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1.
Zhen Ci Yan Jiu ; 49(4): 358-366, 2024 Apr 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38649203

RESUMO

OBJECTIVES: To analyze the effects of electroacupuncture (EA) at "Fenglong" (ST40) and "Zusanli" (ST36) of different intensities and durations on rats with non-alcoholic fatty liver disease (NAFLD) based on the protein kinase R-like endoplasmic reticulum kinase (PERK)-activating transcription factor 4 (ATF4)-C/EBP homologous protein (CHOP) signaling pathway, so as to explore its mechanism underlying improvement of NAFLD. METHODS: SD rats were randomly divided into normal diet group, high-fat model group, sham EA group, strong stimulation EA (SEA) group, and weak stimulation EA (WEA) group, with 15 rats in each group. Each group was further divided into 2, 3, and 4-week subgroups. NAFLD rat model was established by feeding a high-fat diet. After successful modeling, rats in the SEA and WEA groups received EA at bilateral ST40 and ST36 with dense and sparse waves (4 Hz/20 Hz) at current intensities of 4 mA (SEA group) and 2 mA (WEA group), lasting for 20 minutes, once a day, 5 days a week with 2 days of rest. The sham EA group only had the EA apparatus connected without electricity. Different duration subgroups were intervened for 2, 3, and 4 weeks. After the intervention, the contents of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in rats were detected by an automatic biochemical analyzer;liver morphological changes were observed by Oil Red O staining;real-time fluorescence quantitative PCR and Western blot were used to detect the expression of PERK, ATF4, and CHOP mRNAs and proteins in the rat liver tissue. RESULTS: In the high-fat model group, there was a significant accumulation of red lipid droplets in the liver cells, which was reduced significantly in the SEA group at the 4th week. Compared with the normal diet group with the same treatment duration, the contents of serum ALT, AST, and the expression of PERK, ATF4, and CHOP mRNAs and proteins in the liver tissue were elevated (P<0.01) in the high-fat model group . Compared with the high-fat model group with the same treatment duration, the contents of serum ALT, AST, and the expression of PERK, ATF4, CHOP mRNAs and proteins in the liver tissue were decreased (P<0.01, P<0.05) in the SEA and WEA groups. Compared with the sham EA group with the same treatment duration, the contents of serum ALT, AST, and the expression of PERK, ATF4, and CHOP mRNAs were decreased (P<0.01, P<0.05) in the SEA and WEA groups, the expression of PERK, ATF4, and CHOP proteins in the liver tissue was decreased (P<0.01) in the SEA group at the 2nd, 3rd, and 4th week, the expression of PERK and CHOP proteins at the 2nd, 3rd, 4th week and ATF4 protein at 2nd week in the liver tissue were decreased (P<0.01, P<0.05) in the WEA group. Compared with the SEA group with the same treatment duration, the contents of serum ALT, AST, and the expression of PERK, ATF4, and CHOP mRNAs and proteins in the liver tissue were elevated (P<0.05, P<0.01) in the WEA group. Compared with the 2-week time point within the groups, the contents of serum ALT, AST, and the expression of PERK, ATF4, and CHOP mRNAs and PERK proteins in the liver tissue were decreased (P<0.01, P<0.05) in the SEA and WEA groups at 3rd and 4th week, the expression of ATF4 proteins in the liver tissue was decreased (P<0.01) in the SEA group at 3rd and 4th week, and the expression of CHOP proteins in the liver tissue was decreased (P<0.01) in the SEA group at 4th week and in the WEA group at 3rd and 4th week. Compared with the 3-week time point within the groups, the contents of serum ALT, AST, and the expression of PERK, ATF4, and CHOP mRNAs were significantly decreased (P<0.05, P<0.01) in the SEA and WEA groups at 4th week, the expression of PERK and CHOP proteins in the liver tissue was decreased (P<0.01) in the SEA and WEA groups at 4th week, and the expression of ATF4 protein in the liver tissue was decreased (P<0.05) in the SEA group at 4th week. CONCLUSIONS: EA at ST40 and ST36 can significantly improve liver function in NAFLD rats, and its mechanism of action may involve inhibiting PERK expression thereby targeting the downstream ATF4/CHOP signaling pathway to suppress endoplasmic reticulum stress, exerting a liver protective effect;the optimal effect was observed with EA intensity of 4 mA for 4 weeks.


Assuntos
Fator 4 Ativador da Transcrição , Pontos de Acupuntura , Eletroacupuntura , Fígado , Hepatopatia Gordurosa não Alcoólica , Ratos Sprague-Dawley , Transdução de Sinais , Fator de Transcrição CHOP , eIF-2 Quinase , Animais , Ratos , Fator 4 Ativador da Transcrição/metabolismo , Fator 4 Ativador da Transcrição/genética , eIF-2 Quinase/metabolismo , eIF-2 Quinase/genética , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/terapia , Hepatopatia Gordurosa não Alcoólica/genética , Fator de Transcrição CHOP/metabolismo , Fator de Transcrição CHOP/genética
2.
Fitoterapia ; 175: 105960, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38621426

RESUMO

Five undescribed eremophilane-type sesquiterpenes, remophilanetriols E-I (1-5), along with seven known compounds (6-12) were isolated from the fresh roots of Rehmannia glutinosa. Their structures were characterized by extensive spectroscopic data analysis and their absolute configurations were determined by comparing their calculated electronic circular dichroism (ECD) spectra and experimental ECD spectra. The anti-pulmonary fibrosis activities of all compounds were evaluated in vitro by MTT methods, and compounds 2, 8, 10, and 12 exhibited excellent anti-pulmonary fibrosis activities. In addition, compound 2 can reduce the levels of ROS and apoptosis in TGF-ß1-induced BEAS-2B cells.


Assuntos
Compostos Fitoquímicos , Raízes de Plantas , Rehmannia , Raízes de Plantas/química , Estrutura Molecular , Rehmannia/química , Humanos , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Sesquiterpenos/farmacologia , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/química , Apoptose/efeitos dos fármacos , Linhagem Celular , Espécies Reativas de Oxigênio/metabolismo , China , Sesquiterpenos Policíclicos/farmacologia , Sesquiterpenos Policíclicos/isolamento & purificação , Sesquiterpenos Policíclicos/química
3.
Fitoterapia ; 175: 105970, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38653340

RESUMO

Eleven new highly oxygenated eremophilane-type sesquiterpenoids were isolated from the whole plant of Synotis solidaginea, including two pairs of C-8 S/R epimers. The structures of the new compounds were elucidated on the basis of detailed spectroscopic analysis and the absolute configurations of 1 and 9 were confirmed by single-crystal X-ray crystallography using Cu Kα radiation. All the isolates were tested for the inhibition of LPS-stimulated NO production in macrophage-like mouse monocytic leukemia RAW264.7 cells. Compound 1 exhibited weak inhibitory effects with an IC50 of 71.2 µM.


Assuntos
Óxido Nítrico , Compostos Fitoquímicos , Sesquiterpenos , Camundongos , Animais , Células RAW 264.7 , Estrutura Molecular , Óxido Nítrico/metabolismo , Sesquiterpenos/farmacologia , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/química , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , China , Sesquiterpenos Policíclicos/farmacologia , Sesquiterpenos Policíclicos/isolamento & purificação
4.
PLoS One ; 19(4): e0297839, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38603736

RESUMO

Herbal medicine is popularly used among patients who suffer from allergic rhinitis. This systematic review and meta-analysis was conducted to evaluate the efficacy and safety of single medicinal plants in the management of allergic rhinitis. We searched MEDLINE, CENTRAL, and Web of Science for randomised controlled trials which evaluated the use of single medicinal plant for allergic rhinitis among adults and children. Twenty-nine randomised controlled trials (n = 1879) were eligible while 27 (n = 1769) contributed data for meta-analyses. Most studies (studies = 20) compared medicinal plants against placebo and Petasites hybridus was most frequently investigated (studies = 5). Very-low-to-low-certainty evidence suggests that compared to placebo, single medicinal plants may improve overall total nasal symptoms (SMD -0.31, 95% CI -0.59 to -0.02; participants = 249; studies = 5; I2 = 21%) especially nasal congestion and sneezing; and rhinoconjunctivitis quality of life (RQLQ) scores (MD -0.46, 95% CI -0.84 to -0.07; participants = 148; studies = 3; I2 = 0%). Moderate-certainty evidence show no clear differences between single medicinal plants and antihistamine in overall symptoms (Total nasal symptoms: SMD -0.14, 95% CI -0.46 to 0.18; participants = 149; studies = 2; I2 = 0%). As adjunctive therapy, moderate-certainty evidence shows that medicinal plants improved SNOT-22 scores when given as intranasal treatment (MD -7.47, 95% CI -10.75 to -4.18; participants = 124; studies = 2; I2 = 21%). Risk of bias domains were low or not clearly reported in most studies while heterogeneity was substantial in most pooled outcomes. Route of administration and age were identified to be plausible source of heterogeneity for certain outcomes. Medicinal plants appear to be well tolerated up to 8 weeks of use. Clear beneficial evidence of medicinal plants for allergic rhinitis is still lacking. There is a need for improved reporting of herbal trials to allow for critical assessment of the effects of each individual medicinal plant preparation in well-designed future clinical studies.


Assuntos
Plantas Medicinais , Rinite Alérgica , Humanos , Plantas Medicinais/química , Rinite Alérgica/tratamento farmacológico , Qualidade de Vida , Fitoterapia/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Exp Ther Med ; 27(4): 140, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38476915

RESUMO

Urinary tract infections (UTIs) are prevalent and recurrent bacterial infections that affect individuals worldwide, posing a significant burden on healthcare systems. The present study aimed to explore the epidemiology of UTIs, investigating the seasonal, gender-specific and age-related bacterial pathogen distribution to guide clinical diagnosis. Data were retrospectively collected from electronic medical records and laboratory reports of 926 UTIs diagnosed in Fuding Hospital (Fujian University of Traditional Chinese Medicine, Fuding, China). Bacterial isolates were identified using standard microbiological techniques. χ2 tests were performed to assess associations between pathogens and the seasons, sex and age groups. Significant associations were found between bacterial species and seasons. Enterococcus faecium exhibited a substantial prevalence in spring (χ2, 12.824; P=0.005), while Acinetobacter baumannii demonstrated increased prevalence in autumn (χ2, 16.404; P=0.001). Female patients showed a higher incidence of UTIs. Gram-positive bacteria were more prevalent in males, with Staphylococcus aureus showing significant male predominance (χ2, 14.607; P<0.001). E. faecium displayed an age-related increase in prevalence (χ2, 17.775; P<0.001), whereas Escherichia coli tended to be more prevalent in younger patients (χ2, 12.813; P=0.005). These findings highlight the complex nature of UTIs and offer insights for tailored diagnostic and preventive strategies, potentially enhancing healthcare outcomes.

6.
Purinergic Signal ; 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38467962

RESUMO

Dry eye (DE) is a prevalent ocular surface disease in patients with type 2 diabetes (T2DM). However, current medications are ineffective against decreased sensation on the ocular surface. While electroacupuncture (EA) effectively alleviates decreased sensation on ocular surface of DE in patients with T2DM, the neuroprotective mechanism remains unclear. This study explored the pathogenesis and therapeutic targets of T2DM-associated DE through bioinformatics analysis. It further investigated the underlying mechanism by which EA improves decreased sensation on the ocular surface of DE in rats with T2DM. Bioinformatic analysis was applied to annotate the potential pathogenesis of T2DM DE. T2DM and DE was induced in male rats. Following treatment with EA and fluorometholone, comprehensive metrics were assessed. Additionally, the expression patterns of key markers were studied. Key targets such as NLRP3, Caspase-1, and NOD-like receptor signaling may be involved in the pathogenesis of T2DM DE. EA treatment improved ocular measures. Furthermore, EA potently downregulated P2X7R, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-1 expression within the trigeminal ganglion and spinal trigeminal nucleus caudalis. Targeted P2X7R antagonist (A-438079) and agonist (BzATP) employed as controls to decipher the biochemistry of the therapeutic effects of EA showed an anti-inflammatory effect with A-438079, while BzATP blocked the anti-inflammatory effect of EA. EA relieved DE symptoms and attenuated inflammatory damage to sensory nerve pathways in T2DM rats with DE. These findings suggest a crucial role of EA inhibition of the P2X7R-NLRP3 inflammatory cascade to provide these benefits.

7.
J Prim Health Care ; 16(1): 112-114, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38546784
8.
Artigo em Inglês | MEDLINE | ID: mdl-38442634

RESUMO

In this work, a high-speed shear extraction off-line coupling high-speed countercurrent chromatography method was developed to separate maslinic acid and oleanolic acid from olive pomace. To improve extraction efficiency, the polar disparity between maslinic acid and oleanolic acid necessitated the concurrent utilization of both polar and non-polar solvents during high-speed shear extraction. Then, the high-speed shear extraction was directly feed to high-speed countercurrent chromatography for subsequently separation. A total of 250 min were needed to complete the extraction and separation process. This yielded two molecules from 3.3 g of defatted olive pomace: 7.2 mg of 93.8 % pure maslinic acid and 2.3 mg of 90.1 % pure oleanolic acid, both determined by HPLC at 210 nm. Furthermore, the compounds exhibited inhibitory activity against Escherichia coli and Staphylococcus aureus. At a concentration of 100 µg/mL, its efficacy in inhibiting hyaluronidase was comparable to that of the standard drug indomethacin. Compared with the conventional separation method, this coupled technique reduced the whole time due to the direct injection of sample extraction solution. This technique provides a useful approach for the separation of natural products with significant polarity differences.


Assuntos
Olea , Ácido Oleanólico , Ácido Oleanólico/análogos & derivados , Triterpenos , Ácido Oleanólico/análise , Olea/química , Distribuição Contracorrente , Antibacterianos/farmacologia , Triterpenos/química , Cromatografia Líquida de Alta Pressão , Extratos Vegetais/farmacologia , Extratos Vegetais/análise
9.
Fitoterapia ; 175: 105908, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38479621

RESUMO

Three undescribed sesquiterpenes, designed as pichinenoid A-C (1-3), along with nine known ones (4-12) were isolated from the stems and leaves of Picrasma chinensis. The new isolates including their absolute configurations were elucidated based on extensive spectroscopic methods, single crystal X-ray diffraction, and electronic circular dichroism (ECD) experiments, as well as comparison with literature data. Structurally, compounds 1 and 2 are descending sesquiterpenes, while pichinenoid C (3) is a rare sesquiterpene bearing a 2-methylenebut-3-enoic acid moiety at the C-6 side chain. All the isolated compounds were tested for their neuroprotective effects against the H2O2-induced damage on human neuroblastoma SH-SY5Y cells, and most of them showed moderate neuroprotective activity. Especially, compounds 1, 3-5, and 7 showed a potent neuroprotective effect at 25 or 50 µM. Moreover, the neuroprotective effects of compounds 1 and 4 were tested on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model. Results of western blot and immunofluorescence indicated that compound 4 significantly counteract the toxicity of MPTP, and reversed the expression of tyrosine hydroxylase (TH) in substantia nigra (SN) and striatum (ST) of the mouse brain. Interestingly, western blot data suggested compound 4 also enhanced B-cell lymphoma-2 (Bcl-2) and heme oxygenase 1 (HO-1) expressions in the brain tissues from MPTP damaged mouse.


Assuntos
Fármacos Neuroprotetores , Picrasma , Folhas de Planta , Caules de Planta , Sesquiterpenos , Animais , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/isolamento & purificação , Sesquiterpenos/farmacologia , Sesquiterpenos/isolamento & purificação , Camundongos , Humanos , Linhagem Celular Tumoral , Estrutura Molecular , Picrasma/química , Caules de Planta/química , Folhas de Planta/química , Masculino , Heme Oxigenase-1/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , China , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Camundongos Endogâmicos C57BL
10.
Zhongguo Zhong Yao Za Zhi ; 49(1): 70-79, 2024 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-38403340

RESUMO

Flavonoid C-glycosides are a class of natural products that are widely involved in plant defense responses and have diverse pharmacological activities. They are also important active ingredients of Dendrobium huoshanense. Flavanone synthase Ⅱ has been proven to be a key enzyme in the synthesis pathway of flavonoid C-glycosides in plants, and their catalytic product 2-hydroxyflavanone is the precursor compound for the synthesis of various reported flavonoid C-glycosides. In this study, based on the reported amino acid sequence of flavanone synthase Ⅱ, a flavanone synthase Ⅱ gene(DhuFNSⅡ) was screened and verified from the constructed D. huoshanense genome localization database. Functional validation of the enzyme showed that it could in vitro catalyze naringenin and pinocembrin to produce apigenin and chrysin, respectively. The open reading frame(ORF) of DhuFNSⅡ was 1 644 bp in length, encoding 547 amino acids. Subcellular localization showed that the protein was localized on the endoplasmic reticulum. RT-qPCR results showed that DhuFNSⅡ had the highest expression in stems, followed by leaves and roots. The expression levels of DhuFNSⅡ and other target genes in various tissues of D. huoshanense were significantly up-regulated after four kinds of abiotic stresses commonly encountered in the growth process, but the extent of up-regulation varied among treatment groups, with drought and cold stress having more significant effects on gene expression levels. Through the identification and functional analysis of DhuFNSⅡ, this study is expected to contribute to the elucidation of the molecular mechanism of the formation of quality metabolites of D. huoshanense, flavonoid C-glycosides, and provide a reference for its quality formation and scientific cultivation.


Assuntos
Dendrobium , Flavanonas , Dendrobium/genética , Dendrobium/química , Flavanonas/metabolismo , Flavonoides , Clonagem Molecular , Glicosídeos/metabolismo
11.
Zhongguo Zhong Yao Za Zhi ; 49(1): 175-184, 2024 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-38403350

RESUMO

The occurrence and development of tumors are associated with the cell energy metabolism. Inhibiting energy metabolism of lung cancer cells is an important strategy to overcome drug resistance. Based on the cellular energy metabolism pathway, this study observed the effect of combination of shikonin(SKN) and gefitinib(GFB) on the drug resistance in non-small cell lung cancer and explored the underlying mechanism. The human non-small cell lung cancer line HCC827/GR resistant to gefitinib was used as the cell model in vitro. The CCK-8 assay and flow cytometry were employed to investigate the cell viability and apoptosis, respectively. The high performance liquid chromatography was employed to measure the intracellular accumulation of GFB. A Seahorse XFe96 Analyzer was used to detect the changes of cellular energy metabolism. Western blot was employed to determine the expression of the proteins involved in the drug resistance. The tumor-bearing nude mouse model was used to verify the efficacy of SKN+GFB in overcoming drug resistance in vivo. The results showed that SKN+GFB significantly reduced the IC_(50) of GFB on HCC827/GR cells, with the combination index of 0.628, indicating that the combination of the two drugs had a synergistic effect and promoted cell apoptosis. SKN increased the intracellular accumulation of GFB. SKN+GFB lowered the oxygen consumption rate(OCR) and glycolytic proton efflux rate(GlycoPER) in cell energy metabolism, and down-regulated the overexpression of PKM2, p-EGFR, P-gp, and HIF-1α in drug resistance. The results of reversing drug resistance test in vivo showed that GFB or SKN alone had no significant antitumor effect, while the combination at different doses induced the apoptosis of the tumor tissue and inhibited the expression of PKM2 and P-gp, demonstrating a significant antitumor effect. Moreover, the tumor inhibition rate in the high-dose combination group reached 64.01%. In summary, SKN+GFB may interfere with the energy metabolism to limit the function of HCC827/GR cells, thus reversing the GFB resistance in non-small cell lung cancer.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Naftoquinonas , Animais , Camundongos , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Gefitinibe/farmacologia , Gefitinibe/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Quinazolinas/farmacologia , Resistencia a Medicamentos Antineoplásicos , Proliferação de Células , Linhagem Celular Tumoral , Apoptose
12.
Environ Sci Pollut Res Int ; 31(11): 17481-17493, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38342832

RESUMO

Excessive phosphorus will lead to eutrophication in aquatic environment; the efficient removal of phosphorus is crucial for wastewater engineering and surface water management. This study aimed to fabricate a nanorod-like sepiolite-supported MgO (S-MgO) nanocomposite with high specific surface area for efficient phosphate removal using a facile microwave-assisted method and calcining processes. The impact of solution pH, adsorbent dosage, contact time, initial phosphate concentrations, Ca2+ addition, and N/P ratio on the phosphate removal was extensively examined by the batch experiments. The findings demonstrated that the S-MgO nanocomposite exhibited effective removal performance for low-level phosphate (0 ~ 2.0 mM) within the pH range of 3.0 ~ 10.0. Additionally, the nanocomposite can synchronously remove phosphate and ammonium in high-level nutrient conditions (> 2.0 mM), with the maximum removal capacities of 188.49 mg P/g and 89.78 mg N/g. Quantitative and qualitative analyses confirmed the successful harvesting of struvite in effluent with high-phosphate concentrations, with the mechanisms involved attributed to a synergistic combination of sorption and struvite crystallization. Due to its proficient phosphate removal efficiency, cost-effectiveness, and substantial removal capacity, the developed S-MgO nanocomposite exhibits promising potential for application in phosphorus removal from aquatic environments.


Assuntos
Silicatos de Magnésio , Nanocompostos , Poluentes Químicos da Água , Fósforo/química , Estruvita/química , Óxido de Magnésio , Nitrogênio , Fosfatos/química
13.
Neuro Oncol ; 26(7): 1247-1261, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38366847

RESUMO

BACKGROUND: Precision treatment of glioblastoma is increasingly focused on molecular subtyping, with the mesenchymal subtype particularly resistant to temozolomide. Here, we aim to develop a targeted therapy for temozolomide resensitization in the mesenchymal subtype. METHODS: We integrated kinomic profiles and kinase inhibitor screens from patient-derived proneural and mesenchymal glioma-propagating cells and public clinical datasets to identify key protein kinases implicated in temozolomide resistance. RNAseq, apoptosis assays, and comet assays were used to examine the role of p38MAPK signaling and adaptive chemoresistance in mesenchymal cells. The efficacy of dual p38MAPK and MEK/ERK inhibition using ralimetinib (selective orally active p38MAPK inhibitor; phase I/II for glioblastoma) and binimetinib (approved MEK1/2 inhibitor for melanoma; phase II for high-grade glioma) in primary and recurrent mesenchymal tumors was evaluated using an intracranial patient-derived tumor xenograft model, focusing on survival analysis. RESULTS: Our transcriptomic-kinomic integrative analysis revealed p38MAPK as the prime target whose gene signature enables patient stratification based on their molecular subtypes and provides prognostic value. Repurposed p38MAPK inhibitors synergize favorably with temozolomide to promote intracellular retention of temozolomide and exacerbate DNA damage. Mesenchymal cells exhibit adaptive chemoresistance to p38MAPK inhibition through a pH-/calcium-mediated MEK/ERK pathway. Dual p38MAPK and MEK inhibition effectively maintain temozolomide sensitivity in primary and recurrent intracranial mesenchymal glioblastoma xenografts. CONCLUSIONS: Temozolomide resistance in mesenchymal glioblastoma is associated with p38MAPK activation. Adaptive chemoresistance in p38MAPK-resistant cells is mediated by MEK/ERK signaling. Adjuvant therapy with dual p38MAPK and MEK inhibition prolongs temozolomide sensitivity, which can be developed into a precision therapy for the mesenchymal subtype.


Assuntos
Neoplasias Encefálicas , Resistencia a Medicamentos Antineoplásicos , Glioblastoma , Temozolomida , Ensaios Antitumorais Modelo de Xenoenxerto , Proteínas Quinases p38 Ativadas por Mitógeno , Temozolomida/farmacologia , Humanos , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Glioblastoma/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Animais , Camundongos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Antineoplásicos Alquilantes/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Células Tumorais Cultivadas , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Prognóstico
14.
Zhen Ci Yan Jiu ; 49(2): 198-207, 2024 Feb 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38413042

RESUMO

OBJECTIVES: To explore the rules of acupoint selection in the treatment of neurogenic bladder (NB) with acupuncture and moxibustion by using data mining. METHODS: The clinical research literatures on acupuncture treatment of NB were collected from PubMed, Embase, Cochrane Library, CNKI, Wanfang Database, VIP Database and China Biology Medicine from retrieved to January 1, 2023. The acupoint prescription database was established using Excel 2019. SPSS Modeler 18.0 and SPSS Statistics 26.0 softwares were used to conduct the frequency, meri-dians, locations, specific acupoints analysis and association rules analysis, factor analysis, cluster analysis, etc., to explore the characteristics and rules of acupoint selection in acupuncture and moxibustion treatment of NB. RESULTS: Totally 313 papers were included, including 110 acupoints with a total frequency of 1 995. The high-frequency acupoints are Zhongji (CV3), Guanyuan (CV4), Sanyinjiao (SP6), etc. The commonly used meridians are the Bladder Meridian of Foot Taiyang and Conception Vessel. The involved acupoints are mostly located in the lumbosacral region and abdomen, and intersection acupoints, mu-front acupoints and back-shu acupoints are the majority in the specific acupoints. The core acupoints group was analyzed, and 17 groups of association rules, 7 factors and 6 effective cluster groups were obtained. CONCLUSIONS: Acupuncture and moxibustion treatment of NB follows the therapeutic principles of toni-fying the kidney, invigorating the spleen, and soothing the liver. The core acupoints group is CV3-CV4-SP6.


Assuntos
Pontos de Acupuntura , Terapia por Acupuntura , Mineração de Dados , Moxibustão , Bexiga Urinaria Neurogênica , Humanos , Bexiga Urinaria Neurogênica/terapia , Meridianos
15.
Chin J Integr Med ; 30(10): 949-960, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38329655

RESUMO

Acute myocardial infarction (AMI), characterized by high incidence and mortality rates, poses a significant public health threat. Reperfusion therapy, though the preferred treatment for AMI, often exacerbates cardiac damage, leading to myocardial ischemia/reperfusion injury (MI/RI). Consequently, the development of strategies to reduce MI/RI is an urgent priority in cardiovascular therapy. Chinese medicine, recognized for its multi-component, multi-pathway, and multi-target capabilities, provides a novel approach for alleviating MI/RI. A key area of interest is the nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. This pathway is instrumental in regulating inflammatory responses, oxidative stress, apoptosis, endoplasmic reticulum stress, and ferroptosis in MI/RI. This paper presents a comprehensive overview of the Nrf2/HO-1 signaling pathway's structure and its influence on MI/RI. Additionally, it reviews the latest research on leveraging Chinese medicine to modulate the Nrf2/HO-1 pathway in MI/RI treatment.


Assuntos
Heme Oxigenase-1 , Medicina Tradicional Chinesa , Traumatismo por Reperfusão Miocárdica , Fator 2 Relacionado a NF-E2 , Transdução de Sinais , Fator 2 Relacionado a NF-E2/metabolismo , Humanos , Transdução de Sinais/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Heme Oxigenase-1/metabolismo , Animais , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia
16.
Chin J Integr Med ; 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38212496

RESUMO

OBJECTIVE: To investigate the hemostatic effect of modified Sijunzi Granules (MSG) in primary immune thrombocytopenia (ITP) zebrafish model and explore the potential mechanism. METHODS: AB strain wild type zebrafish were treated with simvastatin (6 µmol/L) for 24 h to establish the hemorrhage model (model control group). The zebrafish were treated with MSG at different doses (55.6, 167, and 500 µg/mL), respectively. The hemostatic effect was assessed by examining the intestinal bleeding and hemostatic rate. 5-Hydroxytryptamine (5-HT) content was determined using enzyme-linked immunosorbent assay (ELISA) assay. The expressions of 5-HT2aR, 5-HT2bR, and SERT genes were detected by quantitative real-time polymerase chain reaction(PCR). The protein expressions of protein kinase B (Akt), p-Akt, extracellular regulated protein kinases (Erk), and p-Erk were examined using Western blot analysis. RESULTS: The intestinal bleeding rate was 37%, 40%, and 80% in the 55.6, 167, and 500 µg/mL dose of MSG, respectively, in which 55.6 and 167 µg/mL MSG dose groups were associated with significantly decreased intestinal bleeding rate when compared with the model control group (70%, P<0.05). Significantly higher hemostatic rates were also observed in the 55.6 (54%) and 167 (52%) µg/mL MSG dose groups (P<0.05). MSG increased the 5-HT content and mRNA expression levels of 5-HT2aR, 5-HT2bR, and SERT (P<0.05). In addition, caspase3/7 activity was inhibited (P<0.05). Significant increase in p-Akt and p-Erk was also detected after treatment with MSG (P<0.05). CONCLUSIONS: MSG could reduce the incidence and severity of intestinal bleeding in zebrafish by activating MAPK/Erk and PI3K/Akt signal pathways through regulating the levels of 5-HT and its receptors, which may provide evidence for the treatment of ITP.

17.
Int J Biol Macromol ; 260(Pt 1): 129427, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38219932

RESUMO

Current plant-based foods use plant proteins as a key structuring and texturing ingredient. The use of water for extraction can replace conventional protein extraction methods. Water extraction of protein is environmentally friendly and could prevent the loss of protein functionality due to extreme pH changes. This study demonstrates an aqueous extraction method, coupled with ultrasound as pre-treatment, to obtain buckwheat protein (BWPE) and assess its gelling property and composited gel with kappa-carrageenan (k-carr). Textural and rheological analyses showed that the hardness and storage modulus of the composited gel containing 1 % w/w BWPE and 1 % w/w k-carr was 4.2-fold and 100-fold, respectively, higher than k-carr gel at 1 % w/w. Light microscopy showed a mixed bi-continuous gel system, with k-carr reinforcing the protein gel network. Besides volume exclusion effects, chemical bond and FTIR analyses revealed that adding k-carr to BWPE altered the protein's secondary structure and mediated protein denaturation during heating. This results in greater ß-sheet content, which creates a more organised gel structure. These results demonstrated that ultrasound-assisted water-extracted BWPE, together with varying concentrations of k-carr, can be used to develop composited gels of tailorable textural and rheological properties to suit different food applications.


Assuntos
Produtos Biológicos , Fagopyrum , Carragenina/química , Géis/química , Reologia , Água
18.
Planta Med ; 90(3): 204-218, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38035621

RESUMO

Zingiber zerumbet, a plant native to tropical and subtropical Asia, has a vast range of traditional uses and has been continuously studied for its medicinal properties. However, a systematic methodological approach in evidence synthesis on the plant's efficacy is lacking, and there is a need to elicit the current research status of this plant. This scoping review was conducted to systematically explore and collate the available scientific evidence on the efficacy of Z. zerumbet and its main phytoconstituents in various formulations, their biological mechanisms, and their safety. Results included 54 articles consisting of animal studies, while there were no published human studies. Only half of the included studies provided adequate reporting on the quality-related details of Z. zerumbet formulations. Identified pharmacological activities were analgesic, anti-inflammatory, anti-diabetic, anti-hyperlipidemic, anti-neoplastic, immunomodulatory, antioxidant, antipyretic, hepatoprotective, nephroprotective, gastroprotective, and locomotor-reducing activities. Notably, the ethanolic extract of Z. zerumbet was found to be well tolerated for up to 28 days. In conclusion, Z. zerumbet and zerumbone have various pharmacological effects, especially in analgesic and anti-inflammatory models. However, there is still a pressing need for comprehensive safety data to conduct clinical trials.


Assuntos
Extratos Vegetais , Zingiberaceae , Animais , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Antioxidantes/farmacologia , Anti-Inflamatórios/farmacologia , Analgésicos/farmacologia
19.
Artigo em Chinês | WPRIM | ID: wpr-1018395

RESUMO

Objective To investigate the efficacy of Fuzheng Hejie Prescription(composed of Scutellariae Radix,Lonicerae Japonicae Flos,Agastachis Herba,Bupleuri Radix,Atractylodis Rhizoma,Glycyrrhizae Radix et Rhizoma,etc.)in the treatment of respiratory viral infections in children and to observe its effect on inflammatory factors and immune function.Methods A total of 203 children with respiratory viral infection of H1N1 virus were randomly divided into 101 cases in the observation group and 102 cases in the control group.Both groups were given the routine treatment for subsiding fever,maintaining water-electrolyte balance,and ensuring enough sleep.And additionally,the control group was given Ribavirin Granules and Ibuprofen Granules,and the observation group was given Fuzheng Hejie Prescription based on the treatment for the control group.The course of treatment covered 7 days.The changes of traditional Chinese medicine(TCM)syndrome scores and the levels of immunological indicators and inflammatory factors in the two groups were observed before and after the treatment.Moreover,the clinical efficacy,symptom resolution time and the incidence of adverse reactions were compared between the two groups of children.Results(1)In the course of the trial,one case fell off in the observation group and 2 cases fell off in the control group,and eventually 100 children in each group were included in the trial.(2)After 7 days of treatment,the total effective rate of the observation group was 93.00%(93/100),and that of the control group was 88.00%(88/100),and the intergroup comparison showed that the therapeutic effect of the observation group was superior to that of the control group,but the difference was not statistically significant(χ2= 1.454,P = 0.228).(3)After treatment,the scores of primary symptoms and secondary symptoms as well as the total TCM syndrome scores in the two groups were decreased compared with those before treatment(P<0.05),and the decrease in the observation group was significantly superior to that in the control group(P<0.01).(4)After treatment,the time for the resolution of clinical symptoms such as fever,cough,expectoration and sore throat in the observation group was significantly shorter than that in the control group(P<0.01).(5)After treatment,the levels of immunological indicators of T lymphocyte subset CD3+ and CD4+ in the two groups were increased compared with those before treatment(P<0.05),and the levels of CD8+ and B cells were decreased compared with those before treatment(P<0.05).The intergroup comparison showed that the increase in the levels of CD3+ and CD4+ as well as the decrease in the levels of CD8+ and B cells of the observation group was significantly superior to that of the control group(P<0.01).(6)After treatment,the levels of inflammatory factors of serum amyloid A(SAA),C-reactive protein(CRP),serum tumor necrosis factor alpha(TNF-α),soluble interleukin 2 receptor(SIL-2R),and interleukin 6(IL-6)in the two groups were significantly decreased compared with those before treatment(P<0.05),and the levels of interleukin 2(IL-2)and interferon γ(IFN-γ)ls were all significantly increased compared with those before treatment(P<0.05).The intergroup comparison showed that the decrease of serum SAA,CRP,TNF-α,SIL-2R,and IL-6 levels and the increase of serum IL-2 and IFN-γ levels in the observation group were significantly superior to those in the control group(P<0.01).(7)The incidence of adverse reactions in the observation group was 2.00%(2/100),which was significantly lower than that of 8.00%(8/100)in the control group,but the difference was not statistically significant(χ2 = 3.789,P = 0.052).Conclusion Fuzheng Hejie Prescription exerts certain effect in treating children with respiratory viral infection of H1N1 virus,which can effectively decrease children's TCM syndrome scores,regulate the inflammatory response,improve the immune function,accelerate the relief of clinical symptoms and shorten the course of the disease.

20.
BMC Chem ; 17(1): 182, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38093361

RESUMO

Fraxinus hubeiensis is a plant endemic to China and widely used as folk medicine to treat various diseases. However, its chemical constituents have never been reported sufficiently. Thus, the primary objective of this study was to investigate the phytochemical constituents and biological activities of F. hubeiensis leaves. Hence, combined column chromatographic and spectroscopic techniques were used to identify and characterize the secondary metabolites such as a pair of 3-keto-glycoside epimers (1) and (2), along with five known compounds (3 ~ 7). The results of α-glucosidase inhibitory activity exhibited that 1 and 2 had moderate activity with IC50 values of 359.50 and 468.43 µM, respectively, compared to a positive control acarbose with the IC50 value of 164.08 µM. However, Compounds 1-6 were shown to be inactive against the tested microbes.

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