BACKGROUND: PTEN is well known to function as a tumor suppressor that antagonizes oncogenic signaling and maintains genomic stability. ThePTEN gene is frequently deleted or mutated in human cancers and the wide cancer spectrum associated with PTEN deficiency has been recapitulated in a variety of mouse models ofPten deletion or mutation. Pten mutations are highly penetrant in causing various types of spontaneous tumors that often exhibit resistance to anticancer therapies including immunotherapy. Recent studies demonstrate that PTEN also regulates immune functionality.
OBJECTIVE: To understand the multifaceted functions of PTEN as both a tumor suppressor and an immune regulator.
METHODS: This review will summarize the emerging knowledge of PTEN function in cancer immunoediting. In addition, the mechanisms underlying functional integration of various PTEN pathways in regulating cancer evolution and tumor immunity will be highlighted.
RESULTS: Recent preclinical and clinical studies revealed the essential role of PTEN in maintaining immune homeostasis, which significantly expands the repertoire of PTEN functions. Mechanistically, aberrant PTEN signaling alters the interplay between the immune system and tumors, leading to immunosuppression and tumor escape.
CONCLUSION: Rational design of personalized anti-cancer treatment requires mechanistic understanding of diverse PTEN signaling pathways in modulation of the crosstalk between tumor and immune cells.
BACKGROUND: The prevalence of neurodegenerative disorders such as Parkinson’s disease (PD) is increased by age. Alleviation of their symptoms and protection of normal neurons against degeneration are the main aspects of the researches to establish novel therapeutic strategies. Many studies have shown that mitochondria as the most important organelles in the brain which show impairment in PD models. Succinate dehydrogenase (SDH) as a component of the oxidative phosphorylation system in mitochondria connects Krebs cycle to the electron transport chain. Dysfunction or inhibition of the SDH can trigger mitochondrial impairment and disruption in ATP generation. Excessive in lipid synthesis and induction of the excitotoxicity as inducers in PD are controlled by SDH activity directly and indirectly. On the other hand, mutation in subunits of the SDH correlates with the onset of neurodegenerative disorders. Therefore, SDH could behave as one of the main regulators in neuroprotection.
OBJECTIVE: In this review we will consider contribution of the SDH and its related mechanisms in PD.
METHODS: Pubmed search engine was used to find published studies from 1977 to 2016. “Succinate dehydrogenase”, “lipid and brain”, “mitochondria and Parkinson’s disease” were the main keywords for searching in the engine.
RESULTS: Wide ranges of studies (59 articles) in neurodegenerative disorders especially Parkinson’s disease like genetics of the Parkinson’s disease, effects of the mutant SDH on cell activity and physiology and lipid alteration in neurodegenerative disorders have been used in this review.
CONCLUSION: Mitochondria as key organelles in the energy generation plays crucial roles in PD. ETC complex in this organelle consists four complexes which alteration in their activities cause ROS generation and ATP depletion. Most of complexes are encoded by mtDNA while complex II is the only part of the ETC which is encoded by nuclear genome. So, focusing on the SDH and related pathways which have important role in neuronal survival and SDH has a potential to further studies as a novel neuroprotective agent.
OBJECTIVES: Single nucleotide polymorphisms (SNPs), genetic background, and epigenetics play important roles in rheumatoid arthritis (RA). These factors can be useful in RA diagnosis, prognosis, and treatment response evaluation, particularly with the growing trends in personalized medicine. Therefore, categorizing classic genes and SNPs in RA can present an appropriate guideline for RA management.
DISCUSSION: Prognostic and diagnostic biomarkers play important roles in RA diagnosis and treatment. Categorizing SNPs is not an easy process yet, but selecting classic SNPs can be useful worldwide, according to basic similarities that exist in genomes. In this review, we compiled some of these RA-associated SNPs and biomarkers in a table, according to newly identified factors. The role of epigenetics in RA is undeniable; using epigenetic biomarkers like histone deacetylase (HDACs) can be useful in RA diagnosis and treatment. miRs such as miR-146a, miR-155, and miR-222 are useful in diagnosis and can be used in treatment by interfering with other factors’ functions. Interleukins (ILs) seem to be good prognostic and diagnostic markers and can be targeted in RA treatment.
CONCLUSION: Using multiple types of biomarkers, such as genes, SNPs, and epigenetic biomarkers like HDACs can be useful in RA management and treatment. PTPN22, HLA-DR polymorphisms, miRs, and HDACs are considerable in RA susceptibility; hence, they can be valuable biomarkers in future studies. This article gathered separate information from approximately 100 articles to present useful biomarkers and polymorphisms in one review.
BACKGROUND: Porphyromonas gingivalis is a periodontal pathogen, which is considered to be a keystone pathogen for periodontitis. A diverse conglomerate of P. gingivalis virulence factors including lipopolysaccharide, fimbriae, capsular polysaccharide, haemagglutinin and cysteine proteases (Arg-gingipains and Lys-gingipain) are considered to be involved in the pathogenesis of periodontitis. Leupeptin is a cysteine protease inhibitor which is specific for Arg gingipains. The present review focuses on action of leupeptin on Arg gingipains.
METHOD: A search was carried out systematically from the start till September, 2016. The search was made in Medline database via PubMed. The keywords enlisted were “leupeptin”; “gingipains”; “periodontitis” using Boolean operator “and.”
RESULTS: The result was selection of 58 articles which linked leupeptin to periodontitis and gingipains; pathogenesis of periodontitis, pathogenicity of gingipains and role of leupeptin.
CONCLUSION: It was concluded that leupeptin inhibits and attenuates a number of destructive activities of Arg gingipains including inhibition of platelet aggregation; inhibit degradation of LL-37, which is an antimicrobial peptide; blocking inhibition of monocyte chemoattractant protein; restoring level of interleukin-2; inhibiting degradation of collagen type I and IV to name a few.
BACKGROUND: Curcumin has emerged to be utilized as a superb beneficial agent, due to its naturally occurring anti-oxidant, anti-inflammatory and anti-carcinogenic property.
METHODS: The interaction of curcumin with human serum albumin, the main in vivo transporter of exogenous substances, was investigated using absorption spectroscopy, steady-state fluorescence, excited state life-time studies and circular dichroism spectroscopy.
RESULTS: Isothermal titration calorimetry techniques inferred one class of binding site with binding constant ～1.74×105 M−1 revealing a strong interaction. The binding profile was analyzed through the evaluation of the thermodynamic parameters, which indicated the involvement of hydrophobic interactions (burial of non-polar group). Fluorescence lifetime of tryptophan residue was observed to decrease to 1.94 ns from 2.84 ns in presence of Curcumin. Percentage of α helicity of human serum albumin was also reduced significantly upon binding with curcumin as evidenced by circular dichroism measurement leading to conformational modification of the protein molecule.
CONCLUSIONS: On the basis of such complementary results, it may be concluded that curcumin shows strong binding affinity for human serum albumin, probably at the hydrophobic cavities of the protein and at or around the tryptophan residue. Molecular Docking analysis of HSA and curcumin provided light on the number of binding sites at an atomic level, which were already determined at a molecular level in spectroscopic measurements. Our study unfolds the modes of interaction of curcumin with human serum albumin in the light of different biophysical techniques and molecular modeling analysis.
BACKGROUND: Styrene and its metabolites are known to have serious adverse effects on human health and hence, strategies to prevent its release, eradicate it from the environment, and understand its route of degradation are being considered.
METHODS: A total of 18 strains were isolated from 4 samples of diesel contaminated soils. Among them 5 strains were selected for their ability to degrade styrene and use it as a sole carbon source to produce PHA. These strains were identified as Enterobacter spp. on the basis of 16S rRNA gene sequencing. Bacteria were screened for their ability to produce PHA by utilizing glucose and styrene as a carbon sources. Screening for PHA production was done by Nile blue A, Sudan black B, and phase contrast microscopy and the selected 3 strains showed positive results. Growth kinetics along with time profiling of PHA was performed for glucose and styrene as carbon sources.
RESULTS:PHA extraction was done at equal intervals of 12 h by sodium hypochlorite method which showed that these strains accumulate maximum amount of PHA after 48 h in glucose (30.60%). FTIR analysis of PHA was done which revealed homopolymer PHB and copolymer (PHB-co-PHV) production in strains by utilizing glucose and styrene. Gas chromatography mass spectrometry was carried out to identify the metabolites produced by bacterial strains grown on styrene. Metabolites of styrene degradation included propyne and phenylalanine. Genomic DNA isolation was carried out to amplify phaC gene which encodes PHA synthase enzyme.
CONCLUSIONS: The conversion of styrene to polyhydroxyalkanoates (PHA) provides a new and unique link between an aromatic environmental pollutant and aliphatic PHA accumulation.
BACKGROUND: Nattokinase (NK) is a serine protease enzyme of the subtilisin family. It exhibits a strong fibrinolytic activity. The fibrinolytic enzymes from? Bacillus ?sp. have attracted interest as thrombolytic agents because of their efficiency in the fibrinolytic process including plasmin activation.
METHODS: In the present study, VIT garden soil was collected and subjected to isolation process in order to screen for the NK production. Screening for NK enzyme was performed by radial caseinolytic assay. The production of NK enzyme was done in two different production medium for comparative studies. The NK enzyme was purified by gel permeation chromatography. The activity of the purified NK was checked by clot lysis and casein digestion assay. To investigate the structural basis of NK and fibrinogen interaction and also to identify the best binding mode, molecular dynamics and docking studies were performed.
RESULTS: Based on the morphological and biochemical characterization, the isolate was identified as Bacillus sp. The overall purification fold of NK was about 3 with the specific activity of 664U/mg and 9.9% yield. Homogeneity of the purified enzyme was analyzed and confirmed by the single band obtained in SDS-PAGE. Molecular weight of the purified protease was estimated as 25 kDa. Purified NK enzyme exhibited 97% of effective clot lysis activity. The NK was docked in to the knob region of the fibrinogen at its binding site using Dock server. A total of 26 residues of fibrinogen and 29 residues of NK constitute the interface region. However, 9 residues of fibrinogen (THR238, MET264, LYS266, ARG275, THR277, ALA279, ASN308, MET310, and LYS321) and 8 residues of NK (GLY61, SER63, THR99, PHE189, LEU209, TYR217, ASN218, and MET222) are involved in intact binding.
CONCLUSIONS: A significant amount of NK enzyme was obtained from Bacillus sp. The docking analysis revealed that the NK and fibrinogen adopt an extended binding pattern and interacts with the crucial residues to exhibit their activity.
OBJECTIVES: To trace the critical practicing, clinical and epidemiological risk factors in bacterial load and points of intervention in spread of community-acquired methicillin resistant Staphylococcus aureus (CA-MRSA) in healthy community.
STUDY DESIGN: 2872 individuals with no prominent clinical features were enrolled and administered a pre-tested questionnaire prepared on the basis of outcome of a prior pilot study in same region. Swab samples from skin, throat and nasal nares were tested for MRSA and molecular identification was done to track the strains moving from hospital to community.
METHODS: Swab samples from skin, throat and nasal nares were tested for MRSA culture followed by molecular characterization of isolates and antimicrobial resistance pattern. Bacterial load was estimated to better understand the burden in different categories. Statistical analysis was done using SPSS 16.0 version.
RESULTS: History of prior infection (OR 3.9, 95% CI 1.363 – 5.793), habit of self remedy (OR 3.2, 95% CI 0.991 – 1.473) and incomplete treatment (OR 0.26, 95% CI 0.08 – 0.80) (P<0.05 for each) were the predominant factors that contributed to spread of CA-MRSA. Increased drug resistance in CA-MRSA was observed for 4 different clones: SCCmec+ IVa/PVL+, SCCmec+ IVa/PVL− and SCCmec+ IVc/PVL+, SCCmec+ IVc/PVL−. Bacterial load was found significantly high in below poverty line dwellers and drug abusers (P<0.05).
CONCLUSION: We identified habit of self remedy, drug abusing and incomplete treatment as practicing risk factors where interventions can be made to manage the dissemination of CA-MRSA in rural population.
BACKGROUND: Gastrointestinal disorders are common complaints for which endoscopy and colonoscopy are the most important diagnostic procedures. Anxiety is an unpleasant, ambiguous feeling of apprehension and fear of unknown origin that occurs during stressful situations or injury. Lack of sufficient information and fear of pain can cause anxiety prior to a colonoscopy, reducing the number of patients willing to undergo the procedure and increasing colonoscopy time. The aim of this study was to evaluate the efficacy of psychological preparation on anxiety before colonoscopy in patients presenting to Golestan Hospital during the years 1994 and 1995.
MATERIAL and METHODS: This study was a double-blind clinical trial of patients presenting to the colonoscopy unit in Golestan Hospital in 1994 and 1995. A total of 80 patients were divided into two groups: intervention and control. A primary assessment of anxiety was performed using Spielberger’s State-Trait Anxiety Inventory. Before the colonoscopy, the State-Trait Anxiety Inventory was completed by the patients again. The effectiveness of psychological preparation before colonoscopy and its effect on anxiety were evaluated using statistical software SPSS 20.
RESULTS: The mean age of participants was 46.33±12.2 years in the intervention group and 44.8±12.26 years in the control group. In this study, there were 41 males (51.3%) and 39 females (48.7%); 15 patients (18.7%) were single and the rest married. In terms of demographic variables, there were no significant differences between the two groups (p>0.05). The average scores of state and trait anxiety in the intervention group showed a statistically significant difference before and after the intervention (p = 0.000).
CONCLUSION: Trait and state anxiety levels after psychological preparation showed a statistically significant reduction. This indicates the effectiveness of intervention programs to reduce anxiety before colonoscopy.