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1.
Biomed Pharmacother ; 175: 116601, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38749177

RESUMO

Alzheimer's disease (AD) comprises a group of neurodegenerative disorders with some changes in the brain, which could lead to the deposition of certain proteins and result in the degeneration and death of brain cells. Patients with AD manifest primarily as cognitive decline, psychiatric symptoms, and behavioural disorders. Short-chain fatty acids (SCFAs) are a class of saturated fatty acids (SFAs) produced by gut microorganisms through the fermentation of dietary fibre ingested. SCFAs, as a significant mediator of signalling, can have diverse physiological and pathological roles in the brain through the gut-brain axis, and play a positive effect on AD via multiple pathways. Firstly, differences in SCFAs and microbial changes have been stated in AD cases of humans and mice in this paper. And then, mechanisms of three main SCFAs in treating with AD have been summarized, as well as differences of gut bacteria. Finally, functions of SCFAs played in regulating intestinal flora homeostasis, modulating the immune system, and the metabolic system, which were considered to be beneficial for the treatment of AD, have been elucidated, and the key roles of gut bacteria and SCFAs were pointed out. All in all, this paper provides an overview of SCFAs and gut bacteria in AD, and can help people to understand the importance of gut-brain axis in AD.


Assuntos
Doença de Alzheimer , Eixo Encéfalo-Intestino , Encéfalo , Ácidos Graxos Voláteis , Microbioma Gastrointestinal , Humanos , Ácidos Graxos Voláteis/metabolismo , Doença de Alzheimer/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/microbiologia , Animais , Microbioma Gastrointestinal/fisiologia , Eixo Encéfalo-Intestino/fisiologia , Encéfalo/metabolismo
2.
J Mater Chem B ; 11(16): 3679-3692, 2023 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-37042187

RESUMO

Although oxidative stress-based antitumor modality derived from reactive oxygen species (ROS) storm has attracted considerable attention in copper-based nanomaterials, its efficiency is still weakened by the insufficient hydrogen peroxide (H2O2) and overexpressed glutathione (GSH) in a tumor microenvironment (TME). In view of this, we designed an engineered programmable spike-like nanogenerator via the coordination-driven co-assembly of Evans Blue (EB), copper ions (CuII), and 5-hydroxy-p-naphthoquinone (HND). For programmable nanogenerators, the introduction of EB as a stabilizer-like component can not only adjust its morphology but also achieve its visual tracking. Interestingly, such programmable nanogenerators can be efficiently enriched in tumor regions and then internalized into tumor cells due to ECH with spike-like morphology. Notably, once the nanogenerator is disintegrated and burst to release the drug upon acidic lysosome and endogenous GSH triggering, the released HND can not only efficiently amplify endogenous H2O2 by intracellular oxidoreductases but also down-regulate the peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin 1) activity. In addition, the released CuII ions can efficiently catalyze the degradation of the endogenous H2O2 to amplify hydroxyl radicals (˙OH) and down-regulate the overexpressed GSH to reduce ˙OH elimination for on-demand cascade-amplifying oxidative stress. Importantly, such programmable nanogenerators show an excellent antitumor effect via down-regulating the Pin 1 activity and cascade-amplifying oxidative stress. In this study, we propose a spatiotemporally programmable cascade nanogenerator for oxidative stress-based antitumor therapy.


Assuntos
Cobre , Peróxido de Hidrogênio , Cobre/farmacologia , Peróxido de Hidrogênio/metabolismo , Microambiente Tumoral , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Glutationa/metabolismo
3.
J Obstet Gynaecol ; 43(1): 2188085, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36930892

RESUMO

Ovarian cancer is one of the most common malignant tumours affecting the female reproductive organs. CD147 (BSG) and CD98hc (SLC3A2) are oncogenes that form the CD98hc-CD147 complex, which regulates the proliferation, metastasis, metabolism, and cell cycle of cancer cells. The roles of the CD98hc-CD147 complex in ovarian cancer remain unclear. We analysed the expression and prognostic value of CD147 and CD98hc in ovarian cancer using the TCGA and ICGC databases. The effect of CD147 and CD98hc on the tumour immune response was analysed using the TIMER database. CD98hc was more highly expressed in normal tissues than primary tumour tissues, while CD147 was more highly expressed in primary tumour tissues than normal tissues. CD98hc expression was significantly associated with neutrophil and dendritic cell levels. CD147 and CD98hc were correlated with DNA repair, the cell cycle, and DNA replication. The CD98hc-CD147 complex could serve as a target for ovarian cancer treatment.


What is already known on this subject? CD98hc and CD147 are oncogenes that induce the proliferation and metastasis of cancer cells. The CD98hc-CD147 complex has been identified as a risk factor for cancer patients and causes resistance to cancer treatment.What do the results of this study add? We confirmed the expression levels of CD98hc and CD147 in ovarian cancer tissues and the effects of these oncogenes on the tumour immune response.What are the implications of these findings for clinical practice and/or further research? The CD98hc-CD147 complex may serve as a new target for ovarian cancer therapy.


Assuntos
Relevância Clínica , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/patologia , Prognóstico
4.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 44(4): 699-708, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-36065705

RESUMO

Insulin resistance (IR) is a pathological reaction of hyperinsulinemia and impaired glucose tolerance caused by decreased sensitivity of target tissues such as liver to insulin.The pathogenesis of IR as a typical pathological feature of type 2 diabetes is the focus of anti-diabetes research.In this paper,we reviewed the molecular mechanisms of glucose and lipid metabolism,oxidative stress,mitochondrial dysfunction,endoplasmic reticulum stress,inflammation,and hepatic IR in the case of type 2 diabetes mellitus,which might provide new ideas and theoretical guidance for the treatment of diabetes mellitus.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Humanos , Insulina , Fígado , Estresse Oxidativo
5.
Zhongguo Zhong Yao Za Zhi ; 46(3): 552-559, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33645019

RESUMO

Polysaccharides are macromolecular compounds formed by more than 10 monosaccharide molecules linked by glycosidic bonds. Polysaccharides have a wide range of sources, high safety and low toxicity, with a variety of biological activities, such as anti-tumor, anti-virus, immune regulation, lowering blood glucose, and lowering blood lipids. Type 2 diabetes mellitus(T2 DM) is a chronic metabolic disorder characterized by hyperglycemia, insulin resistance and low inflammation. In recent years, the treatment of T2 DM with polysaccharide has become a research hotspot. Polysaccharides can not only make up for the side effects such as hypoglycemia, weight gain, gastrointestinal injury caused by long-term treatment of acarbose, biguanidine and sulfonylurea, but also play an effective role in reducing glucose by regulating glucose metabolism, oxidative stress, inflammatory response, intestinal flora, etc. In this paper, the research progress of polysaccharides in the treatment of T2 DM was reviewed. In addition, the hot spots such as the hypoglycemic activity of polysaccharides with structural modifications were summarized, providing theoretical guidance for the development of active polysaccharide hypoglycemic medicines and the further study of action mechanism.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Glicemia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hipoglicemiantes/farmacologia , Polissacarídeos
6.
Dalton Trans ; 49(3): 598-602, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31850437

RESUMO

The phosphorescence lifetimes of sulfur heteroatom-containing ligands were increased by more than 400 times through strong coordination bonds in the MOF matrix. Photoelectric measurements exhibited abnormal enhancement in the photocurrent for phosphorescent MOFs when the illumination was turned off.

7.
Zhongguo Zhong Yao Za Zhi ; 42(19): 3713-3717, 2017 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-29235284

RESUMO

Asthma is a kind of chronic respiratory inflammation, commonly with breathlessness, chest tightness, coughing, recurrent episodes of wheezing and airflow obstruction, severely affecting human health. A variety of immunocytes are involved in this chronic disease. Chinese herbal medicine(CHM) has a long history in the treatment of asthma. A large number of studies have shown that CHM could ameliorate asthma symptoms through regulating cellular immune responses. This paper reviewed the studies of CHM on the regulation of immunocytes and their mechanisms in recent years, including the count of inflammatory cells, maturation of dendritic cells, balance of helper T cell subtypes, induction of regulatory T cells and intracellular signaling pathways. We also proposed the future research directions about the effects of CHM on asthma treatment.


Assuntos
Asma/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Pesquisa Biomédica/tendências , Células Dendríticas , Humanos , Transdução de Sinais , Linfócitos T Auxiliares-Indutores
8.
Int J Oncol ; 46(5): 2181-93, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25826779

RESUMO

We have shown that an antimicrobial peptide (AMP) cecropinXJ isolated from the larvae of Bombyx mori selectively inhibits the proliferation of cancer cells. However, the mechanism remains to be determined. In the present study, we examined the antitumor activity of cecropinXJ against human gastric cancer BGC823 cells and explored the mechanism. The results showed that cecropinXJ inhibited the growth of gastric cancer BGC823 cells in vitro and in vivo. MTT and colony formation assays indicated that cecropinXJ suppressed cell proliferation and reduced colony formation of BGC823 cells in a dose- and time-dependent manner, but without inhibitory effect on normal gastric epithelia GES-1 cells. S-phase arrest in BGC823 cells was observed after treatment with cecropinXJ. Annexin V/PI staining suggested that cecropinXJ induced both early and late phases of apoptosis through activation of mitochondrial-mediated caspase pathway, upregulation of Bax expression and downregulation of Bcl-2 expression. Additionally, cecropinXJ treatment increased reactive oxygen species (ROS) production, disrupted the mitochondrial membrane potential (Δψm) and led to release of cytochrome c. Importantly, in vivo study showed that cecropinXJ significantly prevented the growth of xenograft tumor in the BGC823-bearing mice, possibly mediated by the induction of apoptosis and inhibition of angiogenesis. These results suggest that cecropinXJ may be a promising therapeutic candidate for the treatment of gastric cancer.


Assuntos
Antineoplásicos/farmacologia , Cecropinas/farmacologia , Proliferação de Células/efeitos dos fármacos , Neoplasias Gástricas/patologia , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Bombyx , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Proteínas de Insetos/farmacologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Microscopia Eletrônica de Transmissão , Reação em Cadeia da Polimerase , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Tohoku J Exp Med ; 225(1): 51-7, 2011 09.
Artigo em Inglês | MEDLINE | ID: mdl-21869591

RESUMO

Electrical remodeling at infarct border zone has been shown to contribute to the occurrence of ventricular arrhythmias after myocardial infarction (MI). Electrical remodeling is causally associated with sympathetic neural remodeling in MI. Semaphorin 3A (Sema3A), a potent neural chemorepellent for sympathetic axons, has been demonstrated to suppress sympathetic neural remodeling after MI. In the present study, we investigated whether treatment with Sema3A can ameliorate electrical remodeling at infarct border zones using a rat model of MI. Wistar rats underwent sham operation (n = 20), the ligation of left coronary artery (MI group, n = 30), MI with control adenovirus (Ad group, n = 30), and MI with Sema3A adenovirus (Sema3A group, n = 30). Eight weeks after treatment, electrophysiological properties including heart rate variability (HRV), monophasic action potential duration (MAPD) and effective refractory period (ERP) and the expression of arrhythmia-related ion channel proteins including Kv4.2, KChIP2 and Kir2.1 at the infarcted border of the left ventricle were examined. These channel proteins may be required for maintaining normal heart rhythm. Compared with the Ad group, Sema3A significantly increased HRV and shortened MAPD and ERP (all p < 0.05). The expression levels of Kv4.2, KChIP2 and Kir2.1 proteins were significantly decreased in MI group and Ad group, compared to sham control. In contrast, the expression levels of these proteins were restored in Sema3A group, which may represent the molecular basis of the Sema3A-mediated inhibition of electrical remodeling. In conclusion, Sema3A can ameliorate electrical remodeling at infarct border zones after MI.


Assuntos
Fenômenos Eletrofisiológicos , Terapia Genética , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/terapia , Semaforina-3A/genética , Semaforina-3A/uso terapêutico , Remodelação Ventricular/fisiologia , Animais , Pressão Sanguínea/fisiologia , Western Blotting , Frequência Cardíaca/fisiologia , Masculino , Infarto do Miocárdio/patologia , Canais de Potássio/metabolismo , Ratos , Ratos Wistar , Coloração e Rotulagem
10.
J Zhejiang Univ Sci B ; 9(2): 132-40, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18257135

RESUMO

A novel vacuolar Na+/H+ exchanger, CgNHX1, was cloned from a halophytic species Chenopodium glaucum by using reverse transcriptase-polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE) technique. Sequence alignment and phylogenetic analysis of 22 NHX genes from GenBank as well as the new CgNHX1 gene indicate that NHX genes shared a great degree of similarity, regardless of their glycophytic or halophytic origin. Expression of the CgNHX1 gene was induced by NaCl and peaked at 400 mmol/L NaCl. Overexpression of NHX1 genes in rice enhanced their tolerance to salt stress. However, there is no significant difference in salt tolerance among the transgenic rice plants overexpressing the NHX1 genes from either glycophytic or halophytic species. The Na+ content of both the wild type (WT) and transgenic plants increased when exposed to 50 and 100 mmol/L NaCl, and the Na+ concentration in transgenic plants was marginally higher than that of WT. Our data demonstrate that the overexpression of the NHX1 gene from either glycophytic or halophytic species resulted in the enhanced tolerance to salt stress at a similar level, suggesting that NHX gene per se might not be the reason accounting for the difference in salt tolerance between glycophytes and halophytes.


Assuntos
Regulação da Expressão Gênica de Plantas , Oryza/genética , Plantas/genética , Plantas/metabolismo , ATPases Vacuolares Próton-Translocadoras/química , ATPases Vacuolares Próton-Translocadoras/fisiologia , Sequência de Aminoácidos , Clonagem Molecular , DNA Complementar/metabolismo , Dados de Sequência Molecular , Filogenia , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Estrutura Terciária de Proteína , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sais/farmacologia , Homologia de Sequência de Aminoácidos , Cloreto de Sódio/farmacologia
11.
Sheng Wu Gong Cheng Xue Bao ; 19(1): 120-3, 2003 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-15969049

RESUMO

The gene orf25 encodes functional protein that may play an important role in plant fertility control in nature. To clone the orf25 from Salicornia europaea Xinjiang into a T-vector, a single designed primer was used to amplify 1.7kb cDNA fragment with RT-PCR. Sequence analysis reveals that the cloned fragment contains entire orf25 coding region with 98%, 95%, 92% and 88% identity to that of orf25 from Beta vulgaris, Nicotiana, wheat and maize mitochondrion, respectively. This analysis suggests that orf25 gene is highly conserved in terms of evolution in plant; and it also suggests that wild plant Salicornia europaea contain a male-sterility gene similar to crops that is of great importance in improvement of the breed of crop.


Assuntos
Chenopodiaceae/genética , Primers do DNA/genética , Infertilidade das Plantas/fisiologia , Proteínas de Plantas/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Sequência de Bases , Dados de Sequência Molecular , Infertilidade das Plantas/genética , Proteínas de Plantas/química , Homologia de Sequência do Ácido Nucleico
12.
Sheng Wu Gong Cheng Xue Bao ; 19(5): 628-31, 2003 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-15969097

RESUMO

The United Nations Environment Program estimates that approximately 20% of agricultural land and 50% of cropland in the world is salt-stressed. The gene NHX (Na+/H+ exchanger) encodes functional protein that catalyzes the countertransport of Na+ and H+ across membranes and may play an important role in plant salt tolerance. To clone the NHX from the wild plant Populus euphratica collected in Tarim basin and Xinjiang Wujiaqu district into a T-vector, designed primer was used to amplify 1kb NHX cDNA fragment with RT-PCR. Total RNA was extracted from Populus euphratica tissue (plant tissue was collected from Tarim basin and Xinjiang Wujiaqu district and stored in liquid nitrogen) according to the Plant RNA Mini Kits of Omega. First cDNAs were synthesized from 1 microg total RNA of Populus euphratica seedling. A pair of primers were used to perform RT-PCR. The amplified DNA fragment was purified and cloned into pMD18-T vector. However, 1kb and 2.3kb fragment were obtained from Tarim basin and Xinjiang Wujiaqu district and named as PtNHX and PwNHX, respectively. Sequence analysis reveals that the cloned PtNHX fragment of Populus euphratica contains partial NHX coding region with 98%, 86%, 84% and 80% identity comparing with Atriplex gemelini, Suaeda maritima, Arabidopsis thaliana and Oryza sativa, respectively. This analysis suggests that NHX gene would be highly conserved in terms of evolution in plant; and it also suggests that the NHX gene of Populus euphratica also would have the similarity with that of Arabidopsis. It may be of great importance in improvement of the plant salt tolerance and breed of crop. At the same time, sequence analysis shows that PwNHX gene includes a coding region about 1350bp with 99% identity comparing with transposon Tn10 IS10-left transposase of Shigella flexneri. On the one hand, the NHX gene may lose its function because it was inserted a fragment in coding region. On the other hand, its product may play a important role in salt tolerance. Populus grow in saline soil. It speculates that it may have other salt tolerance mechanism in Populus. The transposon can be used as transposon tagging to clone other genes and it will help us to understand farther the salt tolerance mechanism.


Assuntos
Elementos de DNA Transponíveis/genética , Proteínas de Plantas/genética , Populus/genética , Sequência de Aminoácidos , DNA Complementar , Vetores Genéticos/genética , Dados de Sequência Molecular , Proteínas de Plantas/química , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Shigella flexneri/genética
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