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1.
Diabetes Ther ; 15(4): 781-799, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38402331

RESUMO

INTRODUCTION: Tirzepatide is a novel hypoglycemic agent for type 2 diabetes mellitus (T2DM). However, the pathophysiology of T2DM in Asians is different from that in non-Asians, and there is no evidence to explain the differences in the efficacy and safety of tirzepatide between different races. METHODS: A literature search was conducted in China National Knowledge Infrastructure (CNKI), PubMed, Cochrane Library, Clinical Trials.gov, and Embase databases for clinical studies of tirzepatide for T2DM. The data extraction process was done independently by two authors. All analyses were performed using STATA 14.0 software and Review Manager 5.3 software. RESULTS: A total of 2118 patients with T2DM from 6 studies were involved, with doses of tirzepatide ranging from 5 to 15 mg administered subcutaneously once weekly. The results showed that compared with control/placebo, tirzepatide was more effective in decreasing fasting blood glucose (FBG) in non-Asians than in Asians, and 10 mg rather than 15 mg was the optimal dose to decrease FBG. Similarly, non-Asians were more effective than Asians in improving glycated hemoglobin (HbA1c). Asians were significantly more effective than non-Asians in reducing body weight and ≥ 5% weight loss. In terms of adverse events, the incidence of gastrointestinal adverse events was higher in Asians than in non-Asians at the same dose, while the incidence of metabolic and nutrition disorders was higher in non-Asians than in Asians. CONCLUSION: Tirzepatide is a novel agent for the treatment of diabetes and has different efficacy in Asians and non-Asians. Asians were more likely to experience weight loss and gastrointestinal adverse events, whereas non-Asians were more likely to have better glycemic control and more metabolic and nutritional disorders. TRIAL REGISTRATION: PROSPERO registration no. CRD42023489588.

2.
Nat Prod Res ; : 1-7, 2023 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-38143317

RESUMO

Three undescribed compounds, 1-(4-hydroxyphenyl)-3-((4-hydroxyphenyl)thio) -2-propanone (I), 4'-hydroxybenzyl 4-(4''- hydroxybenzyloxy) benzyl thioether (II) and 3-(4'-hydroxybenzyl)-6-hydroxy-quinazolinone (III) were isolated from the seeds of Sinapis alba L. The structures of all compounds were elucidated based on NMR and MS analysis, along with the comparison with published data. The potential targets of compounds I-III were identified by virtual screening. The potential inhibitory effects of these compounds on protein kinase C theta type were compared by molecular docking. The docking score of compound III was the highest.

3.
Gastroenterology ; 165(3): 746-761.e16, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37263311

RESUMO

BACKGROUND & AIMS: Liver fibrosis is an intrinsic wound-healing response to chronic injury and the major cause of liver-related morbidity and mortality worldwide. However, no effective diagnostic or therapeutic strategies are available, owing to its poorly characterized molecular etiology. We aimed to elucidate the mechanisms underlying liver fibrogenesis. METHODS: We performed a quantitative proteomic analysis of clinical fibrotic liver samples to identify dysregulated proteins. Further analyses were performed on the sera of 164 patients with liver fibrosis. Two fibrosis mouse models and several biochemical experiments were used to elucidate liver fibrogenesis. RESULTS: We identified cathepsin S (CTSS) up-regulation as a central node for extracellular matrix remodeling in the human fibrotic liver by proteomic screening. Increased serum CTSS levels efficiently predicted liver fibrosis, even at an early stage. Secreted CTSS cleaved collagen 18A1 at its C-terminus, releasing endostatin peptide, which directly bound to and activated hepatic stellate cells via integrin α5ß1 signaling, whereas genetic ablation of Ctss remarkably suppressed liver fibrogenesis via endostatin reduction in vivo. Further studies identified macrophages as the main source of hepatic CTSS, and splenectomy effectively attenuated macrophage infiltration and CTSS expression in the fibrotic liver. Pharmacologic inhibition of CTSS ameliorated liver fibrosis progression in the mouse models. CONCLUSIONS: CTSS functions as a novel profibrotic factor by remodeling extracellular matrix proteins and may represent a promising target for the diagnosis and treatment of liver fibrosis.


Assuntos
Endostatinas , Proteômica , Camundongos , Animais , Humanos , Endostatinas/metabolismo , Endostatinas/farmacologia , Fígado/metabolismo , Cirrose Hepática/metabolismo , Fibrose , Modelos Animais de Doenças , Células Estreladas do Fígado/metabolismo , Matriz Extracelular , Macrófagos/metabolismo
4.
Small ; 19(24): e2207252, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36922734

RESUMO

The abnormal pressure in tumor tissue is a significant limitation on the drug delivery efficiency of tumor therapy. This work reports a gradient-driven nanomotor as drug nanocarrier with the pressure-counterworking function. The dual-fuel nanomotors are formed by co-electrospinning of the photosensitive polymers with calcium peroxide (CaO2 ) and catalase (CAT), followed by ultraviolet (UV) irradiation and bovine serum albumin (BSA) incubation. The UV-responsive cleavage nanomotors can effectively release O2 molecules at the fractures as a driving force to increase the delivery speed and escape the phagocytosis of macrophage system in normal tissues. Furthermore, CAT catalyzes H2 O2 produced by CaO2 and the tumor interstitial fluids to provide stronger power for the nanomotors. Additionally, according to the analysis of directional motions of the nanomotors, the functional relationship between the rotational diffusion coefficient (DR ) and the physiological viscosity is constructed. The dual-fuel nanocarriers enable up to 13.25% of the injected dose (ID)/per gram tissue and significantly improve the penetration in deep tumor. It is of vital importance to design and obtain the adaptive pressure-gradient counterworking nanomotors, which can effectively improve the drug delivery efficiency in vitro and in vivo.


Assuntos
Sistemas de Liberação de Medicamentos , Líquido Extracelular , Preparações Farmacêuticas , Polímeros
5.
Front Pharmacol ; 14: 1096379, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36817117

RESUMO

Dendrophthoe falcata (L.f.) Ettingsh. (DF) and Dendrophthoe pentandra (L.) Miq. (DP) have been traditionally used for the treatment of various ailments, such as cancer, ulcers, asthma, paralysis, skin diseases, tuberculosis, and menstrual troubles, in the ethnomedicinal systems of India and Indonesia. Currently, the chemical structures of 46 compounds have been elucidated from DF and DP, including flavonoids, triterpenes, tannins, steroids, open-chain aliphatics, benzyl derivates, and cyclic chain derivatives. In vitro assays have revealed their anti-tumor and anti-microbial activities. In vivo studies have unraveled their pharmacological properties against tumors, depression, fertility disorders, inflammatory responses, and so on. Additionally, their weak toxicity to rats and brine shrimp, as well as their promising applications for pharmaceutical preparations and combined medication, were also revealed. Herein, we not only recapitulated traditional medical uses, phytochemistry, pharmacology, toxicity, and applications of DF and DP but also discussed current research limitations and future perspectives, which are instructive for those interested in them and are committed to advancing parasitic plants to the Frontier of phytomedicine. We highlighted that DF and DP will become promising medical plants rather than being discarded as notorious pests, provided that more and deeper research is undertaken.

6.
J Pharm Pharmacol ; 75(3): 328-362, 2023 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-36632823

RESUMO

OBJECTIVES: Solanum lyratum Thunb (SLT) is a perennial plant of the Solanaceae family, and is extensively used in the clinical practice of traditional Chinese medicine. Malaria, oedema, gonorrhoea, cancer, wind and fever, jaundiced hepatitis, cholecystitis and rheumatoid arthritis are among the diseases that it is used to treat. To offer a foundation for further development and usage of SLT, the pieces of literature about the chemical composition and pharmacological action of SLT were reviewed and analysed. KEY FINDINGS: The chemical constituents of SLT mainly included steroids, alkaloids, flavonoids, terpenoids, anthraquinones, phenylpropanoids and others. Pharmacological action mainly contains anti-tumour, antibacterial, anti-inflammatory, anti-oxidation and other pharmacological actions, among them, the anti-tumour effect is particularly outstanding. SUMMARY: At present, studies on the pharmacological effects of SLT mainly focus on alkaloids and steroidal saponins. In the follow-up studies, studies on the pharmacological activities of other chemical components in SLT, such as flavonoids and terpenoids, should be strengthened. It has the potential to pave the way for more research and development of novel SLT medicines.


Assuntos
Medicamentos de Ervas Chinesas , Neoplasias , Solanum , Humanos , Solanum/química , Extratos Vegetais/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Neoplasias/tratamento farmacológico , Flavonoides/uso terapêutico , Terpenos/uso terapêutico
7.
Molecules ; 27(19)2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36234947

RESUMO

In this paper, the confusion of the sources of medicinal materials was briefly expounded, and the differences among the varieties were pointed out. At the same time, the chemical components and pharmacological properties of Elsholtzia ciliata (Thunb.) Hyland (E. ciliata) were reviewed. The structures of 352 compounds that have been identified are listed. These mainly include flavonoids, terpenoids, phenylpropanoids, alkaloids, and other chemical components. They have antioxidant, anti-inflammatory, antimicrobial, insecticidal, antiviral, hypolipidemic, hypoglycemic, analgesic, antiarrhythmic, antitumor, antiacetylcholinesterase, and immunoregulator activities. At present, there are many researches using essential oil and alcohol extract, and the researches on antioxidant, anti-inflammatory, anti-microbial, and other pharmacological activities are relatively mature. This paper aims to summarize the existing research, update the research progress regarding the phytochemicals and pharmacology of E. ciliate, and to provide convenience for subsequent research.


Assuntos
Anti-Infecciosos , Lamiaceae , Óleos Voláteis , Analgésicos , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Antivirais , Etnofarmacologia , Flavonoides , Hipoglicemiantes , Lamiaceae/química , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Terpenos
8.
Nat Prod Res ; : 1-9, 2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36255124

RESUMO

A phytochemical investigation of Bidens procera L.C.Xu ex X.W.Zheng afforded two novel polyacetylenes, tridecane-2E-monoene-4,6,8-triyntylen-1,13-diol-12-O-ß-glucoside (1) and tetradecane-2E,8E-diene-4,6-diyne-1,14-diol-13-O-ß-glucoside (2), together with ten known compounds (3 - 12). Their chemical structures were elucidated by NMR and MS spectrums as well as the comparison of the published data. Furthermore, the chemotaxonomy of the yielded compounds was also discussed.

9.
Molecules ; 27(16)2022 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-36014582

RESUMO

The Broussonetia genus (Moraceae), recognized for its value in many Chinese traditional herbs, mainly includes Broussonetia papyrifera (L.) L'Hér. ex Vent. (BP), Broussonetia kazinoki Siebold (BK), and Broussonetia luzonica (Blanco) Bureau (BL). Hitherto, researchers have found 338 compounds isolated from BP, BK, and BL, which included flavonoids, polyphenols, phenylpropanoids, alkaloids, terpenoids, steroids, and others. Moreover, its active compounds and extracts have exhibited a variety of pharmacological effects such as antitumor, antioxidant, anti-inflammatory, antidiabetic, anti-obesity, antibacterial, and antiviral properties, and its use against skin wrinkles. In this review, the phytochemistry and pharmacology of Broussonetia are updated systematically, after its applications are first summarized. In addition, this review also discusses the limitations of investigations and the potential direction of Broussonetia. This review can help to further understand the phytochemistry, pharmacology, and other applications of Broussonetia, which paves the way for future research.


Assuntos
Alcaloides , Broussonetia , Moraceae , Broussonetia/química , Etnofarmacologia , Flavonoides/farmacologia , Compostos Fitoquímicos/química , Extratos Vegetais/química
10.
J Ethnopharmacol ; 296: 115462, 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-35714877

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Tapinanthus species are hemiparasites that grow on diverse hosts in African regions. Tapinanthus species are locally known as "all purpose herbs" as they are traditionally used to treat various diseases such as diabetes, hypertension, cancer, inflammation, malaria, anemia, anxiety, itching, and so on. AIM OF THE STUDY: A comprehensive review on research outcomes and future perspectives of Tapinanthus species are presented to provide a reference for relevant researchers. MATERIALS AND METHODS: The references regarding Tapinanthus species were retrieved from Google Scholar, Web of Science, Sci-finder, PubMed, Elsevier, Wiley, China National Knowledge Infrastructure, Open Access Library, and SpringerLink between 1963 and 2022. Scientific plant names were provided by "The Plant List" (www.theplantlist.org) and "The world Flora Online" (www.worldfloraonline.org). RESULTS: Even though Tapinanthus species are regarded as notorious pests that can undermine various hosts, they are, as omnipotent herbs in folklore, meaningful for the development of potential phytomedicine sources. Phytochemistry screening has revealed the presence of glycosides, triterpenoids, flavonoids, alkaloids, tannins, steroids, anthraquinones. Among them, the chemical structures of 40 compounds have been elucidated by phytochemical methods without alkaloids and anthraquinones. These secondary metabolites might be responsible for ethnomedical uses and bioactivities of Tapinanthus species. Current research has provided scientific evidence for traditional uses of Tapinanthus species, especially unraveling hypoglycemic, hepatoprotective, antioxidant, antibacterial, anti-anxiety, anti-depression, anti-inflammatory, and other pharmacological properties. Given the fact that ethnomedical uses served as a valuable reference for pharmacology, however, some records to treat arthritis, fever, itching, dysentery, stomach pain, and anemia, have not been confirmed in current research. Furthermore, the toxic effects of Tapinanthus species were susceptible to the dosages, with relative safety across a wide range. CONCLUSIONS: To reasonably yield Tapinanthus species, artificial culture might be a promising method to develop in the future. The discrepancies between phytochemistry screening and structure elucidation, as well as between ethnomedical uses and current pharmacology, need to be further clarified. The identification of bioactive compounds in crude extracts and fractions, the illustration of the underlying mechanisms of pharmacology, along with the addition of cytotoxicity, genotoxicity, and clinical trials of toxic tests, should be carried out in depth. This review highlights that Tapinanthus species can be considered promising phytomedicine sources as long as we adhere to digging more deeply into their potential role.


Assuntos
Botânica , Loranthaceae , Antraquinonas , Etnobotânica , Etnofarmacologia , Compostos Fitoquímicos/uso terapêutico , Compostos Fitoquímicos/toxicidade , Fitoterapia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/toxicidade , Prurido/tratamento farmacológico
11.
Bioengineered ; 13(6): 14460-14471, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35758158

RESUMO

N(6)-methyladenosine (m6A)-modified microRNAs (miRNAs) are relevant to cancer progression. Also, although the involvement of miR-380-3p in regulating cancer progression in bladder cancer and neuroblastoma has been preliminarily explored, its role in other types of cancer, such as pancreatic cancer (PC), has not been studied. Thus, this study aimed to investigate the role of miR-380-3p in regulating PC progression. Here, through performing Real-Time qPCR, we evidenced that miR-380-3p was significantly upregulated in the clinical pancreatic cancer tissues and cells compared to their normal counterparts. Interestingly, miR-380-3p was enriched with m6A modifications, and elimination of m6A modifications by deleting METTL3 and METTL14 synergistically suppressed miR-380-3p expressions in PC cells. Next, the gain and loss-of-function experiments verified that knockdown of miR-380-3p suppressed cell proliferation, epithelial-mesenchymal transition (EMT), and tumorigenesis in PC cells in vitro and in vivo, whereas miR-380-3p overexpression had opposite effects. Furthermore, the underlying mechanisms were uncovered, and our data suggested that miR-380-3p targeted the 3' untranslated regions (3'UTRs) of PTEN for its inhibition and degradation, resulting in the activation of the downstream Akt signal pathway. Moreover, the rescuing experiments validated that both PTEN overexpression and Akt pathway inhibitor LY294002 abrogated the promoting effects of miR-380-3p overexpression on cancer aggressiveness in PC cells. Collectively, this study firstly investigated the role of the m6A-associated miR-380-3p/PTEN/Akt pathway in regulating PC progression, which provided novel therapeutic and diagnostic biomarkers for this cancer.


Assuntos
Adenosina , MicroRNAs , Neoplasias Pancreáticas , Adenosina/análogos & derivados , Adenosina/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Humanos , Metiltransferases/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Regulação para Cima
12.
J Asian Nat Prod Res ; 24(10): 963-970, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34747287

RESUMO

A new dihydroflavone, 2(S)-isookanin-4'-methoxy-8-O-ß-D-glucopyranoside (1), and a new polyacetylene glucoside, (10S)-tridecane-2E-ene-4,6,8-triyne-1-ol-10-O-ß-D-glucopyranoside (2), along with seven known compounds (3-9), were isolated from the herb of Bidens parviflora Willd. The structures of all the extracted compounds were elucidated by HR-ESI-MS, 1 D and 2 D NMR spectra, as well as circular dichroism (CD).


Assuntos
Bidens , Glucosídeos , Glucosídeos/química , Polímero Poliacetilênico , Estrutura Molecular , Poli-Inos/química
13.
Molecules ; 26(23)2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34885647

RESUMO

Cynanchum auriculatum Royle ex Wight. (CA), Cynanchum bungei Decne. (CB) and Cynanchum wilfordii (Maxim.) Hemsl. (CW) are three close species belonging to the Asclepiadaceous family, and their dry roots as the bioactive part have been revealed to exhibit anti-tumor, neuroprotection, organ protection, reducing liver lipid and blood lipid, immunomodulatory, anti-inflammatory, and other activities. Until 2021, phytochemistry investigations have uncovered 232 compounds isolated from three species, which could be classified into C21-steroids, acetophenones, terpenoids, and alkaloids. In this review, the morphology characteristics, species identification, and the relationship of botany, extraction, and the separation of chemical constituents, along with the molecular mechanism and pharmacokinetics of bioactive constituents of three species, are summarized for the first time, and their phytochemistry, pharmacology, and clinical safety are also updated. Moreover, the direction and limitation of current research on three species is also discussed.


Assuntos
Anti-Inflamatórios/química , Antidepressivos/química , Antifúngicos/química , Antineoplásicos/química , Antioxidantes/química , Antivirais/química , Cynanchum/química , Cynanchum/classificação , Agentes de Imunomodulação/química , Fármacos Neuroprotetores/química , Compostos Fitoquímicos/química , Extratos Vegetais/química , Raízes de Plantas/química , Animais , Cynanchum/anatomia & histologia , Humanos
14.
ACS Appl Mater Interfaces ; 13(46): 54715-54726, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34757716

RESUMO

Nowadays, the development of nanoparticles is known to be mainly associated with enhancement of the targeted delivery of the active component to solid tumors. However, the lack of understanding of the nanoparticle morphology restricts the transport efficiency of various nanocarriers, especially offers no consistent mechanism for the delivery. Here, we demonstrate the principles of enhancement of passive delivery utilizing the precise control and analysis of shape-switchable nanomicelles without any functional addition. We successfully regulated the nanomicelle shape with various aspect ratios in the electrospun nanofiber matrix and devised a stretching phase diagram. Using the vascular leakage model, visual laser spectrum, and image analysis in the simulated scene, we found that the deformed nanomicelles with high aspect ratios along with lower equivalent volumes were significantly beneficial to the passive delivery. Further, the enhanced permeability of the shape-variable nanomicelles in the recovering state was up to 4 times of that observed before recovery. Our results challenge the current consensus of passive targeting and provide an important guidance for the design of nanoparticle morphology and active addition in cancer nanomedicine.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Nanofibras/química , Nanopartículas/química , Neoplasias/tratamento farmacológico , Animais , Antibióticos Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Portadores de Fármacos/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Neoplasias Hepáticas Experimentais/patologia , Camundongos , Camundongos Endogâmicos , Micelas , Estrutura Molecular , Neoplasias/patologia , Tamanho da Partícula
15.
Int J Clin Exp Pathol ; 14(7): 811-818, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34367412

RESUMO

OBJECTIVE: Research has proven that the expression of CDC6 is tightly related to tumorigenesis and progression of various tumors. However, the effects of CDC6 in hepatocellular carcinoma remain uncertain. The main purpose of this research is to explore this relationship. METHODS: We assessed the expression levels of CDC6 in a serious of cancers from GEPIA database. The expression of CDC6 in hepatocellular carcinoma tissue and normal liver tissue was compared, and further assessed by immunohistochemical staining. Graphpad software was performed for data analysis, and t-test and χ2 analysis were used to investigate the role of CDC6 in hepatocellular carcinoma. RESULTS: The expression level of CDC6 was significantly higher in malignant carcinoid, melanoma, urothelial tumor, and hepatocellular carcinoma in the GEPIA online database. It was related to clinical progression of hepatocellular carcinoma. We found that the expression of CDC6 was correlated with tumor size (P=0.018) and the number of tumor nodes (P=0.003), but not with age, gender and AFP value (P>0.05). CONCLUSIONS: The expression level of CDC6 in hepatocellular carcinoma is related tightly to clinical findings. Detecting the expression of CDC6 might provide a new biomarker for patients with hepatocellular carcinoma.

16.
Drug Deliv ; 27(1): 1729-1740, 2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33307843

RESUMO

Chemoembolization for hepatocellular carcinoma (HCC) is often suboptimal due to multiple involved signaling and lack of effective drugs. Arsenic trioxide (ATO) is a potent chemotherapeutic agent, which can target multiple signaling and have substantial efficacy on HCC. However, its usage is limited due to systemic toxicity. Using ATO-eluting beads/microspheres for chemoembolization can have locoregional drug delivery and avoid systemic exposure but will require high drug load, which has not been achieved due to low solubility of ATO. Through an innovative approach, we generated the transiently formed ATO microcrystals via micronization and stabilized these microcrystals by solvent exchange. By encapsulating ATO microcrystals, but not individual molecules, with poly(lactide-co-glycolic acid) (PLGA), we developed microspheres cored with extremely high dense ATO. The molar ratio between ATO and PLGA was 157.4:1 and drug load was 40.1%, which is 4-20 fold higher than that of reported ATO nano/microparticles. These microspheres sustainably induced reactive oxygen species, apoptosis, and cytotoxicity on HCC cells and reduced tumor growth by 80% via locoregional delivery. Chemoembolization on mice model showed that ATO-microcrystal loaded microspheres, but not ATO, inhibited HCC growth by 60-75%, which indicates ATO within these microspheres gains the chemoembolizing function via our innovative approach.


Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Trióxido de Arsênio/administração & dosagem , Trióxido de Arsênio/uso terapêutico , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Camundongos Nus , Microesferas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Espécies Reativas de Oxigênio , Solventes , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Kaohsiung J Med Sci ; 36(7): 515-522, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32237034

RESUMO

Gastric cancer (GC) is the fourth most common malignancy worldwide, with 80% mortality rate in over 70% countries. Recently, targeted therapy for GC has great clinical prospects, and it is still badly needed to find novel molecular targets to control the progression and development of GC. Kinesin family member 3B (KIF3B) is known as a microtubule motor kinesin and one of the most ubiquitously expressed KIFs. KIF3B participates in multiple cellular processes such as mitosis and spermatogenesis, and the possible role of KIF3B on tumor progression has been widely revealed. KIF3B affects the progression and metastasis of multiple types of tumors, such as pancreatic cancer, prostate cancer, and hepatocellular carcinoma; however, its potential impact on GC is still unknown. Herein, we explored the possible role of KIF3B on the progression of GC and noticed that KIF3B was high expression in tumor tissues from GC patients. KIF3B was also significantly correlated with clinical pathological characteristics such as tumor size (P = .014*) and recurrence (P = .044*). We further revealed that KIF3B depleted GC cells exhibited impaired proliferation capacity in vitro. Similarly, KIF3B depletion suppressed tumor growth of GC cells in mice. In conclusion, we identified KIF3B as a promising therapeutic target for the treatment of GC.


Assuntos
Regulação Neoplásica da Expressão Gênica , Cinesinas/genética , Recidiva Local de Neoplasia/genética , Neoplasias Gástricas/genética , Adulto , Idoso , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Humanos , Cinesinas/antagonistas & inibidores , Cinesinas/metabolismo , Metástase Linfática , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida , Carga Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
18.
J Proteome Res ; 17(12): 4171-4177, 2018 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-30280576

RESUMO

Subsequent to conducting the Chromosome-Centric Human Proteome Project, we have focused on human testis-enriched missing proteins (MPs) since 2015. For protein coverage to be enhanced, a multiprotease strategy was used for separation of samples by 10% SDS-PAGE. For the separating efficiency to be improved, a high-pH reverse phase (RP) separation strategy was applied to fractionate complex samples in this study. A total of 11,558 proteins was identified, which is the largest proteome data set for single human tissue sample so far. On the basis of this large-scale data set, we verified 14 MPs (PE2) in neXtProt (2018-01) after spectrum quality analysis, isobaric post-translational modification, and single amino acid variant filtering, and synthesized peptide matching. Tissue expression analysis showed that 3 of 14 MPs were testis-specific proteins. Functional analysis showed that 10 of 14 MPs were closely related to liver tumor, liver carcinoma, and hepatocellular carcinoma. Another 100 MPs were listed as candidates but required additional verification information. All MS data sets have been deposited into the ProteomeXchange with the identifier PXD009737.


Assuntos
Proteoma/análise , Testículo/química , Eletroforese em Gel de Poliacrilamida , Variação Genética , Humanos , Neoplasias Hepáticas/química , Masculino , Espectrometria de Massas , Peptídeo Hidrolases/metabolismo , Processamento de Proteína Pós-Traducional , Proteômica/métodos
19.
Oxid Med Cell Longev ; 2018: 7616852, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29743984

RESUMO

Oxidative stress and inflammation undoubtedly contribute to the pathogenesis of many human diseases. The nuclear transcription factor erythroid 2-related factor (Nrf2) and the nuclear factor κB (NF-κB) play central roles in regulation of oxidative stress and inflammation and thus are targets for developing agents against oxidative stress- and inflammation-related diseases. Our previous study indicated that the EtOH extract of Litsea garrettii protected human bronchial epithelial cells against oxidative insult via the activation of Nrf2. In the present study, a systemic phytochemical investigation of L. garrettii led to the isolation of twenty-one chemical ingredients, which were further evaluated for their inhibitions on oxidative stress and inflammation using NAD(P)H:quinone reductase (QR) assay and nitric oxide (NO) production assay. Of these ingredients, 3-methoxy-5-pentyl-phenol (MPP, 5) was identified as an Nrf2 activator and an NF-κB inhibitor. Further studies demonstrated the following: (i) MPP upregulated the protein levels of Nrf2, NAD(P)H:quinone oxidoreductase 1 (NQO1), and glutamate-cysteine ligase regulatory subunit (GCLM); enhanced the nuclear translocation and stabilization of Nrf2; and inhibited arsenic [As(III)]-induced oxidative insult in normal human lung epithelial Beas-2B cells. And (ii) MPP suppressed the nuclear translocation of NF-κB p65 subunit; inhibited the lipopolysaccharide- (LPS-) stimulated increases of NF-κB p65 subunit, COX-2, iNOS, TNF-α, and IL-1ß; and blocked the LPS-induced biodegrade of IκB-α in RAW 264.7 murine macrophages. Taken together, MPP displayed potential preventive effects against inflammation- and oxidative stress-related diseases.


Assuntos
Anti-Inflamatórios/uso terapêutico , Brônquios/patologia , Células Epiteliais/efeitos dos fármacos , Inflamação/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Fenóis/uso terapêutico , Extratos Vegetais/uso terapêutico , Animais , Anti-Inflamatórios/química , Células Epiteliais/fisiologia , Etanol/química , Regulação da Expressão Gênica , Humanos , Interleucina-1beta/metabolismo , Litsea/imunologia , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Fenóis/química , Extratos Vegetais/química , Quinona Redutases/metabolismo , Células RAW 264.7 , Fator de Necrose Tumoral alfa/metabolismo
20.
J Proteome Res ; 14(9): 3583-94, 2015 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-26282447

RESUMO

Investigations of missing proteins (MPs) are being endorsed by many bioanalytical strategies. We proposed that proteogenomics of testis tissue was a feasible approach to identify more MPs because testis tissues have higher gene expression levels. Here we combined proteomics and transcriptomics to survey gene expression in human testis tissues from three post-mortem individuals. Proteins were extracted and separated with glycine- and tricine-SDS-PAGE. A total of 9597 protein groups were identified; of these, 166 protein groups were listed as MPs, including 138 groups (83.1%) with transcriptional evidence. A total of 2948 proteins are designated as MPs, and 5.6% of these were identified in this study. The high incidence of MPs in testis tissue indicates that this is a rich resource for MPs. Functional category analysis revealed that the biological processes that testis MPs are mainly involved in are sexual reproduction and spermatogenesis. Some of the MPs are potentially involved in tumorgenesis in other tissues. Therefore, this proteogenomics analysis of individual testis tissues provides convincing evidence of the discovery of MPs. All mass spectrometry data from this study have been deposited in the ProteomeXchange (data set identifier PXD002179).


Assuntos
Genômica , Proteínas/metabolismo , Proteômica , Testículo/metabolismo , Cromatografia Líquida , Eletroforese em Gel de Poliacrilamida , Humanos , Masculino , Proteínas/isolamento & purificação , Análise de Sequência de RNA , Espectrometria de Massas em Tandem , Transcriptoma
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