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1.
Int J Biol Macromol ; 267(Pt 2): 131551, 2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38621566

RESUMO

Gentiana dahurica Fisch. (G. dahurica) is one of the legitimate sources of Qinjiao in Traditional Chinese Medicine (TCM) and grows on high-altitude plateaus. Plants develop unique biochemical accumulations to resist plateau conditions, especially the strong UV irradiation. Thus, this study aimed to investigate the polysaccharide of G. dahurica (GDP), its structure and its activity against UVB irradiation. Four GDPs were isolated and two of them were subjected to structural elucidation. The results suggested that GDP-1 has 53.5 % Ara and 30.8 % GalA as its main monosaccharides, with a molecular weight (Mw) of 23 kDa; the GDP-2 has 33.9 % Ara and 48.5 % GalA, with a Mw of 82 kDa. Methylation and NMR spectroscopy analysis revealed that GDP-1 contains →5)-α-Araf-(1 â†’ 5)-α-Araf-(1 â†’ 3,5)-α-Araf-(1 â†’ 3,4)-α-GalpA-(6-OMe)-(1→ as the main chain, the branches of GalA (with esterification), and the terminal Ara; the GDP-2 contains →4)-α-GalpA-(1 â†’ 4)-α-GalpA-(6-OMe)-(1 â†’ 5)-α-Araf-(1 â†’ 3,5)-α-Araf-(1→ as the main chain, the branches of →5)-α-Araf-(1-5)-α-Araf, and the terminal GalA. Both GDP-1 and GDP-2 exhibited concentration-dependent antioxidant activity against DPPH, ABTS and hydroxyl radicals. Moreover, GDPs significantly attenuated the decreases in viability and proliferation of HaCaT cells after UVB irradiation. They can scavenge reactive oxygen species (ROS) and improve the activities of endogenous antioxidant enzymes, including superoxide dismutase (SOD) and glutathione peroxidase (GSH). The potential mechanism explored by flow cytometry assays of cell apoptosis and cell cycle distribution suggested that GDPs exert protective effects against UVB irradiation by reducing ROS and attenuating S phase cell arrest. In brief, the GDP-1 and GDP-2 are α-1,3- and α-1,4- arabinogalacturonan, respectively. The high content of Ara could be attributed to biochemical accumulation in resisting to the plateau environment and to prevent UVB irradiation-related damage in cells. These findings provide insight into authentic medicinal herbs and the development of GDPs in the modern pharmaceutical and cosmetics industry.

2.
Carbohydr Polym ; 332: 121889, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38431406

RESUMO

Metabolic alterations within mitochondria, encompassing processes such as autophagy and energy metabolism, play a pivotal role in facilitating the swift proliferation, invasion, and metastasis of cancer cells. Despite this, there is a scarcity of currently available medications with proven anticancer efficacy through the modulation of mitochondrial dysfunction in a clinical setting. Here, we introduce the structural characteristics of RN0D, a galactoglucan isolated and purified from Panax notoginseng flowers, mainly composed of ß-1,4-galactan and ß-1,3/1,6-glucan. RN0D demonstrates the capacity to induce mitochondrial impairment in cancer cells, leading to the accumulation of reactive oxygen species, initiation of mitophagy, and reduction in both mitochondrial number and size. This sequence of events ultimately results in the inhibition of mitochondrial and glycolytic bioenergetics, culminating in the demise of cancer cells due to adenosine triphosphate (ATP) deprivation. Notably, the observed bioactivity is attributed to RN0D's direct targeting of Galectin-3, as affirmed by surface plasmon resonance studies. Furthermore, RN0D is identified as an activator of the PTEN-induced kinase 1 (PINK1)/Parkin pathway, ultimately instigating cytotoxic mitophagy in tumor cells. This comprehensive study substantiates the rationale for advancing RN0D as a potentially efficacious anticancer therapeutic.


Assuntos
Neoplasias , Panax notoginseng , Polissacarídeos Bacterianos , Humanos , Mitofagia , Galactanos , Glucanos , Morte Celular , Ubiquitina-Proteína Ligases/metabolismo , Proteínas Quinases/metabolismo
3.
Chin J Nat Med ; 22(2): 146-160, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38342567

RESUMO

In this study, 37 derivatives of phorbol esters were synthesized and their anti-HIV-1 activities evaluated, building upon our previous synthesis of 51 phorbol derivatives. 12-Para-electron-acceptor-trans-cinnamoyl-13-decanoyl phorbol derivatives stood out, demonstrating remarkable anti-HIV-1 activities and inhibitory effects on syncytia formation. These derivatives exhibited a higher safety index compared with the positive control drug. Among them, 12-(trans-4-fluorocinnamoyl)-13-decanoyl phorbol, designated as compound 3c, exhibited the most potent anti-HIV-1 activity (EC50 2.9 nmol·L-1, CC50/EC50 11 117.24) and significantly inhibited the formation of syncytium (EC50 7.0 nmol·L-1, CC50/EC50 4891.43). Moreover, compound 3c is hypothesized to act both as an HIV-1 entry inhibitor and as an HIV-1 reverse transcriptase inhibitor. Isothermal titration calorimetry and molecular docking studies indicated that compound 3c may also function as a natural activator of protein kinase C (PKC). Therefore, compound 3c emerges as a potential candidate for developing new anti-HIV drugs.


Assuntos
Fármacos Anti-HIV , Forbóis , Simulação de Acoplamento Molecular , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/química , Forbóis/química , Forbóis/farmacologia , Ésteres de Forbol/farmacologia , Transcriptase Reversa do HIV/química , Transcriptase Reversa do HIV/metabolismo , Relação Estrutura-Atividade
4.
Artigo em Inglês | MEDLINE | ID: mdl-38294754

RESUMO

Objective: Klotho protein level are reported to play important roles in the osteoporosis. To investigate the correlation between serum Klotho protein level and related gene (Klotho G395-A gene) polymorphism and osteoporotic fracture in elderly patients with osteoporosis. Methods: A total of 62 elderly patients with osteoporosis admitted to the Department of Orthopedics of our hospital from January 2021 to June 2022 were included in the study group. Another 62 elderly patients without osteoporosis who underwent a physical examination at the same time were selected as the control group. Patients in the study group were divided into group A (n = 23, osteoporotic fracture) and group B (n = 39, osteoporotic fracture) according to the occurrence of osteoporotic fracture. Serum Klotho protein level was detected in all patients, and its related gene (Klotho G395-A gene) polymorphism was analyzed. After fasting in the morning (fasting for more than 8 hours), 3-5 ml venous blood was collected and immediately placed in a centrifuge tube. Serum was separated and serum Klotho protein level was measured by enzyme-linked immunosorbent assay kit. Polymorphism typing was performed by Taqman allele-specific hybridization analysis. At the same time, general information (gender, age, body mass index, systolic blood pressure, diastolic blood pressure, glycated glucose protein, low-density lipoprotein cholesterol, bone mineral density) was collected. The differences in general data, serum Klotho protein level and Klotho G395-A gene polymorphism between the study group and the control group were analyzed. Spearman analysis was used to analyze the correlation between general data, serum Klotho protein level and Klotho G395-A gene and osteoporotic fracture. Logistic analysis was used to analyze the independent risk factors of osteoporotic fracture. Results: There was no significant difference of the sex, systolic blood pressure (SBP), diastolic blood pressure (DBP), Klotho G395-A genotype GG and alleles A and G between the study group and the control group. There was significant difference of body mass index (BMI), glycated glucose protein, low-density lipoprotein cholesterol (LDL-C), bone mineral density, serum Klotho protein level and Klotho G395-A genotype AA and AG were between the study group and the control group. Gender, age, glycated glucose protein and Klotho G395-A genotype AA were positively correlated with osteoporotic fracture (P < .05), while bone mineral density was negatively correlated with osteoporotic fracture (P < .05). There was no correlationship between the serum Klotho protein level and the incidence of osteoporotic fracture (P > .05). Logistic analysis showed that age, bone mineral density and Klotho G395-A genotype AA were independent risk factors for osteoporotic fracture. Conclusion: The level of serum Klotho protein and related gene polymorphisms are both related to osteoporotic fracture in elderly patients with osteoporosis. It is significant to reduce the incidence of osteoporotic fractures. In future, more experiments are needed to explore the underlying mechanism.

5.
Int J Biol Macromol ; 261(Pt 2): 129709, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38286380

RESUMO

The dried root of Pueraria mirifica (P. mirifica) is an edible foodstuff widely used in Asian countries. P. mirifica is known for its high starch content. The isolation of polysaccharides from high-starch plant parts is challenging due to the interference of starch. Therefore, this study aimed to develop a technique for isolating and investigating the structure and activity of non-glucan polysaccharides from P. mirifica (PMP). An effective starch removal process was developed using α-amylase hydrolysis and thorough membrane dialysis. Four non-glucan polysaccharides were isolated, and PMP-2 was subjected to structural elucidation. The results indicated that PMP-2 has a molecular weight of 124.4 kDa and that arabinose and galactose are the main components, accounting for 27.8 % and 58.5 %, respectively. Methylation and NMR analysis suggested that PMP-2 is an Arabinogalactan composed of 1,6-linked Galp and 1,4-linked Galp as the main chain, with arabinan and rhamnose as side chains. Furthermore, PMP-C and PMP-2 exhibited concentration-dependent antioxidant activities against DPPH, ABTS, and hydroxyl radicals and certain immunomodulatory activities related to the release of NO, TNF-α and IL-6. These findings suggest that PMP-2 has potential therapeutically active ingredient in functional foods. The developed method successfully removed starch and isolated non-glucan polysaccharides from the high-starch content plant P. mirifica and can be applied to other high-starch plants.


Assuntos
Pueraria , Pueraria/química , Amido , Diálise Renal , Extratos Vegetais , Antioxidantes , Polissacarídeos/farmacologia
6.
Artigo em Inglês | MEDLINE | ID: mdl-38199058

RESUMO

Heparin-induced thrombocytopenia (HIT) is an immune complication of heparin therapy. Antibodies binding to complexes of platelet factor 4 (PF4) and heparin is the trigger of HIT. A method using size exclusion chromatography with multi-angle laser light scattering detector (SEC-MALS) was developed in this work. The soluble ultra-large complex (ULC) was separated from the small complex (SC) and their molecular weights (MWs) were firstly measured. The complexes of PF4 and three heparins with different MW, including unfractionated heparin (UFH), dalteparin (Daltep) and enoxaparin (Eno) were characterized using this method. The contents and the sizes of ULC increased gradually when heparins were added to PF4 to certain amounts. While, they reduced after more heparins were added. It is the first time to measure the MWs of the biggest ULC of PF4-heparins as millions of Dalton. at the proper ratios of PF4 to heparin (PHR). Meanwhile, those mixtures at those certain PHRs induced the higher expression of CD83 and CD14 markers on dendritic cells (DCs) suggesting that they had stronger immunogenicity and is critical for HIT.


Assuntos
Heparina , Trombocitopenia , Humanos , Heparina/farmacologia , Fator Plaquetário 4/química , Fator Plaquetário 4/metabolismo , Anticoagulantes/química , Trombocitopenia/induzido quimicamente , Fatores Imunológicos , Cromatografia em Gel
7.
Int J Biol Macromol ; 254(Pt 1): 127679, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37890741

RESUMO

The swollen culm (also known as Jiaobai) of Zizania latifolia is formed by the smut Ustilago esculenta invades the Z. latifolia. The new tissue formed due to the symbiotic relationship has entices the attention of researchers to study its polysaccharide structure along with biological evaluation. Five fractions of polysaccharides were obtained owing to hot water extraction, alcoholic precipitation, and chromatographic purification. Bioactivity assays showed that ZLPs have good antioxidant, hypoglycemic activities and protective activity against oxidative damage. The ZLP-1 and ZLP-2 were determined to be neutral polysaccharides with high purity, exhibiting propitious bioactivity, consequently they were subjected to indispensable structural characterization. These results showed that ZLP-1 has molecular weight (Mw) of 103 kDa and glucose (Glc) (76.68 %) as the primary monosaccharide; the ZLP-2 has Mw of 122 kDa and galactose (Gal) (41.04 %) and arabinose (Ara) (27.12 %). Structural elucidation by methylation and nuclear magnetic resonance (NMR) analysis suggested ZLP-1 is a glucan, with →3)-ß-Glcp-(1→3)-ß-Glcp-(1→4)-ß-Glcp-(1→4)-ß-Glcp-(1→3,6)-ß-Galp-(1→3)-ß-Glcp-(1→ as the mainchain and the terminal Araf and Glcp; the ZLP-2 is a Galactoxylan, with →3,4)-ß-xylp-(1→3)-ß-Galp-(1→3,6)-ß-Galp-(1→3,6)-ß-Galp-(1→ as the mainchain and the terminal Araf and Glcp. The structural arrangements provide a chemical basis for understanding the nutritional and pharmacological activities of polysaccharides from Zizania latifolia.


Assuntos
Glucanos , Polissacarídeos , Polissacarídeos/química , Monossacarídeos/análise , Antioxidantes/química , Galactose
8.
Sci Total Environ ; 913: 169282, 2024 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-38141989

RESUMO

Coastal wetlands play a vital role in mitigating climate change, yet the characteristics of buried organic carbon (OC) and carbon cycling are limited due to difficulties in assessing the composition of OC from different sources (allochthonous vs. autochthonous). In this study, we analyzed the total organic carbon (TOC) to total nitrogen (TN) ratio (C/N), stable carbon isotope (δ13C) composition, and n-alkane content to distinguish different sources of OC in the surface sediments of the coastal wetlands on the western coast of the Bohai Sea. The coupling of the C/N ratio with δ13C and n-alkane biomarkers has been proved to be an effective tool for revealing OC sources. The three end-member Bayesian mixing model based on coupling C/N ratios with δ13C showed that the sedimentary OC was dominated by the contribution of terrestrial particulate organic matter (POM), followed by freshwater algae and marine phytoplankton, with relative contributions of 47 ± 21 %, 41 ± 18 % and 12 ± 17 %, respectively. The relative contributions of terrestrial plants, aquatic macrophytes and marine phytoplankton assessed by n-alkanes were 56 ± 8 %, 35 ± 9 % and 9 ± 5 % in the study area, respectively. The relatively high salinity levels and strong hydrodynamic conditions of the Beidagang Reservoir led to higher terrestrial plants source and lower aquatic macrophytes source than these of Qilihai Reservoir based on the assessment of n-alkanes. Both methods showed that sedimentary OC was mainly derived from terrestrial sources (plant-dominated), suggesting that vegetation plays a crucial role in storing carbon in coastal wetlands, thus, the coastal vegetation management needs to be strengthened in the future. Our findings provide insights into the origins and dynamics of OC in coastal wetlands on the western coast of the Bohai Sea and a significant scientific basis for future monitoring of the blue carbon budget balance in coastal wetlands.

9.
Carbohydr Polym ; 316: 121065, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37321745

RESUMO

The lotus (Nelumbo nucifera Gaertn.) is the largest aquatic vegetable in Asia. The lotus seedpod (LS) is an inedible part of the mature flower receptacle of the lotus plant. However, the polysaccharide isolated from the receptacle has been less studied. The purification of LS resulted in two polysaccharides (LSP-1 and LSP-2). Both polysaccharides were found to be medium-sized HG pectin, with a Mw of 74 kDa. Their structures were elucidated via GC-MS and NMR spectrum and proposed as the repeating sugar units of GalA connected via α-1,4-glycosidic linkage, with LSP-1 having a higher degree of esterification. They have certain content of antioxidant and immunomodulatory activities. The esterification of HG pectin would have an adverse effect on these activities. Furthermore, the degradation pattern and kinetics of LSPs by pectinase conformed to the Michaelis-Menten model. There is a large amount of LS, resulting from the by-product of locus seed production, and thus a promising source for the isolation of the polysaccharide. The findings of the structure, bioactivities, and degradation property provide the chemical basis for their applications in the food and pharmaceutical industries.


Assuntos
Antioxidantes , Lotus , Antioxidantes/química , Lotus/química , Sementes/química , Polissacarídeos/química , Pectinas/análise
10.
Dalton Trans ; 52(27): 9215-9228, 2023 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-37350744

RESUMO

The combined structural and functional modeling study of [Fe]-H2ase has remained a great challenge, to date. Now, we report a series of new structural and functional [Fe]-H2ase models (1-6) that contain a mono-, di- or tetrasubstituted pyridine ligand with a biomimetic fac-C, N, and S ligation. While models 1-3, 5 and 6 are conveniently prepared by a novel flexible pyridine ligand (FPL)-based method, model 4 is prepared simply by an intramolecular CO replacement reaction of model 3. More interestingly, the structural study by spectroscopy and X-ray crystallography proves that these new models include a biomimetic fac-acyl (or methylene) C, pyridyl N, and thioether S ligation to an Fe(II) center and the C-Fe(II) σ bond is trans to an iodo ligand. In addition, the chemical reactivity study proves that they all have the enzyme-like H2 activation and hydride transfer functions in the presence of imidazolium Im+, AgBF4 and Et3N. Particularly interesting is that a possible pathway for such H2 activation and hydride transfer reactions catalyzed by a representative model 4 is proposed and the existence of the highly unstable 5-coordinate intermediate M4 and Fe-H species M5 is supported by the isolation and characterization of their MeCN-coordinated derivative 7 and chloro-substituted derivative 8, respectively.

11.
Surg Infect (Larchmt) ; 24(5): 440-447, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37126412

RESUMO

Background: To study the feasibility and efficacy of antibiotic cement in preserving endoplants after infection in patients with early tibial plateau fracture on plate exposure. Patients and Methods: A retrospective analysis of 23 patients treated for post-operative infection with plate exposure after tibial plateau fracture between 2017 and 2021. They were divided into the observation group (10 patients) and the control group (13 patients). Total operation time, length of hospitalization, hospitalization cost, the number of surgeries, white blood cell (WBC) count, neutrophil (NEUT) count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), the post-operative evaluation index, and complications were observed during the follow-up period. Results: All patients were followed up for 6 to 12 months; wound healing was observed in both groups. The total operation time for patients in the control group was longer compared with the observation group. However, the length of hospitalization, hospitalization cost, and number of surgeries in the observation group were less compared with the control group. No difference in WBC, NEUT, ESR, and CRP levels was observed one day after surgery. Furthermore, WBC, NEUT, ESR, and CRP levels were higher in patients in the control group compared with the observation group 72 hours after surgery. There were no differences in the post-operative evaluation index and complications in both groups. Conclusions: The antibiotic cement coating used for treating early post-operative infection in patients with tibial plateau fracture could effectively control infection while retaining endoplant, thereby promoting wound healing. It could also reduce pain and the medical burden on patients.


Assuntos
Antibacterianos , Cimentos Ósseos , Fraturas da Tíbia , Fraturas do Planalto Tibial , Cicatrização , Humanos , Antibacterianos/uso terapêutico , Fixação Interna de Fraturas/efeitos adversos , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fraturas da Tíbia/cirurgia , Resultado do Tratamento , Cicatrização/efeitos dos fármacos , Consolidação da Fratura , Cimentos Ósseos/uso terapêutico , Placas Ósseas
12.
Sci Total Environ ; 887: 164007, 2023 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-37172857

RESUMO

Knowledge of the long-term flooding response to climatic changes is critical for probing the flooding future in an oncoming warmer world. In this paper, three well-dated wetland sedimentary cores with high-resolution grain-size records were employed to reconstruct the historical flooding regime along the Ussuri River during the past 7000 years. The results show that five flooding-prone intervals marked by increased mean rates of sand-fraction accumulation occurred at 6.4-5.9 ka BP, 5.5-5.1 ka BP, 4.6-3.1 ka BP, 2.3-1.8 ka BP, and 0.5-0 ka BP, respectively. These intervals are generally consistent with the higher mean annual precipitation controlled by the strengthened East Asian summer monsoon which has been widely documented in geological records across the monsoonal regions of East Asia. Considering the prevalent monsoonal climate along the modern Ussuri River, we suggest that the regional flooding evolution during the Holocene Epoch should be generally controlled by the East Asian summer monsoon circulation which was initially linked to the ENSO activities in the tropical Pacific Ocean. While for the last interval spanning 0.5-0 ka BP, human influence, compared with the long-serving climatic controls, has played a more critical role in driving the regional flooding regime.

13.
Bioanalysis ; 15(7): 371-390, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37057990

RESUMO

Background: Sodium oligomannate was approved for marketing by the National Medical Products Administration of China in 2019 for improving cognitive functions in mild-to-moderate Alzheimer's disease patients. Method: LC-MS/MS methods were established and validated for the quantitation of sodium oligomannate in human plasma, urine and feces to support clinical development studies. Samples were prepared using liquid-liquid extraction and analyzed by ion-pair reversed-phase LC-MS/MS with calibration standard curve ranges of 25.0-5000 ng/ml, 0.500-100 µg/ml and 100-10,000 µg/g in plasma, urine and feces, respectively. Results & conclusion: All validation parameters met the respective acceptance criteria established by US FDA and International Council for Harmonisation of Technical Requirements for Human Use guidelines. The validated methods were applied to a pharmacokinetics and excretion study in healthy Chinese subjects.


Assuntos
Doença de Alzheimer , Líquidos Corporais , Humanos , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Fezes , Reprodutibilidade dos Testes
14.
J Fungi (Basel) ; 9(3)2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36983546

RESUMO

A endo-1,4-ß-mannanase (CcMan5C) gene was cloned from Coprinopsis cinerea and heterologously expressed in Pichia pastoris, and the recombinant enzyme was purified by Ni-affinity chromatography and identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF-MS). CcMan5C hydrolyzed only locust bean gum galactomannan (LBG) but not α-mannan from S. cerevisiae or Avicel cellulose, oat spelt xylan, or laminarin from Laminaria digitata. CcMan5C exhibited distinctive catalytic features that were different from previously reported ß-mannanases. (1) CcMan5C is the first reported fungal ß-mannase with an optimal alkalic pH of 8.0-9.0 for hydrolytic activity under assay conditions. (2) CcMan5C is the first reported alkalic fungal ß-mannase with an optimal temperature of 70 °C for hydrolytic activity under assay conditions. (3) The organic solvents methanol, ethanol, isopropanol, and acetone at concentrations of 10% or 20% did not inhibit CcMan5C activity, while 10% or 20% isopropanol and acetone even enhanced CcMan5C activity by 9.20-34.98%. Furthermore, CcMan5C tolerated detergents such as Tween 20 and Triton X-100, and its activity was even enhanced to 26.2-45.6% by 1% or 10% Tween 20 and Triton X-100. (4) CcMan5C solution or lyophilized CcMan5C exhibited unchanged activity and even increasing activity after being stored at -20 °C or -80 °C for 12 months and retained above 50% activity after being stored at 4 °C for 12 months. These features make CcMan5C a suitable candidate for the detergent industry and paper and pulp industry.

15.
Se Pu ; 41(2): 107-121, 2023 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-36725707

RESUMO

Heparin (Hp) is the most widely used anticoagulant drug in the clinics, with an annual global output of over 10 billion dollars. Hp, a member of the glycosaminoglycans (GAGs), is prepared from porcine intestinal mucosa via extraction, separation, and purification. Hp is a linear polysaccharide with repeating disaccharide units. Low-molecular-weight heparins (LMWHs) are depolymerized from Hp via chemical or enzymatic degradation. Compared with Hp, LMWHs exhibit less bleeding side effect, milder immunogenicity, and higher bioavailability when injected subcutaneously. In general, Hps, including LMWHs, are high complex drugs with large molecular weights (MWs), inhomogeneous MW distributions, and structural heterogeneity, including different degrees and locations of sulfonation, and unique residues generated from different production processes. Thus, developing efficient analytical methods to elucidate the structures of Hps and characterize or quantitate their properties is extremely challenging. Unfortunately, this problem limits their quality control, production optimization, clinical safety monitoring, and new applications. Research has constantly sought to elucidate the complicated structures of Hp drugs. Among the structural analysis and quality control methods of Hp currently available, chromatographic methods are the most widely studied and used. However, no literature thoroughly summarizes the specific applications of chromatographic methods in the structural analysis, manufacturing process, and quality control of Hp drugs. This paper systematically organizes and describes recent research progresses of the chromatographic methods used to analyze Hp drugs, including the identification and composition of monosaccharides, disaccharides, oligosaccharides, and polysaccharides. The applications, innovations, and limitations of these chromatographic methods are also summarized in this review. The insights obtained in this study will help production and quality control personnel, as well as drug researchers, obtain a deeper understanding of the complex structures of Hp drugs. This paper also provides a comprehensive reference for the structural analysis and quality control of Hps, proposes ideas for the development of new quality control methods, and lays a strong foundation for the in-depth structural elucidation of Hp drugs.


Assuntos
Heparina de Baixo Peso Molecular , Heparina , Animais , Suínos , Anticoagulantes , Cromatografia , Heparina Liase/metabolismo , Dissacarídeos
16.
J Phys Chem B ; 127(9): 1983-1994, 2023 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-36848623

RESUMO

GV-971 (sodium oligomannate) is a China Food and Drug Administration (CFDA)-approved drug for treating Alzheimer's disease, and it could inhibit Aß fibril formation in vitro and in mouse studies. To elucidate the mechanisms for understanding how GV-971 modulates Aß's aggregation, we conducted a systematic biochemical and biophysical study of Aß40/Aß42:GV-971 systems. The integrating analysis of previously published data and our results suggests that the multisite electrostatic interactions between GV-971's carboxylic groups and Aß40/Aß42's three histidine residues might play a dominant role in driving the binding of GV-971 to Aß. The fuzzy-type electrostatic interactions between GV-971 and Aß are expected to protect Aß from aggregation potentially through breaking the histidine-mediated inter-Aß electrostatic interactions. Meanwhile, since GV-971's binding exhibited a slight downregulation effect on the flexibility of Aß's histidine-colonized fragment, which potentially favors Aß aggregation, we conclude that the dynamics alteration plays a minor role in GV-971's modulation on Aß aggregation.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Camundongos , Animais , Peptídeos beta-Amiloides/química , Histidina , Doença de Alzheimer/metabolismo , Fragmentos de Peptídeos/química
17.
Carbohydr Polym ; 301(Pt B): 120370, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36446502

RESUMO

Polyguluronic acid (PG) is a type of polysaccharide found in edible brown seaweeds. This study synthesized a new sulfated saccharide (SOGA) by sulfating PG-derived unsaturated oligoguluronic acid (OGA). The molecular weight and degree of sulfate-group substitution of SOGA were 1.6 kDa and 1.03, respectively. The structures of PG, OGA, and SOGA were elucidated using FT-IR and NMR spectroscopy. Furthermore, the immunomodulatory effects of PG, OGA, and SOGA on LPS-triggered RAW264.7 and BV2 cells were evaluated. SOGA, but not PG or OGA, significantly reduced the LPS-stimulated overproduction of proinflammatory mediators and suppressed the activation of corresponding signalling pathways. Also, SOGA could actively regulate immune balance by inhibiting apoptosis and pyroapoptosis. These results suggested that SOGA is a potential therapeutic agent for the prevention of diseases associated with immune disorders owing to its remarkable immunomodulatory effects, and that sulfate groups in the carbohydrate chain play a crucial role for its bioactivities.


Assuntos
Lipopolissacarídeos , Sulfatos , Lipopolissacarídeos/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Óxidos de Enxofre , Imunomodulação
18.
Chem Commun (Camb) ; 58(87): 12168-12171, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36239209

RESUMO

Despite a variety of [Fe]-H2ase models prepared so far, the structural and functional modeling study of the enzyme has remained a great challenge. Now, we report a new type of flexible pyridine ligand (FPL)-based synthetic method by which two novel [Fe]-H2ase models have been prepared. Notably, the two models contain not only a biomimetic fac-acyl C, pyridyl N, thioether S coordination mode but also possess the enzyme-like H2/D2 activation functions.


Assuntos
Materiais Biomiméticos , Hidrogenase , Proteínas Ferro-Enxofre , Hidrogenase/química , Ligantes , Biomimética , Modelos Moleculares , Proteínas Ferro-Enxofre/química , Piridinas/química , Materiais Biomiméticos/química
19.
Opt Lett ; 47(20): 5385-5388, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36240369

RESUMO

Here we report that a simple chiral metasurface with twisted metallic cut-wire arrays enables highly efficient and continuously tunable chiral absorption over a broad spectral range by scanning the incidence angle over a few degrees. The angle-selective chiral absorption results from the surface plasmon resonance (SPR) excited by diffractive effects of the metasurface. The diffraction-assisted chiral metasurface provides a straightforward strategy for achieving dynamically tunable chiral devices and offers intriguing possibilities for various applications in on-chip chiral detectors/emitters, chiral spectrometers, chiral lasers, and so on.

20.
Anal Chem ; 94(38): 13000-13009, 2022 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-36102213

RESUMO

In this work, the first version of "Glycomapping" software is developed for the analysis of the most common low-molecular-weight heparin (LMWH), enoxaparin. Using ultrahigh-performance liquid chromatography-mass spectrometry, size exclusion chromatography is applied, and a virtual database of glycans in enoxaparin is established for the initial searching. With "Glycomapping", a complex chromatogram can be fitted, significantly improving resolution and confirming an accurate distribution range for each size of glycan within enoxaparin. In addition, randomly matched MS data can be corrected, with the constraint of the corresponding chromatographic retention time range, to remove most false positive data. The analytical stability of "Glycomapping" software was confirmed. Enoxaparin, prepared by different manufacturers and from different animal sources, was analyzed using "Glycomapping." Compared to raw data, data processed with "Glycomapping" are more robust and accurate. Another two LMWHs, nadroparin and dalteparin could also be analyzed with this software. This work lays a solid foundation for the automated analysis of heterogeneous mixtures of natural glycans, such as LMWHs and other complex oligosaccharides and polysaccharides.


Assuntos
Enoxaparina , Heparina de Baixo Peso Molecular , Animais , Anticoagulantes , Cromatografia Líquida , Dalteparina , Enoxaparina/química , Heparina/química , Heparina de Baixo Peso Molecular/análise , Nadroparina/química , Software
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