Displaying publications 41 - 60 of 4048 in total

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  1. Jusoh TNAM, Jaafar IS, Shueb RH
    J Vector Borne Dis, 2024 Jan 01;61(1):61-71.
    PMID: 38648407 DOI: 10.4103/0972-9062.392269
    BACKGROUND OBJECTIVES: Dengue and chikungunya infections are one of the major health problems that have plagued the human population globally. All dengue virus (DENV) serotypes circulate within Malaysia with particular serotypes dominating in different years/outbreaks. In the state of Kelantan, an increasing number of DENV and chikungunya virus (CHIKV) new cases have been reported, including several deaths. This study aimed to isolate and detect these arboviruses from adult mosquitoes in Kelantan.

    METHODS: Adult mo squito samples were collected from January to August 2019 and were identified according to gender, species and locality. The isolation of the virus was done in C6/36 cells. Dengue NS1 antigen was carried out using direct mosquito lysate and mosquito culture supernatant. Detection and serotyping of the DENV was performed using multiplex RT-PCR and CHIKV detection using a one-step RT-PCR assay.

    RESULTS: Of 91 mosquito pools, four were positive for NS1 antigen comprising two pools (2.2%) of male Ae. albopictus (Pulau Melaka and Kubang Siput) and two pools (2.2%) of Ae. aegypti (Kampung Demit Sungai). DENV 1 was detected in one pool (0.9%) of female Ae. albopictus among 114 tested Aedes pools. Two pools of 114 pools (1.7%) from both male Aedes species were positive with double serotypes, DENV 1 and DENV 2 (Pulau Melaka). However, no pool was positive for CHIKV.

    INTERPRETATION CONCLUSION: The presence of DENV and the main vectors of arboviruses in Kelantan are pertinent indicators of the need to improve vector controls to reduce arbovirus infections among people in the localities.

    Matched MeSH terms: Viral Nonstructural Proteins/genetics
  2. Faizal AM, Elias MH, Jin NM, Abu MA, Syafruddin SE, Zainuddin AA, et al.
    Front Endocrinol (Lausanne), 2024;15:1274376.
    PMID: 38524634 DOI: 10.3389/fendo.2024.1274376
    The leading indicator for successful outcomes in in-vitro fertilization (IVF) is the quality of gametes in oocytes and sperm. Thus, advanced research aims to highlight the parameter in assessing these qualities - DNA fragmentation in sperm and oocyte development capacity (ODC) via evaluation of microenvironments involving its maturation process. Regarding oocytes, most evidence reveals the role of cumulus cells as non-invasive methods in assessing their development competency, mainly via gene expression evaluation. Our review aims to consolidate the evidence of GDF-9 derivatives, the HAS2, GREM1, and PTGS2 gene expression in cumulus cells used as ODC markers in relevant publications and tailored to current IVF outcomes. In addition to that, we also added the bioinformatic analysis in our review to strengthen the evidence aiming for a better understanding of the pathways and cluster of the genes of interest - HAS2, GREM1, and PTGS2 in cumulus cell level. Otherwise, the current non-invasive method can be used in exploring various causes of infertility that may affect these gene expressions at the cumulus cell level. Nevertheless, this method can also be used in assessing the ODC in various cohorts of women or as an improvement of markers following targeted tools or procedures by evaluating the advancement of these gene expressions following the targeted intervention.
    Matched MeSH terms: Intercellular Signaling Peptides and Proteins/genetics; Intercellular Signaling Peptides and Proteins/metabolism
  3. Du Y, Lin X, Shao X, Zhao J, Xu H, de Cruz CR, et al.
    Front Immunol, 2024;15:1319698.
    PMID: 38646543 DOI: 10.3389/fimmu.2024.1319698
    This study explored the impacts of supplementation of different levels of coated methionine (Met) in a high-plant protein diet on growth, blood biochemistry, antioxidant capacity, digestive enzymes activity and expression of genes related to TOR signaling pathway in gibel carp (Carassius auratus gibeilo). A high-plant protein diet was formulated and used as a basal diet and supplemented with five different levels of coated Met at 0.15, 0.30, 0.45, 0.60 and 0.75%, corresponding to final analyzed Met levels of 0.34, 0.49, 0.64, 0.76, 0.92 and 1.06%. Three replicate groups of fish (initial mean weight, 11.37 ± 0.02 g) (20 fish per replicate) were fed the test diets over a 10-week feeding period. The results indicated that with the increase of coated Met level, the final weight, weight gain (WG) and specific growth rate initially boosted and then suppressed, peaking at 0.76% Met level (P< 0.05). Increasing dietary Met level led to significantly increased muscle crude protein content (P< 0.05) and reduced serum alanine aminotransferase activity (P< 0.05). Using appropriate dietary Met level led to reduced malondialdehyde concentration in hepatopancreas (P< 0.05), improved superoxide dismutase activity (P< 0.05), and enhanced intestinal amylase and protease activities (P< 0.05). The expression levels of genes associated with muscle protein synthesis such as insulin-like growth factor-1, protein kinase B, target of rapamycin and eukaryotic initiation factor 4E binding protein-1 mRNA were significantly regulated, peaking at Met level of 0.76% (P< 0.05). In conclusion, supplementing optimal level of coated Met improved on fish growth, antioxidant capacity, and the expression of TOR pathway related genes in muscle. The optimal dietary Met level was determined to be 0.71% of the diet based on quadratic regression analysis of WG.
    Matched MeSH terms: Fish Proteins/genetics; Fish Proteins/metabolism
  4. Man RC, Idrus RBH, Ibrahim WIW, Saim AB, Lokanathan Y
    Adv Exp Med Biol, 2024;1450:59-76.
    PMID: 37247133 DOI: 10.1007/5584_2023_777
    Conditioned medium from cultured fibroblast cells is recognized to promote wound healing and growth through the secretion of enzymes, extracellular matrix proteins, and various growth factors and cytokines. The objective of this study was to profile the secreted proteins present in nasal fibroblast conditioned medium (NFCM). Nasal fibroblasts isolated from human nasal turbinates were cultured for 72 h in Defined Keratinocytes Serum Free Medium (DKSFM) or serum-free F12: Dulbecco's Modified Eagle's Medium (DMEM) to collect conditioned medium, denoted as NFCM_DKSFM and NFCM_FD, respectively. SDS-PAGE was performed to detect the presence of protein bands, followed by MALDI-TOF and mass spectrometry analysis. SignalP, SecretomeP, and TMHMM were used to identify the secreted proteins in conditioned media. PANTHER Classification System was performed to categorize the protein according to protein class, whereas STRING 10 was carried out to evaluate the predicted proteins interactions. SDS-PAGE results showed the presence of various protein with molecular weight ranging from ~10 kDa to ~260 kDa. Four protein bands were identified using MALDI-TOF. The analyses identified 104, 83, and 7 secreted proteins in NFCM_FD, NFCM_DKSFM, and DKSFM, respectively. Four protein classes involved in wound healing were identified, namely calcium-binding proteins, cell adhesion molecules, extracellular matrix proteins, and signaling molecules. STRING10 protein prediction successfully identified various pathways regulated by secretory proteins in NFCM. In conclusion, this study successfully profiled the secreted proteins of nasal fibroblasts and these proteins are predicted to play important roles in RECs wound healing through various pathways.
    Matched MeSH terms: Extracellular Matrix Proteins/metabolism
  5. Hambali A, Jusril NA, Md Hashim NF, Abd Manan N, Adam SK, Mehat MZ, et al.
    J Alzheimers Dis, 2024;99(s1):S119-S138.
    PMID: 38250772 DOI: 10.3233/JAD-230875
    BACKGROUND: Neuroinflammation and oxidative stress can aggravate the progression of Alzheimer's disease (AD). Centella asiatica has been traditionally consumed for memory and cognition. The triterpenes (asiaticoside, madecassoside, asiatic acid, madecassic acid) have been standardized in the ethanolic extract of Centella asiatica (SECA). The bioactivity of the triterpenes in different solvent polarities of SECA is still unknown.

    OBJECTIVE: In this study, the antioxidative and anti-neuroinflammatory effects of SECA and its fractions were explored on lipopolysaccharides (LPS)-induced microglial cells.

    METHODS: HPLC measured the four triterpenes in SECA and its fractions. SECA and its fractions were tested for cytotoxicity on microglial cells using MTT assay. NO, pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), ROS, and MDA (lipid peroxidation) produced by LPS-induced microglial cells were measured by colorimetric assays and ELISA. Nrf2 and HO-1 protein expressions were measured using western blotting.

    RESULTS: The SECA and its fractions were non-toxic to BV2 microglial cells at tested concentrations. The levels of NO, TNF-α, IL-6, ROS, and lipid peroxidation in LPS-induced BV2 microglial cells were significantly reduced (p 

    Matched MeSH terms: Membrane Proteins*
  6. Eskandari A, Nezhad NG, Leow TC, Rahman MBA, Oslan SN
    World J Microbiol Biotechnol, 2023 Dec 08;40(1):39.
    PMID: 38062216 DOI: 10.1007/s11274-023-03851-6
    Yeasts serve as exceptional hosts in the manufacturing of functional protein engineering and possess industrial or medical utilities. Considerable focus has been directed towards yeast owing to its inherent benefits and recent advancements in this particular cellular host. The Pichia pastoris expression system is widely recognized as a prominent and widely accepted instrument in molecular biology for the purpose of generating recombinant proteins. The advantages of utilizing the P. pastoris system for protein production encompass the proper folding process occurring within the endoplasmic reticulum (ER), as well as the subsequent secretion mediated by Kex2 as a signal peptidase, ultimately leading to the release of recombinant proteins into the extracellular environment of the cell. In addition, within the P. pastoris expression system, the ease of purifying recombinant protein arises from its restricted synthesis of endogenous secretory proteins. Despite its achievements, scientists often encounter persistent challenges when attempting to utilize yeast for the production of recombinant proteins. This review is dedicated to discussing the current achievements in the usage of P. pastoris as an expression host. Furthermore, it sheds light on the strategies employed in the expression system and the optimization and development of the fermentative process of this yeast. Finally, the impediments (such as identifying high expression strains, improving secretion efficiency, and decreasing hyperglycosylation) and successful resolution of certain difficulties are put forth and deliberated upon in order to assist and promote the expression of complex proteins in this prevalent recombinant host.
    Matched MeSH terms: Recombinant Proteins/metabolism
  7. Siddiqui Q, Ali MSM, Leow ATC, Oslan SN, Mohd Shariff F
    J Biomol Struct Dyn, 2023 Dec;41(20):10347-10367.
    PMID: 36510668 DOI: 10.1080/07391102.2022.2154845
    Leptospirosis is one of the neglected zoonosis, affecting human and animal populations worldwide. Reliable effective therapeutics and concerns to look for more research into the molecular analysis of its genome is therefore needed. In the genomic pool of the Leptospira interrogans many hypothetical proteins are still uncharacterized. In the current research, we performed extensive in silico analysis to prioritize the potential hypothetical proteins of L. interrogans serovar Copenhageni via stepwise reducing the available hypothetical proteins (Total 3606) of the assembly to only 15, based on non-homologous to homosapien, essential, functional, virulent, cellular localization. Out of them, only two proteins WP_000898918.1 (Hypothetical Protein 1) & WP_001014594.1 (Hypothetical Protein 2) were found druggable and involved in protein-protein interaction network. The 3 D structures of these two target proteins were predicted via ab initio homology modeling followed by structures refinement and validation, as no structures were available till date. The analysis also revealed that the functional domains, families and protein-protein interacting partners identified in both proteins are crucial for the survival of the bacteria. The binding cavities were predicted for both the proteins through blind and specific protein-ligand docking with their respective ligands and inhibitors and were found to be in accordance with the druggable sites predicted by DoGSiteScorer. The docking interactions were found within the active functional domains for both the proteins while for Hypothetical Protein 2, the same residues were involved in interactions with Cytidine-5'-triphosphate in blind and specific docking. Furthermore, the simulations of molecular dynamics and free binding energy revealed the stable substrate binding and efficient binding energies, and were in accordance to our docking results. The work predicted two unique hypothetical proteins of L. interrogans as a potential druggable targets for designing of inhibitors for them.Communicated by Ramaswamy H. Sarma.
    Matched MeSH terms: Bacterial Proteins/genetics; Bacterial Proteins/metabolism
  8. Pal P, Hasan SW, Abu Haija M, Sillanpää M, Banat F
    Crit Rev Biotechnol, 2023 Dec;43(7):971-981.
    PMID: 35968911 DOI: 10.1080/07388551.2022.2092716
    Colloidal gas aphrons (CGAs) are highly stable, spherical, micrometer-sized bubbles encapsulated by surfactant multilayers. They have several intriguing properties, including: high stability, large interfacial area, and the ability to maintain the same charge as their parent molecules. The physical properties of CGAs make them ideal for biotechnological applications such as the recovery of a variety of: biomolecules, particularly proteins, yeast, enzymes, and microalgae. In this review, the bio-application of CGAs for the recovery of natural components is presented, as well as: experimental results, technical challenges, and critical research directions for the future. Experimental results from the literature showed that the recovery of biomolecules was mainly determined by electrostatic or hydrophobic interactions between polyphenols and proteins (lysozyme, β-casein, β-lactoglobulin, etc.), yeast, biological molecules (gallic acid and norbixin), and microalgae with CGAs. Knowledge transfer is essential for commercializing CGA-based bio-product recovery, which will be recognized as a viable technology in the future.
    Matched MeSH terms: Proteins
  9. Ojukwu M, Tan HL, Murad M, Nafchi AM, Easa AM
    Food Sci Technol Int, 2023 Dec;29(8):799-808.
    PMID: 36000280 DOI: 10.1177/10820132221121169
    In a bid to produce rice flour noodles with improved texture and reduced cooking time, rice flour-soy protein isolate noodles (RNS) were structurally enhanced by a combined treatment (COM) of microbial transglutaminase (MTG) with glucono-δ-lactone (GDL). The RNS-COM was either dried using superheated steam (SHS) to yield RNS-COM-SHS or steamed for 10 min (S10) before air drying to produce RNS-COM-S10 noodles. Control samples were SHS-dried rice flour (RN-SHS) and air-dried RN-S10 noodles. In general, textural and microstructural properties indicated higher textural properties and a more robust network in RNS-COM-SHS and RNS-COM-S10 than in other noodles. However, optimum cooking time (P < 0.5) was in the order; RN-SHS, RNS-COM-SHS < RN-S10 < RNS-COM-S10. As a result of the COM treatment, structurally enhanced noodles were more resistant to cooking. As applied in RNS-COM-SHS noodles, SHS was able to improve cooking quality, probably through the formation of bigger and evenly spread pores that had promoted faster gelatinisation of starch, with a high order of relative starch crystallinity.
    Matched MeSH terms: Soybean Proteins*
  10. Suphakhonchuwong N, Rungsihirunrat K, Kuesap J
    Parasitol Res, 2023 Dec;122(12):2871-2883.
    PMID: 37725258 DOI: 10.1007/s00436-023-07977-2
    Resistance to antimalarial drugs is a serious issue around the world. Widespread Plasmodium vivax and P. falciparum coinfections are commonly found in Thailand. Dihydroartemisinin and piperaquine (DHA-PPQ) have been used as first-line treatments for P. falciparum since 2015, and chloroquine (CQ) and primaquine (PQ) have remained first-line drugs for P. vivax for more than 60 years. Coinfections may lead parasites to evolve with regard to genetics under selective drug pressure. This study is aimed at investigating genes linked to antimalarial resistance in P. vivax before and after introduction of DHA-PPQ as a new drug regimen in Thailand. A total of 400 P. vivax isolates were collected from samples along the Thai-Myanmar and Thai-Malaysian borders before (2009-2015) and after (2016-2019) introduction of DHA-PPQ. Genomic DNA of P. vivax was obtained and subjected to analysis of five drug resistance-associated genes (Pvdhfr, Pvdhps, Pvmdr1, Pvcrt-o, and PvK12) by nested polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP), and nucleotide sequencing. A high prevalence of Pvdhfr was found in both endemic areas over the period. The quadruple (57I/58R/61M/117T) Pvdhfr haplotype was predominant in both periods in both endemic areas. Although the wild-type haplotype of Pvdhps was predominant in Thai-Malaysian isolates in both periods, a single mutant haplotype (383G) was dominant in Thai-Myanmar isolates during both periods. A low prevalence of the Pvmdr1 976F mutation was found in both periods among Thai-Myanmar isolates. A significant decrease in Pvmdr1 976F was identified in Thai-Malaysian isolates from the second period (p < 0.01). Only one nonsynonymous mutation of Pvcrt-o (193E) and one synonymous mutation of PvK12 (R584) were detected in four isolates (4.7%) and one isolate (0.5%) in the first period among Thai-Myanmar isolates, respectively. Thus, with limited clinical efficacy data, the low prevalence of drug-resistance markers may suggest that there is a low prevalence of P. vivax-resistant strains and that the current drug regimen for P. vivax is still effective for treating this P. vivax parasite population. Continued surveillance of antimalarial drug resistance markers and monitoring of clinical drug efficacy should be conducted for epidemiological and policy implications.
    Matched MeSH terms: Protozoan Proteins/genetics
  11. Goa Y, Du JG, Jirapattharasate C, Galon E, Ji SW, Ran ZG, et al.
    Trop Biomed, 2023 Dec 01;40(4):400-405.
    PMID: 38308826 DOI: 10.47665/tb.40.4.004
    Beta toxin (CPB) is a lethal toxin and plays a key role in enterotoxemia of ruminants caused by Clostridium perfringens type C strain. The existing vaccines based on crude CPB need time-consuming detoxification and difficult quality control steps. In this study, we synthesized the rCPBm4 of C. perfringens type C strain and small ubiquitin-like modifier (SUMO)-tag CPBm4 (rSUMO-CPBm4) by introducing four amino acid substitutions: R212E, Y266A, L268G, and W275A. Compared with rCPBm4, rSUMO-CPBm4 was expressed with higher solubility in Escherichia coli BL21 (DE3). Neither rCPBm4 nor rSUMO-CPBm4 was lethal to mice. Although rCPBm4 and rSUMO-CPBm4 were reactogenic with polyclonal antibodies against crude CPB, rabbits vaccinated with rSUMO-CPBm4 developed significant levels of toxin-neutralizing antibody (TNA) titers that conferred protection against crude toxin challenge. These data suggest that genetically detoxified rSUMO-CPBm4 is a promising subunit vaccine candidate for C. perfringens type C beta enterotoxemia.
    Matched MeSH terms: Recombinant Proteins/genetics
  12. Sun Q, Yang J, Zhang M, Zhang Y, Ma H, Tran NT, et al.
    J Biol Chem, 2023 Dec;299(12):105463.
    PMID: 37977221 DOI: 10.1016/j.jbc.2023.105463
    Ferroptosis, characterized by iron-dependent cell death, has recently emerged as a critical defense mechanism against microbial infections. The present study aims to investigate the involvement of exosomes in the induction of ferroptosis and the inhibition of bacterial infection in crustaceans. Our findings provide compelling evidence for the pivotal role of exosomes in the immune response of crustaceans, wherein they facilitate intracellular iron accumulation and activate the ferroptotic pathways. Using RNA-seq and bioinformatic analysis, we demonstrate that cytochrome P450 (CYP) can effectively trigger ferroptosis. Moreover, by conducting an analysis of exosome cargo proteins, we have identified the participation of six-transmembrane epithelial antigen of prostate 4 in the regulation of hemocyte ferroptotic sensitivity. Subsequent functional investigations unveil that six-transmembrane epithelial antigen of prostate 4 enhances cellular Fe2+ levels, thereby triggering Fenton reactions and accelerating CYP-mediated lipid peroxidation, ultimately culminating in ferroptotic cell death. Additionally, the Fe2+-dependent CYP catalyzes the conversion of arachidonic acid into 20-hydroxyeicosatetraenoic acid, which activates the peroxisome proliferator-activated receptor. Consequently, the downstream target of peroxisome proliferator-activated receptor, cluster of differentiation 36, promotes intracellular fatty acid accumulation, lipid peroxidation, and ferroptosis. These significant findings shed light on the immune defense mechanisms employed by crustaceans and provide potential strategies for combating bacterial infections in this species.
    Matched MeSH terms: Membrane Proteins/metabolism
  13. Zhu C, Liu G, Abdullah ALB, Han M, Jiang Q, Li Y
    Fish Shellfish Immunol, 2023 Dec;143:109207.
    PMID: 37923183 DOI: 10.1016/j.fsi.2023.109207
    Plastics are widely produced for industrial and domestic applications due to their unique properties, and studies on the toxic effects of nanoplastics (NPs) on aquatic animals are essential. In this study, we investigated the transcriptomic patterns of Litopenaeus vannamei after NPs exposure. We found that the lysosome pathway was activated when after NPs exposure, with up-regulated DEGs, including glucocerebrosidase (GBA), hexosaminidase A (HEXA), sphingomyelin phosphodiesterase-1 (SMPD1), and solute carrier family 17 member 5 (SLC17A5). In addition, the PI3K-Akt signaling pathway was strongly affected by NPs, and the upstream genes of PI3K-Akt, including epidermal growth factor receptor (EGFR), integrin subunit beta 1 (ITGB1) and heat shock protein 90 (HSP90) were up-regulation. Other genes involved in lipogenesis, such as sterol regulatory element binding transcription factor 1 (SREBP-1c), fatty acid synthase (FASN) and stearoyl-CoA desaturase (SCD-1), were down-regulated. However, the contents of triglycerides (TG) and total cholesterol (TCH) in L. vanname hepatopancreas were reduced, which indicated that the ingestion of NPs led to the disturbance of hepatic lipid metabolism. What more, NPs treatment of L. vannamei also caused oxidative stress. In addition, NPs can damage part of the tissue structure and affect the physiological function of shrimps. The results of this study provide valuable ecotoxicological data to improve the understanding of the biological fate and effects of nanoplastics in L. vannamei.
    Matched MeSH terms: Proto-Oncogene Proteins c-akt/genetics
  14. Yang TS, Chen HH, Bo-Wen L, Kim TW, Kim JG, Ahn JB, et al.
    Asia Pac J Clin Oncol, 2023 Dec;19(6):672-680.
    PMID: 36855017 DOI: 10.1111/ajco.13920
    AIM: The OPTIM1SE study observed long-term real-world outcomes of cetuximab-based infusional 5-fluorouracil (5-FU) regimens for first-line treatment of metastatic colorectal cancer (mCRC) across Asia-Pacific and Middle East regions, aiming to characterize their use, effectiveness, and safety in routine practice.

    METHODS: OPTIM1SE was a prospective, open-label, observational study. Patients with untreated KRAS wild-type mCRC and distant metastases were treated per locally approved labels and monitored for 3 years via electronic medical records. The primary endpoint was the overall response rate (ORR). Secondary endpoints included safety, progression-free survival (PFS), and overall survival (OS).

    RESULTS: From November 19, 2013, to June 30, 2016, 520 patients were enrolled in 51 sites. Patients were mostly male (61.2%), with a mean age of 58.5 (±12.0) years; 420 patients received leucovorin, 5-FU, and irinotecan-based regimens and 94 received leucovorin, 5-FU, and oxaliplatin. The most common primary tumor site was the rectum (38.8%), with liver metastases (65.0%). ORR was 45.4% (95% CI, 41.1%-49.7%), including 26 patients (5.0%) with a complete response. Median PFS was 9.9 months (95% CI, 8.2-11.0); median OS (mOS) was 30.8 months (95% CI, 27.9-33.6). Higher mOS was associated with tumors of left compared with right-sided origin (hazard ratio, 0.69 [95% CI, 0.49-0.99]); higher ORR was also associated with liver metastases compared with all other metastases (55.4% vs. 40.2%). Adverse events were consistent with the known safety profile of cetuximab.

    CONCLUSION: Cetuximab-based 5-FU regimens were effective first-line treatments for mCRC in routine practice, particularly in patients with left-sided disease and liver metastases only.

  15. Ghazali N, Rahman NA, Kannan TP, Ahmad A, Sulong S
    BMC Oral Health, 2023 Nov 29;23(1):945.
    PMID: 38031027 DOI: 10.1186/s12903-023-03464-3
    BACKGROUND: Nonsyndromic cleft lip and/or without cleft palate (NSCL/P) with or without hypodontia is a common developmental aberration in humans and animals. This study aimed to identify the loss of heterozygosity (LOH) involved in hypodontia and NSCL/P pathogenesis.

    METHODS: This is a cross-sectional study that conducted genome-wide copy number analysis using CytoScan 750K array on salivary samples from Malay subjects with NSCL/P with or without hypodontia aged 7-13 years. To confirm the significant results, simple logistic regression was employed to conduct statistical data analysis using SPSS software.

    RESULTS: The results indicated the most common recurrent copy neutral LOH (cnLOH) observed at 1p33-1p32.3, 1q32.2-1q42.13 and 6p12.1-6p11.1 loci in 8 (13%), 4 (7%), and 3 (5%) of the NSCL/P subjects, respectively. The cnLOHs at 1p33-1p32.3 (D1S197), 1q32.2-1q42.13 (D1S160), and 6p12.1-6p11.1 (D1S1661) were identified observed in NSCL/P and noncleft children using microsatellite analysis markers as a validation analysis. The regions affected by the cnLOHs at 1p33-1p32.3, 1q32.2-1q42.13, and 6p12.1-6p11.1 loci contained selected genes, namely FAF1, WNT3A and BMP5, respectively. There was a significant association between the D1S197 (1p33-32.3) markers containing the FAF1 gene among NSCL/P subjects with or without hypodontia compared with the noncleft subjects (p-value = 0.023).

    CONCLUSION: The results supported the finding that the genetic aberration on 1p33-32.3 significantly contributed to the development of NSCL/P with or without hypodontia. These results have an exciting prospect in the promising field of individualized preventive oral health care.

    Matched MeSH terms: Adaptor Proteins, Signal Transducing/genetics; Apoptosis Regulatory Proteins/genetics
  16. Alhusayni S, Roswanjaya YP, Rutten L, Huisman R, Bertram S, Sharma T, et al.
    BMC Plant Biol, 2023 Nov 24;23(1):587.
    PMID: 37996841 DOI: 10.1186/s12870-023-04594-0
    BACKGROUND: Nitrogen-fixing nodules occur in ten related taxonomic lineages interspersed with lineages of non-nodulating plant species. Nodules result from an endosymbiosis between plants and diazotrophic bacteria; rhizobia in the case of legumes and Parasponia and Frankia in the case of actinorhizal species. Nodulating plants share a conserved set of symbiosis genes, whereas related non-nodulating sister species show pseudogenization of several key nodulation-specific genes. Signalling and cellular mechanisms critical for nodulation have been co-opted from the more ancient plant-fungal arbuscular endomycorrhizal symbiosis. Studies in legumes and actinorhizal plants uncovered a key component in symbiotic signalling, the LRR-type SYMBIOSIS RECEPTOR KINASE (SYMRK). SYMRK is essential for nodulation and arbuscular endomycorrhizal symbiosis. To our surprise, however, despite its arbuscular endomycorrhizal symbiosis capacities, we observed a seemingly critical mutation in a donor splice site in the SYMRK gene of Trema orientalis, the non-nodulating sister species of Parasponia. This led us to investigate the symbiotic functioning of SYMRK in the Trema-Parasponia lineage and to address the question of to what extent a single nucleotide polymorphism in a donor splice site affects the symbiotic functioning of SYMRK.

    RESULTS: We show that SYMRK is essential for nodulation and endomycorrhization in Parasponia andersonii. Subsequently, it is revealed that the 5'-intron donor splice site of SYMRK intron 12 is variable and, in most dicotyledon species, doesn't contain the canonical dinucleotide 'GT' signature but the much less common motif 'GC'. Strikingly, in T. orientalis, this motif is converted into a rare non-canonical 5'-intron donor splice site 'GA'. This SYMRK allele, however, is fully functional and spreads in the T. orientalis population of Malaysian Borneo. A further investigation into the occurrence of the non-canonical GA-AG splice sites confirmed that these are extremely rare.

    CONCLUSION: SYMRK functioning is highly conserved in legumes, actinorhizal plants, and Parasponia. The gene possesses a non-common 5'-intron GC donor splice site in intron 12, which is converted into a GA in T. orientalis accessions of Malaysian Borneo. The discovery of this functional GA-AG splice site in SYMRK highlights a gap in our understanding of splice donor sites.

    Matched MeSH terms: Plant Proteins/genetics; Plant Proteins/metabolism
  17. Chan LC, Mat Yassim AS, Ahmad Fuaad AAH, Leow TC, Sabri S, Radin Yahaya RS, et al.
    Sci Rep, 2023 Nov 17;13(1):20178.
    PMID: 37978223 DOI: 10.1038/s41598-023-47511-z
    COVID-19 results from SARS-CoV-2, which mutates frequently, challenging current treatments. Therefore, it is critical to develop new therapeutic drugs against this disease. This study explores the interaction between SARS-CoV-2 3CLpro and RetroMAD1, a well-characterized coronavirus protein and potential drug target, using in-silico methods. The analysis through the HDOCK server showed stable complex formation with a binding energy of -12.3, the lowest among reference drugs. The RetroMAD1-3CLpro complex underwent a 100 ns molecular dynamics simulation (MDS) in an explicit solvation system, generating various trajectories, including RMSD, RMSF, hydrogen bonding, radius of gyration, and ligand binding energy. MDS results confirmed intact interactions within the RetroMAD1-3CLpro complex during simulations. In vitro experiments validated RetroMAD1's ability to inhibit 3CLpro enzyme activity and prevent SARS-CoV-2 infection in human bronchial cells. RetroMAD1 exhibited antiviral efficacy comparable to Remdesivir without cytotoxicity at effective concentrations. These results suggest RetroMAD1 as a potential drug candidate against SARS-CoV-2, warranting further in vivo and clinical studies to assess its efficiency.
    Matched MeSH terms: Recombinant Fusion Proteins; Viral Nonstructural Proteins/metabolism
  18. Dong L, Zhang Y, Li Y, Liu Y, Chen Q, Liu L, et al.
    Food Funct, 2023 Nov 13;14(22):10221-10231.
    PMID: 37916290 DOI: 10.1039/d3fo02474a
    Heat sterilization of dairy products can promote the formation of advanced glycation end products (AGEs), protein oxidation products (POPs) and α-dicarbonyl compounds, which have a significant influence on health due to the close association of these products with diabetes complications. In this study, eight oat phenolic acids were first analyzed for their inhibitory effect against AGEs formation. Due to their strong inhibitory effects and structural differences, caffeic acid (CA) and gallic acid (GA) were further selected to assess their anti-glycosylation mechanisms using spectroscopy, chromatography and molecular docking. CA/GA reduced the production of total AGEs and POPs in various bovine milk simulation models and protected whey proteins from structural modifications, oxidation, and cross-linking. Comparative analyses showed a structure-effect relationship between CA/GA and AGEs inhibition. Oat phenolic acids against AGEs and POPs might be related to the unique bonding of key amino acid residues in whey proteins, the inhibitory role of early fructosamine and the trapping of reactive α-dicarbonyl groups to form adducts. In conclusion, oat phenolic acids might present a promising dietary strategy to alleviate AGEs production and glycation of proteins in dairy products upon storage.
    Matched MeSH terms: Whey Proteins/analysis
  19. Cheng Z, Hwang SS, Bhave M, Rahman T, Chee Wezen X
    J Chem Inf Model, 2023 Nov 13;63(21):6912-6924.
    PMID: 37883148 DOI: 10.1021/acs.jcim.3c01252
    Polo-like kinase 1 (PLK1) and p38γ mitogen-activated protein kinase (p38γ) play important roles in cancer pathogenesis by controlling cell cycle progression and are therefore attractive cancer targets. The design of multitarget inhibitors may offer synergistic inhibition of distinct targets and reduce the risk of drug-drug interactions to improve the balance between therapeutic efficacy and safety. We combined deep-learning-based quantitative structure-activity relationship (QSAR) modeling and hybrid-based consensus scoring to screen for inhibitors with potential activity against the targeted proteins. Using this combination strategy, we identified a potent PLK1 inhibitor (compound 4) that inhibited PLK1 activity and liver cancer cell growth in the nanomolar range. Next, we deployed both our QSAR models for PLK1 and p38γ on the Enamine compound library to identify dual-targeting inhibitors against PLK1 and p38γ. Likewise, the identified hits were subsequently subjected to hybrid-based consensus scoring. Using this method, we identified a promising compound (compound 14) that could inhibit both PLK1 and p38γ activities. At nanomolar concentrations, compound 14 inhibited the growth of human hepatocellular carcinoma and hepatoblastoma cells in vitro. This study demonstrates the combined screening strategy to identify novel potential inhibitors for existing targets.
    Matched MeSH terms: Cell Cycle Proteins/metabolism
  20. Ho YF, Yajit NLM, Shiau JY, Malek SNA, Shyur LF, Karsani SA
    Appl Biochem Biotechnol, 2023 Nov;195(11):6867-6880.
    PMID: 36947367 DOI: 10.1007/s12010-023-04384-2
    Our previous findings demonstrated that Helichrysetin possessed promising anti-cancer activity. It was able to induce apoptosis in the A549 cell line. However, its mechanism of action is unknown. The present study aimed to unravel possible underlying molecular mechanisms of helichrysetin-induced apoptosis in A549 (human lung carcinoma) cells using comparative quantitative proteomics (iTRAQ labeled), followed by an exhaustive bioinformatics analysis. Our results suggested that DNA damage response (DDR) and cell cycle arrest were responsible for lung cancer cell death with helichrysetin treatment. Among proteins that changed in abundance were Nrf2 and HMOX1. They are oxidative stress-related proteins and were increased in abundance. BRAT1 was also increased in abundance, suggesting an increase in DNA damage repair, indicating the occurrence of DNA damage due to oxidative stress. However, several essential DDR downstream proteins such as p-ATM, BRCA1, FANCD2, and Rb1 that would further increase DNA damage were found to be dramatically decreased in relative abundance. Cell cycle-related proteins, p53, p21, and cyclin D1, were increased while cyclin A, cyclin E, and cdk2 were decreased. This is predicted to facilitate S-phase arrest. Furthermore, excessive DNA damage and prolonged arrest would in turn result in the induction of mitochondrial-mediated apoptosis. Based on these observations, we postulate that the effects of helichrysetin were in part via the suppression of DNA damage response which led to DNA damage and prolonged cell cycle arrest. Subsequently, this event initiated mitochondrial-mediated apoptosis in A549 lung cancer cells.
    Matched MeSH terms: Nuclear Proteins/pharmacology
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