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Background and purpose: Some chemotherapeutic drugs are associated with an increased risk of cardiotoxicity in patients. Protocatechuic acid (PCA) is a phenolic acid with valuable cardiovascular, chemo-preventive, and anticancer activities. Recent studies have shown the cardioprotective effects of PCA in several pathological conditions. This investigation aimed to assess the possible protective effects of PCA on cardiomyocytes against toxicities caused by anti-neoplastic agents, doxorubicin (DOX), and arsenic trioxide (ATO). Experimental approach: H9C2 cells were exposed to DOX (1 μM) or ATO (35 μM) after 24 h pretreatment with PCA (1-100 μM). MTT and lactate dehydrogenase (LDH) tests were used to define cell viability or cytotoxicity. Total oxidant and antioxidant capacities were evaluated by measuring hydroperoxides and ferric-reducing antioxidant power (FRAP) levels. Expression of the TLR4 gene was also quantitatively estimated by real-time polymerase chain reaction. Findings/Results: PCA showed a proliferative effect on cardiomyocytes and significantly enhanced cell viability and reduced cytotoxicity of DOX and ATO during MTT and LDH assays. Pretreatment of cardiomyocytes with PCA significantly decreased hydroperoxide levels and elevated FRAP value. Moreover, PCA meaningfully decreased TLR4 expression in DOX-and ATO-treated cardiomyocytes. Conclusions and implications: In conclusion, antioxidant and cytoprotective activities were found for PCA versus toxicities caused by DOX and ATO in cardiomyocytes. However, further in vivo investigations are recommended to assess its clinical value for the prevention and treatment of cardiotoxicity induced by chemotherapeutic agents.

DNA Fragmentation Factor (DFF) is a heterodimer protein involved in DNA fragmentation during apoptosis, which acts as a trigger downstream of caspase-3 activation. DFF40 catalytically active homo-oligomers break down chromosomal DNA. Previous scientific investigations have revealed a link between DFF40 expression changes and various cancers. DFF40 deletion or down-regulation has been observed in some cancers. Consequently, therapeutic strategies involving the DFF40 molecule compensating led to an increased rate of cancer cell apoptosis. In this review article, we aimed to introduce cancers with low expression of this protein first. The second part of this paper focuses on studies that utilized exogenous DFF40 protein produced by recombinant DNA technology and surveyed during in vitro and in vivo tests. Finally, compensation for diminished expression of the mentioned protein via gene therapy-based techniques to make up for this apoptotic molecule's low expression is the topic of the last part of this review article. [ABSTRACT FROM AUTHOR]

Background: Pain catastrophizing in patients with rheumatoid arthritis exacerbates negative pain‐related outcomes, such as anxiety, depression, and pain intensity. Therefore, it is essential to investigate the severity of pain catastrophizing and the factors contributing to it among these patients. The present study aimed to assess the severity of pain catastrophizing and its association with cognitive flexibility and self‐efficacy in a sample of Iranian patients with rheumatoid arthritis. Methods: A descriptive correlational study was conducted on 220 rheumatoid patients referred to a rheumatology clinic affiliated with Birjand University of Medical Sciences, Birjand, Iran. The instruments used to collect data included a demographic form, the Pain Catastrophizing Scale, the Cognitive Flexibility Inventory, and the Arthritis Self‐Efficacy Scale. The data were analysed using SPSS version 24. Results: The mean age of the participants was 53.25 ± 12.41 years, and the mean duration of their disease was 6.63 ± 3.39 years. The majority of participants, specifically 61.8%, reported high levels of pain catastrophizing. An inverse and significant correlation was found between pain catastrophizing and cognitive flexibility (p < 0.001). Likewise, pain catastrophizing exhibited an inverse and significant correlation with self‐efficacy and all its dimensions (p < 0.001). The results of the multiple linear regression analysis indicate that the final significant predictors of pain catastrophizing were cognitive flexibility (β = −0.34, p < 0.001) and self‐efficacy (β = −0.53, p < 0.001). These predictors were found to significantly explain 51% of the variance in catastrophizing. Conclusions: Through psychosocial interventions aimed at enhancing pain self‐efficacy and cognitive flexibility, healthcare providers can hope to reduce pain catastrophizing and its adverse effects in patients with rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Background and purpose: DNA fragmentation factor 40 (DFF40) as an apoptotic molecule can represent a novel approach to cancer treatment. Lycosin-I (LYC-I), a peptide derived from spider venom, was considered for the targeted delivery of DFF40 to cancer cells. This study attempted to produce soluble DFF40-LYC-I and evaluate its selective lethal effects on HeLa cells. Experimental approach: pTWINl vector was used to produce LYC-I and DFF40-LYC-I in E. coli BL21 (DE3) fused to inteins 1 and 2. IPTG concentration and incubation temperature were optimized to achieve the highest level of soluble product. To remove inteins 1 and 2 from the recombinant peptide or protein, pH shift and dithiothreitol were used for a 24-h incubation period at room temperature, respectively. MTT assay was performed to assess the biological effects of these bio-molecules on HeLa and HUVEC cell lines. Findings/Results: LYC-I and DFF40-LYC-I were detected in SDS-PAGE with bands of approximately 57 and 97 kDa, respectively. Furthermore, the 3 and 43 kDa bands showed the purified molecules. The IC50 value of DFF40-LYC-I and DFF40 was determined as 6.6 and 17.03 μg/mL for HeLa, respectively. LYC-I had no cytotoxic effects on both cell lines, even at high concentrations. Conclusion and implications: A new fusion protein with targeted cancer treatment potential was produced for the first time by LYC-I with a safe profile on normal cells. This fusion protein exhibited higher cytotoxic effects in cancer cells compared to normal cells. However, additional investigations are required to determine the apoptosis induction and evaluate selective toxicity against other cancer and normal cell lines. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19) which is associated with nonspecific respiratory syndromes, varying from mild symptoms of upper airway to required mechanical ventilation hypoxemia. A unique feature of this disease is COVID-19-associated coagulopathy (CAC) that linked with disease severity and hospital mortality. These patients have a profound hypercoagulable state and in patients with severe type arterial and venous thrombotic events are frequent. Abnormal coagulation parameters such as activated partial thromboplastin time (aPTT) were observed in patients with COVID-19. Regarding the above finding it could be considered as a reason to avoid anticoagulation at the both doses of therapeutic and prophylactic. A prolonged aPTT may indicate a coagulation factor deficiency or inhibitor of coagulation, which can be specific (antibody to factor VIII) or nonspecific (lupus anticoagulant, LA). LA can affect laboratory tests of blood coagulation, but is not usually associated with bleeding; however, it can be associated with thrombotic risk as a part of the antiphospholipid syndrome. In a phospholipid concentration-dependent manner LA recognizes a type of antiphospholipid antibodies (aPLs) that prolong clotting tests. In patients with antiphospholipid syndrome (APS) LA is considered as one of the laboratory criteria representing a significant risk factor of both thrombosis and pregnancy morbidity. Similarities between some of the pathophysiological features of COVID-19 and APS has been focused in several reports particularly in the most severe form, catastrophic APS. This study aimed to evaluate the effect of LA on the incidence of thrombophilia in patients with COVID-19, as well as its impact on the inflammation and finally the mortality final rate. [ABSTRACT FROM AUTHOR]

Agricultural extension is a type of non-formal education and plays a key role in transferring knowledge to farmers. However, the knowledge diffusion and application rate produced by the farmers in different agricultural sectors are facing problems. Therefore, in this research, it was aimed to design a promotion model for agricultural knowledge dissemination in Galugah County of Mazandaran province. In order to reach this model, the inductive strategy, qualitative approach (based on systematic data collection) and grounded theory were used. Data collection was done through in-depth semi-structured interviews with 14 researchers, experts, agricultural extension agents, and innovator farmers (facilitators) in Galugah County of Mazandaran province. The data were analyzed through open coding, axial coding, and selective coding using ATLAS.ti 7.5 software. The obtained model showed following issues as the main components influencing the agricultural knowledge in Galugah County: 1. Causal conditions (production of appropriate knowledge and availability of produced knowledge). 2. Strategies (support of the government and private sectors, policies of the country's agricultural sector, rural youth, and farming system.3. Intervening conditions (factors preventing/facilitating the application of knowledge). 4. Contextual conditions (infrastructure, some personal, economic, and social characteristics of the users) and 5. Consequences (agricultural development, and county comprehensive development). [ABSTRACT FROM AUTHOR]

The incidence of invasive fungal infections (IFIs) has increased in recent years as a result of increasing the incidence of hematologic malignancies (HMs). IFIs, as the opportunistic diseases, are the most important concern in these patients with a high mortality rate. These infections are one of the leading causes of morbidity and mortality in HM patients and an important factor in increasing the costs of patients' management because of the prolonged hospitalization and the inevitable need to use antifungal agents. Due to the changes in the pattern of organisms causing IFIs, unavailability of effective and safe antifungal drugs, and high rate of drug resistance as well as lack of fast and accurate diagnostic methods, these infections have become a serious and life-threatening problem necessitating effective prevention and treatment strategies using suitable antifungal agents, especially in high-risk patients. The aim of the present study was to review the pathogens causing various types of IFIs, diagnostic methods, and novel prophylactic and therapeutic antifungal regimens in HM patients according to the new published studies and clinical trials. [ABSTRACT FROM AUTHOR]

Background: Today, knowledge-based economies have become a strategic and important issue in the economies of various societies and fields, including agriculture. Since agriculture is crucial for a country's food security, it is essential for this sector to adopt a knowledge-based approach. Technological and knowledge-based companies, particularly those in agriculture, serve as key institutions that transform knowledge into goods and services. However, these companies in Iran face numerous challenges that hinder their growth and development. Therefore, this research aims to identify the challenges faced by agricultural knowledge-based and technological companies, fairs, and startups in Mazandaran province. Methods: To identify these challenges, an inductive strategy, qualitative data, and thematic analysis were employed. Data collection was conducted through in-depth semi-structured interviews with 20 founders or managers of agricultural technology and knowledge-based companies located in the Mazandaran Science and Technology Park, as well as incubators associated with Sari University of Agricultural Sciences and Natural Resources. Statistical samples were selected using the snowball method, continuing until theoretical saturation was reached. The ATLAS.ti 7.5 software was utilized for data analysis, and a peer review method was used to validate the thematic analysis. Results: The analysis revealed 151 fundamental themes identified through ATLAS.ti 7.5. The main themes in this study included challenges involved in generating ideas and formulating comprehensive business plans, challenges related to establishing a company in an incubator or science and technology park, R&D and sample product production challenges, marketing and product introduction challenges, sales and market stabilization challenges, developing new market challenges, and market survival and competition challenges. Conclusion: It is suggested that the policies and regulations supporting knowledge-based companies be carefully examined and analyzed to ensure they are better aligned with the needs of these technological and innovative ecosystems. [ABSTRACT FROM AUTHOR]

By producing of healthy and organic agricultural products could be help the sustainability of the ecosystem and the health of society, but this bitter truth should be also accepted that organic and healthy farmers has been confronted with many obstacles for this production. Therefore, identifying the production of healthy and organic agricultural products deterrent barriers and its facilitating factors from farmers' perspective is very important. The current qualitative research was conducted using the content analysis method to achieve this purpose. In this study, in order to collect data, in-depth and semi-structured interviews were conducted with 11 farmers in the area of healthy and organic production, and statistical samples were selected in a purposeful way and continued until the theoretical saturation point was reached. Instrument data collection were semi-structured and in-depth interviews with farmers who had the experience of organic agricultural or were a healthy product producer (n=11). Then Data collected were analyzed using MAXQDA Analytics Pro 2020 software. These Data were organized in three stages of open coding, categorization and abstraction. To evaluate the validity and reliability of this qualitative study, four criteria of Credibility, Transferability, Dependability and Confirm ability were used. The results showed that 55 percent of farmers with a healthy production certificate were men and 45 percent were women. Regarding the current situation of production in the province, 25 initial codes were identified in four main categories. The results of the analysis of interviews with farmers regarding deterrents showed that 57 initial codes identified in seven categories: economic and market, government-supportive, attitude-cultural, natural, productive and technical, research and development and education, legal and individual-professional were summarized. Also, 16 initial output codes related to promotional factors were extracted. According to the results of the research, it is suggested that the direction of the government's agricultural policies should be directed towards the environmental and social goals of producing healthy and organic products. [ABSTRACT FROM AUTHOR]

Background and purpose: The treatment of ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) is still a great challenge. This study evaluated the effectiveness of the colistin/levofloxacin regimen compared to the usual colistin/meropenem regimen in the treatment of patients with VAP caused by CRAB. Experimental approach: The patients with VAP were randomly assigned to experimental (n = 26) and control (n = 29) groups. The first group received IV colistin 4.5 MIU every 12 h + levofloxacin 750 mg IV daily, and the second group received IV colistin with the same dose + meropenem 1 g IV every 8 h for 10 days. The clinical (complete response, partial response, or treatment failure) and microbiological responses at the end of the intervention were recorded and compared between the two groups. Findings/Results: The complete response rate was higher (n = 7; 35%) and the failure rate was lower (n = 4; 20%) in the experimental group than in the control group (n = 2; 8%, and n = 11; 44%, respectively), but the differences were not statistically significant. Even though the microbiological response rate was higher in the experimental group (n = 14; 70%) than in the control group (n = 12; 48%), the difference was not statistically significant. The mortality rate was 6 (23.10%) and 4 patients (13.8%) in the experimental and control groups, respectively (P = 0.490). Conclusion and implication: The levofloxacin/colistin combination can be considered an alternative regimen to meropenem/colistin in the treatment of VAP caused by CRAB. [ABSTRACT FROM AUTHOR]

Understanding that cancer is one of the most important health problems, especially in advanced societies, is not difficult. The term of targeted cancer therapy has also been well known as an ideal treatment strategy in the recent years. Peptides with ability to specifically recognize the cancer cells with suitable penetration properties have been used as the targeting motif in this regard. In the present review article, we focus on an individual RGD-derived peptide with ability to recognize the integrin receptor on the cancer cell surface like its ancestor with an additional outstanding feature to penetrate to extravascular space of tumor and ability to penetrate to cancer cells unlike the original peptide. This peptide which has been named "internalizing RGD" or "iRGD" has been the focus of researches as a new targeting motif since it was discovered. To date, many types of molecules have been associated with this peptide for their targeted delivery to cancer cells. In this review article, we have discussed a summary of penetration mechanisms of iRGD and all introduced peptides and proteins attached to this attractive cell-penetrating peptide and have expressed the results of the studies. [ABSTRACT FROM AUTHOR]

We perform a systematic review and meta‐analysis of randomized controlled trials (RCTs) to quantify the effect of resveratrol supplementation on endothelial function. A comprehensive search was performed in electronic databases including PubMed, Scopus, Web of Science, and Cochrane Library up to February 2021 with no limitation in time and language. A meta‐analysis of eligible studies was performed using a random‐effects model to estimate the pooled effect size of flow‐mediated dilation (FMD), intracellular adhesion molecule‐1 (ICAM‐1), vascular adhesion molecule‐1 (VCAM‐1), fibrinogen, and plasminogen activator inhibitor‐1 (PAI‐1). In total, 21 arms from 17 studies were included. The meta‐analysis results showed that resveratrol significantly change the concentrations of FMD (WMD: 1.43%; 95% CI: 0.98 to 1.88, p <.001) and ICAM‐1 (WMD: −7.09 ng/ml, 95% CI: −7.45 to −6.73, p <.001). However, VCAM‐1, fibrinogen, and PAI‐1 did not change significantly after resveratrol supplementation. In conclusion, the results of this study suggest that resveratrol supplementation can improve endothelial function which could be important, especially in patients with cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Background: The risk of cervical cancer was reported to be influenced by dietary components. This study aimed to illustrate the association between cervical cancer with the intake of food groups in women with a history of cervical neoplasia. Methods: This nested case-control study was conducted in 558 people with a history of cervical intraepithelial neoplasia (CIN), including 279 women with cervical cancers and 279 controls with low-grade squamous intraepithelial lesions (LSIL). A validated food frequency questionnaire (FFQ) was used to assess the intake of food groups. Results: The intake of fruits and vegetables in the case group was significantly lower than the control group (P=0.001). Low intake of dairy products, vegetables, and fruits was associated with cervical cancer risk (OR=4.67; 95% CI 1.2-9.49, P=0.001; OR=9.75, 95% CI 1.36-19. 51, P=0.001; and OR=4.82, 95% CI 1.09-7.25, P=0.001, respectively). After adjusting for age, family history, age at first menstruation, number of children, history of vaginal infection, and age at first sexual intercourse, the results were still significant. Additional adjustments to BMI did not change the results. Conclusion: The results indicate that the risk of cervical cancer can be affected by the intake of certain food groups. Further longitudinal studies are needed to confirm these findings and determine the underlying mechanism of the influence of dietary components on cervical cancer risk. [ABSTRACT FROM AUTHOR]

Due to the importance of cancer as a major public health problem and increasing attention to its targeted treatment, investigation of novel options seems to be rational in order to diminish the side effects of routine existing therapeutic approaches, mainly caused by damage of the body’s normal cells as well as cancerous cells. Peptides are attractive options for the targeted delivery of various types of anti-cancer agents because of their small size, a simpler structure, and better tissue distribution and less immunogenicity in comparison to the antibodies, as well as lower accumulation in the vital organs and finally, more stability when compared to aptamers. In this paper, we surveyed a category of peptides with anti-microbial and anti-cancer effects due to their penetration ability to various target cells. Buforin is a well-known anti-microbial peptide with natural origin (obtained by pepsin-digesting of Histone H2A) which was used for the translocation of GFP to the cancer cells, for the first time. Since then, various natural or synthetic forms were introduced and used for the production of new bio-molecule discussed in the current review article. However, there is no evidence about clinical data of these designed Buforin-derivied bio-conjugates and it is a necessary to perform suitable pre-clinical and clinical studies to make a more accurate judgment about the use of these peptides as appropriate tools in the field of targeted cancer therapy. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress has a prominent role in the pathogenesis of diabetes complications. Pramlintide is an injectional amylin analogue used for the treatment of type 1 and type 2 diabetic patients. The present investigation evaluated the effect of pramlintide against oxidative damage induced by hydrogen peroxide (H2O2) in human umbilical vein endothelial cells (HUVECs). Methods: Cell viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Hydroperoxides level, ferric reducing antioxidant power (FRAP), and expression of transcription factor NF-κB were measured in HUVECs that pretreated with pramlintide and, then exposed to H2O2. Results: Pramlintide significantly decreased the cytotoxicity caused by H2O2 at the concentrations of 5 and 10 µg/mL. Pretreatment of HUVECs with pramlintide reduced hydroperoxides and increased FRAP value in intra- and extra-cellular mediums at different concentration ranges compared with H2O2 stimulated cells. Pramlintide (10 µg/mL) remarkably ameliorated the expression of NF-κB gene after 1, 3 and 24 h exposure to H2O2. Conclusions: Findings of the current investigation displayed that pramlintide may act as a protective against oxidative conditions in endothelial cells through modulation of oxidative markers and transcription factor NF-κB. [ABSTRACT FROM AUTHOR]

Background and purpose: Insulin resistance (IR) can negatively affect clinical outcomes in acute ischemic stroke (IS) patients. Safe and cost-saving interventions are still needed to improve glycemic indices in this population. The primary objective was to evaluate L-carnitine (LC) effects in acute IS patients' homeostatic model assessment of IR (HOMA-IR). Experimental approach: In this randomized, double-blind placebo-controlled clinical trial, critically ill IS patients were allocated to receive daily oral L-carnitine (1.5 g) or a placebo for six days. Fasting serum levels of glucose, insulin, C-reactive protein, LC, and HOMA-IR were measured on days 1 and 7. Mechanical ventilation duration, ICU/hospital duration, illness severity score, sepsis, and death events were assessed. Findings/Results: Forty-eight patients were allocated to the research groups, 24 patients in each group, and all were included in the final analysis. LC administration showed a decrease in mean difference of HOMA-IR and insulin levels at day 7 compared to placebo, -0.94 ± 1.92 vs 0.87 ± 2.24 (P = 0.01) and -2.26 ± 6.81 vs 0.88 ± 4.95 (P = 0.03), respectively. However, LC administration did not result in significant improvement in clinical outcomes compared to placebo. The short duration of intervention and low sample size limited our results. Conclusion and implication: Supplementation of L-carnitine improved HOMA-IR index in acute IS patients admitted to the critical care unit. Supplementation of LC would be a potential option to help to control IR in critically ill acute IS patients. [ABSTRACT FROM AUTHOR]

Downregulation of the apoptotic protein DNA fragmentation factor 40 (DFF40) is correlated with poor overall survival in some malignancies, including melanoma. In this study, DFF40 gene expression driven by survivin promoter, a tumor-specific promoter, was used to selectively induce cytotoxicity in melanoma cells. The activity and strength of survivin promoter were examined in B16F10 murine melanoma, and L929 murine normal fibroblast cell lines using enhanced green fluorescent protein reporter assay and reverse transcription polymerase chain reaction. The effect of expression of DFF40 under the control of cytomegalovirus (CMV) or survivin promoter on viability of cancerous and normal cells was determined by MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide] assay. Apoptosis induction by expression of DFF40 was evaluated using Annexin-V/propidium iodide staining. Our findings showed high activity of survivin promoter comparable to the control promoter (ie, CMV) in melanoma cells, while survivin activity in normal cells was negligible. Survivin promoter-derived DFF40 gene expression led to selective inhibition of cell viability and induction of apoptosis in cancerous cells. Low and sublethal concentrations of a chemotherapeutic drug, dacarbazine, significantly enhanced the growth inhibitory effect of DFF40 gene therapy. Combination of survivin-driven gene therapy and chemotherapy could be considered as a potential therapeutic treatment for melanoma and possibly other malignancies with similar features. [ABSTRACT FROM AUTHOR]

This study aimed at designing and fabrication of a novel injectable and thermosensitive melatonin‐loaded pluronic/chitosan hydrogel containing gold nanoparticles (GNPs) and poly glycerol sebacate (PGS) for myocardial tissue engineering. The PGS nanoparticles were used as the melatonin (drug model) carrier. The gelation time, syringeability, stability, and swelling of the hydrogel were scrutinized. Rheological properties, chemical composition, and morphology of the samples were also investigated. The effect of GNPs addition on the electrical conductivity of hydrogel was assessed. The cytotoxicity of hydrogels was assessed through MTT assay in the exposure of H9C2 cells up to 7 days. Scanning electron microscopy was applied to evaluate the morphology of seeded cells. The synthesis parameters of PGS nanoparticles were optimized through which 2.5%w/v of PGS and 1:10 organic phase to aqueous phase (O/A) ratio were found desirable. The optimum hydrogel illustrated 2 min gelation time and was stable up to 20 days with 5% swelling in the first 12 h into phosphate buffered saline. The GNPs with a uniform distribution rendered the hydrogel electrically conductive (1500 μS/cm). According to the MTT assay results, 3.125 μM melatonin was considered as the suitable concentration by which a significant increase in the cell viability was observed. The results exhibited that the prepared hydrogel composed of pluronic/chitosan/GNPs, and 3.125 μM melatonin‐loaded PGS nanoparticles could be applied as a promising scaffold for myocardial tissue engineering. [ABSTRACT FROM AUTHOR]

Background and purpose: An anticancer peptide P28, has shown to be cytolethal on various cancer cells including breast cancer. Moreover, p28 can be alsoused as a targeting moiety in the structure of fusion proteins. IL-24 (or its truncated form, M4) is a cytokine with anticancer activity against a wide range of tumor cells. We aimed at production of a fusion protein consisted of p28 and either IL-24 or M4 to target breast cancer. However, selection of a proper linker to join the two moieties without intervening each other's function is a key factor in the construction of fusion proteins. In the present study, the impact of different linkers on construction of the two chimeric proteins (p28-IL-24 and p28-M4) was assessed in silico. Experimental approach: After selection of some linkers with different lengths and characteristics, a small library of the chimeric proteins was created and assessed. Furthermore, following selection of the most suitable linker, the three-dimensional structures and dynamic behavior of both fusion proteins were evaluated byhomology modeling and molecular dynamic simulation, respectively. Findings / Results: Based on the results, a rigid linker having the peptide sequences of AEAAAKEAAAKA showed highest freedom of action for both moieties. Conclusion and implications: Between the p28-IL-24 and p28-M4 fusion proteins, the former showed better stability as well as solubility and might show stronger anticancer effects in vitro and in vivo, because its peptide moieties showed to exert their activities freely. [ABSTRACT FROM AUTHOR]

In this research, substituent effects on the parameters of 35Cl nuclear quadrupole resonance (NQR) in para‐substituted benzene‐sulphenyl chloride were studied at M062X/6‐311G(d,p) theory level. The 35Cl NQR parameters of the quadrupole coupling constant (QCC) and electric‐field gradient (EFG) tensor, as well as an asymmetric parameter, were shown to be correlated with Hammett constant following their calculations. The frontier orbital energy levels, HOMO‐LUMO gaps, hardness, electrophilicity, and chemical potential values of these molecules were calculated as well. natural bond orbital (NBO) analysis was applied for calculating natural populations at chlorine atoms. [ABSTRACT FROM AUTHOR]

Cancer remains one of the leading causes of death worldwide. Conventional therapeutic strategies usually offer limited specificity, resulting in severe side effects and toxicity to normal tissues. Targeted cancer therapy, on the other hand, can improve the therapeutic potential of anti-cancer agents and decrease unwanted side effects. Targeted applications of cytolethal bacterial toxins have been found to be especially useful for the specific eradication of cancer cells. Targeting is either mediated by peptides or by protein-targeting moieties, such as antibodies, antibody fragments, cell-penetrating peptides (CPPs), growth factors, or cytokines. Together with a toxin domain, these molecules are more commonly referred to as immunotoxins. Targeting can also be achieved through gene delivery and cell-specific expression of a toxin. Of the available cytolethal toxins, diphtheria toxin (DT) is one of the most frequently used for these strategies. Of the many DT-based therapeutic strategies investigated to date, two immunotoxins, OntakTM and TagraxofuspTM, have gained FDA approval for clinical application. Despite some success with immunotoxins, suicide-gene therapy strategies, whereby controlled tumor-specific expression of DT is used for the eradication of malignant cells, are gaining prominence. The first part of this review focuses on DT-based immunotoxins, and it then discusses recent developments in tumor-specific expression of DT. [ABSTRACT FROM AUTHOR]

Interleukin (IL) 24 is a pro-inflammatory and tumor suppressor cytokine capable of inducing selective apoptosis in various cancer cells. BR2, on the other hand, is an anti-microbial peptide with selective penetrability to the cancer cells. In this study, we aimed to produce and purify a fusion protein containing IL24 as the toxic moiety fused to BR2, as targeting moiety, and then to evaluate its cytotoxic activities. For this purpose, the coding sequence of IL24-BR2 fusion protein and IL24 were cloned into the pET28a vector and used to transform E. coli BL21 (DE3) cells. Following induction of expression, protein purification performed using Ni-NTA chromatography. SDS-PAGE and western blotting were performed to confirm the expression and purification. Finally, cytotoxic effects of the purified proteins were evaluated on MCF-7 and HUVEC cell lines. Analysis of crude lysate of induced recombinant E. coli BL21 (DE3) bacteria and also purified proteins showed a band of approximately 22 and 18 KDa on SDS-PAGE and western blotting for IL24-BR2 and IL24, respectively. Finally, statistical analysis showed significant cytotoxic effects of IL24-BR2 on MCF-7 cells at 10, 20, and 40 µg/mL concentrations compared to IL24 alone, which showed no significant cytotoxic effects on cancer cells except in the highest concentration. In conclusion, production and purification of IL24-BR2 fusion protein with potential specific toxicity toward cancer cells was successfully achieved. However, further investigation of the cytotoxic effects of this fusion protein on other cell lines and in vivo cancer models must be performed. [ABSTRACT FROM AUTHOR]

Automatic text summarisation is the process of creating a summary from one or more documents by eliminating the details and preserving the worthwhile information. This article presents a single/multi-document summariser using a novel clustering method for creating summaries. First, a feature selection phase is employed. Then, FarsNet, the Persian WordNet, is utilised to extract the semantic information of words. Therefore, the input sentences are categorised into three main clusters: similarity, relatedness and coherency. Each similarity cluster contains similar sentences to its core, while each relatedness cluster contains sentences that are related (but not similar) to its core. The coherency clusters show the sentences that should be kept together to preserve the coherency of the summary. Finally, the centroid of each similarity cluster having the most feature score is added to an empty summary. The summary is enlarged by including related sentences from relatedness clusters and excluding similar sentences to its content iteratively. Coherency clusters are applied to the created summary in the last step. The proposed method has been compared with three known existing text summarisation systems and techniques for the Persian language: FarsiSum, Parsumist and Ijaz. Our proposed method leads to improvement in experimental results on different measurements including precision, recall, F-measure, ROUGE-N and ROUGE-L. [ABSTRACT FROM AUTHOR]

Background: Tilapia Piscidin 4 (TP4) showed potential anti-tumor effects against various cancer cells. Lycosine-1 (LYC1), is another Antimicrobial Peptides (AMP) from spider venom with targeted penetration to cancer cells without any adverse effects on normal cells. The aim of this study was to produce a soluble recombinant fusion peptide in order to diminish the cytotoxicity of TP4 against normal cells. Methods: In order to express of TP4-LYC-1, TP4, and LYC1 in fusion to the inteins1/2 of pTWIN-1 vector, induction condition was optimized to earn soluble peptides. Autocleavage induction of inteins1/2 was performed based on IMPACT® manual and their effect on cell viability of HeLa and HUVEC cells was surveyed by MTT assay. Results: The best condition for accessing the most soluble peptide in fusion to the inteins was approximately similar for all three peptides (0.1 mM of IPTG, at 22°C). After the induction of self-cleavage of inteins, a band in 3, 3, and 6 kDa was observed on tricine- SDS-PAGE. The IC50 values of TP4-LYC1 and TP4 against HeLa cells were calculated as 0.83, and 2.75 µM, respectively. Conclusion: In the present study, a novel chimeric peptide, TP4-LYC1, was successfully produced. This fusion protein can act as a safe bio-molecule with potent cytotoxic effects against cancer cells, but the penetration ability and determination of cell death mechanism must be performed in order to have more precise view on the apoptosis induction of this recombinant peptide. [ABSTRACT FROM AUTHOR]

The aim of this study was to produce a fusion protein consisting of the catalytic and translocation domains of diphtheria toxin fused to BR2, a cancer specific cell penetrating peptide, and evaluation of its cytotoxic effects for targeted eradication of cancer cells. For this purpose, The DT386-BR2 structure was predicted using Modeller 9.14 and the best predicted model was selected based on the minimum DOPE score. A synthetic gene encoding DT386-BR2 was cloned in pET28a expression vector, expressed and purified by affinity chromatography. SDS-PAGE and Western blotting confirmed the expression of the DT386-BR2 fusion protein by revealing a band of about 47 kDa after the induction of the expression. Finally, the purified protein was subjected to MTT assay for evaluation of its cyto-lethal effects on cancer and normal cell lines. Statistical analysis showed significant reduction in survival percent of HeLa and MCF-7 cancer cells in comparison to negative control (PBS), while the cytotoxic effect was not significant on the normal cells, i.e. HUVEC and HEK 293. The IC50 of DT386-BR2 for HeLa and MCF-7 was about 0.55 and 2.08 μg/ml, respectively. In conclusion, the production and purification of DT386-BR2 fusion protein was successfully achieved and its cytotoxic effects on the studied cancer cell lines was established. The promising cytotoxic effects of this newly constructed fusion protein made it a suitable candidate for targeted therapy of cancer, and further in vitro and in vivo studies on this fusion protein is underway. [ABSTRACT FROM AUTHOR]

The aim of this study was to produce a recombinant protein consisting of the catalytic and translocation domains of diphtheria toxin for its later application as a vaccine candidate against Corynebacterium diphtheria. To achieve this goal, at first, the amino acid sequence of DT386 was used for prediction of T and B cell epitopes using on-line servers. The DT386 coding sequence was synthesized and subcloned into the NcoI and XhoI sites of pET28a plasmid and recombinant pET28a plasmid was used to transform Escherichia coli BL21 (DE3) host cells. Afterwards, recombinant cells were selected and subjected to induction of expression by 1 mM isopropyl β-D-1-thiogalactopyranoside, (IPTG). Expression of the desired protein was evaluated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting, and finally, the recombinant protein was purified using nickel affinity chromatography. The results of epitope prediction using on-line servers established the ability of DT386 for stimulation of immune system against diphtheria toxin. Restriction digestion of the recombinant plasmids using NcoI and XhoI enzymes confirmed the fidelity of cloning by producing a band of about 1200 bp. SDS-PAGE analysis following induction of expression and also purification step confirmed the expression of the desired protein by showing a band of about 45 kDa. In addition, Western blot analysis using anti-6X-His antibody confirmed the identity of the expected protein. In conclusion, in the present study we amplified and cloned the coding sequence of DT386 fragment, followed by its expression by E. coli BL21 (DE3) cells. Then, the expressed protein was purified and will be used for later studies of evaluation of its immunogenic properties. [ABSTRACT FROM AUTHOR]

Reteplase is a part of tissue plasminogen activator (t-PA) used for the removal of thrombi in blood vessels. In the present study we express the Reteplase gene in Escherichia coli TOP10 and then its thrombolytic activity was measured. The recombinant plasmid pBADgIIIA was transformed into the competent Escherichia coli TOP10 and then transformed bacteria was seeded into bioreactor containing 1.5 L LB medium and induced by 0.02% LArabinoseat 37°C, pH 7, and 180 rpm until OD 600 of 0.6 was reached. Samples were analyzed by SDS-PAGE and western blotting and the expression of Reteplase was examined. Finally the activity of this recombinant protein was evaluated using Chromogenic Activity Assay Kit. The presence of Reteplase in transformed Escherichia coli TOP10 was examined by western blotting which revealed that the target protein in form inclusion body was expressed as a unique band at 39 and the refolded Reteplase was 66 KDa. The amount of protein produced was 90.5 μg/mL and its activity was determined as 0.8 units. In this study, the expression of Reteplase in Escherichia coli TOP10 was scaled up under optimum condition. Furthermore we earned Reteplase with partially suitable thrombolytic activity. [ABSTRACT FROM AUTHOR]

Lipases are diversified enzymes in their properties and substrate specificity, which make them attractive tools for various industrial applications. In this study, an alkalinethermostable lipase producing bacteria were isolated from soil of different regions of Isfahan province (Iran) and its lipase was purified by ammonium sulfate precipitation and ion exchange chromatography. To select a thermoalkalophil lipase producing bacterium, Rhodamine B and Horikoshi media were used and the strain that can grow at 45 °C was selected. The isolated strain was identified using microbial and biochemical tests. One strain showed an orange colored zone on plate and grew on Horikoshi plate. Microbial and biochemical tests showed that the isolated strain was Bacillus subtilis, a Gram positive rod. In PCR, an expected band was obtained with about 371 bp. The activity of the purified lipase was 10.2 folds that of the standard enzyme using ammonium sulfate precipitation and ion exchange chromatography. The molecular weight of lipase determined by SDS-PAGE electrophoresis, was 21 and 35 KDa. Existence of two bands in SDS-PAGE electrophoresis and low amount of obtained purified enzyme highlights the necessity of optimization of purification and concentrating process. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to evaluate the antibiotic resistance pattern of Helicobacter pylori strains isolated from patients in Isfahan province. Materials and Methods: Gastric antrum biopsy specimens of patients undergoing endoscopy were cultured. The samples with the growth of H. pylori underwent antibiotic susceptibility test by disk diffusion method. Reaults: Of 96 samples, 50 samples (53%) were positive for H. pylori. The rates of antibiotic resistance were as follows: amoxicillin, 6%; azithromycin, 20%; furazolidone, 22%; levofloxacin, 16%; metronidazole, 20%; rifampin, 12%; and tetracycline, 22%. Conclusion: H. pylori strains in our area have high rates of resistance to azithromycin, levofloxacin, metronidazole, tetracycline, and furazolidone. [ABSTRACT FROM AUTHOR]