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Objective: According to the importance of evaluating the antimicrobial resistance pattern in the management of nosocomial infections (NIs), we decided to investigate the prevalence of antimicrobial resistance in Chamran Heart Hospital. Methods: This retrospective cross-sectional observational study was performed for 6 months from February to July 2022 at Shahid Chamran Hospital of Isfahan, Iran. All hospitalized patients with any NIs were eligible for the study. Clinical specimens were obtained from patients with NIs. All specimens underwent microbial culture, and if bacterial growth developed, differential tests were performed. Antibiotic susceptibility testing also was performed per the standards of Clinical and Laboratory Standards Institute, 2022. Findings: Out of 201 examined samples, urinary infection (34.83%), pneumonia (27.86%), and sepsis (13.43%) were reported to be the most prevalent infections. Among Gram-negatives (76.12%), Citrobacter spp. (26.37%), Escherichia coli (24.87%), and Klebsiella spp. (11.44%) were the most common pathogens. About 54.9% of Citrobacter spp., 33.3% of E. coli, and 45.45% of Klebsiella spp. were resistant to carbapenems. About 1.88% and 15% of Citrobacter spp. were identified as pan-drug-resistant bacteria and extensively drug-resistant (XDR), respectively. In addition, 4.34% of Klebsiella spp. were identified as XDR. Among Gram-positives (23.88%), Enterococcus spp. (8.95%) was identified as the most common pathogen, and the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) was 11.11% and 61.11%, respectively. Conclusion: In our study, carbapenem-resistant Enterobacteriaceae accounts for about 50% of all NIs. Moreover, despite the low prevalence of MRSA, VRE was reported to be high in our center when compared with other studies.

Extended Abstract Background: Today, medicinal plants play a vital role in health, creating employment, and economic development. Despite paying attention to the development of medicinal plant cultivation in Mazandaran province in recent years, resulting in employment creation in rural communities and the reduction of migration, farmers in rural areas are facing challenges to cultivate these plants and employment in this field. Furthermore, the unemployment rate index in this county is higher than the country and the province. Therefore, this research aimed to analyze employment challenges and obstacles in the field of medicinal plants in North Svadkuh County, Mazandaran province. Methods: In this survey with a quantitative approach, the statistical population consisted of the farmers in North Savadkuh county of Mazandaran province, and 204 farmers were selected using Daniel's formula and simple random sampling. The data collection tool was a questionnaire, and its content validity was confirmed by a group of horticultural, extensional, and educational experts. In addition, Cronbach's alpha coefficient was used to determine its reliability with an appropriate value (0.7-0.9). Moreover, 175 out of 204 distributed questionnaires were returned to the researchers. Data were analyzed using SPSSV26 software. Results: The findings in the descriptive statistics section showed that most of the farmers (64.6%) were men, mostly with a bachelor’s educational level (37.1%), and their main occupation was agriculture for the majority of the farmers (60.6%). In total, four factors were identified based on the results of exploratory factor analysis on 15 variables of the farmers facing challenges and obstacles in Northern Svadkuh county, Mazandaran province. These factors include skill-logistic factors (17.749%), harvesting and postharvest stage problems, lack of good stories for harvested medicinal plants, damage to the product due to improper handling, and the absence of harvesting machines for medicinal plants in the region, extension-infrastructural factors (17.493%), planting, growing, harvesting, and postharvest stages problems, inattention to medicinal plant cultivation capacity in the region by policymakers, the absence of experts and specialists of medicinal plants in the Agricultural Jihad Organization of the city, the absence of model farms for medicinal plants in the region, limited extension training and classes-farmer field school (FFS), and lack of proper mechanization in the planting, growing, harvesting, and processing of medicinal plants. The rest of the factors include processing industries-marketing factors (16.735%) postharvest stage problems, raw sales and non-processing of medicinal plant products, the absence of medicinal plant packaging companies in the region, the problem of sending raw medicinal plants to other cities, traditional use (without processing) of most medicinal plants in the region, the absence of foreign market and export of medicinal plant products, technical knowledge and information factors (10.983%), growing stage problems, limited knowledge of experts and farmers in the non-chemical control of weeds and diseases of medicinal plant in the region, and farmers' unfamiliarity with the water requirements of medicinal plants). Conclusion: According to the results, the main challenges of farmers for employment in the field of medicinal plants are skills and logistics, extension and infrastructure problems, and transformation and marketing industries of these plants. Thus, it is suggested to teach the skills of harvesting medicinal plants to the farmers and rural youth of the region by holding educational-extension classes. Besides, policymakers, executives, and planners are suggested to pay more attention to the creation of employment in rural areas, which is achieved through the cultivation of these plants, considering the conditions of the province and the capabilities of the Northern Svadkuh County in the production of medicinal plants. It is suggested to try in every district center, especially in the central and eastern regions of the province, which are susceptible to the cultivation of medicinal plants according to the document of the province. The presence of one or more experts with expertise in medicinal plants and proficiency in educational-extension methods should be facilitated to train farmers to promote employment and increase the cultivated area of the mentioned plants. The farmers should be trained in a practical and individual or group form by using suitable extension methods such as result and method demonstrations, a model site, and holding the FFS. In addition, it is possible to provide suitable tools and mechanization in all production stages of medicinal plants for the farmers of the region. The next suggestions are to create processing and packaging industries by providing low-interest and long-term facilities in the region, empowering farmers in terms of knowledge and skills regarding the marketing and processing of medicinal plant products, creating permanent and seasonal markets for direct sales, guaranteed purchase of products, facilitating domestic shipping to different provinces, paying attention to exports, and removing obstacles to international exports. The last suggestion is that a revision is necessary for the training courses of Agricultural Jihad experts of the county and the region, as well as agricultural students. The training should be changed from the theoretical presentation of topics, information, and knowledge into practical and field activities that lead to gaining more experience.

Background and purpose: Anakinra must be injected daily due to its short half-life and this leads to lower patient compliance. Therefore, the aim of this study was to produce an interleukin-1 receptor antagonist (IL-1Ra) with albumin binding domain (ABD) as a novel fusion protein and evaluate its binding ability to albumin and its biological effects. Experimental approach: The three-dimensional structure of IL-1Ra-ABD was predicted by MODELLER software and its interaction with IL-1R was evaluated by the HADDOCK server. The expression of IL-1Ra-ABD was performed in E. coli in fusion with intein 1 of pTWIN1 in soluble form and then purified. The affinity of IL-1Ra-ABD to human serum albumin (HSA) was determined on native-PAGE, and its release percent toward time was evaluated. Moreover, an MTT assay was used to determine the antagonizing properties of recombinant IL-1Ra-ABD against IL-1β in A375 and HEK293 cell lines. Findings/Results: The stable complex of IL-1Ra-ABD with IL-1R established the absence of steric hindrance due to the addition of ABD to IL-1Ra. The expression induction of intein 1-IL-1Ra-ABD using 0.1 mM IPTG at 15 °C, and its cleavage represented bands approximately in 50 and 23 kDa. Furthermore, about 78% of IL-1Ra-ABD was attached to the HSA after 2 h of incubation, and the MTT assay showed no significant differences between the effects of IL-1Ra-ABD and native IL-1Ra in cell survival. Conclusions and implications: The production of soluble IL-1Ra-ABD with no significant differences in IL-1Ra antagonizing effects was successfully performed. IL-1Ra-ABD showed suitable interaction with HSA and was released over time. However, the half-life of IL-1Ra-ABD in vivo must be determined in the subsequent investigations.

Developments in information and communication technologies have created a new type of voluntary activity called online volunteering, in which volunteers fulfill their duties from outside the workplace. Therefore, this study aims to identify and categorize online voluntary activities available to public libraries and information centers. This applied research was conducted using the survey method. Data collection was performed using observation and Delphi method. The participants in the Delphi survey rounds included 15 experts in the field of information and knowledge science (faculty members, library managers, and library sections' directors) who were interviewed in two rounds, and their opinions were used to conclude. The present study's findings suggest that 33 different voluntary activities can be performed as virtual volunteering in public libraries. These services can be divided into three general categories: content development, training/counseling, and promoting/informing. Among these, content development with 22 different activities has the most possibility of online volunteering activities, training/counseling with six activities, and promoting/informing with five activities are the following categories, respectively. In addition, for each of these three categories, relevant general competencies are presented separately, while for 33 voluntary activities, specialized goals and competencies are suggested by experts. Considering the variety of activities that public libraries can perform virtually through their volunteers, it seems necessary to identify the capacities and capabilities of libraries and volunteers so that the maximum efficiency of volunteers is achieved in reaching the library's goals. No study on identifying and categorizing voluntary activities in public libraries and information centers is available. While identifying and categorizing these activities, the present research mentions the goals for each activity and specifies general and specialized conditions for volunteers to perform the same activity.

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.

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.

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 Candidiasis is one of the most common fungal infections of oral cavity in humans, causing great oral discomfort, pain and aversion to food. To develop more effective antifungal systems for the treatment of oral candidiasis, an oral mucoadhesive wafer containing sertaconazole solid dispersion (STZ-SD) was developed in this study. Dispersion of STZ in Soluplus® as a solubility enhancement excipient was done by melting, solvent evaporation and freeze drying method at various STZ to Soluplus® ratios. The optimized STZ-SD was then incorporated in the sodium carboxymethyl cellulose (SCMC) gel, xanthan gum gel, or their combination to prepare the lyophilized wafers. The swelling capacity, porosity, and mechanical, release and mucoadhesive properties of the wafers, together with their antifungal activity, were then evaluated. The melting method sample with the ratio of 8:1 showed the best results in terms of saturation solubility and dissolution rate. The STZ-SD-composite wafer exhibited higher hardness and mucoadhesion, as compared to those made of the SCMC polymer. The STZ-SD-wafer also exhibited a greater antifungal effect when compared to the STZ-wafer. The present study, thus, suggested that the STZ-SD-wafer could serve as a novel effective delivery system for oral candidiasis treatment.

Background and objectives: The aim of this study was extraction, isolation, and identification of potent metabolites from aerial parts of Artemisia kermanensis Podl.“Dermaneh kermani’, the Iranian endemic species of Asteraceae family, and finally evaluation the anti-proliferative and apoptotic effects against normal and breast cancer cell lines. Methods: Air-dried aerial parts of A. kermanensis Podl. were extracted by maceration method with acetone/dichloromethane and then fractionated with MPLC apparatus using a gradient solvent system. The chemical structures of the isolated compounds were determined based on analysis of mass and nuclear magnetic resonance spectra. Anti-proliferative effects of the three compounds were determined by MTT assay against HUVEC, MDA-MB-231 and MCF-7 cells. The apoptotic effects of compounds 2 and 3 were determined by flow cytometry on MCF-7 cells. Results: Compound 1 (5,7-dihydroxy-3',4',6-trimethoxyflavone, eupatilin), compound 2 (5,7,3'-Trihydroxy-6,4',5'-trimethoxyflavone) and compound 3 (1-acetoxy-3,7-dimethyl-7-hydroxy-octa-2E,5E-dien-4-one) were isolated from the plant extract. Compound 3 was identified for the first time from A. kermanensis. Statistical studies revealed that this compound showed the most anti-proliferative properties on all three cell lines. In MCF-7 cells treated with concentration of 10 µg/mL of compound 3, 36% apoptosis was observed. Furthermore, compound 2 (5,7,3'-Trihydroxy-6,4',5'-trimethoxyflavone) showed 33% apoptosis at 650 µg/mL. Conclusion: In the present study, the cytotoxic and apoptotic effects of 5,7,3'-trihydroxy-6,4',5'-trimethoxyflavone and Compound 3 (1-acetoxy-3,7-dimethyl-7-hydroxy-octa-2E,5E-dien-4-one) were determined for the first time. On the other hand, since Compound 3 showed the most cytotoxic effects on the cancer cell lines, investigation of its biological effects is recommended.

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.

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.

Background: Cyclomyrsinane diterpenes especially those extracted from various Euphorbia species have shown interesting biological properties in recent years. Because of the high prevalence of breast cancer and the challenges ahead in its treatment, the use of these compounds as potential anti cancer agents seem reasonable. Objectives: The aim of the present study was to evaluate the cytotoxic effects of some myrsinane type diterpenoids extracted from Euphorbia sogdiana Popov and determine their induced cell death mechanism. Methods: MTT assay was used to determine the cytotoxicity of six various myrsinane compounds on MCF 7 and 4T1 breast cancer cell lines. Human umbilical vein endothelial cells were used as the normal cell line too. The apoptotic effects of the structure with the most cytotoxic effects were determined using flow cytometry assay in IC50 concentration for 24 h of incubation. Results: Compound (6) showed the most cytotoxic effects with IC50 of about 8 ± 4 and 24 ± 4 μg/mL for MCF 7 and 4T1 cell lines, respectively. Furthermore, the cells treated with 5 and 10 μg/mL of compound (6) for 24 h, showed 37 and 55% of apoptotic cells. Conclusions: These surveyed compounds have the potential to be considered as useful anti-breast cancer agents due to the great cytotoxicity and apoptotic effects against these cancer cells and the fact that there was no significant cytotoxicity on normal cells.

Background: Anakinra (Kineret®), an IL-1 receptor antagonist, is the first FDA approved biologic drug for antagonizing IL-1 effects in patients with Rheumatoid arthritis. Notably, the less expensive production of this drug might help reduce the final therapeutic costs. Objectives: This study aimed to evaluate the possibility of producing biologically active recombinant IL-1Ra by a single step purification procedure mediated by a self-cleavable intein. Methods: Soluble expression of the rIL-1Ra was performed in E. coli BL21 (DE3) in fusion to intein1 of pTWIN-1 vector and its cleavage induction using an elution buffer (pH 6.8) at room temperature. Evaluation of the antagonizing efficacy of this protein in various concentrations, was performed on A375 and HEK293 cells treated by a constant concentration of IL-1β (2ng/mL). Results: IPTG induction of E. coli BL21 (DE3) transformed with the recombinant pTWIN-1, revealed a band approximately in 45 kDa, which is related to the intein1-rIL-1Ra fusion protein in the SDS-PAGE. Moreover, protein purification was confirmed by observing a band in 18 kDa. Finally, the percentage of inhibition effects of rIL-1Ra and Kineret® against IL-1β was not statistically significant in IL-1-responsive A375 cells. The inhibition percentage was calculated as 86% in cells treated with 15µg/mL of rIL-1Ra, which it was 96% for the inhibitory effects of the standard drug. Conclusion: In this study, biologically active soluble rIL1-Ra was successfully produced with high purity through a one-step procedure. This method can reduce the cost and time of production for this protein and might be applicable for producing other biologics.

Background and Objectives: Bacterial antibiotic resistance is one of the most important threats for public health around the world. Carbapenemase-producing Gram-negative bacteria have resistance to most antibiotics including carbapenems complicating the treatment of infections. The aim of this study was to determine the antimicrobial susceptibility pattern of carbapenemase-producing nosocomial Gram-negative pathogens at a referral teaching hospital to reveal the best options for treatment of related infections. Materials and Methods: Gram-negative bacteria, isolated from hospitalized patients with nosocomial infections, underwent meropenem susceptibility test by disk diffusion method. Meropenem-resistant strains were evaluated for the presence of carbapenemase using Modified Hodge test (MHT). Finally, the antibiotic susceptibility test was performed to determine the sensitivity of each carbapenemase-positive strain against various antimicrobial agents according to the guidelines of Clinical and Laboratory Standards Institute (CLSI). Results: Over the study period, 155 carbapenemase-positive isolates were detected. Pneumonia was the most frequent related nosocomial infection (67.1%) followed by UTI (23.2%). Acinetobacter baumannii (53.5%) and Klebsiella pneumoniae (40%) were the most frequently isolated pathogens. The pathogens had high rate of resistance to all antibiotics. Colistin had the most in vitro effect against all pathogens. Also, K. pneumoniae had a co-trimoxazole sensitivity rate equal to colistin (30.6%). Conclusion: Carbapenemase-positive Gram-negative bacteria causing nosocomial infections are common in our hospital and have high rate of resistance to most antibiotics. Improvement in the pattern of antibiotic use and infection control measures are necessary to overcome this resistance.

Objective: The present study aimed to evaluate the effectiveness of N-Acetylcysteine (NAC), as an antioxidant, in preventing nephrotoxicity in patients receiving colistin. Methods: In a randomized controlled clinical trial, eligible participants receiving colistin were divided into two groups including drug (n = 43) and control (n = 39). In the drug group, 1200 mg of NAC was administered daily for 10 days concurrently with colistin. Patients in the control group received only colistin. The serum creatinine level (SCr), blood urea nitrogen (BUN), and creatinine clearance (CrCl) at baseline and every other day, and the number of cases with acute kidney injury (AKI) during the study were recorded. Before starting treatment and on day 5, the level of urinary neutrophil gelatinase-associated lipocalin (NGAL) was determined. Finally, the values were compared between the groups. Findings: There was a significant increase in SCr and BUN and a significant reduction in CrCl in both groups, but there was not any significant difference between the two groups at any time. Changes in the urine NGAL levels were not significantly different between the two groups. Even though the number of cases with AKI in the drug group (8 cases, 18.6%) was less than the control group (11 cases, 28.2%), the difference was not statistically significant (P = 0.303). Conclusion: Simultaneous administration of NAC with a dose of 1200 mg daily does not have any effect in the prevention of colistin-induced nephrotoxicity.

Several evidence have shown the beneficial effects of pentoxifylline in the improvement of oral aphthous ulcers. However, the data in this regard are sparse. So, the efficacy and safety of pentoxifylline in oral route was systematically reviewed to elucidate its effects on the size and number of ulcers, as well as the healing time and recurrence frequency in RAS patients. PubMed (Medline), Web of Science, Scopus, ScienceDirect, Cochrane Library, ProQuest, and Clinicaltrial.gov were searched for related articles. The investigated outcomes were pain level, the size and number of ulcers, the frequency of recurrence, the healing time, and finally the pentoxifylline related side effects. Only 6 related study that investigate the efficiency of Pentoxifylline on RAS (n =107) were identified. Decreasing in the pain level, improving the ulcer size and number were establishe in approximately all studies. Pentoxifylline established its ability to shorten the healing time of this type of mouth ulcers. However, its potential to prevent the recurrence of the disease could not established based the data presented here. In conclusion, this systematic review suggests pentoxifylline in RAS patients because it confirmed that RAS patients who received this agent as oral administration reported suitable response. However, conducting more clinical trials with larger sample size and long follow-up time especially to efficiently judge about its ability to the recurrence prevention still is necessary to develop clinical practice guidelines for management of RAS.

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.

Coronavirus disease-19 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 virus strains has geographical diversity associated with diverse severity, mortality rate, and response to treatment that were characterized using phylogenetic network analysis of SARS-CoV-2 genomes. Although, there is no explicit and integrative explanation for these variations, the genetic arrangement, and stability of SARS-CoV-2 are basic contributing factors to its virulence and pathogenesis. Hence, understanding these features can be used to predict the future transmission dynamics of SARS-CoV-2 infection, drug development, and vaccine. In this review, we discuss the most recent findings on the mutations in the SARS-CoV-2, which provide valuable information on the genetic diversity of SARS-CoV-2, especially for DNA-based diagnosis, antivirals, and vaccine development for COVID-19.

Natural compounds and especially herbal medicine are of great interest due to their various biological effects and their potential to act as a drug for the treatment of various neoplasms especially breast cancer that we are facing with its increasing prevalence around the world. The aim of this study was to evaluate the cytotoxic and cell death mechanism of some diterpenoids (Lathyrane or Tigliane) extracted from the Euphorbia sogdiana Popov against two breast cancer cell lines, MCF-7 and 4T1. Determination the cytotoxic effects of four various diterpenoids was performed using MTT assay against MCF-7, 4T1, and HUVEC cell lines. The IC50 of each compound against cell lines was determined by drawing the dose-response graph using graph Pad prism software. Finally, the apoptotic effects of compound with the most cytotoxic effects was determined by flow cytometry assay for 24 hrs of incubation in IC50 concentration. Statistical analysis confirmed compound (3) with the most cytotoxicity against both cancer cell lines. The IC50 of compound (3) was determined as 10.1 ± 5, 28 ± 5, and 50 ± 3 µg/ml, for MCF-7, 4T1, and HUVEC cells, respectively. Furthermore, the cells treated with 5 and 10 μg/ml of compound (3) for 24 hrs, showed 49 and 57% of apoptosis. These surveyed compounds have the potential to be considered as useful anti-breast cancer agents due to the great cytotoxicity and apoptotic effects against related cancer cell lines and safety profile according to their rational selectivity index.

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.

Background and objectives: Cancer is a major health problem in the world. The aim of this study was to extract the flowers of Allium austroiranicum used by Iranian people as a condiment or for its medicinal effects followed by bioassay guided fractionation of the extracts and fractions, using anti-proliferative effects against ovarian and cervical cancer cells. Methods: The air-dried flowers of Allium austroiranicum were extracted in a four-step extraction method, resulting hexan, chloroform, chloroform: methanol (9: 1), butanol and aqueous extracts. Anti-proliferative effects of the extracts were evaluated by MTT assay against OVCAR-3, HeLa, and HUVEC cell lines. The most potent cytotoxic extract was then subjected to fractionation by MPLC method on a RP-18 silicagel column. Finally, the cytotoxic effects of resulted fractions were analyzed again and the most potent cytotoxic fraction and its IC50 were determined. Results: Statistical analysis showed thatbutanol extract of A. austroiranicum showed the most potent cytotoxic effects against OVCAR-3, HeLa and HUVEC cell lines with IC50 values of 38±2, 56±1.4, and 60±3.5 µg/mL, respectively. On the other hand, for 7 fractions resulting from fractionation of the butanol extract, MTT assay results showed that 6th fraction (F) was the most cytotoxic fraction with IC50 of 2.7±0.26 and 7.5±0.5 µg/mL for OVCAR-3 and HeLa cancer cell lines, respectively. Primary evaluation of the fraction by TLC and NMR analysis suggested the steroidal saponins as the main constituents. Conclusion: Allium austroiranicum showed significant cytotoxic effects against ovarian cancer cell line especiallyfractions assumed to contain steroidal saponins. The fraction constituents have the potential of being strong cytotoxic agents and the isolation and identification of compounds are suggested.

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.

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.

Background: Cancer is one of the greatest health-related problems and due to increasing drug resistance and severe side effects of chemotherapeutic agents, production of targeted anticancer agents with lower side effects is under consideration. Previously, we produced a fusion protein consisted of catalytic and translocation domains of diphtheria toxin (DT386) fused to BR2, a cancer specific cell penetrating peptide. First steps of this study showed selective antiproliferative effects of DT386-BR2 on cancer cells but not on normal cell lines. The aim of the present study was evaluation of its in-vivo non-specific toxicity in healthy mice. Methods: The fusion protein was produced and purified through recombinant DNA technology. Intraperitoneal injections with various concentrations of DT386-BR2 were done in healthy mice for five consecutive days and they observed for 14 days after the last injection inspecting their food consumption, body weight, body temperature, and finally being dead or alive. Negative controls were injected with normal saline solution. Findings: There was not any significant effect on temperature, body weight, and viability of mice received various concentrations of DT386-BR2 (P < 0.05), and increasing the protein concentration did not show any adverse effects on mice. Conclusion: DT386-BR2 can be used for further pre-clinical studies to determine its pharmacokinetics/pharmacodynamics profiles and evaluation of its anticancer efficacy in suitable xenograft animal models.

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.

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.

Background: Opioid drugs are the most effective drugs for the treatment of moderate to severe pain. Rates of opioid use are influenced by a variety of factors. The aim of this study was to determine the pattern of use of parenteral opioid drugs in hospitalized patients in a referral teaching hospital. Methods: In a retrospective study, required data were extracted from medical records of adult patients who had received any parenteral opioid analgesic in the 6-month period from March 2013 to September 2013. The Anatomical Therapeutic Chemical Classification/Defined Daily Doses (ATC/DDD) system method was used for evaluation of opioid analgesic use in patients. Results: The overall usage of parenteral opioid analgesics was 730.51 DDDs with meperidine (Pethidine) having the most amounts of use (588.69 DDDs and 33.23 DDDs/100 bed-days). Overall, the male surgery ward and emergency department had the most amounts of use based on the number of DDDs (445.8 DDDs) and per 100 bed-days (1046 DDDs/100 bed-days), respectively. Methadone use was most in the infectious diseases ward. Conclusion: The trend of parenteral opioid analgesics consumption is increasing in this hospital. Therefore, better adherence to pain treatment guidelines by medical staff is necessary for rational use of these drugs.

Background: Antirrhinum majus contains aurone with excellent antibacterial and antifungal activities. In addition, visible light activates the endogenous porphyrins of Propionibacterium acne, which results in bacterial death. Therefore, considering the above-mentioned facts, the aim of the present study was to prepare a topical herbal gel of A. majus hydroalcoholic extract and to evaluate its antiacne effects with or without blue light combination as an activator of the porphyrins. Materials and Methods: Antibacterial activity of the shoot or petal extracts was evaluated by disc diffusion method and the minimum inhibitory concentration (MIC) was calculated. Various gel formulations were developed by the Experimental Design software. The obtained gel formulations were prepared and tested for pharmaceutical parameters including organoleptic features, pH, viscosity, drug content, and release studies. Finally, the antibacterial activity was evaluated against (P. acnes) with or without blue light. Results: The MIC of the extracts showed to be 0.25 μg/ml. Evaluation of the gel formulation showed acceptable properties of the best formulation in comparison to a gel in the market. Pharmaceutical parameters were also in accordance with the standard parameters of the marketed gel. Furthermore, statistical analyses showed significant antibacterial effect for gel when compared to negative control. However, combination of blue light with gel did not show any significant difference on the observed antibacterial effect. Conclusion: Because of the statistically significant in vitro antiacne effects of the formulated gel, further clinical studies for evaluation of the healing effects of the prepared gel formulation on acne lesions must be performed.

Background: The aim of this study was to determine the best condition for the production of DT386-BR2 fusion protein, an immunotoxin consisting of catalytic and translocation domains of diphtheria toxin fused to BR2, a cancer specific cell penetrating peptide, for targeted eradication of cancer cells, in terms of the host, cultivation condition, and culture medium. Materials and Methods: Recombinant pET28a vector containing the codons optimized for the expression of the DT386-BR2 gene was transformed to different strains of Escherichia coli (E. coli BL21 DE3, E. coli Rosetta DE3 and E. coli Rosetta-gami 2 DE3), followed by the induction of expression using 1 mM IPTG. Then, the strain with the highest ability to produce recombinant protein was selected and used to determine the best expression condition using response surface methodology (RSM). Finally, the best culture medium was selected. Results: Densitometry analysis of sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the expressed fusion protein showed that E. coli Rosetta DE3 produced the highest amounts of the recombinant fusion protein when quantified by 1 mg/ml bovine serum albumin (178.07 μg/ml). Results of RSM also showed the best condition for the production of the recombinant fusion protein was induction with 1 mM IPTG for 2 h at 37°C. Finally, it was established that terrific broth could produce higher amounts of the fusion protein when compared to other culture media. Conclusion: In this study, we expressed the recombinant DT386-BR2 fusion protein in large amounts by optimizing the expression host, cultivation condition, and culture medium. This fusion protein will be subjected to purification and evaluation of its cytotoxic effects in future studies.

Developments in information and communication technologies have created a new type of voluntary activity called online volunteering, in which volunteers fulfill their duties from outside the workplace. Therefore, this study aims to identify and categorize online voluntary activities available to public libraries and information centers. This applied research was conducted using the survey method. Data collection was performed using observation and Delphi method. The participants in the Delphi survey rounds included 15 experts in the field of information and knowledge science (faculty members, library managers, and library sections' directors) who were interviewed in two rounds, and their opinions were used to conclude. The present study's findings suggest that 33 different voluntary activities can be performed as virtual volunteering in public libraries. These services can be divided into three general categories: content development, training/counseling, and promoting/informing. Among these, content development with 22 different activities has the most possibility of online volunteering activities, training/counseling with six activities, and promoting/informing with five activities are the following categories, respectively. In addition, for each of these three categories, relevant general competencies are presented separately, while for 33 voluntary activities, specialized goals and competencies are suggested by experts. Considering the variety of activities that public libraries can perform virtually through their volunteers, it seems necessary to identify the capacities and capabilities of libraries and volunteers so that the maximum efficiency of volunteers is achieved in reaching the library's goals. No study on identifying and categorizing voluntary activities in public libraries and information centers is available. While identifying and categorizing these activities, the present research mentions the goals for each activity and specifies general and specialized conditions for volunteers to perform the same activity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]