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Fulltext Cardiac biomarkers in chronic kidney disease are independently associated with myocardial edema and diffuse fibrosis by cardiovascular magnetic resonance

Arcari L, Engel J, Freiwald T, Zhou H, Zainal H, Gawor M, et al.

J Cardiovasc Magn Reson, 2021 06 07;23(1):71.
PMID: 34092229 DOI: 10.1186/s12968-021-00762-z

BACKGROUND: High sensitivity cardiac troponin T (hs-cTnT) and NT-pro-brain natriuretic peptide (NT-pro BNP) are often elevated in chronic kidney disease (CKD) and associated with both cardiovascular remodeling and outcome. Relationship between these biomarkers and quantitative imaging measures of myocardial fibrosis and edema by T1 and T2 mapping remains unknown.
METHODS: Consecutive patients with established CKD and estimated glomerular filtration rate (eGFR)

Matched MeSH terms: Peptide Fragments
Fulltext Consensus Statement on the Use of Bone Turnover Markers for Short-Term Monitoring of Osteoporosis Treatment in the Asia-Pacific Region

Wu CH, Chang YF, Chen CH, Lewiecki EM, Wüster C, Reid I, et al.

J Clin Densitom, 2021;24(1):3-13.
PMID: 31010789 DOI: 10.1016/j.jocd.2019.03.004

Osteoporosis is a major health issue. By 2050, a greater than 2-fold increase in patients number with hip fractures will occur in Asia representing 50% of all hip fractures worldwide. For the Asia-Pacific (AP) region, more efforts on controlling osteoporosis and the subsequent fractures are crucial. Bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA) is commonly used to diagnose osteoporosis and monitor osteoporosis treatment. However, the inconvenience, cost, limited availability of DXA and the delay in detection of BMD changes after treatment initiation support an important role for bone turnover markers (BTMs), as short-term tools to monitor therapy. With regards to low adherence rates of medical treatment of osteoporosis, the experts reached consensus on the use of BTMs for both raising awareness and short-term monitoring of osteoporosis treatment in the AP region. The experts endorse the use of BTMs, especially serum C-terminal telopeptide of type 1 collagen (CTX) and serum procollagen type 1 N propeptide (P1NP), as short-term monitoring tools to help clinicians assess the responses to osteoporosis therapies and appropriately adjust treatment regimens earlier than BMD. Either the absolute values or the degree of change from baseline in BTMs can be used to monitor the potential efficacy of osteoporosis therapies. The use of BTMs can be incorporated in osteoporosis care programs, such as fracture liaison service (FLS), to improve patient adherence and treatment outcomes. Encouraging sufficient reimbursement from health care systems may facilitate widespread use of BTMs in clinical practice in the AP region.

Matched MeSH terms: Peptide Fragments
Serum levels of bone-specific alkaline phosphatase and procollagen type I carboxyterminal peptide in vitamin D deficiency

Nawawi H, Girgis SI

Southeast Asian J. Trop. Med. Public Health, 2002;33 Suppl 2:124-30.
PMID: 12755282

Vitamin D deficiency in adults causes osteomalacia where there is a defect in bone mineralization resulting in an excess of unmineralised osteoid in the bone matrix. The aim of this study was to evaluate the markers of bone formation: total (TALP), bone-specific alkaline phosphatase (BSALP) and procollagen type I carboxyterminal peptide (PICP) in vitamin D deficiency. We studied 100 vitamin D deficient subjects and 82 gender-matched controls. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D level of less than 7 ng/ml, and greater than 10 ng/ml for normal controls. Serum TALP assay was performed by a standard automated method, BSALP and PICP were measured by enzyme immunoassays (Metra Biosystems) and vitamin D by radioimmunoassay. There was significant difference in the TALP between female vitamin D deficient and control subjects (mean +/- sem = 99.8 +/- 8.2 vs 70.5 +/- 2.8 iu/l, p<0.001). Elevated serum TALP (>130 iu/l) was found in 20% (20/100) of the vitamin D deficient patients. There were no significant differences in BSALP or PICP between vitamin D deficient patients and gender-matched control subjects. There was no correlation between vitamin D and PICP in patients but in control subjects, a significant negative correlation (r= -0.431, p<0.0001) was found. In conclusion, although elevated TALP was observed in a minority of vitamin D deficient patients, it is a better marker than PICP. The lack of PICP response in vitamin D deficient subjects suggests the possibility of vitamin D deficiency leading to a block in osteoblast differentiation.

Matched MeSH terms: Peptide Fragments/blood*
Pathotyping of Newcastle disease virus with a filamentous bacteriophage

Ramanujam P, Tan WS, Nathan S, Yusoff K

Biotechniques, 2004 Feb;36(2):296-300, 302.
PMID: 14989094

A filamentous phage bearing the peptide sequence TLTTKLY was isolated from a heptapeptide phage display library against a velogenic Newcastle disease virus (NDV). In order to investigate the potential of this specific phage as an immunological reagent in virus pathotyping, an enzyme-linked immunosorbent assay (ELISA)-based method was developed. This method can differentiate the velogenic strains from the mesogenic and lentogenic strains. An equilibrium-binding assay in solution showed that the interactions between the phage and all the NDV strains gave rise to two widely differing dissociation constants (Kdrel). Based upon the first Kdrel values, NDV strains can be classified into two groups; the first comprises the velogenic strains, and the second consists of the mesogenic and lentogenic strains. These results indicate a high degree of correlation between the binding affinities and pathotyping of NDV strains using the TLTTKLY phage.

Matched MeSH terms: Peptide Fragments/genetics
Graphene oxide-gold nanoparticle-aptamer complexed probe for detecting amyloid beta oligomer by ELISA-based immunoassay

Zhao J, Chang W, Liu L, Xing X, Zhang C, Meng H, et al.

J Immunol Methods, 2021 02;489:112942.
PMID: 33333060 DOI: 10.1016/j.jim.2020.112942

Highly sensitive and easy detection method for Alzheimer's disease (AD) with a suitable biomarker is mandatory for preventing the factors resulting from AD. This research reports a modified ELISA with graphene for the detection of AD biomarker amyloid beta (Aβ) oligomer. Gold nanoparticle (AuNP) conjugated aptamer was used as the capture probe and attached on ELISA-graphene oxide surface through the amine linker. Antibody was used as the detection molecule to reach the maximum detection of Aβ oligomer. Suitable level of APTMS (2%), size of AuNP (30 nm) and aptamer concentration (2 μM) were optimized. This sandwich pattern of aptamer-Aβ oligomer-antibody helps to reach the detection at 50 pM on the optimized ELISA surface and the control experiments in the absence of Aβ oligomer or anti-Aβ oligomer antibody did not show the significant optical detection at 492 nm, indicting the specific detection. Further, Aβ oligomer spiked artificial cerebrospinal fluid did not interfere the detection of Aβ oligomer, confirming the selective detection. This new and modified ELISA surface helps to reach the lower detection of Aβ oligomer and diagnose AD.

Matched MeSH terms: Peptide Fragments/analysis*
Evaluation of the Expression of Amyloid Precursor Protein and the Ratio of Secreted Amyloid Beta 42 to Amyloid Beta 40 in SH-SY5Y Cells Stably Transfected with Wild-Type, Single-Mutant and Double-Mutant Forms of the APP Gene for the Study of Alzheimer's Disease Pathology

Pahrudin Arrozi A, Shukri SNS, Wan Ngah WZ, Mohd Yusof YA, Ahmad Damanhuri MH, Makpol S

Appl Biochem Biotechnol, 2017 Nov;183(3):853-866.
PMID: 28417423 DOI: 10.1007/s12010-017-2468-6

Neuroblastoma cell lines such as SH-SY5Y are the most frequently utilized models in neurodegenerative research, and their use has advanced the understanding of the pathology of neurodegeneration over the past few decades. In Alzheimer's disease (AD), several pathogenic mutations have been described, all of which cause elevated levels of pathological hallmarks such as amyloid-beta (Aβ). Although the genetics of Alzheimer's disease is well known, familial AD only accounts for a small number of cases in the population, with the rest being sporadic AD, which contains no known mutations. Currently, most of the in vitro models used to study AD pathogenesis only examine the level of Aβ42 as a confirmation of successful model generation and only perform comparisons between wild-type APP and single mutants of the APP gene. Recent findings have shown that the Aβ42/40 ratio in cerebrospinal fluid (CSF) is a better diagnostic indicator for AD patients than is Aβ42 alone and that more extensive Aβ formation, such as accumulation of intraneuronal Aβ, Aβ plaques, soluble oligomeric Aβ (oAβ), and insoluble fibrillar Aβ (fAβ) occurs in TgCRND8 mice expressing a double-mutant form (Swedish and Indiana) of APP, later leading to greater progressive impairment of the brain. In this study, we generated SH-SY5Y cells stably transfected separately with wild-type APP, the Swedish mutation of APP, and the Swedish and Indiana mutations of APP and evaluated the APP expression as well as the Aβ42/40 ratio in those cells. The double-mutant form of APP (Swedish/Indiana) expressed markedly high levels of APP protein and showed a high Aβ2/40 ratio compared to wild-type and single-mutant cells.

Matched MeSH terms: Peptide Fragments/secretion*
An impedimetric micro-immunosensing assay to detect Alzheimer's disease biomarker: Aβ40

Zakaria N, Ramli MZ, Ramasamy K, Meng LS, Yean CY, Banga Singh KK, et al.

Anal Biochem, 2018 08 15;555:12-21.
PMID: 29879415 DOI: 10.1016/j.ab.2018.05.031

A miniaturized biosensing platform, based on monoclonal amyloid-beta antibodies (mAβab) that were immobilized on a disc-shaped platinum/iridium (Pt/Ir) microelectrode surface coupled with an impedimetric signal transducer, was developed for the label-free and sensitive detection of amyloid-beta peptide fragment 1-40 (Aβ40); a reliable biomarker for early diagnosis of Alzheimer's disease (AD). A Pt/Ir microelectrode was electropolymerized with poly (ortho-phenylenediamine), a conducting free amine-containing aromatic polymer; followed by crosslinking with glutaraldehyde for subsequent coupling of mAβab on the microelectrode surface. This modification strategy efficiently improved the impedimetric detection performance of Aβ40 in terms of charge transfer resistance (∼400-fold difference) and normalized impedance magnitude percentage change (∼40% increase) compared with a passive adsorption-based immobilization method. The sensitivity of the micro-immunosensing assay was found to be 1056 kΩ/(pg/mL)/cm2 and the limit of detection was found to be 4.81 pg/mL with a dynamic range of 1-104 pg/mL (R2 = 0.9932). The overall precision of the assay, as measured by relative standard deviation, ranged from 0.84 to 5.15%, demonstrating its reliability and accuracy; while in respect to assay durability and stability, the immobilized mAβab were able to maintain 80% of their binding activity to Aβ40 after incubation for 48 h at ambient temperature (25 °C). To validate the practical applicability, the assay was tested using brain tissue lysates prepared from AD-induced rats. Results indicate that the proposed impedimetric micro-immunosensing platform is highly versatile and adaptable for the quantitative detection of other disease-related biomarkers.

Matched MeSH terms: Peptide Fragments/blood*
Fulltext Effect of Sequence of Fruit Intake in a Meal on Satiety

Abdul Hakim BN, Yahya HM, Shahar S, Abdul Manaf Z, Damanhuri H

Int J Environ Res Public Health, 2019 11 13;16(22).
PMID: 31766283 DOI: 10.3390/ijerph16224464

Little is known about the effects of manipulating sequence of fruit consumption during a meal in suppressing an individual's appetite. Therefore, we investigate the effects of the sequence of fruit intake on satiety and blood glucose in a group of 17 healthy, young male adults. This intervention study repeatedly measured the effects of fruit intake (120 g red apple) before and after a meal and control (no fruit). Ad libitum test meal was weighed before and after a meal. Subjective appetite rating and appetite-related hormones were assessed at regular time intervals. The satiety score was significantly higher for fruit intake before a meal followed by after a meal and control (p < 0.05). Eating fruit before a meal reduced 18.5% (166 kcal) subsequent energy intake compared to control (p < 0.05). Fruit intake before a meal had a significantly higher incremental area under the curve (iAUC) of Glucagon-like peptide 1 (GLP-1), compared to after a meal (p < 0.05). There were no differences in plasma changes of ghrelin, Cholecystokinin 8 (CCK8), or blood glucose in all sessions. Consuming fruit before a meal potentially enhanced satiety. Further research is required to confirm both short- and long-term effects of the sequence of fruit intake on appetite regulation in a wider population.

Matched MeSH terms: Peptide Fragments/blood
Fulltext Asymptomatic neurotoxicity of amyloid β-peptides (Aβ1-42 and Aβ25-35) on mouse embryonic stem cell-derived neural cells

Mansor NI, Ntimi CM, Abdul-Aziz NM, Ling KH, Adam A, Rosli R, et al.

Bosn J Basic Med Sci, 2021 Feb 01;21(1):98-110.
PMID: 32156249 DOI: 10.17305/bjbms.2020.4639

One of the strategies in the establishment of in vitro oxidative stress models for neurodegenerative diseases, such as Alzheimer's disease (AD), is to induce neurotoxicity by amyloid beta (Aβ) peptides in suitable neural cells. Presently, data on the neurotoxicity of Aβ in neural cells differentiated from stem cells are limited. In this study, we attempted to induce oxidative stress in transgenic 46C mouse embryonic stem cell-derived neurons via treatment with Aβ peptides (Aβ1-42 and Aβ25-35). 46C neural cells were generated by promoting the formation of multicellular aggregates, embryoid bodies in the absence of leukemia inhibitory factor, followed by the addition of all-trans retinoic acid as the neural inducer. Mature neuronal cells were exposed to different concentrations of Aβ1-42 and Aβ25-35 for 24 h. Morphological changes, cell viability, and intracellular reactive oxygen species (ROS) production were assessed. We found that 100 µM Aβ1-42 and 50 µM Aβ25-35 only promoted 40% and 10%, respectively, of cell injury and death in the 46C-derived neuronal cells. Interestingly, treatment with each of the Aβ peptides resulted in a significant increase of intracellular ROS activity, as compared to untreated neurons. These findings indicate the potential of using neurons derived from stem cells and Aβ peptides in generating oxidative stress for the establishment of an in vitro AD model that could be useful for drug screening and natural product studies.

Matched MeSH terms: Peptide Fragments/toxicity*
Fulltext Generation of High Affinity Anti-Peptide Polyclonal Antibodies Recognizing Goat αs1-Casein

Mohsin AZ, Sukor R, Selamat J, Meor Hussin AS, Ismail IH, Jambari NN, et al.

Molecules, 2020 Jun 05;25(11).
PMID: 32516919 DOI: 10.3390/molecules25112622

The chemical, technological and allergy properties of goat's milk are significantly affected by the level of αs1-casein. Detection and quantification of αs1-casein requires high-specificity methods to overcome high-sequence similarity between this protein and others in the casein family. Unavailability of antibodies with high affinity and specificity towards goat αs1-casein hinders the development of immuno-based analytical methods such as enzyme-linked immunosorbent assay (ELISA) and biosensors. Here, we report the generation of polyclonal antibodies (or immunoglobulins, IgGs) raised towards goat αs1-casein N- (Nter) and C-terminal (Cter) peptide sequences. The Nter and Cter peptides of goat αs1-casein were immunized in rabbits for the generation of antisera, which were purified using protein G affinity chromatography. The binding affinity of the antisera and purified IgGs were tested and compared using indirect ELISA, where peptide-BSA conjugates and goat αs1-casein were used as the coating antigens. The Nter antiserum displayed higher titer than Cter antiserum, at 1/64,000 and 1/32,000 dilutions, respectively. The purification step further yielded 0.5 mg/mL of purified IgGs from 3 mL of antisera. The purified Nter IgG showed a significantly (p < 0.05) higher binding affinity towards peptide-BSA and goat αs1-casein, with lower Kd value at 5.063 × 10-3 μM compared to 9.046 × 10-3 μM for the Cter IgG. A cross-reactivity test showed that there was no binding in neither Nter nor Cter IgGs towards protein extracts from the milk of cow, buffalo, horse and camel. High-quality antibodies generated will allow further development of immuno-based analytical methods and future in vitro studies to be conducted on goat αs1-casein.

Matched MeSH terms: Peptide Fragments/immunology*
Isolation and characterization of pepsin-solubilized collagen from the integument of sea cucumber (Stichopus vastus)

Abedin MZ, Karim AA, Ahmed F, Latiff AA, Gan CY, Che Ghazali F, et al.

J Sci Food Agric, 2013 Mar 30;93(5):1083-8.
PMID: 22936269 DOI: 10.1002/jsfa.5854

Sea cucumber (Stichopus vastus) is considered an underutilized resource, since only its stomach and intestines are eaten raw as salad in a few countries and the remaining parts, especially the integument rich in collagen, is discarded. Hence a valuable by-product having potential nutraceutical and pharmaceutical applications is wasted. In the present investigation, pepsin-solubilized collagen (PSC) from the integument of S. vastus was isolated, purified and characterized.

Matched MeSH terms: Peptide Fragments/economics; Peptide Fragments/isolation & purification; Peptide Fragments/metabolism; Peptide Fragments/chemistry
Biological evaluation of synthetic α,β-unsaturated carbonyl based cyclohexanone derivatives as neuroprotective novel inhibitors of acetylcholinesterase, butyrylcholinesterase and amyloid-β aggregation

Zha GF, Zhang CP, Qin HL, Jantan I, Sher M, Amjad MW, et al.

Bioorg Med Chem, 2016 05 15;24(10):2352-9.
PMID: 27083471 DOI: 10.1016/j.bmc.2016.04.015

A series of new α,β-unsaturated carbonyl-based cyclohexanone derivatives was synthesized by simple condensation method and all compounds were characterized by using various spectroscopic techniques. New compounds were evaluated for their effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). These compounds were also screened for in vitro cytotoxicity and for inhibitory activity for self-induced Aβ1-42 aggregation. The effect of these compounds against amyloid β-induced cytotoxicity was also investigated. The findings of in vitro experiment revealed that most of these compounds exhibited potent inhibitory activity against AChE and self-induced Aβ1-42 aggregation. The compound 3o exhibited best AChE (IC50=0.037μM) inhibitory potential. Furthermore, compound 3o disassembled the Aβ fibrils produced by self-induced Aβ aggregation by 76.6%. Compounds containing N-methyl-4-piperidone linker, showed high acetylcholinesterase and self-induced Aβ aggregation inhibitory activities as compared to reference drug donepezil. The pre-treatment of cells with synthetic compounds protected them against Aβ-induced cell death by up to 92%. Collectively, these findings suggest that some compounds from this series have potential to be promising multifunctional agents for AD treatment and our study suggest the cyclohexanone derivatives as promising new inhibitors for AChE and BuChE, potentially useful to treat neurodegenerative diseases.

Matched MeSH terms: Peptide Fragments/antagonists & inhibitors; Peptide Fragments/metabolism*
Human immunodeficiency virus type 1 subtypes among Malaysian intravenous drug users

Saraswathy TS, Ng KP, Sinniah M

Southeast Asian J. Trop. Med. Public Health, 2000 Jun;31(2):283-6.
PMID: 11127327

The HIV-1 genetic variation in 60 infected Malaysian intravenous drug users (IDU) was studied by comparison of the nucleotide sequences and their predicted amino acid sequences in the V3 loop of the external glycoprotein gp120. In this study, HIV-1 B, C and E subtypes were identified among Malaysian IDU, with HIV-1 B being the predominant subtype (91.7%). HIV-1 C and HIV-1 E were minority subtypes among Malaysian IDU. Analysis of the amino acid alignment of the C2-V3 region of the env gene suggests a genetic relationship between Thai and Malaysian B and E subtype strains. This study serves as a baseline for monitoring HIV-1 genetic diversity and spread in Malaysia.

Matched MeSH terms: Peptide Fragments/genetics*; Peptide Fragments/chemistry
Inhibition of hepatitis B virus assembly with synthetic peptides derived from the viral surface and core antigens

Tan WS

J Gen Appl Microbiol, 2002 Apr;48(2):103-7.
PMID: 12469306

The long surface antigen (L-HBsAg) of hepatitis B virus (HBV) plays a central role in the production of infectious virions. During HBV morphogenesis, both the PreS and S domains of L-HBsAg form docking sites for the viral nucleocapsids. Thus, a compound that disrupts the interaction between the L-HBsAg and nucleocapsids could serve as a therapeutic agent against the virus based upon inhibition of morphogenesis. Synthetic peptides correspond to the binding sites in L-HBsAg inhibited the association of L-HBsAg with core antigen (HBcAg). A synthetic peptide carrying the epitope for a monoclonal antibody to the PreS1 domain competed weakly with L-HBsAg for HBcAg, but peptides corresponding to a linear sequence at the tip of the nucleocapsid spike did not, showing that the competing peptide does not resemble the tip of the spike.

Matched MeSH terms: Peptide Fragments/chemical synthesis; Peptide Fragments/pharmacology*
Fulltext Sandwich Electrochemical Immunosensor for Early Detection of Tuberculosis Based on Graphene/Polyaniline-Modified Screen-Printed Gold Electrode

Mohd Azmi UZ, Yusof NA, Kusnin N, Abdullah J, Suraiya S, Ong PS, et al.

Sensors (Basel), 2018 Nov 14;18(11).
PMID: 30441776 DOI: 10.3390/s18113926

A rapid and sensitive sandwich electrochemical immunosensor was developed based on the fabrication of the graphene/polyaniline (GP/PANI) nanocomposite onto screen-printed gold electrode (SPGE) for detection of tuberculosis biomarker 10-kDa culture filtrate protein (CFP10). The prepared GP/PANI nanocomposite was characterized using Fourier transform infrared spectroscopy (FTIR) and field emission scanning electron microscopy (FESEM). The chemical bonding and morphology of GP/PANI-modified SPGE were studied by Raman spectroscopy and FESEM coupled with energy dispersive X-ray spectroscopy, respectively. From both studies, it clearly showed that GP/PANI was successfully coated onto SPGE through drop cast technique. Cyclic voltammetry was used to study the electrochemical properties of the modified electrode. The effective surface area for GP/PANI-modified SPGE was enhanced about five times compared with bare SPGE. Differential pulse voltammetry was used to detect the CFP10 antigen. The GP/PANI-modified SPGE that was fortified with sandwich type immunosensor exhibited a wide linear range (20⁻100 ng/mL) with a low detection limit of 15 ng/mL. This proposed electrochemical immunosensor is sensitive, low sample volume, rapid and disposable, which is suitable for tuberculosis detection in real samples.

Matched MeSH terms: Peptide Fragments/immunology; Peptide Fragments/isolation & purification*
Activation of sphingosine 1-phosphate receptor-1 by SEW2871 improves cognitive function in Alzheimer's disease model rats

Asle-Rousta M, Oryan S, Ahmadiani A, Rahnema M

EXCLI J, 2013;12:449-61.
PMID: 26417237

Sphingosine-1 phosphate (S1P) is involved in a variety of cellular processes via activation of S1P receptors (S1PRs; S1PR1 to S1PR5) that are highly expressed in the brain. It has been shown that the level of S1P is reduced in the brain of Alzheimer's disease (AD) patients. However, there is no study designed to evaluate the expression of S1PRs in AD brains. The objectives of the present work are (1) to examine the expression of S1PR1-3 in the hippocampus of beta amyloid (Aβ) 1-42 injected rats and (2) to clarify the effects of chronic S1PR1 activation on S1PR1-3 levels, spatial memory deficit and hippocampal damage in AD rats. SEW2871, the S1PR1 selective agonist, repeatedly was injected intraperitoneally during a period of two weeks. Upon Western Blot data bilateral intrahippocampal injection of Aβ1-42 decreased the expression of S1PR1 while increased S1PR2 level and did not affect that of S1PR3. We found that chronic administration of SEW2871 inhibited the reduction of S1PR1 expression and ameliorated spatial memory impairment in the Morris water maze task in rats. In addition, SEW2871 attenuated the Aβ1-42-induced hippocampal neuronal loss according to Nissl staining findings. Data in the current study highlights the importance of S1PR1 signaling pathway deregulation in AD development and suggests that activation of S1PR1 may represent a potential approach for developing new therapeutics to manage memory deficit and apoptosis associated with neurodegenerative disorders such as AD.

Matched MeSH terms: Peptide Fragments
Synthesis, Structural Characterization, and Bioactivity of the Stable Peptide RCB-1 from Ricinus communis

Boldbaatar D, Gunasekera S, El-Seedi HR, Göransson U

J Nat Prod, 2015 Nov 25;78(11):2545-51.
PMID: 26509914 DOI: 10.1021/acs.jnatprod.5b00463

The Ricinus communis biomarker peptides RCB-1 to -3 comprise homologous sequences of 19 (RCB-1) or 18 (RCB-2 and -3) amino acid residues. They all include four cysteine moieties, which form two disulfide bonds. However, neither the 3D structure nor the biological activity of any of these peptides is known. The synthesis of RCB-1, using microwave-assisted, Fmoc-based solid-phase peptide synthesis, and a method for its oxidative folding are reported. The tertiary structure of RCB-1, subsequently established using solution-state NMR, reveals a twisted loop fold with antiparallel β-sheets reinforced by the two disulfide bonds. Moreover, RCB-1 was tested for antibacterial, antifungal, and cytotoxic activity, as well as in a serum stability assay, in which it proved to be remarkably stable.

Matched MeSH terms: Peptide Fragments/isolation & purification*; Peptide Fragments/pharmacology; Peptide Fragments/chemistry
Modulation of LOX and COX pathways via inhibition of amyloidogenesis contributes to mitoprotection against β-amyloid oligomer-induced toxicity in an animal model of Alzheimer's disease in rats

Kalra J, Kumar P, Majeed AB, Prakash A

Pharmacol. Biochem. Behav., 2016 Jul-Aug;146-147:1-12.
PMID: 27106205 DOI: 10.1016/j.pbb.2016.04.002

Several lines of evidence indicate that beta amyloid (β-A) production, neurofibrillary tangles and neuroinflammation are interrelated in the pathogenesis of Alzheimer's disease (AD). AD is associated with enhanced β-A production and accumulation resulting in neuroinflammation probably via activation of lipoxygenase (LOX) and cyclooxygenase (COX) pathways. Therefore, the present study was designed to investigate the role of LOX and COX inhibitors (zafirlukast and valdecoxib) in amyloidogenesis in β-A1-42 oligomer induced experimental AD in rats. The behavioral activities were assessed using actophotometer, novel object recognition test (ORT), Morris water maze (MWM) followed by biochemical assessments, determination of proinflammatory cytokines and mediators (TNF-α, IL-1β and PGE2), β-A1-42 levels and histopathological analysis. ICV administration of β-A1-42 oligomer produced significant impairment in memory consolidation. In addition to this significant increase in mito-oxidative stress, neuroinflammatory markers, acetylcholinesterase (AChE) toxicity, β-A1-42 level, neuronal cell death and neuroinflammation are more profound in β-A1-42 oligomer treated AD rats. Administration of zafirlukast (15 and 30mg/kg), and valdecoxib (5 and 10mg/kg) significantly improved the behavioral performances and showed significant reversal of mito-oxidative damage declining the neuroinflammation in β-A1-42 oligomer treated rats. Furthermore, more profound effects were observed at the sub-therapeutic dose combination of zafirlukast (15mg/kg) and valdecoxib (5mg/kg). The results of the present study indicate that protective effects of zafirlukast and valdecoxib are achieved through the blockade of release of LOX and COX metabolites therefore, representing a new therapeutic target for treating AD and other neurodegenerative disorders.

Matched MeSH terms: Peptide Fragments/administration & dosage; Peptide Fragments/metabolism; Peptide Fragments/toxicity*
Renal Outcomes Associated with the Use of Non-Insulin Antidiabetic Pharmacotherapy: A Review of Current Evidence and Recommendations

Elnaem MH, Mansour NO, Nahas AF, Baraka MA, Elkalmi R, Cheema E

Int J Gen Med, 2020;13:1395-1409.
PMID: 33324086 DOI: 10.2147/IJGM.S285191

Background: This study aims to discuss, summarize and compare the renal outcomes associated with non-insulin antidiabetic (AD) pharmacotherapy prescribed for patients with type 2 diabetes mellitus (T2DM).
Methods: A systematic search using predefined search terms in three scholarly databases, ScienceDirect, Google Scholar, and PubMed, was conducted. Original research articles published in the English language between 2012 and 2020 that reported renal outcomes associated with the use of non-insulin AD pharmacotherapy were eligible for inclusion. Review articles, meta-analysis studies, and conference proceedings were excluded. A study-specific data extraction form was designed to extract the author's name, country, publication year, study design, study population, objectives, key findings, and conclusions. A narrative review of the key findings that focused on renal outcomes and renal safety issues was conducted.
Results: Of the 18,872 results identified through the initial search, a total of 32 articles were included in this review. Of these, 18 of the included articles reported the renal outcomes of newer antidiabetic medications, eg, SGLT2 inhibitors and GLP-1 agonists. Eight studies focussed on the well-established antidiabetic medications, eg, metformin and sulphonylureas. The review reported three main types of the clinical impact of the prescribed AD on the renal outcomes: "renoprotective effects", "no additional risk" and "associated with a decline in renal parameters". Seventeen studies reported the renoprotective effects of AD, including SGLT2i studies (n=8), GLP1 studies (n=6), and DPP4i studies (n=3). The reported renoprotective effects included slowing down the GFR decline, improving albuminuria, and reducing renal adverse events. The "no additional risk" impact was reported in eight studies, including DPP4i studies (n=3), two SGLT2i studies (n=2), metformin studies (n=2), and one study involving pioglitazone. Furthermore, seven studies highlighted the "associated with a decline in renal parameters" effect. Of these, three involved SGLT2i, two with metformin, and one for each DPP4i and sulphonylurea.
Conclusion: More than half of the studies included in this review supported the renoprotective effects associated with the use of AD medications, particularly GLP-1A, SGLT2i, and some of the DPP4i. Further studies involving patients with various stages of chronic kidney disease (CKD) are required to compare AD medications' renal effects, particularly the newer agents.

Matched MeSH terms: Peptide Fragments
Nuclear magnetic resonance structure and IgE epitopes of Blo t 5, a major dust mite allergen

Chan SL, Ong TC, Gao YF, Tiong YS, Wang de Y, Chew FT, et al.

J Immunol, 2008 Aug 15;181(4):2586-96.
PMID: 18684949

A high incidence of sensitization to Blomia tropicalis, the predominant house dust mite species in tropical regions, is strongly associated with allergic diseases in Singapore, Malaysia, and Brazil. IgE binding to the group 5 allergen, Blo t 5, is found to be the most prevalent among all B. tropicalis allergens. The NMR structure of Blo t 5 determined represents a novel helical bundle structure consisting of three antiparallel alpha-helices. Based on the structure and sequence alignment with other known group 5 dust mite allergens, surface-exposed charged residues have been identified for site-directed mutagenesis and IgE binding assays. Four charged residues, Glu76, Asp81, Glu86, and Glu91 at around the turn region connecting helices alpha2 and alpha3 have been identified to be involved in the IgE binding. Using overlapping peptides, we have confirmed that these charged residues are located on a major putative linear IgE epitope of Blo t 5 from residues 76-91 comprising the sequence ELKRTDLNILERFNYE. Triple and quadruple mutants have been generated and found to exhibit significantly lower IgE binding and reduced responses in skin prick tests. The mutants induced similar PBMC proliferation as the wild-type protein but with reduced Th2:Th1 cytokines ratio. Mass screening on a quadruple mutant showed a 40% reduction in IgE binding in 35 of 42 sera of atopic individuals. Findings in this study further stressed the importance of surface-charged residues on IgE binding and have implications in the cross-reactivity and use of Blo t 5 mutants as a hypoallergen for immunotherapy.

Matched MeSH terms: Peptide Fragments/immunology; Peptide Fragments/metabolism; Peptide Fragments/chemistry

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