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1.
Biomed Pharmacother ; 173: 116415, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38479182

RESUMO

Tetramethylpyrazine nitrone (TBN), a novel derivative of tetramethylpyrazine (TMP) designed and synthesized by our group, possesses multi-functional mechanisms of action and displays broad protective effects in vitro and in animal models of age-related brain disorders such as stroke, Alzheimer's disease (AD), Amyotrophic Lateral Sclerosis (ALS) and Parkinson's disease (PD). In the present report, we investigated the effects of TBN on aging, specifically on muscle aging and the associated decline of motor functions. Using a D-galactose-induced aging mouse model, we found that TBN could reverse the levels of several senescence and aging markers including p16, p21, ceramides, and telomere length and increase the wet-weight ratio of gastrocnemius muscle tissue, demonstrating its efficacy in ameliorating muscle aging. Additionally, the pharmacological effects of TBN on motor deficits (gait analysis, pole-climbing test and grip strength test), muscle fibrosis (hematoxylin & eosin (HE), Masson staining, and αSMA staining), inflammatory response (IL-1ß, IL-6, and TNF-α), and mitochondrial function (ATP, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) were also confirmed in the D-galactose-induced aging models. Further experiments demonstrated that TBN alleviated muscle aging and improved the decline of age-related motor deficits through an AMPK-dependent mechanism. These findings highlight the significance of TBN as a potential anti-aging agent to combat the occurrence and development of aging and age-related diseases.


Assuntos
Galactose , Fármacos Neuroprotetores , Pirazinas , Camundongos , Animais , Proteínas Quinases Ativadas por AMP , Fármacos Neuroprotetores/farmacologia , Envelhecimento , Transdução de Sinais , Músculo Esquelético
2.
J Agric Food Chem ; 72(11): 5816-5827, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38442258

RESUMO

Marine biomass stands out as a sustainable resource for generating value-added chemicals. In particular, anhydrosugars derived from carrageenans exhibit a variety of biological functions, rendering them highly promising for utilization and cascading in food, cosmetic, and biotechnological applications. However, the limitation of available sulfatases to break down the complex sulfation patterns of carrageenans poses a significant limitation for the sustainable production of valuable bioproducts from red algae. In this study, we screened several carrageenolytic polysaccharide utilization loci for novel sulfatase activities to assist the efficient conversion of a variety of sulfated galactans into the target product 3,6-anhydro-D-galactose. Inspired by the carrageenolytic pathways in marine heterotrophic bacteria, we systematically combined these novel sulfatases with other carrageenolytic enzymes, facilitating the development of the first enzymatic one-pot biotransformation of ι- and κ-carrageenan to 3,6-anhdyro-D-galactose. We further showed the applicability of this enzymatic bioconversion to a broad series of hybrid carrageenans, rendering this process a promising and sustainable approach for the production of value-added biomolecules from red-algal feedstocks.


Assuntos
Galactose , Rodófitas , Carragenina/química , Galactanos/química , Polissacarídeos , Rodófitas/química , Sulfatases
3.
Cell Biochem Funct ; 42(2): e3983, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38493450

RESUMO

Many of the cancer cells produce energy with accelerated glycolysis and perform lactic acid production even under normoxic conditions called the "Warburg effect". Metabolism can directly or indirectly regulate the apoptotic mechanism so that cancer cells take advantage of reprogrammed metabolism to avoid apoptosis. The aim of this study is to examine the mechanism of apoptosis by incubating human lung carcinoma cells (A549) under different metabolic conditions in hypoxia or normoxia environments. A549 cells were incubated in the normoxic or hypoxic condition that contained 5 mM glucose (Glc 5), 25 mM glucose (Glc 25), or 10 mM galactose (OXPHOS/aglycemic), and the mechanism of apoptosis was investigated. In the hypoxia condition, the rate of early apoptosis in aglycemic OXPHOS cells was increased (15.5% ±7.1). In addition, the activity of caspase-3 (6.1% ± 0.9), caspase-9 (30.4% ± 0.9), and cytochrome c expression level increased; however, the mitochondrial membrane potential (51.9% ± 0.4) was found to be decreased. Changing the amount of oxygen in glycolytic cells had no effect on apoptosis. However, it has been determined that apoptosis is stimulated under hypoxia conditions in aglycemic cells in which galactose is used instead of glucose. Considering that the majority of cancer cells are hypoxic, these data are important in determining targets in therapeutic intervention.


Assuntos
Galactose , Hipóxia , Humanos , Células A549 , Galactose/farmacologia , Apoptose , Glicólise , Hipóxia Celular , Glucose/farmacologia , Glucose/metabolismo
4.
PLoS Biol ; 22(3): e3002549, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38502638

RESUMO

Sugar metabolism plays a pivotal role in sustaining life. Its dynamics within organisms is less understood compared to its intracellular metabolism. Galactose, a hexose stereoisomer of glucose, is a monosaccharide transported via the same transporters with glucose. Galactose feeds into glycolysis and regulates protein glycosylation. Defects in galactose metabolism are lethal for animals. Here, by transgenically implementing the yeast galactose sensing system into Drosophila, we developed a genetically encoded sensor, GALDAR, which detects galactose in vivo. Using this heterologous system, we revealed dynamics of galactose metabolism in various tissues. Notably, we discovered that intestinal stem cells do not uptake detectable levels of galactose or glucose. GALDAR elucidates the role for galactokinase in metabolism of galactose and a transition of galactose metabolism during the larval period. This work provides a new system that enables analyses of in vivo sugar metabolism.


Assuntos
Galactose , Glicólise , Animais , Galactose/metabolismo , Glicólise/genética , Glicosilação , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Drosophila/metabolismo , Glucose/metabolismo
5.
Aging (Albany NY) ; 16(5): 4541-4562, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38428403

RESUMO

Ningxin-Tongyu-Zishen formula (NTZF) is a clinical experience formula for the treatment of premature ovarian insufficiency (POI) in traditional Chinese medicine (TCM), and the potential mechanism is unknown. For in vivo experiments, POI mouse models (C57BL/6 mice), were constructed by subcutaneous injection of D-galactose (D-gal, 200 mg/kg). After treatment of NTZF (10.14, 20.27, 40.54 g/kg;) or estradiol valerate (0.15 mg/kg), ovarian function, oxidative stress (OS) and protein expression of Sirt1/p53 were evaluated. For in vitro experiments, H2O2 (200 µM) was used to treat KGN to construct ovarian granulosa cells (OGCs) cell senescence model. Pretreatment with NTZF (1.06 mg/mL) or p53 inhibitor (Pifithrin-α, 1 µM) was performed before induction of senescence, and further evaluated the cell senescence, OS, mRNA and protein expression of Sirt1/p53. In vivo, NTZF improved ovarian function, alleviated OS and Sirt1/p53 signaling abnormalities in POI mice. In vitro experiments showed that NTZF reduced the level of OS and alleviated the senescence of H2O2-induced KGN. In addition, NTZF activated the protein expression of Sirt1, inhibited the mRNA transcription and protein expression of p53 and p21. Alleviating OGCs senescence and protecting ovarian function through Sirt1/p53 is one of the potential mechanisms of NTZF in the treatment of POI.


Assuntos
Galactose , Insuficiência Ovariana Primária , Humanos , Feminino , Camundongos , Animais , Galactose/toxicidade , Sirtuína 1/genética , Sirtuína 1/metabolismo , Peróxido de Hidrogênio/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Camundongos Endogâmicos C57BL , Insuficiência Ovariana Primária/induzido quimicamente , Insuficiência Ovariana Primária/tratamento farmacológico , Insuficiência Ovariana Primária/genética , Células da Granulosa/metabolismo , Senescência Celular , RNA Mensageiro/metabolismo
6.
J Immunol Res ; 2024: 9307906, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38516617

RESUMO

A decline in immune response, exhibited in the form of immunosenescence and inflammaging, is an age-associated disturbance of the immune system known to predispose the elderly to a greater susceptibility to infection and poor vaccine response. Polysaccharides and polyphenols from botanicals are known for their immune modulation effects. Here we evaluated a standardized mushroom-based composition, UP360, from Aloe barbadensis, Poria cocos, and Rosmarinus officinalis, as a natural nutritional supplement for a balanced immune response in an accelerated aging mouse model. Immunosenescence was induced by continual subcutaneous injection of D-galactose (D-gal) at a dose of 500 mg/kg/day to CD-1 mice. UP360 was administered at oral doses of 200 and 400 mg/kg to the mice starting on the 5th week of D-gal injection. The study lasted for a total of 9 weeks. All mice were given a quadrivalent influenza vaccine at 3 µg/animal via intramuscular injection 14 days before the end of the study. A group of D-gal-treated mice treated at 400 mg/kg/day UP360 was kept without vaccination. Whole blood, serum, spleen homogenate, and thymus tissues were used for analysis. UP360 was found to improve the immune response as evidenced by stimulation of innate and adaptive immune responses, increase antioxidant capacity as reflected by augmented SOD and Nrf2, and preserve vital immune organs, such as the thymus, from aging-associated damage. The findings depicted in this report show the effect of the composition in activating and maintaining homeostasis of the immune system both during active infections and as a preventive measure to help prime the immune system. These data warrant further clinical study to explore the potential application of the mushroom-based composition as an adjunct nutritional supplement for a balanced immune response.


Assuntos
Aloe , Imunossenescência , Humanos , Camundongos , Animais , Idoso , Galactose/farmacologia , Polifenóis/farmacologia , Envelhecimento , Polissacarídeos/farmacologia , Estresse Oxidativo
7.
Carbohydr Polym ; 333: 121976, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38494228

RESUMO

White tea, one of the six traditional teas in China, is made only through natural withering and low-temperature drying processes. It demonstrates diverse pharmacological and health-promoting effects, including antioxidant, antiviral, anticancer, and hypolipidemic activities. Despite the significance of polysaccharides in white tea leaves, their fine structure and physiological functions remain unexplored. In this study, the polysaccharide fragment WTP-80a with anticancer activity was isolated and purified from white tea through water extraction, alcohol precipitation, DEAE-52 ion exchange column chromatography, and sephacryl S-200 dextran gel column chromatography. WTP-80a exhibited a molecular weight of 1.14 × 105 Da and consisted of galactose (Gal), arabinose (Ara), rhamnose (Rha), and glucuronic acid (Glc-UA). The main chain skeleton of WTP-80a contained 3,6)-ß-Galp-(1→, 3)-α-Galp-(1→, 5)-α-Araf-(1 â†’ and 3)-α-Glcp-UA-(1→. Branch chains included α-Araf-(1 â†’ and ß-Rhap-(1 â†’ connected to the C3 and C6 positions of →3,6)-ß-Galp-(1→, respectively. In vitro anticancer experiments revealed that WTP-80a effectively hindered the proliferation, colony formation, migration, and invasion of B16F10 cells. Additionally, it induced apoptosis in B16F10 cells by blocking the G2/M phase, increasing active oxygen content, and reducing mitochondrial membrane potential. These findings provide a solid theoretical foundation for the application of white tea polysaccharides as anticancer products.


Assuntos
Galactose , Polissacarídeos , Polissacarídeos/química , Galactose/análise , Ramnose , Ácido Glucurônico , Chá
8.
Carbohydr Polym ; 333: 121986, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38494237

RESUMO

Heparin, an anticoagulant with a century-long history of use, has been investigated over the past decade as a potential drug delivery vehicle. Despite its safety and efficacy, its interactions with many proteins through specific sulfate patterns can complicate drug delivery by mediating diverse biological functions. Here, we present the synthesis of a three-component drug delivery system comprising de-sulfated heparin as the carrier, galactose as the targeting moiety, and paclitaxel as the therapeutic drug. Removal of sulfates eliminated most of its anticoagulant effects in all intermediates. Through coupling with galactose and paclitaxel, the system improved the solubility of the drug and achieved selective targeting and efficient drug delivery to HepG2 cells, a liver carcinoma cell line with high galactose receptor expression. While the three-component system exhibited a slightly higher IC50 value than native paclitaxel, demonstrating its efficacy as a drug carrier, the IC50 value for the normal human liver cell line QSG7701 was significantly higher, indicating its selectivity and safety. Our study introduces a novel approach utilizing desulfated heparin as a carrier, warranting further investigation to unlock its potential in targeted drug delivery strategies.


Assuntos
Heparina , Paclitaxel , Humanos , Paclitaxel/farmacologia , Galactose , Sulfatos/metabolismo , Anticoagulantes , Sistemas de Liberação de Medicamentos
9.
Front Immunol ; 15: 1358178, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38469303

RESUMO

The prevalence of food allergy is rising and is estimated to approach 10%. Red meat allergy is the first known food allergy elicited by immunoglobulin E (IgE) antibodies recognizing a carbohydrate. Due to the loss of function of the alpha-1,3-galactosyltransferase (GGTA1) gene in humans, the disaccharide galactose-α-1,3-galactose (α-Gal) cannot be synthesized and therefore became immunogenic. IgE sensitization is elicited through the skin by repetitive tick bites transmitting α-Gal. The underlying mechanisms regarding innate and adaptive immune cell activation, including the B-cell isotype switch to IgE, are poorly understood, requiring further research and physiologically relevant animal models. Here, we describe a new animal model of red meat allergy using percutaneous α-Gal sensitization of gene-edited GGTA1-deficient pigs. Total and α-Gal-specific IgG, IgG1, IgG2, IgG4, and IgE levels were tracked. Further key factors associated with allergic skin inflammation, type 2 immunity, and allergy development were measured in PBMCs and skin samples. Significant increases in α-Gal-specific IgG1 and IgE levels indicated successful sensitization to the allergen α-Gal. Intracutaneous sensitizations with α-Gal recruited lymphocytes to the skin, including elevated numbers of T helper 2 (Th2) cells. Finally, α-Gal-sensitized pigs not only recognized α-Gal as non-self-antigen following α-Gal exposure through the skin but also developed anaphylaxis upon antigen challenge. Based on the similarities between the porcine and human skin, this new large animal model for α-Gal allergy should help to unveil the consecutive steps of cutaneous sensitization and aid the development of prophylactic and treatment interventions.


Assuntos
Anafilaxia , Hipersensibilidade Alimentar , Humanos , Animais , Suínos , Galactose , Edição de Genes , Imunoglobulina E , Imunoglobulina G
10.
Biotechnol J ; 19(2): e2300415, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38375553

RESUMO

We designed and constructed a green and sustainable bioprocess to efficiently coproduce D -tagatose, bioethanol, and microbial protein from whey powder. First, a one-pot biosynthesis process involving lactose hydrolysis and D -galactose redox reactions for D -tagatose production was established in vitro via a three-enzyme cascade. Second, a nicotinamide adenine dinucleotide phosphate-dependent galactitol dehydrogenase mutant, D36A/I37R, based on the nicotinamide adenine dinucleotide-dependent polyol dehydrogenase from Paracoccus denitrificans was created through rational design and screening. Moreover, an NADPH recycling module was created in the oxidoreductive pathway, and the tagatose yield increased by 3.35-fold compared with that achieved through the pathway without the cofactor cycle. The reaction process was accelerated using an enzyme assembly with a glycine-serine linker, and the tagatose production rate was 9.28-fold higher than the initial yield. Finally, Saccharomyces cerevisiae was introduced into the reaction solution, and 266.5 g of D -tagatose, 162.6 g of bioethanol, and 215.4 g of dry yeast (including 38% protein) were obtained from 1 kg of whey powder (including 810 g lactose). This study provides a promising sustainable process for functional food (D -tagatose) production. Moreover, this process fully utilized whey powder, demonstrating good atom economy.


Assuntos
Hexoses , Lactose , Soro do Leite , Soro do Leite/metabolismo , Pós/metabolismo , Lactose/metabolismo , Indústria de Laticínios , Galactose/metabolismo
11.
Medicine (Baltimore) ; 103(5): e37067, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38306560

RESUMO

BACKGROUND: Serum galactomannan (GM) and ß-D-glucan (BG) are known markers of invasive aspergillosis (IA). The aim of this meta-analysis was to evaluate the efficiency of serum GM and BG as diagnostic markers of symptomatic IA infection and compare the performance of the combined tests with that of either test individually. METHODS: A literature search was carried out using PubMed, Web of Science, and EMBASE databases to include relevant studies published in English up to May 2023. The quality assessment was performed using Review Manager 5.3 software. A bivariate model was applied to pool diagnostic parameters using Stata 14.0 software. We used Cochrane I2 index to assess heterogeneity and identify the potential source of heterogeneity by meta-regression. Paired t tests were used to compare the value of GM and BG for IA diagnosis when used in combination or alone. RESULTS: Sixteen studies were eligible for inclusion in the meta-analysis. For proven or probable IA, serum GM and BG yielded a pooled sensitivity of 0.53 (95% CI 0.40-0.66) vs 0.72 (95% CI 0.61-0.81) and a pooled specificity of 0.94 (95% CI 0.91-0.97) vs 0.82 (95% CI 0.73-0.88). The area under the curve (AUC) of ROC was 0.90 (95% CI 0.87-0.92) vs 0.83 (95% CI 0.80-0.86) for all studies. The pooled sensitivity and specificity for IA diagnosis by combined GM and BG assays (GM/BG) were 0.84 (95% CI 0.69-0.86) and 0.76 (95% CI 0.69-0.81), respectively. The sensitivity of the combined GM/BG test to diagnose IA was higher than of the GM or BG test alone. CONCLUSION: Serum GM and BG tests had a relatively high accuracy for IA diagnosis in suspected patients. The diagnostic accuracy of both assays is comparable, and the diagnostic sensitivity is further improved by the combined detection of the 2 markers.


Assuntos
Aspergilose , Galactose/análogos & derivados , Infecções Fúngicas Invasivas , Aspergilose Pulmonar Invasiva , beta-Glucanas , Humanos , Aspergilose/diagnóstico , Sensibilidade e Especificidade , Mananas , Infecções Fúngicas Invasivas/diagnóstico , Aspergilose Pulmonar Invasiva/diagnóstico
12.
J Agric Food Chem ; 72(7): 3644-3653, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38335068

RESUMO

The limited availability of high-cost nucleotide sugars is a significant constraint on the application of their downstream products (glycosides and prebiotics) in the food or pharmaceutical industry. To better solve the problem, this study presented a one-pot approach for the biosynthesis of UDP-Gal using a thermophilic multienzyme system consisting of GalK, UGPase, and PPase. Under optimal conditions, a 2 h reaction resulted in a UTP conversion rate of 87.4%. In a fed-batch reaction with Gal/ATP = 20 mM:10 mM, UDP-Gal accumulated to 33.76 mM with a space-time yield (STY) of 6.36 g/L·h-1 after the second feeding. In repetitive batch synthesis, the average yield of UDP-Gal over 8 cycles reached 10.80 g/L with a very low biocatalyst loading of 0.002 genzymes/gproduct. Interestingly, Galk (Tth0595) could synthesize Gal-1P using ADP as a donor of phosphate groups, which had never been reported before. This approach possessed the benefits of high synthesis efficiency, low cost, and superior reaction system stability, and it provided new insights into the rapid one-pot synthesis of UDP-Gal and high-value glycosidic compounds.


Assuntos
Nucleotídeos , Uridina Difosfato Galactose , Difosfato de Uridina , Galactose
13.
Nutrients ; 16(4)2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38398836

RESUMO

Eggs, with their high nutritional value, are great carriers for enriching nutrients. In this study, selenium- and/or zinc-enriched eggs (SZE) were obtained and their effects on ameliorating oxidative stress injury, alleviating cognitive impairment, and maintaining intestinal flora balance in a D-gal-induced aging mice model were investigated. As determined by the Y-maze test, SZE restored the learning and memory abilities and increased the Ach level and AChE activity of aging mice (p < 0.05). Meanwhile, supplementation of low-dose SZE increased antioxidant levels and decreased inflammation levels (p < 0.05). High-dose SZE increased anti-inflammatory levels but were less effective than low dose. Additionally, SZE maintained the intestinal flora balance and significantly increased the ratio of Firmicutes and Bacteroidota. Blautia, as a probiotic, was negatively correlated with pro-inflammatory factors and positively correlated with antioxidant levels (p < 0.05). These results suggest that SZE might improve organ damage and cognitive function by attenuating oxidative stress and inflammatory response and maintaining healthy gut flora.


Assuntos
Microbioma Gastrointestinal , Selênio , Camundongos , Animais , Selênio/farmacologia , Antioxidantes/farmacologia , Zinco/farmacologia , Estresse Oxidativo , Envelhecimento , Dieta , Galactose/farmacologia
14.
Sci Rep ; 14(1): 4123, 2024 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-38374148

RESUMO

Although cataract is the leading cause of blindness worldwide, the detailed pathogenesis of cataract remains unclear, and clinically useful drug treatments are still lacking. In this study, we examined the effects of glutamate using an ex vivo model in which rat lens is cultured in a galactose-containing medium to induce opacity formation. After inducing lens opacity formation in galactose medium, glutamate was added, and the opacity decreased when the culture was continued. Next, microarray analysis was performed using samples in which the opacity was reduced by glutamate, and genes whose expression increased with galactose culture and decreased with the addition of glutamate were extracted. Subsequently, STRING analysis was performed on a group of genes that showed variation as a result of quantitative measurement of gene expression by RT-qPCR. The results suggest that apoptosis, oxidative stress, endoplasmic reticulum (ER) stress, cell proliferation, epithelial-mesenchymal transition (EMT), cytoskeleton, and histones are involved in the formation and reduction of opacity. Therefore, glutamate may reduce opacity by inhibiting oxidative stress and its downstream functions, and by regulating the cytoskeleton and cell proliferation.


Assuntos
Catarata , Cristalino , Ratos , Animais , Galactose/metabolismo , Ácido Glutâmico/metabolismo , Catarata/induzido quimicamente , Catarata/genética , Cristalino/metabolismo , Apoptose , Células Epiteliais/metabolismo
15.
PLoS One ; 19(2): e0299145, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38416732

RESUMO

Cataract is an eye disease, in which the lens becomes opaque, causing vision loss and blindness. The detailed mechanism of cataract development has not been characterized, and effective drug therapies remain unavailable. Here, we investigated the effects of Hypoxia-inducible factor 1 (HIF-1) inhibitors using an ex vivo model, in which rat lenses were cultured in galactose-containing medium to induce opacity formation. We found that treatment with the HIF-1 inhibitors 2-Methoxyestradiol (2ME2), YC-1, and Bavachinin decreased lens opacity. Microarray analysis on 2ME2-treated samples, in which opacity was decreased, identified genes upregulated by galactose and downregulated by inhibitor treatment. Subsequent STRING analysis on genes that showed expression change by RT-qPCR identified two clusters. First cluster related to the cytoskeleton and epithelial-mesenchymal transition (EMT). Second cluster related to the oxidative stress, and apoptosis. ACTA2, a known marker for EMT, and TXNIP, a suppressor of cell proliferation and activator of apoptosis, were present in each cluster. Thus, suppression of EMT and apoptosis, as well as activation of cell proliferation, appear to underlie the decrease in lens opacity.


Assuntos
Catarata , Cristalino , Ratos , Animais , Galactose/metabolismo , Fator 1 Induzível por Hipóxia/metabolismo , Catarata/induzido quimicamente , Catarata/tratamento farmacológico , Cristalino/metabolismo , Apoptose , Proteínas de Ciclo Celular/metabolismo
16.
Int J Med Mushrooms ; 26(2): 57-70, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38421696

RESUMO

In the present study, a new galectin designated Cyclocybe cylindracea lectin (CCL) was extracted from the fruiting bodies of the wild black popular mushroom C. cylindracea grown in Algeria. The protein was isolated using sepharose 4B as affinity chromatography matrix, and galactose as elutant. The purified galectin was composed of two subunits of 17.873 kDa each, with a total molecular mass of 35.6 kDa. Its agglutinant activity was impeded by galactose and its derivatives, as well as melibiose. Lactose showed the highest affinity, with a minimal inhibitory concentration of 0.0781 mM. CCL was sensitive to extreme pH conditions, and its binding function decreased when incubated with 10 mM EDTA, and it could be restored by metallic cations such as Ca2+, Mg2+, and Zn2+. CCL agglutinated human red blood cells, without any discernible specificity. Circular dichroism spectra demonstrated that its secondary structure contained ß-sheet as dominant fold. In addition, bioinformatics investigation on their peptide fingerprint obtained after MALDI-TOF/TOF ionization using mascot software confirmed that CCL was not like any previous purified lectin from mushroom: instead, it possessed an amino acid composition with high similarity to that of the putative urea carboxylase of Emericella nidulans (strain FGSC A4/ATCC 38163/CBS 112.46/NRRL 194/M139) with 44% of similarity score.


Assuntos
Agaricales , Basidiomycota , Populus , Humanos , Galectinas , Argélia , Galactose
17.
Eur J Med Chem ; 267: 116183, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38354520

RESUMO

Triggering ferroptosis is a potential therapeutic pathway and strategy for the prospective treatment of lethal hepatocellular carcinoma (HCC). The asialo-glycoprotein receptor (ASGPR) is an over-expressed receptor on the membranes of hepatocellular carcinoma cells (HCCs) and binds specifically to galactose (Gal) ligand. Celastrol (CE) is a potent anticancer natural product, but its poor water solubility and severe toxicity restrict its clinical application. In this study, a carrier-free self-assembled nanoparticles, CE-Gal-NPs, were designed and prepared by nanoprecipitation method, which could recognize ASGPR receptor by active targeting (Gal ligand) and passive targeting (EPR effect), access to the cell through the clathrin pathway and finally internalize to lysosomes. CE-Gal-NPs triggered reactive oxygen species (ROS)-mediated ferroptosis pathway and exerted anti-HCC effects in vitro and in vivo by down-regulating GPX4 and up-regulating COX-2 expression, depleting glutathione (GSH) levels, and increasing lipid peroxidation levels in cells and tumor tissues. In the H22 xenograft mouse model, the CE-Gal-NPs group exhibited dramatically superior tumor inhibition than the CE group, while Gal conjugating diminished the systemic toxicity of CE. Consequently, this study presented a promising strategy for CE potentiation and toxicity reduction, as well as a potential guideline for the development of clinically targeted therapeutic agents for HCC.


Assuntos
Carcinoma Hepatocelular , Ferroptose , Neoplasias Hepáticas , Triterpenos Pentacíclicos , Humanos , Camundongos , Animais , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Galactose , Nanomedicina , Ligantes , Células Hep G2
18.
Mar Drugs ; 22(2)2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38393052

RESUMO

Three different populations of sulfated polysaccharides can be found in the cell wall of the red alga Botryocladia occidentalis. In a previous work, the structures of the two more sulfated polysaccharides were revised. In this work, NMR-based structural analysis was performed on the least sulfated polysaccharide and its chemically modified derivatives. Results have revealed the presence of both 4-linked α- and 3-linked ß-galactose units having the following chemical features: more than half of the total galactose units are not sulfated, the α-units occur primarily as 3,6-anhydrogalactose units either 2-O-methylated or 2-O-sulfated, and the ß-galactose units can be 4-O-sulfated or 2,4-O-disulfated. SPR-based results indicated weaker binding of the least sulfated galactan to thrombin, factor Xa, and antithrombin, but stronger binding to heparin cofactor II than unfractionated heparin. This report together with our previous publication completes the structural characterization of the three polysaccharides found in the cell wall of the red alga B. occidentalis and correlates the impact of their composing chemical groups with the levels of interaction with the blood co-factors.


Assuntos
Galactanos , Rodófitas , Galactanos/química , Heparina , Sulfatos/química , Galactose , Anticoagulantes/química , Rodófitas/química , Polissacarídeos/química , Parede Celular
19.
Parasite ; 31: 6, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38334686

RESUMO

Previous studies have shown that recombinant Trichinella spiralis galectin (rTsgal) is characterized by a carbohydrate recognition domain sequence motif binding to beta-galactoside, and that rTsgal promotes larval invasion of intestinal epithelial cells. Galactomannan is an immunostimulatory polysaccharide composed of a mannan backbone with galactose residues. The aim of this study was to investigate whether galactomannan inhibits larval intrusion of intestinal epithelial cells and enhances antibody-dependent cellular cytotoxicity (ADCC), killing newborn larvae by polarizing macrophages to the M1 phenotype. The results showed that galactomannan specially binds to rTsgal, and abrogated rTsgal facilitation of larval invasion of intestinal epithelial cells. The results of qPCR, Western blotting, and flow cytometry showed that galactomannan and rTsgal activated macrophage M1 polarization, as demonstrated by high expression of iNOS (M1 marker) and M1 related genes (IL-1ß, IL-6, and TNF-α), and increased CD86+ macrophages. Galactomannan and rTsgal also increased NO production. The killing ability of macrophage-mediated ADCC on larvae was also significantly enhanced in galactomannan- and rTsgal-treated macrophages. The results demonstrated that Tsgal may be considered a potential vaccine target molecule against T. spiralis invasion, and galactomannan may be a novel adjuvant therapeutic agent and potential vaccine adjuvant against T. spiralis infection.


Title: Le galactomannane inhibe l'invasion par Trichinella spiralis des cellules de l'épithélium intestinal et améliore la cytotoxicité cellulaire dépendante des anticorps tuant les larves en activant la polarisation des macrophages. Abstract: Des études antérieures ont montré que la galectine recombinante de Trichinella spiralis (rTsgal) est caractérisée par un motif de séquence de domaines de reconnaissance des glucides se liant au bêta-galactoside, et que la rTsgal favorise l'invasion larvaire des cellules épithéliales intestinales. Le galactomannane est un polysaccharide immunostimulateur composé d'un squelette mannane avec des résidus galactose. Le but de cette étude était de déterminer si le galactomannane inhibe l'intrusion larvaire des cellules épithéliales intestinales et améliore la cytotoxicité cellulaire dépendante des anticorps (CCDA) tuant les larves nouvelles-nées en polarisant les macrophages au phénotype M1. Les résultats ont montré que le galactomannane se liait spécialement au rTsgal et supprimait la facilitation du rTsgal sur l'invasion larvaire des cellules épithéliales intestinales. Les résultats de la qPCR, du Western blot et de la cytométrie en flux ont montré que le galactomannane et le rTsgal activaient la polarisation des macrophages M1, comme le démontre la forte expression de l'iNOS (marqueur de M1) et des gènes liés à M1 (IL-1ß, IL-6 et TNF-α), et l'augmentation des macrophages CD86+. Le galactomannane et le rTsgal ont également augmenté la production de NO. La capacité de destruction de la CCDA médiée par les macrophages sur les larves était également significativement améliorée dans les macrophages traités au galactomannane et au rTsgal. Les résultats ont démontré que Tsgal pourrait être considéré comme une molécule cible potentielle d'un vaccin contre l'invasion par T. spiralis, et que le galactomannane pourrait être un nouvel agent thérapeutique adjuvant et un adjuvant vaccinal potentiel contre l'infection à T. spiralis.


Assuntos
Galactose/análogos & derivados , Doenças dos Roedores , Trichinella spiralis , Triquinelose , Animais , Camundongos , Mananas/farmacologia , Mananas/metabolismo , Larva/genética , Mucosa Intestinal , Citotoxicidade Celular Dependente de Anticorpos , Camundongos Endogâmicos BALB C
20.
Int J Mol Sci ; 25(3)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38339050

RESUMO

Human milk is abundant in carbohydrates and includes human milk oligosaccharides (HMOs) and N/O-glycans conjugated to proteins. HMO compositions and concentrations vary in individuals according to the maternal secretor status based on the fucosyltransferase 2 genotype; however, the profile of N/O-glycans remains uninvestigated because of the analytical complexity. Herein, we applied a label-free chromatography-mass spectrometry (LC-MS) technique to elucidate the variation in the composition and concentration of N/O-glycans in human milk. We used label-free LC-MS to relatively quantify 16 N-glycans and 12 O-glycans in 200 samples of Japanese human milk (1-2 months postpartum) and applied high performance anion exchange chromatography with pulsed amperometric detection to absolutely quantify the concentrations of 11 representative HMOs. Cluster analysis of the quantitative data revealed that O-glycans and several HMOs were classified according to the presence or absence of fucose linked to galactose while N-glycans were classified into a different group from O-glycans and HMOs. O-glycans and HMOs with fucose linked to galactose were more abundant in human milk from secretor mothers than from nonsecretor mothers. Thus, secretor status influenced the composition and concentration of HMOs and O-glycans but not those of N-glycans in human milk.


Assuntos
Fucose , Leite Humano , Feminino , Humanos , Leite Humano/química , Japão , Fucose/análise , Galactose , Polissacarídeos/análise , Espectrometria de Massas , Oligossacarídeos/química
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