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1.
Org Biomol Chem ; 22(19): 3986-3994, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38695061

RESUMO

Algae-based marine carbohydrate drugs are typically decorated with negative ion groups such as carboxylate and sulfate groups. However, the precise synthesis of highly sulfated alginates is challenging, thus impeding their structure-activity relationship studies. Herein we achieve a microwave-assisted synthesis of a range of highly sulfated mannuronate glycans with up to 17 sulfation sites by overcoming the incomplete sulfation due to the electrostatic repulsion of crowded polyanionic groups. Although the partially sulfated tetrasaccharide had the highest affinity for the receptor binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, the fully sulfated octasaccharide showed the most potent interference with the binding of the RBD to angiotensin-converting enzyme 2 (ACE2) and Vero E6 cells, indicating that the sulfated oligosaccharides might inhibit the RBD binding to ACE2 in a length-dependent manner.


Assuntos
Enzima de Conversão de Angiotensina 2 , Antivirais , Micro-Ondas , Polissacarídeos , SARS-CoV-2 , SARS-CoV-2/efeitos dos fármacos , Antivirais/farmacologia , Antivirais/síntese química , Antivirais/química , Chlorocebus aethiops , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/antagonistas & inibidores , Enzima de Conversão de Angiotensina 2/química , Células Vero , Polissacarídeos/química , Polissacarídeos/farmacologia , Polissacarídeos/síntese química , Humanos , Animais , Glicoproteína da Espícula de Coronavírus/antagonistas & inibidores , Glicoproteína da Espícula de Coronavírus/metabolismo , Glicoproteína da Espícula de Coronavírus/química , Ácidos Hexurônicos/química , Ácidos Hexurônicos/farmacologia , Ácidos Hexurônicos/síntese química , Sulfatos/química , Sulfatos/farmacologia , Sulfatos/síntese química , Tratamento Farmacológico da COVID-19 , Relação Estrutura-Atividade
2.
Carbohydr Polym ; 337: 122157, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38710573

RESUMO

Seaweed polysaccharides, particularly sulfated ones, exhibited potent antiviral activity against a wide variety of enveloped viruses, such as herpes simplex virus and respiratory viruses. Different mechanisms of action were suggested, which may range from preventing infection to intracellular antiviral activity, at different stages of the viral cycle. Herein, we generated two chemically engineered sulfated fucans (C303 and C304) from Cystoseira indica by an amalgamated extraction-sulfation procedure using chlorosulfonic acid-pyridine/N,N-dimethylformamide and sulfur trioxide-pyridine/N,N-dimethylformamide reagents, respectively. These compounds exhibited activity against HSV-1 and RSV with 50 % inhibitory concentration values in the range of 0.75-2.5 µg/mL and low cytotoxicity at concentrations up to 500 µg/mL. The antiviral activities of chemically sulfated fucans (C303 and C304) were higher than the water (C301) and CaCl2 extracted (C302) polysaccharides. Compound C303 had a (1,3)-linked fucan backbone and was branched. Sulfates were present at positions C-2, C-4, and C-2,4 of Fucp, and C-6 of Galp residues of this polymer. Compound C304 had a comparable structure but with more sulfates at C-4 of Fucp residue. Both C303 and C304 were potent antiviral candidates, acting in a dose-dependent manner on the adsorption and other intracellular stages of HSV-1 and RSV replication, in vitro.


Assuntos
Antivirais , Herpesvirus Humano 1 , Polissacarídeos , Antivirais/farmacologia , Antivirais/química , Chlorocebus aethiops , Herpesvirus Humano 1/efeitos dos fármacos , Polissacarídeos/farmacologia , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Animais , Células Vero , Humanos , Sulfatos/química , Sulfatos/farmacologia , Vírus Sinciciais Respiratórios/efeitos dos fármacos
3.
Environ Microbiol Rep ; 16(3): e13263, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38705733

RESUMO

Deep-sea methane seeps are amongst the most biologically productive environments on Earth and are often characterised by stable, low oxygen concentrations and microbial communities that couple the anaerobic oxidation of methane to sulfate reduction or iron reduction in the underlying sediment. At these sites, ferrous iron (Fe2+) can be produced by organoclastic iron reduction, methanotrophic-coupled iron reduction, or through the abiotic reduction by sulfide produced by the abundant sulfate-reducing bacteria at these sites. The prevalence of Fe2+in the anoxic sediments, as well as the availability of oxygen in the overlying water, suggests that seeps could also harbour communities of iron-oxidising microbes. However, it is unclear to what extent Fe2+ remains bioavailable and in solution given that the abiotic reaction between sulfide and ferrous iron is often assumed to scavenge all ferrous iron as insoluble iron sulfides and pyrite. Accordingly, we searched the sea floor at methane seeps along the Cascadia Margin for microaerobic, neutrophilic iron-oxidising bacteria, operating under the reasoning that if iron-oxidising bacteria could be isolated from these environments, it could indicate that porewater Fe2+ can persist is long enough for biology to outcompete pyritisation. We found that the presence of sulfate in our enrichment media muted any obvious microbially-driven iron oxidation with most iron being precipitated as iron sulfides. Transfer of enrichment cultures to sulfate-depleted media led to dynamic iron redox cycling relative to abiotic controls and sulfate-containing cultures, and demonstrated the capacity for biogenic iron (oxyhydr)oxides from a methane seep-derived community. 16S rRNA analyses revealed that removing sulfate drastically reduced the diversity of enrichment cultures and caused a general shift from a Gammaproteobacteria-domainated ecosystem to one dominated by Rhodobacteraceae (Alphaproteobacteria). Our data suggest that, in most cases, sulfur cycling may restrict the biological "ferrous wheel" in contemporary environments through a combination of the sulfur-adapted sediment-dwelling ecosystems and the abiotic reactions they influence.


Assuntos
Bactérias , Sedimentos Geológicos , Ferro , Metano , Oxirredução , Enxofre , Metano/metabolismo , Ferro/metabolismo , Enxofre/metabolismo , Sedimentos Geológicos/microbiologia , Sedimentos Geológicos/química , Bactérias/metabolismo , Bactérias/genética , Bactérias/classificação , Água do Mar/microbiologia , Água do Mar/química , Sulfetos/metabolismo , Sulfatos/metabolismo , RNA Ribossômico 16S/genética , Filogenia
4.
Int J Biol Macromol ; 267(Pt 1): 131506, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38604422

RESUMO

Marine green algae produce sulfated polysaccharides with diverse structures and a wide range of biological activities. This study aimed to enhance the biotechnological potential of sulfated heterorhamnan (Gb1) from Gayralia brasiliensis by chemically modifying it for improved or new biological functions. Using controlled Smith Degradation (GBS) and O-alkylation with 3-chloropropylamine, we synthesized partially water-soluble amine derivatives. GBS modification increase sulfate groups (29.3 to 37.5 %) and α-l-rhamnose units (69.9 to 81.2 mol%), reducing xylose and glucose, compared to Gb1. The backbone featured predominantly 3- and 2-linked α-l-rhamnosyl and 2,3- linked α-l-rhamnosyl units as branching points. Infrared and NMR analyses confirmed the substitution of hydroxyl groups with aminoalkyl groups. The modified compounds, GBS-AHCs and GBS-AHK, exhibited altered anticoagulant properties. GBS-AHCs showed reduced effectiveness in the APTT assay, while GBS-AHK maintained a similar anticoagulant activity level to Gb1 and GBS. Increased nitrogen content and N-alkylation in GBS-AHCs compared to GBS-AHK may explain their structural differences. The chemical modification proposed did not enhance its anticoagulant activity, possibly due to the introduction of amino groups and a positive charge to the polymer. This characteristic presents new opportunities for investigating the potential of these polysaccharides in various biological applications, such as antimicrobial and antitumoral activities.


Assuntos
Anticoagulantes , Clorófitas , Mananas , Alga Marinha , Sulfatos , Anticoagulantes/farmacologia , Anticoagulantes/química , Anticoagulantes/síntese química , Clorófitas/química , Alga Marinha/química , Sulfatos/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Polissacarídeos/síntese química , Humanos , Desoxiaçúcares/química , Desoxiaçúcares/farmacologia
5.
FEMS Microbiol Ecol ; 100(6)2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38658197

RESUMO

The dihydrogen (H2) sector is undergoing development and will require massive storage solutions. To minimize costs, the conversion of underground geological storage sites, such as deep aquifers, used for natural gas storage into future underground hydrogen storage sites is the favored scenario. However, these sites contain microorganisms capable of consuming H2, mainly sulfate reducers and methanogens. Methanogenesis is, therefore expected but its intensity must be evaluated. Here, in a deep aquifer used for underground geological storage, 17 sites were sampled, with low sulfate concentrations ranging from 21.9 to 197.8 µM and a slow renewal of formation water. H2-selected communities mainly were composed of the families Methanobacteriaceae and Methanothermobacteriaceae and the genera Desulfovibrio, Thermodesulfovibrio, and Desulforamulus. Experiments were done under different conditions, and sulfate reduction, as well as methanogenesis, were demonstrated in the presence of a H2 or H2/CO2 (80/20) gas phase, with or without calcite/site rock. These metabolisms led to an increase in pH up to 10.2 under certain conditions (without CO2). The results suggest competition for CO2 between lithoautotrophs and carbonate mineral precipitation, which could limit microbial H2 consumption.


Assuntos
Água Subterrânea , Hidrogênio , Metano , Gás Natural , Metano/metabolismo , Água Subterrânea/microbiologia , Hidrogênio/metabolismo , Sulfatos/metabolismo , Methanobacteriaceae/metabolismo , Methanobacteriaceae/genética , Methanobacteriaceae/crescimento & desenvolvimento , Dióxido de Carbono/metabolismo , Bactérias/metabolismo , Bactérias/genética , Bactérias/classificação , Concentração de Íons de Hidrogênio , Microbiologia da Água
6.
Bioorg Med Chem Lett ; 105: 129760, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38641151

RESUMO

The naturally occurring bile acid lithocholic acid (LCA) has been a crucial core structure for many non-sugar-containing sialyltranferase (ST) inhibitors documented in literature. With the aim of elucidating the impact of the terminal carboxyl acid substituent of LCA on its ST inhibition, in this present study, we report the (bio)isosteric replacement-based design and synthesis of sulfonate and sulfate analogues of LCA. Among these compounds, the sulfate analogue SPP-002 was found to selectively inhibit N-glycan sialylation by at least an order of magnitude, indicating a substantial improvement in both potency and selectivity when compared to the unmodified parent bile acid. Molecular docking analysis supported the stronger binding of the synthetic analogue in the enzyme active site. Treatment with SPP-002 also hampered the migration, adhesion, and invasion of MDA-MB-231 cells in vitro by suppressing the expression of signaling proteins involved in the cancer metastasis-associated integrin/FAK/paxillin pathway. In totality, these findings offer not only a novel structural scaffold but also valuable insights for the future development of more potent and selective ST inhibitors with potential therapeutic effects against tumor cancer metastasis.


Assuntos
Ácido Litocólico , Simulação de Acoplamento Molecular , Sialiltransferases , Ácido Litocólico/farmacologia , Ácido Litocólico/química , Ácido Litocólico/síntese química , Ácido Litocólico/análogos & derivados , Humanos , Sialiltransferases/antagonistas & inibidores , Sialiltransferases/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/síntese química , Relação Estrutura-Atividade , Sulfatos/química , Sulfatos/farmacologia , Sulfatos/síntese química , Metástase Neoplásica , Ácidos Sulfônicos/farmacologia , Ácidos Sulfônicos/química , Ácidos Sulfônicos/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Estrutura Molecular , Adesão Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Paxilina/metabolismo , Paxilina/antagonistas & inibidores , Quinase 1 de Adesão Focal/antagonistas & inibidores , Quinase 1 de Adesão Focal/metabolismo , Descoberta de Drogas
7.
Chem Commun (Camb) ; 60(33): 4495-4498, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38567462

RESUMO

We have demonstrated that cisplatin (CP), an anticancer drug, showed a preference for binding the sulfated-L-iduronic acid (S-L-IdoA) unit over the sulfated-D-glucuronic acid unit of heparan sulfate. The multivalency of S-L-IdoA, such as in the proteoglycan mimic, resulted in distinct modes of cell-surface engineering in normal and cancer cells, with these disparities having a significant impact on CP-mediated toxicity.


Assuntos
Cisplatino , Proteoglicanas , Heparitina Sulfato/química , Ácido Glucurônico/metabolismo , Ácido Idurônico , Sulfatos
8.
J Environ Manage ; 355: 120488, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38457892

RESUMO

Sulfidation enhances the reactivity of zero-valent iron (ZVI) for Cr(VI) removal from groundwater. Current sulfidation methods mainly focus on chemical and mechanical sulfidation, and there has been little research on biosulfidation using sulfate-reducing bacteria (SRB) and its performance in Cr(VI) removal. Herein, the ability of the SRB-biosulfidated ZVI (SRB-ZVI) system was evaluated and compared with that of the Na2S-sulfidated ZVI system. The SRB-ZVI system forms a thicker and more porous FeSx layer than the Na2S-sulfidated ZVI system, resulting in more sufficient sulfidation of ZVI and a 2.5-times higher Cr(VI) removal rate than that of the Na2S-sulfidated ZVI system. The biosulfidated-ZVI granules and FeSx suspension are the major components of the SRB-ZVI system. The SRB-ZVI system exhibits a long-lasting (11 cycles) Cr(VI) removal performance owing to the regeneration of FeSx. However, the Na2S-sulfidated ZVI system can perform only two Cr(VI) removal cycles. SRB attached to biosulfidated-ZVI can survive in the presence of Cr(VI) because of the protection of the biogenic porous structure, whereas SRB in the suspension is inhibited. After Cr(VI) removal, SRB repopulates in the suspension from biosulfidated-ZVI and produce FeSx, thus providing conditions for subsequent Cr(VI) removal cycles. Overall, the synergistic effect of SRB and ZVI provides a more powerful and environmentally friendly sulfidation method, which has more advantageous for Cr(VI) removal than those of chemical sulfidation. This study provides a visionary in situ remediation strategy for groundwater contamination using ZVI-based technologies.


Assuntos
Água Subterrânea , Poluentes Químicos da Água , Ferro/química , Cromo/química , Bactérias , Sulfatos , Poluentes Químicos da Água/química
9.
Environ Sci Technol ; 58(12): 5578-5588, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38477971

RESUMO

The removal of antibiotic-resistant bacteria (ARB) and antibiotic-resistance genes (ARGs) using sulfate anion radical (SO4•-)-based advanced oxidation processes has gained considerable attention recently. However, immense uncertainties persist in technology transfer. Particularly, the impact of dichlorine radical (Cl2•-) generation during SO4•--mediated disinfection on ARB/ARGs removal remains unclear, despite the Cl2•- concentration reaching levels notably higher than those of SO4•- in certain SO4•--based procedures applied to secondary effluents, hospital wastewaters, and marine waters. The experimental results of this study reveal a detrimental effect on the disinfection efficiency of tetracycline-resistant Escherichia coli (Tc-ARB) during SO4•--mediated treatment owing to Cl2•- generation. Through a comparative investigation of the distinct inactivation mechanisms of Tc-ARB in the Cl2•-- and SO4•--mediated disinfection processes, encompassing various perspectives, we confirm that Cl2•- is less effective in inducing cellular structural damage, perturbing cellular metabolic activity, disrupting antioxidant enzyme system, damaging genetic material, and inducing the viable but nonculturable state. Consequently, this diminishes the disinfection efficiency of SO4•--mediated treatment owing to Cl2•- generation. Importantly, the results indicate that Cl2•- generation increases the potential risk associated with the dark reactivation of Tc-ARB and the vertical gene transfer process of tetracycline-resistant genes following SO4•--mediated disinfection. This study underscores the undesired role of Cl2•- for ARB/ARGs removal during the SO4•--mediated disinfection process.


Assuntos
Bactérias , Sulfatos , Purificação da Água , Bactérias/genética , Genes Bacterianos , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Desinfecção/métodos , Antibacterianos/farmacologia , Tetraciclina , Purificação da Água/métodos
10.
BMC Genom Data ; 25(1): 35, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38532320

RESUMO

Pungency of garlic (Allium sativum L.) is generated from breakdown of the alk(en)yl cysteine sulphoxide (CSO), alliin and its subsequent breakdown to allicin under the activity of alliinase (All). Based on recent evidence, two other important genes including Sulfite reductase (SiR) and Superoxide dismutase (SOD) are thought to be related to sulfur metabolism. These three gene functions are in sulfate assimilation pathway. However, whether it is involved in stress response in crops is largely unknown. In this research, the order and priority of simultaneous expression of three genes including All, SiR and SOD were measured on some garlic ecotypes of Iran, collected from Zanjan, Hamedan and Gilan, provinces under sulfur concentrations (0, 6, 12, 24 and 60 g/ per experimental unit: pot) using real-time quantitative PCR (RT-qPCR) analysis. For understanding the network interactions between studied genes and other related genes, in silico gene network analysis was constructed to investigate various mechanisms underlying stimulation of A. sativum L. to cope with imposed sulfur. Complicated network including TF-TF, miRNA-TF, and miRNA-TF-gene, was split into sub-networks to have a deeper insight. Analysis of q-RT-PCR data revealed the highest expression in All and SiR genes respectively. To distinguish and select significant pathways in sulfur metabolism, RESNET Plant database of Pathway Studio software v.10 (Elsevier), and other relative data such as chemical reactions, TFs, miRNAs, enzymes, and small molecules were extracted. Complex sub-network exhibited plenty of routes between stress response and sulfate assimilation pathway. Even though Alliinase did not display any connectivity with other stress response genes, it showed binding relation with lectin functional class, as a result of which connected to leucine zipper, exocellulase, peroxidase and ARF functional class indirectly. Integration network of these genes revealed their involvement in various biological processes such as, RNA splicing, stress response, gene silencing by miRNAs, and epigenetic. The findings of this research can be used to extend further research on the garlic metabolic engineering, garlic stress related genes, and also reducing or enhancing the activity of the responsible genes for garlic pungency for health benefits and industry demands.


Assuntos
Alho , MicroRNAs , Alho/química , Alho/genética , Alho/metabolismo , Redes Reguladoras de Genes , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Sulfatos/metabolismo
11.
Sci Total Environ ; 925: 171763, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38494030

RESUMO

Microbial biofilms are behind microbiologically influenced corrosion (MIC). Sessile cells in biofilms are many times more concentrated volumetrically than planktonic cells in the bulk fluids, thus providing locally high concentrations of chemicals. More importantly, "electroactive" sessile cells in biofilms are capable of utilizing extracellularly supplied electrons (e.g., from elemental Fe) for intracellular reduction of an oxidant such as sulfate in energy metabolism. MIC directly caused by anaerobic biofilms is classified into two main types based on their mechanisms: extracellular electron transfer MIC (EET-MIC) and metabolite MIC (M-MIC). Sulfate-reducing bacteria (SRB) are notorious for their corrosivity. They can cause EET-MIC in carbon steel, but they can also secrete biogenic H2S to corrode other metals such as Cu directly via M-MIC. This study investigated the use of conductive magnetic nanowires as electron mediators to accelerate and thus identify EET-MIC of C1020 by Desulfovibrio vulgaris. The presence of 40 ppm (w/w) nanowires in ATCC 1249 culture medium at 37 °C resulted in 45 % higher weight loss and 57 % deeper corrosion pits after 7-day incubation. Electrochemical tests using linear polarization resistance and potentiodynamic polarization supported the weight loss data trend. These findings suggest that conductive magnetic nanowires can be employed to identify EET-MIC. The use of insoluble 2 µm long nanowires proved that the extracellular section of the electron transfer process is a bottleneck in SRB MIC of carbon steel.


Assuntos
Desulfovibrio vulgaris , Desulfovibrio , Nanofios , Humanos , Aço , Elétrons , Carbono/metabolismo , Biofilmes , Desulfovibrio/metabolismo , Corrosão , Sulfatos/metabolismo , Redução de Peso
12.
Food Funct ; 15(6): 3158-3173, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38440931

RESUMO

The gut health-promoting properties of saponin-rich Polygonatum cyrtonema Hua (FP) fermented with Lactobacillus plantarum P9 were explored in a dextran sulfate sodium (DSS)-induced colitis mouse model. FP supplementation effectively inhibited DSS-induced physiological alteration and impaired immune responses by reducing the disease activity index (DAI) score and restoring the T helper (Th) 1/Th2 and regulatory T (Treg)/Th17 ratios. In addition, FP supplementation protected the gut barrier function against DSS-induced damage via upregulation of zonula occludens (ZO)-1 and occludin and downregulation of pro-inflammatory cytokines, including interleukin (IL)-1ß, tumor necrosis factor-α (TNF-α), IL-18, and the granulocyte-macrophage colony-stimulating factor (GM-CSF). This study further elucidated the potential mechanisms underlying the FP-mediated suppression of the plasticity of type 3 innate lymphoid cells (ILC3) and subsequent macrophage polarization. Therefore, the FP supplementation effectively restored mucosal immune homeostasis and enhanced gut integrity. In addition, it suppressed the growth of Escherichia-Shigella and Enterococcus and promoted the enrichment of probiotics and short-chain fatty acid-producing microbes, such as Romboutsia, Faecalibaculum, and Blautia. In conclusion, P. cyrtonema Hua fermented with L. plantarum P9 might be a promising dietary intervention to improve gut health by sustaining overall gut homeostasis and related gut integrity.


Assuntos
Colite , Polygonatum , Animais , Camundongos , Dextranos , Imunidade Inata , Linfócitos , Colite/induzido quimicamente , Colite/tratamento farmacológico , Homeostase , Interleucina-1beta , Sulfatos , Sódio
13.
Clin Chim Acta ; 557: 117860, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38508572

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common infertility disorder which affects reproductive-aged women. However, metabolic change profiles of follicular fluid (FF) in lean and obese women diagnosed with and without PCOS remains unclear. METHODS: 95 infertile women were divided into four subgroups: LC (lean control), OC (overweight control), LP (lean PCOS), and OP (overweight PCOS). The FF samples were collected during oocyte retrieval and assayed by ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS) metabolomics. RESULTS: A total of 236 metabolites were identified by metabolic analysis. The pathway enrichment analysis revealed that the glycerophospholipid metabolism (impact = 0.11182), ether lipid metabolism (impact = 0.14458), and primary bile acid biosynthesis (impact = 0.03267) were related to metabolic pathway between PCOS and control. Correlation analyses showed that epitestosterone sulfate was found positively correlated with fertilization rate in PCOS, while falcarindione, lucidone C. and notoginsenoside I was found to be negatively correlated. The combined four biomarkers including lucidone C, epitestosterone sulfate, falcarindione, and notoginsenoside I was better in predicting live birth rate, with AUC of 0.779. CONCLUSION: The follicular fluid of women with PCOS showed unique metabolic characteristics. Our study provides better identification of PCOS follicular fluid metabolic dynamics, which may serve as potential biomarkers of live birth.


Assuntos
Ciclopentanos , Infertilidade Feminina , Síndrome do Ovário Policístico , Gravidez , Feminino , Humanos , Adulto , Líquido Folicular/metabolismo , Nascido Vivo , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/metabolismo , Infertilidade Feminina/diagnóstico , Espectrometria de Massa com Cromatografia Líquida , Sobrepeso , Epitestosterona/análise , Epitestosterona/metabolismo , Cromatografia Líquida , Espectrometria de Massas em Tandem , Fertilização in vitro , Biomarcadores/análise , Sulfatos/análise , Sulfatos/metabolismo
14.
Sci Total Environ ; 926: 171918, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38522553

RESUMO

The disposal of spent nuclear fuel in deep subsurface repositories using multi-barrier systems is considered to be the most promising method for preventing radionuclide leakage. However, the stability of the barriers can be affected by the activities of diverse microbes in subsurface environments. Therefore, this study investigated groundwater geochemistry and microbial populations, activities, and community structures at three potential spent nuclear fuel repository construction sites. The microbial analysis involved a multi-approach including both culture-dependent, culture-independent, and sequence-based methods for a comprehensive understanding of groundwater biogeochemistry. The results from all three sites showed that geochemical properties were closely related to microbial population and activities. Total number of cells estimates were strongly correlated to high dissolved organic carbon; while the ratio of adenosine-triphosphate:total number of cells indicated substantial activities of sulfate reducing bacteria. The 16S rRNA gene sequencing revealed that the microbial communities differed across the three sites, with each featuring microbes performing distinctive functions. In addition, our multi-approach provided some intriguing findings: a site with a low relative abundance of sulfate reducing bacteria based on the 16S rRNA gene sequencing showed high populations during most probable number incubation, implying that despite their low abundance, sulfate reducing bacteria still played an important role in sulfate reduction within the groundwater. Moreover, a redundancy analysis indicated a significant correlation between uranium concentrations and microbial community compositions, which suggests a potential impact of uranium on microbial community. These findings together highlight the importance of multi-methodological assessments in better characterizing groundwater biogeochemical properties for the selection of potential spent nuclear fuel disposal sites.


Assuntos
Desulfovibrio , Água Subterrânea , Urânio , Bactérias , Urânio/análise , RNA Ribossômico 16S/genética , Estudos Prospectivos , Água Subterrânea/química , Sulfatos/análise
15.
ACS Appl Mater Interfaces ; 16(12): 14573-14582, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38484043

RESUMO

Pseudomonas aeruginosa biofilms comprise three main polysaccharides: alginate, psl, and pel, which all imbue tolerance against exogenous antimicrobials. Nanoparticles (NPs) are an exciting new strategy to overcome the biofilm matrix for therapeutic delivery applications; however, zero existing FDA approvals for biofilm-specific NP formulations can be attributed to the complex interplay of physiochemical forces at the biofilm-NP interface. Here, we leverage a set of inducible, polysaccharide-specific, expressing isogenic P. aeruginosa mutants coupled with an assembled layer-by-layer NP (LbL NP) panel to characterize biofilm-NP interactions. When investigating these interactions using confocal microscopy, alginate-layered NPs associated more than dextran-sulfate-layered NPs with biofilms that had increased alginate production, including biofilms produced by mucoid P. aeruginosa isolates from people with cystic fibrosis. These differences were further confirmed in LbL NPs layered with polysaccharide- or hydrocarbon-based polymers with pendent carboxylate or sulfate functional groups. These data suggest carboxylated NP surfaces have enhanced interactions specifically with mucoid biofilms as compared to sulfated surfaces and lay the foundation for their inclusion as a design element for increasing biofilm-NP interactions and efficacious drug delivery.


Assuntos
Nanopartículas , Pseudomonas aeruginosa , Humanos , Polissacarídeos Bacterianos , Biofilmes , Ácidos Carboxílicos , Alginatos , Sulfatos
16.
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
17.
Carbohydr Polym ; 332: 121916, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38431417

RESUMO

Resveratrol (RES) is a natural polyphenol with excellent biological activity. But the poor stability and bioavailability of RES severely limit its application. Thus, the resveratrol-loaded sulfated Hericium erinaceus ß-glucan-chitosan nanoparticles (DS-CS-RES NPs) were prepared using electrostatic self-assembly to solve these problems in this study. The structure of DS-CS-RES NPs was spherical or sub spherical shape with small average particle size (191.07 nm), which was characterized by FT-IR, FS, XRD and TEM. DS-CS-RES NPs exhibited good stability and RES had a sustainable release from the nanoparticles in gastrointestinal digestion. Meanwhile, DS-CS-RES NPs could improve the inflammatory injury of LPS stimulated RAW264.7 macrophages by inhibiting the production of NO, IL-1ß, IL-6 and TNF-α. Furthermore, DS-CS-RES NPs had strong anti-inflammatory activity by regulating protein levels of NF-κB p65, STAT1 and TLR4 through NF-κB and JAK-STAT1 signaling pathway in vitro, and sulfated H. erinaceus ß-glucan-chitosan nanoparticle (DS-CS NPs) and RES had synergistic anti-inflammatory effect. Overall, DS-CS NPs can serve as a potential green and safe functional carrier for encapsulating resveratrol, which can improve its anti-inflammatory activity. This work may be conducive to the development of functional carrier for encapsulating RES and applications of hydrophobic active molecules in functional foods or medicines.


Assuntos
Quitosana , Hericium , Nanopartículas , Resveratrol/farmacologia , Quitosana/química , Portadores de Fármacos/química , NF-kappa B , Sulfatos , Espectroscopia de Infravermelho com Transformada de Fourier , Nanopartículas/química , Anti-Inflamatórios/farmacologia , Tamanho da Partícula
18.
Environ Pollut ; 347: 123786, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38484962

RESUMO

Water management in paddy soils can effectively reduce the soil-to-rice grain transfer of either As or Cd, but not of both elements simultaneously due to the higher mobility of As under reducing and Cd under oxidizing soil conditions. Limestone amendment, the common form of liming, is well known for decreasing Cd accumulation in rice grown on acidic soils. Sulfate amendment was suggested to effectively decrease As accumulation in rice, especially under intermittent soil flooding. To study the unknown effects of combined sulfate and limestone amendment under intermittent flooding for simultaneously decreasing As and Cd in rice, we performed a pot experiment using an acidic sandy loam paddy soil. We also included a clay loam paddy soil to study the role of soil texture in low-As rice production under intermittent flooding. We found that liming not only decreased rice Cd concentrations but also greatly decreased dimethylarsenate (DMA) accumulation in rice. We hypothesize that this is due to suppressed sulfate reduction, As methylation, and As thiolation by liming in the sulfate-amended soil and a higher share of deprotonated DMA at higher pH which is taken up less readily than protonated DMA. Decreased gene abundance of potential soil sulfate-reducers by liming further supported our hypothesis. Combined sulfate and limestone amendment to the acidic sandy loam soil produced rice with 43% lower inorganic As, 72% lower DMA, and 68% lower Cd compared to the control soil without amendment. A tradeoff between soil aeration and water availability was observed for the clay loam soil, suggesting difficulties to decrease As in rice while avoiding plant water stress under intermittent flooding in fine-textured soils. Our results suggest that combining sulfate amendment, liming, and intermittent flooding can help to secure rice safety when the presence of both As and Cd in coarse-textured soils is of concern.


Assuntos
Arsênio , Compostos de Cálcio , Oryza , Óxidos , Poluentes do Solo , Cádmio/análise , Arsênio/análise , Carbonato de Cálcio , Solo , Sulfatos , Argila , Óxidos de Enxofre , Areia , Poluentes do Solo/análise
19.
J Gastroenterol ; 59(5): 402-410, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38492010

RESUMO

BACKGROUND: We compared the efficacy, tolerability, and safety of oral sulfate tablets (OST, which contains simethicone) and 2 L-polyethylene glycol/ascorbate (2 L-PEG/Asc) with a split-dosing regimen in older individuals aged ≥ 70 years who underwent scheduled colonoscopy. METHODS: This prospective, randomized, investigator-blinded, multicenter study was conducted between June 2022 and October 2023. Participants aged ≥ 70 years were randomized at a ratio of 1:1 to the OST or 2 L-PEG/Asc groups. RESULTS: In total, 254 patients were evaluated using a modified full analysis set. Successful overall bowel preparation was excellent and similar between the OST and 2 L-PEG/Asc groups for the Boston Bowel Preparation Scale (BBPS) (96.5% vs. 96.6%) and Harefield Cleansing Scale (HCS) (96.5% vs. 97.4%). The overall high-quality preparation rate was higher in the OST group than in the 2 L-PEG/Asc group (BBPS: 55.7% vs. 28.4%, P < 0.001; HCS: 66.1% vs. 38.8%, P < 0.001). The overall adenoma detection rate (54.8% vs. 35.3, P = 0.003) was superior in the OST group compared to the 2 L-PEG/Asc group. Tolerability scores, including overall satisfaction, were generally higher in the OST group than in the 2 L-PEG/Asc group. The incidence of major solicited adverse events was comparable between the two groups (55.7% vs. 68.1, P = 0.051), and there were no clinically significant changes in the serum laboratory profiles on the day of or 7 days after colonoscopy. CONCLUSIONS: OST is an effective and safe low-volume agent for colonoscopy, with better tolerance than 2 L-PEG/Asc, in older individuals aged ≥ 70 years.


Assuntos
Catárticos , Polietilenoglicóis , Humanos , Idoso , Polietilenoglicóis/efeitos adversos , Catárticos/efeitos adversos , Sulfatos , Estudos Prospectivos , Laxantes , Colonoscopia , Ácido Ascórbico/efeitos adversos
20.
Int J Biol Macromol ; 263(Pt 2): 130364, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38401579

RESUMO

It is believed that polysaccharides will become a focal point for future production of food, pharmaceuticals, and materials due to their ubiquitous and renewable nature, as well as their exceptional properties that have been extensively validated in the fields of nutrition, healthcare, and materials. Sulfated polysaccharides derived from seaweed sources have attracted considerable attention owing to their distinctive structures and properties. The genus Codium, represented by the species C. fragile, holds significance as a vital economic green seaweed and serves as a traditional Chinese medicinal herb. To date, the cell walls of the genus Codium have been found to contain at least four types of sulfated polysaccharides, specifically pyruvylated ß-d-galactan sulfates, sulfated arabinogalactans, sulfated ß-l-arabinans, and sulfated ß-d-mannans. These sulfated polysaccharides exhibit diverse biofunctions, including anticoagulant, immune-enhancing, anticancer, antioxidant activities, and drug-carrying capacity. This review explores the structural and biofunctional diversity of sulfated polysaccharides derived from the genus Codium. Additionally, in addressing the impending challenges within the industrialization of these polysaccharides, encompassing concerns regarding scale-up production and quality control, we outline potential strategies to address these challenges from the perspectives of raw materials, extraction processes, purification technologies, and methods for quality control.


Assuntos
Clorófitas , Alga Marinha , Sulfatos/química , Clorófitas/química , Polissacarídeos/farmacologia , Polissacarídeos/química , Alga Marinha/química , Mananas , Anticoagulantes/química
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