Therapeutic effect of ferrous sulfate in diabetic patients with iron deficiency anaemia: a randomised controlled trial.

Iron deficiency anaemia (IDA) and diabetes mellitus (DM) are most prevalent disease, that diabetic patients are more prone to IDA. Therefore, the main aim of this study was to investigate the relationship between patients with diabetes and IDA in relation to taking iron pills daily and every other day to reduce the effects related to it. Ninety-one participants were enroled and randomly divided into two groups, with a final analysis cohort of 72 patients. The primary focus was on changes in serum Hb and Ferritin levels. The screening phase lasted 24 weeks, leading to 72 eligible participants meeting the criteria for entry into the study. Additionally, the study examined alternations in Hb and Hb A1C levels after treating patients with iron deficiency. The Hb and ferritin level contrasts between groups were not significant (P = 0.096 and P = 0.500, respectively). The relationship between Hb A1C and Hb levels before and after treatment was positive and significant (r 2 = 0.187). The results of the present study show that although the effectiveness of using oral iron supplements did not have a significant difference in terms of increasing haemoglobin and ferritin, the use of oral iron once every other day was more effective than the use of oral iron every day, and also in this study Like other studies, this result concluded that there is a negative correlation between Hb A1C and Hb, and to check the status of Hb A1C in diabetics, the level of Hb should be considered first.

Comparison of metabolic risk factors, lipid indices, healthy eating index, and physical activity among premenopausal, menopausal, and postmenopausal women.

INTRODUCTION: In this study, we aimed to compare metabolic risk factors, lipid indices, healthy eating index, and physical activity among premenopausal, menopausal, and postmenopausal women. METHODS: In this cross-sectional study, a total of 4,732 women participating in the Hoveyzeh Cohort Study were placed into three groups of premenopausal (n=736), menopausal (n=396), and postmenopausal (n=917) women, according to the inclusion and exclusion criteria . RESULTS: The prevalence of metabolic syndrome was 43.3%, 55.6%, and 62.8% in premenopausal, menopausal, and postmenopausal women, respectively. After menopause, the prevalence of hypertension (50.2%), dyslipidemia (61.2%), diabetes (37.7%), and abdominal obesity according to the Iranian guidelines (75.9%) was higher than before menopause. Based on the results, cardiovascular disease had the highest prevalence after menopause (23%). The weight-adjusted waist index (WWI) had the highest odds ratio (OR) among indices, with values of 2.94 and 1.93 in menopausal and postmenopausal women, respectively (P<0.001). According to the Healthy Eating Index-2015 (HEI-2015), the total consumption of fruits, vegetables, seafood, and protein was higher in premenopausal women than in postmenopausal women, and the consumption of foods containing sugar was higher in menopausal women than in premenopausal women. The results showed that the level of physical activity was the highest and the lowest in premenopausal and postmenopausal women, respectively (P<0.001). CONCLUSION: Menopause leads to an increase in the prevalence of metabolic syndrome. The Atherogenic Index of Plasma (AIP), Triglyceride Glucose (TyG) index, WWI, and physical activity index increased in postmenopausal women compared to premenopausal women. The TyG index, WWI, and HEI-2015 did not show significant differences between the groups, based on the multiple regression analysis.

Clinical significance of CD166 and HER-2 in different types of gastric cancer.

INTRODUCTION: Cluster of differentiation 166 (CD166), a cancer stem cell (CSC) marker, and human epidermal growth factor receptor 2 (HER-2) are expressed in a diversity of malignancies and is associated with tumor progression. Although studies regarding the importance of CSC markers and HER-2 in gastric cancer (GC) have rapidly developed, their clinicopathological, prognosis, and diagnosis value still remain unsatisfying in GC. Therefore, the present study aims to investigate the clinical, prognostic, and diagnostic significance of CD166 and HER-2 in different histological types of GC. MATERIALS AND METHODS: Bioinformatic analysis was applied to determine the clinical importance of CD166 and HER-2 expression based on their tissue localization in primary GC tumors and the normal adjacent samples. The expression patterns, clinical significance, prognosis, and diagnosis value of CD166 and HER-2 proteins in tissue microarrays (TMAs) of 206 GC samples, including Signet Ring Cell (SRC) and intestinal types and also 28 adjacent normal tissues were evaluated using immunohistochemistry (IHC). RESULTS: The results indicated that the expression of CD166 (membranous and cytoplasmic) and HER-2 were significantly up-regulated in tumor cells compared to adjacent normal tissues (P = 0.010, P < 0.001, and P = 0.011, respectively). A statistically significant association was detected between a high level of membranous expression of CD166 and lymphovascular invasion (P = 0.006); We also observed a statistically significant association between high cytoplasmic expression of CD166 protein and more invasion of the subserosa (P = 0.040) in the SRC type. In contrast, there was no correlation between the expression of HER-2 and clinicopathologic characteristics. Both CD166 and HER-2 showed reasonable accuracy and high specificity as diagnostic markers. CONCLUSION: Our results confirmed that increased membranous and cytoplasmic expression of CD166 showed clinical significance in the SRC type and is associated with the progression of the disease and more aggressive tumor behaviors. These findings can be used to assist in designating subgroups of patients that require different follow-up strategies, and also, they might be utilized as the prognostic or diagnostic biomarkers in these types of GC for prospective clinical application.

Clinical and immunological characteristics of 69 leukocyte adhesion deficiency-I patients.

BACKGROUND: In order to support the comprehensive classification of Leukocyte Adhesion Deficiency-I (LAD-I) severity by simultaneous screening of CD11a/CD18, this study assessed clinical, laboratory, and genetic findings along with outcomes of 69 LAD-I patients during the last 15 years. METHODS: Sixty-nine patients (40 females and 29 males) with a clinical phenotype suspected of LAD-I were referred to Immunology, Asthma, and Allergy research institute, Tehran, Iran between 2007 and 2022 for further advanced immunological screening and genetic evaluations as well as treatment, were enrolled in this study. RESULTS: The diagnosis median age of the patients was 6 months. Delayed umbilical cord separation was found in 25 patients (36.2%). The median diagnostic delay time was 4 months (min-max: 0-82 months). Forty-six patients (66.7%) were categorized as severe (CD18 and/or CD11a: below 2%); while 23 children (33.3%) were in moderate category (CD18 and/or CD11a: 2%-30%). During the follow-ups, 55.1% of children were alive with a mortality rate of 44.9%. Skin ulcers (75.4%), omphalitis (65.2%), and gingivitis (37.7%) were the most frequent complaints. Genetic analysis of the patients revealed 14 previously reported and three novel pathogenic mutations in the ITGB2 gene. The overall survival of patients with and without hematopoietic stem cell transplantation was 79.3% and 55.6%, respectively. CONCLUSION: Physicians' awareness of LAD-I considering delayed separation of umbilical cord marked neutrophilic leukocytosis, and variability in CD11 and CD18 expression levels, and genetic analysis leads to early diagnosis and defining disease severity. Moreover, the prenatal diagnosis would benefit families with a history of LAD-I.

Molecular findings and clinical manifestations of 18 Iranian children with Griscelli syndrome type 2: Two novel homozygote mutations in RAB27A gene in a patient.

Griscelli syndrome type 2 (GS2) is an autosomal recessive immunodeficiency characterized by hair hypopigmentation, recurrent fever, hepatosplenomegaly and pancytopenia. This study aims to find new genetic changes and clinical features in 18 children with GS2 caused by the RAB27A gene defect. In all, 18 Iranian children with GS2 who presented with silver grey hair and frequent pyogenic infection were included in this study. After recording demographic and clinical data, PCR sequencing of the RAB27A gene was performed for all exons and exon-intron boundaries. Two patients in this study were subjected to whole-exome sequencing followed by Sanger sequencing. Light microscopy study of hair showed large irregular clumps of pigment with the absence of giant granules on the blood smear. Mutation analysis of the RAB27A gene identified two novel missense mutations as homozygous in a patient, one in exon 2, c.140G>C and another in exon 4, c.328G>T. In addition, for 17 other patients, 6 reported mutations were obtained including c.514_518delCAAGC, c.150_151delAGinsC, c.400_401delAA, c.340delA, c.428T>C and c.221A>G. The mutation c.514_518delCAAGC was the most frequent and found in 10 patients; this mutation may be considered a hotspot in Iran. Early diagnosis and treatment of RAB27A deficiency can contribute to better disease outcomes. In affected families, genetic results could be urgently needed to make a timely decision about haematopoietic stem cell transplantation and prenatal diagnosis.

Risk Reassessment of Differentiated Thyroid Cancer in Ahvaz, Iran: A Cross-sectional Retrospective Study.

Background: Accurate evaluation of response to treatment in differentiated thyroid cancer (DTC) is the sine qua non of preventing over-treatment in low-risk patients and implementing appropriate interventions in high-risk individuals. Objectives: This study aimed to assess the response to therapy in DTC patients based on dynamic stratification method. Methods: In this cross-sectional study, 154 medical records of subjects with DTC (with at least 6 months after total thyroidectomy) and referred to endocrinology clinics in Ahvaz, Iran, from April 2020 to May 2021 were examined. Patients were stratified according to a dynamic risk stratification system (informed by their specific clinical, histopathological, and ultrasonography findings, and other diagnostic imagines) into four groups: Excellent response (ER), indeterminate response (IR), biochemical incomplete response (BIR), and structural incomplete response (SIR). Results: For a mean follow-up period of 28.59 months, excellent response to treatment was observed in 92 patients (59.7%), indeterminate response to treatment was found in 32 patients (20.8%), biochemical incomplete response was detected in 2 patients (1.3%), and structural incomplete response was seen in 28 patients (18.2%). In the group with low risk of recurrence, ER and IR were observed in 79.2% and 15.6% of the patients, respectively (P < 0.0001). In the group with an intermediate risk of recurrence, ER was found in 32% of the patients, while IR and SIR + BIR were seen in 34% and 34% of the patients, respectively (P < 0.0001). No cases of ER or IR were observed in the group with high risk (P = 0.001). Conclusions: In sum, response to treatment significantly varied based on dynamic risk stratification, with ER being highest in the low-risk group, less likely in moderate risk group, and undetected in the high-risk group.

The effects of rutin flavonoid supplement on glycemic status, lipid profile, atherogenic index of plasma, brain-derived neurotrophic factor (BDNF), some serum inflammatory, and oxidative stress factors in patients with type 2 diabetes mellitus: A double-blind, placebo-controlled trial.

This study aimed to investigate the effects of rutin flavonoid in type 2 diabetes mellitus (T2DM) patients. In this trial (double-blind, placebo-controlled), 50 T2DM patients (supplement, n = 25 and placebo, n = 25) were randomized and supplemented with 500 mg rutin or placebo per day for 3-months. At the beginning and at the end of the study, metabolic parameters including fasting blood glucose (FBG), insulin, glycosylated hemoglobin (HbA1c), homeostasis model assessment of insulin resistance (HOMO-IR), quantitative insulin sensitivity check index (QUICKI), homeostasis model assessment of ß-cell function (HOMA-ß), triglyceride (TG), total cholesterol (CHOL), high-density and low-density lipoprotein cholesterol (HDL-c and LDL-c), and atherogenic index of plasma (AIP), inflammatory and oxidative stress markers such as interleukin 6 (IL-6), total antioxidant capacity (TAC), and malondialdehyde (MDA) and brain-derived neurotrophic factor (BDNF) were assessed. The results showed a significant decrease in FBG, insulin, HbA1c, HOMO-IR, LDL-c, TG, VLDL, CHOL, LDL-c.HDL-c ratio, AIP, IL-6, and MDA and a significant increase in HDL-c, QUICKI index, BDNF, and TAC compared with the initial value (p for all <.05). In the adjusted model, the mean changes of FBG, insulin, HbA1c, HOMO-IR, LDL-c, CHOL, LDL.HDL ratio, AIP, MDA, and IL-6 were significantly lower and mean changes of QUICKI index, HDL-c, and TAC were significantly higher in the rutin group compared with the placebo group (adjusted p for all <.05). It seems that rutin may have beneficial effects on improving metabolic parameters, BDNF, and inflammatory and oxidative stress factors in T2DM patients.

Nanotechnology-based cell-mediated delivery systems for cancer therapy and diagnosis.

The global prevalence of cancer is increasing, necessitating new additions to traditional treatments and diagnoses to address shortcomings such as ineffectiveness, complications, and high cost. In this context, nano and microparticulate carriers stand out due to their unique properties such as controlled release, higher bioavailability, and lower toxicity. Despite their popularity, they face several challenges including rapid liver uptake, low chemical stability in blood circulation, immunogenicity concerns, and acute adverse effects. Cell-mediated delivery systems are important topics to research because of their biocompatibility, biodegradability, prolonged delivery, high loading capacity, and targeted drug delivery capabilities. To date, a variety of cells including blood, immune, cancer, and stem cells, sperm, and bacteria have been combined with nanoparticles to develop efficient targeted cancer delivery or diagnosis systems. The review paper aimed to provide an overview of the potential applications of cell-based delivery systems in cancer therapy and diagnosis.

Multi-targeting of K-Ras domains and mutations by peptide and small molecule inhibitors.

K-Ras activating mutations are significantly associated with tumor progression and aggressive metastatic behavior in various human cancers including pancreatic cancer. So far, despite a large number of concerted efforts, targeting of mutant-type K-Ras has not been successful. In this regard, we aimed to target this oncogene by a combinational approach consisting of small peptide and small molecule inhibitors. Based on a comprehensive analysis of structural and physicochemical properties of predominantly K-Ras mutants, an anti-cancer peptide library and a small molecule library were screened to simultaneously target oncogenic mutations and functional domains of mutant-type K-Ras located in the P-loop, switch I, and switch II regions. The selected peptide and small molecule showed notable binding affinities to their corresponding binding sites, and hindered the growth of tumor cells carrying K-RasG12D and K-RasG12C mutations. Of note, the expression of K-Ras downstream genes (i.e., CTNNB1, CCND1) was diminished in the treated Kras-positive cells. In conclusion, our combinational platform signifies a new potential for blockade of oncogenic K-Ras and thereby prevention of tumor progression and metastasis. However, further validations are still required regarding the in vitro and in vivo efficacy and safety of this approach.

Motivation System of Healthy and Safe Nutrition in Iranian Adolescent Girls: A Qualitative Study.

OBJECTIVE: Motivation determines the possibility of an individual's intention to accept health-related behaviors. Despite the important role of the motivational system in conducting healthy and safe nutrition behavior, this issue has not been adequately addressed. The purpose of this qualitative study was to explain the healthy and safe nutrition motivation system among Iranian adolescent girls. METHOD: In this qualitative study, conventional content analysis was used and participants were selected using the purposive sampling method. Semistructured in-depth interviews were conducted with 42 adolescent girls in Shiraz, Iran. The interviews continued until data saturation was obtained. Qualitative data were analyzed using the Graneheim and Lundman qualitative content analysis by MAX-Q-DA (version 10) software. RESULTS: The data analysis resulted in three main categories for the participants' motivational factors for healthy and safe nutrition: (1) maintaining health and social functions, (2) maintaining the family's mental and economic health, and (3) achieving goals and success in life. The first category included two subcategories: "desire to have an appropriate look and appearance" and "fear of diseases and their complications." The second category included two subcategories of "maintaining the family's mental health" and "maintaining the family's economic health." The third category consisted of two subcategories: "desire to form a family and be successful in life" and "achieving the future career goals." CONCLUSION: The motivation to maintain health and social functions, to maintain the family's mental and economic health, and to achieve goals and be successful in life has a powerful impact on the decisions and behaviors of adolescent girls to have safe and healthy nutrition. Therefore, recognizing the motivational system, as a key and determinative factor in developing the adolescents' intention to adopt health-related behaviors, is an effective step to design and develop successful interventions in promoting nutritional behaviors.

Invasive Rasamsonia argillacea infection in chronic granulomatous disease: Report of a new case and literature review.

Invasive Rasamsonia spp. infections are rare and usually associated with chronic granulomatous disease (CGD). We present a case of pulmonary and possible cerebral infection due to Rasamsonia argillacea in a girl with CGD receiving no primary antifungal prophylaxis. There was a fatal outcome despite the combination of antifungal therapy and surgical interventions. We also conducted a literature review on reported invasive Rasamsonia spp. infections in the setting of CGD.

Associations between new and old anthropometric indices with type 2 diabetes mellitus and risk of metabolic complications: a cross-sectional analytical study / Associação de índices antropométricos novos e antigos com diabetes melito tipo 2 e risco de complicações metabólicas: um estudo analítico de corte transversal

Abstract Background Obesity can increase the risk of diabetes mellitus and complications associated with it. Objectives The aim of this study was to estimate the associations between new and old anthropometric indices and the risk of type 2 diabetes mellitus (T2DM) and its metabolic complications. Methods In this cross-sectional analytical study, 110 T2DM subjects and 110 healthy controls were selected by convenience sampling. Metabolic factors were evaluated including the atherogenic index of plasma (AIP), glycemic status, lipid profile, blood pressure, kidney indices, new anthropometric indices (abdominal volume index [AVI], body shape index [ABSI], lipid accumulation product [LAP], body adiposity index [BAI], and conicity index [CI]), and old anthropometric indices (weight, body mass index [BMI], and waist and hip circumference [WC and HC]). Results Significant positive correlations were observed between AVI, LAP, and BAI and fasting blood glucose and HbA1c in the T2DM group (p < 0.001 for all associations). The odds ratio (OR) for T2DM elevated significantly with increasing BMI (OR: 1.30, 95% CI: 1.20-1.42), LAP (OR: 1.20, 95% CI: 1.13-1.27), and BAI (OR: 1.32, 95% CI: 1.21-1.43). The indices AVI (OR: 1.90, 95% CI: 1.57-2.29), LAP (OR: 1.19, 95% CI: 1.13-1.27), BAI (OR: 1.19, 95% CI: 1.12-1.26), WC (OR: 1.29, 95% CI: 1.18, 1.42), and HC (OR: 1.07, 95% CI: 1.01, 1.14) significantly increased the risk of metabolic syndrome (MetS). Conclusions Associations were identified between obesity indices and diabetes. These indices could be used in clinical practice for evaluation and control of T2DM.

Resumo Contexto A obesidade pode aumentar o risco de diabetes melito e complicações associadas. Objetivos O objetivo deste estudo foi estimar a associação de índices antropométricos novos e antigos com o risco de diabetes melito tipo 2 (DM2) e suas complicações metabólicas. Métodos Neste estudo analítico transversal, 110 indivíduos com DM2 e 110 controles saudáveis foram selecionados por amostragem de conveniência. Foram avaliados os fatores metabólicos, incluindo índice aterogênico plasmático, estado glicêmico, perfil lipídico, pressão arterial, índices renais, índices antropométricos novos [índice de volume abdominal (AVI), índice de formato corporal (ABSI), produto de acumulação lipídica (LAP), índice de adiposidade corporal (BAI) e índice de conicidade (CI)] e índices antropométricos antigos [peso, índice de massa corporal (IMC), circunferência de cintura e quadril]. Resultados Foi observada uma correlação positiva significativa de AVI, LAP e BAI com glicemia de jejum e hemoglobina glicada no grupo DM2 (p para todos < 0,001). A odds ratio (OR) do grupo DM2 foi significativamente elevada com aumento de IMC [OR: 1,30, intervalo de confiança (IC) de 95%: 1,20-1,42], LAP (OR: 1,20, IC95%: 1,13-1,27) e BAI (OR: 1,32, IC95%: 1,21-1,43). Os índices AVI (OR: 1,90, IC95%: 1,57-2,29), LAP (OR: 1,19, IC95%: 1,13-1,27), BAI (OR: 1,19, IC95%: 1,12-1,26), WC (OR: 1,29, IC95%: 1,18-1,42) e HC (OR: 1,07, IC95%: 1,01-1,14) aumentaram significativamente o risco de síndrome metabólica. Conclusões Foi reconhecida uma associação entre índices de obesidade e diabetes. Esses índices podem ser usados na prática clínica para avaliação e controle do DM2.

Behavioral factors influencing childhood obesity: a systematic review and meta-analysis.

BACKGROUND: This report provides information on 14 behavioral and nutritional factors that can be addressed in childhood overweight/obesity prevention programs. METHODS: Web of Science, PubMed, and Scopus were searched through November 2018. Reference lists were also screened for additional references. Observational studies addressing the associations between overweight/obesity in children/adolescents aged between 5 to 19 years and associated risk factors were analyzed. Between-studies heterogeneity was assessed by χ2, τ2, and I2 statistics. The likelihood of publication bias was evaluated using the Begg and Egger tests and trim & fill analysis. Effect sizes were expressed as odds ratios (ORs) with 95% confidence intervals (CIs) using a random-effects model. RESULTS: Of 34,537 retrieved studies, 199 including 1,636,049 participants were eligible. The ORs (95% CI) of factors associated with childhood overweight/obesity were as follows: sufficient physical activity 0.70 (0.66, 0.75); eating breakfast every day 0.66 (0.59, 0.74); sufficient consumption of fruits/vegetables 0.92 (0.84, 1.01); breastfeeding <4 months 1.24 (1.16, 1.33); inadequate sleep 1.26 (1.13, 1.40); watching TV >1-2 h/day 1.42 (1.35, 1.49); playing computer games >2 h/day 1.08 (0.95, 1.23); eating sweets ≥3 times/week 0.78 (0.71, 0.85); eating snack ≥4 times/week 0.84 (0.71, 1.00); drinking sugar-sweetened beverages ≥4 times/week 1.24 (1.07, 1.43); eating fast-food ≥3 times/week 1.03 (0.89, 1.18); eating fried-food ≥3 times/week 1.09 (0.90, 1.33); smoking 1.17 (1.07, 1.29); and drinking alcohol 1.05 (0.95, 1.16). CONCLUSIONS: This meta-analysis provided a clear picture of the behavioral and nutritional factors associated with weight gain in children.

Risk factors for stomach cancer: a systematic review and meta-analysis.

OBJECTIVES: This report provides information on 14 behavioral and nutritional factors that can be addressed in stomach cancer prevention programs. METHODS: PubMed, Web of Science, and Scopus were searched through December 2018. Reference lists were also screened. Observational studies addressing the associations between stomach cancer and behavioral factors were analyzed. Between-study heterogeneity was investigated using the χ2, τ2, and I2 statistics. The likelihood of publication bias was explored using the Begg and Egger tests and trim-and-fill analysis. Effect sizes were expressed as odds ratios (ORs) with 95% confidence intervals (CIs) using a random-effects model. RESULTS: Of 52,916 identified studies, 232 (including 33,831,063 participants) were eligible. The OR (95% CI) of factors associated with stomach cancer were as follows: Helicobacter pylori infection, 2.56 (95% CI, 2.18 to 3.00); current smoking, 1.61 (95% CI, 1.49 to 1.75); former smoking 1.43 (95% CI, 1.29 to 1.59); current drinking, 1.19 (95% CI, 1.10 to 1.29); former drinking, 1.73 (95% CI, 1.17 to 2.56); overweight/obesity, 0.89 (95% CI, 0.74 to 1.08); sufficient physical activity, 0.83 (95% CI, 0.68 to 1.02); consumption of fruits ≥3 times/wk, 0.48 (95% CI, 0.37 to 0.63); consumption of vegetables ≥3 times/wk, 0.62 (95% CI, 0.49 to 0.79); eating pickled vegetables, 1.28 (95% CI, 1.09 to 1.51); drinking black tea, 1.00 (95% CI, 0.84 to 1.20); drinking green tea, 0.88 (95% CI, 0.80 to 0.97); drinking coffee, 0.99 (95% CI, 0.88 to 1.11); eating fish ≥1 time/wk 0.79 (95% CI, 0.61 to 1.03); eating red meat ≥4 times/wk 1.31 (95% CI, 0.87 to 1.96), and high salt intake 3.78 (95% CI, 1.74 to 5.44) and 1.34 (95% CI, 0.88 to 2.03), based on two different studies. CONCLUSIONS: This meta-analysis provided a clear picture of the behavioral and nutritional factors associated with the development of stomach cancer. These results may be utilized for ranking and prioritizing preventable risk factors to implement effective prevention programs.

The chromene derivative 4-Clpgc inhibits cell proliferation and induces apoptosis in the K562 cell line.

Chronic myeloid leukemia (CML) is a malignant blood disease with a particular chromosomal aberration that is known as a common form of leukemia. The chromene family exhibits strong anti-cancer effects. Therefore, the effects of six members of the dihydropyrano [2,3-g] chromene family on cell toxicity and apoptosis induction in K562 cancer cells were investigated and compared with those of normal peripheral blood mononuclear cells (PBMCs). The K562 cells were cultured in the presence of the aforementioned chromene derivatives at concentrations of 40 to 200 µM for 24 to 72 h. The effects of these compounds on the growth and viability of the K562 cell line and PBMCs were studied through MTT assay. Furthermore, apoptosis induction was investigated using flow cytometry. Real-time PCR was used for relative quantification of BCL2, Bax, TP53 and BCR- ABL genes after 48 h of exposing K562 cells and PBMCs to 4-Clpgc. Based on the results, these chromene derivatives inhibited the growth of K562 cells. According to the obtained data, 4-Clpgc was the strongest compound with IC50 values of 102 ± 1.6 µM and 143 ± 9.41 µM in K562 cells and PBMCs, while pgc was the weakest one with IC50 levels of 278 ± 2.7 µM and 366 ± 47 µM in K562 cells and PBMCs (after 72 h), respectively. The results demonstrated that the apoptotic cell percentage in the control group increased from 6.09% to 84.10% and 17.2% to 20.06% in K562 cells and PBMCs after 48 h of treatment, respectively. Moreover, 4-Clpgc treatment increased the expression of Bax and TP53 genes by 42.74 and 35.88 folds in K562 cells and 9.60 and 7.75 folds in PBMCs, respectively. On the other hand, the expression of BCL2 was reduced by 1.47 and 1.38 folds in K562 cells and PBMCs, respectively. These compounds were associated with less toxic effects on normal cells, compared to the cancer cells. In conclusion, these derivatives can be considered as appropriate candidates for leukemia treatment.

Insulin resistance and pseudoacromegaly: A case report.

Patients with acromegaly have soft tissue overgrowth that induced characteristic clinical presentation. A growth hormone-secreting adenoma of the anterior pituitary gland is the most common cause of acromegaly. Metabolic and somatic features of acromegaly caused by high serum concentrations of insulin-like growth factor-I (IGF-I) and excess growth hormone (GH) production. we present a case of 'pseudoacromegaly' with an acromegaloid features, suppressed IGF-I levels and marked elevation of serum insulin. Endocrinologists should consider this diagnosis when assessing patients with clinical features of acromegaly and insulin resistance, in the absence of elevated levels of GH and IGF-I.

The effects of melatonin supplementation in adjunct with non-surgical periodontal therapy on periodontal status, serum melatonin and inflammatory markers in type 2 diabetes mellitus patients with chronic periodontitis: a double-blind, placebo-controlled trial.

BACKGROUND: Diabetes mellitus (DM) and periodontitis are two common chronic diseases with bidirectional relationship. Oxidative stress plays a key role in the pathogenesis of these two diseases. The aim of this study was to investigate the effects of melatonin supplementation in adjunct with non-surgical periodontal therapy on periodontal status, serum melatonin and inflammatory markers in type 2 DM patients with chronic periodontitis (CP). MATERIALS AND METHODS: In this double-blind clinical trial study, 50 type 2 DM patients with CP were randomly allocated to the intervention and control groups. The intervention and control groups received either 6 mg melatonin or placebo (2 tablets) once a day. Serum levels of melatonin, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), hs-C-reactive protein (hs-CRP), clinical attachment loss (CAL), pocket depth (PD), bleeding on probing (BOP) and plaque index were evaluated in all subjects pre- and post-intervention. RESULTS: Melatonin supplementation significantly increased the mean serum levels of melatonin after intervention. The mean changes of melatonin were significantly higher in intervention group compared with control group. IL-6 and hs-CRP levels were significantly (p = 0.008 and p = 0.017, respectively) reduced in the intervention group. The mean changes of IL-6 were significantly lower in the intervention group compared with the control group (p = 0.04). In the intervention group, PD and CAL were significantly decreased after intervention (p < 0.001). There were significant differences in the mean change of PD and CAL between the intervention and control groups after intervention (p < 0.001). CONCLUSIONS: Melatonin supplementation in adjunct with non-surgical periodontal therapy might improve inflammatory and periodontal status in T2DM with CP.

Clinical and Genetic Analysis of Nine Suspected Familial Haemophagocytic Lymphohistiocytosis Patients for MUNC13-4 Deficiency and Introducing Four Novel Mutations in UNC13D.

Familial haemophagocytic lymphohistiocytosis (FHL) is a rare disorder of immune dysregulation. FHL inherited in an autosomal recessive pattern is classified into five subtypes based on underlying genetic defects. Mutations in four genes including PRF1, UNC13D, STX11 and STXBP2 are responsible for FHL2 to FHL5 respectively. The cause of FHL1 is associated with mutations in an unknown gene located at 9q21.3-22. This study aims to report the clinical features and genetic results of nine Iranian patients suffering from -haemophagocytic lymphohistiocytosis. Nine patients (five males and four females) suspected to FHL whose genetic evaluation of PRF1 and STX11 revealed no mutations, were entered the study to investigate UNC13D mutations. Primers were designed to amplify all coding regions and exon-intron boundaries of the gene. PCR products were then sequenced and analyzed by sequence analysis tools including BLAST. The most frequent clinical manifestations observed in the patients were fever and hepatosplenomegaly. In this study, five mutations were detected in UNC13D including four novel mutations (c.1434_1446delACCCATGGTGCAGinsTGGTGCT, c.1933C>T, c.1389+1G>C and c.2091+1G>A) besides to a previously reported deletion (c.627delT). The pathogenicity of the missense mutation was assessed using online prediction tools including SIFT and PolyPhen2. The study results may provide valuable information for genetic counseling especially for those who have a history of immunodeficiency diseases in their family and can be used for prenatal diagnosis.

Femtomolar level detection of RASSF1A tumor suppressor gene methylation by electrochemical nano-genosensor based on Fe3O4/TMC/Au nanocomposite and PT-modified electrode.

The alterations in DNA methylation pattern have been identified as one of the most frequent molecular phenomenon in human cancers. The RASSF1A tumor suppressor gene was shown to be often inactivated by hypermethylation of its promoter region. In the present study, a novel chip format sandwich electrochemical genosensor has been developed for the analysis of gene-specific methylation using Fe3O4/N-trimethyl chitosan/gold (Fe3O4/TMC/Au) nanocomposite as tracing tag to label DNA probe and polythiophene (PT) as immobilization platform of sensing element. However, no attempt has yet been made to conjugate DNA probe to Fe3O4/TMC/Au nanocomposite as electrochemical label for strip-based genosensing. Cyclic voltammetric (CV) analysis indicated that modification procedure was well performed. Differential pulse voltammetry (DPV) was employed for quantitative assessment of RASSF1A DNA promoter methylation. The electrochemical measurements accomplished using non-specific DNA fragments mixed with samples, revealed the high specificity and selectivity in methylation analysis by means of this DNA nanobiosensor. With the linear range of concentration from 1 × 10(-14)M to 5 × 10(-9)M and the detection limit of 2 × 10(-15)M, this new strategy has shown such a promising application to be used for universal analysis of any DNA sequence.