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1.
Molecules ; 29(13)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38999021

RESUMO

Cancer represents one of the most significant health challenges currently facing humanity, and plant-derived antitumour drugs represent a prominent class of anticancer medications in clinical practice. Isovaleryl sucrose esters, which are natural constituents, have been identified as having potential antitumour effects. However, the mechanism of action remains unclear. In this study, 12 isovaleryl sucrose ester components, including five new (1-5) and seven known compounds (6-12), were isolated from the roots of Atractylodes japonica. The structures of the compounds were elucidated using 1D and 2D-NMR spectroscopy, complemented by HR-ESI-MS mass spectrometry. The cytotoxic activities of all the compounds against human colon cancer cells (HCT-116) and human lung adenocarcinoma cells (A549) were also evaluated using the CCK8 assay. The results demonstrated that compounds 2, 4, and 6 were moderately inhibitory to HCT-116 cells, with IC50 values of 7.49 ± 0.48, 9.03 ± 0.21, and 13.49 ± 1.45 µM, respectively. Compounds 1 and 6 were moderately inhibitory to A549, with IC50 values of 8.36 ± 0.77 and 7.10 ± 0.52 µM, respectively. Molecular docking revealed that compounds 1-9 exhibited a stronger affinity for FGFR3 and BRAF, with binding energies below -7 kcal/mol. Compound 2 exhibited the lowest binding energy of -10.63 kcal/mol to FGFR3. We screened the compounds with lower binding energies, and the protein-ligand complexes already obtained after molecular docking were subjected to exhaustive molecular dynamics simulation experiments, which simulated the dynamic behaviour of the molecules in close proximity to the actual biological environment, thus providing a deeper understanding of their functions and interaction mechanisms. The present study provides a reference for the development and use of iso-valeryl sucrose esters in the antitumour field.


Assuntos
Atractylodes , Ésteres , Simulação de Acoplamento Molecular , Sacarose , Humanos , Sacarose/química , Sacarose/análogos & derivados , Sacarose/farmacologia , Ésteres/química , Ésteres/farmacologia , Atractylodes/química , Estrutura Molecular , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Células HCT116 , Linhagem Celular Tumoral , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Células A549 , Simulação de Dinâmica Molecular , Proliferação de Células/efeitos dos fármacos
2.
Molecules ; 29(13)2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38999057

RESUMO

Porphyra haitanensis (P. haitanensis), an important food source for coastal residents in China, has a long history of medicinal and edible value. P. haitanensis polysaccharides are some of the main active ingredients in P. haitanensis. It is worth noting that P. haitanensis polysaccharides have a surprising and satisfactory biological activity, which explains the various benefits of P. haitanensis to human health, such as anti-oxidation, immune regulation, anti-allergy, and anticancer properties. Hence, a systematic review aimed at comprehensively summarizing the recent research advances in P. haitanensis polysaccharides is necessary for promoting their better understanding. In this review, we systematically and comprehensively summarize the research progress on the extraction, purification, structural characterization, modification, and biological activity of P. haitanensis polysaccharides and address the shortcomings of the published research and suggest area of focus for future research, providing a new reference for the exploitation of polysaccharides from P. haitanensis in the fields of medicine and functional foods.


Assuntos
Polissacarídeos , Porphyra , Porphyra/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Polissacarídeos/isolamento & purificação , Humanos , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificação , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/isolamento & purificação
3.
Mol Ther Oncol ; 32(3): 200827, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39027379

RESUMO

Inadequate antigen-specific T cells activation hampers immunotherapy due to complex antigen presentation. In addition, therapeutic in vivo T cell expansion is constrained by slow expansion rates and limited functionality. Herein, we introduce a model fusion protein termed antigen-presenting cell-mimic fusion protein (APC-mimic), designed to greatly mimicking the natural antigen presentation pattern of antigen-presenting cells and directly expand T cells both in vitro and in vivo. The APC-mimic comprises the cognate peptide-human leukocyte antigen (pHLA) complex and the co-stimulatory marker CD80, which are natural ligands on APCs. Following a single stimulation, APC-mimic leads to an approximately 400-fold increase in the polyclonal expansion of antigen-specific T cells compared with the untreated group in vitro without the requirement for specialized antigen-presenting cells. Through the combination of single-cell TCR sequencing (scTCR-seq) and single-cell RNA sequencing (scRNA-seq), we identify an approximately 600-fold monoclonal expansion clonotype among these polyclonal clonotypes. It also exhibits suitability for in vivo applications confirmed in the OT-1 mouse model. Furthermore, T cells expanded by APC-mimic effectively inhibits tumor growth in adoptive cell transfer (ACT) murine models. These findings pave the way for the versatile APC-mimic platform for personalized therapeutics, enabling direct expansion of polyfunctional antigen-specific T cell subsets in vitro and in vivo.

4.
J Mater Chem B ; 12(28): 6917-6926, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38904147

RESUMO

Improving the regenerative ability of senescent stem cells is a critical issue in combating aging. The destiny and function of senescent stem cells are controlled by the niche, including the physical architecture of the surface of the extracellular matrix (ECM). In this study, we explored the functions of TiO2 nanotube topography on mesenchymal stem cells (MSCs) under senescence, as well as its mechanical effects on senescence. First, we created different nanotube topographies on the titanium samples. Next, we cultured senescent mesenchymal stem cells (S-MSCs) on samples with various nanotube topographies to determine suitable parameters. We found nanotube with a diameter of 10 nm significantly alleviated the cellular senescence of S-MSCs and improved the osteogenic differentiation of S-MSCs in vitro. Using an ectopic periodontium regeneration model, we confirmed that specific nanotube topography could promote tissue regeneration of S-MSCs in vivo. Moreover, we demonstrated that nanotube topography activated YAP in S-MSCs and reformed nuclear-cytoskeletal morphology to inhibit senescence. Taken together, our study establishes a bridge linking between nano-topography, mechanics, and senescence, suggesting a potential strategy to improve tissue regeneration in aged individuals by providing optimized surface topography on biomaterials.


Assuntos
Senescência Celular , Células-Tronco Mesenquimais , Nanotubos , Transdução de Sinais , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Senescência Celular/efeitos dos fármacos , Nanotubos/química , Animais , Titânio/química , Titânio/farmacologia , Humanos , Propriedades de Superfície , Células Cultivadas , Proteínas de Sinalização YAP/metabolismo , Osteogênese/efeitos dos fármacos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Diferenciação Celular/efeitos dos fármacos , Camundongos , Fatores de Transcrição/metabolismo
5.
Int J Biol Macromol ; 271(Pt 1): 132617, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38795891

RESUMO

Platycodon grandiflorum (P. grandiflorum) has long been used as a food and traditional herbal medicine. As a food, P. grandiflorum is often transformed into pickles for consumption, and as a traditional Chinese medicine, P. grandiflorum clears the lung, nourishes the pharynx, dispels phlegm, and discharges pus. Polysaccharides are among the main active components of P. grandiflorum. Recent literature has described the preparation, identification, and pharmacological activity of these polysaccharides. Studies have shown that these polysaccharides exhibit a variety of significant biological effects in vitro and in vivo, such as immune stimulation and antioxidant, anti-liver injury, anti-apoptosis and antitumour effects. However, there is no systematic summary of the related research articles on P. grandiflorum polysaccharide, which undoubtedly brings some difficulties to the future research. The purpose of this review is to comprehensively describe research progress on the extraction, purification, structural characterization, modification, and biological activity of P. grandiflorum polysaccharides. The shortcomings of recent research are summarized, further research on their biological activity is proposed to provide new reference value for the application of P. grandiflorum polysaccharides in drugs and health products in the future.


Assuntos
Platycodon , Polissacarídeos , Platycodon/química , Polissacarídeos/farmacologia , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Humanos , Animais , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/farmacologia
6.
Anal Bioanal Chem ; 416(17): 3923-3944, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38705905

RESUMO

Gold nanoclusters (AuNCs) are a class of novel luminescent nanomaterials that exhibit unique properties of ultra-small size, featuring strong anti-photo-bleaching ability, substantial Stokes shift, good biocompatibility, and low toxicity. Various biomolecules have been developed as templates or ligands to protect AuNCs with enhanced stability and luminescent properties for biomedical applications. In this review, the synthesis of AuNCs based on biomolecules including amino acids, peptides, proteins and DNA are summarized. Owing to the advantages of biomolecule-protected AuNCs, they have been employed extensively for diverse applications. The biological applications, particularly in bioimaging, biosensing, disease therapy and biocatalysis have been described in detail herein. Finally, current challenges and future potential prospects of bio-templated AuNCs in biological research are briefly discussed.


Assuntos
Ouro , Nanopartículas Metálicas , Ouro/química , Nanopartículas Metálicas/química , Humanos , Técnicas Biossensoriais/métodos , Luminescência , Animais , Peptídeos/química , DNA/química , Proteínas/química , Substâncias Luminescentes/química , Aminoácidos/química
7.
Phytother Res ; 38(7): 3417-3443, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38666435

RESUMO

Natural products are closely associated with human health. Luteolin (LUT), a flavonoid polyphenolic compound, is widely found in fruits, vegetables, flowers, and herbs. It is noteworthy that LUT exhibits a variety of beneficial pharmacological properties and holds significant potential for clinical applications, particularly in antitumor, anti-convulsion, diabetes control, anti-inflammatory, neuroprotection, anti-oxidation, anti-cardiovascular, and other aspects. The potential mechanism of action has been partially elucidated, including the mediation of NF-κB, toll-like receptor, MAPK, Wnt/ß-catenin, PI3K/Akt, AMPK/mTOR, and Nrf-2, among others. The review that aimed to comprehensively consolidate essential information on natural sources, pharmacological effects, therapeutic and preventive potential, as well as potential mechanisms of LUT. The objective is to establish a theoretical basis for the continued development and application of LUT.


Assuntos
Luteolina , Humanos , Luteolina/farmacologia , Flavonoides/farmacologia , Flavonoides/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Animais , Antioxidantes/farmacologia
8.
J Extracell Vesicles ; 13(4): e12434, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38634538

RESUMO

Apoptosis releases numerous apoptotic vesicles that regulate processes such as cell proliferation, immunity, and tissue regeneration and repair. Now, it has also emerged as an attractive candidate for biotherapeutics. However, apoptotic vesicles encompass a diverse range of subtypes, and it remains unclear which specific subtypes play a pivotal role. In this study, we successfully isolated different apoptotic vesicle subtypes based on their sizes and characterized them using NTA and TEM techniques, respectively. We compared the functional variances among the distinct subtypes of apoptotic vesicles in terms of stem cell proliferation, migration, and differentiation, as well as for endothelial cell and macrophage function, effectively identifying subtypes that exhibit discernible functional differences. ApoSEV (with diameter <1000 nm) promoted stem cell proliferation, migration, and multi-potent differentiation, and accelerated skin wound healing of diabetes mouse model, while apoBD (with diameter >1000 nm) played the opposite effect on cell function and tissue regeneration. Lastly, employing protein analysis and gene sequencing techniques, we elucidated the intrinsic mechanisms underlying these differences between different subtypes of apoEVs. Collectively, this study identified that apoptotic vesicle subtypes possessed distinct bio-functions in regulating stem cell function and behaviour and modulating tissue regeneration, which primarily attribute to the distinct profiling of protein and mRNA in different subtypes. This comprehensive analysis of specific subtypes of apoEVs would provide novel insights for potential therapeutic applications in cell biology and tissue regeneration.


Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , Camundongos , Animais , Células-Tronco Mesenquimais/metabolismo , Cicatrização/fisiologia , Diferenciação Celular , Proliferação de Células
9.
Artigo em Inglês | MEDLINE | ID: mdl-38503500

RESUMO

The broad application of noninvasive imaging has transformed preclinical cancer research, providing a powerful means to measure dynamic processes in living animals. While imaging technologies are routinely used to monitor tumor growth in model systems, their greatest potential lies in their ability to answer fundamental biological questions. Here we present the broad range of potential imaging applications according to the needs of a cancer biologist with a focus on some of the common biological processes that can be used to visualize and measure. Topics include imaging metastasis; biophysical properties such as perfusion, diffusion, oxygenation, and stiffness; imaging the immune system and tumor microenvironment; and imaging tumor metabolism. We also discuss the general ability of each approach and the level of training needed to both acquire and analyze images. The overall goal is to provide a practical guide for cancer biologists interested in answering biological questions with preclinical imaging technologies.

10.
Biosensors (Basel) ; 14(3)2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38534224

RESUMO

Bimetallic coordination polymers (CPs) have two different metal ions as connecting nodes in their polymer structure. The synthesis methods of bimetallic CPs are mainly categorized into the one-pot method and post-synthesis modifications according to various needs. Compared with monometallic CPs, bimetallic CPs have synergistic effects and excellent properties, such as higher gas adsorption rate, more efficient catalytic properties, stronger luminescent properties, and more stable loading platforms, which have been widely applied in the fields of gas adsorption, catalysis, energy storage as well as conversion, and biosensing. In recent years, the study of bimetallic CPs synergized with cancer drugs and functional nanomaterials for the therapy of cancer has increasingly attracted the attention of scientists. This review presents the research progress of bimetallic CPs in biosensing and biomedicine in the last five years and provides a perspective for their future development.


Assuntos
Nanoestruturas , Polímeros , Polímeros/química , Metais , Catálise , Adsorção
12.
Dent Mater ; 40(1): 90-101, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37923673

RESUMO

OBJECTIVES: Regenerating the periodontium poses a critical challenge in oral medicine. To repair various periodontal defects, it is necessary to adopt a bio-scaffold that provides both the architecture and bioactive cues for local stem cells to migrate, reside, proliferate, and differentiate. The objective of this study is to combine a cell-specific decellularized extracellular matrix (ECM) and a biomimetic electrospinning scaffold to regenerate severely destructed periodontium. METHODS: SEM, water contact angle (WCA), live/dead staining, swelling ratio, tensile test and immune-fluorescent staining were used to define the suitable topography for certain dental stem cells seeding and culturing. Transwell assay, CCK-8, Alizarin Red staining and PCR immune-fluorescent staining were used to determine ideal cell-specific ECM for PDLSCs/BMSCs migration, viability, and oriented differentiation. A biodegradable triple-layered electrospun scaffold (TLS) was fabricated by electrospinning with aligned fibers on both surfaces and a polyporous structure in the middle. The morphology and inter-porous structure of the TLS were characterized by SEM and mercury intrusion porosimetry (MIP). The surface of the TLS was functionalized with cell-specific ECM (Bi-ECM-TLS) through decellularization of the cell sheets cultured on the scaffold. The regenerative outcome of Bi-ECM-TLS was assessed by an in-situ rat periodontal defect model. Micro-CT, HE-staining, Masson's trichome staining, Sirius Red staining and Immunofluorescent staining were used for histological analysis. RESULTS: Aligned Gelatin/PCL fibrous membrane (GPA) was most effective for both PDLSCs and BMSCs in culture with WCA around 50 degrees and better mechanical strength than the rest. MSCs favored the same type of ECM (cell-specific ECM), and their regenerative properties were effectively induced with better chemotaxis, proliferative and differentiating behaviors. TLS characterization showed that TLS possessed aligned-random-aligned structure and inter-porous structure. In a rat model of periodontal defects, the TLS functionalized by BMSC-specific ECM for bone regeneration and PDLSC-specific ECM demonstrated highest BV/TV ratio, best bone structure and ligament fiber orientation and blood vessel formation, suggesting optimal performance in regenerating both alveolar bone and periodontal ligaments over TLS, single-ECM loaded TLS and r-Bi-ECM-TLS. SIGNIFICANCE: This study highlights the importance of combining a cell-specific decellularized ECM and a biomimetic electrospinning scaffold for targeted periodontal tissue regeneration, with potential implications for periodontal tissue engineering and improved patient outcomes.


Assuntos
Gelatina , Alicerces Teciduais , Humanos , Ratos , Animais , Alicerces Teciduais/química , Matriz Extracelular/química , Periodonto , Engenharia Tecidual , Ligamento Periodontal , Diferenciação Celular
13.
Phlebology ; 39(2): 96-107, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37921696

RESUMO

OBJECTIVE: The contribution of hypoxia to the pathophysiology of vascular smooth muscle cells (VSMCs) has not yet been fully elucidated. This study evaluated the effect of hypoxia on the phenotype and function of SMCs derived from the human normal great saphenous veins (NGSVs). METHODS: Fifteen NGSV tissue samples were collected. SMCs were isolated and cultured. Proliferation, migration, adhesion, senescence, and the structure of cytoskeletal filaments in SMCs were observed. mRNA and protein expression of Bax, Bcl-2, caspase-3, matrix metalloproteinases (MMP)-2, MMP-9, tissue inhibitor of metalloproteinases (TIMP)-1, and TIMP-2 was detected by fluorescent quantitative polymerase chain reaction and immunoblotting in the cobalt chloride (CoCl2) and the control groups. RESULTS: A decrease in the number of cytoskeletal filaments was observed. mRNA and protein expression of Bas and caspase-3 was significantly decreased, while the quantity of proliferation, migration, adhesion, senescence, and mRNA and protein expression of Bcl-2, MMP-2, MMP-9, TIMP-1, and TIMP-2 in SMCs in the CoCl2 group were significantly increased compared with the control group. CONCLUSION: Under hypoxic conditions, the phenotype and function of SMCs derived from the human NGSVs were dysregulated, suggesting that VSMCs switch from the contractile phenotype to the secretory or synthetic phenotype, and more dedifferentiate, resulting in extracellular matrix deposition and apoptotic decrease through the intrinsic pathway.


Assuntos
Cobalto , Metaloproteinase 9 da Matriz , Inibidor Tecidual de Metaloproteinase-2 , Humanos , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Caspase 3/metabolismo , Caspase 3/farmacologia , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Veia Safena/metabolismo , Músculo Liso Vascular/metabolismo , Fenótipo , Metaloproteinase 2 da Matriz/metabolismo , Miócitos de Músculo Liso/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/farmacologia , RNA Mensageiro/metabolismo
14.
Arq. bras. oftalmol ; 87(4): e2022, 2024.
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1520239

RESUMO

ABSTRACT Purpose: Opsoclonus-myoclonus syndrome is extremely uncommon in adults with an autoimmune pathophysiology. Because of the rarity of the syndrome, international recognition of opsoclonus-myoclonus-ataxia syndrome needs to be improved urgently. Therefore, the goal of this study was to raise the awareness of the opsoclonus-myoclonus-ataxia syndrome and help doctors in better diagnosing and using immunotherapy. Methods: We present a case study of an adult-onset case of idiopathic opsoclonus-myoclonus syndrome characterized by spontaneous arrhythmic multidirectional conjugate eye movements, myoclonus, ataxia, sleep disorders, and intense fear. Additionally, we conduct a literature search and summarize the pathophysiology, clinical presentation, diagnosis, and treatment of opsoclonus-myoclonus-ataxia syndrome. Results: Immunotherapies successfully treated the patient's opsoclonus, myoclonus, and ataxia. Further, the article also includes an update summary of the opsoclonus-myoclonus-ataxia syndrome. Conclusion: The prevalence of residual sequela in adults with opsoclonus-myoclonus-ataxia syndrome is low. Early diagnosis and treatment may result in a better prognosis. Furthermore, combined immunotherapy is expected to reduce the incidence of refractory and reoccurring opsoclonus-myoclonus-ataxia syndrome.


RESUMO Objetivo: A síndrome de opsoclonia-mioclonia é extremamente rara em adultos e tem uma fisiopatologia autoimune. Devido à raridade dessa síndrome, o reconhecimento da síndrome de opsoclonia-mioclonia-ataxia precisa melhorar urgentemente em todo o mundo. Assim sendo, este estudo visou aumentar a conscientização sobre a síndrome de opsoclonia-mioclonia-ataxia e ajudar os médicos para um melhor diagnóstico e o uso correto da imunoterapia. Métodos: Este é o relato de um caso adulto de síndrome de opsoclonia-mioclonia idiopática com movimentos oculares conjugados, multidirecionais, arrítmicos e espontâneos, mioclonia, ataxia, distúrbios do sono e medo intenso. Além disso, foram pesquisadas as publicações recentes relevantes e resumiu-se a fisiopatologia, a apresentação clínica, o diagnóstico e o tratamento da síndrome de opsoclonia-mioclonia-ataxia. Resultados: A paciente recuperou-se totalmente da opsoclonia, da mioclonia e da ataxia através de imunoterapia. O artigo também fornece um resumo atualizado sobre a síndrome de opsoclonia-mioclonia-ataxia. Conclusão: Adultos com síndrome de opsoclonia-mioclonia-ataxia têm uma baixa frequência de sequelas residuais. O diagnóstico e o tratamento precoces podem levar a melhores prognósticos. Espera-se que a imunoterapia combinada reduza a incidência da síndrome de opsoclonia-mioclonia-ataxia refratária e recorrente.

15.
Mol Neurobiol ; 61(7): 4454-4472, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38097915

RESUMO

Depression poses a significant threat to global physical and mental health, impacting around 3.8% of the population with a rising incidence. Current treatment options primarily involve medication and psychological support, yet their effectiveness remains limited, contributing to high relapse rates. There is an urgent need for innovative and more efficacious treatment modalities. Stem cell therapy, a promising avenue in regenerative medicine for a spectrum of neurodegenerative conditions, has recently garnered attention for its potential application in depression. While much of this work remains preclinical, it has demonstrated considerable promise. Identified mechanisms underlying the antidepressant effects of stem cell therapy encompass the stimulation of neurotrophic factors, immune function modulation, and augmented monoamine levels. Nonetheless, these pathways and other undiscovered mechanisms necessitate further investigation. Depression fundamentally manifests as a neurodegenerative disorder. Given stem cell therapy's success in addressing a range of neurodegenerative pathologies, it opens the door to explore its application in depression treatment. This exploration may include repairing damaged nerves directly or indirectly and inhibiting neurotoxicity. Nevertheless, significant challenges must be overcome before stem cell therapies can be applied clinically. Successful resolution of these issues will ultimately determine the feasibility of incorporating stem cell therapies into the clinical landscape. This narrative review provides insights into the progress of research, potential avenues for exploration, and the prevailing challenges in the implementation of stem cell therapy for treatment of depression.


Assuntos
Transtorno Depressivo , Transplante de Células-Tronco , Humanos , Transplante de Células-Tronco/métodos , Animais , Transtorno Depressivo/terapia , Células-Tronco
16.
Front Immunol ; 14: 1280049, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38022670

RESUMO

Catalpol (CA), extracted from Rehmannia Radix, holds extensive promise as a natural medicinal compound. This study employed 16S rRNA gene sequencing and combined serum and spleen metabolomics to profoundly investigate the therapeutic effects of CA on blood deficiency syndrome (BDS) and the underlying mechanisms. Notably, CA exhibited effectiveness against BDS induced by cyclophosphamide (CP) and acetylphenylhydrazine (APH) in rats-CA substantially elevated levels of crucial indicators such as erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF), tumor necrosis factor-alpha (TNF-a), and interleukin-6 (IL-6). Additionally, CA could alleviate peripheral blood cytopenia. Furthermore, the analysis of 16S rRNA revealed that CA had the potential to reverse the Firmicutes/Bacteroidetes (F/B) ratio associated with BDS. Through comprehensive serum and spleen metabolomic profiling, we successfully identified 22 significant biomarkers in the serum and 23 in the spleen, respectively. Enrichment analysis underscored Glycerophospholipid metabolism and Sphingolipid metabolism as potential pathways through which CA exerts its therapeutic effects on BDS.


Assuntos
Microbioma Gastrointestinal , Baço , Ratos , Animais , RNA Ribossômico 16S/genética , Ciclofosfamida/efeitos adversos
17.
Front Pharmacol ; 14: 1159985, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37063281

RESUMO

Cancer poses a serious threat to human health, and the search for safe and effective drugs for its treatment has aroused interest and become a long-term goal. Traditional Chinese herbal medicine (TCM), an ancient science with unique anti-cancer advantages, has achieved outstanding results in long-term clinical practice. Accumulating evidence shows that saponins are key bioactive components in TCM and have great research and development applications for their significant role in the treatment of cancer. Saponins are a class of glycosides comprising nonpolar triterpenes or sterols attached to hydrophilic oligosaccharide groups that exert antitumor effects by targeting the NF-κB, PI3Ks-Akt-mTOR, MAPK, Wnt-ß-catenin, JAK-STAT3, APMK, p53, and EGFR signaling pathways. Presently, few advances have been made in physiological and pathological studies on the effect of saponins on signal transduction pathways involved in cancer treatment. This paper reviews the phytochemistry and extraction methods of saponins of TCM and their effects on signal transduction pathways in cancer. It aims to provide theoretical support for in-depth studies on the anticancer effects of saponins.

18.
Arq Bras Oftalmol ; 2023 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-36995813

RESUMO

PURPOSE: Opsoclonus-myoclonus syndrome is extremely uncommon in adults with an autoimmune pathophysiology. Because of the rarity of the syndrome, international recognition of opsoclonus-myoclonus-ataxia syndrome needs to be improved urgently. Therefore, the goal of this study was to raise the awareness of the opsoclonus-myoclonus-ataxia syndrome and help doctors in better diagnosing and using immunotherapy. METHODS: We present a case study of an adult-onset case of idiopathic opsoclonus-myoclonus syndrome characterized by spontaneous arrhythmic multidirectional conjugate eye movements, myoclonus, ataxia, sleep disorders, and intense fear. Additionally, we conduct a literature search and summarize the pathophysiology, clinical presentation, diagnosis, and treatment of opsoclonus-myoclonus-ataxia syndrome. RESULTS: Immunotherapies successfully treated the patient's opsoclonus, myoclonus, and ataxia. Further, the article also includes an update summary of the opsoclonus-myoclonus-ataxia syndrome. CONCLUSION: The prevalence of residual sequela in adults with opsoclonus-myoclonus-ataxia syndrome is low. Early diagnosis and treatment may result in a better prognosis. Furthermore, combined immunotherapy is expected to reduce the incidence of refractory and reoccurring opsoclonus-myoclonus-ataxia syndrome.

19.
Molecules ; 28(3)2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36770631

RESUMO

The purpose of this work was to illustrate the effect of processing with vinegar on saikosaponins of Bupleurum chinense DC. (BC) and the protective effects of saikosaponin A (SSA), saikosaponin b1 (SSb1), saikosaponin b2 (SSb2), and saikosaponin D (SSD) in lipopolysaccharide (LPS)-induced acute lung injury (ALI) mice. We comprehensively evaluated the anti-inflammatory effects and potential mechanisms of SSA, SSb1, SSb2, and SSD through an LPS-induced ALI model using intratracheal injection. The results showed that SSA, SSb1, SSb2, and SSD significantly decreased pulmonary edema; reduced the levels of IL-6, TNF-α, and IL-1ß in serum and lung tissues; alleviated pulmonary pathological damage; and decreased the levels of the IL-6, TNF-α, and IL-1ß genes and the expression of NF-κB/TLR4-related proteins. Interestingly, they were similar in structure, but SSb2 had a better anti-inflammatory effect at the same dose, according to a principal component analysis. These findings indicated that it may not have been comprehensive to only use SSA and SSD as indicators to evaluate the quality of BC, especially as the contents of SSb1 and SSb2 in vinegar-processed BC were significantly increased.


Assuntos
Lesão Pulmonar Aguda , Ácido Oleanólico , Saponinas , Animais , Camundongos , Lipopolissacarídeos/efeitos adversos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Ácido Acético , Interleucina-6 , Saponinas/farmacologia , Saponinas/química , Ácido Oleanólico/farmacologia , Ácido Oleanólico/química , NF-kappa B/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/farmacologia
20.
J Mater Chem B ; 11(12): 2550-2567, 2023 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-36852826

RESUMO

Mesenchymal stem/stromal cells (MSCs) serve as essential components of regenerative medicine. Their destiny is influenced by the interaction of the cells with the external environment. In addition to the biochemical cues in a microenvironment, physical cues of the topography of the surrounding materials such as the extracellular matrix emerge as a crucial regulator of stem cell destiny and function. With recent advances in technologies of materials production and surface modification, surfaces with micro/nanotopographical characteristics can be fabricated to mimic the micro/nanoscale mechanical stimuli of the extracellular matrix environment and regulate the biological behavior of cells. Understanding the interaction of cells with the topography of a surface is conducive to the control of stem cell fate for application in regenerative medicine. However, the mechanisms by which topography affects the biological behavior of stem cells have not been fully elucidated. This review will present the effects of surface topography at the nano/micrometer scale on stem cell adhesion, morphology, proliferation, migration, and differentiation. It also focuses on discussing current theories about the sensing and recognition of surface topology cues, the transduction of the extracellular cues into plasma, and the final activation of related signaling pathways and downstream gene expression in MSCs. These insights will provide a theoretical basis for the future design of biomaterial scaffolds for application in regenerative medicine and tissue engineering.


Assuntos
Células-Tronco Mesenquimais , Células-Tronco , Diferenciação Celular , Materiais Biocompatíveis/metabolismo , Engenharia Tecidual
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