Displaying publications 1541 - 1560 of 9214 in total

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  1. Antioxidants improve β-cypermethrin degradation by alleviating oxidative damage and increasing bioavailability by Bacillus cereus GW-01
    Xie Y, Gong L, Liu S, Yan J, Zhao S, Xia C, et al.
    Environ Res, 2023 Nov 01;236(Pt 1):116680.
    PMID: 37500036 DOI: 10.1016/j.envres.2023.116680
    Microbial degradation of pesticide residues has the potential to reduce their hazards to human and environmental health. However, in some cases, degradation can activate pesticides, making them more toxic to microbes. Here we report on the β-cypermethrin (β-CY) toxicity to Bacillus cereus GW-01, a recently described β-CY degrader, and effects of antioxidants on β-CY degradation. GW-01 exposed to β-CY negatively affected the growth rate. The highest maximum specific growth rate (μm) appeared at 25 mg/L β-CY. β-CY induced the oxidative stress in GW-01. The activities of superoxide dismutase (SOD), catalyse (CAT), and glutathione-S-transferase (GST) were significantly higher than that in control (p 
    Matched MeSH terms: Adenosine Monophosphate/metabolism; Bacillus cereus/metabolism
  2. Hepatitis B virus DNA methylation and its potential role in chronic hepatitis B
    Low WF, Ngeow YF, Chook JB, Tee KK, Ong SK, Peh SC, et al.
    Expert Rev Mol Med, 2022 Nov 16;25:e11.
    PMID: 36380484 DOI: 10.1017/erm.2022.38
    Hepatitis B virus (HBV) infection led to 66% liver deaths world-wide in year 2015. Thirty-seven per cent of these deaths were the result of chronic hepatitis B (CHB)-associated hepatocellular carcinoma (HCC). Although early diagnosis of HCC improves survival, early detection is rare. Methylation of HBV DNA including covalently closed circular DNA (cccDNA) is more often encountered in HCC cases than those in CHB and cirrhosis. Three typical CpG islands within the HBV genome are the common sites for methylation. The HBV cccDNA methylation affects the viral replication and protein expression in the course of infection and may associate with the disease pathogenesis and HCC development. We review the current findings in HBV DNA methylation that provide insights into its role in HCC diagnosis.
    Matched MeSH terms: DNA, Viral/metabolism; Hepatitis B virus/metabolism
  3. Fulltext Recent progress in mass spectrometry-based strategies for elucidating protein-protein interactions
    Low TY, Syafruddin SE, Mohtar MA, Vellaichamy A, A Rahman NS, Pung YF, et al.
    Cell Mol Life Sci, 2021 Jul;78(13):5325-5339.
    PMID: 34046695 DOI: 10.1007/s00018-021-03856-0
    Protein-protein interactions are fundamental to various aspects of cell biology with many protein complexes participating in numerous fundamental biological processes such as transcription, translation and cell cycle. MS-based proteomics techniques are routinely applied for characterising the interactome, such as affinity purification coupled to mass spectrometry that has been used to selectively enrich and identify interacting partners of a bait protein. In recent years, many orthogonal MS-based techniques and approaches have surfaced including proximity-dependent labelling of neighbouring proteins, chemical cross-linking of two interacting proteins, as well as inferring PPIs from the co-behaviour of proteins such as the co-fractionating profiles and the thermal solubility profiles of proteins. This review discusses the underlying principles, advantages, limitations and experimental considerations of these emerging techniques. In addition, a brief account on how MS-based techniques are used to investigate the structural and functional properties of protein complexes, including their topology, stoichiometry, copy number and dynamics, are discussed.
    Matched MeSH terms: Proteins/metabolism*; Proteome/metabolism*
  4. Fulltext Role of Cytokines and Chemokines in NSCLC Immune Navigation and Proliferation
    Ramachandran S, Verma AK, Dev K, Goyal Y, Bhatt D, Alsahli MA, et al.
    Oxid Med Cell Longev, 2021;2021:5563746.
    PMID: 34336101 DOI: 10.1155/2021/5563746
    With over a million deaths every year around the world, lung cancer is found to be the most recurrent cancer among all types. Nonsmall cell lung carcinoma (NSCLC) amounts to about 85% of the entire cases. The other 15% owes it to small cell lung carcinoma (SCLC). Despite decades of research, the prognosis for NSCLC patients is poorly understood with treatment options limited. First, this article emphasises on the part that tumour microenvironment (TME) and its constituents play in lung cancer progression. This review also highlights the inflammatory (pro- or anti-) roles of different cytokines (ILs, TGF-β, and TNF-α) and chemokine (CC, CXC, C, and CX3C) families in the lung TME, provoking tumour growth and subsequent metastasis. The write-up also pinpoints recent developments in the field of chemokine biology. Additionally, it covers the role of extracellular vesicles (EVs), as alternate carriers of cytokines and chemokines. This allows the cytokines/chemokines to modulate the EVs for their secretion, trafficking, and aid in cancer proliferation. In the end, this review also stresses on the role of these factors as prognostic biomarkers for lung immunotherapy, apart from focusing on inflammatory actions of these chemoattractants.
    Matched MeSH terms: Cytokines/metabolism*; Chemokines/metabolism*
  5. Cluster of differentiation 147 (CD147) as potential membrane protein biomarker for bladder cancer cells
    Roslan A, Said DS, Sulaiman N, Mohd Ghani KA, Nurdin A
    J Pharm Biomed Anal, 2023 Nov 30;236:115729.
    PMID: 37778199 DOI: 10.1016/j.jpba.2023.115729
    Studies reveal that alterations in membrane protein (MP) patterns are associated with underlying drug resistance to chemotherapy. Therefore, the tryptic-digested MPs from the bladder cancer cell line were subjected to global proteomics using LC-MS/MS to identify the highly expressed potential MPs in bladder cancer cells. Our findings revealed the identification of MP biomarkers, CD147, and caveolin-1. Immunocytochemistry analysis confirmed the presence of CD147 on the cell membrane, while caveolin-1 showed positive signals without apparent staining on the membrane, suggesting its existence in multiple locations. Western blot analysis confirmed the higher expression of CD147 in non-invasive (RT 112) and metastatic (UM-UC-13) bladder cancer cells compared to invasive bladder cancer cells (5637 and J82), suggesting its potential as an MP biomarker for both of the former subtypes. The identified MPs could be used as drug therapy targets aimed at improving drug sensitivity and enhancing treatment outcomes in bladder cancer patients. SIGNIFICANCE: Identification of the membrane proteins associated with bladder cancer recurrence is crucial to understanding the mechanisms underlying the drug resistance to chemotherapy.
    Matched MeSH terms: Caveolin 1/metabolism; Antigens, CD147/metabolism
  6. Fulltext Bioprospecting of microalgae metabolites against cytokine storm syndrome during COVID-19
    Wan Afifudeen CL, Teh KY, Cha TS
    Mol Biol Rep, 2022 Feb;49(2):1475-1490.
    PMID: 34751914 DOI: 10.1007/s11033-021-06903-y
    In viral respiratory infections, disrupted pathophysiological outcomes have been attributed to hyper-activated and unresolved inflammation responses of the immune system. Integration between available drugs and natural therapeutics have reported benefits in relieving inflammation-related physiological outcomes and microalgae may be a feasible source from which to draw from against future coronavirus-infections. Microalgae represent a large and diverse source of chemically functional compounds such as carotenoids and lipids that possess various bioactivities, including anti-inflammatory properties. Therefore in this paper, some implicated pathways causing inflammation in viral respiratory infections are discussed and juxtaposed along with available research done on several microalgal metabolites. Additionally, the therapeutic properties of some known anti-inflammatory, antioxidant and immunomodulating compounds sourced from microalgae are reported for added clarity.
    Matched MeSH terms: Inflammation/metabolism; Microalgae/metabolism*
  7. Combination of QSAR Modeling and Hybrid-Based Consensus Scoring to Identify Dual-Targeting Inhibitors of PLK1 and p38γ
    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; Protein Kinase Inhibitors/metabolism
  8. Orbital fluid shear stress promotes osteoblast metabolism, proliferation and alkaline phosphates activity in vitro
    Aisha MD, Nor-Ashikin MN, Sharaniza AB, Nawawi H, Froemming GR
    Exp Cell Res, 2015 Sep 10;337(1):87-93.
    PMID: 26163894 DOI: 10.1016/j.yexcr.2015.07.002
    Prolonged disuse of the musculoskeletal system is associated with reduced mechanical loading and lack of anabolic stimulus. As a form of mechanical signal, the multidirectional orbital fluid shear stress transmits anabolic signal to bone forming cells in promoting cell differentiation, metabolism and proliferation. Signals are channeled through the cytoskeleton framework, directly modifying gene and protein expression. For that reason, we aimed to study the organization of Normal Human Osteoblast (NHOst) cytoskeleton with regards to orbital fluid shear (OFS) stress. Of special interest were the consequences of cytoskeletal reorganization on NHOst metabolism, proliferation, and osteogenic functional markers. Cells stimulated at 250 RPM in a shaking incubator resulted in the rearrangement of actin and tubulin fibers after 72 h. Orbital shear stress increased NHOst mitochondrial metabolism and proliferation, simultaneously preventing apoptosis. The ratio of RANKL/OPG was reduced, suggesting that orbital shear stress has the potential to inhibit osteoclastogenesis and osteoclast activity. Increase in ALP activity and OCN protein production suggests that stimulation retained osteoblast function. Shear stress possibly generated through actin seemed to hold an anabolic response as osteoblast metabolism and functional markers were enhanced. We hypothesize that by applying orbital shear stress with suitable magnitude and duration as a non-drug anabolic treatment can help improve bone regeneration in prolonged disuse cases.
    Matched MeSH terms: Alkaline Phosphatase/metabolism; Cytoskeleton/metabolism
  9. Molecular Cloning, Expression, Sequence Characterization and Structural Insight of Bubalus bubalis Growth Hormone-Receptor
    Gul R, Hanif MU, Gul F, Rehman HM, Saleem M, Ahmad MS, et al.
    Mol Biotechnol, 2023 Jul;65(7):1062-1075.
    PMID: 36437440 DOI: 10.1007/s12033-022-00612-y
    The current study focuses on molecular cloning, expression and structural characterization of growth hormone-receptor (GHR) and its extracellular domain as growth hormone binding protein (GHBP) from the liver of Nili-Ravi buffalo (Bubalus bubalis; Bb). RNA was isolated, genes were amplified by reverse transcriptase-polymerase chain reaction and sequence was characterized. The BbGHR sequence showed three amino acid variations in the extracellular domain when compared with Indian BbGHR. For the production of full length BbGHR and BbGHBP in Escherichia coli (E. coli) BL21 (RIPL) Codon Plus, expression plasmids were constructed under the control of T7lac promoter and isopropyl β-D thiogalactopyranoside was used as an inducer. BbGHR and BbGHBP were expressed as inclusion bodies at ~ 40% and > 30% of the total E. coli proteins, respectively. The BbGHBP was solubilized and refolded by dilution method using cysteine-cystine redox potential. The recombinant BbGHBP was purified and biological activity was checked on HeLa cell lines showing increase cell proliferation in the presence of ovine GH (oGH), hence justifying the increase in the half-life of GH in the presence of BbGHBP. For the molecular interactions of oGH-BbGHBP multiple docking programs were employed to explore the subsequent interactions which showed high binding affinity and presence of large number of hydrogen bonds. Molecular Dynamics studies performed to examine the stability of proteins and exhibited stable structures along with favorable molecular interactions. This study has described the sequence characterization of BbGHR in Nili-Ravi buffaloes and hence provided the basis for the assessment of GH-GHR binding in other Bovidae species.
    Matched MeSH terms: Escherichia coli/metabolism; Growth Hormone/metabolism
  10. Fulltext Metformin: A Review of Potential Mechanism and Therapeutic Utility Beyond Diabetes
    Dutta S, Shah RB, Singhal S, Dutta SB, Bansal S, Sinha S, et al.
    Drug Des Devel Ther, 2023;17:1907-1932.
    PMID: 37397787 DOI: 10.2147/DDDT.S409373
    Metformin has been designated as one of the most crucial first-line therapeutic agents in the management of type 2 diabetes mellitus. Primarily being an antihyperglycemic agent, metformin also has a plethora of pleiotropic effects on various systems and processes. It acts majorly by activating AMPK (Adenosine Monophosphate-Activated Protein Kinase) in the cells and reducing glucose output from the liver. It also decreases advanced glycation end products and reactive oxygen species production in the endothelium apart from regulating the glucose and lipid metabolism in the cardiomyocytes, hence minimizing the cardiovascular risks. Its anticancer, antiproliferative and apoptosis-inducing effects on malignant cells might prove instrumental in the malignancy of organs like the breast, kidney, brain, ovary, lung, and endometrium. Preclinical studies have also shown some evidence of metformin's neuroprotective role in Parkinson's disease, Alzheimer's disease, multiple sclerosis and Huntington's disease. Metformin exerts its pleiotropic effects through varied pathways of intracellular signalling and exact mechanism in the majority of them remains yet to be clearly defined. This article has extensively reviewed the therapeutic benefits of metformin and the details of its mechanism for a molecule of boon in various conditions like diabetes, prediabetes, obesity, polycystic ovarian disease, metabolic derangement in HIV, various cancers and aging.
    Matched MeSH terms: Glucose/metabolism; AMP-Activated Protein Kinases/metabolism
  11. Nano-TiO2 aggravates the adverse effect of pentachlorophenol on antioxidant and immune response in anti-predatory mussels
    Wei S, Sun B, Liu C, Sokolova I, Waiho K, Fang JKH, et al.
    Sci Total Environ, 2023 Oct 01;893:164836.
    PMID: 37321498 DOI: 10.1016/j.scitotenv.2023.164836
    Nano-TiO2 can act as a vector to organic compounds, such as pentachlorophenol (PCP) posing a potential threat to the marine ecosystems. Studies showed that nano pollutant toxicity can be modulated by abiotic factors, but little is known about the potential influence of biotic stressors (such as predators) on the physiological responses to pollutants in marine organisms. We explored the effects of n-TiO2 and PCP on the mussel Mytilus coruscus in the presence of its natural predator, the swimming crab Portunus trituberculatus. Exposure to n-TiO2, PCP, and predation risk showed interactive effects on antioxidant and immune parameters of the mussels. Elevated activities of catalase (CAT), glutathione peroxidase (GPX), acid phosphatase (ACP) and alkaline phosphatase (AKP), suppressed activity of superoxide dismutase (SOD), lower levels of glutathione (GSH) and increased malondialdehyde (MDA) levels indicated dysregulation of the antioxidant system and immune stress induced by single PCP or n-TiO2 exposure. Integrated biomarker (IBR) response values showed the effect of PCP was concentration dependent. Of the two used n-TiO2 sizes (25 and 100 nm), larger particles induced higher antioxidant and immune disturbances indicating higher toxicity possibly due to higher bioavailability. Compared to single PCP exposure, the combination of n-TiO2 and PCP enhanced the imbalance of SOD/CAT and GSH/GPX and led to elevated oxidative lesions and activation of immune-related enzymes. Overall, the combined impacts of pollutants and biotic stress exhibited a greater magnitude of adverse effects on antioxidant defense and immune parameters in mussels. The toxicological effects of PCP were exacerbated in the presence of n-TiO2, and the deleterious impact of these stressors was further amplified under predator-induced risk after prolonged (28 days) exposure. However, the underlying physiological regulatory mechanisms governing the interplay of these stressors and predatory cues on mussels remain elusive, warranting further investigation.
    Matched MeSH terms: Antioxidants/metabolism; Superoxide Dismutase/metabolism
  12. Phage N15-Based Vectors for Gene Cloning and Expression in Bacteria and Mammalian Cells
    Wong YC, Ng AWR, Chen Q, Liew PS, Lee CW, Sim EUH, et al.
    ACS Synth Biol, 2023 Apr 21;12(4):909-921.
    PMID: 37026178 DOI: 10.1021/acssynbio.2c00580
    Bacteriophage N15 is the first virus known to deliver linear prophage into Escherichia coli. During its lysogenic cycle, N15 protelomerase (TelN) resolves its telomerase occupancy site (tos) into hairpin telomeres. This protects the N15 prophage from bacterial exonuclease degradation, enabling it to stably replicate as a linear plasmid in E. coli. Interestingly, purely proteinaceous TelN can retain phage DNA linearization and hairpin formation without involving host- or phage-derived intermediates or cofactors in the heterologous environment. This unique feature has led to the advent of synthetic linear DNA vector systems derived from the TelN-tos module for the genetic engineering of bacterial and mammalian cells. This review will focus on the development and advantages of N15-based novel cloning and expression vectors in the bacterial and mammalian environments. To date, N15 is the most widely exploited molecular tool for the development of linear vector systems, especially the production of therapeutically useful miniDNA vectors without a bacterial backbone. Compared to typical circular plasmids, linear N15-based plasmids display remarkable cloning fidelity in propagating unstable repetitive DNA sequences and large genomic fragments. Additionally, TelN-linearized vectors with the relevant origin of replication can replicate extrachromosomally and retain transgenes functionality in bacterial and mammalian cells without compromising host cell viability. Currently, this DNA linearization system has shown robust results in the development of gene delivery vehicles, DNA vaccines and engineering mammalian cells against infectious diseases or cancers, highlighting its multifaceted importance in genetic studies and gene medicine.
    Matched MeSH terms: DNA/metabolism; Escherichia coli/metabolism
  13. Augmentation index is a better marker for cardiovascular risk in young Malaysian males. A comparison of involvement of pulse wave velocity, augmentation index, and C-reactive protein
    Aminuddin A, Chellappan K, Maskon O, Zakaria Z, Karim AA, Ngah WZ, et al.
    Saudi Med J, 2014 Feb;35(2):138-46.
    PMID: 24562512
    To determine the association between carotid femoral pulse wave velocity (PWVCF) and augmentation index (AI) with future cardiovascular disease (CVD) risk, and to assess whether high sensitivity C-reactive protein (hs-CRP) is an important mediator towards these vascular changes, among young men.
    Matched MeSH terms: C-Reactive Protein/metabolism*; Cardiovascular Diseases/metabolism*
  14. Fulltext Ophthalmic Intervention of Naringenin Decreases Vascular Endothelial Growth Factor by Counteracting Oxidative Stress and Cellular Damage in In Vivo Zebrafish
    Sudhakaran G, Chandran A, Sreekutty AR, Madesh S, Pachaiappan R, Almutairi BO, et al.
    Molecules, 2023 Jul 12;28(14).
    PMID: 37513223 DOI: 10.3390/molecules28145350
    Diabetes Mellitus is a metabolic disease that leads to microvascular complications like Diabetic retinopathy (DR), a major cause of blindness worldwide. Current medications for DR are expensive and report multiple side effects; therefore, an alternative medication that alleviates the disease condition is required. An interventional approach targeting the vascular endothelial growth factor (VEGF) remains a treatment strategy for DR. Anti-VEGF medicines are being investigated as the main therapy for managing vision-threatening complications of DR, such as diabetic macular oedema. Therefore, this study investigated the effect of flavonoid naringenin (NG) from citrus fruits on inhibiting early DR in zebrafish. When exposed to 130 mM glucose, the zebrafish larvae developed a hyperglycaemic condition accompanied by oxidative stress, cellular damage, and lipid peroxidation. Similarly, when adult zebrafish were exposed to 4% Glucose, high glucose levels were observed in the ocular region and massive destruction in the retinal membrane. High glucose upregulated the expression of VEGF. In comparison, the co-exposure to NG inhibited oxidative stress and cellular damage and restored the glutathione levels in the ocular region of the zebrafish larvae. NG regressed the glucose levels and cellular damage along with an inhibition of macular degeneration in the retina of adult zebrafish and normalized the overexpression of VEGF as a promising strategy for treating DR. Therefore, intervention of NG could alleviate the domestication of alternative medicine in ophthalmic research.
    Matched MeSH terms: Vascular Endothelial Growth Factors/metabolism; Vascular Endothelial Growth Factor A/metabolism
  15. Fulltext Omicron (BA.1) and sub-variants (BA.1.1, BA.2, and BA.3) of SARS-CoV-2 spike infectivity and pathogenicity: A comparative sequence and structural-based computational assessment
    Kumar S, Karuppanan K, Subramaniam G
    J Med Virol, 2022 Oct;94(10):4780-4791.
    PMID: 35680610 DOI: 10.1002/jmv.27927
    The Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now spread throughout the world. We used computational tools to assess the spike infectivity, transmission, and pathogenicity of Omicron (BA.1) and sub-variants (BA.1.1, BA.2, and BA.3) in this study. BA.1 has 39 mutations, BA.1.1 has 40 mutations, BA.2 has 31 mutations, and BA.3 has 34 mutations, with 21 shared mutations between all. We observed 11 common mutations in Omicron's receptor-binding domain (RBD) and sub-variants. In pathogenicity analysis, the Y505H, N786K, T95I, N211I, N856K, and V213R mutations in omicron and sub-variants are predicted to be deleterious. Due to the major effect of the mutations characterizing in the RBD, we found that Omicron and sub-variants had a higher positive electrostatic surface potential. This could increase interaction between RBD and negative electrostatic surface potential human angiotensin-converting enzyme 2 (hACE2). Omicron and sub-variants had a higher affinity for hACE2 and the potential for increased transmission when compared to the wild-type (WT). Negative electrostatic potential of N-terminal domain (NTD) of the spike protein value indicates that the Omicron variant binds receptors less efficiently than the WT. Given that at least one receptor is highly expressed in lung and bronchial cells, the electrostatic potential of NTD negative value could be one of the factors contributing to why the Omicron variant is thought to be less harmful to the lower respiratory tract. Among Omicron sub-lineages, BA.2 and BA.3 have a higher transmission potential than BA.1 and BA.1.1. We predicted that mutated residues in BA.1.1 (K478), BA.2 (R400, R490, and R495), and BA.3 (R397 and H499) formation of new salt bridges and hydrogen bonds. Omicron and sub-variant mutations at Receptor-binding Motif (RBM) residues such as Q493R, N501Y, Q498, T478K, and Y505H all contribute significantly to binding affinity with human ACE2. Interactions with Omicron variant mutations at residues 493, 496, 498, and 501 seem to restore ACE2 binding effectiveness lost due to other mutations like K417N.
    Matched MeSH terms: Peptidyl-Dipeptidase A/metabolism; Receptors, Virus/metabolism
  16. Mechanistic insight into immunomodulatory effects of food-functioned plant secondary metabolites
    Ali Reza ASM, Nasrin MS, Hossen MA, Rahman MA, Jantan I, Haque MA, et al.
    Crit Rev Food Sci Nutr, 2023;63(22):5546-5576.
    PMID: 34955042 DOI: 10.1080/10408398.2021.2021138
    Medicinally important plant-foods offer a balanced immune function, which is essential for protecting the body against antigenic invasion, mainly by microorganisms. Immunomodulators play pivotal roles in supporting immune function either suppressing or stimulating the immune system's response to invading pathogens. Among different immunomodulators, plant-based secondary metabolites have emerged as high potential not only for immune defense but also for cellular immunoresponsiveness. These natural immunomodulators can be developed into safer alternatives to the clinically used immunosuppressants and immunostimulant cytotoxic drugs which possess serious side effects. Many plants of different species have been reported to possess strong immunomodulating properties. The immunomodulatory effects of plant extracts and their bioactive metabolites have been suggested due to their diverse mechanisms of modulation of the complex immune system and their multifarious molecular targets. Phytochemicals such as alkaloids, flavonoids, terpenoids, carbohydrates and polyphenols have been reported as responsible for the immunomodulatory effects of several medicinal plants. This review illustrates the potent immunomodulatory effects of 65 plant secondary metabolites, including dietary compounds and their underlying mechanisms of action on cellular and humoral immune functions in in vitro and in vivo studies. The clinical potential of some of the compounds to be used for various immune-related disorders is highlighted.
    Matched MeSH terms: Adjuvants, Immunologic/metabolism; Phytochemicals/metabolism
  17. Fulltext Exercise and pre-habilitation with high whey-protein-based meal replacement therapy promote weight loss and preserve muscle mass before bariatric surgery
    Ho C, Samwil SNM, Kahairudin Z, Jamhuri N, Abd Aziz A
    Asian J Surg, 2023 Sep;46(9):3716-3721.
    PMID: 36931924 DOI: 10.1016/j.asjsur.2023.03.026
    BACKGROUND: Bariatric surgery is considered as an effective therapy for those with morbid obesity. Preoperative weight loss with a very low-calorie diet is commonly used to ease the bariatric surgery. Pre-habilitation increases functional and physiological capacity. The study demonstrated the changes of body composition and functional status following short term pre-habilitation before bariatric surgery.

    METHOD: This prospective study targeted those admitted for bariatric surgery. Participants underwent the biweekly pre-habilitation program included an individualized high whey-based protein very low-calorie (VLCHP) enteral regime (600-900 kcal/day) and moderate intensive exercise before bariatric surgery. Body composition and waist circumference were assessed after fortnight. Participants were segregated into morbid obese (MOG) (BMI <49 kg/m2) and super morbid obese group (SMOG) (BMI ≥50 kg/m2) for analysis.

    RESULT: Majority of participants were female (71%) with median age 36.0 years old (MOG) and 34.3 years old (SMOG) respectively. SMOG achieved significant greater loss in weight (-7.4 kg vs -4.0 kg), fat percentage (-4.4% vs -1.7%) and fat mass (-9.9 kg vs -3.8 kg); but MOG had a significant increment in muscle mass (3.2 kg vs 2.8 kg) as compared to SOG (p 

    Matched MeSH terms: Whey/metabolism; Muscles/metabolism
  18. Fulltext Alcohol Dependence Modulates Amygdalar mTORC2 and PKCε Expression in a Rodent Model
    Hanim A, Mohamed IN, Mohamed RMP, Mokhtar MH, Makpol S, Naomi R, et al.
    Nutrients, 2023 Jul 05;15(13).
    PMID: 37447362 DOI: 10.3390/nu15133036
    Multiple alcohol use disorder (AUD)-related behavioral alterations are governed by protein kinase C epsilon (PKCε), particularly in the amygdala. Protein kinase C (PKC) is readily phosphorylated at Ser729 before activation by the mTORC2 protein complex. In keeping with this, the current study was conducted to assess the variations in mTORC2 and PKCε during different ethanol exposure stages. The following groups of rats were employed: control, acute, chronic, ethanol withdrawal (EW), and EW + ethanol (EtOH). Ethanol-containing and non-ethanol-containing modified liquid diets (MLDs) were administered for 27 days. On day 28, either saline or ethanol (2.5 g/kg, 20% v/v) was intraperitoneally administered, followed by bilateral amygdala extraction. PKCε mRNA levels were noticeably increased in the amygdala of the EW + EtOH and EW groups. Following chronic ethanol consumption, the stress-activated map kinase-interacting protein 1 (Sin1) gene expression was markedly decreased. In the EW, EW + EtOH, and chronic ethanol groups, there was a profound increase in the protein expression of mTOR, Sin1, PKCε, and phosphorylated PKCε (Ser729). The PKCε gene and protein expressions showed a statistically significant moderate association, according to a correlation analysis. Our results suggest that an elevated PKCε protein expression in the amygdala during EW and EW + EtOH occurred at the transcriptional level. However, an elevation in the PKCε protein expression, but not its mRNA, after chronic ethanol intake warrants further investigation to fully understand the signaling pathways during different episodes of AUD.
    Matched MeSH terms: RNA, Messenger/metabolism; Protein Kinase C-epsilon/metabolism
  19. Fulltext HIF-1-Independent Mechanisms Regulating Metabolic Adaptation in Hypoxic Cancer Cells
    Lee SH, Golinska M, Griffiths JR
    Cells, 2021 Sep 09;10(9).
    PMID: 34572020 DOI: 10.3390/cells10092371
    In solid tumours, cancer cells exist within hypoxic microenvironments, and their metabolic adaptation to this hypoxia is driven by HIF-1 transcription factor, which is overexpressed in a broad range of human cancers. HIF inhibitors are under pre-clinical investigation and clinical trials, but there is evidence that hypoxic cancer cells can adapt metabolically to HIF-1 inhibition, which would provide a potential route for drug resistance. Here, we review accumulating evidence of such adaptions in carbohydrate and creatine metabolism and other HIF-1-independent mechanisms that might allow cancers to survive hypoxia despite anti-HIF-1 therapy. These include pathways in glucose, glutamine, and lipid metabolism; epigenetic mechanisms; post-translational protein modifications; spatial reorganization of enzymes; signalling pathways such as Myc, PI3K-Akt, 2-hyxdroxyglutarate and AMP-activated protein kinase (AMPK); and activation of the HIF-2 pathway. All of these should be investigated in future work on hypoxia bypass mechanisms in anti-HIF-1 cancer therapy. In principle, agents targeted toward HIF-1β rather than HIF-1α might be advantageous, as both HIF-1 and HIF-2 require HIF-1β for activation. However, HIF-1β is also the aryl hydrocarbon nuclear transporter (ARNT), which has functions in many tissues, so off-target effects should be expected. In general, cancer therapy by HIF inhibition will need careful attention to potential resistance mechanisms.
    Matched MeSH terms: Neoplasms/metabolism*; Hypoxia-Inducible Factor 1/metabolism*
  20. Fulltext Chitinase: diversity, limitations, and trends in engineering for suitable applications
    Oyeleye A, Normi YM
    Biosci Rep, 2018 Sep 03;38(4).
    PMID: 30042170 DOI: 10.1042/BSR20180323
    Chitinases catalyze the degradation of chitin, a ubiquitous polymer generated from the cell walls of fungi, shells of crustaceans, and cuticles of insects. They are gaining increasing attention in medicine, agriculture, food and drug industries, and environmental management. Their roles in the degradation of chitin for the production of industrially useful products and in the control of fungal pathogens and insect pests render them attractive for such purposes. However, chitinases have diverse sources, characteristics, and mechanisms of action that seem to restrain optimization procedures and render standardization techniques for enhanced practical applications complex. Hence, results of laboratory trials are not usually consistent with real-life applications. With the growing field of protein engineering, these complexities can be overcome by modifying or redesigning chitinases to enhance specific features required for specific applications. In this review, the variations in features and mechanisms of chitinases that limit their exploitation in biotechnological applications are compiled. Recent attempts to engineer chitinases for improved efficiency are also highlighted.
    Matched MeSH terms: Chitin/metabolism; Chitinase/metabolism*
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