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Colorectal Peritoneal Metastases Treated by Perioperative Systemic Chemotherapy and Cytoreductive Surgery With or Without Mitomycin C-Based HIPEC: A Comparative Study Using the Peritoneal Surface Disease Severity Score (PSDSS)

Baratti D, Kusamura S, Azmi N, Guaglio M, Montenovo M, Deraco M

Ann Surg Oncol, 2020 Jan;27(1):98-106.
PMID: 31691116 DOI: 10.1245/s10434-019-07935-2

BACKGROUND: The Prodige-7 trial has questioned the role of hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal metastases from colorectal cancer (CRC-PM).
PATIENTS AND METHODS: We compared a prospectively collected group of 48 patients undergoing oxaliplatin/irinotecan-based perioperative systemic chemotherapy (s-CT) with targeted agents, and cytoreductive surgery (CRS) (no-HIPEC group) with 48 controls undergoing the same perioperative s-CT and CRS/HIPEC (HIPEC group). Patients were matched (1:1) according to the Peritoneal Surface Disease Severity Score, completeness of cytoreduction, history of extraperitoneal disease (EPD), and Peritoneal Cancer Index.
RESULTS: The groups were comparable, except for a higher number of patients in the HIPEC group with World Health Organization performance status 0, pN2 stage primary tumor, and treated with preoperative s-CT. Forty-one patients in the no-HIPEC group and 43 patients in the HIPEC group had optimal comprehensive treatment (P = 0.759), defined as complete cytoreduction of PM and margin-negative EPD resection. Median follow-up was 31.6 months in the no-HIPEC group and 39.9 months in the HIPEC group. Median overall survival was 39.3 months in the no-HIPEC group and 34.8 months in the HIPEC group (P = 0.702). In the two groups, severe morbidity occurred in 14 (29.2%) and 13 (27.1%) patients, respectively (P = 1.000), with no operative deaths. On multivariate analysis, left-sided primary and curative treatment independently correlated with better survival while HIPEC did not (hazard ratio 0.73; 95% confidence interval 0.47-1.15; P = 0.178).
CONCLUSIONS: Our results confirmed that, in selected patients, perioperative s-CT and surgical treatment of CRC-PM resulted in unexpectedly high survival rates. Mitomycin C-based HIPEC did not increase morbidity but did not impact prognosis.

Matched MeSH terms: Peritoneal Neoplasms/secondary
Fulltext Attitudes toward opioid substitution therapy and pre-incarceration HIV transmission behaviors among HIV-infected prisoners in Malaysia: implications for secondary prevention

Bachireddy C, Bazazi AR, Kavasery R, Govindasamy S, Kamarulzaman A, Altice FL

Drug Alcohol Depend, 2011 Jul 01;116(1-3):151-7.
PMID: 21232882 DOI: 10.1016/j.drugalcdep.2010.12.001

BACKGROUND: Pre-incarceration HIV transmission behaviors and current attitudes toward opioid substitution therapy (OST) among HIV-infected male prisoners in Malaysia have important implications for secondary HIV prevention efforts.
METHODS: In June 2007, 102 HIV-infected male prisoners within 6 months of community-release were anonymously surveyed in Kota Bharu, Malaysia.
RESULTS: Nearly all subjects (95%) met criteria for opioid dependence. Overall, 66% of participants reported sharing needles, and 37% reported unprotected sex in the 30 days prior to incarceration. During this period, 77% reported injection drug use, with 71% injecting daily and 65% injecting more than one substance. Injection of buprenorphine (28%), benzodiazepines (28%) and methamphetamines (49%) was reported. Nearly all (97%) of those reporting unprotected sex did so with someone not known to be HIV-infected. While 51% believed that opioid substitution therapy (OST) would be helpful, only 33% believed they needed it to prevent relapse after prison release. Most participants (70%) expressed interest in learning more about OST. Those reporting the highest injection risks were more likely to believe OST would be helpful (p<0.05), to believe that it was needed to prevent relapse post-release (p<0.05), and to express interest in learning more about OST (p<0.01).
CONCLUSIONS: Secondary HIV prevention among prisoners in Malaysia is crucial to reduce community HIV transmission after release. Effectively reducing HIV risk associated with opioid injection will require OST expansion, including social marketing to improve its acceptability and careful monitoring. Access to sterile injection equipment, particularly for non-opioid injectors, and behavioral interventions that reduce sexual risk will also be required.

Matched MeSH terms: Secondary Prevention/methods*
Crystal structure of truncated haemoglobin from an extremely thermophilic and acidophilic bacterium

Jamil F, Teh AH, Schadich E, Saito JA, Najimudin N, Alam M

J. Biochem., 2014 Aug;156(2):97-106.
PMID: 24733432 DOI: 10.1093/jb/mvu023

A truncated haemoglobin (tHb) has been identified in an acidophilic and thermophilic methanotroph Methylacidiphilium infernorum. Hell's Gate Globin IV (HGbIV) and its related tHbs differ from all other bacterial tHbs due to their distinctively large sequence and polar distal haem pocket residues. Here we report the crystal structure of HGbIV determined at 1.96 Å resolution. The HGbIV structure has the distinctive 2/2 α-helical structure with extensions at both termini. It has a large distal site cavity in the haem pocket surrounded by four polar residues: His70(B9), His71(B10), Ser97(E11) and Trp137(G8). This cavity can bind bulky ligands such as a phosphate ion. Conformational shifts of His71(B10), Leu90(E4) and Leu93(E7) can also provide more space to accommodate larger ligands than the phosphate ion. The entrance/exit of such bulky ligands might be facilitated by positional flexibility in the CD1 loop, E helix and haem-propionate A. Therefore, the large cavity in HGbIV with polar His70(B9) and His71(B10), in contrast to the distal sites of other bacterial tHbs surrounded by non-polar residues, suggests its distinct physiological functions.

Matched MeSH terms: Protein Structure, Secondary
Use of antidepressants in the treatment of depression in Asia: guidelines, clinical evidence, and experience revisited

Treuer T, Liu CY, Salazar G, Kongsakon R, Jia F, Habil H, et al.

Asia Pac Psychiatry, 2013 Dec;5(4):219-30.
PMID: 23857712 DOI: 10.1111/appy.12090

Major depressive disorder is prevalent worldwide, and only about half of those affected will experience no further episodes or symptoms. Additionally, depressive symptoms can be challenging to identify, with many patients going undiagnosed despite a wide variety of available treatment options. Antidepressants are the cornerstone of depression treatment; however, a large number of factors must be considered in selecting the treatment best suited to the individual. To help support physicians in this process, international and national treatment guidelines have been developed. This review evaluates the current use of antidepressant treatment for major depressive disorder in six Asian countries (China, Korea, Malaysia, Philippines, Taiwan, and Thailand). No remarkable differences were noted between Asian and international treatment guidelines or among those from within Asia as these are adapted from western guidelines, although there were some local variations. Importantly, a shortage of evidence-based information at a country level is the primary problem in developing guidelines appropriate for Asia, so most of the guidelines are consensus opinions derived from western research data utilized in western guidelines. Treatment guidelines need to evolve from being consensus based to evidence based when evidence is available, taking into consideration cost/effectiveness or cost/benefit with an evidence-based approach that more accurately reflects clinical experience as well as the attributes of each antidepressant. In everyday practice, physicians must tailor their treatment to the patient's clinical needs while considering associated external factors; better tools are needed to help them reach the best possible prescribing decisions which are of maximum benefit to patients.

Matched MeSH terms: Secondary Prevention
A novel pathogenic variant of the LDLR gene in the Asian population and its clinical correlation with familial hypercholesterolemia

Chahil JK, Lye SH, Bagali PG, Alex L

Mol Biol Rep, 2012 Jul;39(7):7831-8.
PMID: 22544571 DOI: 10.1007/s11033-012-1626-8

Familial hypercholesterolemia (FH) is a disease implicated with defects in either, Low density lipoprotein receptor gene (LDLR), Apolipoprotein B-100 gene (APOB), the Proprotein convertase subtilisin/kexin type 9 gene (PCSK9) or other related genes of the lipid metabolism pathway. The general characterization of heterozygous FH is by elevated low-density lipoprotein (LDL) cholesterol and early-onset cardiovascular diseases, while the more severe type, the homozygous FH results in extreme elevated levels of LDL cholesterol and usually death of an affected individual by early twenties. We present here a novel non-synonymous, missense mutation in exon 14 of the LDLR gene in two siblings of the Malay ethnicity discovered during an in-house genetic test. We postulate that their elevated cholesterol is due to this novel mutation and they are positive for homozygous FH. This is the first report of a C711Y mutation in patients with elevated cholesterol in Asia.

Matched MeSH terms: Protein Structure, Secondary
Fulltext Smokers can quit regardless of motivation stage in a worksite smoking cessation programme in Malaysia

Yasin SM, Retneswari M, Moy FM, Koh D, Isahak M

Asian Pac J Cancer Prev, 2011;12(9):2193-8.
PMID: 22296355

BACKGROUND: There is an unclear relationship between smoker's early motivation and success rates. Here we aimed to explore the correlates of motivation and smoking abstinence and relapse in worksite smoking cessation programmes.
METHODS: This prospective cohort study involved employees from two major public universities in Malaysia. Participants were actively recruited into a smoking cessation programme. At the start of treatment, participants were administered a questionnaire on sociodemographic variables, smoking habits and 'stage of change'. Behaviour therapy with free nicotine replacement therapy (NRT) was given as treatment for two months. A similar stage of change questionnaire was given at six months, and their smoking status was determined.
RESULTS: There were 185 smokers from both Universities, who joined the programme. At six months, 24 smokers reported sustained abstinence while the others had relapsed. Prior to the programme, the majority of smokers were seriously planning on quitting (59.5%--preparation stage), but over a third had no plans to quit (35.5%--contemplation stage). There was no significant difference noted in changes of motivation stage among the relapsers and the non quitters. In addition, logistic regression showed that sustained abstinence was not predicted by pre-session motivation stage, but this did predict higher relapse for the participants, compared to those in the preparation stage.
CONCLUSION: It is possible to help smokers in the lower motivation groups to quit, provided extra caution is taken to prevent relapse. Healthcare providers' recruitment strategies for cessation programmes should thus encompass smokers in all motivation stages.

Matched MeSH terms: Secondary Prevention
Mutations in mitochondrial NADH dehydrogenase subunit 1 (mtND1) gene in colorectal carcinoma

Yusnita Y, Norsiah MD, Rahman AJ

Malays J Pathol, 2010 Dec;32(2):103-10.
PMID: 21329181 MyJurnal

Mitochondrial Subunit ND1 (mtND1) gene is involved in the first step of the electron transport chain of oxidative phosphorylation (OXPHOS). Alteration of the electron transport components by mutations in mtDNA may compromise the normal electron flow. This could lead to an increase of bifurcation and generation of superoxidase radicals and increase oxidative stress in various types of cancer cells. Genomic DNA was extracted from thirty matched primary colorectal tumour tissues and matching non-tumour tissues. Blood samples were obtained from twenty-five normal people. The mtNDI coding region was amplified by step-down PCR. The purified products were then subjected to direct sequencing and subsequently, the DNA sequences obtained were compared with the revised Cambridge Reference Sequence (rCRS) and MITOMAP. From the analysis, the mtND1 gene showed 11 (45.8%) different mutations and also 13 (54.2%) polymorphisms. The heteroplasmic mutation A4123A/G (I273I/V) might have a pathogenic significance as it fulfills various pathogenic criteria. Three mutations, T3394C (Y30H), A3434G (Y43C) and C3497T (A64V) which occur in a highly conserved region were likely to alter the structure and function of the ND1 protein. We suggest that these mutations, and in combination with the polymorphic variance in mtDNA, may cause slight changes that generate subtly higher levels of toxic reactive oxygen species (ROS).

Matched MeSH terms: Protein Structure, Secondary
Prevention of aspiration following recurrent dislodgement of voice prosthesis: a patient's innovation

Masaany M, Marina MB, Asma A, Sani A

J Laryngol Otol, 2009 Jun;123(6):680-2.
PMID: 18544175 DOI: 10.1017/S0022215108002958

To demonstrate a simple, practical, cheap method of preventing potentially fatal aspiration of a dislodged voice prosthesis; this method was developed by a laryngectomised patient.

Matched MeSH terms: Secondary Prevention
Fulltext Solution structures, dynamics, and ice growth inhibitory activity of peptide fragments derived from an antarctic yeast protein

Shah SH, Kar RK, Asmawi AA, Rahman MB, Murad AM, Mahadi NM, et al.

PLoS One, 2012;7(11):e49788.
PMID: 23209600 DOI: 10.1371/journal.pone.0049788

Exotic functions of antifreeze proteins (AFP) and antifreeze glycopeptides (AFGP) have recently been attracted with much interest to develop them as commercial products. AFPs and AFGPs inhibit ice crystal growth by lowering the water freezing point without changing the water melting point. Our group isolated the Antarctic yeast Glaciozyma antarctica that expresses antifreeze protein to assist it in its survival mechanism at sub-zero temperatures. The protein is unique and novel, indicated by its low sequence homology compared to those of other AFPs. We explore the structure-function relationship of G. antarctica AFP using various approaches ranging from protein structure prediction, peptide design and antifreeze activity assays, nuclear magnetic resonance (NMR) studies and molecular dynamics simulation. The predicted secondary structure of G. antarctica AFP shows several α-helices, assumed to be responsible for its antifreeze activity. We designed several peptide fragments derived from the amino acid sequences of α-helical regions of the parent AFP and they also showed substantial antifreeze activities, below that of the original AFP. The relationship between peptide structure and activity was explored by NMR spectroscopy and molecular dynamics simulation. NMR results show that the antifreeze activity of the peptides correlates with their helicity and geometrical straightforwardness. Furthermore, molecular dynamics simulation also suggests that the activity of the designed peptides can be explained in terms of the structural rigidity/flexibility, i.e., the most active peptide demonstrates higher structural stability, lower flexibility than that of the other peptides with lower activities, and of lower rigidity. This report represents the first detailed report of downsizing a yeast AFP into its peptide fragments with measurable antifreeze activities.

Matched MeSH terms: Protein Structure, Secondary
Solution structure and in silico binding of a cyclic peptide with hepatitis B surface antigen

Muhamad A, Ho KL, Rahman MB, Uhrín D, Tan WS

Chem Biol Drug Des, 2013 Jun;81(6):784-94.
PMID: 23405984 DOI: 10.1111/cbdd.12120

A specific ligand targeting the immunodominant region of hepatitis B virus is desired in neutralizing the infectivity of the virus. In a previous study, a disulfide constrained cyclic peptide cyclo S(1) ,S(9) Cys-Glu-Thr-Gly-Ala-Lys-Pro-His-Cys (S(1) , S(9) -cyclo-CETGAKPHC) was isolated from a phage displayed cyclic peptide library using an affinity selection method against hepatitis B surface antigen. The cyclic peptide binds tightly to hepatitis B surface antigen with a relative dissociation constant (KD (rel) ) of 2.9 nm. The binding site of the peptide was located at the immunodominant region on hepatitis B surface antigen. Consequently, this study was aimed to elucidate the structure of the cyclic peptide and its interaction with hepatitis B surface antigen in silico. The solution structure of this cyclic peptide was solved using (1) H, (13) C, and (15) N NMR spectroscopy and molecular dynamics simulations with NMR-derived distance and torsion angle restraints. The cyclic peptide adopted two distinct conformations due to the isomerization of the Pro residue with one structured region in the ETGA sequence. Docking studies of the peptide ensemble with a model structure of hepatitis B surface antigen revealed that the cyclic peptide can potentially be developed as a therapeutic drug that inhibits the virus-host interactions.

Matched MeSH terms: Protein Structure, Secondary
Fulltext Cloning, expression, purification, crystallization and X-ray crystallographic analysis of recombinant human C1ORF123 protein

Rahaman SN, Mat Yusop J, Mohamed-Hussein ZA, Ho KL, Teh AH, Waterman J, et al.

Acta Crystallogr F Struct Biol Commun, 2016 Mar;72(Pt 3):207-13.
PMID: 26919524 DOI: 10.1107/S2053230X16002016

C1ORF123 is a human hypothetical protein found in open reading frame 123 of chromosome 1. The protein belongs to the DUF866 protein family comprising eukaryote-conserved proteins with unknown function. Recent proteomic and bioinformatic analyses identified the presence of C1ORF123 in brain, frontal cortex and synapses, as well as its involvement in endocrine function and polycystic ovary syndrome (PCOS), indicating the importance of its biological role. In order to provide a better understanding of the biological function of the human C1ORF123 protein, the characterization and analysis of recombinant C1ORF123 (rC1ORF123), including overexpression and purification, verification by mass spectrometry and a Western blot using anti-C1ORF123 antibodies, crystallization and X-ray diffraction analysis of the protein crystals, are reported here. The rC1ORF123 protein was crystallized by the hanging-drop vapor-diffusion method with a reservoir solution comprised of 20% PEG 3350, 0.2 M magnesium chloride hexahydrate, 0.1 M sodium citrate pH 6.5. The crystals diffracted to 1.9 Å resolution and belonged to an orthorhombic space group with unit-cell parameters a = 59.32, b = 65.35, c = 95.05 Å. The calculated Matthews coefficient (VM) value of 2.27 Å(3) Da(-1) suggests that there are two molecules per asymmetric unit, with an estimated solvent content of 45.7%.

Matched MeSH terms: Protein Structure, Secondary
Fulltext The genome of newly classified Ochroconis mirabilis: Insights into fungal adaptation to different living conditions

Yew SM, Chan CL, Kuan CS, Toh YF, Ngeow YF, Na SL, et al.

BMC Genomics, 2016 Feb 03;17:91.
PMID: 26842951 DOI: 10.1186/s12864-016-2409-8

Ochroconis mirabilis, a recently introduced water-borne dematiaceous fungus, is occasionally isolated from human skin lesions and nails. We identified an isolate of O. mirabilis from a skin scraping with morphological and molecular studies. Its genome was then sequenced and analysed for genetic features related to classification and biological characteristics.

Matched MeSH terms: Secondary Metabolism
Quality Improvement Initiatives in Fragility Fracture Care and Prevention

Mitchell PJ, Cooper C, Fujita M, Halbout P, Åkesson K, Costa M, et al.

Curr Osteoporos Rep, 2019 12;17(6):510-520.
PMID: 31734907 DOI: 10.1007/s11914-019-00544-8

PURPOSE OF REVIEW: This review sought to describe quality improvement initiatives in fragility fracture care and prevention.
RECENT FINDINGS: A major care gap persists throughout the world in the secondary prevention of fragility fractures. Systematic reviews have confirmed that the Fracture Liaison Service (FLS) model of care is associated with significant improvements in rates of bone mineral density testing, initiation of osteoporosis treatment and adherence with treatment for individuals who sustain fragility fractures. Further, these improvements in the processes of care resulted in significant reductions in refracture risk and lower post-fracture mortality. The primary challenge facing health systems now is to ensure that best practice is delivered effectively in the local healthcare setting. Publication of clinical standards for FLS at the organisational and patient level in combination with the establishment of national registries has provided a mechanism for FLS to benchmark and improve their performance. Major efforts are ongoing at the global, regional and national level to improve the acute care, rehabilitation and secondary prevention for individuals who sustain fragility fractures. Active participation in these initiatives has the potential to eliminate current care gaps in the coming decade.

Matched MeSH terms: Secondary Prevention
Fulltext Tolerability, safety and intermediary pharmacological effects of cilostazol and isosorbide mononitrate, alone and combined, in patients with lacunar ischaemic stroke: The LACunar Intervention-1 (LACI-1) trial, a randomised clinical trial

Blair GW, Appleton JP, Flaherty K, Doubal F, Sprigg N, Dooley R, et al.

EClinicalMedicine, 2019 04 24;11:34-43.
PMID: 31317131 DOI: 10.1016/j.eclinm.2019.04.001

Background: Lacunar stroke, a frequent clinical manifestation of small vessel disease (SVD), differs pathologically from other ischaemic stroke subtypes and has no specific long-term secondary prevention. Licenced drugs, isosorbide mononitrate (ISMN) and cilostazol, have relevant actions to prevent SVD progression.
Methods: We recruited independent patients with clinically confirmed lacunar ischaemic stroke without cognitive impairment to a prospective randomised clinical trial, LACunar Intervention-1 (LACI-1). We randomised patients using a central web-based system, 1:1:1:1 with minimisation, to masked ISMN 25 mg bd, cilostazol 100 mg bd, both ISMN and cilostazol started immediately, or both with start delayed. We escalated doses to target over two weeks, sustained for eight weeks. Primary outcome was the proportion achieving target dose. Secondary outcomes included symptoms, safety (haemorrhage, recurrent vascular events), cognition, haematology, vascular function, and neuroimaging. LACI-1 was powered (80%, alpha 0.05) to detect 35% (90% versus 55%) difference between the proportion reaching target dose on one versus both drugs at 55 patients. Registration ISRCTN12580546.
Findings: LACI-1 enrolled 57 participants between March 2016 and August 2017: 18 (32%) females, mean age 66 (SD 11, range 40-85) years, onset-randomisation 203 (range 6-920) days. Most achieved full (64%) or over half (87%) dose, with no difference between cilostazol vs ISMN, single vs dual drugs. Headache and palpitations increased initially then declined similarly with dual versus single drugs. There was no between-group difference in BP, pulse-wave velocity, haemoglobin or platelet function, but pulse rate was higher (mean difference, MD, 6.4, 95%CI 1.2-11.7, p = 0.02), platelet count higher (MD 35.7, 95%CI 2.8, 68.7, p = 0.03) and white matter hyperintensities reduced more (Chi-square p = 0.007) with cilostazol versus no cilostazol.
Interpretation: Cilostazol and ISMN are well tolerated when the dose is escalated, without safety concerns, in patients with lacunar stroke. Larger trials with longer term follow-up are justified.
Funding: Alzheimer's Society (AS-PG-14-033).

Matched MeSH terms: Secondary Prevention
Optimising the Bariatric Patients' Outcome through Cardiac Rehabilitation Approach

Hanapi NHM, Yuliawiratman BS, Lai LL, Halil H, Koo JG, Suhaimi A

Obes Surg, 2018 07;28(7):2130-2134.
PMID: 29696574 DOI: 10.1007/s11695-018-3256-2

Bariatric surgery offers a therapeutic alternative with favourable weight management, cardiovascular, metabolic and functional outcomes. Bariatric individuals often have functional impairments pre-operatively that can be addressed to improve post-operative results and eventual functional independence. Multidisciplinary team offers the best approach to address peri-operative needs and sustainable weight loss thereafter. We exemplified the application of cardiac rehabilitation therapeutic model in managing two bariatric clients with specific bariatric-related challenges. Our approach focuses on adaptive physical activity, sustainable lifestyle changes to promote post-operative weight loss through education and problem solving as well as secondary prevention of cardiovascular disease. Putting emphasis on addressing physical and psychosocial barriers towards physical activity alongside nutritional aspects potentially confers sustained if not better outcomes on weight reduction and functional improvement.

Matched MeSH terms: Secondary Prevention
The statins effects on HbA1c control among diabetic patients: An umbrella review of systematic reviews and meta-analyses of observational studies and clinical trials

Hammad MA, Abdo MS, Mashaly AM, Syed Sulaiman SA, Alghamdi S, Mangi AA, et al.

Diabetes Metab Syndr, 2019 07 08;13(4):2557-2564.
PMID: 31405676 DOI: 10.1016/j.dsx.2019.07.005

Statins have impacts on the metabolism of glucose that might influence the progress of diabetes in non-diabetics or affect glycemic control in patients with existing diabetes. Experimental proof has been contradictory about whether some statins display beneficial properties while others indicate harmful impressions. Some systematic reviews of statins had stated conflicting findings on the concern of glucose metabolism. The current study investigates the published systematic reviews and meta-analyses to combine their results and give a clear situation regarding the influence of statins therapy on glycated hemoglobin (HbA1c). This study has valuable strength points; long follow-up period and big sample size.

Matched MeSH terms: Secondary Prevention
Fulltext Organ-Specific Analysis of Morus alba Using a Gel-Free/Label-Free Proteomic Technique

Zhu W, Zhong Z, Liu S, Yang B, Komatsu S, Ge Z, et al.

Int J Mol Sci, 2019 Jan 16;20(2).
PMID: 30654535 DOI: 10.3390/ijms20020365

Morus alba is an important medicinal plant that is used to treat human diseases. The leaf, branch, and root of Morus can be applied as antidiabetic, antioxidant, and anti-inflammatory medicines, respectively. To explore the molecular mechanisms underlying the various pharmacological functions within different parts of Morus, organ-specific proteomics were performed. Protein profiles of the Morus leaf, branch, and root were determined using a gel-free/label-free proteomic technique. In the Morus leaf, branch, and root, a total of 492, 414, and 355 proteins were identified, respectively, including 84 common proteins. In leaf, the main function was related to protein degradation, photosynthesis, and redox ascorbate/glutathione metabolism. In branch, the main function was related to protein synthesis/degradation, stress, and redox ascorbate/glutathione metabolism. In root, the main function was related to protein synthesis/degradation, stress, and cell wall. Additionally, organ-specific metabolites and antioxidant activities were analyzed. These results revealed that flavonoids were highly accumulated in Morus root compared with the branch and leaf. Accordingly, two root-specific proteins named chalcone flavanone isomerase and flavonoid 3,5-hydroxylase were accumulated in the flavonoid pathway. Consistent with this finding, the content of the total flavonoids was higher in root compared to those detected in branch and leaf. These results suggest that the flavonoids in Morus root might be responsible for its biological activity and the root is the main part for flavonoid biosynthesis in Morus.

Matched MeSH terms: Secondary Metabolism
Fulltext Characterization and comparative sequence analysis of the DNA mismatch repair MSH2 and MSH7 genes from tomato

Tam SM, Samipak S, Britt A, Chetelat RT

Genetica, 2009 Dec;137(3):341-54.
PMID: 19690966 DOI: 10.1007/s10709-009-9398-3

DNA mismatch repair proteins play an essential role in maintaining genomic integrity during replication and genetic recombination. We successfully isolated a full length MSH2 and partial MSH7 cDNAs from tomato, based on sequence similarity between MutS and plant MSH homologues. Semi-quantitative RT-PCR reveals higher levels of mRNA expression of both genes in young leaves and floral buds. Genetic mapping placed MSH2 and MSH7 on chromosomes 6 and 7, respectively, and indicates that these genes exist as single copies in the tomato genome. Analysis of protein sequences and phylogeny of the plant MSH gene family show that these proteins are evolutionarily conserved, and follow the classical model of asymmetric protein evolution. Genetic manipulation of the expression of these MSH genes in tomato will provide a potentially useful tool for modifying genetic recombination and hybrid fertility between wide crosses.

Matched MeSH terms: Protein Structure, Secondary
Investigating the binding preferences of small molecule inhibitors of human protein arginine methyltransferase 1 using molecular modelling

Hong W, Li J, Laughton CA, Yap LF, Paterson IC, Wang H

J Mol Graph Model, 2014 Jun;51:193-202.
PMID: 24937176 DOI: 10.1016/j.jmgm.2014.05.010

Protein arginine methyltransferases (PRMTs) catalyse the methylation of arginine residues of target proteins. PRMTs utilise S-adenosyl methionine (SAM) as the methyl group donor, leading to S-adenosyl homocysteine (SAH) and monomethylarginine (mMA). A combination of homology modelling, molecular docking, Active Site Pressurisation, molecular dynamic simulations and MM-PBSA free energy calculations is used to investigate the binding poses of three PRMT1 inhibitors (ligands 1-3), which target both SAM and substrate arginine binding sites by containing a guanidine group joined by short linkers with the SAM derivative. It was assumed initially that the adenine moieties of the inhibitors would bind in sub-site 1 (PHE44, GLU137, VAL136 and GLU108), the guanidine side chain would occupy sub-site 2 (GLU 161, TYR160, TYR156 and TRP302), with the amino acid side chain occupying sub-site 3 (GLU152, ARG62, GLY86 and ASP84; pose 1). However, the SAH homocysteine moiety does not fully occupy sub-site 3, suggesting another binding pose may exist (pose 2), whereby the adenine moiety binds in sub-site 1, the guanidine side chain occupies sub-site 3, and the amino acid side chain occupies sub-site 2. Our results indicate that ligand 1 (pose 1 or 2), ligand 2 (pose 2) and ligand 3 (pose 1) are the predominant binding poses and we demonstrate for the first time that sub-site 3 contains a large space that could be exploited in the future to develop novel inhibitors with higher binding affinities.

Matched MeSH terms: Protein Structure, Secondary
Toluene promotes lid 2 interfacial activation of cold active solvent tolerant lipase from Pseudomonas fluorescens strain AMS8

Yaacob N, Mohamad Ali MS, Salleh AB, Rahman RNZRA, Leow ATC

J Mol Graph Model, 2016 07;68:224-235.
PMID: 27474867 DOI: 10.1016/j.jmgm.2016.07.003

The utilization of cold active lipases in organic solvents proves an excellent approach for chiral synthesis and modification of fats and oil due to the inherent flexibility of lipases under low water conditions. In order to verify whether this lipase can function as a valuable synthetic catalyst, the mechanism concerning activation of the lid and interacting solvent residues in the presence of organic solvent must be well understood. A new alkaline cold-adapted lipase, AMS8, from Pseudomonas fluorescens was studied for its structural adaptation and flexibility prior to its exposure to non-polar, polar aprotic and protic solvents. Solvents such as ethanol, toluene, DMSO and 2-propanol showed to have good interactions with active sites. Asparagine (Asn) and tyrosine (Tyr) were key residues attracted to solvents because they could form hydrogen bonds. Unlike in other solvents, Phe-18, Tyr-236 and Tyr-318 were predicted to have aromatic-aromatic side-chain interactions with toluene. Non-polar solvent also was found to possess highest energy binding compared to polar solvents. Due to this circumstance, the interaction of toluene and AMS8 lipase was primarily based on hydrophobicity and molecular recognition. The molecular dynamic simulation showed that lid 2 (residues 148-167) was very flexible in toluene and Ca(2+). As a result, lid 2 moves away from the catalytic areas, leaving an opening for better substrate accessibility which promotes protein activation. Only a single lid (lid 2) showed the movement following interactions with toluene, although AMS8 lipase displayed double lids. The secondary conformation of AMS8 lipase that was affected by toluene observed a reduction of helical strands and increased coil structure. Overall, this work shows that cold active lipase, AMS8 exhibits distinguish interfacial activation and stability in the presence of polar and non-polar solvents.

Matched MeSH terms: Protein Structure, Secondary

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