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  1. Durairajanayagam D, Singh D, Agarwal A, Henkel R
    Andrologia, 2021 Feb;53(1):e13666.
    PMID: 32510691 DOI: 10.1111/and.13666
    Mitochondria have multiple functions, including synthesis of adenine triphosphate, production of reactive oxygen species, calcium signalling, thermogenesis and apoptosis. Mitochondria have a significant contribution in regulating the various physiological aspects of reproductive function, from spermatogenesis up to fertilisation. Mitochondrial functionality and intact mitochondrial membrane potential are a pre-requisite for sperm motility, hyperactivation, capacitation, acrosin activity, acrosome reaction and DNA integrity. Optimal mitochondrial activity is therefore crucial for human sperm function and semen quality. However, the precise role of mitochondria in spermatozoa remains to be fully explored. Defects in sperm mitochondrial function severely impair the maintenance of energy production required for sperm motility and may be an underlying cause of asthenozoospermia. Sperm mtDNA is susceptible to oxidative damage and mutations that could compromise sperm function leading to infertility. Males with abnormal semen parameters have increased mtDNA copy number and reduced mtDNA integrity. This review discusses the role of mitochondria in sperm function, along with the causes and impact of its dysfunction on male fertility. Greater understanding of sperm mitochondrial function and its correlation with sperm quality could provide further insights into their contribution in the assessment of the infertile male.
    Matched MeSH terms: DNA, Mitochondrial/metabolism; Spermatozoa/metabolism
  2. Zhang X, Seman NA, Falhammar H, Brismar K, Gu HF
    J Diabetes Res, 2020;2020:8305460.
    PMID: 32626783 DOI: 10.1155/2020/8305460
    Diabetic kidney disease (DKD) is a complex disease, in which local inflammatory stress results from both metabolic and hemodynamic derangements. Intercellular adhesion molecule 1 (ICAM-1) is an acute-phase protein marker of inflammation. In the recent years, clinical observations have reported that increased serum/plasma ICAM-1 levels are positively correlated with albuminuria in the patients with type 1 (T1D) and type 2 diabetes (T2D). Genetic association studies have demonstrated that genetic polymorphisms, including SNP rs5498 (E469K, G/A), in the ICAM1 gene is associated with DKD. rs5498 is a nonsynonymous SNP and caused by substitution between E (Glu) and K (Lys) for ICAM-1 protein. In this review, we first summarized the genetic effects of ICAM1 E469K polymorphism in DKD and then demonstrated the possible changes of ICAM-1 protein crystal structures according to the genotypes of this polymorphism. Finally, we discussed the genetic effects of the ICAM1 E469K polymorphism and the biological role of increased circulating ICAM-1 protein and its formation changes in DKD.
    Matched MeSH terms: Diabetic Nephropathies/metabolism; Intercellular Adhesion Molecule-1/metabolism
  3. Wong MM, Chan HY, Aziz NA, Ramasamy TS, Bong JJ, Ch'ng ES, et al.
    Mol Biol Rep, 2021 Apr;48(4):3695-3717.
    PMID: 33893928 DOI: 10.1007/s11033-021-06334-9
    Liver cancer is the sixth most common cancer and the fourth leading cause of cancer deaths in the world. The most common type of liver cancers is hepatocellular carcinoma (HCC). Autophagy is the cellular digestion of harmful components by sequestering the waste products into autophagosomes followed by lysosomal degradation for the maintenance of cellular homeostasis. The impairment of autophagy is highly associated with the development and progression of HCC although autophagy may be involved in tumour-suppressing cellular events. In regards to its protecting role, autophagy also shelters the cells from anoikis- a programmed cell death in anchorage-dependent cells detached from the surrounding extracellular matrix which facilitates metastasis in HCC. Liver cancer stem cells (LCSCs) have the ability for self-renewal and differentiation and are associated with the development and progression of HCC by regulating stemness, resistance and angiogenesis. Interestingly, autophagy is also known to regulate normal stem cells by promoting cellular survival and differentiation and maintaining cellular homeostasis. In this review, we discuss the basal autophagic mechanisms and double-faceted roles of autophagy as both tumour suppressor and tumour promoter in HCC, as well as its association with and contribution to self-renewal and differentiation of LCSCs.
    Matched MeSH terms: Liver Neoplasms/metabolism*; Neoplastic Stem Cells/metabolism*
  4. Kim SE, Lee B, Jang H, Chin J, Khoo CS, Choe YS, et al.
    Alzheimers Res Ther, 2021 02 19;13(1):48.
    PMID: 33608041 DOI: 10.1186/s13195-021-00787-7
    BACKGROUND: The presence of ß-amyloid (Aß) in the brain can be identified using amyloid PET. In clinical practice, the amyloid PET is interpreted based on dichotomous visual rating, which renders focal Aß accumulation be read as positive for Aß. However, the prognosis of patients with focal Aß deposition is not well established. Thus, we investigated cognitive trajectories of patients with focal Aß deposition.

    METHODS: We followed up 240 participants (112 cognitively unimpaired [CU], 78 amnestic mild cognitive impairment [aMCI], and 50 Alzheimer's disease (AD) dementia [ADD]) for 2 years from 9 referral centers in South Korea. Participants were assessed with neuropsychological tests and 18F-flutemetamol (FMM) positron emission tomography (PET). Ten regions (frontal, precuneus/posterior cingulate (PPC), lateral temporal, parietal, and striatum of each hemisphere) were visually examined in the FMM scan, and participants were divided into three groups: No-FMM, Focal-FMM (FMM uptake in 1-9 regions), and Diffuse-FMM. We used mixed-effects model to investigate the speed of cognitive decline in the Focal-FMM group according to the cognitive level, extent, and location of Aß involvement, in comparison with the No- or Diffuse-FMM group.

    RESULTS: Forty-five of 240 (18.8%) individuals were categorized as Focal-FMM. The rate of cognitive decline in the Focal-FMM group was faster than the No-FMM group (especially in the CU and aMCI stage) and slower than the Diffuse-FMM group (in particular in the CU stage). Within the Focal-FMM group, participants with FMM uptake to a larger extent (7-9 regions) showed faster cognitive decline compared to those with uptake to a smaller extent (1-3 or 4-6 regions). The Focal-FMM group was found to have faster cognitive decline in comparison with the No-FMM when there was uptake in the PPC, striatum, and frontal cortex.

    CONCLUSIONS: When predicting cognitive decline of patients with focal Aß deposition, the patients' cognitive level, extent, and location of the focal involvement are important.

    Matched MeSH terms: Brain/metabolism; Amyloid beta-Peptides/metabolism
  5. Mannan S, Fakhru'l-Razi A, Alam MZ
    Water Res, 2005 Aug;39(13):2935-43.
    PMID: 16000208
    The present study was designed to evaluate the potential of microbial adaptation and its affinity to biodegradation as well as bioconversion of soluble/insoluble (organic) substances of domestic wastewater treatment plant (DWTP) sludge (activated domestic sludge) under natural/non-sterilized conditions. The two filamentous fungi, Penicillium corylophilum (WWZP1003) and Aspergillus niger (SCahmA103) were used to achieve the objectives. It was observed that P. corylophilum (WWZP1003) was the better strain compared to A. niger (SCahmA103) for the bioconversion of domestic activated sludge through adaptation. The visual observation in plate culture showed that about 95-98% of cultured microbes (P. corylophilum and A. niger) dominated in treated sludge after 2 days of treatment. In this study, it was also found that the P. corylophilum was capable of removing 94.40% of COD and 98.95% of turbidity of filtrate with minimum dose of inoculum of 10% v/v in DWTP sludge (1% w/w). The pH level was lower (acidic condition) in the fungal treatment and maximum reduction of COD and turbidity was observed (at lower pH). The results for specific resistance to filtration (SRF) showed that the fungi played a great role in enhancing the dewaterability and filterability. In particular, the strain Penicillium had a more significant capability (than A. niger) of reducing 93.20% of SRF compared to the uninoculated sample. Effective results were observed by using fungal inoculum after 2 days of treatment. The developed LSB process is a new biotechnological approach for sludge management strategy.
    Matched MeSH terms: Aspergillus niger/metabolism*; Penicillium/metabolism*
  6. Soo TCC, See SA, Bhassu S
    J Invertebr Pathol, 2020 11;177:107497.
    PMID: 33130047 DOI: 10.1016/j.jip.2020.107497
    Global shrimp aquaculture farmers have suffered major economic losses due to disease outbreaks. A notable shrimp disease is Acute Hepatopancreatic Necrosis Disease (AHPND), which is caused by a new strain of Vibrio parahaemolyticus bacteria (VpAHPND) that mainly inhabits the shrimp gut and damages the hepatopancreas. Fewer studies have investigated whether this disease will affect shrimp muscle functioning or cause any muscle damage. We challenged Penaeus monodon shrimp with VpAHPND bacteria using an immersion method. Expression of Dystrophin gene, an important regulatory gene for maintenance of muscle integrity, was quantified from muscle samples using qRT-PCR. Additional verification was conducted by determining calcium concentration and bta-miR-4286 and dre-miR-107b miRNAs expression. P. monodon dystrophin gene demonstrated the highest expression level during AHPND infection when muscle calcium concentration was detected at its lowest level at 6 h post-infection (hpi). The highest muscle calcium concentration, determined at 36 hpi, was supported by higher bta-miR-4286 miRNA expression and lower dre-miR-107b miRNA expression in VpAHPND-infected samples compared to uninfected samples at the same time point. We deduced an interactive relationship between dystrophin gene expression, calcium concentration, and miRNA expression in P. monodon muscle tissues triggered by the invading VpAHPND bacterium.
    Matched MeSH terms: Calcium/metabolism*; MicroRNAs/metabolism*
  7. Sambanthamurthi R, Rajanaidu N, Hasnah Parman S
    Biochem Soc Trans, 2000 Dec;28(6):769-70.
    PMID: 11171201
    The oil palm mesocarp contains an endogenous lipase which is strongly activated at low temperature. Lipase activity is thus very conveniently assayed by prior exposure of the fruits to low temperature. More than 100 oil palm samples from the germplasm collection of the Palm Oil Research Institute of Malaysia (now known as the Malaysian Palm Oil Board) were screened for non-esterified fatty acid activity using both the low-temperature activation assay and a radioactivity assay. The results showed good correlation between assay procedures. The different samples had a very wide range of lipase activity. Elaeis oleifera samples had significantly lower lipase activity compared with E. guineensis (var. tenera) samples. Even within E. guineensis (var. tenera), there was a wide range of activity. The results confirmed that lipase activity is genotype-dependent. Selection for lipase genotypes is thus possible and this will have obvious commercial value.
    Matched MeSH terms: Fatty Acids, Nonesterified/metabolism*; Lipase/metabolism*
  8. Panda S, Mishra L, Arbildo-Vega HI, Lapinska B, Lukomska-Szymanska M, Khijmatgar S, et al.
    Cells, 2020 10 07;9(10).
    PMID: 33036462 DOI: 10.3390/cells9102241
    The use of autologous platelet concentrates (APCs) in regenerative endodontic procedures is inconsistent and unclear. The aim of this meta-analysis was to evaluate the effectiveness of autologous platelet concentrates compared to traditional blood-clot regeneration for the management of young, immature, necrotic, permanent teeth. The digital databases MEDLINE, SCOPUS, CENTRAL, Web of Science, and EMBASE were searched to identify ten randomized clinical trials. The outcomes at postoperative follow-up, such as dentinal wall thickness (DWT), increase in root length (RL), calcific barrier formation (CB), apical closure (AC), vitality response (VR), and success rate (SR), were subjected to both qualitative synthesis and quantitative meta-analysis. The meta-analysis showed that APCs significantly improved apical closure (risk ratio (RR) = 1.17; 95% CI: 1.01, 1.37; p = 0.04) and response to vitality pulp tests (RR = 1.61; 95% CI: 1.03, 2.52; p = 0.04), whereas no significant effect was observed on root lengthening, dentin wall thickness, or success rate of immature, necrotic teeth treated with regenerative endodontics. APCs could be beneficial when treating young, immature, necrotic, permanent teeth regarding better apical closure and improved response to vitality tests.
    Matched MeSH terms: Blood Platelets/metabolism; Tooth/metabolism
  9. Burgeiro A, Fuhrmann A, Cherian S, Espinoza D, Jarak I, Carvalho RA, et al.
    Am J Physiol Endocrinol Metab, 2016 Apr 01;310(7):E550-64.
    PMID: 26814014 DOI: 10.1152/ajpendo.00384.2015
    Type 2 diabetes mellitus is a complex metabolic disease, and cardiovascular disease is a leading complication of diabetes. Epicardial adipose tissue surrounding the heart displays biochemical, thermogenic, and cardioprotective properties. However, the metabolic cross-talk between epicardial fat and the myocardium is largely unknown. This study sought to understand epicardial adipose tissue metabolism from heart failure patients with or without diabetes. We aimed to unravel possible differences in glucose and lipid metabolism between human epicardial and subcutaneous adipocytes and elucidate the potential underlying mechanisms involved in heart failure. Insulin-stimulated [(14)C]glucose uptake and isoproterenol-stimulated lipolysis were measured in isolated epicardial and subcutaneous adipocytes. The expression of genes involved in glucose and lipid metabolism was analyzed by reverse transcription-polymerase chain reaction in adipocytes. In addition, epicardial and subcutaneous fatty acid composition was analyzed by high-resolution proton nuclear magnetic resonance spectroscopy. The difference between basal and insulin conditions in glucose uptake was significantly decreased (P= 0.006) in epicardial compared with subcutaneous adipocytes. Moreover, a significant (P< 0.001) decrease in the isoproterenol-stimulated lipolysis was also observed when the two fat depots were compared, and it was strongly correlated with lipolysis, lipid storage, and inflammation-related gene expression. Moreover, the fatty acid composition of these tissues was significantly altered by diabetes. These results emphasize potential metabolic differences between both fat depots in the presence of heart failure and highlight epicardial fat as a possible therapeutic target in situ in the cardiac microenvironment.
    Matched MeSH terms: Adipose Tissue/metabolism*; Blood Glucose/metabolism*; Diabetes Mellitus, Type 2/metabolism*; Fatty Acids/metabolism*; Glucose/metabolism; Heart Failure/metabolism*; Pericardium/metabolism*; Adipocytes/metabolism*; Lipid Metabolism/drug effects; Lipid Metabolism/physiology*
  10. Bondhon TA, Fatima A, Jannat K, Hasan A, Jahan R, Nissapatorn V, et al.
    Trop Biomed, 2021 Jun 01;38(2):214-221.
    PMID: 34172713 DOI: 10.47665/tb.38.2.060
    Corona virus SARS-CoV-2-induced viral disease (COVID-19) is a zoonotic disease that was initially transmitted from animals to humans. The virus surfaced towards the end of December 2019 in Wuhan, China where earlier SARS (Severe Acute Respiratory Syndrome) had also surfaced in 2003. Unlike SARS, SARS-CoV-2 (a close relative of the SARS virus) created a pandemic, and as of February 24 2021, caused 112,778,672 infections and 2,499,252 deaths world-wide. Despite the best efforts of scientists, no drugs against COVID-19 are yet in sight; five vaccines have received emergency approval in various countries, but it would be a difficult task to vaccinate twice the world population of 8 billion. The objective of the present study was to evaluate through in silico screening a number of phytochemicals in Allium cepa (onion) regarding their ability to bind to the main protease of COVID-19 known as the 3C-like protease or 3CLpro, (PDB ID: 6LU7), 3CLpro of SARS (PDB ID: 3M3V), and human angiotensin converting enzyme-2 (ACE-2), [PDB ID: 1R42], which functions as a receptor for entry of the virus into humans. Molecular docking (blind docking, that is docking not only against any target pocket) were done with the help of AutoDockVina. It was observed that of the twenty-two phytochemicals screened, twelve showed good binding affinities to the main protease of SARS-CoV-2. Surprisingly, the compounds also demonstrated good binding affinities to ACE-2. It is therefore very likely that the binding affinities shown by these compounds against both 3CLpro and ACE-2 merit further study for their potential use as therapeutic agents.
    Matched MeSH terms: Phytochemicals/metabolism*; Spike Glycoprotein, Coronavirus/metabolism
  11. Chee JW, Amirul AA, Majid MI, Mansor SM
    Int J Pharm, 2008 Sep 1;361(1-2):1-6.
    PMID: 18584978 DOI: 10.1016/j.ijpharm.2008.05.007
    Copolyesters of 3-hydroxybutyrate (3HB) and 4-hydroxybutyrate (4HB) were produced by Cupriavidus sp. (USMAA2-4) (DSM 19379) from carbon sources of 1,4-butanediol and gamma-butyrolactone. The composition of copolyesters produced varied from 0 to 45 mol% 4HB, depending on the combination of carbon sources supplied. The P(3HB-co-4HB) films containing Mitragyna speciosa crude extract were prepared with the ratio varying from 10 to 40% (w/w). The in vitro crude extract release of the films was studied in 0.1M phosphate buffer (pH 7.4) at 37 degrees C. Although the release rate was slow, it was maintained at a constant rate. This suggests that the crude extract release was due to the polymer degradation because the amount of crude extract released was consistent. The amount of degradation was based on the films' dry weight loss, decrease in molecular weight and surface morphology changes. The degradation rate increased with the 4HB content. This showed that the polymer degradation is dependant on the molecular weight, crystallinity, thermal properties and water permeability. The different drug loading ratio which led to surface morphology changes also gave an effect on polymer degradation.
    Matched MeSH terms: Plant Extracts/metabolism*; Water/metabolism
  12. Chatterjee B, Gorain B, Mohananaidu K, Sengupta P, Mandal UK, Choudhury H
    Int J Pharm, 2019 Jun 30;565:258-268.
    PMID: 31095983 DOI: 10.1016/j.ijpharm.2019.05.032
    Intranasal delivery has shown to circumvent blood-brain-barrier (BBB) and deliver the drugs into the CNS at a higher rate and extent than other conventional routes. The mechanism of drug transport from nose-to-brain is not fully understood yet, but several neuronal pathways are considered to be involved. Intranasal nanoemulsion for brain targeting is investigated extensively. Higher brain distribution of drug after administering intranasal nanoemulsion was established by many researchers. Issues with nasomucosal clearance are solved by formulating modified nanoemulsion; for instance, mucoadhesive nanoemulsion or in situ nanoemulgel. However, no intranasal nanoemulsion for brain targeted drug delivery has been able to cross the way from 'benches to bed-side' of patients. Possibilities of toxicity by repeated administration, irregular nasal absorption during the diseased condition, use of a high amount of surfactants are few of the persisting challenges that need to overcome in coming days. Understanding the ways how current developments has solved some challenges is necessary. At the same time, the future direction of the research on intranasal nanoemulsion should be figured out based on existing challenges. This review is focused on the current developments of intranasal nanoemulsion with special emphasis on the existing challenges that would help to set future research direction.
    Matched MeSH terms: Brain/metabolism*; Nasal Mucosa/metabolism*
  13. Chong ZX, Yeap SK, Ho WY
    J Biomed Sci, 2021 Mar 25;28(1):21.
    PMID: 33761957 DOI: 10.1186/s12929-021-00715-9
    Breast cancer is the most common solid cancer that affects female population globally. MicroRNAs (miRNAs) are short non-coding RNAs that can regulate post-transcriptional modification of multiple downstream genes. Autophagy is a conserved cellular catabolic activity that aims to provide nutrients and degrade un-usable macromolecules in mammalian cells. A number of in vitro, in vivo and clinical studies have reported that some miRNAs could modulate autophagy activity in human breast cancer cells, and these would influence human breast cancer progression and treatment response. Therefore, this review was aimed to discuss the roles of autophagy-regulating miRNAs in influencing breast cancer development and treatment response. The review would first introduce autophagy types and process, followed by the discussion of the roles of different miRNAs in modulating autophagy in human breast cancer, and to explore how would this miRNA-autophagy regulatory process affect the disease progression or treatment response. Lastly, the potential applications and challenges of utilizing autophagy-regulating miRNAs as breast cancer biomarkers and novel therapeutic agents would be discussed.
    Matched MeSH terms: Biomarkers, Tumor/metabolism*; MicroRNAs/metabolism*
  14. Lee WQ, Affandi IS, Feroz SR, Mohamad SB, Tayyab S
    J Biochem Mol Toxicol, 2017 Feb;31(2).
    PMID: 27636401 DOI: 10.1002/jbt.21839
    Interaction of pendimethalin (PM) herbicide with the major transporter in human circulation, human serum albumin (HSA), was studied using fluorescence, circular dichroism (CD), and molecular modeling methods. The attenuation of the fluorescence intensity of HSA in the presence of PM revealed formation of the PM-HSA complex. Analysis of the fluorescence quenching data showed moderately strong binding affinity between PM and HSA. Both hydrophobic interactions and hydrogen bonding were suggested to stabilize the PM-HSA complex, based on thermodynamic data. Binding of PM to HSA induced perturbation in the microenvironment around the aromatic fluorophores as well as secondary and tertiary structural changes in the protein. Complexation of PM with HSA led to an increase in its thermal stability. Both site marker displacement and molecular modeling results suggested site I, located in subdomain IIA as the preferred binding site of PM on HSA.
    Matched MeSH terms: Aniline Compounds/metabolism*; Serum Albumin/metabolism*
  15. Wisitponchai T, Shoombuatong W, Lee VS, Kitidee K, Tayapiwatana C
    BMC Bioinformatics, 2017 Apr 19;18(1):220.
    PMID: 28424069 DOI: 10.1186/s12859-017-1628-6
    BACKGROUND: Computational analysis of protein-protein interaction provided the crucial information to increase the binding affinity without a change in basic conformation. Several docking programs were used to predict the near-native poses of the protein-protein complex in 10 top-rankings. The universal criteria for discriminating the near-native pose are not available since there are several classes of recognition protein. Currently, the explicit criteria for identifying the near-native pose of ankyrin-protein complexes (APKs) have not been reported yet.

    RESULTS: In this study, we established an ensemble computational model for discriminating the near-native docking pose of APKs named "AnkPlex". A dataset of APKs was generated from seven X-ray APKs, which consisted of 3 internal domains, using the reliable docking tool ZDOCK. The dataset was composed of 669 and 44,334 near-native and non-near-native poses, respectively, and it was used to generate eleven informative features. Subsequently, a re-scoring rank was generated by AnkPlex using a combination of a decision tree algorithm and logistic regression. AnkPlex achieved superior efficiency with ≥1 near-native complexes in the 10 top-rankings for nine X-ray complexes compared to ZDOCK, which only obtained six X-ray complexes. In addition, feature analysis demonstrated that the van der Waals feature was the dominant near-native pose out of the potential ankyrin-protein docking poses.

    CONCLUSION: The AnkPlex model achieved a success at predicting near-native docking poses and led to the discovery of informative characteristics that could further improve our understanding of the ankyrin-protein complex. Our computational study could be useful for predicting the near-native poses of binding proteins and desired targets, especially for ankyrin-protein complexes. The AnkPlex web server is freely accessible at http://ankplex.ams.cmu.ac.th .

    Matched MeSH terms: Proteins/metabolism*; Ankyrins/metabolism*
  16. Gan CS, Lim PJ, Razif MF, Yusof R, Othman S
    Rev Soc Bras Med Trop, 2017 Jan-Feb;50(1):99-103.
    PMID: 28327809 DOI: 10.1590/0037-8682-0207-2016
    INTRODUCTION:: Infection with all serotypes of dengue virus (DV) results in augmented antigen presentation by MHC class I molecules. However, the upregulation of immunoproteasome subunits only results from infection with two serotypes. This study aims to elucidate changes in the expression of immunoproteasome subunits resulting from infection with DV, particularly DV serotype 2 (DV2).

    METHODS:: HepG2 cells were grown in various culture milieu. Total cellular RNA and proteins were extracted and quantified.

    RESULTS:: Results demonstrated sequestration of immunoproteasome subunits LMP2 and LMP7 in DV2-infected cells.

    CONCLUSIONS:: This study provides insights into the mechanisms underlying immune evasion by DV.
    Matched MeSH terms: Dengue Virus/metabolism*; Proteasome Endopeptidase Complex/metabolism*
  17. Migasena P, Maegraith BG
    Med J Malaya, 1968 Mar;22(3):251.
    PMID: 4234389
    Matched MeSH terms: Malaria/metabolism*; Serum Albumin/metabolism*
  18. Cheng WK, Oon CE
    Biomed Pharmacother, 2018 Jul;103:1246-1252.
    PMID: 29864905 DOI: 10.1016/j.biopha.2018.04.119
    Glycosylation is an enzymatic process in which a carbohydrate is attached to a functional group from another molecule. Glycosylation is a crucial post translational process in protein modification. The tumor microenvironment produces altered glycans that contribute to cancer progression and aggressiveness. Abnormal glycosylation is widely observed in tumor angiogenesis. Despite many attempts to decipher the role of glycosylation in different aspects of cancer, little is known regarding the roles of glycans in angiogenesis. The blood vessels in tumors are often used to transport oxygen and nutrients for tumor progression and metastasis. The crosstalk within the tumor microenvironment can induce angiogenesis by manipulating these glycans to hijack the normal angiogenesis process, thus promoting tumor growth. Abnormal glycosylation has been shown to promote tumor angiogenesis by degrading the extracellular matrix to activate the angiogenic signaling pathways. This review highlights the latest update on how glycosylation can contribute to tumor angiogenesis that may affect treatment outcomes.
    Matched MeSH terms: Neoplasms/metabolism*; Neovascularization, Pathologic/metabolism*
  19. Minayoshi Y, Maeda H, Yanagisawa H, Hamasaki K, Mizuta Y, Nishida K, et al.
    Drug Deliv, 2018 Nov;25(1):1067-1077.
    PMID: 29688069 DOI: 10.1080/10717544.2018.1464083
    Because of its multifaceted anti-inflammatory and immunomodulatory effects, delivering type-I interferon to Kupffer cells has the potential to function as a novel type of therapy for the treatment of various types of hepatitis. We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis. The presence of this unique oligosaccharide permits the protein to be efficiently, rapidly and preferentially distributed to Kupffer cells. Likewise IFNα2b, Man-HSA(D494N)-IFNα2b caused a significant induction in the mRNA levels of IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells, and these inductions were largely inhibited by blocking the interferon receptor. These data indicate that Man-HSA(D494N)-IFNα2b retained the biological activities of type-I interferon. Man-HSA(D494N)-IFNα2b significantly inhibited liver injury in Concanavalin A (Con-A)-induced hepatitis model mice, and consequently improved their survival rate. Moreover, the post-administration of Man-HSA(D494N)-IFNα2b at 2 h after the Con-A challenge also exerted hepato-protective effects. In conclusion, this proof-of-concept study demonstrates the therapeutic effectiveness and utility of Kupffer cell targeting type-I interferon against hepatitis via its anti-inflammatory and immunomodulatory actions.
    Matched MeSH terms: Hepatitis/metabolism; Interferon Type I/metabolism*; Kupffer Cells/metabolism*; Liver/metabolism; Mannose/metabolism; Recombinant Proteins/metabolism; Serum Albumin/metabolism; Interleukin-10/metabolism; Interferon-alpha/metabolism; Interleukin 1 Receptor Antagonist Protein/metabolism; Antigens, CD274/metabolism
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