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1.
Chin J Integr Med ; 2024 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-39671057

RESUMEN

OBJECTIVE: To evaluate the protective effects of gentiopicroside (GPS) against reactive oxygen species (ROS)-induced NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation in endothelial cells, aiming to reduce atherosclerosis. METHODS: Eight-week-old male ApoE-deficient mice were randomly divided into 2 groups (n=10 per group): the vehicle group and the GPS treatment group. Both groups were fed a high-fat diet for 16 weeks. GPS (40 mg/kg per day) was administered by oral gavage to the GPS group, while the vehicle group received an equivalent volume of the vehicle solution. At the end of the treatment, blood and aortic tissues were collected for assessments of atherosclerosis, lipid profiles, oxidative stress, and molecular expressions related to NLRP3 inflammasome activation, ROS production, and apoptosis. Additionally, in vitro experiments on human aortic endothelial cells treated with oxidized low-density lipoprotein (ox-LDL) were conducted to evaluate the effects of GPS on NLRP3 inflammasome activation, pyroptosis, apoptosis, and ROS production, specifically examining the role of the sirtuin 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. SIRT1 and Nrf2 inhibitors were used to confirm the pathway's role. RESULTS: GPS treatment significantly reduced atherosclerotic lesions in the en face aorta (P<0.01), as well as in the thoracic and abdominal aortic regions, and markedly decreased sinus lesions within the aortic root (P<0.05 or P<0.01). Additionally, GPS reduced oxidative stress markers and proinflammatory cytokines, including interleukin (IL)-1 ß and IL-18, in lesion areas (P<0.05, P<0.01). In vitro, GPS inhibited ox-LDL-induced NLRP3 activation, as evidenced by reduced NLRP3 (P<0.01), apoptosis-associated speck-like protein containing a CARD, cleaved-caspase-1, and cleaved-gasdermin D expressions (all P<0.01). GPS also decreased ROS production, apoptosis, and pyroptosis, with the beneficial effects being significantly reversed by SIRT1 or Nrf2 inhibitors. CONCLUSION: GPS exerts an antiatherogenic effect by inhibiting ROS-dependent NLRP3 inflammasome activation via the SIRT1/Nrf2 pathway.

2.
Phytomedicine ; 136: 156338, 2024 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-39731834

RESUMEN

BACKGROUND: Arnebiae Radix has long been used in traditional medicine for its pleiotropic properties. However, distinguishing Arnebiae Radix from its substitutes or closely related species has been challenging due to limited phenotypic characteristics. PURPOSE: We aimed to identify the molecular markers for distinguishing Arnebiae Radix from its confusion species. STUDY DESIGN: Chloroplast genome sequences were used to identify the markers. METHODS: Chloroplast genomes from 15 species across five genera, including all historically used source plants, were sequenced and assembled. RESULTS: The results revealed significant similarities across all chloroplast genomes in terms of structure, size, gene content, repeat sequences pattens, and codon usage patterns. Phylogenetic analysis showed that the genera Lithospermum, Buglossoides, and Aegonychon formed one clade, while Arnebia guttata, Ar. decumbens, and Ar. euchroma form another. Despite most regions of the chloroplast genomes are highly conserved, three regions-petA-psbJ, ndhF-rpl32, and ycf1-exhibited high variability among difference species, providing high-resolution markers for species identification. Specifically, 376 and 325 species-specific sites were identified in Ar. euchroma and Ar. guttata, respectively. Additionally, four species-specific sites were identified as novel molecular markers, potentially aiding in distinguishing Arnebiae Radix and its confusion or substitute species. CONCLUSION: This study provided new genetic insights for differentiating Arnebiae Radix and its confusion species, paving the way for further exploration of these medicinal plants.

3.
Phytomedicine ; 136: 156336, 2024 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-39708589

RESUMEN

BACKGROUND AND PURPOSE: Chuanxiong Qingnao Granles (CQG), has been used to treat migraine headache (MH) for many years. However, current investigation of CQG have primarily focused on clinical studies, and the potential mechanisms underlying of its effects on MH have not been fully elucidated. In the present study, we applied an integrated approach of transcriptomics and metabolomics to elucidate the therapeutic mechanisms of CQG in nitroglycerin (NTG)-induced MH injury. METHODS AND RESULTS: Fifty rats were allocated into five random groups: control (Con), NTG, flunarizine (NTG + Flu) group, and two CQG groups (NTG + CQG-L and NTG + CQG-H). CQG notably reduced the duration of ear redness and the frequency of head scratching frequency in rats. It also lowered the levels of 5-hydroxytryptamine (5-HT), endothelin-1 (ET-1), calcitonin gene-related peptide type 1 receptor (CGPR1), and tumor necrosis factor alpha (TNF-α) and enhanced neuronal morphology following NTG-induced MH damage. Transcriptomic and metabolomic analyses pinpointed interleukin (IL)-17A, IL-13, and CC chemokine receptor type 3 (CCR3) as central CQG targets, glycerophospholipid metabolism as key metabolic pathway, and further experiments confirmed that CQG reduced the expression of IL-17A, IL-13, CCR3, and inhibited the expression of inflammatory cytokines by suppressing PI3K/Akt signaling pathway and glycerophospholipid metabolism, to attenuate neuroinflammation in MH rats. CONCLUSIONS: Taken together, CQG inhibited PI3K/Akt signaling pathway to reduced neuroinflammation, and modulated metabolic pathway of glycerophospholipid metabolism in MH. The findings of this study offer novel insights into the mechanisms underlying the therapeutic effects of CQG, highlighting its potential clinical application in treatment of MH.

4.
Am J Transl Res ; 16(11): 7155-7164, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39678567

RESUMEN

OBJECTIVE: To evaluate the impact of connective tissue growth factor (CTGF) and inflammatory factors on the condition and prognosis of patients undergoing reperfusion therapy for acute ischemic stroke (AIS). METHODS: A retrospective analysis was conducted on 212 AIS patients who received reperfusion therapy at Wu Xi Traditional Chinese Medicine Hospital, Suqian Hospital of Traditional Chinese Medicine, The Affiliated Wuxi People's Hospital of Nanjing Medical University from January 2021 to January 2024. Patients were divided into a control group (modified Rankin Scale [mRS] score = 0-3, n = 132) and a study group (mRS score = 4-6, n = 80). The mRS and National Institutes of Health Stroke Scale (NIHSS) scores were compared between the two groups 90 days post-reperfusion. Levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and CTGF at the time of reperfusion were measured, and their correlations with the mRS and NIHSS scores were analyzed. Logistic regression was used to identify factors influencing patient prognosis. RESULTS: The control group had significantly lower levels of IL-6, TNF-α, and CTGF at reperfusion compared to the study group (all P < 0.050). Ninety days post-reperfusion, the control group showed significantly lower mRS and NIHSS scores than the study group (both P < 0.001). Levels of IL-6, TNF-α, and CTGF at reperfusion were positively correlated with mRS and NIHSS scores 90 days post-reperfusion (all P < 0.050). Logistic regression analysis identified age, and IL-6, TNF-α, and CTGF levels at reperfusion, as independent factors influencing prognosis. CONCLUSION: In AIS patients undergoing reperfusion, higher levels of CTGF, IL-6, and TNF-α at reperfusion were associated with worse mRS and NIHSS scores 90 days later. Age and elevated levels of these markers were independent predictors of poorer prognosis.

5.
Front Med (Lausanne) ; 11: 1482066, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39722820

RESUMEN

Aim: Functional Constipation (FC) is a common gastrointestinal disorder that imposes a considerable strain on global health. It negatively impacts the quality of life and results in significant healthcare expenditures. Current treatments, such as lifestyle changes and medications, fail to meet patient satisfaction due to efficacy and safety issues. Electroacupuncture (EA), with its precise stimulation control and standardized protocols, shows promise in FC management. However, optimal EA parameters for FC treatment are yet to be established. Our study reviews EA applications in FC to inform a standardized treatment approach and explore EA's therapeutic mechanisms. Methods: This comprehensive study utilized research literature from databases including PubMed, Embase, OVID, Web of Science, the Cochrane Library, CNKI, VIP, and Wanfang to perform a descriptive analysis of acupoint selection and EA parameters. It proceeded to analyze high-frequency acupoint groupings and stimulus parameters, followed by the excavation and analysis of core acupoint prescriptions. Subsequent steps integrated potential target identification for these core formulas, the assembly of a "core acupoint-prescription-target-constipation" network, and the construction of a protein-protein interaction (PPI) network to extract central targets. Additionally, Gene Ontology (GO) and KEGG enrichment analyses were conducted to prognosticate the underlying mechanisms by which EA may exert its therapeutic effects on FC. Results: In our study, we analyzed 141EA prescriptions for FC and identified a core set of acupoints including Tianshu (ST25), Fujie (SP14), Shangjuxu (ST37), and Zusanli (ST36) through data mining. The frequency of use was highest for Tianshu (ST25) with 119 occurrences, followed by Fujie (SP14) with 59, Shangjuxu (ST37) with 42, and Zusanli (ST36) with 23. PPI network analysis revealed key targets such as NFKB1, IL6, MyD88, TLR4, TNF, TLR2, and IL1B. GO and KEGG analyses of 49 constipation-associated targets identified 257 BP, 37 CC, and 41 MF terms, and 154 significant pathways, with the top 20 visualized for further analysis. Conclusion: The core acupoint prescription of EA for FC can exert its therapeutic effects by acting on multiple targets and pathways synergistically especially on NFKB1, IL6, MyD88, TLR4, TNF, TLR2, and IL1B. The research findings have preliminarily validated the fundamental effects and related mechanisms of EA parameters and core prescriptions, providing direction for further in-depth exploration of the mechanisms of action.

6.
Medicine (Baltimore) ; 103(45): e40275, 2024 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-39533556

RESUMEN

BACKGROUND: The study was designed to systematically evaluate the efficacy and safety of Fuzheng-Buyi formula in treating castration-resistant prostate cancer (CRPC). METHODS: A computer-based search were conducted in the databases, including CNKI, WanFang Data, VIP, CBM, PubMed, EMbase, and the Cochrane database to identify all randomized controlled trials. The studies investigating the efficacy and safety of Fuzheng-Buyi formula combined with Western medicine for the treatment of CRPC were included from January 1st, 2010 to December 31st, 2023. The quality of the included studies was evaluated according to the Cochrane Handbook manual, and meta-analysis was performed using Review Manager 5.3 and R Studio 4.2.3 software. RESULTS: In this study, a total of 18 trials were included, encompassing a population of 1093 patients diagnosed with CRPC. The results of the meta-analysis showed that the combination of Fuzheng-Buyi formula and Western drugs was more effective in increasing the overall efficacy rate (risk ratio = 1.31, 95% confidence interval [CI] [1.17, 1.46], P < .00001), decreasing Traditional Chinese Medicine syndrome score (mean difference [MD] = -4.40, 95% CI [-6.10, -2.70], P < .00001), and quality of life scale (physiological condition MD = -2.31, 95% CI [-3.13, -1.48], P < .00001; social well-being MD = 1.26, 95% CI [0. 59, 1.94], P = .0002; emotional well-being MD = -2.04, 95% CI [-2.96, -1.12], P < .00001; functional well-being MD = -3.18, 95% CI [2.11, 4.26], P < .00001; others should be paid to MD = -3.15, 95% CI [-4.93, -1.37], P = .0005) compared with the Western medicine alone. And the incidence of adverse events was significantly lower in the combination treatment group compared with Western medicine group (risk ratio = 0.58, 95% CI [0.46, 0.73], P < .00001). CONCLUSION: The combination of Fuzheng-Buyi formula and Western medicine was more effective in improving the clinical efficacy and quality of life of CRPC patients, with lower incidence of adverse events compared with Western medicine alone.


Asunto(s)
Medicamentos Herbarios Chinos , Neoplasias de la Próstata Resistentes a la Castración , Humanos , Masculino , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto , Calidad de Vida
7.
Nutrients ; 16(22)2024 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-39599584

RESUMEN

BACKGROUND: Selenium (Se) is an essential trace element for maintaining human health, with significant antioxidant and immunoregulatory functions. Inadequate Se intake may be associated with Keshan disease, Kashin-Beck disease, and hypothyroidism. However, effective indicators for scientifically guiding Se supplementation in Se-deficient populations are still lacking. OBJECTIVES: This study aims to explore the dynamic distribution of Se across various nutritional biomarkers and major organs in rats through a Se supplementation experiment, as well as the pairwise correlations between them, in order to identify reliable nutritional indicators for evaluating Se levels in the body. METHODS: Se levels in hair, blood, and major tissues and organs were determined by atomic fluorescence spectrometry, and glutathione peroxidase (GSH-Px) levels were measured using an ELISA. RESULTS: Se supplementation significantly increased Se levels in rat blood, hair, and major organs, as well as GSH-Px levels in blood. Se primarily accumulated in the liver and kidneys, followed by myocardium, spleen, and muscles. Serum and plasma Se were found to be the best indicators of short-term Se intake, while erythrocyte Se levels showed a stronger correlation with Se levels in tissues and organs, making it a better marker for assessing long-term Se nutritional status compared to hair Se. CONCLUSIONS: This study demonstrates the potential of erythrocyte Se levels as an indicator for evaluating long-term Se nutritional status, providing scientific evidence for Se nutritional assessments.


Asunto(s)
Biomarcadores , Suplementos Dietéticos , Eritrocitos , Ratas Wistar , Selenio , Animales , Selenio/sangre , Selenio/administración & dosificación , Eritrocitos/metabolismo , Eritrocitos/química , Ratas , Masculino , Biomarcadores/sangre , Estado Nutricional , Cabello/química , Glutatión Peroxidasa/metabolismo , Glutatión Peroxidasa/sangre
8.
NPJ Sci Food ; 8(1): 99, 2024 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-39572563

RESUMEN

The typical edible medicinal plants of Viola inconspicua were compared with leaf-green, biomass, metabolomes, and bacterial communities, after leaf-spraying water (A), brown sugar water (B), brown sugar, urea, and KH2PO4 water (C), or KH2PO4 and urea water (D). The plants sprayed with C solution presented relatively normal leaf-green and the highest biomass. In contrast of A group, B, C, and D groups were found with 72, 94, and 104 leaf differently accumulated metabolites (DAMs) and 105, 88, and 92 root DAMs, respectively. Typically, relative abundances of amino acids were elevated in C and D groups, while those of leaf flavonoids were increased in B group. Noticeably, leaf DAMs of C group versus A group had strong correlations with one to more phylum- or/and genus-dominant bacteria of C group. Taken together, leaf-spraying brown sugar, urea, and KH2PO4 water are ideal for holding leaf-green and biomass in V. inconspicua plants.

9.
Metab Brain Dis ; 40(1): 31, 2024 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-39570470

RESUMEN

The study aims to investigate the regulatory role of NPs lncRNA NONHSAT159592.1 in glioblastoma cells and its molecular mechanism. We have designed a reduction-responsive nanoparticle (NP) platform for efficient delivery of si-lncRNA (si-lnc). The size of siRNA nanoparticles was observed and determined by transmission electron microscopy. The distribution size of nanoparticles was analyzed by the NanoSight nanoparticle tracking analyzer. The fluorescence spectrum and UV spectrum were determined. The level of lncRNA in glioblastoma cells was detected by RT-qPCR analysis. The localization of lncRNA NONHSAT159592.1 in glioblastoma cells was detected by fluorescence in situ hybridization. Cell proliferation activity was evaluated by clonal formation experiment and CCK-8 kit. Cell migration and invasion were detected by wound healing assay and Transwell experiment. Western blot assay was used to detect the expression level of EMT-related proteins in cells. EdU staining was used to detect cell proliferation. NPs or PBS and IR780 were injected intravenously into nude mice with tumors, and fluorescence imaging was performed in vivo to evaluate the proliferation of tumor tissue. The positive rate of Ki67 and Vimentin in tumor tissue was detected by immunohistochemical staining. We found that lncRNA NONHSAT159592.1 was significantly down-regulated in glioblastoma cell lines, localized in the nucleus and cytoplasm. In U87 and U251 cells, we found that NPs-si-lncRNA NONHSAT159592.1 significantly inhibited glioblastoma cell proliferation, invasion, and EMT progression. In the orthotopic xenograft model, we found that silencing lncRNA could significantly inhibit tumor proliferation and prolong the survival time of tumor-bearing mice. Further studies confirmed that overexpression of ITGA3 reversed the inhibitory effects of NPs-si-lnc on the proliferation, invasion, and migration of glioblastoma cell lines. Our study suggested that NPs (si-lnc) could inhibit the malignant development of glioma by a mechanism that may be linked to the activation of the ITGA3/FAK/PI3K/AKT signaling pathway.


Asunto(s)
Proliferación Celular , Glioblastoma , Ratones Desnudos , Nanopartículas , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , ARN Largo no Codificante , Transducción de Señal , Glioblastoma/patología , Glioblastoma/metabolismo , Glioblastoma/tratamiento farmacológico , Animales , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Ratones , Proteínas Proto-Oncogénicas c-akt/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Fosfatidilinositol 3-Quinasas/metabolismo , Movimiento Celular/efectos de los fármacos , Invasividad Neoplásica , Quinasa 1 de Adhesión Focal/metabolismo , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/tratamiento farmacológico , Progresión de la Enfermedad , ARN Interferente Pequeño/farmacología , ARN Interferente Pequeño/administración & dosificación
10.
Nat Prod Res ; : 1-8, 2024 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-39560922

RESUMEN

Eleven polyketide derivatives, including two new compounds, xanthoradone D (1) and arisochromophilone (2), were isolated from Arcopilus aureus HJ-7, a Chinese medicinal plant Ardisia mamillata Hance-associated fungus. Their structures were elucidated on the basis of spectroscopic analysis and ECD (Electronic Circular Dichroism) calculations. The antibacterial and antifungal activities of the compounds were evaluated. Compound 1 showed the significant inhibitory activity against Staphylococcus aureus and Xanthomonas axonopodis pv. citri (Hasse) Dye with the MIC (Minimum Inhibitory Concentration) value of 6.25 µg/mL, and 1 also showed strong antifungal activities against Cochliobolus miyabeanus and Ceratocystis paradoxa with the MIC value of 3.125 µg/mL.

11.
Environ Res ; 263(Pt 3): 120219, 2024 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-39448008

RESUMEN

Addressing the risks of cyanobacterial blooms and toxin production under ongoing and accelerating eutrophication and climate warming is crucial for both water ecosystem services and human health. Therefore, we here explored the interactive effects of eutrophication and warming on freshwater ecosystems, focusing on Microcystis and its cyanotoxin production. We employed a large-scale mesocosm system simulating future climate warming scenarios in concert with varying degrees of nutrient enrichment. We explored the full range of identified cyanobacterial toxins and cyanotoxin-producing genes under different experimental conditions and assessed the effects of both eutrophication and warming on both phytoplankton community structure (algal densities, community stability) and function (resource use efficiency, RUE). We show here that eutrophication increases the RUE of Microcystis and promotes an increase in toxin-producing genes, leading to a substantial increase in the dominance of Microcystis. This increase correlates with enhanced cyanotoxin production, a trend exacerbated under the influence of future climate warming, suggesting interactions between eutrophication and climate warming on Microcystis ecology and cyanotoxin dynamics. Hence, heatwaves and eutrophication lead the phytoplankton community to be dominated by a minority of algal species with higher toxic capacity. In a broader context, our study underscores the urgent need for holistic management strategies, addressing both nutrient control and climate mitigation, to effectively manage the escalating ecological risks associated with cyanobacterial dominance and toxin production.


Asunto(s)
Eutrofización , Microcystis , Fitoplancton , Microcystis/metabolismo , Microcystis/crecimiento & desarrollo , Fitoplancton/metabolismo , Cambio Climático , Toxinas Bacterianas , Microcistinas/biosíntesis , Calentamiento Global , Ecosistema , Toxinas de Cianobacterias
12.
Pharmacol Ther ; 264: 108728, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39389315

RESUMEN

Oral administration of Chinese Herbal Medicine (CHM) faces various challenges in reaching the target organs including absorption and conversion in the gastrointestinal tract, hepatic metabolism via the portal vein, and eventual systemic circulation. During this process, factors such as gut microbes, physical or chemical barriers, metabolic enzymes, and transporters play crucial roles. Particularly, interactions between different herbs in CHM have been observed both in vitro and in vivo. In vitro, interactions typically manifest as detectable physical or chemical changes, such as facilitating solubilization or producing precipitates when decoctions of multiple herbs are administered. In vivo, such interactions cause alterations in the ADME (absorption, distribution, metabolism, and excretion) profile on metabolic enzymes or transporters in the body, leading to competition, antagonism, inhibition, or activation. These interactions ultimately contribute to differences in the therapeutic and pharmacological effects of multi-herb formulas in CHM. Over the past two thousand years, China has cultivated profound expertise and solid theoretical frameworks over the scientific use of herbs. The combination of multiple herbs in one decoction has been frequently employed to synergistically enhance therapeutic efficacy or mitigate toxic and side effects in clinical settings. Additionally combining herbs with increased toxicity or decreased effect is also regarded as a remedy, a practice that should be approached with caution according to Traditional Chinese Medicine (TCM) physicians. Such historical records and practices serve as a foundation for predicting favorable multi-herb combinations and their potential risks. However, systematic data that are available to support the clinical practice and the exploration of novel herbal formulas remain limited. Therefore, this review aims to summarize the pharmacokinetic interactions and mechanisms of herb-herb or herb-drug combinations from existing works, and to offer guidance as well as evidence for optimizing CHM and developing new medicines with CHM characteristics.


Asunto(s)
Medicamentos Herbarios Chinos , Interacciones de Hierba-Droga , Medicamentos Herbarios Chinos/farmacocinética , Medicamentos Herbarios Chinos/farmacología , Humanos , Animales , Medicina Tradicional China , Administración Oral
13.
Zhongguo Zhong Yao Za Zhi ; 49(17): 4695-4701, 2024 Sep.
Artículo en Chino | MEDLINE | ID: mdl-39307807

RESUMEN

The chemical constituents in the ethanol extract of Viburnum utile were isolated by column chromatography with D101 macroporous resin, silica gel, and Sephadex LH-20. Their structures were identified by spectroscopic techniques such as NMR and MS. All the compounds were evaluated for the inhibitory activities against α-glucosidase. Sixteen compounds were obtained and identified as viburnumide A(1), vitamin E(2), α-amyrin(3), α-tocoquinone(4), narjatamanin B(5), ethyl caffeate(6), naringenin(7), apigenin(8), ethyl ß-D-ribo-hex-3-ulopyranoside(9), trans-p-hydroxycinnamic acid(10), amentoflavone(11), apigenin-7-O-ß-D-glucoside(12), luteolin-7-O-ß-D-glucoside(13), henryoside(14), ursolic acid(15), and 2α-hydroxy-oleanolic acid(16). Among them, compound 1 was a new compound, and compounds 2-16 were isolated from V. utile for the first time. The inhibitory activity(IC_(50) of 4.0 µmol·L~(-1)) of compound 11 against α-glucosidase was comparable to that of the positive control acarbose(IC_(50) of 2.3 µmol·L~(-1)).


Asunto(s)
Inhibidores de Glicósido Hidrolasas , Viburnum , alfa-Glucosidasas , Viburnum/química , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/farmacología , alfa-Glucosidasas/química , Estructura Molecular , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología
14.
J Agric Food Chem ; 72(34): 19093-19106, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39161099

RESUMEN

Luteolin-7-O-glucoside(L7G), a glycosylation product of luteolin, is present in a variety of foods, vegetables, and medicinal herbs and is commonly used in dietary supplements due to its health benefits. Meanwhile, luteolin-7-O-glucoside is an indicator component for the quality control of honeysuckle in the pharmacopoeia. However, its low content in plants has hindered its use in animal pharmacological studies and clinical practice. In this study, a novel 7-O-glycosyltransferase CmGT from Cucurbita moschata was cloned, which could efficiently convert luteolin into luteolin-7-O-glucoside under optimal conditions (40 °C and pH 8.5). To further improve the catalytic efficiency of CmGT, a 3D structure of CmGT was constructed, and directed evolution was performed. The mutant CmGT-S16A-T80W was obtained by using alanine scanning and iterative saturation mutagenesis. This mutant exhibited a kcat/Km value of 772 s-1·M-1, which was 3.16-fold of the wild-type enzyme CmGT. Finally, by introducing a soluble tag and UDPG synthesis pathway, the strain BXC was able to convert 1.25 g/L of luteolin into 1.91 g/L of luteolin-7-O-glucoside under optimal conditions, achieving a molar conversion rate of 96% and a space-time yield of 27.08 mg/L/h. This study provides an efficient method for the biosynthesis of luteolin-7-O-glucoside, which holds broad application prospects in the food and pharmaceutical industry.


Asunto(s)
Biocatálisis , Cucurbita , Glucósidos , Glicosiltransferasas , Luteolina , Proteínas de Plantas , Glucósidos/metabolismo , Glucósidos/química , Glucósidos/biosíntesis , Luteolina/química , Luteolina/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/química , Glicosiltransferasas/genética , Glicosiltransferasas/metabolismo , Glicosiltransferasas/química , Cucurbita/genética , Cucurbita/enzimología , Cucurbita/química , Cucurbita/metabolismo , Clonación Molecular , Cinética , Evolución Molecular Dirigida
15.
Brain Res Bull ; 215: 111031, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39002935

RESUMEN

We have previously reported that the expression of miR-34c-5p was up-regulated during acupuncture treatment in the setting of a cerebral ischemia/reperfusion injury (CIRI), indicating that miR-34c-5p plays an important role in healing from a CIRI-induced brain injury. This study sought to evaluate the effects of acupuncture on miR-34c-5p expression and autophagy in the forward and reverse directions using a rat focal cerebral ischemia/reperfusion model. After 120 minutes of middle cerebral artery occlusion and reperfusion, rats were treated with acupuncture at the "Dazhui" (DU20), "Baihui" (DU26) and "Renzhong" (DU14) points. Neurologic function deficit score, cerebral infarct area ratio, neuronal apoptosis and miR-34c-5p expression were evaluated 72 hr after treatment. The autophagy agonist RAPA and the antagonist 3MA were used to evaluate the neuro protective effects of autophagy-mediated acupuncture. We found that acupuncture treatment improved autophagy in the brain tissue of CIRI rats. Acupuncture reversed the negative effects of 3MA on CIRI, and acupuncture combined with RAPA further enhanced autophagy. We also found that acupuncture could increase miR-34c-5p expression in hippocampal neurons after ischemia/reperfusion. Acupuncture and a miR-34c agomir were able to enhance autophagy, improve neurologic deficits, and reduce the cerebral infarct area ratio and apoptosis rate by promoting the expression of miR-34c-5p. Silencing miR-34c resulted in a significantly reduced activating effect of acupuncture on autophagy and increased apoptosis, neurologic deficit symptoms, and cerebral infarct area ratio. This confirms that acupuncture can upregulate miR-34c-5p expression, which is beneficial in the treatment of CIRI.


Asunto(s)
Terapia por Acupuntura , Autofagia , Isquemia Encefálica , MicroARNs , Ratas Sprague-Dawley , Daño por Reperfusión , Animales , MicroARNs/metabolismo , MicroARNs/genética , Daño por Reperfusión/metabolismo , Daño por Reperfusión/terapia , Autofagia/fisiología , Masculino , Terapia por Acupuntura/métodos , Ratas , Isquemia Encefálica/metabolismo , Isquemia Encefálica/terapia , Infarto de la Arteria Cerebral Media/terapia , Infarto de la Arteria Cerebral Media/metabolismo , Apoptosis/fisiología , Neuronas/metabolismo , Modelos Animales de Enfermedad , Encéfalo/metabolismo
16.
Biomed Pharmacother ; 177: 117112, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39018869

RESUMEN

Ferroptosis is a novel form of cell demise characterized primarily by the reduction of trivalent iron to divalent iron, leading to the release of reactive oxygen species (ROS) and consequent induction of intense oxidative stress. In atherosclerosis (AS), highly accumulated lipids are modified by ROS to promote the formation of lipid peroxides, further amplifying cellular oxidative stress damage to influence all stages of atherosclerotic development. Macrophages are regarded as pivotal executors in the progression of AS and the handling of iron, thus targeting macrophage iron metabolism holds significant guiding implications for exploring potential therapeutic strategies against AS. In this comprehensive review, we elucidate the potential interplay among iron overload, inflammation, and lipid dysregulation, summarizing the potential mechanisms underlying the suppression of AS by alleviating iron overload. Furthermore, the application of Traditional Chinese Medicine (TCM) is increasingly widespread. Based on extant research and the pharmacological foundations of active compounds of TCM, we propose alternative therapeutic agents for AS in the context of iron overload, aiming to diversify the therapeutic avenues.


Asunto(s)
Aterosclerosis , Sobrecarga de Hierro , Estrés Oxidativo , Estrés Oxidativo/efectos de los fármacos , Humanos , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/metabolismo , Sobrecarga de Hierro/tratamiento farmacológico , Sobrecarga de Hierro/metabolismo , Animales , Especies Reactivas de Oxígeno/metabolismo , Ferroptosis/efectos de los fármacos , Hierro/metabolismo , Productos Biológicos/farmacología , Productos Biológicos/uso terapéutico , Medicina Tradicional China/métodos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo
17.
J Trace Elem Med Biol ; 85: 127496, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39032317

RESUMEN

BACKGROUND: The essential mineral elements play important roles in proper growth, development and maintenance of physiological homeostasis of an organism. Women are at greater risk of mineral deficiency during pregnancy. However, the predictors of mineral element levels in pregnant women remain unclear. This study was conducted to determine the urinary levels of calcium (Ca), iron (Fe), copper (Cu), manganese (Mn) and selenium (Se) in women during early pregnancy and to explore the predictors of urinary exposure to each mineral element and high co-exposure to mineral element mixture. METHODS: 298 pregnant women in first trimester were recruited when they attended antenatal care in a hospital in Jinan, Shandong Province, China. We collected their spot urine samples and questionnaire data on their sociodemographic characteristics, lifestyle habits, food and dietary supplement intake, and residential environment. The concentrations of Ca, Fe, Cu, Mn and Se in all urine samples were measured. LASSO regression, multiple linear regression and binary logistic regression were used to analyze the predictors affecting mineral element levels. RESULTS: The geometric means of creatinine-corrected Ca, Fe, Cu, Mn and Se concentrations were 99.37 mg/g, 1.75 µg/g, 8.97 µg/g, 0.16 µg/g and 16.83 µg/g creatinine, respectively. Factors that influenced the concentrations of individual mineral element were as follows: (1) Se and Ca concentrations increased with maternal age; (2) women taking tap water as family drinking water had higher Ca levels and those taking polyunsaturated fatty acids intermittently had higher Cu levels; (3) Fe was adversely related to consumption frequency of barbecued foods; (4) Pregnant women with more frequent consumption of shellfish/shrimp/crab and living near green spaces or parks had higher Mn exposure, and those with higher frequency of meat consumption had lower Mn exposure. In addition, maternal age and the frequency of egg consumption were associated with odds of exposure to a mixture of high Ca, Fe, Cu and Se. CONCLUSIONS: The pregnant women in this study had comparable concentrations of urinary Cu and Se but lower concentrations of Ca, Fe and Mn compared with those in other areas. Predictors of urinary mineral elements included maternal age (Se and Ca), type of domestic drinking water (Ca), consumption frequency of barbecued food (Fe), polyunsaturated fatty acid use (Cu), the presence of urban green spaces or parks near the home and frequency of meat and shellfish/shrimp/crab intake (Mn). Moreover, maternal age and egg consumption frequency were significant predictors of high-level co-exposure to urinary Ca, Fe, Cu and Se.


Asunto(s)
Oligoelementos , Humanos , Femenino , China , Embarazo , Adulto , Oligoelementos/orina , Minerales/orina , Adulto Joven , Calcio/orina , Manganeso/orina , Cobre/orina , Hierro/orina , Selenio/orina
18.
Phytomedicine ; 132: 155795, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38878524

RESUMEN

BACKGROUND: PRM1201 is a traditional medicine with beneficial effects against colorectal cancer (CRC) metastasis. However, the underlying mechanism of this action remains to be determined. HYPOTHESIS: Remodeling microbiota and short-chain fatty acids (SCFAs) metabolism might be a potential mechanism to explain the anti-metastatic action of PRM1201, as this gut-microbiota dependent effect involves downregulation of histone deacetylation and EMT. METHODS: To investigate this possibility, clinical specimens were sequenced and the correlation between the anti-metastatic efficacy of PRM1201 and the restoration of SCFA-producing bacteria was studied. To obtain solid causal evidence, a mouse metastasis model was established to detect the influence of PRM1201 on cancer metastasis. Specifically, 16S amplicon sequencing, ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis, and bacterial manipulation were used to examine the gut microbiota-driven anti-metastatic action of PRM1201. RESULTS: Clinical data showed that PRM1201 increased both the number of SCFA-producing bacteria and generation of SCFAs in the feces of CRC patients. A positive correlation between the anti-metastatic efficacy of PRM1201 and the restoration of SCFAs observed. The animal experiments demonstrated that PRM1201 effectively blocked CRC metastasis in a dose-dependent manner. PRM1201 treatment modulated the composition of gut microbiota, and promoted the proliferation of beneficial SCFAs producers such as Akkermansia, Lachnospiraceae_NK4A136_group and Blautia, while simultaneously reducing the abundance of pathogenic bacteria like Escherichia-Shigella. In addition, PRM1201 led to augmentation of SCFAs content. Further results indicated that the anti-cancer metastatic mechanism of PRM1201 was linked to inhibition of histone deacetylation and suppression of epithelial-to-mesenchymal transition (EMT) in metastatic lesions. Microbiota depletion treatment and fecal microbiota transplantation (FMT) underscored the microbiota-dependent nature of this phenomenon. Moreover, this anti-colorectal cancer metastatic effect and mechanism of total SCFAs and single SCFA were also confirmed. CONCLUSION: In summary, PRM1201 exerts its anti-metastatic effects by modulating SCFA-producing bacteria and enhancing the production of SCFAs. Furthermore, the prebiotic-like actions of PRM1201, along with the PRM1201-treated bacteria, function as inhibitors of histone deacetylases (DHACs) thereby effectively suppressing EMT events.


Asunto(s)
Neoplasias Colorrectales , Ácidos Grasos Volátiles , Microbioma Gastrointestinal , Microbioma Gastrointestinal/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Ácidos Grasos Volátiles/metabolismo , Ácidos Grasos Volátiles/farmacología , Animales , Humanos , Ratones , Masculino , Femenino , Metástasis de la Neoplasia , Ratones Endogámicos BALB C , Heces/microbiología , Persona de Mediana Edad , Espectrometría de Masas en Tándem , Transición Epitelial-Mesenquimal/efectos de los fármacos
19.
Mol Pharm ; 21(8): 3866-3879, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-38920116

RESUMEN

The continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evaded the efficacy of previously developed antibodies and vaccines, thus remaining a significant global public health threat. Therefore, it is imperative to develop additional antibodies that are capable of neutralizing emerging variants. Nanobodies, as the smallest functional single-domain antibodies, exhibit enhanced stability and penetration ability, enabling them to recognize numerous concealed epitopes that are inaccessible to conventional antibodies. Herein, we constructed an immune library based on the immunization of alpaca with the S1 subunit of the SARS-CoV-2 spike protein, from which two nanobodies, Nb1 and Nb2, were selected using phage display technology for further characterization. Both nanobodies, with the binding residues residing within the receptor-binding domain (RBD) region of the spike, exhibited high affinity toward the S1 subunit. Moreover, they displayed cross-neutralizing activity against both wild-type SARS-CoV-2 and 10 ο variants, including BA.1, BA.2, BA.3, BA.5, BA.2.75, BF.7, BQ.1, EG.5.1, XBB.1.5, and JN.1. Molecular modeling and dynamics simulations predicted that both nanobodies interacted with the viral RBD through their complementarity determining region 1 (CDR1) and CDR2. These two nanobodies are novel tools for the development of therapeutic and diagnostic countermeasures targeting SARS-CoV-2 variants and potentially emerging coronaviruses.


Asunto(s)
Anticuerpos Neutralizantes , COVID-19 , SARS-CoV-2 , Anticuerpos de Dominio Único , Glicoproteína de la Espiga del Coronavirus , Anticuerpos de Dominio Único/inmunología , SARS-CoV-2/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/química , Animales , COVID-19/inmunología , COVID-19/terapia , COVID-19/virología , COVID-19/diagnóstico , Humanos , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Camélidos del Nuevo Mundo/inmunología , Epítopos/inmunología
20.
J Med Internet Res ; 26: e45719, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38718388

RESUMEN

BACKGROUND: International health policies and researchers have emphasized the value of evaluating patient-reported outcomes (PROs) in clinical studies. However, the characteristics of PROs in adult tumor clinical trials in China remain insufficiently elucidated. OBJECTIVE: This study aims to assess the application and characteristics of PRO instruments as primary or secondary outcomes in adult randomized clinical trials related to tumors in China. METHODS: This cross-sectional study identified tumor-focused randomized clinical trials conducted in China between January 1, 2010, and June 30, 2022. The ClinicalTrials.gov database and the Chinese Clinical Trial Registry were selected as the databases. Trials were classified into four groups based on the use of PRO instruments: (1) trials listing PRO instruments as primary outcomes, (2) trials listing PRO instruments as secondary outcomes, (3) trials listing PRO instruments as coprimary outcomes, and (4) trials without any mention of PRO instruments. Pertinent data, including study phase, settings, geographic regions, centers, participant demographics (age and sex), funding sources, intervention types, target diseases, and the names of PRO instruments, were extracted from these trials. The target diseases involved in the trials were grouped according to the American Joint Committee on Cancer Staging Manual, 8th Edition. RESULTS: Among the 6445 trials examined, 2390 (37.08%) incorporated PRO instruments as part of their outcomes. Within this subset, 26.82% (641/2390) listed PRO instruments as primary outcomes, 52.72% (1260/2390) as secondary outcomes, and 20.46% (489/2390) as coprimary outcomes. Among the 2,155,306 participants included in these trials, PRO instruments were used to collect data from 613,648 (28.47%) patients as primary or secondary outcomes and from 74,287 (3.45%) patients as coprimary outcomes. The most common conditions explicitly using specified PRO instruments included thorax tumors (217/1280, 16.95%), breast tumors (176/1280, 13.75%), and lower gastrointestinal tract tumors (173/1280, 13.52%). Frequently used PRO instruments included the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire-30, the visual analog scale, the numeric rating scale, the Traditional Chinese Medicine Symptom Scale, and the Pittsburgh Sleep Quality Index. CONCLUSIONS: Over recent years, the incorporation of PROs has demonstrated an upward trajectory in adult randomized clinical trials on tumors in China. Nonetheless, the infrequent measurement of the patient's voice remains noteworthy. Disease-specific PRO instruments should be more effectively incorporated into various tumor disease categories in clinical trials, and there is room for improvement in the inclusion of PRO instruments as clinical trial end points.


Asunto(s)
Neoplasias , Medición de Resultados Informados por el Paciente , Humanos , Estudios Transversales , China , Neoplasias/terapia , Adulto , Femenino , Masculino , Ensayos Clínicos Controlados Aleatorios como Asunto , Persona de Mediana Edad , Ensayos Clínicos como Asunto
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