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1.
Sci Rep ; 14(1): 12651, 2024 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-38825618

RESUMO

Effective disinfection methods are crucial in the cold chain transportation process of food due to the specificity of temperature and the diversity of contaminated flora. The objective of this study was to investigate the sanitizing effect of different disinfectants on various fungi at - 20 °C to achieve accurate disinfection of diverse bacterial populations. Peracetic acid, hydrogen peroxide, and potassium bisulfate were selected as low-temperature disinfectants and were combined with antifreeze. The sanitizing effect of these cryogenic disinfectants on pathogens such as Bacillus subtilis black variant spores (ATCC9372), Staphylococcus aureus (ATCC 6538), Candida albicans (ATCC 10231), Escherichia coli (8099), and poliovirus (PV-1) was sequentially verified by bactericidal and virus inactivation experiments. After a specified time of disinfection, a neutralizing agent was used to halt the sanitizing process. The study demonstrates that different disinfectants exhibit selective effects during the low-temperature disinfection process. Peracetic acid, hydrogen peroxide, and potassium monopersulfate are suitable for the low-temperature environmental disinfection of bacterial propagules, viruses, and fungal contaminants. However, for microorganisms with strong resistance to spores, a low-temperature disinfectant based on peracetic acid should be chosen for effective disinfection treatment. Our results provide a valuable reference for selecting appropriate disinfectants to sanitize various potential pathogens in the future.


Assuntos
Temperatura Baixa , Desinfetantes , Desinfecção , Peróxido de Hidrogênio , Ácido Peracético , Desinfetantes/farmacologia , Desinfecção/métodos , Peróxido de Hidrogênio/farmacologia , Ácido Peracético/farmacologia , Sulfatos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Compostos de Potássio/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Poliovirus/efeitos dos fármacos
2.
Mar Drugs ; 22(5)2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38786622

RESUMO

Five new sulfated arylpyrrole and arylpyrrolone alkaloids, denigrins H-L (1-5), along with two known compounds, dictyodendrin B and denigrin G, were isolated from an extract of a New Zealand Dictyodendrilla c.f. dendyi marine sponge. Denigrins H-L represent the first examples of sulfated denigrins, with denigrins H and I (1-2), as derivatives of denigrin D, containing a pyrrolone core, and denigrins J-L (3-5), as derivatives of denigrin E (6), containing a pyrrole core. Their structures were elucidated by interpretation of 1D and 2D NMR spectroscopic data, ESI, and HR-ESI-MS spectrometric data, as well as comparison with literature data. Compounds 1-5, along with six known compounds previously isolated from the same extract, showed minimal cytotoxicity against the HeLa cervical cancer cell line.


Assuntos
Alcaloides , Poríferos , Pirróis , Animais , Poríferos/química , Humanos , Nova Zelândia , Pirróis/farmacologia , Pirróis/química , Pirróis/isolamento & purificação , Células HeLa , Alcaloides/farmacologia , Alcaloides/química , Alcaloides/isolamento & purificação , Sulfatos/química , Sulfatos/farmacologia , Estrutura Molecular , Espectroscopia de Ressonância Magnética , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação
3.
Mar Drugs ; 22(5)2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38786623

RESUMO

Mycoplasma pneumoniae, a notable pathogen behind respiratory infections, employs specialized proteins to adhere to the respiratory epithelium, an essential process for initiating infection. The role of glycosaminoglycans, especially heparan sulfate, is critical in facilitating pathogen-host interactions, presenting a strategic target for therapeutic intervention. In this study, we assembled a glycan library comprising heparin, its oligosaccharide derivatives, and a variety of marine-derived sulfated glycans to screen the potential inhibitors for the pathogen-host interactions. By using Surface Plasmon Resonance spectroscopy, we evaluated the library's efficacy in inhibiting the interaction between M. pneumoniae adhesion proteins and heparin. Our findings offer a promising avenue for developing novel therapeutic strategies against M. pneumoniae infections.


Assuntos
Heparina , Mycoplasma pneumoniae , Polissacarídeos , Mycoplasma pneumoniae/efeitos dos fármacos , Heparina/farmacologia , Heparina/química , Polissacarídeos/farmacologia , Polissacarídeos/química , Organismos Aquáticos , Humanos , Adesinas Bacterianas/metabolismo , Adesinas Bacterianas/efeitos dos fármacos , Aderência Bacteriana/efeitos dos fármacos , Pneumonia por Mycoplasma/tratamento farmacológico , Pneumonia por Mycoplasma/microbiologia , Antibacterianos/farmacologia , Antibacterianos/química , Animais , Interações Hospedeiro-Patógeno , Sulfatos/química , Sulfatos/farmacologia
4.
Bioresour Technol ; 402: 130806, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38718906

RESUMO

The study investigated the inactivation of Microcystis aeruginosa using a combined approach involving thermally activated peroxyacetic acid (Heat/PAA) and thermally activated persulfate (Heat/PDS). The Heat/PDS algal inactivation process conforms to first-order reaction kinetics. Both hydroxyl radical (•OH) and sulfate radical (SO4-•) significantly impact the disruption of cell integrity, with SO4-• assuming a predominant role. PAA appears to activate organic radicals (RO•), hydroxyl (•OH), and a minimal amount of singlet oxygen (1O2). A thorough analysis underscores persulfate's superior ability to disrupt algal cell membranes. Additionally, SO4-• can convert small-molecule proteins into aromatic hydrocarbons, accelerating cell lysis. PAA can accelerate cell death by diffusing into the cell membrane and triggering advanced oxidative reactions within the cell. This study validates the effectiveness of the thermally activated persulfate process and the thermally activated peroxyacetic acid as strategies for algae inactivation.


Assuntos
Microcystis , Oxirredução , Espécies Reativas de Oxigênio , Microcystis/efeitos dos fármacos , Microcystis/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sulfatos/metabolismo , Sulfatos/farmacologia , Sulfatos/química , Ácido Peracético/farmacologia , Temperatura Alta , Radical Hidroxila/metabolismo , Cinética
5.
Org Biomol Chem ; 22(19): 3986-3994, 2024 05 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
6.
Biomed Pharmacother ; 175: 116750, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38749174

RESUMO

Connective tissue growth factor (CTGF) holds great promise for enhancing the wound healing process; however, its clinical application is hindered by its low stability and the challenge of maintaining its effective concentration at the wound site. Herein, we developed novel double-emulsion alginate (Alg) and heparin-mimetic alginate sulfate (AlgSulf)/polycaprolactone (PCL) nanoparticles (NPs) for controlled CTGF delivery to promote accelerated wound healing. The NPs' physicochemical properties, cytocompatibility, and wound healing activity were assessed on immortalized human keratinocytes (HaCaT), primary human dermal fibroblasts (HDF), and a murine cutaneous wound model. The synthesized NPs had a minimum hydrodynamic size of 200.25 nm. Treatment of HaCaT and HDF cells with Alg and AlgSulf2.0/PCL NPs did not show any toxicity when used at concentrations <50 µg/mL for up to 72 h. Moreover, the NPs' size was not affected by elevated temperatures, acidic pH, or the presence of a protein-rich medium. The NPs have slow lysozyme-mediated degradation implying that they have an extended tissue retention time. Furthermore, we found that treatment of HaCaT and HDF cells with CTGF-loaded Alg and AlgSulf2.0/PCL NPs, respectively, induced rapid cell migration (76.12% and 79.49%, P<0.05). Finally, in vivo studies showed that CTGF-loaded Alg and AlgSulf2.0/PCL NPs result in the fastest and highest wound closure at the early and late stages of wound healing, respectively (36.49%, P<0.001 on day 1; 90.45%, P<0.05 on day 10), outperforming free CTGF. Double-emulsion NPs based on Alg or AlgSulf represent a viable strategy for delivering heparin-binding GF and other therapeutics, potentially aiding various disease treatments.


Assuntos
Alginatos , Fator de Crescimento do Tecido Conjuntivo , Nanopartículas , Poliésteres , Cicatrização , Cicatrização/efeitos dos fármacos , Alginatos/química , Poliésteres/química , Humanos , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Animais , Nanopartículas/química , Camundongos , Células HaCaT , Fibroblastos/efeitos dos fármacos , Masculino , Portadores de Fármacos/química , Linhagem Celular , Sistemas de Liberação de Medicamentos/métodos , Queratinócitos/efeitos dos fármacos , Tamanho da Partícula , Sulfatos/química , Sulfatos/farmacologia
7.
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
8.
ACS Appl Mater Interfaces ; 16(15): 18591-18607, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38564431

RESUMO

Coronavirus disease 2019 (COVID-19) has caused a global pandemic since its onset in 2019, and the development of effective vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to induce potent and long-lasting immunity remains a priority. Herein, we prepared two Lactobacillus exopolysaccharide (EPS) nanoparticle adjuvants (NPs 7-4 and NPs 8-2) that were constructed by using sulfation-modified EPS and quaternization-modified chitosan. These two NPs displayed a spherical morphology with sizes of 39 and 47 nm. Furthermore, the zeta potentials of NPs 7-4 and NPs 8-2 were 50.40 and 44.40 mV, respectively. In vitro assays demonstrated that NPs could effectively adsorb antigenic proteins and exhibited a sustained release effect. Mouse immunization tests showed that the NPs induced the expression of cytokines and chemokines at the injection site and promoted the uptake of antigenic proteins by macrophages. Mechanically, the NPs upregulated the expression of pattern recognition receptors (toll-like receptors and nod-like receptors) and activated the immune response of T cells and the production of neutralizing antibodies. In addition, the NP adjuvants had favorable immune-enhancing effects in cats, which are of great significance for controlling the trans-host transmission and re-endemicity of SARS-CoV-2. Overall, we demonstrated that NP-adjuvanted SARS-CoV-2 receptor binding domain proteins could induce robust specific humoral and cellular immunity.


Assuntos
COVID-19 , Nanopartículas , Animais , Camundongos , Gatos , Vacinas contra COVID-19 , SARS-CoV-2 , Sulfatos/farmacologia , Adjuvantes Imunológicos/química , Nanopartículas/química , Adjuvantes Farmacêuticos/farmacologia , Imunidade Celular , Vacinas de Subunidades Antigênicas/farmacologia
9.
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
10.
Nano Lett ; 24(17): 5214-5223, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38649327

RESUMO

Stroke is a leading cause of global mortality and severe disability. However, current strategies used for treating ischemic stroke lack specific targeting capabilities, exhibit poor immune escape ability, and have limited drug release control. Herein, we developed an ROS-responsive nanocarrier for targeted delivery of the neuroprotective agent rapamycin (RAPA) to mitigate ischemic brain damage. The nanocarrier consisted of a sulfated chitosan (SCS) polymer core modified with a ROS-responsive boronic ester enveloped by a red blood cell membrane shell incorporating a stroke homing peptide. When encountering high levels of intracellular ROS in ischemic brain tissues, the release of SCS combined with RAPA from nanoparticle disintegration facilitates effective microglia polarization and, in turn, maintains blood-brain barrier integrity, reduces cerebral infarction, and promotes cerebral neurovascular remodeling in a mouse stroke model involving transient middle cerebral artery occlusion (tMCAO). This work offers a promising strategy to treat ischemic stroke therapy.


Assuntos
Barreira Hematoencefálica , Quitosana , Portadores de Fármacos , AVC Isquêmico , Nanopartículas , Sirolimo , Animais , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/patologia , Camundongos , Quitosana/química , Portadores de Fármacos/química , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Sirolimo/farmacologia , Sirolimo/química , Sirolimo/uso terapêutico , Nanopartículas/química , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/uso terapêutico , Infarto da Artéria Cerebral Média/tratamento farmacológico , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/patologia , Modelos Animais de Doenças , Polissacarídeos/química , Polissacarídeos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Sulfatos/química , Sulfatos/farmacologia , Microglia/efeitos dos fármacos , Microglia/metabolismo
11.
Colloids Surf B Biointerfaces ; 238: 113915, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38631281

RESUMO

Hydrogels have emerged as a new type of wound dressing materials that involved in different stages of the healing processes. However, most of the existing wound dressings mainly offer a protective and moisturizing layer to prevent cross-infection, while the anti-inflammatory and anti-oxidative properties are frequently induced by extra addition of other bioactive molecules. Here, a novel type of sulfated glyco-functionalized hydrogels for wound dressing was prepared through the hybrid supramolecular co-assembly of carbohydrate segments (FG, FGS and FG3S), fluorenylmethoxycarbonyl-diphenylalanine (Fmoc-FF), and diphenylalanine-dopamine (FFD). Implanting sulfated carbohydrates can mimic the structure of glycosaminoglycans (GAGs), promoting cell proliferation and migration, along with anti-inflammatory effects. In situ polymerization of FFD introduced a secondary covalent network to the hydrogel, meanwhile, providing anti-oxidation and adhesion properties to wound surfaces. Furthermore, the dynamic supramolecular interactions within the hydrogels also confer self-healing capabilities to the wound dressing materials. In vivo experiments further demonstrated significantly accelerated healing rates with the multifunctional hydrogel FG3S-FFD, indicating high application potential.


Assuntos
Anti-Inflamatórios , Bandagens , Hidrogéis , Cicatrização , Cicatrização/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Hidrogéis/síntese química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Animais , Camundongos , Proliferação de Células/efeitos dos fármacos , Humanos , Sulfatos/química , Sulfatos/farmacologia , Adesivos/química , Adesivos/farmacologia , Movimento Celular/efeitos dos fármacos , Masculino
12.
Carbohydr Polym ; 334: 122025, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38553224

RESUMO

Diabetic foot ulcers (DFUs) are one of the most serious and devastating complication of diabetes, manifesting as foot ulcers and impaired wound healing in patients with diabetes mellitus. To solve this problem, sulfated hyaluronic acid (SHA)/collagen-based nanofibrous biomimetic skins was developed and used to promote the diabetic wound healing and skin remodeling. First, SHA was successfully synthetized using chemical sulfation and incorporated into collagen (COL) matrix for preparing the SHA/COL hybrid nanofiber skins. The polyurethane (PU) was added into those hybrid scaffolds to make up the insufficient mechanical properties of SHA/COL nanofibers, the morphology, surface properties and degradation rate of hybrid nanofibers, as well as cell responses upon the nanofibrous scaffolds were studied to evaluate their potential for skin reconstruction. The results demonstrated that the SHA/COL, SHA/HA/COL hybrid nanofiber skins were stimulatory of cell behaviors, including a high proliferation rate and maintaining normal phenotypes of specific cells. Notably, SHA/COL and SHA/HA/COL hybrid nanofibers exhibited a significantly accelerated wound healing and a high skin remodeling effect in diabetic mice compared with the control group. Overall, SHA/COL-based hybrid scaffolds are promising candidates as biomimetic hybrid nanofiber skin for accelerating diabetic wound healing.


Assuntos
Diabetes Mellitus Experimental , Nanofibras , Humanos , Camundongos , Animais , Nanofibras/uso terapêutico , Nanofibras/química , Ácido Hialurônico/química , Biomimética/métodos , Sulfatos/farmacologia , Cicatrização , Colágeno/química , Alicerces Teciduais/química
13.
Neurochem Res ; 49(6): 1592-1602, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38305960

RESUMO

In the present study, sulfated polysaccharides were obtained by digestion of Sargassum horneri and preparation with enzyme-assisted extraction using three food-grade enzymes, and their anti- Alzheimer's activities were investigated. The results demonstrated that the crude sulfated polysaccharides extracted using AMGSP, CSP and VSP dose-dependently (25-100 µg·mL- 1) raised the spontaneous alternating manner (%) in the Y maze experiment of mice and reduced the escape latency time in Morris maze test. AMGSP, CSP and VSP also exhibited good anti-AChE and moderate anti-BuChE activities. CSP displayed the best inhibitory efficacy against AChE. with IC50 values of 9.77 µM. And, CSP also exhibited good inhibitory selectivity of AChE over BuChE. Next, CSP of the best active crude extract was separated by the preparation type high performance liquid phase to obtain the sulphated fucooligosaccharide section: SFcup (→3-α-L-fucp(2-SO3-)-1→4-α-L-fucp(2,3-SO3-)-1→section), SFcup showed a best inhibitory efficacy against AChE with IC50 values of 4.03 µM. The kinetic research showed that SFcup inhibited AChE through dual binding sites. Moreover, the molecular docking of SFcup at the AChE active site was in accordance with the acquired pharmacological results.


Assuntos
Acetilcolinesterase , Doença de Alzheimer , Inibidores da Colinesterase , Simulação de Acoplamento Molecular , Oligossacarídeos , Sargassum , Sargassum/química , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/isolamento & purificação , Inibidores da Colinesterase/química , Inibidores da Colinesterase/uso terapêutico , Camundongos , Acetilcolinesterase/metabolismo , Oligossacarídeos/farmacologia , Oligossacarídeos/química , Oligossacarídeos/isolamento & purificação , Masculino , Sulfatos/química , Sulfatos/farmacologia , Butirilcolinesterase/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Polissacarídeos/farmacologia , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Relação Dose-Resposta a Droga
14.
Cell Transplant ; 33: 9636897241226847, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38288604

RESUMO

Ischemic wounds are chronic wounds with poor blood supply that delays wound reconstruction. To accelerate wound healing and promote angiogenesis, adipose-derived stem cells (ADSCs) are ideal seed cells for stem cell-based therapies. Nevertheless, providing a favorable environment for cell proliferation and metabolism poses a substantial challenge. A highly sulfated heparin-like polysaccharide 2-N, 6-O-sulfated chitosan (26SCS)-doped poly(lactic-co-glycolic acid) scaffold (S-PLGA) can be used due to their biocompatibility, mechanical properties, and coagent 26SCS high affinity for growth factors. In this study, a nano-scaffold system, constructed from ADSCs seeded on electrospun fibers of modified PLGA, was designed to promote ischemic wound healing. The S-PLGA nanofiber membrane loaded with adipose stem cells ADSCs@S-PLGA was prepared by a co-culture in vitro, and the adhesion and compatibility of cells on the nano-scaffolds were explored. Scanning electron microscopy was used to observe the growth state and morphological changes of ADSCs after co-culture with PLGA electrospun fibers. The proliferation and apoptosis after co-culture were detected using a Cell Counting Kit-8 kit and flow cytometry, respectively. An ischemic wound model was then established, and we further studied the ability of ADSCs@S-PLGA to promote wound healing and angiogenesis. We successfully established ischemic wounds on the backs of rats and demonstrated that electrospun fibers combined with the biological effects of adipose stem cells effectively promoted wound healing and the growth of microvessels around the ischemic wounds. Phased research results can provide a theoretical and experimental basis for a new method for promoting clinical ischemic wound healing.


Assuntos
Quitosana , Nanofibras , Ratos , Animais , Quitosana/farmacologia , Alicerces Teciduais , Sulfatos/farmacologia , Cicatrização , Células-Tronco
15.
Mar Biotechnol (NY) ; 26(1): 181-198, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38273163

RESUMO

Natural substances are strategic candidates for drug development in cancer research. Marine-derived molecules are of special interest due to their wide range of biological activities and sustainable large-scale production. Melanoma is a type of skin cancer that originates from genetic mutations in melanocytes. BRAF, RAS, and NF1 mutations are described as the major melanoma drivers, but approximately 20% of patients lack these mutations and are included in the triple wild-type (tripleWT) classification. Recent advances in targeted therapy directed at driver mutations along with immunotherapy have only partially improved patients' overall survival, and consequently, melanoma remains deadly when in advanced stages. Fucose-containing sulfated polysaccharides (FCSP) are potential candidates to treat melanoma; therefore, we investigated Fucan A, a FCSP from Spatoglossum schröederi brown seaweed, in vitro in human melanoma cell lines presenting different mutations. Up to 72 h Fucan A treatment was not cytotoxic either to normal melanocytes or melanoma cell lines. Interestingly, it was able to impair the tripleWT CHL-1 cell proliferation (57%), comparable to the chemotherapeutic cytotoxic drug cisplatin results, with the advantage of not causing cytotoxicity. Fucan A increased CHL-1 doubling time, an effect attributed to cell cycle arrest. Vascular mimicry, a close related angiogenesis process, was also impaired (73%). Fucan A mode of action could be related to gene expression modulation, in special ß-catenin downregulation, a molecule with protagonist roles in important signaling pathways. Taken together, results indicate that Fucan A is a potential anticancer molecule and, therefore, deserves further investigation.


Assuntos
Antineoplásicos , Melanoma , Phaeophyceae , Humanos , Fucose , Sulfatos/farmacologia , Melanoma/tratamento farmacológico , Linhagem Celular , Polissacarídeos/farmacologia , Polissacarídeos/metabolismo , Antineoplásicos/farmacologia
16.
Int J Biol Macromol ; 257(Pt 2): 128699, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38092106

RESUMO

Fungal sulfated polysaccharides (SPS) have been used in the pharmaceutical industry. In this study, sodium sulfate was employed as an elicitor to induce stress on the mycelia of Antrodia cinnamomea for the biosynthesis of SPS with high sulfate content. Sodium sulfate treatments increased the yield of SPS to 4.46 % and increased the sulfate content to 6.8 mmol/g of SPS. SPS were extracted from A. cinnamomea cultured with 500 mM sodium sulfate; these SPSs are denoted as Na500. Na500 exhibited the highest sulfate content and dose-dependent inhibitory activity against LPS-induced production of macrophage interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and interleukin 1ß (IL-1ß). Mechanistically, Na500 hindered the phosphorylation of transforming growth factor-ß receptor II (TGFRII), extracellular signal-regulated kinases (ERK), and protein kinase B (AKT) expression. A purified 7.79 kDa galactoglucan, Na500 F3, augmented the anti-inflammation activity by inhibiting LPS-induced TGFß release. Additionally, Na500 F3 restrained the LPS-induced phosphorylation of p-38, ERK, AKT, and TGFRII in RAW264.7 cells. Na500 F3 impeded the proliferation of lung cancer H1975 cells by inhibiting the phosphorylation of focal adhesion kinase, ERK, and Slug. The anti-inflammation and anticancer properties of Antrodia SPS contribute to its health benefits, suggesting its utility in functional foods.


Assuntos
Antrodia , Polissacarídeos Fúngicos , Polyporales , Proteínas Proto-Oncogênicas c-akt/metabolismo , Lipopolissacarídeos , Polissacarídeos/farmacologia , Sulfatos/farmacologia , Polissacarídeos Fúngicos/farmacologia , Antrodia/metabolismo
17.
Int J Biol Macromol ; 256(Pt 2): 128537, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38043665

RESUMO

Rheumatoid arthritis (RA) is a chronic autoimmune disease. NSAIDS, cyclophosphamide and glucocorticoid were commonly used to treat RA in clinical application, which long-term administration of these drugs caused serious adverse reactions. Therefore, sulfated hyaluronic acid (sHA) gel (SG) was prepared to firstly treat the RA and avoid the problem of toxic side effect caused by long-term application. In vitro evaluation showed that sHA inhibited the level of reactive oxygen species and TNF-α, IL-1ß, and IL-6, and decreased the ratio of macrophage M1/M2 type, which exerted better anti-inflammatory capacity. In vivo studies showed that the injection of SG into the joint cavity of collagen-induced rheumatoid arthritis (CIA) rats could effectively treat joint swelling and reduce the level of inflammatory factors in the serum. Immunofluorescence showed that SG exerted its anti-inflammatory activity by decreasing the ratio of M1/M2 type macrophages in synovial tissue. Cartilage tissue sections showed that SG reduced bone erosion and elevated chondrocyte expression. These results confirmed that sHA is expected to be developed as a drug to treat or relieve RA, which could effectively regulate the level of macrophages in rat RA, alleviate the physiological state of inflammatory over-excitation, and improve its anti-inflammatory and antioxidant capacity.


Assuntos
Artrite Experimental , Artrite Reumatoide , Ratos , Animais , Ácido Hialurônico/farmacologia , Sulfatos/farmacologia , Artrite Reumatoide/metabolismo , Articulações , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Artrite Experimental/tratamento farmacológico
18.
Int J Biol Macromol ; 258(Pt 1): 128824, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38103665

RESUMO

Herpes simplex viruses (HSVs) have an affinity for heparan sulfate proteoglycans on cell surfaces, which is a determinant for virus entry. Herein, several sulfated galactans that mimic the active domain of the entry receptor were employed to prevent HSV infection. They were produced from Grateloupia indica using chlorosulfonic acid-pyridine (ClSO3H.Py)/N,N-dimethylformamide reagent (fraction G-402), SO3.Py/DMF reagent (G-403), or by aqueous extraction (G-401). These galactans contained varied molecular masses (33-55 kDa), and sulfate contents (12-20 %), and have different antiviral activities. Especially, the galactan (G-402) generated by using ClSO3H.Py/DMF, a novel reagent, exhibited the highest level of antiviral activity (EC50 = 0.36 µg/mL) compared to G-403 (EC50 = 15.6 µg/mL) and G-401 (EC50 = 17.9 µg/mL). This most active sulfated galactan possessed a linear chain containing ß-(1 â†’ 3)- and α-(1 â†’ 4)-linked Galp units with sulfate group at the O-2/4/6 and O-2/3/6 positions, respectively. The HSV-1 and HSV-2 strains were specifically inhibited by this novel 33 ± 15 kDa galactan, which also blocked the virus from entering the host cell. These results highlight the significant potential of this sulfated galactan for antiviral research and drug development. Additionally, the reagent used for the effective conversion of galactan hydroxy groups to sulfate during extraction may also be useful for the chemical transformation of other natural products.


Assuntos
Herpesvirus Humano 1 , Rodófitas , Galactanos/química , Rodófitas/química , Sulfatos/farmacologia , Antivirais/farmacologia
19.
Environ Sci Pollut Res Int ; 31(3): 4269-4279, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38097840

RESUMO

Microbiologically influenced corrosion (MIC) is one of the reasons leading to the service failure of pipelines buried in the soil. In this work, the effect of sulfate-reducing bacteria (SRB) on the corrosion behavior of Q235 carbon steel in groundwater was investigated by electrochemical methods, surface analysis, and biological analysis. The results show that SRB utilizes iron as electron donor to sustain the vital activities of organic carbon-starved groundwater during the 14-day experimental period. The microbial community composition analysis at the genus level demonstrate that the diversity and richness decrease after corrosion, and the dominant SRB species has changed from Desulfovibrio to Desulfosporosinus. Moreover, the impedance of the carbon steel in the presence of biofilm was 1 order of magnitude higher than that of other periods in the electrochemical test, indicating that the biofilm and formed ferrous sulfide layer impeded the occurrence of corrosion. Although the 3D topography indicated that the surface of carbon steel was more uneven and pits were increased in the presence of SRB, the average weight loss (0.0396 ± 0.0050 g) was much higher than that without SRB (0.0139 ± 0.0007 g). These results implied that the growth of SRB makes the corrosion process of Q235 carbon steel more complicated.


Assuntos
Desulfovibrio , Água Subterrânea , Microbiota , Aço/química , Corrosão , Carbono/farmacologia , Biofilmes , Sulfatos/farmacologia
20.
Biofouling ; 39(9-10): 897-915, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38073525

RESUMO

Sulphate-reducing bacteria (SRB) are known to cause severe corrosion of steel structures in various industries, resulting in significant economic and environmental consequences. This review paper critically examines the impact of SRB-induced corrosion on steel, including the formation of SRB biofilms, the effect on different types of steel, and the various models developed to investigate this phenomenon. The role of environmental factors in SRB-induced corrosion, molecular techniques for studying SRBs, and strategies for mitigating corrosion are discussed. Additionally, the sustainability implications of SRB-induced corrosion and the potential use of alternative materials were explored. By examining the current state of knowledge on this topic, this review aims to provide a comprehensive understanding of the impact of SRB-induced corrosion on steel and identify opportunities for further research and development.


Assuntos
Biofilmes , Desulfovibrio , Aço/química , Corrosão , Sulfatos/farmacologia
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