Antimalarial Effects of Nano Chloroquine Loaded Curcumin In vivo.

BACKGROUND: Malaria is still the deadliest parasitic disease caused by Plasmodium spp. Due to drug resistance and their unpleasant side effects, of conventional researchers are enormously seeking to achieve antimalarial drugs with more curative effective, less toxic and cost-affordable drugs using more advanced technology such as nanodrugs. PURPOSE: The present study aimed to examine the antimalarial effects of a novel synthesized nonochloroquine-loaded curcumin relying on dendrimer G2 in susceptible mice. METHODS: Antimalarial activity and toxicity of the nanocomposite were examined on BALB/C mice with microscopy, checking RBCs morphology and related enzymatic activity rate. RESULTS: The maximum inhibitory effect of the nanocomposite was seen at 10 mg/kg, killing 98% of P. berghei compared to sole chloroquine, whereas ED50 was reported at 5.5 mg/kg. The safety of the synthesized nanocomposite was confirmed with biochemical tests with no detrimental effects on mice. The sustainability and longevity of the nanodrug increased significantly with the NDC-CQ assay compared to the control groups. CONCLUSION: The study showed that nonochloroquine-loaded curcumin had a promising inhibitory effect on P. berghei growth in infected mice compared to standard drugs. However, further studies and clinical trials with large samples are recommended to study different aspects of using nanodrug.

Evaluation of Hydatid Cyst Antigen for Serological Diagnosis.

Background: Hydatidosis, a chronic zoonotic disease, has a distribution worldwide and is caused by the larval stage of the Echinococcus helminth. The Dot-ELISA test can diagnose hydatidosis quickly and accurately. Additionally, unlike other hydatid disease tests now used, this quick and affordable enzyme immunoassay is very serum-conservative and antigen-conservative, needing just nanogram levels of parasite antigen. Methods: In the present cross-sectional study, crude and B antigens of hydatid cyst fluid were obtained to diagnose human hydatidosis using CIEP (Counter Immunoelectrophoresis), ELISA (Enzyme-linked Immuno Sorbent assay), and Dot- ELISA (Dot Enzyme linked Immuno Sorbent Assay) methods. Infected liver with a hydatid cyst was collected from Tehran's slaughterhouses to prepare cyst fluid in different stages. After extracting and purifying the Cyst fluid, it is centrifuged at 4ºc, then prepared to concentrate. The study also included sera from hydatidosis (n=60), samples of helminth parasites (n=55), fascioliasis (n=35), toxocariasis (n=20) and negative control (n=35) were tested by CIEP (Counter Immunoelectrophoresis), ELISA (Enzyme-linked Immune Sorbent assay), and Dot- ELISA (Dot Enzyme linked Immuno Sorbent Assay) methods. All statistical analyses were performed using Statistical Package for the Social Sciences (SPSS) for Windows release 25.0 (SPSS Inc., Chicago, IL, USA). Results: Crude antigen of hydatid cyst showed a specificity of 76.7%, a sensitivity of 93.3% using the ELISA method, and B antigen showed a specificity of 96.7% and sensitivity of 88.3% using the same method. The crude antigen of the hydatid cyst exhibited a specificity of 68.9% and a sensitivity of 86.7% using CIEP. The B antigen showed a specificity of 87.8% and sensitivity of 83.3% using the same method.The crude antigen of hydatid cyst having serum dilution at 1:800 exhibited a specificity of 83.3% and sensitivity of 100% using the Dot-ELISA method and B antigen having serum dilution at 1:800 serum showed a specificity of 100% and sensitivity of 98.3% using the same method. The results of this finding showed that B antigen has the maximum specificity to diagnose hydatid test using the Dot- ELISA method. Conclusion: Hydatid cysts present with varied symptomatology. History of exposure to infected animals may not be present. A high degree of clinical suspicion combined with meticulous history and clinical examination supported by laboratory investigations are required for its diagnosis. The Dot-ELISA system with native antigen B is a viable approach for the immunodiagnosis of human hydatidosis that is preferred to infection.

Detection of receptor tyrosine kinase-orphan receptor-2 using an electrochemical immunosensor modified with electrospun nanofibers comprising polyvinylpyrrolidone, soy, and gold nanoparticles.

An electrochemical immunosensing platform was developed for the detection of receptor tyrosine kinase-orphan receptor-2 (ROR2) at a glassy carbon electrode (GCE) modified with the electrospun nanofiber containing polyvinylpyrrolidone (PVP), soy, and Au nanoparticles (AuNPs). The PVP/soy/AuNP nanofiber exhibited good electrochemical behavior due to synergistic effects between PVP, soy, and AuNPs. The PVP/soy in the modified film provided good mechanical strength, high porosity, flexible structures, and high specific surface area. On the other hand, the presence of AuNPs effectively improved conductivity, as well as the immobilization of anti-ROR2 on the modified GCE, leading to enhanced sensitivity. Various characterization approaches such as FE-SEM, FTIR, and EDS were used for investigating the morphological and structural features, and the elemental composition. The designed immunosensor performance was investigated using electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), and differential pulse voltammetry (DPV). Under optimum conditions with a working potential range from -0.2 to 0.6 V (vs. SCE), sensitivity, linear range (LR), limit of detection (LOD), and correlation coefficient (R2) were acquired at 122.26 µA/cm2 dec, 0.01-1000 pg/mL, 3.39 fg/mL, and 0.9974, respectively. Furthermore, the determination of ROR2 in human plasma samples using the designed immunosensing platform was examined and exhibited satisfactory results including good selectivity against other proteins, reproducibility, and cyclic stability.

Rhinocerebral Mucormycosis Following COVID-19 Infection in Iran.

Background & Objective: Mucormycosis (also called black fungus) is an opportunistic serious fungal infection caused by mucormycetes. It can occur in diabetes mellitus patients and other immunosuppressive conditions with recent predisposing factors such as maxillofacial surgery and corticosteroid usage. Methods: In this study, 14 patients were referred to the otorhinolaryngology or ophthalmology ward of Shafa Hospital (Kerman, Iran) with primary symptoms of nasal fullness and facial nerve dysfunction; they were admitted to the hospital to rule out the fungal infection. An endoscopic biopsy was taken from facial sinuses or orbit, and a microscopic evaluation was performed using hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining methods to rule out mucormycosis. Results: In the histopathological examination, broad-based nonseptate branching fungal hyphae were found in nasal sinuses through the endoscopic biopsy. Most of the patients had diabetes mellitus with a primary symptom of facial nerve palsy; also, most of them received corticosteroids (intravenous [IV] or intramuscular [IM] injection). All patients have recently been infected with COVID-19 (less than 1 month ago). Conclusion: COVID-19 infection might be a predisposing factor for many opportunistic infections, such as fungal elements); thus, the physician should be aware of the dosage and duration of corticosteroid therapy to prevent the development of these infections.

Label-free electrochemical immunosensor for detection of insulin-like growth factor-1 (IGF-1) using a specific monoclonal receptor on electrospun Zein-based nanofibers/rGO-modified electrode.

A novel electrochemical immunosensor was developed for ultrasensitive determination of the hormone insulin-like growth factor 1 (IGF-1) based on immobilization of a specific monoclonal antibody on the electrospun nanofibers of Polyacrylonitrile (PAN)/Zein-reduced graphene oxide (rGO) nanoparticle. The nanofibers deposited on glassy carbon electrode (GCE) showed good electrochemical behaviors with synergistic effects between PAN, Zein, and rGO. PAN/Zein nanofibers were used due to flexibility, high porosity, good mechanical strength, high specific surface area, and flexible structures, while rGO nanoparticles were used to improve the detection sensitivity and anti-IGF-1 immobilizing. Different characterization techniques were applied consisting of FE-SEM, FT-IR, and EDS for the investigation of morphological features and nanofiber size. The redox reactions of [Fe(CN)6]4-/3- on the modified electrode surface were probed for studying the immobilization and determination processes, using differential pulse voltammetry (DPV) and cyclic voltammetry (CV). Under optimal conditions, LOD (limit of detection) and LOQ (limit of quantification) were obtained as 55.72 fg/mL and 185.73 fg/mL respectively, and sensitivity was acquired 136.29 µA/cm2.dec. Moreover, a wide linear range was obtained ranging from 1 pg/mL to 10 ng/mL for IGF-1. Furthermore, the proposed method was applied for the analysis of IGF-1 in several human plasma samples with acceptable results, and it also exhibited high selectivity, stability, and reproducibility.

Investigating the Anti-tumor and Apoptosis-inducing Effects of Coumarin Derivatives as Potent 15-Lipoxygenase Inhibitors on PC-3 Prostate Cancer Cells.

INTRODUCTION: Prostate cancer is the second most prevalent cancer among men. Despite different treatments, including surgery, chemotherapy, radiation therapy, hormone therapy and immunotherapy for this disease, patients ultimately progress to advanced states. Thus, there is a need for new treatment options targeting cell growth and apoptosis to better control the proliferation and metastasis of these cells. There are many reports indicating overexpression of the 15-lipoxygenase-1 (15-LOX-1) enzyme in prostate tumors. Studies have also shown that inhibition of this enzyme prevents the progression of prostate cancer. OBJECTIVE: This study was conducted to assess the anti-cancer properties of some coumarin derivatives as possible 15- LOX-1 inhibitors, on PC-3 prostate cancer cells. METHODS: In this study, the activity of 15-LOX-1 was evaluated in PC-3 cells by a spectrophotometric assay. In addition, due to high similarity between the 15-LOX-1 and soybean 15-lipoxygenase (SLO) (L1; EC 1, 13, 11, 12) active sites, the soybean SLO was used to investigate inhibitory effects of synthetic coumarin compounds 8- isopentenyloxycoumarin (8-IC), 8-isopentenyloxy-3-carboxycoumarin (8-ICC), 8-geranyloxycoumarin (8-GC), 8- geranyloxy-3-carboxycoumarin (8-GCC), and 8-farnesyloxy-3-carboxycoumarin (8-FCC) on this enzyme. Moreover, the cytotoxic and anticancer effects of the coumarin compounds were examined on PC-3 (Prostate Cancer) and HDF-1 (Human Dermal Fibroblast) cells by alamarBlue assay. Finally, apoptosis-inducing effects of all synthetic compounds were determined by flow cytometry. RESULTS: The IC50 values obtained by the alamarBlue test revealed that 8-IC, 8-GC and 8-GCC had cytotoxic effects on PC-3 cells. Treating both PC-3 and HDF-1 cells with 8-ICC and 8-FCC did not significantly reduce cell number. Furthermore, the IC50 values of 8-IC on HDF-1 cells showed cytotoxic effects, while treating these cells with 8-GC and 8- GCC did not show any significant cytotoxicity on these normal human fibroblasts. Assessing the ability of 4-MMPB (as a specific inhibitor of 15-LOX-1), 8-GC, and 8-GCC compounds to inhibit SLO revealed that these compounds exerted strong 15-LOX-1 inhibitory activity, while 8-IC and 8-FCC had a weak inhibitory effect and also 8-ICC showed no inhibitory effect on SLO enzyme. In addition, flow cytometric analysis by FITC (fluorescein isothiocyanate)- annexin V and propidium iodide showed that treatment with IC50 values of 8-GC and 8-GCC induced apoptosis in 35.2% and 30.8% of PC-3 cells, respectively. CONCLUSION: Thus, 8-GC and 8-GCC can be introduced as effective anticancer agents with apoptosis-inducing properties. Furthermore, our results suggest that the cytotoxic effects of these compounds might be related to the inhibition of 15-LOX-1 enzyme in PC-3 cells. On the other hand, the cytotoxic effects of 8-IC might be due to the inhibition of other signaling pathways in PC-3 cells. However, further in vivo experiments are required to determine the exact mechanisms involved in the anticancer effects of these coumarin compounds.

Home health care of Iranian elderly with dementia: Study protocol for guideline adaptation.

BACKGROUND: Advanced stages of dementia interfere with elderly self-care. Consequently, they need caregivers who take responsibility for their care in the long-term. Restrictions to the caregiver's access to information, resources, and organizational support have created problems in their caregiver role, which is why the World Health Organization (WHO) emphasizes caring for caregivers by providing evidence-based information and training programs. As there is no clinical practice guideline for home care in the Islamic Republic of Iran, this study aims to develop a home health care guideline for the elderly with dementia. MATERIALS AND METHODS: The ADAPTE process provided by the Guidelines International Network was considered as the basis. In order to identify the care needs of Iranian patients with dementia, semi-structured interviews were added to this guideline. DISCUSSION: The identification and implementation of the perspectives of patients and caregivers during the process of guidelines adaptation increase the applicability of the guidelines. Improved quality of life for the patients in their place of residence is one of the expected consequences of this guideline's implementation. The developed guidelines will be used at home health care centers, and dementia and Alzheimer's associations in Iran.

Electrochemical-Based Sensing Platforms for Detection of Glucose and H2O2 by Porous Metal-Organic Frameworks: A Review of Status and Prospects.

Establishing enzyme-free sensing assays with great selectivity and sensitivity for glucose and H2O2 detection has been highly required in biological science. In particular, the exploitation of nanomaterials by using noble metals of high conductivity and surface area has been widely investigated to act as selective catalytic agents for molecular recognition in sensing platforms. Several approaches for a straightforward, speedy, selective, and sensitive recognition of glucose and H2O2 were requested. This paper reviews the current progress in electrochemical detection using metal-organic frameworks (MOFs) for H2O2 and glucose recognition. We have reviewed the latest electrochemical sensing assays for in-place detection with priorities including straightforward procedure and manipulation, high sensitivity, varied linear range, and economic prospects. The mentioned sensing assays apply electrochemical systems through a rapid detection time that enables real-time recognition. In profitable fields, the obstacles that have been associated with sample preparation and tool expense can be solved by applying these sensing means. Some parameters, including the impedance, intensity, and potential difference measurement methods have permitted low limit of detections (LODs) and noticeable durations in agricultural, water, and foodstuff samples with high levels of glucose and H2O2.

Point-of-Care Tests' Role in Time Metrics of Urgent Interventions in Emergency Department; a Systematic Review of Literature.

Introduction: Point-of-Care Testing (POCT) could be helpful in clinical decisions, treatment selection, monitoring, prognostication, operational decision-making, and resource utilization. This study aimed to review the role of POCT in time metrics of performing urgent interventions in the emergency department (ED) or disposition time to proper care. Methods: This was a systematic review of the literature based on the PRISMA statement. PubMed, Scopus, Web of Science, and EMBASE databases were searched for studies reporting the application of the POCT in the ED with outcomes of the time to intervention or disposition. Results: After reviewing 3708 articles, 16 studies with 100,224 participants were included in this systematic review. There were 5 randomized clinical trials (RCTs), 5 retrospective cohorts, 2 prospective cohorts, and 4 before-after studies. All studies were performed in an ED setting except for one study of prehospital EMS air medical transport. Different panels, ultrasound, cardiac parameters, echocardiography, and polymerase chain reaction (PCR) POCTs were used in the studies. Regarding the outcome measures, studies with many types of patients referring to ED used different indices of time to intervention or time to disposition. Studies on different shock circumstances used the time to the first bolus of hydration or vasopressor or intravenous antibiotics for septic shock patients and central venous catheterization (CVC) placement time in one study. Time to imaging was considered as the outcome in some studies. Overall, there was a high risk of bias, especially in case of the randomization methods, and non-blinded designs in RCTs. There was lower possibility of bias in non-randomized studies but the studies did not have enough follow-ups and in case of studies using advanced panels of POCT, results do not seem to be easily applicable to public health care in many countries. Conclusion: In synthesis of the evidence, all included studies were reporting the benefits of the POCT in decreasing the time to proper interventions and increasing the time to negative interventions in the last lines of critical care as well as the intubation and CVC placement.

Comparison of the Relationship Between SI and RASI Scores With the Outcome of Sepsis Patients.

The aim of this study was to compare the relationship between shock index (SI) and respiratory adjusted shock index (RASI) scores with the final outcome of sepsis patients referred to the emergency department. This was prospective research that examined individuals who had been diagnosed with sepsis, determined by the presence of at least two of the three quick sepsis-related organ failure assessment (qSOFA) criteria and the presence of an infectious disease based on a diagnosis made by a hospital physician of Imam Reza and Ghaemshahr of Mashhad in 2019. Demographic information of patients, SI score, RASI score, and information related to the patient's clinical symptoms were recorded in the checklist. The final outcome of this study was considered mortality. Data analysis was performed using descriptive and inferential tests. In the present study, a total of 178 patients, 46 patients (25.8%) were transferred to the intensive care unit, and 98 patients (55.1%) were admitted to the normal wards. Eighty-five patients (47.75%) died and the mean length of hospital stay of all patients was 11.07 ± 9.23 days. Forty-four patients (24.7%) had referred with a decreased level of consciousness and 44 patients (24.7%) presented with confusion. The rest of the patients reported normal levels of consciousness. Kaplan Mir analysis with log-rank was performed to determine the difference in survival distribution in different SI groups: Survival distribution was not statistically different for the four defined groups (based on statistical quartiles (P = 0.320). Receiver operator curves were considered as the date of death in the case of the deceased and the date of discharge from the hospital in the case of the living as censored. The AUC of the RASI scoring system for predicting mortality was 0.614 (P = 0.009) while this value was not significant for SI (P = 0.152). In logistic regression analysis, it was found that by adjusting for the variables of age, sex, sepsis etiology, blood pressure and heart rate, level of consciousness, and gender, patients with the lower respiratory rate (OR 1.6, z = -0.159 p = 0.007), younger age (OR 1.6, z = -0.029 p = 0.006) and higher RASI score are more in risk of mortality (OR 1.29, z = 1.209, p = 0.031). The results of our study showed that RASI scoring can be a good criterion for predicting the chance of mortality in patients with sepsis and could be used complementary to previous criteria such as SI. Patients with high RASI scores should be given more attention to reducing the chance of death.

Efficient and specific bioaccumulation of arsenic in the transgenic Escherichia coli expressing ArsR1 from Corynebacterium glutamicum.

The toxic nature of arsenic has left a trail of disastrous health consequences around the world. Microorganisms have developed various strategies to deal with arsenic. The presence of plasmid and chromosomal ars operons is one of the most important mechanisms for the detoxification of arsenic in bacteria. ArsR is a trans-acting regulatory protein and acts as a repressor on ars operon. The gene encoding ArsR from Corynebacterium glutamicum (CgArsR1) was cloned in expression vectors pET28a. The resulting constructs were transformed into Escherichia coli strains Rosetta (DE3) and Rosetta gami 2. Following the induction with Isopropyl ß-D-1-thiogalactopyranoside, the protein His-CgArsR1 was found in the soluble fraction of strain Rg-CgArsR1. For comparison, ArsR from E. coli was also overexpressed in E. coli (strain Rosetta gami 2) as His-EcArsR. A strain containing empty vector pET28a was also used as a control strain. In the medium containing either arsenite (0.5 mM) or arsenate (0.5 mM), the strain Rg-CgArsR1 and Rg-EcArsR were able to accumulate 1200 and 700 µg/g DCW As3+, respectively. In comparison, the accumulation of As5+ in these strains was 338 and 232 µg/g DCW, respectively. Whereas both strains Rg-CgArsR1 and Rg-EcArsR were able to accumulate higher amounts of As3+ and As5+ with respect to control strain, the accumulation of arsenic in the strain Rg-CgArsR1 was significantly more efficient than strain Rg-EcArsR for removing As3+ and As5+. Based on the results the gene encoding CgArsR1 is a useful and efficient target gene for the modification of bacteria for bioremediation of arsenic from polluted soil and water.

Incidence of Pediatric Perforated Appendicitis during the COVID-19 Pandemic; a Systematic Review and Meta-Analysis.

INTRODUCTION: COVID-19 has affected the pattern of referral to medical centers and quarantine against COVID-19 might delay referral and management of surgical emergencies. This study aimed to compare the pooled event rate of pediatric perforated appendicitis before and during the COVID-19 pandemic. METHODS: This was a systematic review and meta-analysis study based on the PRISMA guidelines. Scopus, Web of Sciences, and PubMed databases were searched for studies reporting the rate of perforated appendicitis based on the post-appendectomy observations or imaging methods. The Egger bias test and funnel plot were used to detect and depict publication bias. Statistical analysis was performed in Comprehensive Meta-analysis package version 3. RESULTS: Twelve studies were eligible for inclusion in our study. The pooled prevalence of pediatric perforated appendicitis in the pre-COVID era was 28.5% (CI95%: 28.3 to 28.7%) with a heterogeneity of 99%. In the COVID era, the event rate proportion was 39.4% (CI95%: 36.6 to 42.3%) with a heterogeneity of 99%. There was a significant difference in the subgroup analysis within the pre-COVID and COVID era (P<0.001), showing a higher perforation rate in the COVID era. CONCLUSION: Our study showed that during the COVID-19 pandemic, the rate of perforated appendicitis has significantly increased in comparison to before the COVID-19 pandemic.

Accuracy of CREST Guideline in Management of Cellulitis in Emergency Department; a Systematic Review and Meta-analysis.

INTRODUCTION: Skin and soft tissue infections are important causes of outpatient visits to medical clinics or hospitals. This study aimed to review the literature for the accuracy of Clinical Resource Efficiency Support Team (CREST) guideline in management of cellulitis in emergency department. METHOD: Studies that had evaluated cellulitis patients using the CREST guideline were quarried in Scopus, Web of Science, and PubMed database, from 2005 to the end of 2020. The quality of the studies was evaluated using Scottish Intercollegiate Guideline Network (SIGN) checklist for cohort studies. Pooled area under the receiver operating characteristic curve (AUROC) of CREST guideline regarding the rate of hospital stay more than 24 hours, rate of revisit, and appropriateness of antimicrobial treatment in management of cellulitis in emergency department was evaluated. RESULTS: Seven studies evaluating a total of 1640 adult cellulitis patients were finally entered to the study. In evaluation of the rate of the appropriate treatment versus over-treatment, the pooled AUROC was estimated to be 0.38 (95% confidence interval (CI): 0.06 - 0.82), indicating low accuracy (AUROC lower than 0.5) of guideline for antimicrobial choice. CREST II patients had a significantly lower odds ratio (OR) of revisiting the Emergency Department, OR=0.21 (95% CI: 0.009 - 0.47). Pooled AUROC value of 0.86 (CI95%: 0.84 - 0.89) showed accuracy of the CREST classification in prediction of being hospitalized more or less than 24 hours. CONCLUSION: CREST classification shows good accuracy in determining the duration of hospitalization or observation in ED but it could lead to inevitable over/under treatment with empirical antimicrobial agents.

Multivariate optimization of removing of cobalt(II) with an efficient aminated-GMA polypropylene adsorbent by induced-grafted polymerization under simultaneous gamma-ray irradiation.

Nowadays, radiation grafting polymer adsorbents have been widely developed due to their advantages, such as low operating cost, high efficiency. In this research, glycidyl methacrylate monomers were grafted on polypropylene polymer fibers by simultaneous irradiation of gamma-ray with a dose of 20 kGy. The grafted polymer was then modified using different amino groups and tested for adsorption of cobalt ions in an aqueous solution. Finally, the modified polymer adsorbent with a high efficiency for cobalt ions adsorption was synthesized and tested. Different modes of cobalt ions adsorption were tested in other adsorption conditions, including adsorption contact time, pH, different amounts of adsorbent mass, and different concentrations of cobalt ions solution. The adsorbent structure was characterized with FT-IR, XRD, TG and SEM techniques and illustrated having an efficient grafting percentage and adsorption capability for cobalt removing by batch experiments. The optimum conditions were obtained by a central composite design: adsorbent mass = 0.07 g, initial concentration = 40 mg/L, time = 182 min, and pH = 4.5 with ethylenediamine as a modified monomer and high amination percentage. Kinetics and equilibrium isotherms observation described that the experimental data followed pseudo-second-order and Langmuir models, respectively. The maximum adsorption capacity from Langmuir isotherm capacity is obtained equal to 68.02 mg/g.

The Metabolomic Profiles of Sera of Mice Infected with Plasmodium berghei and Treated by Effective Fraction of Naja naja oxiana Using 1H Nuclear Magnetic Resonance Spectroscopy.

BACKGROUND: The use of venom fractions from the Iranian cobra could be useful adjunct treatments of malaria with chloroquine. A metabolomic investigation with 1HNMR spectroscopy was conducted on an effective fraction tested earlier using Plasmodium berghei as an experimental murine model. PURPOSE: We sought to ascertain both safety and anti-parasitic effects of experimental therapies. METHODS: After purification of the venom fractions, 25 mice were infected, then treated for 4 days with 0.2 ml of 5 mg/kg, 2.5 mg/kg and 1 mg/kg of the effective fraction, chloroquine, and a drug vehicle. An ED50 was obtained using Giemsa staining and real-time PCR analysis. The toxicity tests inspecting both liver and kidney tissues were performed. RESULTS: A clear inhibitory effect on parasitaemia was observed (with 75% inhibition with 5 mg/kg and 50% reduction when 2.5 mg/kg dosage used). ED50 obtained 2.5 mg/kg. The metabolomics were identified as differentiation of aminoacyl-t-RNA biosynthesis, valine, leucine, isoleucine biosynthesis and degradation pathways were observed. CONCLUSION: Upon therapeutic effects of cobra venom fraction, further optimization of dose-dependent response of pharmacokinetics would be worthwhile for further exploration in adjunct experimental venom therapies.

Consolidated bioprocessing for bioethanol production by metabolically engineered Bacillus subtilis strains.

Bioethanol produced by fermentative microorganisms is regarded as an alternative to fossil fuel. Bioethanol to be used as a viable energy source must be produced cost-effectively by removing expense-intensive steps such as the enzymatic hydrolysis of substrate. Consolidated bioprocessing (CBP) is believed to be a practical solution combining saccharification and fermentation in a single step catalyzed by a microorganism. Bacillus subtills with innate ability to grow on a diversity of carbohydrates seems promising for affordable CBP bioethanol production using renewable plant biomass and wastes. In this study, the genes encoding alcohol dehydrogenase from Z. mobilis (adhZ) and S. cerevisiae (adhS) were each used with Z. mobilis pyruvate decarboxylase gene (pdcZ) to create ethanologenic operons in a lactate-deficient (Δldh) B. subtilis resulting in NZ and NZS strains, respectively. The S. cerevisiae adhS caused significantly more ethanol production by NZS and therefore was used to make two other operons including one with double copies of both pdcZ and adhS and the other with a single pdcZ but double adhS genes expressed in N(ZS)2 and NZS2 strains, respectively. In addition, two fusion genes were constructed with pdcZ and adhS in alternate orientations and used for ethanol production by the harboring strains namely NZ:S and NS:Z, respectively. While the increase of gene dosage was not associated with elevated carbon flow for ethanol production, the fusion gene adhS:pdcZ resulted in a more than two times increase of productivity by strain NS:Z as compared with NZS during 48 h fermentation. The CBP ethanol production by NZS and NS:Z using potatoes resulted in 16.3 g/L and 21.5 g/L ethanol during 96 h fermentation, respectively. For the first time in this study, B. subtilis was successfully used for CBP ethanol production with S. cerevisiae alcohol dehydrogenase. The results of the study provide insights on the potentials of B. subtilis for affordable bioethanol production from inexpensive plant biomass and wastes. However, the potentials need to be improved by metabolic and process engineering for higher yields of ethanol production and plant biomass utilization.

Community-Based Preventive Interventions for Depression and Anxiety in Women.

BACKGROUND: Depression and anxiety are the most common mental disorders and currently, they constitute one of the main causes of disability and death. The high prevalence of psychiatric disorders and their increasing burden are noteworthy. The aim of this study is to investigate the effectiveness of community-based preventive interventions for depression and anxiety in women. METHODS: We systematically searched for articles published up to the beginning of 2018, which addressed community-based preventive interventions for depression and anxiety in women. The studies were searched in PubMed, Scopus, Cochrane Library, Web of Science, PsycInfo, IranMedex, SID and EMBASE electronic databases. Articles that complied with our inclusion criteria (preventive interventions involving healthy adult women aged 18 to 65 years) were reviewed. Quality assessment of the articles was performed using standard tools. We extracted the required data and reported the results in a narrative form. RESULTS: Twenty-three articles were identified and entered into the final review. Depression and anxiety symptoms were decreased in more than 70% of interventions. Cognitive behavioral therapy (CBT) and exercise were the most effective interventions. In addition, computer and internet-based programs had positive outcomes in both categories of depression and anxiety. CONCLUSION: Community-based preventive programs for depression and anxiety in women had promising and positive results. CBT and exercise were the most effortless, yet the most effective interventions to apply. Computer and internet-based programs had the benefit of covering many people simultaneously. These interventions are cost-effective and feasible among Iranian women.

The In Vitro Study of Anti-leishmanial Effect of Naja naja oxiana Snake Venom on Leishmania major.

BACKGROUND: Although a majority of patients with cutaneous leishmaniasis (CL) are healed with Glucantime chemotherapy, the increased drug resistance rate following its application is a concern. In this study, Naja naja oxiana crude venom of cobra snakes was used for the first time as an assembled combination of bioactive pharmaceutical components on Leishmania major (L. major) standard strain. OBJECTIVE: To evaluate the efficacy of the Naja naja oxiana crude venom of Iranian cobra snakes on Leishmania major standard strain in vitro. METHODS: Five concentrations (1.25, 2.5, 5, 10 and 20 µg/mL) of venom were added to Leishmania major cultures at 24, 48 and 72 h. The viability of the parasites and venom toxicity were assessed by MTT test. The apoptosis was determined by flow cytometry, while IC50 was determined by counting parasites compared to that of glucantime. Each test was conducted in triplicate. RESULTS: After the exposure of the venom for 72 h, IC50 value was 0.36 µg/mL and 14.12 µg/mL for promastigotes and amastigotes, respectively. MTT valuation clarified 1.01% promastigotes viability. Furthermore, the results indicated that the venom of Naja naja oxiana induced early and late apoptosis in parasites. CONCLUSIONS: The venom of Naja naja oxiana revealed remarkable anti-leishmanial effects as a novel anti-parasitic alternative. Thus, the bioactive and effective fractions of this venom may be considered as anti-leishmanial candidates in future studies.

Stylosin and some of its synthetic derivatives induce apoptosis in prostate cancer cells as 15-lipoxygenase enzyme inhibitors.

Overexpression of 15-lipoxygenase-1 (15-LOX-1) enzyme has been reported in prostate tumors, and its expression levels are associated with the degree of cancer malignancy. The aim of this study was to investigate inhibitory effects of stylosin and some similar synthetic monoterpenoids on 15-LOX and also their cytotoxic and anti-cancer activities on prostate cancer cells. Cytotoxicity of compounds was evaluated on prostate cancer cell line "PC-3" and normal human fibroblast "HFF3" cells using AlamarBlue reduction test. The inhibitory effects of the compounds against soybean 15-LOX, a commercially available enzyme, were also assessed. Finally, mechanism of cell death was investigated by flow cytometry. Some of these terpenoids had cytotoxic effects on PC-3 cells, and strong positive correlation was observed between the 15-LOX-1 inhibition potential and the cytotoxicity of the compounds. Moreover, flow cytometry results indicated that apoptosis was the predominant mechanism of induced cell death, which emphasizes the potential of these compounds in prostate cancer therapy. Among studied terpenoids, "fenchyl ferulate" exhibited about three times more cytotoxicity than cisplatin. Strong positive correlation observed between 15-LOX inhibition potential and cytotoxicity of the compounds indicates selective anti-cancer properties of the compounds might be exerted via inhibition of 15-LOX-1 in PC-3 cells. Furthermore, observed cytotoxicity is mediated through apoptosis, which is probably triggered via 15-LOX-1 inhibition.

Relationship of gray values in cone beam computed tomography and bone mineral density obtained by dual energy X-ray absorptiometry.

OBJECTIVES: The aim of this study was to assess the correlation between bone mineral density (BMD) determined with cone beam computed tomography (CBCT) gray values and BMD determined by dual energy X-ray absorptiometry (DEXA). STUDY DESIGN: Women age greater than 50 years requiring CBCT for implant treatment were included in the study. BMD was determined by calculating the mean gray value of CBCT cross-sectional images of anterior, premolar, retromolar, and tuberosity areas of the mandible and maxilla. Patients were then subjected to DEXA of the femoral neck and lumbar spine. Independent t tests, analysis of variance (ANOVA), Pearson's correlation tests, and receiver operating characteristic (ROC) evaluation were used for data analysis. RESULTS: Of 61 asymptomatic patients (mean age 64 years), 47.5% and 55.7% had abnormal BMD, based on the T-scores of the femoral neck and lumbar spine, respectively. Significant correlations were noted between the T-scores of the femoral neck and lumbar spine and the gray values of the maxillary incisor and tuberosity areas. CONCLUSIONS: A strong correlation exists between the CBCT gray values at different sites in the maxilla and the results of DEXA. A gray value less than 298 at the maxillary tuberosity can help distinguish patients with osteoporosis from normal individuals, with 66% to 67% accuracy and suggests the need for DEXA analysis.