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Fulltext Antigenic membrane proteins of virulent variant of Entamoeba histolytica HM-1:IMSS

Kumarasamy G, Abdus Sani AA, Olivos-García A, Noordin R, Othman N

Pathog Glob Health, 2020 09;114(6):333-342.
PMID: 32536281 DOI: 10.1080/20477724.2020.1780402

Amoebiasis, caused by Entamoeba histolytica, is one of the leading parasitic infections in the world. This study was aimed at profiling antigenic membrane proteins of a virulent variant of E. histolytica HM-1:IMSS. The membrane proteins were extracted using ProteoExtract® kit (Merck, Darmstadt, Germany) or conventional method, separated using OFFGEL 3100 fractionator (Agilent Technologies, Santa Clara, California), followed by SDS-PAGE and Western blot analysis. Selected antigenic membrane proteins were identified using LC-ESI-MS/MS. Subsequently, the proteins were classified according to their biological processes and predictions were made on membrane and membrane-associated proteins. When the proteins were probed with pooled sera from amoebic liver abscess (ALA) patients, 10 and 15 antigenic proteins with molecular weights 25 to 200 kDa were identified using the ProteoExtract® kit and conventional method, respectively. LC-ESI-MS/MS identified 13 antigenic proteins, and both extraction methods predicted six of them as membrane and membrane-associated proteins. The topmost biological processes which comprised of six proteins were involved in cellular processes.. These antigenic membrane proteins merit further investigations as potential candidates for vaccine studies.

Matched MeSH terms: Membrane Proteins/immunology*; Protozoan Proteins/immunology*
Fulltext Survei penjagaan kanta sentuh di kalangan pemakai di Kuala Lumpur

Norhani Mohidin, Bakyah Lorenza Zaimuri

Jurnal Sains Kesihatan Malaysia, 2012;10(1):41-48.
MyJurnal

Kanta sentuh merupakan alat optikal yang sepatutnya selamat digunakan untuk pembetulan ralat refraksi atau kosmetik. Namun demikian terdapat permasalahan berkaitan kesihatan mata yang timbul akibat sikap pemakai yang tidak patuh kepada garis panduan penjagaan kanta yang disaran oleh pengamal kesihatan mata. Justeru itu satu soal selidik berkaitan penjagaan kanta sentuh dilakukan di kalangan pemakai kanta sentuh di sekitar Kuala Lumpur. Ia berdasarkan 22 set soalan terfokus kepada penjagaan kanta sentuh termasuklah tatacara pembersihan dan disifeksi, rawatan enzim, penggunaan agen pembasah dan kekerapan menghadiri pemeriksaan lanjutan. Di samping itu, terdapat enam soalan yang diaju untuk meninjau pengetahuan pemakai berkaitan penjagaan kanta sentuh yang selamat. Seramai 104 pemakai kanta sentuh mengambil bahagian dalam kajian ini. Lebih kurang 86% daripada mereka adalah wanita dengan min umur 24 ± 6 tahun. Lebih setengah daripada mereka memakai kanta sentuh jenis pakai buang. Hampir kesemuanya (98%) menggunakan sistem disinfeksi kimia. Hanya 68% pemakai yang dikaji mencuci kanta mereka setiap kali sebelum memakai dan selepas menanggalkannya. Tiga puluh peratus (30%) pemakai kanta sentuh menggunakan agen pembasah dan 40% menggunakan tablet protein. Enam puluh satu peratus (61%) daripada mereka menyatakan tidak membuat temu janji untuk pemeriksaan lanjutan. Enam soalan tertumpu kepada pengetahuan pemakai mengenai penjagaan kanta yang selamat dan min jawapan yang betul ialah 61.4%. Sebahagian pemakai kanta sentuh tidak mengikut arahan penjagaan kanta sentuh seperti yang disaran oleh pengamal kesihatan mata. Ramai yang tidak faham akan garis panduan pemakaian kanta yang selamat. Kajian ini menunjukkan sebahagian daripada pemakai kanta sentuh tidak mempunyai pengetahuan yang cukup mengenai risiko dan bahaya ke atas mata mereka kerana ketidakpatuhan pada arahan yang disaran oleh pengamal kesihatan mata. Pengamal kanta sentuh perlu memikirkan semula strategi untuk memastikan pemakai patuh kepada arahan berkaitan penjagaan kanta sentuh supaya komplikasi dapat dikurangkan.

Matched MeSH terms: Proteins
Current Updates on Bone Grafting Biomaterials and Recombinant Human Growth Factors Implanted Biotherapy for Spinal Fusion: A Review of Human Clinical Studies

Li G, Li P, Chen Q, Thu HE, Hussain Z

Curr Drug Deliv, 2019;16(2):94-110.
PMID: 30360738 DOI: 10.2174/1567201815666181024142354

BACKGROUND: Owing to their great promise in the spinal surgeries, bone graft substitutes have been widely investigated for their safety and clinical potential. By the current advances in the spinal surgery, an understanding of the precise biological mechanism of each bone graft substitute is mandatory for upholding the induction of solid spinal fusion.
OBJECTIVE: The aim of the present review is to critically discuss various surgical implications and level of evidence of most commonly employed bone graft substitutes for spinal fusion.
METHOD: Data was collected via electronic search using "PubMed", "SciFinder", "ScienceDirect", "Google Scholar", "Web of Science" and a library search for articles published in peer-reviewed journals, conferences, and e-books.
RESULTS: Despite having exceptional inherent osteogenic, osteoinductive, and osteoconductive features, clinical acceptability of autografts (patient's own bone) is limited due to several perioperative and postoperative complications i.e., donor-site morbidities and limited graft supply. Alternatively, allografts (bone harvested from cadaver) have shown great promise in achieving acceptable bone fusion rate while alleviating the donor-site morbidities associated with implantation of autografts. As an adjuvant to allograft, demineralized bone matrix (DBM) has shown remarkable efficacy of bone fusion, when employed as graft extender or graft enhancer. Recent advances in recombinant technologies have made it possible to implant growth and differentiation factors (bone morphogenetic proteins) for spinal fusion.
CONCLUSION: Selection of a particular bone grafting biotherapy can be rationalized based on the level of spine fusion, clinical experience and preference of orthopaedic surgeon, and prevalence of donor-site morbidities.

Matched MeSH terms: Recombinant Proteins/administration & dosage; Bone Morphogenetic Proteins/administration & dosage
Pengambilan Fe, Mn dan Cu oleh Nepenthes sp. dalam tanih bekas lombong Pelepah Kanan Kota Tinggi, Johor

Sahibin Abd. Rahim, Tukimat Lihan, Zulfahmi Ali Rahman, Wan Mohd. Razi Idris, Azman Hashim, Sharilnizam M. Yusof, et al.

Sains Malaysiana, 2007;36:9-13.

Kandungan logam berat Fe, Cu dan Mn dalam tanih serta tumbuhan Nepenthes sp yang diambil daripada kawasan bekas lombong bijih timah dan besi di Lombong Pelepah Kanan, Kota Tinggi, Johor telah dikaji. Kandungan logam berat telah ditentukan di dalam empat bahagian tumbuhan Nepenthes sp. iaitu di dalam akar, batang, daun dan periuk. Sebanyak 15 sampel tumbuhan Nepenthes sp dan tanih dikumpul untuk dianalisis. Komposisi logam-logam berat dalam sampel tanih diekstrak dengan menggunakan campuran asid nitrik dan asid perklorik. Kandungan logam berat dalam tumbuhan pula diekstrak melalui kaedah penghadaman basah. Kandungan logam berat di dalam larutan ekstrak tanih dan tumbuhan ditentukan dengan menggunakan alat Spektrofotometer Serapan Atom Kaedah Nyalaan (FAAS). Nilai Koefisien Penyerapan Biologi (BAC) dikira sebagai nisbah kandungan logam berat dalam tumbuhan kepada kandungan logam berat dalam tanih. Analisis tanih menunjukkan kawasan bekas lombong didominasi oleh pasir dan bersifat asid. Ia juga mempunyai kandungan bahan organik dan nilai kekonduksian elektrik yang rendah. Logam Fe mencatatkan kepekatan purata paling tinggi di dalam tanih diikuti oleh Mn dan Cu. Tumbuhan Nepenthes sp boleh dijadikan sebagai pengumpul biologi untuk logam Fe kerana nilai BACnya adalah tinggi.

Matched MeSH terms: Blood Proteins
Blood plasma in food from islam and science perspectives

Mohd izhar ariff mohd kashim, Nur asmadayana hasim, Rizafizahothaman, Mohammad zaini yahaya, Rozida khalid, Muhammad adibsamsudin, et al.

Sains Malaysiana, 2017;46:1779-1787.

Makanan dan minuman yang halal dan baik merupakan tuntutan dalam Islam. Pada zaman serba moden ini, timbul
kebimbangan terhadap status halal plasma darah yang digunakan secara meluas terutamanya dalam industri makanan.
Objektif penyelidikan ini ialah untuk mengkaji kegunaan, kebaikan dan keburukan plasma darah serta pandangan ulama
mengenai isu ini. Kajian ini dijalankan dengan menggunakan ulasan kepustakaan secara deskriptif. Kajian mendapati
bahawa plasma darah mempunyai kemampuan melarut dan pengemulsi yang tinggi, kelikatan yang rendah serta
kemampuan untuk membentuk gel yang kuat. Selain itu, plasma darah boleh menambah baik tekstur dan menjadi pengikat
dalam penghasilan produk makanan moden. Ia juga merupakan alternatif protein yang murah bagi pengganti lemak dalam
penghasilan produk daging rendah lemak. Walau bagaimanapun, kajian mendapati plasma darah mengandungi pelbagai
mikroorganisma dan hasilan metabolisme yang berkemungkinan merbahaya akibat daripada toksin dan protein darah.
Kini, terdapat pelbagai kaedah pengesanan yang boleh dijalankan untuk mengesan plasma darah dalam makanan bagi
menentukan status halal. Terdapat dua pandangan berkenaan hukum penggunaan plasma darah, pandangan pertama
bersependapat, penggunaan plasma darah dalam produk makanan adalah harus jika telah berlaku proses istihalah
yang sempurna. Manakala pandangan kedua, mengharamkan plasma darah kerana ia adalah proses tidak sempurna
(istihalah fasidah). Oleh itu, penentuan hukum terhadap istihalah dalam penghasilan plasma darah mestilah menepati
kehendak syariat Islam di samping memastikan hukum berkaitan isu ini tidak ketinggalan zaman.

Matched MeSH terms: Proteins
Conductivity comparison of Calix[8]arene-MWCNTs through spin coating technique

Faridah Lisa Supian, Darvina Lim Choo Kheng, Amira Shakila Razali

Sains Malaysiana, 2017;46:91-96.

In this study, we investigated the conductivity enhancement of calix[8]arene-multi-walled CNTs (MWCNTs) thin film.
Two types of calix[8]arenes were used, which were 5,11,17,23,29,35,41,47-p-tert-butyl-49,50,51,52,53,54,55,56-
oktakis[(carboxy)-pentoxy] -calix[8]arene (C[8]1) and 49,50,51,52,53,54,55,56 -octahydroxycalix[8]arene (C[8]2).
The monolayer properties of these two types of calix[8]arene on water subphase were examined. Later, the thin films
were fabricated by combining different ratios of each types of calix[8]arene with MWCNTs using spin coating deposition
technique. Then, the developed thin films were characterized using surface potential meter and four point probe. Thin
films of C[8]2 with hydroxyl groups at lower rims demonstrated higher surface potential and conductivity as compared
to the thin films of C[8]1 with upper rims of tert-butyl groups and lower rims of carboxyl groups. These results indicated
that the conductivity of calixarene thin films can be enhanced by MWCNTs through simple spin coating technique.

Matched MeSH terms: Nuclear Proteins
Efficiency of PV/T collector using spiral thermal absorber design

Cheku Nurul Aisyah, Ahmad Fudholi, Mohd Yusof Othman, Adnan Ibrahim, Mohd Hafidz Ruslan, Kamaruzzaman Sopian

Sains Malaysiana, 2018;47:853-859.

Kajian ini bertujuan untuk mereka bentuk dan mengkaji prestasi pengumpul fotovoltan-terma (PV/T) dengan menggunakan
reka bentuk pengumpul terma aliran air secara pilin. Reka bentuk pengumpul terma aliran air secara pilin telah dibina
semula daripada reka bentuk penyelidik sebelum ini. Pengumpul terma ini menggunakan saiz tiub yang lebih besar dan
jarak antara tiub lebih dekat berbanding dengan reka bentuk penyelidik sebelum ini. Pengumpul PV/T ini telah diuji di
bawah tiga keamatan yang berbeza iaitu 300, 500 dan 700 W/m2 serta diuji pada kadar aliran jisim air yang berbeza
iaitu 0.01, 0.02 dan 0.04 kg/s. Pada keadaan yang sama, kecekapan fotovoltan, terma dan tergabung juga menunjukkan
nilai yang paling tinggi, iaitu 4.18%, 76.68% dan 80.86%. Kecekapan terma yang dihasilkan pada kajian ini lebih tinggi
dibandingkan dengan kajian sebelumnya.

Matched MeSH terms: Fimbriae Proteins
Fulltext The recognition of multi-class protein folds by adding average chemical shifts of secondary structure elements

Feng Z, Hu X, Jiang Z, Song H, Ashraf MA

Saudi J Biol Sci, 2016 Mar;23(2):189-97.
PMID: 26980999 DOI: 10.1016/j.sjbs.2015.10.008

The recognition of protein folds is an important step in the prediction of protein structure and function. Recently, an increasing number of researchers have sought to improve the methods for protein fold recognition. Following the construction of a dataset consisting of 27 protein fold classes by Ding and Dubchak in 2001, prediction algorithms, parameters and the construction of new datasets have improved for the prediction of protein folds. In this study, we reorganized a dataset consisting of 76-fold classes constructed by Liu et al. and used the values of the increment of diversity, average chemical shifts of secondary structure elements and secondary structure motifs as feature parameters in the recognition of multi-class protein folds. With the combined feature vector as the input parameter for the Random Forests algorithm and ensemble classification strategy, we propose a novel method to identify the 76 protein fold classes. The overall accuracy of the test dataset using an independent test was 66.69%; when the training and test sets were combined, with 5-fold cross-validation, the overall accuracy was 73.43%. This method was further used to predict the test dataset and the corresponding structural classification of the first 27-protein fold class dataset, resulting in overall accuracies of 79.66% and 93.40%, respectively. Moreover, when the training set and test sets were combined, the accuracy using 5-fold cross-validation was 81.21%. Additionally, this approach resulted in improved prediction results using the 27-protein fold class dataset constructed by Ding and Dubchak.

Matched MeSH terms: Proteins
Thermostable lipases and their dynamics of improved enzymatic properties

Hamdan SH, Maiangwa J, Ali MSM, Normi YM, Sabri S, Leow TC

Appl Microbiol Biotechnol, 2021 Oct;105(19):7069-7094.
PMID: 34487207 DOI: 10.1007/s00253-021-11520-7

Thermal stability is one of the most desirable characteristics in the search for novel lipases. The search for thermophilic microorganisms for synthesising functional enzyme biocatalysts with the ability to withstand high temperature, and capacity to maintain their native state in extreme conditions opens up new opportunities for their biotechnological applications. Thermophilic organisms are one of the most favoured organisms, whose distinctive characteristics are extremely related to their cellular constituent particularly biologically active proteins. Modifications on the enzyme structure are critical in optimizing the stability of enzyme to thermophilic conditions. Thermostable lipases are one of the most favourable enzymes used in food industries, pharmaceutical field, and actively been studied as potential biocatalyst in biodiesel production and other biotechnology application. Particularly, there is a trade-off between the use of enzymes in high concentration of organic solvents and product generation. Enhancement of the enzyme stability needs to be achieved for them to maintain their enzymatic activity regardless the environment. Various approaches on protein modification applied since decades ago conveyed a better understanding on how to improve the enzymatic properties in thermophilic bacteria. In fact, preliminary approach using advanced computational analysis is practically conducted before any modification is being performed experimentally. Apart from that, isolation of novel extremozymes from various microorganisms are offering great frontier in explaining the crucial native interaction within the molecules which could help in protein engineering. In this review, the thermostability prospect of lipases and the utility of protein engineering insights into achieving functional industrial usefulness at their high temperature habitat are highlighted. Similarly, the underlying thermodynamic and structural basis that defines the forces that stabilize these thermostable lipase is discussed. KEY POINTS: • The dynamics of lipases contributes to their non-covalent interactions and structural stability. • Thermostability can be enhanced by well-established genetic tools for improved kinetic efficiency. • Molecular dynamics greatly provides structure-function insights on thermodynamics of lipase.

Matched MeSH terms: Bacterial Proteins
Genetic diversity of the full length apical membrane antigen-1 of Plasmodium knowlesi clinical isolates from Peninsular Malaysia

Ng YL, Fong MY, Lau YL

Trop Biomed, 2021 Jun 01;38(2):159-164.
PMID: 34172705 DOI: 10.47665/tb.38.2.052

The Plasmodium knowlesi apical membrane antigen-1 (PkAMA-1) plays an important role in the invasion of the parasite into its host erythrocyte, and it has been regarded as a potential vaccine candidate against human knowlesi malaria. This study investigates genetic diversity and natural selection of the full length PkAMA-1 of P. knowlesi clinical isolates from Peninsular Malaysia. Blood samples were collected from P. knowlesi malaria patients from Peninsular Malaysia. The PkAMA-1 gene was amplified from DNA samples using PCR, cloned into a plasmid vector and sequenced. Results showed that nucleotide diversity of the full length PkAMA-1 from Peninsular Malaysia isolates (π: 0.006) was almost similar to that of Sarawak (π: 0.005) and Sabah (π: 0.004) isolates reported in other studies. Deeper analysis revealed Domain I (π: 0.007) in the PkAMA-1 had the highest diversity as compared to Domain II (π: 0.004) and Domain III (π: 0.003). Z-test indicated negative (purifying) selection of the gene. Combined alignment analysis at the amino acid level for the Peninsular Malaysia and Sarawak PkAMA-1 sequences revealed 34 polymorphic sites. Thirty-one of these sites were dimorphic, and 3 were trimorphic. The amino acid sequences could be categorised into 31 haplotypes. In the haplotype network, PkAMA-1 from Peninsular Malaysia and Sarawak were separated into two groups.

Matched MeSH terms: Membrane Proteins/genetics*; Protozoan Proteins/genetics*
RAS and BRAF genes as biomarkers and target for personalised colorectal cancer therapy: An update

Ooi ZS, Pang SW, Teow SY

Malays J Pathol, 2022 Dec;44(3):415-428.
PMID: 36591710

Colorectal cancer (CRC) remains among the most commonly diagnosed cancers and has been on the rise. It is also one of the most lethal diseases globally, being the third leading cause of cancerrelated death. Depending on the stages and disease conditions, CRC is treated by surgery, chemo-, radio-therapy, immunotherapy or in combination. However, these therapies have subpar results with unwanted side effects, hence continuous effort is ongoing to explore new type of therapeutic modalities. Among the sub-types of CRC, KRAS, BRAF and NRAS mutated CRC comprise approximately 43%, 10% and 3% of the total cases, respectively. These mutations are associated with tumour progression and anti-epidermal growth factor receptor (EGFR) treatment resistance. Due to their important role in CRC, these genes have thus become targets in the development of novel treatments. In this paper, we discuss the current and upcoming treatment on CRC by targeting these mutated genes, with more focus on KRAS and BRAF due to the higher occurrence of mutations in CRC.

Matched MeSH terms: Proto-Oncogene Proteins B-raf/genetics
Fulltext Twitching motility of Stenotrophomonas maltophilia under iron limitation: In-silico, phenotypic and proteomic approaches

V K, Neela VK

Virulence, 2020 Dec;11(1):104-112.
PMID: 31957553 DOI: 10.1080/21505594.2020.1713649

This study investigates the twitching ability of 28 clinical and five environmental strains of S. maltophilia grown under iron-depleted condition through in-silico, phenotypic and proteomics approaches. Rapid Annotations using Subsystem Technology (RAST) analysis revealed the presence of 21 targets of type IV pilus shared across S. maltophilia strains K279a, R551-3, D457 and JV3. The macroscopic twitching assay showed that only clinical isolates produced a zone of twitching with a mean of 22.00 mm under normal and 25.00 mm under iron-depleted conditions. (p = 0.002). Environmental isolates did not show any significant twitching activity in both conditions tested. Isobaric Tags for Relative and Absolute Quantification (ITRAQ) analysis showed altered expression of twitching motility protein PilT (99.08-fold change), flagellar biosynthesis protein FliC (20.14-fold change), and fimbrial protein (0.70-fold change) in response to iron-depleted condition. Most of the strains that have the ability to twitch under the normal condition, exhibit enhanced twitching during iron limitation.

Matched MeSH terms: Bacterial Proteins/metabolism; Fimbriae Proteins/metabolism
Mapping the global research landscape on malnutrition for patients with chronic kidney disease: a visualization analysis

Shakhshir MH, Vanoh D, Hassan M, Zyoud SH

J Health Popul Nutr, 2023 Sep 23;42(1):101.
PMID: 37742012 DOI: 10.1186/s41043-023-00445-8

BACKGROUND: Chronic kidney disease (CKD) is seen as a diverse disease and a primary contributor to global mortality. Malnutrition arises within chronic illness, which involves protein energy depletion and inadequate levels of essential nutrients. These factors increase the likelihood of death and the overall impact of the disease on affected individuals. Consequently, this study aims to utilize bibliometric and visual analysis to assess the current state of research, the latest advances and emerging patterns in the fields of CKD and malnutrition.
METHODS: Extensive research was conducted using the Scopus database, which is the most authoritative database of research publications and citations, to focus on CKD research between 2003 and 2022, as indicated by title and author keywords. Then, within this vast collection of academic publications, a notable subset of articles was exclusively dedicated to investigating the relationship between CKD and malnutrition. Finally, we performed bibliometric analysis and visualization using VOSviewer 1.6.19 and Microsoft Excel 2013.
RESULTS: Large global research between 2003 and 2022 resulted in 50,588 documents focused on CKD, as indicated by title and author keywords. In this extensive collection of scientific publications, a staggering portion of 823 articles is devoted exclusively to investigating the link between CKD and malnutrition. Further analysis reveals that this body of work consists of 565 articles (68.65%), 221 reviews (26.85%), and 37 miscellaneous entries (4.50%), which encompass letters and editorials. The USA was found to be the most productive country (n = 173; 21.02%), followed by Italy (n = 83; 10.09%), Sweden (n = 56; 6.80%), Brazil (n = 54; 6.56%) and China (n = 51; 6.20%). The most common terms on the map include those related to the topic of (a) malnutrition in hemodialysis patients and predicting factors; terms associated with the (b) impact of malnutrition on cardiovascular risk and complications in CKD patients; and terms related to the (c) dietary protein intake and malnutrition in CKD.
CONCLUSIONS: This study is the first of its kind to analyze CKD and malnutrition research using data from Scopus for visualization and network mapping. Recent trends indicate an increasing focus on protein-energy wasting/malnutrition in hemodialysis patients and predicting factors, dietary protein intake, and malnutrition in CKD. These topics have gained significant attention and reflect the latest scientific advances. Intervention studies are crucial to examining diet therapy's impact on patients with stages 1 to 5 CKD. We hope this study will offer researchers, dietitians and nephrologists valuable information.

Matched MeSH terms: Dietary Proteins
Potential application of polysaccharide mucilages as a substitute for emulsifiers: A review

Yang Y, Gupta VK, Du Y, Aghbashlo M, Show PL, Pan J, et al.

Int J Biol Macromol, 2023 Jul 01;242(Pt 2):124800.
PMID: 37178880 DOI: 10.1016/j.ijbiomac.2023.124800

Mucilages are natural compounds consisting mainly of polysaccharides with complex chemical structures. Mucilages also contain uronic acids, proteins, lipids, and bioactive compounds. Because of their unique properties, mucilages are used in various industries, including food, cosmetics, and pharmaceuticals. Typically, commercial gums are composed only of polysaccharides, which increase their hydrophilicity and surface tension, reducing their emulsifying ability. As a result of the presence of proteins in combination with polysaccharides, mucilages possess unique emulsifying properties due to their ability to reduce surface tension. In recent years, various studies have been conducted on using mucilages as emulsifiers in classical and Pickering emulsions because of their unique emulsifying feature. Studies have shown that some mucilages, such as yellow mustard, mutamba, and flaxseed mucilages, have a higher emulsifying capacity than commercial gums. A synergistic effect has also been shown in some mucilages, such as Dioscorea opposita mucilage when combined with commercial gums. This review article investigates whether mucilages can be used as emulsifiers and what factors affect their emulsifying properties. A discussion of the challenges and prospects of using mucilages as emulsifiers is also presented in this review.

Matched MeSH terms: Proteins
MiRNAs Overexpression and Their Role in Breast Cancer: Implications for Cancer Therapeutics

Lee SH, Ng CX, Wong SR, Chong PP

Curr Drug Targets, 2023;24(6):484-508.
PMID: 36999414 DOI: 10.2174/1389450124666230329123409

MicroRNAs have a plethora of roles in various biological processes in the cells and most human cancers have been shown to be associated with dysregulation of the expression of miRNA genes. MiRNA biogenesis involves two alternative pathways, the canonical pathway which requires the successful cooperation of various proteins forming the miRNA-inducing silencing complex (miRISC), and the non-canonical pathway, such as the mirtrons, simtrons, or agotrons pathway, which bypasses and deviates from specific steps in the canonical pathway. Mature miRNAs are secreted from cells and circulated in the body bound to argonaute 2 (AGO2) and miRISC or transported in vesicles. These miRNAs may regulate their downstream target genes via positive or negative regulation through different molecular mechanisms. This review focuses on the role and mechanisms of miRNAs in different stages of breast cancer progression, including breast cancer stem cell formation, breast cancer initiation, invasion, and metastasis as well as angiogenesis. The design, chemical modifications, and therapeutic applications of synthetic anti-sense miRNA oligonucleotides and RNA mimics are also discussed in detail. The strategies for systemic delivery and local targeted delivery of the antisense miRNAs encompass the use of polymeric and liposomal nanoparticles, inorganic nanoparticles, extracellular vesicles, as well as viral vectors and viruslike particles (VLPs). Although several miRNAs have been identified as good candidates for the design of antisense and other synthetic modified oligonucleotides in targeting breast cancer, further efforts are still needed to study the most optimal delivery method in order to drive the research beyond preclinical studies.

Matched MeSH terms: Proteins
Fulltext The association between VSX1 exon3 gene variants and keratoconus in Malaysian patients

Deva JP, Ngeow YF, Zin T

Indian J Ophthalmol, 2023 Jun;71(6):2443-2447.
PMID: 37322657 DOI: 10.4103/IJO.IJO_2894_22

PURPOSE: This case-control study aims to examine possible associations of VSX1 exon3 gene variants with the development of keratoconus (KC) in Malaysian patients.
METHODS: A case-control study was done on 42 keratoconus cases, 127 family member controls, and 96 normal controls.
RESULTS: Three gene variants, p.A182A, p.P237P, and p.R217H showed significant associations with keratoconus (P < 0.05). While p.A182A and p.P227P were more prevalent than in the family and normal controls (OR 3.14-4.05), the reverse was observed with p.R217H (OR 0.086-1.59). With Haploview analysis, p.A182A and p.P237P were shown to be in linkage disequilibrium (LD) (LOD (logarithm of the odds score) score of 2.0, r2 of 0.957, and 95% confidence interval (CI) of 0.96-1.00).
CONCLUSION: The study results suggest that the p.A182A and p.P237P variants could have contributed to the development of keratoconus in some Malaysians and that these two variants are likely to be co-inherited. In contrast, the p.R217H variant appeared to confer some protection against the development of keratoconus.

Matched MeSH terms: Eye Proteins/genetics; Homeodomain Proteins/genetics
Fulltext Autosomal recessive progeroid syndrome due to homozygosity for a TOMM7 variant

Garg A, Keng WT, Chen Z, Sathe AA, Xing C, Kailasam PD, et al.

J Clin Invest, 2022 Dec 01;132(23).
PMID: 36282599 DOI: 10.1172/JCI156864

Multiple genetic loci have been reported for progeroid syndromes. However, the molecular defects in some extremely rare forms of progeria have yet to be elucidated. Here, we report a 21-year-old man of Chinese ancestry who has an autosomal recessive form of progeria, characterized by severe dwarfism, mandibular hypoplasia, hyperopia, and partial lipodystrophy. Analyses of exome sequencing data from the entire family revealed only 1 rare homozygous missense variant (c.86C>T; p.Pro29Leu) in TOMM7 in the proband, while the parents and 2 unaffected siblings were heterozygous for the variant. TOMM7, a nuclear gene, encodes a translocase in the outer mitochondrial membrane. The TOMM complex makes up the outer membrane pore, which is responsible for importing many preproteins into the mitochondria. A proteomic comparison of mitochondria from control and proband-derived cultured fibroblasts revealed an increase in abundance of several proteins involved in oxidative phosphorylation, as well as a reduction in abundance of proteins involved in phospholipid metabolism. We also observed elevated basal and maximal oxygen consumption rates in the fibroblasts from the proband as compared with control fibroblasts. We concluded that altered mitochondrial protein import due to biallelic loss-of-function TOMM7 can cause severe growth retardation and progeroid features.

Matched MeSH terms: Membrane Proteins/genetics; Mitochondrial Proteins/genetics
Fulltext Ultrasound in the deproteinization process for chitin and chitosan production

Vallejo-Domínguez D, Rubio-Rosas E, Aguila-Almanza E, Hernández-Cocoletzi H, Ramos-Cassellis ME, Luna-Guevara ML, et al.

Ultrason Sonochem, 2021 Apr;72:105417.
PMID: 33352467 DOI: 10.1016/j.ultsonch.2020.105417

Recently, chitin and chitosan are widely investigated for food preservation and active packaging applications. Chemical, as well as biological methods, are usually adopted for the production of these biopolymers. In this study, modification to a chemical method of chitin synthesis from shrimp shells has been proposed through the application of high-frequency ultrasound. The impact of sonication time on the deproteinization step of chitin and chitosan preparation was examined. The chemical identities of chitin and chitosan were verified using infrared spectroscopy. The influence of ultrasound on the deacetylation degree, molecular weight and particle size of the biopolymer products was analysed. The microscopic characteristics, crystallinity and the colour characteristics of the as-obtained biopolymers were investigated. Application of ultrasound for the production of biopolymers reduced the protein content as well as the particle size of chitin. Chitosan of high deacetylation degree and medium molecular weight was produced through ultrasound assistance. Finally, the as-derived chitosan was applied for beef preservation. High values of luminosity, chromatid and chrome were noted for the beef samples preserved using chitosan films, which were obtained by employing biopolymer subjected to sonication for 15, 25 and 40 min. Notably; these characteristics were maintained even after ten days of packaging. The molecular weight of these samples are 73.61 KDa, 86.82 KDa and 55.66 KDa, while the deacetylation degree are 80.60%, 92.86% and 94.03%, respectively; in the same order, the particle size of chitosan are 35.70 μm, 25.51 μm and 20.10 μm.

Matched MeSH terms: Proteins/analysis; Proteins/isolation & purification*; Proteins/chemistry
Fulltext ATG16L1 rs2241880/T300A increases susceptibility to perianal Crohn's disease: An updated meta-analysis on inflammatory bowel disease risk and clinical outcomes

Simovic I, Hilmi I, Ng RT, Chew KS, Wong SY, Lee WS, et al.

United European Gastroenterol J, 2024 Feb;12(1):103-121.
PMID: 37837511 DOI: 10.1002/ueg2.12477

BACKGROUND: ATG16L1 plays a fundamental role in the degradative intracellular pathway known as autophagy, being a mediator of inflammation and microbial homeostasis. The variant rs2241880 can diminish these capabilities, potentially contributing to inflammatory bowel disease (IBD) pathogenesis.
OBJECTIVES: To perform an updated meta-analysis on the association between ATG16L1 rs2241880 and IBD susceptibility by exploring the impact of age, ethnicity, and geography. Moreover, to investigate the association between rs2241880 and clinical features.
METHODS: Literature searches up until September 2022 across 7 electronic public databases were performed for all case-control studies on ATG16L1 rs2241880 and IBD. Pooled odds ratios (ORP ) and 95% CI were calculated under the random effects model.
RESULTS: Our analyses included a total of 30,606 IBD patients, comprising 21,270 Crohn's disease (CD) and 9336 ulcerative colitis (UC) patients, and 33,329 controls. ATG16L1 rs2241880 was significantly associated with CD susceptibility, where the A allele was protective (ORP : 0.74, 95% CI: 0.72-0.77, p-value: <0.001), while the G allele was a risk factor (ORP : 1.23, 95% CI: 1.09-1.39, p-value: 0.001), depending on the minor allele frequencies observed in this multi-ancestry study sample. rs2241880 was predominantly relevant in Caucasians from North America and Europe, and in Latin American populations. Importantly, CD patients harbouring the G allele were significantly more predisposed to perianal disease (ORP : 1.21, 95% CI: 1.07-1.38, p-value: 0.003).
CONCLUSIONS: ATG16L1 rs2241880 (G allele) is a consistent risk factor for IBD in Caucasian cohorts and influences clinical outcomes. As its role in non-Caucasian populations remains ambiguous, further studies in under-reported populations are necessary.

Matched MeSH terms: Carrier Proteins/genetics; Autophagy-Related Proteins/genetics
Bi-allelic variants of FILIP1 cause congenital myopathy, dysmorphism and neurological defects

Roos A, van der Ven PFM, Alrohaif H, Kölbel H, Heil L, Della Marina A, et al.

Brain, 2023 Oct 03;146(10):4200-4216.
PMID: 37163662 DOI: 10.1093/brain/awad152

Filamin-A-interacting protein 1 (FILIP1) is a structural protein that is involved in neuronal and muscle function and integrity and interacts with FLNa and FLNc. Pathogenic variants in filamin-encoding genes have been linked to neurological disorders (FLNA) and muscle diseases characterized by myofibrillar perturbations (FLNC), but human diseases associated with FILIP1 variants have not yet been described. Here, we report on five patients from four unrelated consanguineous families with homozygous FILIP1 variants (two nonsense and two missense). Functional studies indicated altered stability of the FILIP1 protein carrying the p.[Pro1133Leu] variant. Patients exhibit a broad spectrum of neurological symptoms including brain malformations, neurodevelopmental delay, muscle weakness and pathology and dysmorphic features. Electron and immunofluorescence microscopy on the muscle biopsy derived from the patient harbouring the homozygous p.[Pro1133Leu] missense variant revealed core-like zones of myofibrillar disintegration, autophagic vacuoles and accumulation of FLNc. Proteomic studies on the fibroblasts derived from the same patient showed dysregulation of a variety of proteins including FLNc and alpha-B-crystallin, a finding (confirmed by immunofluorescence) which is in line with the manifestation of symptoms associated with the syndromic phenotype of FILIP1opathy. The combined findings of this study show that the loss of functional FILIP1 leads to a recessive disorder characterized by neurological and muscular manifestations as well as dysmorphic features accompanied by perturbed proteostasis and myopathology.

Matched MeSH terms: Carrier Proteins/genetics; Cytoskeletal Proteins/genetics

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