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Frontiers in Biology

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, Volume 13 Issue 6 Previous Issue   
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Intracellular trafficking of planar cell polarity proteins
Yan Huang, Tianji Ma, Yusong Guo
Front. Biol.. 2018, 13 (6): 395-405.
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BACKGROUND: Planar cell polarity (PCP) is a phenomenon in which epithelial cells are polarized along the plane of a tissue. PCP is critical for a variety of developmental processes and is regulated by a set of evolutionarily conserved PCP signaling proteins. Many of the PCP proteins adopt characteristic asymmetric localizations on the opposing cellular boundaries. Currently, the molecular mechanisms that establish and maintain this PCP asymmetry remain largely unclear. Newly synthesized integral PCP proteins are transported along the secretory transport pathway to the plasma membranes. Once delivered to the plasma membranes, PCP proteins undergo endocytosis. Recent studies reveal insights into the intracellular trafficking of PCP proteins, suggesting that intracellular trafficking of PCP proteins contributes to establishing the PCP asymmetry.

OBJECTIVE: To understand the intracellular trafficking of planar cell polarity proteins in the secretory transport pathway and endocytic transport pathway.

METHODS: This review summarizes our current understanding of the intracellular trafficking of PCP proteins. We highlights the molecular mechanisms that regulate sorting of PCP proteins into transport vesicles and how the intracellular trafficking process regulates the asymmetric localizations of PCP proteins.

RESULTS: Current studies reveal novel insights into the molecular mechanisms mediating intracellular trafficking of PCP proteins. This process is critical for delivering newly synthesized PCP proteins to their specific destinations, removing the unstable or mislocalized PCP proteins from the plasma membranes and preserving tissue polarity during proliferation of mammalian skin cells.

CONCLUSION: Understanding how PCP proteins are delivered in the secretory and endocytic transport pathway will provide mechanistic insights into how the asymmetric localizations of PCP proteins are established and maintained.

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Association of mitochondrial dysfunction and lipid metabolism with type 2 diabetes mellitus: A review of literature
Karimeh Haghani, Pouyan Asadi, Gholamreza Taheripak, Ali Noori-Zadeh, Shahram Darabi, Salar Bakhtiyari
Front. Biol.. 2018, 13 (6): 406-417.
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BACKGROUND: Diabetes mellitus (DM) is one of the most prevalent chronic diseases, and its prevalence continues to increase globally. The impact of mitochondrial dysfunction and lipid metabolism on diabetes mellitus and insulin resistance (IR) has been implicated in several previous reports; however, the results of studies are confusing despite four decades of study.

METHODS/RESULTS: This review has evaluated updated understanding of the role of mitochondrial dysfunction and lipid metabolism on type 2 diabetes, and found that mitochondrial dysfunction and lipid metabolism disorder induce the dysregulation of liver and pancreatic beta cells, insulin resistance, and type 2 diabetes.

CONCLUSION: Mitochondrial dysfunction and lipid metabolism induce metabolic dysregulation and finally increasing the possibility of diabetes.

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Process optimization of benzo[ghi]perylene biodegradation by yeast consortium in presence of ZnO nanoparticles and produced biosurfactant using Box-Behnken design
Sanjeeb Kumar Mandal, Nupur Ojha, Nilanjana Das
Front. Biol.. 2018, 13 (6): 418-424.
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BACKGROUND: Benzo[ghi]perylene (BghiP), a polycyclic aromatic hydrocarbon (PAH) containing six fused benzene rings is considered as priority pollutant because of its carcinogenicity, mutagenicity and acute toxicity.

METHODS: The synthesis of ZnO nanoparticles was done following the standard method. Biosurfactant production by yeast consortium YC04 in MSM was confirmed by various tests viz. drop collapse test, methylene blue agar plate method and emulsification test (E24) using the standard procedures. Efficiency of YC04 was tested to remediate BghiP in presence of ZnO nanoparticles and produced biosurfactant in the growth medium.

RESULTS: Response surface methodology (RSM), 3-level five variables Box-Behnken design (BBD) was employed to optimize the factors viz. pH 7.0, temperature 30°C, shaking speed 130 rpm, inoculum dosage 3% and ZnO nanoparticles concentration 2 g/L after a period of 6 days of incubation for the enhanced degradation of BghiP (63.83±0.01%). It was well in close agreement with the predicated value obtained by RSM model yield (63.83±0.08%). Analysis of variance (ANOVA) showed F-value of 51.70, R2 of 0.9764, probability of<0.0001 and coefficient of variation of 1.25% confirmed the validity of the model. Degradation of BghiP was assessed using GC-MS and FTIR analysis. Kinetic study demonstrated that BghiP degradation fitted first order kinetic model.

CONCLUSIONS: To the best of our knowledge, this is the first report on process optimization toward nanobioremediation of BghiP using yeast consortium in presence of ZnO nanoparticles and produced biosurfactant in medium.

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Design, molecular docking, synthesis, characterization, biological activity evaluation (against MES model), in-silico biological activity spectrum (PASS analysis), toxicological and predicted oral rat LD50 studies of novel sulphonamide derivatives
Ajeet, Arvind Kumar, Arun K. Mishra
Front. Biol.. 2018, 13 (6): 425-451.
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BACKGROUND: Among the reported potential agents to treat the epilepsy, sulphonamides are important and their significance cannot be ignored. A series of substituted 4-amino-benzene sulfonamides were designed, keeping in view the structural requirement of pharmacophore.

METHODS: Lipinski rule of five has been calculated; failure to Lipinski rule was not observed. Docking was performed through AutoDock Vina. Molecules have been screened out through docking. Compounds were synthesized and characterized through IR, 1HNMR, 13C NMR, Mass and elemental analysis. The anticonvulsant activity of the synthesized compounds was assessed using the Maximal Electroshock Seizure (MES) model. In-silico biological activity spectrum, toxicological studies, predicted oral rats LD50 were performed.

RESULTS: Docking studies showed good interaction with lyase (Oxo-acid) - human carbonic anhydrase-I (1AZM). The in-silico studies proved them to be with good drug-likeness properties, especially 4-(3-Acetyl-phenylamino)-methyl)-benzenesulfonamide (2g). These results revealed that the synthesized compounds (1a-1c, 2a-2q) exhibited promising anticonvulsant effect against MES model for inhibition of Lyase- Human Carbonic Anhydrase-I.

CONCLUSION: After investigating all the results, the compound 4-(3-Acetyl-phenylamino)-methyl)-benzenesulfonamide (2g) is found to be best in the series. A comparatively good activity of compound 2g suggests us that sulphonamide can be leads to further optimization for building potent and chemically diversified anti-convulsant agents.

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The comparison of insulin and uric acid levels in adolescents with and without metabolic syndrome
Homeira Rashidi, Hajieh Shahbazian, Forogh Nokhostin, Seyed Mahmood Latifi, Mehrian Jafarizade
Front. Biol.. 2018, 13 (6): 452-457.
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BACKGROUND and AIM: The prevalence of metabolic syndrome (MS) increased in recent years in both adolescents and children groups. The aim of the study is evaluating the relationship between insulin and uric acid (UA) level in MS in adolescents

MATERIALS and METHODS: we studied 120 adolescence aged 10 to 19 in two groups: control group without metabolic syndrome and case group with metabolic syndrome. The Criteria of ATP III was considered as a diagnosis factor for metabolic syndrome.

DISCUSSION: Various studies have been conducted in various populations to evaluate the relationship between UA level and MS in adolescents. Abdominal obesity, low HDL, hypertriglyceridemia and hypertension are associated with high UA level. In their analysis, the MS OR in UA level≤4.9, 4.9-5.8 and≥5.8 mg/dl was 1, 2.53 and 9.03, respectively, which were higher than our findings in current study. Hyperinsulinemia caused by insulin resistance is one of the complications associated with MS, which puts individuals at risk of diabetes and cardiovascular events.

RESULTS: Uric acid level in the Case group was significantly higher than the control group (p = 0.0001, 43.8±1.4 vs. 4.1±1 mg/dl, respectively). Insulin level was significantly higher in the case group in compare to the control group (p = 0.008, 9.8±5.3 vs. 12.2±6 mU/ml, respectively).

CONCLUSION: The findings of this case-control study showed that adolescents with metabolic syndrome have a higher uric acid and insulin level in compare to normal subjects. We hypothesis that increase in serum insulin and uric acid level can be a risk factor in the development of metabolic syndrome.

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Effectiveness of revascularization of the ulcerated foot in diabetic patients with peripheral artery disease for one year follow-up
Mohammad Momen Gharibvand, Mina Mounesi, Arman Shahriari, Asghar Sharif Najafi, Azim Motamed far, Atefeh Roumi
Front. Biol.. 2018, 13 (6): 458-463.
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BACKGROUND: Diabetes is an important risk factor for atherosclerosis. The diabetic foot is characterized by the presence of arteriopathy and neuropathy.When ischemia is diagnosed, restoration of pulsatile blood flow by revascularization may be considered for salvaging the limb. The treatment options are angioplasty with or without stenting and surgical bypass or hybrid procedures combining the two.

AIMS: To evaluate the outcomes of severe ischemic diabetic foot ulcers for which percutaneous transluminal angioplasty (PTA) was considered as the first-line vascular procedure. Factors associated with successful PTA were also evaluated.

METHODS: In 80 consecutive diabetic patients with foot ulcers and severe limb ischemia, PTA was performed if feasible. All patients were followed until healing or for one year. Clinical and angiographic factors in fluencing outcomes after PTA were sought by univariate and multivariate analysis.

RESULTS: PTA was done in 73 of the 80 (91.2%) patients, and considered clinically succe ssful in 58(79.9%). Successful PTA was significantly higher in patients with Superficial femoral artery, posterior Tibialis and dorsalis pedis arteries involvement in the univariate analysis. Seven patients were expired during the study follow up due to MI, pulmonary thromboembolism and GI bleeding.

CONCLUSION: PTA in diabetic patients with severe ischemic foot ulcers provided favorable. Some parameters could be used for predicting PTA successfulness.

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Prevalence of fragile X syndrome among patients with mental retardation in the west of Iran
Peyman Hadi, Karimeh Haghani, Ali Noori-Zadeh, Salar Bakhtiyari
Front. Biol.. 2018, 13 (6): 464-468.
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BACKGROUND: Fragile X syndrome (FXS), an X-linked disorder, is the most common cause of inherited mental retardation. This is caused by a trinucleotide CGG repeat expansion (>200) on the fragile X mental retardation 1 gene (FMR1) becoming methylated leading to a deficiency or absence of the FMR1 protein. Determining FXS prevalence in the mentally retarded individuals in the west of Iran was the aim of this study.

METHODS: 200 patients with moderate mental retardation who were clinically suspicious to FXS were screened using cytogenetic and molecular methods. Blood samples were collected and cultured in the specific culture media. The G-Banding method was used for karyotyping and DNA sequencing performed for verifying the results of the cytogenetic tests.

RESULTS: 16 patients (8%) were found to have fragile X syndrome. The results showed that there is no significant association between the fragile X syndrome and economic status and place of residence, however, the relationship between fragile X syndrome and mental retardation in the family history is significant.

CONCLUSION: The frequency of FXS was similar to other reports in the preselected patients. For diagnosis of FXS, chromosome analysis must be accompanied by molecular studies.

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Widely distribution of hematological parameters in thalassemia patients with similar α-globin genotype
Bijan Keikhaei, Pejman Salehi-Fard, Mostafa Paridar, Mehraneh Karimzadeh, Razie Dehghani, Asma Zamiri, Vahideh Takhviji
Front. Biol.. 2018, 13 (6): 469-474.
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BACKGROUND: Thalassemia is known as the commonest monogenic disorder with an imbalanced rate of globin chains production of adult hemoglobin. Despite the available information about the thalassemia etiology, its phenotype varies from each patient to another. This study aimed to evaluate the hematological parameters of patients with the same -α3.7 homozygote and heterozygote genotypes to amend screening programs.

METHODS: In this observational study, we evaluated 1301 thalassemia suspected patients who referred to the Thalassemia and Hemoglobinopathy Research Center of Ahvaz University of Medical Sciences, Khuzestan, Iran during 2014-2016. According to the genotyping studies, patients divided into 2 groups with -α3.7/aa (n = 646) and -α3.7/-α3.7 (n = 181) genotypes. Thereafter, distribution of hematological parameters evaluated in both groups.

RESULTS: The mean age in heterozygous and homozygous groups was 25.7±4.5 and 26±4.4 years old, respectively. The degree of anemia was considerably varied in patients with the same genotype. MCV, RBC and MCH showed a wide distribution in patients.

CONCLUSION: The findings presented here suggest that other molecular mechanisms along with α-globin gene mutations could be involved in determining the phenotypes of alpha thalassemia patients.

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The positive effects of Mediterranean-neutropenic diet on nutritional status of acute myeloid leukemia patients under chemotherapy
Jalali, Seyyed Mostafa, Morteza Abdollahi, Atiyeh Hosseini, Dehghani Kari Bozorg, Ajami, Marjan Azadeh, Kimia Moiniafshar
Front. Biol.. 2018, 13 (6): 475-480.
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INTRODUCTION: Cancer and chemotherapy-induced malnutrition increase death, reduce the response to treatment, and increase multiple kinds of side effects. The aim of this study was to investigate the effects of Mediterranean-neutropenic diet on the nutritional status of acute myeloid leukemia patients under chemotherapy.

MATERIALS AND METHODS: 50 patients were divided into two groups by a random allocation scheme: the Mediterranean-neutropenic diet (n = 25) and the neutropenic diet group (n = 25). The intervention was implemented during a one month period. The nutritional status was evaluated based on PG-SGA. Serum albumin levels and dietary intake were also measured.

RESULTS: After the intervention, the mean serum albumin level in the intervention group was significantly higher than the beginning of the study (p = 0.09) and in comparison with the control group (p = 0.01). Also, the mean serum albumin level in the control group significantly decreased at the end of the study compared to the beginning of the study (p = 0.03). After intervention, the nutritional status of the patients in the intervention group was significantly improved compared to the control group.

CONCLUSION: In general, based on the results of this study, the Mediterranean neutropenic diet improves nutritional status during chemotherapy by increasing food intake, preventing weight loss and increasing serum albumin levels

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