Displaying publications 1 - 20 of 113 in total

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  1. Fulltext Exploring the molecular pathogenesis, diagnosis and treatment of fibrolamellar hepatocellular carcinoma: A state of art review of the current literature
    Alshareefy Y, Shen CY, Prekash RJ
    Pathol Res Pract, 2023 Aug;248:154655.
    PMID: 37429175 DOI: 10.1016/j.prp.2023.154655
    This paper aims to present a detailed overview of fibrolamellar carcinoma (FLC), a variant of hepatocellular carcinoma (HCC) that accounts for approximately 1-9% of all cases a. according to the SEER database. Despite ongoing research, the aetiology of FLC tumours remains unclear. Nevertheless, FLC is believed to have a better overall prognosis than other primary liver tumours, such as hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma. This study aims to present a comprehensive overview of fibrolamellar carcinoma (FLC), with a focus on its epidemiology, pathogenesis, diagnosis, treatment, and prognosis. FLC frequently incorporate features of stomach pain, weight loss, and malaise in their clinical signs and symptoms, which are generally nonspecific Ultimately, the most common physical finding is an abdominal mass or hepatomegaly. With this said, several unusual presentations have been documented such as Budd Chiari syndrome, severe anaemia, non-bacterial thrombotic endocarditis and many more. In regards to this tumour's genetic analysis, it is characterised by a 400 kb deletion on chromosome 19 leading to a functional DNAJB1-PRKACA chimeric transcript in addition to tetraploidy in 50% of cases. FLC is chromosomally stable as compared to typical HCC. mTOR pathway activation has also been found to play a critical role in 47% of these tumours and EFGR over-expression is also evident. Fibrolamellar carcinomas (FLCs) exhibit a distinctive gross appearance, characterized by a yellow to pale tan colour, with a consistency that can vary from soft to firm and hard. In addition, a central scar is observed in 60-70% of FLC cases. The central scar is typically white or grey in colour and has a fibrous appearance, which is often surrounded by nodular, tumour-like tissue. Its histologic appearance is characterized by large polygonal cells with abundant eosinophilic cytoplasm, large vesiculated nuclei, large nucleoli, and arranged in lamellar bands of collagen fibres. Lamellar bands of fibrosis, consisting of collagen type I, III and IV, have also been identified as a distinctive histologic feature that is observed under low power magnification. Ultrasound, CT and MRI along with image guided biopsy are the primary modalities in diagnosis. Current management options include systemic therapy which has thus far been unremarkable with platinum-based therapies as well combination therapy with interferon alpha-2b being the most successful options. Surgical resection remains the primary treatment modality and there have been no advances in targeted therapies. Although the prognosis for FLC is favourable as compared to other hepatic cancer subtypes such as intrahepatic cholangiocarcinoma, there is a high rate of recurrence ranging from 33% to 100% with a median recurrence-free survival of 20-48 months. As a result of this there is a low overall cure rate associated with this tumour type and much more research is required to gain an in-depth understanding of the molecular mechanisms occurring in order to provide more adequate treatment to patients who suffer from this condition.
    Matched MeSH terms: HSP40 Heat-Shock Proteins
  2. Improving animal welfare status and meat quality through assessment of stress biomarkers: A critical review
    Kumar P, Ahmed MA, Abubakar AA, Hayat MN, Kaka U, Ajat M, et al.
    Meat Sci, 2023 Mar;197:109048.
    PMID: 36469986 DOI: 10.1016/j.meatsci.2022.109048
    Stress induces various physiological and biochemical alterations in the animal body, which are used to assess the stress status of animals. Blood profiles, serum hormones, enzymes, and physiological conditions such as body temperature, heart, and breathing rate of animals are the most commonly used stress biomarkers in the livestock sector. Previous exposure, genetics, stress adaptation, intensity, duration, and rearing practices result in wide intra- and inter-animal variations in the expression of various stress biomarkers. The use of meat proteomics by adequately analyzing the expression of various muscle proteins such as heat shock proteins (HSPs), acute phase proteins (APPs), texture, and tenderness biomarkers help predict meat quality and stress in animals before slaughter. Thus, there is a need to identify non-invasive, rapid, and accurate stress biomarkers that can objectively assess stress in animals. The present manuscript critically reviews various aspects of stress biomarkers in animals and their application in mitigating preslaughter stress in meat production.
    Matched MeSH terms: Heat-Shock Proteins*
  3. Fulltext Prenatal auditory stimulation induces physiological stress responses in developing embryos and newly hatched chicks
    Hanafi SA, Zulkifli I, Ramiah SK, Chung ELT, Kamil R, Awad EA
    Poult Sci, 2023 Feb;102(2):102390.
    PMID: 36608455 DOI: 10.1016/j.psj.2022.102390
    Prenatal stress may evoke considerable physiological consequences on the developing poultry embryos and neonates. The present study aimed to determine prenatal auditory stimulation effects on serum levels of ceruloplasmin (CPN), alpha-1-acid glycoprotein (AGP), corticosterone (CORT), and heat shock protein 70 (Hsp70) regulations in developing chicken embryos and newly hatched chicks. Hatching eggs were subjected to the following auditory treatments; 1) control (no additional sound treatment other than the background sound of the incubator's compressors at 40 dB), 2) noise exposure (eggs were exposed to pre-recorded traffic noise at 90 dB) (NOISE), and 3) music exposure (eggs were exposed to Mozart's Sonata for Two Pianos in D Major, K 488 at 90 dB) (MUSIC). The NOISE and MUSIC treatments were for 20 min/h for 24 h (a total of 8 h/d), starting from embryonic days (ED) 12 to hatching. The MUSIC (1.37 ± 0.1 ng/mL) and NOISE (1.49 ± 0.2 ng/mL) treatments significantly elevated CPN at ED 15 compared to the Control (0.82 ± 0.04 ng/mL) group and post-hatch day 1 (Control, 1.86 ± 0.2 ng/mL; MUSIC, 2.84 ± 0.4 ng/mL; NOISE, 3.04 ± 0.3 ng/mL), AGP at ED 15 (Control, 39.1 ± 7.1 mg/mL; MUSIC, 85.5 ± 12.9 mg/mL; NOISE, 85.4 ± 15.1 mg/mL) and post-hatch day 1 (Control, 20.4 ± 2.2 mg/mL; MUSIC, 30.5 ± 4.7 mg/mL; NOISE, 30.3 ± 1.4 mg/mL). CORT significantly increased at ED 15 in both MUSIC (9.024 ± 1.4 ng/mL) and NOISE (12.15 ± 1.6 ng/mL) compared to the Control (4.39 ± 0.7 ng/mL) group. On the other hand, MUSIC exposed embryos had significantly higher Hsp70 expression than their Control and NOISE counterparts at ED 18 (Control, 12.9 ± 1.2 ng/mL; MUSIC, 129.6 ± 26.4 ng/mL; NOISE, 13.3 ± 2.3 ng/mL) and post-hatch day 1 (Control, 15.2 ± 1.7 ng/mL; MUSIC, 195.5 ± 68.5 ng/mL; NOISE, 13.2 ± 2.7 ng/mL). In conclusion, developing chicken embryos respond to auditory stimulation by altering CPN, AGP, CORT, and Hsp70. The alterations of these analytes could be important in developing embryos and newly hatched chicks to cope with stress attributed to auditory stimulation.
    Matched MeSH terms: HSP70 Heat-Shock Proteins/metabolism
  4. Fulltext Timosaponin AIII promotes non-small-cell lung cancer ferroptosis through targeting and facilitating HSP90 mediated GPX4 ubiquitination and degradation
    Zhou C, Yu T, Zhu R, Lu J, Ouyang X, Zhang Z, et al.
    Int J Biol Sci, 2023;19(5):1471-1489.
    PMID: 37056925 DOI: 10.7150/ijbs.77979
    Timosaponin AIII (Tim-AIII), a steroid saponin, exhibits strong anticancer activity in a variety of cancers, especially breast cancer and liver cancer. However, the underlying mechanism of the effects of Tim-AIII-mediated anti-lung cancer effects remain obscure. In this study, we showed that Tim-AIII suppressed cell proliferation and migration, induced G2/M phase arrest and ultimately triggered cell death of non-small cell lung cancer (NSCLC) cell lines accompanied by the release of reactive oxygen species (ROS) and iron accumulation, malondialdehyde (MDA) production, and glutathione (GSH) depletion. Interestingly, we found that Tim-AIII-mediated cell death was reversed by ferroptosis inhibitor ferrostatin-1 (Fer-1). Meanwhile, the heat shock protein 90 (HSP90) was predicted and verified as the direct binding target of Tim-AIII by SwissTargetPrediction (STP) and surface plasmon resonance (SPR) assay. Further study showed that Tim-AIII promoted HSP90 expression and Tim-AIII induced cell death was blocked by the HSP90 inhibitor tanespimycin, indicating that HSP90 was the main target of Tim-AIII to further trigger intracellular events. Mechanical analysis revealed that the Tim-AIII-HSP90 complex further targeted and degraded glutathione peroxidase 4 (GPX4), and promoted the ubiquitination of GPX4, as shown by an immunoprecipitation, degradation and in vitro ubiquitination assay. In addition, Tim-AIII inhibited cell proliferation, induced cell death, led to ROS and iron accumulation, MDA production, GSH depletion, as well as GPX4 ubiquitination and degradation, were markedly abrogated when HSP90 was knockdown by HSP90-shRNA transfection. Importantly, Tim-AIII also showed a strong capacity of preventing tumor growth by promoting ferroptosis in a subcutaneous xenograft tumor model, whether C57BL/6J or BALB/c-nu/nu nude mice. Together, HSP90 was identified as a new target of Tim-AIII. Tim-AIII, by binding and forming a complex with HSP90, further targeted and degraded GPX4, ultimately induced ferroptosis in NSCLC. These findings provided solid evidence that Tim-AIII can serve as a potential candidate for NSCLC treatment.
    Matched MeSH terms: HSP90 Heat-Shock Proteins/metabolism
  5. Fulltext A novel sequence-based predictor for identifying and characterizing thermophilic proteins using estimated propensity scores of dipeptides
    Charoenkwan P, Chotpatiwetchkul W, Lee VS, Nantasenamat C, Shoombuatong W
    Sci Rep, 2021 Dec 10;11(1):23782.
    PMID: 34893688 DOI: 10.1038/s41598-021-03293-w
    Owing to their ability to maintain a thermodynamically stable fold at extremely high temperatures, thermophilic proteins (TTPs) play a critical role in basic research and a variety of applications in the food industry. As a result, the development of computation models for rapidly and accurately identifying novel TTPs from a large number of uncharacterized protein sequences is desirable. In spite of existing computational models that have already been developed for characterizing thermophilic proteins, their performance and interpretability remain unsatisfactory. We present a novel sequence-based thermophilic protein predictor, termed SCMTPP, for improving model predictability and interpretability. First, an up-to-date and high-quality dataset consisting of 1853 TPPs and 3233 non-TPPs was compiled from published literature. Second, the SCMTPP predictor was created by combining the scoring card method (SCM) with estimated propensity scores of g-gap dipeptides. Benchmarking experiments revealed that SCMTPP had a cross-validation accuracy of 0.883, which was comparable to that of a support vector machine-based predictor (0.906-0.910) and 2-17% higher than that of commonly used machine learning models. Furthermore, SCMTPP outperformed the state-of-the-art approach (ThermoPred) on the independent test dataset, with accuracy and MCC of 0.865 and 0.731, respectively. Finally, the SCMTPP-derived propensity scores were used to elucidate the critical physicochemical properties for protein thermostability enhancement. In terms of interpretability and generalizability, comparative results showed that SCMTPP was effective for identifying and characterizing TPPs. We had implemented the proposed predictor as a user-friendly online web server at http://pmlabstack.pythonanywhere.com/SCMTPP in order to allow easy access to the model. SCMTPP is expected to be a powerful tool for facilitating community-wide efforts to identify TPPs on a large scale and guiding experimental characterization of TPPs.
    Matched MeSH terms: Heat-Shock Proteins/metabolism; Heat-Shock Proteins/chemistry*
  6. Benchtop Isolation and Characterisation of Small Extracellular Vesicles from Human Mesenchymal Stem Cells
    Tan KL, Chia WC, How CW, Tor YS, Show PL, Looi QHD, et al.
    Mol Biotechnol, 2021 Sep;63(9):780-791.
    PMID: 34061307 DOI: 10.1007/s12033-021-00339-2
    The objective of this study is to develop a simple protocol to isolate and characterise small extracellular vesicles (sEVs) from human umbilical cord-derived MSCs (hUC-MSCs). hUC-MSCs were characterised through analysis of morphology, immunophenotyping and multidifferentiation ability. SEVs were successfully isolated by ultrafiltration from the conditioned medium of hUC-MSCs. The sEVs' size distribution, intensity within a specific surface marker population were measured with zetasizer or nanoparticle tracking analysis. The expression of surface and internal markers of sEVs was also assessed by western blotting. Morphology of hUC-MSCs displayed as spindle-shaped, fibroblast-like adherent cells. Phenotypic analysis by flow cytometry revealed that hUC-MSCs expressed MSC surface marker, including CD90, CD73, CD105, CD44 and exhibited the capacity for osteogenic, adipogenic and chondrogenic differentiation. Populations of sEVs with CD9, CD63 and CD81 positive were detected with size distribution in the diameter of 63.2 to 162.5 nm. Typical sEVs biomarkers such as CD9, CD63, CD81, HSP70 and TSG101 were also detected with western blotting. Our study showed that sEVs from hUC-MSCs conditioned medium were successfully isolated and characterised. Downstream application of hUC-MSCs-sEVs will be further explored.
    Matched MeSH terms: HSP70 Heat-Shock Proteins/genetics; HSP70 Heat-Shock Proteins/metabolism
  7. Short- and long-term probiotic effects of Enterococcus hirae isolated from fermented vegetable wastes on the growth, immune responses, and disease resistance of hybrid catfish (Clarias gariepinus × Clarias macrocephalus)
    Hamid NH, Daud HM, Kayansamruaj P, Hassim HA, Mohd Yusoff MS, Abu Bakar SN, et al.
    Fish Shellfish Immunol, 2021 Jul;114:1-19.
    PMID: 33872754 DOI: 10.1016/j.fsi.2021.04.012
    This study evaluated the short- and long-term effects of dietary supplementation with Enterococcus hirae strain UPM02 on the growth performance, immunity, and disease resistance of hybrid catfish (Clarias gariepinus × Clarias macrocephalus) against Aeromonas hydrophila infection. In the long-term trial, fingerling fish were fed diets containing 0 (control), 2 × 105, or 2 × 107 CFU/g E. hirae UPM02 for 120 days. Administration of E. hirae UPM02 had significant effects on the specific growth rate (SGR), feed utilization efficiency, body indices (P heat shock protein 70 (HSP70) gene expression was slightly downregulated in these organs. Interestingly, fish fed the diets containing 2 × 105 and 2 × 107 CFU/g E. hirae UPM02 exhibited a significantly lower (P 
    Matched MeSH terms: HSP70 Heat-Shock Proteins
  8. Fulltext Antimicrobial activity and mode of action of terpene linalyl anthranilate against carbapenemase-producing Klebsiella pneumoniae
    Yang SK, Yusoff K, Ajat M, Yap WS, Lim SE, Lai KS
    J Pharm Anal, 2021 Apr;11(2):210-219.
    PMID: 34012697 DOI: 10.1016/j.jpha.2020.05.014
    Mining of plant-derived antimicrobials is the major focus at current to counter antibiotic resistance. This study was conducted to characterize the antimicrobial activity and mode of action of linalyl anthranilate (LNA) against carbapenemase-producing Klebsiella pneumoniae (KPC-KP). LNA alone exhibited bactericidal activity at 2.5% (V/V), and in combination with meropenem (MPM) at 1.25% (V/V). Comparative proteomic analysis showed a significant reduction in the number of cytoplasmic and membrane proteins, indicating membrane damage in LNA-treated KPC-KP cells. Up-regulation of oxidative stress regulator proteins and down-regulation of oxidative stress-sensitive proteins indicated oxidative stress. Zeta potential measurement and outer membrane permeability assay revealed that LNA increases both bacterial surface charge and membrane permeability. Ethidium bromide influx/efflux assay showed increased uptake of ethidium bromide in LNA-treated cells, inferring membrane damage. Furthermore, intracellular leakage of nucleic acid and proteins was detected upon LNA treatment. Scanning and transmission electron microscopies again revealed the breakage of bacterial membrane and loss of intracellular materials. LNA was found to induce oxidative stress by generating reactive oxygen species (ROS) that initiate lipid peroxidation and damage the bacterial membrane. In conclusion, LNA generates ROS, initiates lipid peroxidation, and damages the bacterial membrane, resulting in intracellular leakage and eventually killing the KPC-KP cells.
    Matched MeSH terms: Heat-Shock Proteins
  9. Fulltext Supplementation of postbiotic RI11 improves antioxidant enzyme activity, upregulated gut barrier genes, and reduced cytokine, acute phase protein, and heat shock protein 70 gene expression levels in heat-stressed broilers
    Humam AM, Loh TC, Foo HL, Izuddin WI, Zulkifli I, Samsudin AA, et al.
    Poult Sci, 2021 Mar;100(3):100908.
    PMID: 33518339 DOI: 10.1016/j.psj.2020.12.011
    The aim of this work was to evaluate the impacts of feeding different levels of postbiotic RI11 on antioxidant enzyme activity, physiological stress indicators, and cytokine and gut barrier gene expression in broilers under heat stress. A total of 252 male broilers Cobb 500 were allocated in cages in environmentally controlled chambers. All the broilers received the same basal diet from 1 to 21 d. On day 22, the broilers were weighed and grouped into 7 treatment groups and exhibited to cyclic high temperature at 36 ± 1°C for 3 h per day until the end of the experiment. From day 22 to 42, broilers were fed with one of the 7 following diets: negative control, basal diet (0.0% RI11) (NC group); positive control, NC diet + 0.02% (w/w) oxytetracycline (OTC group); antioxidant control, NC diet + 0.02% (w/w) ascorbic acid. The other 4 other groups were as follows: NC diet + 0.2% cell-free supernatant (postbiotic RI11) (v/w), NC diet + 0.4% cell-free supernatant (postbiotic RI11) (v/w), NC diet + 0.6% cell-free supernatant (postbiotic RI11) (v/w), and NC diet + 0.8% cell-free supernatant (postbiotic RI11) (v/w). Supplementation of different levels (0.4, 0.6, and 0.8%) of postbiotic RI11 increased plasma glutathione peroxidase, catalase, and glutathione enzyme activity. Postbiotic RI11 groups particularly at levels of 0.4 and 0.6% upregulated the mRNA expression of IL-10 and downregulated the IL-8, tumor necrosis factor alpha, heat shock protein 70, and alpha-1-acid glycoprotein levels compared with the NC and OTC groups. Feeding postbiotic RI11, particularly at the level of 0.6%, upregulated ileum zonula occludens-1 and mucin 2 mRNA expressions. However, no difference was observed in ileum claudin 1, ceruloplasmin, IL-6, IL-2, and interferon expression, but downregulation of occludin expression was observed as compared with the NC group. Supplementation of postbiotic RI11 at different levels quadratically increased plasma glutathione peroxidase, catalase and glutathione, IL-10, mucin 2, and zonula occludens-1 mRNA expression and reduced plasma IL-8, tumor necrosis factor alpha, alpha-1-acid glycoprotein, and heat shock protein 70 mRNA expression. The results suggested that postbiotics produced from Lactiplantibacillus plantarum RI11 especially at the level of 0.6% (v/w) could be used as an alternative to antibiotics and natural sources of antioxidants in poultry feeding.
    Matched MeSH terms: HSP70 Heat-Shock Proteins/genetics
  10. Fulltext Histological study of gonadal tissues of adult Artemia salina (Linnaeus 1758) and immunohistochemistry by Caspase 3 and HSP70 to detect specific apoptosis markers on gonadal tissues after exposure to TBTCl
    Abushaala NM, Elfituri AM, Zulkifli SZ
    Open Vet J, 2021 02 08;11(1):112-120.
    PMID: 33898292 DOI: 10.4314/ovj.v11i1.17
    Background: Several types of research have been recently carried out on the biological effects of TBTs, including investigations of genitals in invertebrates in response to exposure to TBTs in marine water.

    Aim: The objective of this research was to investigate the acute effects of tributyltin chloride (TBTCl) on gonads in the adult stage of Artemia salina by use normal histology and immunohistochemistry (IHC) (Caspase 3 and HSP70) to see specific apoptosis markers.

    Methods: After exposure of A. salina to different concentrations of TBTCl (25, 50, 100, 200, and 300 ng.l-1), 50 adult A. salina (25 male and 25 female) were selected randomly from each concentration to histologically study the gonads. The gonad tissue was sectioned (5 μm) and some slides were stained with hematoxylin and eosin and others were stained with IHC avidin-biotin complex, and were examined under a light microscope.

    Results: The results showed significant differences (p < 0.05) in histological lesions between different concentrations of TBTCl. The histological lesions in the testis and ovary section were undifferentiated cells, degenerating yolk globules, and follicle cells enveloping the oocyte which was then compared with control tissue, and these effects were found to be increased in females more than in males with the highest concentration of TBTCl. Immunohistochemistry (IHC) showed that positive immunostaining was observed in the testis and ovary as brownish deposits to Caspase 3 and HSP70 antibody after exposure to TBTCl, while the testis and ovary section in control tissue had no immunoreactivity to Caspase 3 and HSP70 antibody; these effects were profoundly increased with the highest concentration of TBTCl in females more than in males. Finally, the histological lesions and IHC (Caspase 3 and HSP70) revealed that the apoptosis and immune system stress of A. salina gonad tissue damage in females were more sensitive to TBTCl toxicity as compared to white males.

    Conclusion: In general, the present study aimed to observe the effects TBTCl on A. salina gonads by using histological sections and IHC (Caspase 3 and HSP70), which were evaluated for the first time and have been proven to possess an important function in apoptosis marker and immune system stress in Artemia. Finally, the specific mechanisms through which TBTCl affects A. salina Caspase 3 and HSP70 expression need further investigation.

    Matched MeSH terms: HSP70 Heat-Shock Proteins/metabolism
  11. Pandanus tectorius fruit extract promotes Hsp70 accumulation, immune-related genes expression and Vibrio parahaemolyticus tolerance in the white-leg shrimp Penaeus vannamei
    Anirudhan A, Okomoda VT, Mimi Iryani MT, Andriani Y, Abd Wahid ME, Tan MP, et al.
    Fish Shellfish Immunol, 2021 Feb;109:97-105.
    PMID: 33352338 DOI: 10.1016/j.fsi.2020.12.011
    Plants and herbal extracts are indispensable for controlling the spread of disease-causing bacteria, including those that infect aquatic organisms used in aquaculture. The use of plant or herbal extract is expected to be safe for aquatic animals and less harmful to the environment, as opposed to conventional therapeutic alternatives such as antibiotics that promote the occurrence of potential antibiotic-resistant bacteria when used improperly. The efficacy of Pandanus tectorius fruit extract in the regulation of Hsp70 expression, pro-phenoloxidase (ProPO), peroxinectin, penaeidin, crustin and transglutaminase, all immune peptides essential for Vibrio tolerance in white leg shrimp, Penaeus vannamei, was investigated in this study, which included the determination of the safety levels of the extract. Tolerance of shrimp against Vibrio parahaemolyticus, a pathogenic bacteria that causes Acute Hepatopancreas Necrosis Disease (AHPND), was assessed on the basis of median lethal dose challenge survival (LD50 = 106 cells/ml). Mortality was not observed 24 h after exposure of 0.5-6 g/L of the fruit extract, indicating that P. tectorius was not toxic to shrimp at these concentrations. A 24-h incubation of 2-6 g/L of the fruit extract increased shrimp tolerance to V. parahaemolyticus, with survival doubled when the maximum dose tested in this study was used. Concomitant with a rise in survival was the increase in immune-related proteins, with Hsp70, ProPO, peroxinectin, penaeidin, crustin and transglutaminase increased 10, 11, 11, 0.4, 8 and 13-fold respectively. Histological examination of the hepatopancreas and muscle tissues of Vibrio-infected shrimp primed with P. tectorius extract revealed reduced signs of histopathological degeneration, possibly due to the accumulation of Hsp70, a molecular chaperone crucial to cellular protein folding, tissue repair and immune response of living organisms, including Penaeid shrimp.
    Matched MeSH terms: HSP70 Heat-Shock Proteins/immunology*
  12. Fulltext Combinatorial Antimicrobial Efficacy and Mechanism of Linalool Against Clinically Relevant Klebsiella pneumoniae
    Yang SK, Yusoff K, Ajat M, Wee CY, Yap PS, Lim SH, et al.
    Front Microbiol, 2021;12:635016.
    PMID: 33815320 DOI: 10.3389/fmicb.2021.635016
    Antibiotic-adjuvant combinatory therapy serves as a viable treatment option in addressing antibiotic resistance in the clinical setting. This study was carried out to assess and characterize the adjuvant potential and mode of action of linalool against carbapenemase-producing Klebsiella pneumoniae (KPC-KP). Linalool exhibited bactericidal activity alone (11,250 μg/ml) and in combination with meropenem (5,625 μg/ml). Comparative proteomic analysis showed significant reduction in the number of cytoplasmic and membrane proteins, indicating membrane damage in linalool-treated KPC-KP cells. Upregulation of oxidative stress regulator proteins and downregulation of oxidative stress-sensitive proteins indicated oxidative stress. Zeta potential measurement and outer membrane permeability assay revealed that linalool increases the bacterial surface charge as well as the membrane permeability. Intracellular leakage of nucleic acid and proteins was detected upon linalool treatment. Scanning and transmission electron microscopies further revealed the breakage of bacterial membrane and loss of intracellular materials. Linalool induced oxidative stress by generating reactive oxygen species (ROS) which initiates lipid peroxidation, leading to damage of the bacterial membrane. This leads to intracellular leakage, eventually killing the KPC-KP cells. Our study demonstrated that linalool possesses great potential in future clinical applications as an adjuvant along with existing antibiotics attributed to their ability in disrupting the bacterial membrane by inducing oxidative stress. This facilitates the uptake of antibiotics into the bacterial cells, enhancing bacterial killing.
    Matched MeSH terms: Heat-Shock Proteins
  13. Palmatine Inhibits Up-Regulation of GRP78 and CALR Protein in an STZ-Induced Diabetic Rat Model
    Okechukwu PN, Ekeuku SO, Chan HK, Eluri K, Froemming GRA
    Curr Pharm Biotechnol, 2021;22(2):288-298.
    PMID: 32744968 DOI: 10.2174/1389201021666200730124208
    BACKGROUND: Diabetes Mellitus (DM) is characterized by hyperglycemia (high blood glucose levels) which is due to the destruction of insulin-producing β-cells in the islets of Langerhans in the pancreas. It is associated with oxidative and endoplasmic reticulum stress. The plant alkaloid Palmatine has been previously reported to possess antidiabetic and antioxidant properties as well as other protective properties against kidney and liver tissue damage.

    OBJECTIVE: Here, we investigated the ability of Palmatine to reduce the up-regulation of chaperone proteins Glucose Regulatory Protein 78 (GRP78), and Calreticulin (CALR) protein in a Streptozotocin (STZ)-induced diabetic rat model.

    METHODS: Streptozotocin (STZ) induced diabetes in Sprague Dawley rats treated with 2mg/kg of Palmatine for 12 weeks after the elevation of plasma glucose levels above 11mmol/L post-STZ administration. Proteins were extracted from the pancreas after treatment and Two-Dimensional gel electrophoresis (2-DE), PDQuest 2-D analysis software genomic solutions and mass spectrometer were used to analyze differentially expressed protein. Mass Spectrometry (MS/MS), Multidimensional Protein Identification Technology (MudPIT) was used for protein identification.

    RESULTS: There was an up-regulation of the expression of chaperone proteins CALR and GRP78 and down-regulation of the expression of antioxidant and protection proteins peroxidoxin 4 (Prdx4), protein disulfide isomerase (PDIA2/3), Glutathione-S-Transferase (GSTs), and Serum Albumin (ALB) in non-diabetic rats. Palmatine treatment down-regulated the expression of chaperone proteins CALR and GRP78 and up-regulated the expression of Prdx4, PDIA2/3, GST, and ALB.

    CONCLUSION: Palmatine may have activated antioxidant proteins, which protected the cells against reactive oxygen species and endoplasmic stress. The result is in consonance with our previous report on Palmatine.

    Matched MeSH terms: Heat-Shock Proteins/antagonists & inhibitors*; Heat-Shock Proteins/biosynthesis
  14. Fulltext Proteomic Analysis on Anti-Proliferative and Apoptosis Effects of Curcumin Analog, 1,5-bis(4-Hydroxy-3-Methyoxyphenyl)-1,4-Pentadiene-3-One-Treated Human Glioblastoma and Neuroblastoma Cells
    Lee YQ, Rajadurai P, Abas F, Othman I, Naidu R
    Front Mol Biosci, 2021;8:645856.
    PMID: 33996900 DOI: 10.3389/fmolb.2021.645856
    Curcumin analogs with excellent biological properties have been synthesized to address and overcome the poor pharmacokinetic profiles of curcumin. This study aims to investigate the cytotoxicity, anti-proliferative, and apoptosis-inducing ability of curcumin analog, MS13 on human glioblastoma U-87 MG, and neuroblastoma SH-SY5Y cells, and to examine the global proteome changes in these cells following treatment. Our current findings showed that MS13 induced potent cytotoxicity and anti-proliferative effects on both cells. Increased caspase-3 activity and decreased bcl-2 concentration upon treatment indicate that MS13 induces apoptosis in these cells in a dose- and time-dependent manner. The label-free shotgun proteomic analysis has defined the protein profiles in both glioblastoma and neuroblastoma cells, whereby a total of nine common DEPs, inclusive of glyceraldehyde 3-phosphate dehydrogenase (GAPDH), alpha-enolase (ENO1), heat shock protein HSP 90-alpha (HSP90AA1), Heat shock protein HSP 90-beta (HSP90AB1), Eukaryotic translation initiation factor 5A-1 (EFI5A), heterogenous nuclear ribonucleoprotein K (HNRNPK), tubulin beta chain (TUBB), histone H2AX (H2AFX), and Protein SET were identified. Pathway analysis further elucidated that MS13 may induce its anti-tumor effects in both cells via the common enriched pathways, "Glycolysis" and "Post-translational protein modification." Conclusively, MS13 demonstrates an anti-cancer effect that may indicate its potential use in the management of brain malignancies.
    Matched MeSH terms: Heat-Shock Proteins
  15. Local acclimatisation-driven differential gene and protein expression patterns of Hsp70 in Acropora muricata: Implications for coral tolerance to bleaching
    Louis YD, Bhagooli R, Seveso D, Maggioni D, Galli P, Vai M, et al.
    Mol Ecol, 2020 11;29(22):4382-4394.
    PMID: 32967057 DOI: 10.1111/mec.15642
    Corals show spatial acclimatisation to local environment conditions. However, the various cellular mechanisms involved in local acclimatisation and variable bleaching patterns in corals remain to be thoroughly understood. In this study, the modulation of a protein implicated in cellular heat stress tolerance, the heat shock protein 70, was compared at both gene (hsp70) and protein (Hsp70) expression level in bleaching tolerant near-coast Acropora muricata colonies and bleaching susceptible reef colonies, in the lagoon of Belle Mare (Mauritius). The relative Hsp70 levels varied significantly between colonies from the two different locations, colonies having different health conditions and the year of collection. Before the bleaching event of 2016, near-coast colonies had higher basal levels of both Hsp70 gene and protein compared to reef colonies. During the bleaching event, the near-coast colonies did not bleach and had significantly higher relative levels of both Hsp70 gene and protein compared to bleached reef colonies. No significant genetic differentiation between the two studied coral populations was observed and all the colonies analysed were associated with Symbiodiniaceae of the genus Symbiodinium (Clade A) irrespective of location and sampling period. These findings provide further evidence of the involvement of Hsp70 in conferring bleaching tolerance to corals. Moreover, the consistent expression differences of Hsp70 gene and protein between the near-coast and reef coral populations in a natural setting indicate that the modulation of this Hsp is involved in local acclimatisation of corals to their environments.
    Matched MeSH terms: HSP70 Heat-Shock Proteins/genetics
  16. Fulltext Cyst viability and stress tolerance upon heat shock protein 70 knockdown in the brine shrimp Artemia franciscana
    Iryani MTM, Sorgeloos P, Danish-Daniel M, Tan MP, Wong LL, Mok WJ, et al.
    Cell Stress Chaperones, 2020 Nov;25(6):1099-1103.
    PMID: 32383141 DOI: 10.1007/s12192-020-01113-0
    Females of the brine shrimp Artemia franciscana produce either free-swimming nauplii via ovoviviparous pathway of reproduction or encysted embryos, known as cysts, via oviparous pathway, in which biological processes are arrested. While previous study has shown a crucial role of ATP-dependent molecular chaperone, heat shock protein 70 (Hsp70) in protecting A. franciscana nauplii against various abiotic and abiotic stressors, the function of this protein in diapausing embryos and cyst development, however, remains unknown. RNA interference (RNAi) was applied in this study to examine the role of Hsp70 in cyst development and stress tolerance, with the latter performed by desiccation and freezing, a common method used for diapause termination in Artemia cysts. Hsp70 knockdown was apparent in cysts released from females that were injected with Hsp70 dsRNA. The loss of Hsp70 affected neither the development nor morphology of the cysts. The time between fertilization and cyst release from Artemia females injected with Hsp70 dsRNA was delayed slightly, but the differences were not significant when compared to the controls. However, the hatching percentage of cysts which lacks Hsp70 were reduced following desiccation and freezing. Taken together, these results indicated that Hsp70 possibly plays a role in the stress tolerance but not in the development of diapause-destined embryos of Artemia. This research makes fundamental contributions to our understanding of the role molecular chaperone Hsp70 plays in Artemia, an excellent model organism for diapause studies of the crustaceans.
    Matched MeSH terms: HSP70 Heat-Shock Proteins/genetics; HSP70 Heat-Shock Proteins/metabolism*
  17. Fulltext Effects of zinc oxide nanoparticles on regulatory appetite and heat stress protein genes in broiler chickens subjected to heat stress
    Ramiah SK, Atta Awad E, Hemly NIM, Ebrahimi M, Joshua O, Jamshed M, et al.
    J Anim Sci, 2020 Oct 01;98(10).
    PMID: 32936879 DOI: 10.1093/jas/skaa300
    This study was conducted to explore the effect of the zinc oxide nanoparticles (ZnONPs) supplement on the regulatory appetite and heat stress (HS) genes in broiler chickens raised under high or normal ambient temperatures. In this study, 240 one-day-old male broiler chicks (Cobb 500) were randomly assigned to 48 battery cages. From day 1, these 48 cages were randomly subjected to four different treatment strategies: Control (wherein, their basal diet included 60 mg/kg of ZnO), ZNONPs 40 (wherein basal diet included 40 mg/kg of ZnONPs), ZnONPs 60 (basal diet included 60 mg/kg of ZnONPs), and ZnONPs 100 (basal diet included 100 mg/kg of ZnONPs). Thereafter, from day 22 to 42, the chickens from each dietary treatment group were subjected to different temperature stresses either normal (23 ± 1 °C constant) or HS (34 ± 1 °C for 6 h/d), which divided them into eight different treatment groups. Our findings revealed that dietary ZnONPs altered the gene expression of cholecystokinin (ileum), heat stress proteins (HSP) 70 (jejunum and ileum), and HSP 90 (duodenum, jejunum, and ileum). The gene expression of ghrelin was affected by the interaction between the ZnONPs concentration and temperature in the duodenum and stomach. More studies are required to elucidate its complex physiological and biochemical functions of the regulation of gene expression within the intestine in heat-stressed broiler chickens.
    Matched MeSH terms: HSP70 Heat-Shock Proteins/metabolism
  18. TCR-like domain antibody against Mycobacterium tuberculosis (Mtb) heat shock protein antigen presented by HLA-A*11 and HLA-A*24
    Dass SA, Norazmi MN, Acosta A, Sarmiento ME, Tye GJ
    Int J Biol Macromol, 2020 Jul 15;155:305-314.
    PMID: 32240734 DOI: 10.1016/j.ijbiomac.2020.03.229
    T cell receptor (TCR)-like antibodies, obtained with the use of phage display technology, sandwich the best of the both arms of the adaptive immune system. In this study, in vitro selections against the latency associated Mycobacterium tuberculosis (Mtb) heat shock protein 16 kDa antigen (16 kDa) presented by HLA-A*011 and HLA-A*24 were carried out with the use of a human domain phage antibody library. TCR-like domain antibodies (A11Ab and A24Ab) were successfully generated recognizing 16 kDa epitopes presented by HLA-A*011 and HLA-A*24 molecules respectively. Both antibodies were found to be functional in soluble form and exhibited strong binding capacity against its targets. The results obtained support the future evaluation of these ligands for the development of diagnostic and therapeutic tools for tuberculosis infection.
    Matched MeSH terms: Heat-Shock Proteins/immunology*
  19. Fulltext Heat alleviation strategies for athletic performance: A review and practitioner guidelines
    Gibson OR, James CA, Mee JA, Willmott AGB, Turner G, Hayes M, et al.
    Temperature (Austin), 2020;7(1):3-36.
    PMID: 32166103 DOI: 10.1080/23328940.2019.1666624
    International competition inevitably presents logistical challenges for athletes. Events such as the Tokyo 2020 Olympic Games require further consideration given historical climate data suggest athletes will experience significant heat stress. Given the expected climate, athletes face major challenges to health and performance. With this in mind, heat alleviation strategies should be a fundamental consideration. This review provides a focused perspective of the relevant literature describing how practitioners can structure male and female athlete preparations for performance in hot, humid conditions. Whilst scientific literature commonly describes experimental work, with a primary focus on maximizing magnitudes of adaptive responses, this may sacrifice ecological validity, particularly for athletes whom must balance logistical considerations aligned with integrating environmental preparation around training, tapering and travel plans. Additionally, opportunities for sophisticated interventions may not be possible in the constrained environment of the athlete village or event arenas. This review therefore takes knowledge gained from robust experimental work, interprets it and provides direction on how practitioners/coaches can optimize their athletes' heat alleviation strategies. This review identifies two distinct heat alleviation themes that should be considered to form an individualized strategy for the athlete to enhance thermoregulatory/performance physiology. First, chronic heat alleviation techniques are outlined, these describe interventions such as heat acclimation, which are implemented pre, during and post-training to prepare for the increased heat stress. Second, acute heat alleviation techniques that are implemented immediately prior to, and sometimes during the event are discussed. Abbreviations: CWI: Cold water immersion; HA: Heat acclimation; HR: Heart rate; HSP: Heat shock protein; HWI: Hot water immersion; LTHA: Long-term heat acclimation; MTHA: Medium-term heat acclimation; ODHA: Once-daily heat acclimation; RH: Relative humidity; RPE: Rating of perceived exertion; STHA: Short-term heat acclimation; TCORE: Core temperature; TDHA: Twice-daily heat acclimation; TS: Thermal sensation; TSKIN: Skin temperature; V̇O2max: Maximal oxygen uptake; WGBT: Wet bulb globe temperature.
    Matched MeSH terms: Heat-Shock Proteins
  20. Fulltext Mitragynine, an euphoric compound inhibits hERG1a/1b channel current and upregulates the complexation of hERG1a-Hsp90 in HEK293-hERG1a/1b cells
    Tay YL, Amanah A, Adenan MI, Wahab HA, Tan ML
    Sci Rep, 2019 12 24;9(1):19757.
    PMID: 31874991 DOI: 10.1038/s41598-019-56106-6
    Mitragyna speciosa Korth (M. speciosa) has been widely used as a recreational product, however, there are growing concerns on the abuse potentials and toxicity of the plant. Several poisoning and fatal cases involving kratom and mitragynine have been reported but the underlying causes remain unclear. The human ether-a-go-go-related gene 1 (hERG1) encodes the pore-forming subunit underlying cardiac rapidly delayed rectifier potassium current (IKr). Pharmacological blockade of the IKr can cause acquired long QT syndrome, leading to lethal cardiac arrhythmias. This study aims to elucidate the mechanisms of mitragynine-induced inhibition on hERG1a/1b current. Electrophysiology experiments were carried out using Port-a-Patch system. Quantitative RT-PCR, Western blot analysis, immunofluorescence and co-immunoprecipitation methods were used to determine the effects of mitragynine on hERG1a/1b expression and hERG1-cytosolic chaperones interaction. Mitragynine was found to inhibit the IKr current with an IC50 value of 332.70 nM. It causes a significant reduction of the fully-glycosylated (fg) hERG1a protein expression but upregulates both core-glycosylated (cg) expression and hERG1a-Hsp90 complexes, suggesting possible impaired hERG1a trafficking. In conclusion, mitragynine inhibits hERG1a/1b current through direct channel blockade at lower concentration, but at higher concentration, it upregulates the complexation of hERG1a-Hsp90 which may be inhibitory towards channel trafficking.
    Matched MeSH terms: HSP90 Heat-Shock Proteins/metabolism*
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