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1.
J Am Chem Soc ; 146(15): 10889-10898, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38584517

RESUMO

Full-color luminophores have advanced applications in materials and engineering, but constructing color-tunable clusteroluminescence (CL) from nonconjugated polymers based on through-space interactions remains a huge challenge. Herein, we develop phosphine-capped nonconjugated polyesters exhibiting blue-to-red CL (400-700 nm) based on phosphine-initiated copolymerization of epoxides and cyclic anhydrides, especially P1-0.5TPP, which exhibits red CL (610 nm) with a high quantum yield of 32%. Experiments and theoretical calculations disclose that the phosphine-capped effect in polyesters brings about conformational changes and induces phosphine-ester clusters by through-space (n,π*) interactions. Moreover, CL colors and efficiencies can be easily tailored by types of phosphines, compositions and structures of polyesters, and concentration. Significantly, the role of polymer motions (group, segmental, and chain motions) on CL originating from microregions inside polyesters is revealed. Further, phosphine-capped nonconjugated polyesters are demonstrated to be nonconjugated dyes and fluorescent fibers and are also used for multicolor light-emitting diodes including white light. This work not only provides an engineering strategy based on the end-group effect to prepare full-color clusteroluminogens but also broadens the prospects for material applications.

2.
Environ Sci Technol ; 58(9): 4127-4136, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38382014

RESUMO

Tetrabromobisphenol A-bis(2,3-dibromo-2-methylpropyl ether) (TBBPA-DBMPE) has come into use as an alternative to hexabromocyclododecane (HBCD), but it is unclear whether TBBPA-DBMPE has less hazard than HBCD. Here, we compared the bioaccumulation and male reproductive toxicity between TBBPA-DBMPE and HBCD in mice following long-term oral exposure after birth. We found that the concentrations of TBBPA-DBMPE in livers significantly increased with time, exhibiting a bioaccumulation potency not substantially different from HBCD. Lactational exposure to 1000 µg/kg/d TBBPA-DBMPE as well as 50 µg/kg/d HBCD inhibited testis development in suckling pups, and extended exposure up to adulthood resulted in significant molecular and cellular alterations in testes, with slighter effects of 50 µg/kg/d TBBPA-DBMPE. When exposure was extended to 8 month age, severe reproductive impairments including reduced sperm count, increased abnormal sperm, and subfertility occurred in all treated animals, although 50 µg/kg/d TBBPA-DBMPE exerted lower effects than 50 µg/kg/d HBCD. Altogether, all data led us to conclude that TBBPA-DBMPE exerted weaker male reproductive toxicity than HBCD at the same doses but exhibited bioaccumulation potential roughly equivalent to HBCD. Our study fills the data gap regarding the bioaccumulation and toxicity of TBBPA-DBMPE and raises concerns about its use as an alternative to HBCD.


Assuntos
Retardadores de Chama , Hidrocarbonetos Bromados , Bifenil Polibromatos , Masculino , Animais , Camundongos , Retardadores de Chama/toxicidade , Éter , Bioacumulação , Sêmen , Hidrocarbonetos Bromados/toxicidade , Bifenil Polibromatos/toxicidade , Éteres , Etil-Éteres
3.
Acta Pharmacol Sin ; 45(9): 1861-1878, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38719955

RESUMO

Pulmonary hypertension (PH) is a progressive fatal disease with no cure. Canagliflozin (CANA), a novel medication for diabetes, has been found to have remarkable cardiovascular benefits. However, few studies have addressed the effect and pharmacological mechanism of CANA in the treatment of PH. Therefore, our study aimed to investigate the effect and pharmacological mechanism of CANA in treating PH. First, CANA suppressed increased pulmonary artery pressure, right ventricular hypertrophy, and vascular remodeling in both mouse and rat PH models. Network pharmacology, transcriptomics, and biological results suggested that CANA could ameliorate PH by suppressing excessive oxidative stress and pulmonary artery smooth muscle cell proliferation partially through the activation of PPARγ. Further studies demonstrated that CANA inhibited phosphorylation of PPARγ at Ser225 (a novel serine phosphorylation site in PPARγ), thereby promoting the nuclear translocation of PPARγ and increasing its ability to resist oxidative stress and proliferation. Taken together, our study not only highlighted the potential pharmacological effect of CANA on PH but also revealed that CANA-induced inhibition of PPARγ Ser225 phosphorylation increases its capacity to counteract oxidative stress and inhibits proliferation. These findings may stimulate further research and encourage future clinical trials exploring the therapeutic potential of CANA in PH treatment.


Assuntos
Canagliflozina , Proliferação de Células , Hipertensão Pulmonar , Estresse Oxidativo , PPAR gama , Animais , Masculino , Camundongos , Ratos , Canagliflozina/farmacologia , Canagliflozina/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/metabolismo , Camundongos Endogâmicos C57BL , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , PPAR gama/metabolismo , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/metabolismo , Ratos Sprague-Dawley , Remodelação Vascular/efeitos dos fármacos , Serina/química , Serina/metabolismo
4.
Artigo em Inglês | MEDLINE | ID: mdl-38443260

RESUMO

INTRODUCTION: Flumatinib, a highly selective ABL kinase inhibitor, exhibits stronger inhibition of intracellular BCR-ABL tyrosine kinase activity, compared to Imatinib. However, there is limited research comparing the real-world efficacy and safety of flumatinib and dasatinib in patients with Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). OBJECTIVE: Investigating the differences in therapeutic efficacy and safety between flumatinib and dasatinib in combination with multi-drug chemotherapy for the treatment of newly diagnosed Ph+ ALL. METHOD: In this study, we assessed 43 patients with newly diagnosed Ph+ ALL (20 in the flumatinib group, 23 in the dasatinib group). RESULTS: There were no significant differences in gender, age, fusion gene type, initial blood routine, bone marrow blast cell ratio or chromosome karyotype between the two groups. Within 1 month, there were no significant differences in the complete response (CR), major molecular response (MMR) or minimal residual disease (MRD) negativity rate between the flumatinib and dasatinib groups. Similarly, within 3 months, there were no significant differences in CR or MMR rates between the two groups. However, the rates of complete molecular response (CMR) and MRD negativity within 3 months were significantly higher in the flumatinib group, compared to the dasatinib group (P < 0.05). Additionally, the flumatinib group exhibited fewer adverse reactions compared to the dasatinib group. CONCLUSION: These findings suggest that flumatinib is a safe and effective tyrosine kinase inhibitor (TKI) for achieving CMR and MRD negativity in patients with Ph+ ALL, as supported by this small series of patients.

5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(1): 14-19, 2024 Feb.
Artigo em Zh | MEDLINE | ID: mdl-38387893

RESUMO

OBJECTIVE: To explore the clinical efficacy and safety of flumatinib mesylate produced in China in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP). METHODS: 32 newly diagnosed CML-CP patients admitted to the Hematology Department of the Affiliated Hospital of Southwest Medical University from March 1, 2020 to March 31, 2022, who had never received any tyrosine kinase inhibitor (TKI) were included in the study. The patients were treated by flumatinib mesylate 600mg once daily. The hematologic, cytogenetic and molecular responses were assessed at 3-, 6- and 12-month, and adverse effects of the drug were evaluated. RESULTS: 31 patients were treated with flumatinib for≥3 months, of which 24 patients were treated for ≥6 months and 14 patients were treated for≥12 months. At 3rd month of treatment, 30 out of 31 patients achieved complete hematologic response (CHR); 24 patients underwent cytogenetic testing and 22 cases achieved major cytogenetic response(MCyR), of which 21 cases achieved complete cytogenetic response (CCyR); Among 25 patients who underwent molecular testing, 22 patients had BCR-ABLIS≤10%, including 10 patients with BCR-ABLIS≤0.1%, and 6 patients with BCR-ABLIS≤0.01%. At 6th month of treatment, 23 out of 24 patients achieved CHR; 17 patients underwent cytogenetic testing and all achieved CCyR; Among 23 patients who underwent molecular testing, 20 patients had BCR-ABLIS≤1%, including 16 patients with BCR-ABLIS≤0.1% and 12 patients with BCR-ABLIS≤0.01%. At 12nd month of treatment, all 14 patients achieved CHR and CCyR; Among them, 10 patients had BCR-ABLIS≤0.1%, including 9 patients with BCR-ABLIS≤0.01%. The grade Ⅲ/Ⅳ leukopenia, thrombocytopenia and anemia rates in the patients were 13.3%, 20.0% and 3.3%, respectively. One patient stopped flumatinib therapy due to severe and persistent hematologic toxicity. The major non-hematologic adverse events were abnormal liver function (20%), diarrhea (10%), bone/joint pain (10%), muscle spasm (10%), rash (6.7%), acute kidney injury (6.7%) and nausea(3.3%), most of which were grade I-II. No patient experienced grade Ⅳ non-hematologic adverse events. No drug toxicity-related death occurred. CONCLUSION: Flumatinib mesglate, as the first-line treatment for newly diagnosed CML-CP, can enable the patients to achieve early and deep molecular and cytogenetic responses, and shows good safety.


Assuntos
Anemia , Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Trombocitopenia , Humanos , Mesilato de Imatinib/uso terapêutico , Pirimidinas/farmacologia , Proteínas de Fusão bcr-abl , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Benzamidas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Resultado do Tratamento , Resposta Patológica Completa , Mesilatos/uso terapêutico , Antineoplásicos/uso terapêutico
6.
Chem Biol Interact ; 398: 111095, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38844256

RESUMO

It is established that organophosphorus pesticide (OPP) toxicity results from modification of amino acids in active sites of target proteins. OPPs can also modify unrelated target proteins such as histones and such covalent histone modifications can alter DNA-binding properties and lead to aberrant gene expression. In the present study, we report on non-enzymatic covalent modifications of calf thymus histones adducted to selected OPPs and organophosphate flame retardants (OPFRs) in vitro using a bottom-up proteomics method approach. Histones were not found to form detectable adducts with the two tested OPFRs but were avidly modified by a few of the seven OPPs that were tested in vitro. Dimethyl phosphate (or diethyl phosphate) adducts were identified on Tyr, Lys and Ser residues. Most of the dialkyl phosphate adducts were identified on Tyr residues. Methyl and ethyl modified histones were also detected. Eleven amino residues in histones showed non-enzymatic covalent methylation by exposure of dichlorvos and malathion. Our bottom-up proteomics approach showing histone-OPP adduct formation warrants future studies on the underlying mechanism of chronic illness from exposure to OPPs.


Assuntos
Histonas , Compostos Organofosforados , Praguicidas , Histonas/metabolismo , Histonas/química , Compostos Organofosforados/química , Compostos Organofosforados/metabolismo , Compostos Organofosforados/toxicidade , Animais , Praguicidas/química , Praguicidas/metabolismo , Praguicidas/toxicidade , Bovinos , Metilação , Malation/química , Malation/metabolismo , Malation/toxicidade , Proteômica , Retardadores de Chama/toxicidade , Retardadores de Chama/metabolismo , Sequência de Aminoácidos , Diclorvós/química , Diclorvós/toxicidade
7.
Ying Yong Sheng Tai Xue Bao ; 35(3): 606-614, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38646747

RESUMO

As the most senstitive plant organs to environmental changes, leaves serve as crucial indicators of plant survival strategies. We measured the morphology, anatomical traits, gas exchange parameters, and chlorophyll fluorescence parameters of Quercus aquifolioides (evergreen broad-leaved) and Sorbus rehderiana (deciduous broad-leaved) at altitudes of 2600, 2800, 3000, 3200 and 3400 m on the eastern edge of the Qinghai-Tibet Plateau, China. We explored the similarity and difference in their responses to altitude change and the ecological adaptation strategy. The results showed that as the altitude increased, leaf dry matter content of Q. aquifolioides decreased, that of S. rehderiana increased, leaf size for both species gradually decreased, and the palisade coefficient of Q. aquifolioides showed a decreasing trend, contrasting with the increasing trend in S. rehderiana. As the altitude increased, the thickness of leaves, palisade tissue, spongy tissue, upper epidermis, and lower epidermis of both species increased significantly, with the increment of 22.4%, 4.9%, 45.1%, 23.3%, 19.6%, and 28.2%, 46.9%, 8.9%, 25.9%, 20.8% at altitude of 3400 m, respectively, compared with the altitude of 2600 m. The gas exchange and chlorophyll fluorescence parameters of S. rehderiana significantly increased with increasing altitude, while Q. aquifolioides showed the opposite trend. Leaf anatomical traits, gas exchange, and chlorophyll fluorescence parameters of both species displayed considerable plasticity. There were significant correlations among most leaf traits and between leaf traits and altitude. The survival strategy of Q. aquifolioides was more conservative in response to altitude changes, while that of S. rehderiana was more active. Both species adapted to different altitudes by adjusting their own traits.


Assuntos
Altitude , Folhas de Planta , Quercus , Sorbus , Quercus/fisiologia , Quercus/crescimento & desenvolvimento , China , Ecossistema , Tibet , Adaptação Fisiológica
8.
Ying Yong Sheng Tai Xue Bao ; 35(4): 877-885, 2024 Apr 18.
Artigo em Zh | MEDLINE | ID: mdl-38884222

RESUMO

The natural abundance of stable carbon and nitrogen isotopes (δ13C and δ15N) in leaves can provide comprehensive information on the physiological and ecological processes of plants and has been widely used in ecological research. However, recent studies on leaf δ13C and δ15N have focused mainly on woody species, few studies have been conducted on herbs in different vegetation types, and their differences and driving factors are still unclear. In this study, we focused on the herbs in subalpine coniferous forests, alpine shrublands, and alpine mea-dows on the eastern Qinghai-Tibet Plateau, and investigated the differences in leaf δ13C and δ15N of herbs and the driving factors. The results showed that there were significant differences in leaf δ13C and δ15N values of herbs among different vegetation types, with the highest δ13C and δ15N values in alpine meadows, followed by alpine shrublands, and the lowest in subalpine coniferous forests. Using variation partitioning analysis, we revealed that differences in leaf δ13C and δ15N of herbs among various vegetation types were driven by both leaf functional traits and climate factors, with the contribution of leaf functional traits being relatively higher than that of climate factors. Hierarchical partitioning results indicated that mean annual temperature (MAT), chlorophyll content index, leaf nitrogen content per unit area (Narea), and leaf mass per area were the main drivers of leaf δ13C variations of herbs across different vegetation types, while the relative importance of Narea and MAT for variation in leaf δ15N of herbs was much higher than those other variables. There was a strong coupling relationship between leaf δ13C and δ15N as indicated by the result of the ordinary least squares regression. Our findings could provide new insights into understanding the key drivers of leaf δ13C and δ15N variations in herbs across different vegetation types.


Assuntos
Isótopos de Carbono , Ecossistema , Isótopos de Nitrogênio , Folhas de Planta , Folhas de Planta/química , Folhas de Planta/metabolismo , Isótopos de Nitrogênio/análise , Isótopos de Carbono/análise , Tibet , China , Florestas , Altitude , Árvores/crescimento & desenvolvimento , Árvores/metabolismo , Árvores/química , Traqueófitas/crescimento & desenvolvimento , Traqueófitas/química , Traqueófitas/metabolismo , Pradaria , Poaceae/crescimento & desenvolvimento , Poaceae/química , Poaceae/metabolismo
9.
Front Endocrinol (Lausanne) ; 15: 1304512, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38379860

RESUMO

Background: Previous research has indicated a vital association between hypertension, intraocular pressure (IOP), and diabetic retinopathy (DR); however, the relationship has not been elucidated. In this study, we aim to investigate the causal association of hypertension, IOP, and DR. Methods: The genome-wide association study (GWAS) IDs for DR, hypertension, and IOP were identified from the Integrative Epidemiology Unit (IEU) Open GWAS database. There were 33,519,037 single-nucleotide polymorphisms (SNPs) and a sample size of 1,030,836 for DR. There were 16,380,466 SNPs and 218,754 participants in the hypertension experiment. There were 9,851,867 SNPs and a sample size of 97,465 for IOP. Univariable, multivariable, and bidirectional Mendelian randomization (MR) studies were conducted to estimate the risk of hypertension and IOP in DR. Moreover, causality was examined using the inverse variance weighted method, and MR results were verified by numerous sensitivity analyses. Results: A total of 62 SNPs at the genome-wide significance level were selected as instrumental variables (IVs) for hypertension-DR. The results of univariable MR analysis suggested a causal relationship between hypertension and DR and regarded hypertension as a risk factor for DR [p = 0.006, odds ratio (OR) = 1.080]. A total of 95 SNPs at the genome-wide significance level were selected as IVs for IOP-DR. Similarly, IOP was causally associated with DR and was a risk factor for DR (p = 0.029, OR = 1.090). The results of reverse MR analysis showed that DR was a risk factor for hypertension (p = 1.27×10-10, OR = 1.119), but there was no causal relationship between DR and IOP (p > 0.05). The results of multivariate MR analysis revealed that hypertension and IOP were risk factors for DR, which exhibited higher risk scores (p = 0.001, OR = 1.121 and p = 0.030, OR = 1.124, respectively) than those in univariable MR analysis. Therefore, hypertension remained a risk factor for DR after excluding the interference of IOP, and IOP was still a risk factor for DR after excluding the interference of hypertension. Conclusion: This study validated the potential causal relationship between hypertension, IOP, and DR using MR analysis, providing a reference for the targeted prevention of DR.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Oftalmopatias , Hipertensão , Humanos , Pressão Intraocular , Retinopatia Diabética/etiologia , Retinopatia Diabética/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Hipertensão/etiologia , Hipertensão/genética
10.
Nat Commun ; 15(1): 366, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38191597

RESUMO

Near-infrared luminophores have many advantages in advanced applications, especially for structures without π-conjugation aromatic rings. However, the fabrication of red clusteroluminogens from nonconjugated polymers is still a big challenge, let alone the near-infrared clusteroluminogens. Here, we develop nonconjugated luminophores with full-spectrum from blue to near-infrared light (470 ~ 780 nm), based on color phenomenon of nonconjugated polyesters synthesized from the amine-initiated copolymerization of epoxides and cyclic anhydrides. We reveal that amines act as initiators attached to polymer chain ends. The formation of various amine-ester complexes in polyesters induces red to near-infrared light, conceptually, amine-ester complexed clusteroluminescence via intra/inter-chain charge transfer. Significantly, emission colors can be easily tuned by the contents and types of amines, microstructures of polyesters, and their concentration. This work provides a low-cost, scalable platform and strategy for the production of high-efficiency, multicolor luminescent materials.

11.
Heliyon ; 10(2): e23875, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38293397

RESUMO

Objective: In recent decades, thyroid cancer (TC) has exhibited a rising incidence pattern. Elevated levels of the transcription factor FOXP4 have been strongly linked to the progression of diverse tumors; nevertheless, its specific role in thyroid cancer remains underexplored. The primary objective of this study was to elucidate the functions of FOXP4 and its associated target gene, FBXW7, in the context of thyroid cancer. Methods: FOXP4 and FBXW7 expression levels in TC tissues and cell lines were assessed through immunohistochemistry and RT-qPCR analyses. The functional aspects of FOXP4, including its effects on cell proliferation, migration capabilities, cell cycle regulation, and epithelial-mesenchymal transition (EMT), were investigated. Furthermore, the interaction between FOXP4 and FBXW7 was confirmed using chromatin immunoprecipitation (ChIP) assays. The impact of FBXW7 on FOXP4-mediated cellular phenotypes was subsequently examined. Additionally, the in vivo role of FOXP4 and FBXW7 in tumor growth was elucidated through the establishment of a murine tumor model. Results: Elevated levels of FOXP4 were observed in papillary carcinoma tissues, and patients exhibiting high FBXW7 levels showed a more favorable prognosis. KTC-1 cells displayed a concomitant increase in FOXP4 expression and decrease in FBXW7 expression. FOXP4 overexpression in these cells enhanced cell proliferation, migration capabilities, and EMT. The interaction between the FOXP4 protein and the FBXW7 promoter was confirmed, and the effects of FOXP4 were mitigated upon overexpression of FBXW7. Furthermore, knockdown of FOXP4 led to decelerated growth of transplanted tumors and increased FBXW7 levels within the tumors. Conclusion: The findings of the current study underscore the regulatory role of FOXP4 in the transcription of FBXW7 and establish a clear link between aberrations in FBXW7 expression and the manifestation of malignant phenotypes in highly aggressive TC cells.

12.
Zhen Ci Yan Jiu ; 49(4): 398-402, 2024 Apr 25.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-38649208

RESUMO

OBJECTIVES: To compare the clinical effect of combined therapy of acupotomy and electroacupuncture (EA) with the simple application of EA on knee osteoarthritis (KOA), and their influence on knee function. METHODS: Sixty-eight KOA patients were randomly divided into 2 groups, an acupotomy group and an EA group. In the acupotomy group, the combined therapy of acupotomy and EA was adopted. In the EA group, EA was simply used, delivered once every two days, 3 treatments a week;and the duration of treatment was 4 weeks. In the acupotomy group, besides the treatment as the EA group, acupotomy was combined once weekly, and the duration of treatment was 4 weeks. Separately, before and after treatment, and in 4 and 12 weeks after treatment completion (1-month and 3-month follow-up), the results of the timed up and go test (TUG), the 9-step stair climb test (9-SCT) and the knee function (Western Ontario and McMaster University osteoarthritis index visualization scale [WOMAC]) were measured in the two groups. RESULTS: By the intention-to-treat analysis, the results of TUG, 9-SCT and WOMAC scores were reduced after treatment and in 1-month and 3-month follow-up when compared with those before treatment in the patients of the two groups (P<0.05). Compared with the EA group at the same time point, TUG results were decreased after treatment and in 1-month follow-up, and WOMAC score was reduced after treatment in the acupotomy group. WOMAC score in 1-month follow-up was reduced when compared with that before treatment within the acupotomy group (P<0.05). CONCLUSIONS: Either the simple application of EA or the combined therapy of acupotomy and EA can improve knee function, but the combined therapy obviously increases the walking speed and relieves the symptoms such as joint pain and morning stiffness. The treatment with acupotomy and EA is safe and effective on KOA and the long-term effect is satisfactory.


Assuntos
Terapia por Acupuntura , Eletroacupuntura , Osteoartrite do Joelho , Humanos , Osteoartrite do Joelho/terapia , Osteoartrite do Joelho/fisiopatologia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Terapia Combinada , Articulação do Joelho/fisiopatologia , Pontos de Acupuntura
13.
Heliyon ; 10(3): e24455, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38314298

RESUMO

Purpose: Eukaryotic translation elongation factor 1α2 (eEF1A2) promotes tumour progression in various cancers. We performed a pan-cancer analysis of eEF1A2 and explored its role in thyroid carcinoma (THCA). Methods: Databases from The Cancer Genome Atlas (TCGA), the University of Alabama at Birmingham Cancer data analysis Portal (UALCAN), and the Human Protein Atlas (HPA) were used to investigate the differential expression of eEF1A2 in pan-cancer. The pathological stage, prognostic characteristics, tumour microenvironment (TME), tumour mutational burden (TMB), and microsatellite instability (MSI) were analysed in diverse tumours with different expression levels of eEF1A2. The expression levels in papillary thyroid carcinoma (PTC) and its specific role in cell proliferation, migration, invasion, and cell glycolysis in PTC cells were verified by quantitative real time polymerase chain reaction (qRT-PCR), immunohistochemistry, cell counting kit-8, colony formation, wound healing, Transwell assay, and lactate acid and glucose assays.Results:eEF1A2 was differentially expressed in various malignant tumour tissues compared to control tissues and was associated with poor pathological stage and prognosis in most types of tumours. Moreover, eEF1A2 expression closely correlated with the infiltration of immunosuppressive cells, TMB, and MSI in some tumour types. Expression of eEF1A2 in PTC is higher than the para-carcinoma, and eEF1A2 downregulation suppressed TPC-1 and BCPAP cell proliferation, migration, invasion, and glycolysis. Conclusion: Our study suggests that the expression of eEF1A2 is related to the prognosis and immune infiltration of some tumours and may be a predictor of prognosis and immunotherapy. eEF1A2 could promote malignant behaviour of PTC cells.

14.
J Ethnopharmacol ; 332: 118357, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-38763374

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Chuanminshen violaceum M. L. Sheh & R. H. Shan (CV) is used as a medicine with roots, which have the effects of benefiting the lungs, harmonizing the stomach, resolving phlegm and detoxifying. Polysaccharide is one of its main active components and has various pharmacological activities, but the structural characterization and pharmacological activities of polysaccharide from the stems and leaves parts of CV are still unclear. AIM OF THE STUDY: The aim of this study was to investigate the optimal extraction conditions for ultrasound-assisted extraction of polysaccharide from CV stems and leaves, and to carry out preliminary structural analyses, anti-inflammatory and antioxidant effects of the obtained polysaccharide and to elucidate the underlying mechanisms. MATERIALS AND METHODS: The ultrasonic-assisted extraction of CV stems and leaves polysaccharides was carried out, and the response surface methodology (RSM) was used to optimize the extraction process to obtain CV polysaccharides (CVP) under the optimal conditions. Subsequently, we isolated and purified CVP to obtain the homogeneous polysaccharide CVP-AP-I, and evaluated the composition, molecular weight, and structural features of CVP-AP-I using a variety of technical methods. Finally, we tested the pharmacological activity of CVP-AP-Ⅰ in an LPS-induced model of oxidative stress and inflammation in intestinal porcine epithelial cells (IPEC-J2) and explored its possible mechanism of action. RESULTS: The crude polysaccharide was obtained under optimal extraction conditions and subsequently isolated and purified to obtain CVP-AP-Ⅰ (35.34 kDa), and the structural characterization indicated that CVP-AP-Ⅰ was mainly composed of galactose, galactose, rhamnose and glucose, which was a typical pectic polysaccharide. In addition, CVP-AP-Ⅰ attenuates LPS-induced inflammation and oxidative stress by inhibiting the expression of pro-inflammatory factor genes and proteins and up-regulating the expression of antioxidant enzyme-related genes and proteins in IPEC-J2, by a mechanism related to the activation of the Nrf2/Keap1 signaling pathway. CONCLUSION: The results of this study suggest that the polysaccharide isolated from CV stems and leaves was a pectic polysaccharide with similar pharmacological activities as CV roots, exhibiting strong anti-inflammatory and antioxidant activities, suggesting that CV stems and leaves could possess the same traditional efficacy as CV roots, which is expected to be used in the treatment of intestinal diseases.


Assuntos
Anti-Inflamatórios , Antioxidantes , Folhas de Planta , Caules de Planta , Polissacarídeos , Folhas de Planta/química , Polissacarídeos/farmacologia , Polissacarídeos/isolamento & purificação , Polissacarídeos/química , Animais , Caules de Planta/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/química , Antioxidantes/farmacologia , Antioxidantes/isolamento & purificação , Camundongos , Suínos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Intestinos/efeitos dos fármacos , Células RAW 264.7
15.
Int J Biol Macromol ; 268(Pt 2): 131816, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38677682

RESUMO

Paeoniae Radix alba is used in Traditional Chinese Medicine for the treatment of gastrointestinal disorders, immunomodulatory, cancer, and other diseases. In the current study, the yield of Paeoniae Radix alba polysaccharide (PRP) was significantly increased with optimal ultrasound-assisted extraction compared to hot water extraction. Further, an acidic polysaccharide (PRP-AP) was isolated from PRP after chromatographic separation and was characterized as a typical pectic polysaccharide with side chains of arabinogalactans types I and II. Moreover, it showed antioxidant effects on LPS-induced damage on IPEC-J2 cells determined by qRT-PCR and ELISA, including decreasing the pro-inflammatory factors' expressions and increasing the antioxidant enzymes activities, which was shown to be related to the Nrf2/Keap1 pathway modulated by PRP-AP. The metabolites change (such as itaconate, cholesterol sulfate, etc.) detected by untargeted metabolomic analysis in cells was also shown to be modulated by PRP-AP, and these metabolites were further utilized and protected cells damaged by LPS. These results revealed the cellular active mechanism of the macromolecular PRP-AP on protecting cells, and supported the hypothesis that PRP-AP has strong benefits as an alternative dietary supplement for the prevention of intestinal oxidative stress by modulating cellular metabolism.


Assuntos
Antioxidantes , Paeonia , Polissacarídeos , Polissacarídeos/farmacologia , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Paeonia/química , Ondas Ultrassônicas , Linhagem Celular , Animais , Estresse Oxidativo/efeitos dos fármacos , Fracionamento Químico/métodos , Lipopolissacarídeos/farmacologia
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