabolic abnormalities that leads to diabetes mellitus and cardiovascular diseases. Plant extracts, due to their unique advantages like anti-inflammatory, antioxidant, and insulin sensitizing properties, are interesting therapeutic options to manage MetS; however, the poor solubility and low bioavailability of lipophilic bioactive components in the herbal extracts are two critical challenges. Nano-scale delivery systems are suitable to improve delivery of herbal extracts. This review, for the first time, focuses on nanoformulations of herbal extracts in MetS and related complications. Included studies showed that several forms of nano drug delivery systems such as nanoemulsions, solid lipid nanoparticles, nanobiocomposites, and green-synthesized silver, gold, and zinc oxide nanoparticles have been developed using herbal extracts. It was shown that the method of preparation and related parameters such as temperature and type of polymer are important factors affecting physicochemical stability and therapeutic activity of the final product. Many of these formulations could successfully decrease the lipid profile, inflammation, oxidative damage, and insulin resistance in in vitro and in vivo models of MetS-related complications. Further studies are still needed to confirm the safety and efficacy of these novel herbal formulations for clinical application.

Nanotechnology is one of the methods that influenced human life in different ways and is a substantial approach that assists to overcome the multiple limitations of various diseases, particularly neurodegenerative disorders (NDs). Diverse nanostructures such as polymer nanoparticles, lipid nanoparticles, nanoliposomes, nano-micelles, and carbon nanotubes (CNTs); as well as different vehicle systems including poly lactic-co-glycolic acid, lactoferrin, and polybutylcyanoacrylate could significantly increase the effectiveness, reduce the side effects, enhance the stability, and improve the pharmacokinetics of many drugs. NDs belong to a group of annoying and debilitating diseases that involve millions of people worldwide. Previous studies revealed that several nanoformulations from a number of natural products such as curcumin (Cur), quercetin (QC), resveratrol (RSV), piperine (PIP), Ginkgo biloba, and Nigella sativa significantly improved the condition of patients diagnosed with NDs. Drug delivery to the central nervous system (CNS) has several limitations, in which the blood brain barrier (BBB) is the main drawback for treatment of NDs. This review discusses the effects of herbal-based nanoformulations, their advantages and disadvantages, to manage NDs. In summary, we conclude that herbal-based nano systems have promising proficiency in treatment of NDs, either alone or in combination with other drugs.

Misfolded proteins are the main common feature of neurodegenerative diseases, thereby, normal proteostasis is an important mechanism to regulate the neural survival and the central nervous system functionality. The ubiquitin-proteasome system (UPS) is a non-lysosomal proteolytic pathway involved in numerous normal functions of the nervous system, modulation of neurotransmitter release, synaptic plasticity, and recycling of membrane receptors or degradation of damaged and regulatory intracellular proteins. Aberrant accumulation of intracellular ubiquitin-positive inclusions has been implicated to a variety of neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington disease (HD), Amyotrophic Lateral Sclerosis (ALS), and Multiple Myeloma (MM). Genetic mutation in deubiquitinating enzyme could disrupt UPS and results in destructive effects on neuron survival. To date, various agents were characterized with proteasome-inhibitory potential. Proteins of the ubiquitin-proteasome system, and in particular, E3 ubiquitin ligases, may be promising molecular targets for neurodegenerative drug discovery. Phytochemicals, specifically polyphenols (PPs), were reported to act as proteasome-inhibitors or may modulate the proteasome activity. PPs modify the UPS by means of accumulation of ubiquitinated proteins, suppression of neuronal apoptosis, reduction of neurotoxicity, and improvement of synaptic plasticity and transmission. This is the first comprehensive review on the effect of PPs on UPS. Here, we review the recent findings describing various aspects of UPS dysregulation in neurodegenerative disorders. This review attempts to summarize the latest reports on the neuroprotective properties involved in the proper functioning of natural polyphenolic compounds with implication for targeting ubiquitin-proteasome pathway in the neurodegenerative diseases. We highlight the evidence suggesting that polyphenolic compounds have a dose and disorder dependent effects in improving neurological dysfunctions, and so their mechanism of action could stimulate the UPS, induce the protein degradation or inhibit UPS and reduce protein degradation. Future studies should focus on molecular mechanisms by which PPs can interfere this complex regulatory system at specific stages of the disease development and progression.

Background: Tributyltin (TBT) is known as an endocrine disruptor able to interfere with estrogen receptors (ERs) leading to toxic effects on the related endocrine pathways. TBT is an obesogen, reported to disrupt glucose homeostasis leading to diabetes. The aim of this study was to assess the influence of TBT and β-estradiol on the pancreatic islets of Langerhans in simultaneous exposures. Experimental: Pancreatic islets of 15 male rat were isolated and exposed to TBT (10 μM), β-estradiol, and TBT plus β-estradiol for 24 h. Therewith, cellular viability, oxidative stress, apoptosis, and insulin secretion markers were investigated. Results: TBT decreased the viability and increased the apoptosis, reactive oxygen species, and insulin secretion TBT led to increased amounts of apaptosis, reactive oxygen species (ROS), and insulin secretion in pancreatic islets; however, cellular viability was reduced. Co-exposure with β-estradiol ameliorated the entire mentioned variables near to the control level. Conclusion: These results showed that β-estradiol protect pancreatic islets of Langerhans against TBT-induced toxicity by counteracting oxidative stress and apoptosis as well as insulin secretion. In this way, it is postulated that pancreatic ER pathways particularly in β-cells might be the determinant target of toxic effects of xenoestrogens like TBT. Hence, evaluation of xenoestrogens-induced ER dysfunction in the endocrine pancreas can be helpful in diabetic risk assessment of these contaminants. Pharmacological modifications of ER pathway in the β-cells seems promising for better management of diabetes.

A carbon paste electrode modified with 4-(((4-mercaptophenyl)imino)methyl)benzene-1,2-diol (MIB) and multi-walled carbon nanotubes MIB /CNT/CPE) was prepared for determination of epinefrine (EP) in the presence of acetaminophen (AC). Cyclic voltammetry, chronoamperometry and differential pulse voltammetry (DPV) techniques were used to investigate the modified electrode for the electrocatalytic oxidation of (EP) and (AC) in aqueous solutions. The separation of the oxidation peak potential for EP- AC was 200 mV. Under the optimum conditions, the calibration curve for EP was obtained in the range of 1.0 to 25.0 µM and 25.0 to 500.0 µM. The diffusion coefficient for the oxidation of EP at the surface of modified electrode was calculated as 5.76×10-5 cm2s-1.

Objective(s): During type-1 diabetes treating by pancreatic islet transplantation, increasing oxidative stress and microbial contaminations are the main reasons of transplantation failure. In this study, we evaluated anti-apoptotic, antioxidant and antimicrobial potentials of phenolic compounds called ellagic acid (EA) and silybin on rat pancreatic islets. Materials and Methods: By doing MTT assay, effective concentrations of EA and silybin were determined as 1500 and 2100 μM, respectively. Then, ELISA methods, flow cytometry and MIC were done to investigate antioxidant, anti-apoptotic and antibacterial effects of those compounds, respectively.Results: Results of FITC Annexin-V and PI staining via flow cytometry, and also caspase-3 and -9 activities performed that EA has anti-apoptotic effects on pancreatic cells. Both compounds significantly diminished reactive oxygen species, and enhanced antioxidant power and insulin secretion. Furthermore, the minimum inhibitory concentration test indicated that these two have antibacterial effects on both Gram-positive and Gram-negative bacteria which usually contaminate the pancreatic islets.Conclusion: These findings support that use of EA and silybin can improve the function of islets which are used in transplantation, along with decreasing islets bacterial contamination.

Background: Aluminium phosphide (ALP) is a highly effective insecticide and rodenticide used frequently to protect stored grain. Acute poisoning with this compound is common in some countries including India and Iran, and is a serious health problem. The objective of this study was to survey ALP poisoning and the outcome in hospitals in Karaj, Iran. Materials and Methods: The study was a retrospective study from April 2006 to April 2011. Records of all patients admitted and hospitalized to hospital during the five-year period were collected. Information including gender, age, amount of ALP consumed, route of exposure and outcome were extracted from the patients notes. Results: During the five-year period, 67 patients, 53.7% men and 46.3% women were admitted with ALP poisoning. Most poisoned people were under the age of 21 years.The most common signs and symptoms at admission were nausea (79.4%), vomiting (76.5%), abdominal pain (31.4%) and metabolic acidosis (41.1%). Suicidal intention was the most common cause of poisoning leading to 44.8% deaths and most cases were male (P

Diabetes mellitus (DM) is a chronic metabolic disorder in which blood glucose level raises that can result in severe complications. However, the incidence increased mostly by obesity, pregnancy, persistent corpus luteum, and diestrus phase in humans and animals. This review has focused on addressing the possible understanding and pathogenesis of spontaneous DM in canine, feline, and few wild animals. Furthermore, pancreatic associated disorders, diabetic ketoacidosis, hormonal and drug interaction with diabetes, and herbal remedies associated with DM are elucidated. Bibliographic search for the present review was done using PubMed, Scopus, and Google Scholar for articles on concurrent DM in small and wild animals. Persistent corpus luteal and pseudopregnancy in female dogs generate gestational DM (GDM). GDM can also be caused by extensive use of drugs/hormones such as glucocorticosteroids. Although many similarities are present between diabetic cats and diabetic humans which present islet amyloidosis, there was a progressive loss of β- and α-cells and the normal number of δ-cells. The most prominent similarity is the occurrence of islet amyloidosis in all cases of diabetic cat and over 90% of human non-insulin dependent DM Type-2. Acute pancreatic necrosis (APN) occurs due to predisposing factors such as insulin antagonism, insulin resistance, alteration in glucose tolerance, obesity, hyperadrenocorticism, and persistent usage of glucocorticoids, as these play a vital role in the progression of APN. To manage such conditions, it is important to deal with the etiological agent, risk factors, diagnosis of diabetes, and hormonal and drug interaction along with its termination with suitable therapy (herbal) protocols. It should be noted that the protocols used for the diagnosis and treatment of human DM are not appropriate for animals. Further investigations regarding diabetic conditions of pets and wild animals are required, which will benefit the health status of all animals health worldwide.

Arsenic (As) poisoning is widespread due to exposure to pollution. The toxic level of (As) causes oxidative stress-induced aging and tissue damage. Since melatonin (MLT) has anti-oxidant and anti-aging properties, we aimed to evaluate the protective effect of MLT against the toxicity of sodium arsenite (NaAsO2). Healthy male NMRI mice were divided into eight different groups. The control group received a standard regular diet. Other groups were treated with varying diets, including MLT alone, NaAsO2, and NaAsO2 plus MLT. After one month of treatment, biochemical and pathological tests were performed on blood, heart, and lung tissue samples. NaAsO2 increased the levels of TNF-α, 8-hydroxy-2-deoxy guanosine (8OHdG), malondialdehyde (MDA), reactive oxygen species (ROS), and high mobility group box 1 (HMGB1), increased the expression of TNF receptor type 1-associated death domain (TRADD) mRNA and telomerase reverse transcriptase, and decreased the expression of Klotho (KL) mRNA in both plasma and tissues. In contrast, MLT reduced MDA, ROS, HMGB1, lactate, and TNF-α enhanced the mRNA expression of KL, and suppressed the mRNA expression of the TERT and TRADD genes. Thus, MLT confers potent protection against NaAsO2- induced tissue injury and oxidative stress.