Comprehensive review on glucose 6 phosphate dehydrogenase: A critical immunometabolic and redox switch in insects.

Mounting an active immune response is energy intensive and demands the reallocation of nutrients to maintain the body's resistance and tolerance against infections. Central to this metabolic adaptation is Glucose-6-phosphate dehydrogenase (G6PDH), a housekeeping enzyme involve in pentose phosphate pathway (PPP). PPP play an essential role in generating ribose, which is critical for nicotinamide adenine dinucleotide phosphate (NADPH). It is vital for physiological and cellular processes such as generating nucleotides, fatty acids and reducing oxidative stress. The G6PDH is extremely conserved enzyme across species in PP shunt. The deficiency of enzymes leads to serious consequences on organism, particularly on adaptation and development. Acute deficiency can lead to impaired cell development, halted embryonic growth, reduce sensitivity to insulin, hypertension and increase inflammation. Historically, research focusing on G6PDH and PPP have primarily targeted diseases on mammalian. However, our review has investigated the unique functions of the G6PDH enzyme in insects and greatly improved mechanistic understanding of its operations. This review explore how G6PDH in insects plays a crucial role in managing the redox balance and immune related metabolism. This study aims to investigate the enzyme's role in different metabolic adaptations.

Molecular characterization, immune functions and DNA protective effects of peroxiredoxin-1 gene in Antheraea pernyi.

Peroxiredoxins are antioxidant proteins that detoxify peroxynitrite, hydrogen peroxide, and organic hydroperoxides, impacting various physiological processes such as immune responses, apoptosis, cellular homeostasis, and so on. In the present study, we identified and characterized peroxiredoxin 1 from Antheraea pernyi (thereafter designated as ApPrx-1) that encodes a predicted 195 amino acid residue protein with a 21.8 kDa molecular weight. Quantitative real-time PCR analysis revealed that the mRNA level of ApPrx-1 was highest in the hemocyte, fat body, and midgut. Immune-challenged larval fat bodies and hemocytes showed increased ApPrx-1 transcript. Moreover, ApPrx-1 expression was induced in hemocytes and the whole body of A. pernyi following exogenous H2O2 administration. A DNA cleavage assay performed using recombinant ApPrx-1 protein showed that rApPrx-1 protein manifests the ability to protect supercoiled DNA damage from oxidative stress. To test the rApPrx-1 protein antioxidant activity, the ability of the rApPrx-1 protein to remove H2O2 was assessed in vitro using rApPrx-1 protein and DTT, while BSA + DDT served as a control group. The results revealed that ApPrx-1 can efficiently remove H2O2 in vitro. In the loss of function analysis, we found that ApPrx-1 significantly increased the levels of H2O2 in ApPrx-1-depleted larvae compared to the control group. We also found a significantly lower survival rate in the larvae in which ApPrx-1 was knocked down. Interestingly, the antibacterial activity was significantly higher in the ApPrx-1 depleted larvae, compared to the control. Collectively, evidence strongly suggests that ApPrx-1 may regulate physiological activities and provides a reference for further studies to validate the utility of the key genes involved in reliving oxidative stress conditions and regulating the immune responses of insects.

Screening of anti-melanoma compounds from Morus alba L.: Sanggenon C promotes melanoma cell apoptosis by disrupting intracellular Ca2+ homeostasis.

ETHNOPHARMACOLOGICAL RELEVANCE: Morus alba L. is a widespread plant that has long been considered to have remarkable medical values, including anti-inflammation in Traditional Chinese Medicine (TCM). The components of Morus Alba L. constituents have been extensively studied and have been shown to have high prospects for cancer therapy. However, limited investigations have been done on the bioactive compounds in Morus alba L. AIM OF THE STUDY: This study aimed to systematically examine the anticancer properties of 28 commercially available compounds from Morus alba L. against melanoma cells in vitro. Additionally, the anticancer mechanisms of the bioactive compound exhibiting the most significant potential were further studied. MATERIALS AND METHODS: The anti-proliferative effects of Morus alba L.-derived compounds on melanoma cells were determined by colony formation assays. Their effects on cell viability and apoptosis were determined using the CCK8 assay and flow cytometry, respectively. The binding affinity of identified Morus alba L. compounds with anticancer activities towards melanoma targets was analyzed via molecular docking. The molecular mechanism of Sanggenon C was explored using soft agar assays, EdU incorporation assays, flow cytometry, western blotting, transcriptome analysis, and xenograft assays. RESULTS: Based on colony formation assays, 11 compounds at 20 µM significantly inhibited colony growth on a panel of melanoma cells. These compounds displayed IC50 values (half maximal inhibitory concentrations) ranging from 5 µM to 30 µM. Importantly, six compounds were identified as novel anti-melanoma agents, including Sanggenon C, 3'-Geranyl-3-prenyl-2',4',5,7-tetrahydroxyflavone, Moracin P, Moracin O, Kuwanon A, and Kuwanon E. Among them, Sanggenon C showed the most potent effects, with an IC50 of about 5 µM, significantly reducing proliferation and inducing apoptosis in melanoma cells. Based on the xenograft model assay, Sanggenon C significantly inhibited melanoma cell proliferation in vivo. Sanggenon C triggered ER stress in a dose-dependent manner, which further disrupted cellular calcium ion (Ca2+) homeostasis. The Ca2+ chelator BAPTA partially restored cell apoptosis induced by Sanggenon C, confirming that Ca2+ signaling contributed to the anticancer activity of Sanggenon C against melanoma. CONCLUSIONS: In our study, 11 compounds demonstrated anti-melanoma properties. Notably, Sanggenon C was found to promote apoptosis by disrupting the intracellular calcium homeostasis in melanoma cells. This study provides valuable information for the future development of novel cancer therapeutic agents from Morus alba L.

Effect of 810 nm Diode Laser Irradiation on the Time of Initiation and Depth of Anesthesia for Endodontic Treatment of Mandibular First Molars with Symptomatic Irreversible Pulpitis: A Clinical Trial.

Objective: In endodontic treatments, performing appropriate anesthesia in patients with irreversible pulpitis in mandibular molars may result in pain and severe problems. The irradiation of low-level lasers could be effective in this regard due to its anti-inflammatory and regenerative properties. This study aimed to assess the effect of 810 nm diode laser on the time of initiation and depth of anesthesia for endodontic treatment of mandibular first molars with symptomatic irreversible pulpitis. Materials and methods: This randomized controlled clinical trial evaluated 60 patients requiring endodontic treatment of mandibular first molars with symptomatic irreversible pulpitis and pain score ≥114 according to the Heft-Parker visual analog scale (HP-VAS). The teeth were randomized into two groups of diode laser and control. In the diode laser group, 810 nm diode laser with 300 mW power and 15 J/cm2 energy density was irradiated to the buccal surface of tooth crowns for 20 sec at 2 mm distance immediately before anesthesia administration. Laser in off mode was used in the control group. Inferior alveolar nerve block was then performed using 2% lidocaine with 1:80,000 epinephrine. After anesthetic injection, the mandibular first molar and canine teeth (control) were tested by an electric pulp tester every 2 min. Two consecutive negative responses to 80 mA indicated the initiation of anesthesia. HP-VAS forms were filled out by patients to assess their level of pain during the procedure. Data were analyzed by the Student's t and Chi-square tests, and analysis of variance (α = 0.05). Results: No remarkable difference was noted between the laser group and control groups in pain severity or anesthesia onset (p > 0.05). Conclusions: Low-level (810 nm) diode laser did not affect the time of initiation or depth of anesthesia in endodontic treatment of mandibular first molars with symptomatic irreversible pulpitis. Clinical trials registration: Iranian Registry of Clinical Trials (IRCT20181222042076N1).

A qualitative quantitative mixed methods study of domestic violence against women.

BACKGROUND: Violence against women is one of the most widespread, persistent and detrimental violations of human rights in today's world, which has not been reported in most cases due to impunity, silence, stigma and shame, even in the age of social communication. Domestic violence against women harms individuals, families, and society. The objective of this study was to investigate the prevalence and experiences of domestic violence against women in Semnan. METHODS: This study was conducted as mixed research (cross-sectional descriptive and phenomenological qualitative methods) to investigate domestic violence against women, and some related factors (quantitative) and experiences of such violence (qualitative) simultaneously in Semnan. In quantitative study, cluster sampling was conducted based on the areas covered by health centers from married women living in Semnan since March 2021 to March 2022 using Domestic Violence Questionnaire. Then, the obtained data were analyzed by descriptive and inferential statistics. In qualitative study by phenomenological approach and purposive sampling until data saturation, 9 women were selected who had referred to the counseling units of Semnan health centers due to domestic violence, since March 2021 to March 2022 and in-depth and semi-structured interviews were conducted. The conducted interviews were analyzed using Colaizzi's 7-step method. RESULTS: In qualitative study, seven themes were found including "Facilitators", "Role failure", "Repressors", "Efforts to preserve the family", "Inappropriate solving of family conflicts", "Consequences", and "Inefficient supportive systems". In quantitative study, the variables of age, age difference and number of years of marriage had a positive and significant relationship, and the variable of the number of children had a negative and significant relationship with the total score and all fields of the questionnaire (p < 0.05). Also, increasing the level of female education and income both independently showed a significant relationship with increasing the score of violence. CONCLUSIONS: Some of the variables of violence against women are known and the need for prevention and plans to take action before their occurrence is well felt. Also, supportive mechanisms with objective and taboo-breaking results should be implemented to minimize harm to women, and their children and families seriously.

Colistin induced acute kidney injury in critically ill children: a prospective study utilizing RIFLE criteria.

BACKGROUND: Colistin is one of the last resort antibiotic options for resistant gram-negative pathogens. Renal injury is the most common side effect of colistin. Characteristics of nephrotoxicity are well described in adults. However, this data is sparse in children. OBJECTIVES: In this study we evaluated the incidence, severity, time course and risk factors of colistin nephrotoxicity in a pediatric population. METHODS: In a prospective study over a 9-month period, children who received intravenous colistin for at least 48 h were evaluated for renal side effect by utilizing Risk-Injury-Failure-Loss-End Stage Kidney Disease (RIFLE) criteria. Children receiving renal replacement therapy (RRT) or received a repeated course of colistin were excluded. RESULTS: Thirty-seven children were included. Median age of participants was 4.5 months. Overall, 48.6% of the cases developed AKI and consisted 56% in the Risk, 33% in the Injury and 11% in the Failure categories of RIFLE criteria. AKI was reversible while colistin continued and no one required RRT. Mean ± SD time to AKI development was 10.94 ± 7.51 days. Multivariate logistic regression analysis demonstrated that total cumulative dose of colistin was an independent predictor of nephrotoxicity (standardized ß = 1.024, P = 0.034). CONCLUSION: AKI is a common side effect of colistin therapy in critically ill children developing in nearly half of recipients. However, with the dosage range utilized in this study, in the majority of children, renal injury seemed to be mild to moderate in nature. Given the limited treatment options available in critically ill children with resistant gram-negative pathogens, colistin remains a marvelous therapeutic option. Further studies are required to fully elucidate the risk factors and clinical pictures of colistin-induced nephrotoxicity.

SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19.

BACKGROUND: Monoclonal antibodies (mAbs) are laboratory-produced molecules derived from the B cells of an infected host. They are being investigated as a potential therapy for coronavirus disease 2019 (COVID-19). OBJECTIVES: To assess the effectiveness and safety of SARS-CoV-2-neutralising mAbs for treating patients with COVID-19, compared to an active comparator, placebo, or no intervention. To maintain the currency of the evidence, we will use a living systematic review approach. A secondary objective is to track newly developed SARS-CoV-2-targeting mAbs from first tests in humans onwards.  SEARCH METHODS: We searched MEDLINE, Embase, the Cochrane COVID-19 Study Register, and three other databases on 17 June 2021. We also checked references, searched citations, and contacted study authors to identify additional studies. Between submission and publication, we conducted a shortened randomised controlled trial (RCT)-only search on 30 July 2021. SELECTION CRITERIA: We included studies that evaluated SARS-CoV-2-neutralising mAbs, alone or combined, compared to an active comparator, placebo, or no intervention, to treat people with COVID-19. We excluded studies on prophylactic use of SARS-CoV-2-neutralising mAbs. DATA COLLECTION AND ANALYSIS: Two authors independently assessed search results, extracted data, and assessed risk of bias using the Cochrane risk of bias tool (RoB2). Prioritised outcomes were all-cause mortality by days 30 and 60, clinical progression, quality of life, admission to hospital, adverse events (AEs), and serious adverse events (SAEs). We rated the certainty of evidence using GRADE. MAIN RESULTS: We identified six RCTs that provided results from 17,495 participants with planned completion dates between July 2021 and December 2031. Target sample sizes varied from 1020 to 10,000 participants. Average age was 42 to 53 years across four studies of non-hospitalised participants, and 61 years in two studies of hospitalised participants. Non-hospitalised individuals with COVID-19 Four studies evaluated single agents bamlanivimab (N = 465), sotrovimab (N = 868), regdanvimab (N = 307), and combinations of bamlanivimab/etesevimab (N = 1035), and casirivimab/imdevimab (N = 799). We did not identify data for mortality at 60 days or quality of life. Our certainty of the evidence is low for all outcomes due to too few events (very serious imprecision).  Bamlanivimab compared to placebo No deaths occurred in the study by day 29. There were nine people admitted to hospital by day 29 out of 156 in the placebo group compared with one out of 101 in the group treated with 0.7 g bamlanivimab (risk ratio (RR) 0.17, 95% confidence interval (CI) 0.02 to 1.33), 2 from 107 in the group treated with 2.8 g (RR 0.32, 95% CI 0.07 to 1.47) and 2 from 101 in the group treated with 7.0 g (RR 0.34, 95% CI 0.08 to 1.56). Treatment with 0.7 g, 2.8 g and 7.0 g bamlanivimab may have similar rates of AEs as placebo (RR 0.99, 95% CI 0.66 to 1.50; RR 0.90, 95% CI 0.59 to 1.38; RR 0.81, 95% CI 0.52 to 1.27). The effect on SAEs is uncertain. Clinical progression/improvement of symptoms or development of severe symptoms were not reported. Bamlanivimab/etesevimab compared to placebo There were 10 deaths in the placebo group and none in bamlanivimab/etesevimab group by day 30 (RR 0.05, 95% CI 0.00 to 0.81). Bamlanivimab/etesevimab may decrease hospital admission by day 29 (RR 0.30, 95% CI 0.16 to 0.59), may result in a slight increase in any grade AEs (RR 1.15, 95% CI 0.83 to 1.59) and may increase SAEs (RR 1.40, 95% CI 0.45 to 4.37). Clinical progression/improvement of symptoms or development of severe symptoms were not reported. Casirivimab/imdevimab compared to placebo Casirivimab/imdevimab may reduce hospital admissions or death (2.4 g: RR 0.43, 95% CI 0.08 to 2.19; 8.0 g: RR 0.21, 95% CI 0.02 to 1.79). We are uncertain of the effect on grades 3-4 AEs (2.4 g: RR 0.76, 95% CI 0.17 to 3.37; 8.0 g: RR 0.50, 95% CI 0.09 to 2.73) and SAEs (2.4 g: RR 0.68, 95% CI 0.19 to 2.37; 8.0 g: RR 0.34, 95% CI 0.07 to 1.65). Mortality by day 30 and clinical progression/improvement of symptoms or development of severe symptoms were not reported. Sotrovimab compared to placebo We are uncertain whether sotrovimab has an effect on mortality (RR 0.33, 95% CI 0.01 to 8.18) and invasive mechanical ventilation (IMV) requirement or death (RR 0.14, 95% CI 0.01 to 2.76). Treatment with sotrovimab may reduce the number of participants with oxygen requirement (RR 0.11, 95 % CI 0.02 to 0.45), hospital admission or death by day 30 (RR 0.14, 95% CI 0.04 to 0.48), grades 3-4 AEs (RR 0.26, 95% CI 0.12 to 0.60), SAEs (RR 0.27, 95% CI 0.12 to 0.63) and may have little or no effect on any grade AEs (RR 0.87, 95% CI 0.66 to 1.16).  Regdanvimab compared to placebo Treatment with either dose (40 or 80 mg/kg) compared with placebo may decrease hospital admissions or death (RR 0.45, 95% CI 0.14 to 1.42; RR 0.56, 95% CI 0.19 to 1.60, 206 participants), but may increase grades 3-4 AEs (RR 2.62, 95% CI 0.52 to 13.12; RR 2.00, 95% CI 0.37 to 10.70). 80 mg/kg may reduce any grade AEs (RR 0.79, 95% CI 0.52 to 1.22) but 40 mg/kg may have little to no effect (RR 0.96, 95% CI 0.64 to 1.43). There were too few events to allow meaningful judgment for the outcomes mortality by 30 days, IMV requirement, and SAEs.  Hospitalised individuals with COVID-19 Two studies evaluating bamlanivimab as a single agent (N = 314) and casirivimab/imdevimab as a combination therapy (N = 9785) were included.   Bamlanivimab compared to placebo  We are uncertain whether bamlanivimab has an effect on mortality by day 30 (RR 1.39, 95% CI 0.40 to 4.83) and SAEs by day 28 (RR 0.93, 95% CI 0.27 to 3.14). Bamlanivimab may have little to no effect on time to hospital discharge (HR 0.97, 95% CI 0.78 to 1.20) and mortality by day 90 (HR 1.09, 95% CI 0.49 to 2.43). The effect of bamlanivimab on the development of severe symptoms at day 5 (RR 1.17, 95% CI 0.75 to 1.85) is uncertain. Bamlanivimab may increase grades 3-4 AEs at day 28 (RR 1.27, 95% CI 0.81 to 1.98). We assessed the evidence as low certainty for all outcomes due to serious imprecision, and very low certainty for severe symptoms because of additional concerns about indirectness. Casirivimab/imdevimab with usual care compared to usual care alone Treatment with casirivimab/imdevimab compared to usual care probably has little or no effect on mortality by day 30 (RR 0.94, 95% CI 0.87 to 1.02), IMV requirement or death (RR 0.96, 95% CI 0.90 to 1.04), nor alive at hospital discharge by day 30 (RR 1.01, 95% CI 0.98 to 1.04). We assessed the evidence as moderate certainty due to study limitations (lack of blinding). AEs and SAEs were not reported.  AUTHORS' CONCLUSIONS: The evidence for each comparison is based on single studies. None of these measured quality of life. Our certainty in the evidence for all non-hospitalised individuals is low, and for hospitalised individuals is very low to moderate. We consider the current evidence insufficient to draw meaningful conclusions regarding treatment with SARS-CoV-2-neutralising mAbs. Further studies and long-term data from the existing studies are needed to confirm or refute these initial findings, and to understand how the emergence of SARS-CoV-2 variants may impact the effectiveness of SARS-CoV-2-neutralising mAbs. Publication of the 36 ongoing studies may resolve uncertainties about the effectiveness and safety of SARS-CoV-2-neutralising mAbs for the treatment of COVID-19 and possible subgroup differences.

Electromechanical rolling whiteboard for improving posture and comfort of users in classrooms.

BACKGROUND: The prevalence of musculoskeletal disorders is high among teachers. Poor posture when writing on whiteboards is considered among the important causes of these disorders. OBJECTIVE: The present study aimed to evaluate an electromechanical rolling whiteboard for educational environments as an ergonomic intervention. METHODS: Thirty university lecturers volunteered to take part in the study. Participants performed a 5-minute writing task on a regular board and on the newly modified whiteboard in random order. The comfort and effectiveness of the boards and the perceived physical effort and posture of the participants were evaluated and compared by applying the verbal rating scale, Borg's rating of physical exertion scale, and rapid entire body assessment, respectively. RESULTS: A total of 83.2% of participants reported the new whiteboard to be comfortable or more comfortable to use than the regular whiteboard, and 76.6% of them found the new whiteboard to be higher or much higher in effectiveness and usefulness in comparison with the regular whiteboard. The comfort and posture ratings revealed that exertion was significantly less and posture improved while writing on the new board as compared to its counterpart (p < 0.0001). CONCLUSION: The new whiteboard increased user comfort, reduced physical effort, and improved posture, hopefully leading to a decreased number of work-related musculoskeletal disorders.

Submicron polymeric particles accelerate insulin fibrillation by surface adsorption.

Insulin fibrillation is caused by the interaction of partially unfolded protein molecules resulting in the formation of insoluble aggregates. Engineered nano- and submicron particles have been reported to accelerate or inhibit the fibrillation of insulin. However, the mechanism by which engineered particles regulate insulin fibrillation kinetics is not fully understood. In the current study, insulin fibrillation in the presence of surface engineered, amine- or sulfate-modified polystyrene particles (200 nm) was investigated. Both particles were found to enhance the rate of protein fibrillation at high particle concentrations (1:1 mass ratio of proteins to particles) as evidenced by increased fluorescence of thioflavin T. A significant amount of proteins was found to adsorb on the surface of both particles, suggesting that the particles served as a nucleation site for fibrillation. Insulin fibrillation was associated with a change in the protein's secondary structure from α-helix to ß-sheet. This change of structure was not significantly affected by the presence of particles. Monte Carlo simulations of protein fibrillation in the presence of different surfaces confirmed experimental results and demonstrated that protein fibrillation is enhanced as the affinity of protein molecules toward the surface increases. Along with increasing the local concentration of proteins, the presence of a surface stabilizes unfolded intermediates, which are precursors to fibrillation. These results provide insight into the mechanisms by which engineered particles promote protein fibrillation and can be important in the context of nanotoxicity.

Effect of Vitamin D Supplementation on Weight Loss, Glycemic Indices, and Lipid Profile in Obese and Overweight Women: A Clinical Trial Study.

INTRODUCTION: Vitamin D (vit D) deficiency has defined as a health problem worldwide. World Health Organization (WHO) has declared that obesity is an epidemic of the 21st century. Previous studies have shown that obesity may increase the risk of Vit D deficiency. Furthermore, other studies have demonstrated that vit D insufficiency was accompanied with higher risk of type 2 diabetes, cardiovascular diseases, hypertension, and obesity. The aim of this study was to survey the effect of vit D supplementation on weight loss among overweight and obese women aged 20-40 years in Isfahan. METHODS: This double-blind clinical trial was done on 50 overweight and obese women who were divided into two groups, in which one group received vit D supplements and the other group received placebo. Intervention group received vit D with dozes 50,000 IU/w for 6 weeks. The levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), fasting blood sugar (FBS), insulin (ins), homeostasis model assessment of ins resistance (IR), C-reactive protein (CRP), height, weight (WT), waist circumference (WC), hip circumference (HC), and blood pressure (BP) were measured before and after intervention. RESULTS: After using vit D supplementation for 6 weeks, WT, WC, and body mass index (BMI) were decreased significantly and serum vit D increased significantly compared to control group (P < 0.001). Other factors including TC, TG, LDL-c, HDL-c, FBS, CRP, ins, IR, and waist to hip ratio (WHR) did not change significantly (P > 0.05). CONCLUSIONS: After 6 weeks of intervention, the means of WT, BMI, WC, and HC decreased significantly. Previous studies have shown that vit D deficiency was more prevalence in obese people and there was an inverse association among vit D with BMI and WC. The relationship between vit D and lipid profiles such as glycemic indexes, anthropometric indexes, CRP, and BP is not clear and needs more study in the future.

Efficacy of articaine infiltration versus lidocaine inferior alveolar nerve block for pulpotomy in mandibular primary second molars: A randomized clinical trial.

Background: Successful anesthesia is a major concern in during pulpotomy treatment. The aim of this study was to compare the anesthetic efficacy of inferior alveolar nerve block using 2% lidocaine and buccal infiltration using 4% articaine for pulpotomy of mandibular primary second molars. Methods: This randomized cross-over clinical trial was performed in 23 children (five to eight-year-old) from July through November 2016, referred to the Department of Pediatric Dentistry, Tehran University of Medical Sciences who needed pulpotomy treatment in both mandibular primary second molars. The Patients' feeling during injection and their behavior during pulpotomy and post-treatment complications were registered. Wilcoxon Signed Ranks test was used for analyzing the data. A significant level of differences was taken as p≤ 0.05. Results: Patients' feeling during injection and post-treatment complications did not significantly differ between two groups (p>0.05). Patients' behavior during pulpotomy was significantly better in articaine group (p=0.004). Conclusion: Articaine buccal infiltration can be used successfully in pulpotomy of mandibular primary second molars. Iranian Registry of Clinical Trial: (IRCT2015042321484N2).

The Molecular Chaperone Artemin Efficiently Blocks Fibrillization of TAU Protein In Vitro.

OBJECTIVES: Aggregation of the TAU proteins in the form of neurofibrillary tangles (NFTs) in the brain is a common risk factor in tauopathies including Alzheimer's disease (AD). Several strategies have been implemented to target NFTs, among which chaperones, which facilitate the proper folding of proteins, appear to hold great promise in effectively inhibiting TAU polymerization. The aim of this study was to analyze the impact of the chaperone Artemin on TAU aggregation in vitro. MATERIALS AND METHODS: In this experimental study, recombinant TAU- or Artemin proteins were expressed in E.coli bacteria, and purified using ion-exchange and affinity chromatography. Sodium dodecyl sulfate-poly acrylamide gel electrophoresis (SDS-PAGE) was used to run the extracted proteins and check their purity. Heparin was used as an aggregation inducer. The interaction kinetics of TAU aggregation and disassembly was performed using thioflavin T (ThT) fluorescence analysis and circular dichroism (CD) spectroscopy. RESULTS: Ion-exchange and affinity chromatography yielded highly pure TAU and Artemin proteins for subsequent analyses. In addition, we found that heparin efficiently induced TAU fibrillization 48 hours post-incubation, as evidenced by ThT assay. Importantly, Artemin was observed to effectively block the aggregation of both physiologic- and supraphysiologic TAU concentrations in a dose-dependent manner, as judged by ThT and CD spectroscopy analyses. CONCLUSIONS: Our collective results show, for the first time, that the chaperone Artemin could significantly inhibit aggregation of the TAU proteins in a dose-dependent manner, and support Artemin as a potential potent blocker of TAU aggregation in people with AD.

Honey bee venom combined with 1,25-dihydroxyvitamin D3as a highly efficient inducer of differentiation in human acute myeloid leukemia cells.

PURPOSE: Most cancer cells exhibit a defect in their capacity to mature into nonreplicating adult cells and existing in a highly proliferating state. Differentiation therapy by agents such as 1,25-dihydroxyvitamin D3(1,25-(OH)2 VD3) represents a useful approach for the treatment of cancer including acute myeloid leukemia. Human myeloid leukemia cell lines are induced to terminal differentiation into monocyte lineage by 1,25-(OH)2 VD3. However, usage of these findings in the clinical trials is limited by calcemic effects of 1,25-(OH)2 VD3. Attempts to overcome this problem have focused on a combination of low concentrations 1,25-(OH)2 VD3 with other compounds to induce differentiation of HL-60 cells. In this study, the effect of honey bee venom (BV) and 1,25-(OH)2 VD3, individually and in combination, on proliferation and differentiation of human myeloid leukemia HL-60 cells were assayed. MATERIALS AND METHODS: In this in vitro study, toxic and nontoxic concentrations of BV and 1,25-(OH)2 VD3 were tested using Trypan blue stained cell counting and (3[4, 5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. In addition, differentiation of cells was assayed using a Wright-Giemsa staining and nitroblue tetrazolium reduction test. Data were analyzed by a one-way analysis of the variance test using SPSS software. RESULTS: Our findings showed that both the BV and 1,25-(OH)2 VD3, in a dose and time-dependent manner, caused cell death at high concentrations and inhibited cell proliferation at lower concentrations. About 5 nM of 1,25-(OH)2 VD3 induced differentiation of HL-60 cells to monocytes after 72 h. 2.5 µg/ml of BV suppressed proliferation of HL-60 cells but had not any effects on their differentiation, whereas in combination with 5 nM of 1,25-(OH)2 VD3, it enhanced antiproliferative and differentiation potency of 1,25-(OH)2 VD3. CONCLUSIONS: These results indicate that BV potentiates the 1,25-(OH)2 VD3-induced HL-60 cell differentiation into monocytes.

Ameloblastic Fibro-Odontoma in a 4-Year-Old Boy.

INTRODUCTION: Ameloblastic fibro-odontoma (AFO) is defined as a benign odontogenic tumor with slow growing behavior. Its prevalence is rare. AFO is characterized by histologic features of ameloblastic fibroma (AF) with the formation of enamel and dentine. CASE PRESENTATION: This is a case report of AFO accompanied with a number of impacted deciduous teeth and its management in a 4-year old boy. Examination of oral cavity revealed an extensive swelling from midline to left deciduous maxillary first molar, covered with normal mucosa. Radiographic examination showed a well-defined mixed radiolucent-radiopaque lesion that extended horizontally from midline to mesial border of the left maxillary primary first molar and vertically from alveolar crest to the floor of nose. The differential diagnosis was odontoma (ameloblastic fibro-odontoma, complex odontoma). Surgical enucleation and curettage was performed under general anesthesia. Histopathologic sections show bone trabeculae in marrow spaces. There was myxoid matrix in some spaces which contained odontogenic epithelial cells. These findings led to diagnosis of AFO. No sign of recurrence has been observed during the 12-month follow-up period. CONCLUSION: Although AFO is a rare tumor, it is more prevalent in children's jaw. Conservative surgical treatment allowed the normal development of teeth.

Assessing the micronutrient and macronutrient intakes in female students and comparing them with the set standard values.

BACKGROUND: Healthy nutrition particularly the energy intake and the essential nutrients in female students is very important. This study aims to assess micro- and macronutrient intakes in female students of Isfahan University of Medical Sciences, Iran. MATERIALS AND METHODS: This cross-sectional study involved 100 female students aged between 18 and 25 years in 2008-2009. Anthropometrics measures were performed and two 24-hours food recalls were used to collect the dietary information and were analyzed using food processor 2 and compared with the dietary reference intakes (DRIs) 2008. FINDINGS: As many as 61.1% of subjects resided in dormitories; 12.7% were married. Prevalence of overweight or obesity and abdominal obesity in the subjects studied were 6.9% and 46.1%, respectively. The mean (±SD) systolic blood pressure was 105.2 ± 15.6 mmHg and the diastolic was 62.2 ± 10.4 mmHg. Totally, 3.9% of the subjects had hypertension. Food intake analysis indicated that B12, folate, magnesium, potassium, and calcium were below the recommended level, and vitamin C, E, pantothenic acid, B1, B3, phosphate, and zinc were above, and energy intake, macronutrient, vitamin A, pyridoxine, iron, and selenium were, in general, adequate. CONCLUSION: The findings of the study indicated that macronutrients intake was appropriate, but the problem mainly existed in the consumption of micronutrients. It is recommended to increase the intakes of important food groups such as dairy, vegetable, and fruit that are proper sources of micronutrients, and it is also suggested to improve strategies and the competence in this area of nutrition.

Hypertension control in industrial employees: findings from SHIMSCO study.

BACKGROUND: Hypertension prevention and control are among the most important public health priorities. We evaluated the impacts of a workplace intervention project "Stop Hypertension in Mobarakeh Steel Company" (SHIMSCO) on controlling hypertension in industrial workers. METHODS: The study was carried out in Mobarakeh Steel Company in Isfahan among 7286 male workers and employees. All individuals were evaluated for the presence of hypertension (HTN). According to examinations, 500 subjects with systolic blood pressure (SBP) ≥ 140 mmHg, and/or diastolic blood pressure (DBP) ≥ 90 mmHg, and/or those using antihypertensive medications were confirmed to have HTN and thus included in this study. They were questioned for sociodemographic characteristics, past medical history and medication use. They received an educational program including healthy lifestyle and self-care recommendations of HTN management and control as well as training for accurate blood pressure measurement and home monitoring for two years. SBP, DBP, weight, height and routine lab tests were measured for all hypertensive subjects before and after the interventions. Paired t-test, generalized estimation equation (GEE) and ordinary linear regression (OLR) were used for statistical analysis in SPSS. RESULTS: The comparison of SBP and DBP before and after the educational program showed significant reductions in both parameters (-7.97 ± 14.72 and -2.66 ± 9.96 mmHg, respectively). However, a greater decrease was detected in case of DBP. GEE showed SBP and DBP to decrease about -0.115 and -0.054 mmHg/month. OLR also revealed reductions of 4.88 and 2.57 mmHg respectively in SBP and DBP upon adding each antihypertensive drug. CONCLUSION: SHIMSCO, a 3-year interventional project in workplaces, was effective in reducing SBP and DBP among hypertensive employees and workers. We conclude that implementing simple educational programs in worksites can improve the management and control of hypertension and perhaps other chronic diseases.

Risk factors of atherosclerosis in male smokers, passive smokers, and hypertensive nonsmokers in central Iran.

BACKGROUND: Some studies showed that smoking follows an upward trend in Asian countries as compared with other countries. The purpose of this study was to examine the effect of cigarette smoking on cardiovascular diseases and risk factors of atherosclerosis in patients with hypertension. METHODS: This study was conducted on 6123 men residing in central Iran (Isfahan and Markazi Provinces) that participated in Isfahan Healthy Heart Project (IHHP). Subjects were randomly selected using cluster sampling method. All the subjects were studied in terms of their history of cardiovascular disease, demographic characteristics, smoking, blood pressure, physical examination, pulse rate, respiratory rate, weight, height, waist circumference, and blood measurements including LDL-C, HDL-C, total cholesterol, triglyceride, fasting blood sugar and 2-hour post prandial test. RESULTS: While 893 subjects suffered from hypertension, 5230 subjects were healthy. The hypertension prevalence was 2.5 times more in urban areas compared to rural areas that showed a significant difference as it increased to 3.5 times smoking factor was considered. The prevalence of risk factors of atherosclerosis and also cardiovascular complications in patients with hypertension were significantly higher than healthy people. Furthermore, they were higher in smokers with hypertension and those exposed to the cigarette smoke than nonsmokers. CONCLUSION: Smoking and passive smoking had an increasing effect on the prevalence of risk factors of atherosclerosis and consequently the incidence of cardiovascular diseases in patients with hypertension.

The Relationship between Weight and CVD Risk Factors in a Sample Population from Central Iran (Based on IHHP).

BACKGROUND: Atherosclerosis is one of the leading causes of mortality all around the world. Obesity is an independent risk factor for atherosclerosis and cardiovascular diseases (CVD). In this respect, we decided to examine the effect of the subgroups of weight on cardiovascular risk factors. METHODS: This cross-sectional study was done in 2006 using the data obtained by the Iranian Healthy Heart Program (IHHP) and based on classification of obesity by the World Health Organization (WHO). In this study, the samples were tested based on the Framingham risk score, Metabolic Measuring Score (MMS) and classification of obesity. Chi-square and ANOVA were used for statistical analysis. RESULTS: 12514 people with a mean age of 38 participated in this study. 6.8% of women and 14% of men had university degrees (higher than diploma). Obesity was seen in women more than men: 56.4% of women and 40% of men had a Body Mass Index of (BMI) ≥ 25 Kg/m2. 13% of the subjects had FBS > 110 and13.9% of them were using hypertensive drugs. In this study, we found that all risk factors, except HDL cholesterol in men, increased with an increase in weight. This finding is also confirmed by the Framingham flowfigure for men and women. CONCLUSION: One of every two Americans, of any age and sex, has a Body Mass Index of (BMI) ≥ 25 Kg/m2. Obesity associated CVD and other serious diseases. Many studies have been done in different countries to find the relationship between obesity and CVD risk factors. For example, in the U.S.A and Canada they found that emteropiotic parameters, blood presser and lipids increased by age(of both sexes). Moreover, another study done in China, which is a country in Asia like Iran, shows that BMI has an indirect effect on HDL cholesterol, LDL cholesterol and triglyceride. This data is consistent with the results of the current study. However, In China they found that this relationship in men is stronger than women, but our study reveals the opposite.

Comparison of pregnancy outcome among nulliparas with and without microalbuminuria at the end of the second trimester.

OBJECTIVE: To evaluate the rate of poor pregnancy outcome among nulliparas who had microalbuminuria at the end of the second trimester of their pregnancy. METHODS: A prospective cohort study was performed on 490 nulliparous women who were at the end of the second trimester of pregnancy. Urine tests for albuminuria and creatinine measurements were performed in all women and the albumin to creatinine ratio (ACR) was calculated. The women with microalbuminuria (exposed group) and those without microalbuminuria (nonexposed group) were monitored until the end of their pregnancy and compared for pregnancy outcome. RESULTS: Preterm labor (57.9% versus 13.5%), preeclampsia (50.0% versus 8.6%), intrauterine growth restriction (42.1% versus 6.4%), and preterm premature rupture of membranes (31.6% versus 10.2%) were significantly more common in the exposed group. The rates of gestational diabetes did not differ significantly between the 2 groups. In multivariate logistic regression analyses, microalbuminuria increased the risks for preterm labor (adjusted OR 2.4; 95% CI 1.1-5.5, P=0.03) and preeclampsia (adjusted OR 9.5; 95% CI 4.6-19.3, P<0.001). CONCLUSION: Microalbuminuria at the end of the second trimester of pregnancy might increase the risks of preterm labor, preeclampsia, intrauterine growth restriction, and preterm premature rupture of membranes.