Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 248
Filtrar
1.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(5): 534-537, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34816668

RESUMO

Objective: To investigate the effects of Sitagliptin on myocardial remodeling and autophagy in diabetic mice and its possible mechanisms. Methods: C57 mice aged ten weeks were treated with streptozocin (STZ) at the dose of 50 mg/(kg·d) by intraperitoneal injections for five consecutive days, and the level of fasting blood glucose concentration was higher than 16.7 mmol/l after seven days indicated that the diabetic model was established successfully. Mice were divided into four groups, including control group (n=10) which was intraperitoneally injected with the same volum of saline, the model group (n=8), Sitagliptin treatment group(diabetic mice were treated with Sitagliptin at the dose of 10 mg/(kg·d)by gavage, n=8) and the inhibitor group(diabetic mice were treated with Compound C, an AMPK inhibitor, at the dose of 10 mg/(kg·d) by intraperitoneal injection, n=8). After six weeks, all the mices were weighted and then put to death and the hearts were separated to caculate ventricular /body weight ratio. Hemaloxylin-Eosin (HE) staining was used to observe the cell morphology and masson staining was used to observe interstitial fibrosis. Western blot was used to test the heart protein expressions of Connexin43(Cx43), adenosine 5'-monophosphate -activated protein kinase (AMPK), brain natriuretic peptide(BNP), transforming growth factor(TGF-ß) and LC3B. Results: After six weeks of treatment, compared with control group, the ventricular /body weight ratio was improved (P<0.05), The cardiomyocyte hypertrophy and increased fibrosis were observed in the model group. The expression levels of BNP and TGF-ß were increased, while the expression levels of Cx43,LC3B and AMPK were decreased significantly(P<0.05). However, compared with model group, treatment with Sitagliptin decreased BNP, TGF-ß protein levels and increased Cx43 and LC3B protein levels, while Compound C could inhibit the upregulation of Cx43, LC3B and AMPK protein (P<0.05). Conclusion: Sitagliptin could improve cardiac hypertrophy and decrease interstitial fibrosis and AMPK-related signaling pathways was involved in the regulation of Cx43 and autophagy.


Assuntos
Diabetes Mellitus Experimental , Fosfato de Sitagliptina , Animais , Autofagia , Diabetes Mellitus Experimental/tratamento farmacológico , Camundongos , Miocárdio , Fosfato de Sitagliptina/farmacologia , Estreptozocina
2.
Chin Med J (Engl) ; 134(22): 2656-2665, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34759230

RESUMO

OBJECTIVE: Cardiovascular diseases are associated with an increased risk of depression, but it remains unclear whether treatment with cardiovascular agents decreases or increases this risk. The effects of drugs on individual usage are also often unknown. This review aimed to examine the correlation between depression and common cardiovascular drugs, develop more potent interventions for depression in cardiovascular patients, and further research on the bio-behavioural mechanisms linking cardiovascular drugs to depression. DATA SOURCES: The data in this review were obtained from articles included in PubMed, EMBASE, and Web of Science. STUDY SELECTION: Clinical trials, observational studies, review literature, and guidelines about depression and cardiovascular drugs were selected for the article. RESULTS: We systematically investigated whether the seven most used cardiovascular drugs were associated with altered risk of incident depression in this literature review. Statins have been proven to have antidepressant effects. Some studies believe angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blocker (ARB) can exert an antidepressant influence by acting on the renin-angiotensin system, but further clinical trials are needed to confirm this. Beta-blockers have previously been associated with depression, but the current study found no significant association between beta blockers and the risk of depression. Aspirin may have antidepressant effects by suppressing the immune response, but its role as an antidepressant remains controversial. calcium channel blockers (CCBs) can regulate nerve signal transduction by adjusting calcium channels, but whether this effect is beneficial or harmful to depression remains unclear. Finally, some cases have reported that nitrates and diuretics are associated with depression, but the current clinical evidence is insufficient. CONCLUSIONS: Statins have been proven to have antidepressant effect, and the antidepressant effects of ACEIs/ARB and aspirin are still controversial. CCBs are associated with depression, but it is unclear whether it is beneficial or harmful. No association has been found with ß-blockers, diuretics, and nitrates.

3.
MedComm (2020) ; 2(3): 297-314, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34766148

RESUMO

As key performers in intercellular communication, exosomes released by tumor cells play an important role in cancer development, including angiogenesis, cancer-associated fibroblasts activation, epithelial-mesenchymal transformation (EMT), immune escape, and pre-metastatic niche formation. Meanwhile, other cells in tumor microenvironment (TME) can secrete exosomes and facilitate tumor progression. Elucidating mechanisms regarding these processes may offer perspectives for exosome-based antitumor strategies. In this review, we mainly introduce the versatile roles of tumor or stromal cell derived exosomes in cancer development, with a particular focus on the biological capabilities and functionalities of their diverse contents, such as miRNAs, lncRNAs, and circRNAs. The potential clinical application of exosomes as biomarkers in cancer diagnosis and prognosis is also discussed. Finally, the current antitumor strategies based on exosomes in immunotherapy and targeted delivery for chemotherapeutic or biological agents are summarized.

4.
Zhongguo Zhong Yao Za Zhi ; 46(19): 5123-5129, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34738410

RESUMO

The systematic collation and mining of ethnic medicine literature is the key to the screening and textual research of classic prescriptions. This study focused on the textual research of such key issues as the source of prescriptions, the translation of minority languages into Chinese characters and their corresponding medical terms, the original plants of drugs, and the standard dosage. It is believed that the methods and experience of textual research of classic prescriptions in traditional Chinese medicine(TCM) can be utilized by the ethnic medicine. At the same time, the prominent problems unique to ethnic medicine cannot be neglected.(1)Attention should be paid to extraterritorial traditional medical literature in the textual research of the source of prescriptions. For instance, Indian medical literature is the source of many classic prescriptions in Tibetan medicine, Ibn Sina's Canon of Medicine the source of those in Uygur and Hui medicine, and ancient Indian Buddhist classics the source of those in Dai medicine.(2)The translation and comparison of medical terms in different language systems requires the cooperation of linguists, historians, and medical experts, the combination of historical research, historical linguistics and clinical research methods, and the use of cross-language comparison. In recent years, the related research achievements like multiple translated and annotated versions of classical literature in ethnic medicine and their respective terminology standards have been constantly emerging.(3)In textual research of the original plants of drugs, the following two points deserve attention: one is that the same drug is used in different ethnic medical systems, but there are differences in the understanding of drug properties and active parts; the other is that the original plants of the same drug vary in different ethnic medical systems.(4)The derivation of some classic prescriptions in ethnic medicine from foreign classics results in the difference among measurement systems. In addition, the detailed dosage fails to be covered in some ethnic literature, so the dosage standard should be determined depending on clinical practice and expert consensus.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Medicina Tradicional Tibetana , Prescrições , Publicações
5.
Phytomedicine ; 93: 153799, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34715511

RESUMO

BACKGROUND: Natural medicines have a long history in the prevention and treatment of various diseases in East Asian region, especially in China. Modern research has proved that the pharmacological effects of numerous natural medicines involve the participation of ubiquitin proteasome system (UPS). UPS can degrade the unwanted and damaged proteins widely distributed in the nucleus and cytoplasm of various eukaryotes. PURPOSE: The objective of the present study was to review and discuss the regulatory effects of natural products and extracts on proteasome components, which may help to find new proteasome regulators for drug development and clinical applications. METHODS: The related information was compiled using the major scientific databases, such as CNKI, Elsevier, ScienceDirect, PubMed, SpringerLink, Wiley Online, and GeenMedical. The keywords "natural product" and "proteasome" were applied to extract the literature. Nature derived extracts, compounds and their derivatives involved in proteasome regulation were included, and the publications related to synthetic proteasome agents were excluded. RESULTS: The pharmacological effects of more than 80 natural products and extracts derived from phytomedicines related to the proteasome regulation were reviewed. These natural products were classified according to their chemical properties. We also summarized some laws of action of natural products as proteasome regulators in the treatment of diseases, and listed the action characteristics of the typical natural products. CONCLUSION: Natural products derived from nature can induce the degradation of damaged proteins through UPS or act as regulators to directly regulate the activity of proteasome. But few proteasome modulators are applied clinically. Summary of known rules for proteasome modulators will contribute to discover, modify and synthesize more proteasome modulators for clinical applications.


Assuntos
Produtos Biológicos , Complexo de Endopeptidases do Proteassoma , Produtos Biológicos/farmacologia , China , Citoplasma , Ubiquitina
6.
Am J Transl Res ; 13(8): 8683-8696, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539987

RESUMO

Downregulation of inward rectifier potassium (IK1) channel is a hallmark in cardiac hypertrophy and failure. The cardioprotection of zacopride (a selective IK1 agonist) and underlying mechanisms were investigated in L-thyroxine (T4) or Triiodothyronine (T3)-induced cardiac remodeling. In the in vivo study, adult male Sprague-Dawley (SD) rats were randomly divided into control, L-thyroxine, L-thy+zacopride, and L-thy+zacopride+chloroquine (an IK1 antagonist) groups. Echocardiography, histopathology, TUNEL assay, western blotting and confocal imaging for intracellular Ca2+ fluorescence were performed. In the in vitro study, zacopride and nifedipine (a LTCC blocker) were used to compare their effects on Kir2.1, SAP97, autophagy, and [Ca2+]i in H9C2 (2-1) cardiomyocytes. Zacopride treatment attenuated L-thyroxine- or T3 induced cardiac remodeling and dysfunction which manifested as cardiac hypertrophy and collagen deposition, dilated ventricle, decreased ejection fraction (EF), increased cardiomyocytes apoptosis, hyper-activation of CaMKII and PI3K/Akt/mTOR signaling, decreased cardiac autophagy, and increased expression of integrin ß3. The cardioprotection of zacopride is strongly associated with the upregulation of IK1, SAP97, and [Ca2+]i homeostasis in cardiomyocytes. IK1 antagonist chloroquine or BaCl2 reversed these effects. Nifedipine could attenuate intracellular Ca2+ overload with no significant effects on IK1, SAP97, and autophagy. This study showed that zacopride could improve cardiac remodeling via facilitating Kir2.1 forward trafficking, and negatively regulating calcium-activated and PI3K/Akt/mTOR signalings, in an IK1-dependent manner.

8.
Chin Med J (Engl) ; 134(16): 1897-1907, 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34415890

RESUMO

ABSTRACT: Oxidative stress is caused by the imbalance between the generation of free radicals/reactive oxygen species (ROS) and the antioxidant defense systems, which can activate various transcription factors and affect their transcriptional pathways. Oxidative stress plays an important role in the occurrence and development of leukemia and is closely related to the treatment and prognosis of leukemia. The standard chemotherapy strategies for the pre-treatment of leukemia have many drawbacks. Hence, the usage of antioxidants and oxidants in the treatment of leukemia is being explored and has been preliminarily applied. This article reviews the research progress of oxidative stress and leukemia. In addition, the application of antioxidants treatment in leukemia has been summarized.


Assuntos
Antioxidantes , Leucemia , Antioxidantes/uso terapêutico , Humanos , Leucemia/tratamento farmacológico , Estresse Oxidativo , Espécies Reativas de Oxigênio
9.
Oxid Med Cell Longev ; 2021: 6677687, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34234887

RESUMO

Cervical cancer is a common female malignant tumor that seriously threatens human health. This study explored the anticervical cancer effects and potential mechanisms of Rotundifuran (RTF), a natural product isolated from Vitex trifolia L. In this study, we found that RTF can suppress the proliferation of cervical cancer cell lines, including HeLa and SiHa cells (with the IC50 less than 10 µM), via induction of apoptosis in vitro, and the antitumor effect of RTF is further confirmed on the HeLa cell-inoculated xenograft model. In addition, our results proved that the antitumor effects of RTF might be related with the reactive oxygen species- (ROS-) induced mitochondrial-dependent apoptosis through MAPK and PI3K/Akt signal pathways. Using proteomics analysis and the drug affinity responsive target stability- (DARTS-) combined mass spectrometry (DARTS-MS), Cyr61 was indicated as a potential target for RTF in cervical cancer cells. Our present study would be beneficial for the development of RTF as a candidate for treatment of cervical cancer in the future.

10.
J Clin Sleep Med ; 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34319229

RESUMO

STUDY OBJECTIVES: The aims of this study were to explore changes in the telomere length (relative telomere repeat copy/single-copy gene, T/S ratio) and serum neurofilament light chain (sNfL) levels in female patients with chronic insomnia disorder (CID), examine their relationships with emotional abnormalities and cognitive impairment, and determine whether these 2 indicators were independently associated with sleep quality. METHODS: The CID group contained 80 patients diagnosed with CID, and 51 individuals constituted a healthy control group (HC). Participants completed sleep, emotion, and cognition assessments. Telomere length was detected through quantitative real-time polymerase chain reaction (qRT-PCR). Enzyme-linked immunosorbent assay was used to determine sNfL concentrations. RESULTS: Relative to the HC group, the CID group had elevated Pittsburgh Sleep Quality Index (PSQI), Hamilton Anxiety scale-14 (HAMA-14), and Hamilton Depression Rating scale-17 (HAMD-17) scores and reduced Montreal Cognitive Assessment scale (MoCA) scores, a decreased T/S ratio, and an increased sNfL concentration. Subgroup analysis according to various CID-associated sleep factors showed that poor sleep performance corresponded with a lower T/S ratio. Higher anxiety levels and more cognitive dysfunction correlated with shorter telomere lengths. The T/S ratio negatively correlated with age, whereas the sNfL concentration positively correlated with age in the CID group. The PSQI score negatively correlated with the T/S ratio but did not correlate with sNfL levels. Multiple linear regression analysis showed that the T/S ratio had a negative and independent effect on PSQI scores. CONCLUSIONS: The CID group had shorter telomeres and higher sNfL concentrations, and reduced telomere length independently affected sleep quality.

11.
Arch Insect Biochem Physiol ; 108(1): e21797, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34272770

RESUMO

Cold temperatures are one of the factors influencing color polymorphisms in Acyrthosiphon pisum, resulting in a change from a red to greenish color. Here we characterized gene expression profiles of A. pisum under different low temperatures (1°C, 4°C, 8°C, and 14°C) and durations (3, 6, 12, and 24 h). The number of differentially expressed genes (DEGs) increased as temperatures decreased and time increased, but only a small number of significant DEGs were identified. Genes involved in pigment metabolism were downregulated. An interaction network analysis for 506 common DEGs in comparisons among aphids exposed to 1°C for four durations indicated that a cytochrome P450 gene (CYP, LOC112935894) significantly downregulated may interact with a carotenoid metabolism gene (LOC100574964), similar to other genes encoding CYP, lycopene dehydrogenase and fatty acid synthase. We proposed that the body color shift in A. pisum responding to low temperatures may be regulated by CYPs.


Assuntos
Afídeos , Temperatura Baixa , Sistema Enzimático do Citocromo P-450/genética , Pigmentação/genética , Animais , Afídeos/genética , Afídeos/metabolismo , Ácido Graxo Sintases/genética , Genoma de Inseto , RNA-Seq/métodos , Transcriptoma
12.
Biomater Sci ; 9(19): 6403-6415, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34259235

RESUMO

Tumor hypoxic stress after photodynamic therapy (PDT) will be inevitably exacerbated by the vascular blocking effects and oxygen consumption in the tumor microenvironment (TME) which usually leads to compromised efficacy and clinical performance. Increasing evidence links the hypoxia induced up-regulation of hypoxia inducible factor 1α (HIF-1α) with immunosuppressive TME, including the polarization of M2 phenotype tumor associated macrophages (TAMs), which promote the recurrence and metastasis. Here, we reported NIR-triggered core-satellite upconverting nanoparticles (CSNPs) with curcumin (Cur) embedded as a difunctional photosensitizer, which could realize PDT in deep tumors with long excitation wavelength (980 nm) and reverse the immunosuppressive TME induced by up-regulated HIF-1α at the same time. This Cur-loaded CSNPs (Cur-CSNPs)-mediated PDT could successfully induce the immunogenic cell death (ICD) of triple negative breast cancer (TNBC) cell lines (4T1 and MDA-MB-231) in vitro and repolarize the 4T1 cells co-cultured TAMs from pro-tumor M2 to the anti-tumor M1 phenotype. Furthermore, Cur-CSNPs-mediated PDT could suppress the 4T1 tumor growth in primary and distant sites through the synergistic immunotherapeutic effects in vivo by priming M1 type TAMs and CD4+/CD8+ T cells' infiltration. Our data highlight the novel application of CSNPs-embedded Cur as a difunctional photosensitizer to enhance the anti-tumor efficacy of PDT.


Assuntos
Curcumina , Nanopartículas , Fotoquimioterapia , Linfócitos T CD8-Positivos , Linhagem Celular Tumoral , Curcumina/farmacologia
13.
Front Microbiol ; 12: 620322, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34163438

RESUMO

Objective: Gasdermin D (GSDMD), controlling pyroptosis in cells, has multiple physiological functions. The diagnostic role of GSDMD in pleural effusion (PE) remains unknown. Methods: Sandwich ELISA kits that we developed were applied to measure the level of GSDMD for 335 patients with a definite cause of PE, including transudative PE, tuberculous pleural effusion (TPE), parapneumonic pleural effusion (PPE), and malignant pleural effusion (MPE). The diagnostic accuracy of Light's criteria vs. the new marker GSDMD was performed. Clinical follow-up of 40 cases of PPE was conducted and divided into efficacy and non-efficacy groups according to the therapeutic outcome. Nucleated cells (NCs) in PE were isolated and further infected with bacteria to verify the cell source of GSDMD. Results: The diagnostic accuracy of GSDMD for the diagnosis of PE were 96% (sensitivity) and 94% (specificity). The receiver operating characteristic (ROC) curve indicated that GSDMD can be an efficient biomarker for the differential diagnosis of transudative PE and other groups (all AUC > 0.973). Noteworthily, the highest AUC belonged to tuberculosis diagnosis of 0.990, and the cut-off value was 18.40 ng/mL. Moreover, the same cut-off value of PPE and MPE was 9.35 ng/mL. The combination of GSDMD, adenosine deaminase (ADA), and lactate dehydrogenase (LDH) will further improve the diagnostic efficiency especially between TPE and PPE (AUC = 0.968). The AUC of GSDMD change at day 4, which could predict the therapeutic effect at an early stage, was 0.945 (P < 0.0001). Interestingly, bacterial infection experiments further confirm that the pleural fluid GSDMD was expressed and secreted mainly by the NCs. Conclusion: GSDMD and its combination are candidates as a potentially novel biomarker not only to separate PEs early and effectively, but also monitor disease progression.

14.
Biomed Pharmacother ; 141: 111833, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34175822

RESUMO

Natural products continue to be an unparalleled source of pharmacologically active lead compounds because of their unprecedented structures and unique biological activities. Natural product target discovery is a vital component of natural product-based medicine translation and development and is required to understand and potentially reduce mechanisms that may be associated with off-target side effects and toxicity. Omics-based techniques, including genomics, transcriptomics, proteomics, metabolomics, and bioinformatics, have become recognized as effective tools needed to construct innovative strategies to discover natural product targets. Although considerable progress has been made, the successful discovery of natural product targets remains a challenging time-consuming process that has come to increasingly rely on the effective integration of multi-omics-based technologies to create emerging panomics (a.k.a., integrative omics, pan-omics, multiomics)-based strategies. This review summarizes a series of successful studies regarding the application of integrative omics-based methods in natural product target discovery. The advantages and disadvantages of each technique are discussed, with a particular focus on the systematic integration of multi-omics strategies. Further, emerging micro-scale single-cell-based techniques are introduced, especially to deal with minute natural product samples.

15.
Front Oncol ; 11: 687120, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34109132

RESUMO

Despite the dramatic advances in cancer research in the past few years, effective therapeutic strategies are urgently needed. Endothelial cell-specific molecule 1 (ESM-1), a soluble dermatan sulfate proteoglycan, also known as endocan, serves as a diagnostic and prognostic indicator due to its aberrant expression under pathological conditions, including cancer, sepsis, kidney diseases, and cardiovascular disease. Significantly, ESM-1 can promote cancer progression and metastasis through the regulation of tumor cell proliferation, migration, invasion, and drug resistant. In addition, ESM-1 is involved in the tumor microenvironment, containing inflammation, angiogenesis, and lymph angiogenesis. This article reviews the molecular and biological characteristics of ESM-1 in cancer, the underlying mechanisms, the currently clinical and pre-clinical applications, and potential therapeutic strategies. Herein, we propose that ESM-1 is a new therapeutic target for cancer therapy.

16.
Mitochondrial DNA B Resour ; 6(4): 1326-1327, 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33889740

RESUMO

Here, we sequenced and annotated the complete mitochondrial genome (mitogenome) of Palomena viridissima (Hemiptera: Pentatomidae). This mitogenome was 15,118 bp long, comprising of 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), 2 ribosomal RNA genes (rrnL and rrnS) and a large non-coding control region. The P. viridissima mitogenome with an A + T content of 76.0%, presented a positive AT-skew (0.11) and a negative GC-skew (-0.13). Ten PCGs started with a typical ATN codon, two PCGs started with TTG (atp8, nad1), whereas the remaining one used AAC (cox1). All tRNAs had a typical secondary cloverleaf structure, except for trnS1 which lacked the dihydrouridine arm. The Bayesian phylogenetic analysis based on mitogenomic data supported a sister relationship of P. viridissima and Nezara viridula from the same tribe Nezarini and recovered a phylogeny of Pentatominae: (Menidini + (Strachiini + (Pentatomini + ((Cappaeini + Halyini) + (Eysarcorini + (Nezarini + Carpocori)))))).

17.
Phytomedicine ; 85: 153540, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33773188

RESUMO

BACKGROUND: Neuroinflammation is defined as innate immune system activation in the central nervous system, and is a complex response involved in removing pathogens, toxic components, and dead cells by activating microglial cells. However, over-activated microglia have been implicated in the pathogenesis of neurodegenerative diseases, because they release large amounts of neurotoxic factors. Thus, inhibiting microglial activation may represent an attractive approach for preventing neuroinflammatory disorders. The objective of this study was to investigate the effect of narciclasine (NA) on lipopolysaccharide (LPS)-induced neuroinflammation by evaluating related markers and neurotoxic factors. METHODS: BV-2 cells were pre-incubated with NA at 0.1, 0.2, and 0.3 µM for 1h, and then co-treated with LPS for 12 h. Cellular medium and lysates were measured using a nitric oxide assay, enzyme-link immunosorbent assay (ELISA), western blotting, kinase activity assay, luciferase assay, and immunofluorescence assay. C57BL/6N mice were orally administered NA and intraperitoneally injected with LPS, and the cerebral cortex was examined using western blotting and immunofluorescence assays. RESULTS: NA showed novel pharmacological activity, inhibiting pro-inflammatory factors, including TNF-α, IL-6, IL-18, NO, and PGE2, but increasing the anti-inflammatory cytokines IL-10 and TGF-ß1 in LPS-induced microglial cells. Moreover, NA also attenuated the LPS-induced mRNA and proteins of iNOS and COX-2. The mechanistic study indicated that NA attenuates the secretion of pro-inflammatory factor by down-regulating the Akt/IKK/NF-κB and JNK signaling pathways, and directly inhibits the catalytic activity of IKKα/ß. Furthermore, we found that NA also reduced the expression of the microglial markers Iba-1, COX-2, and TNF-α in the mouse brain. CONCLUSION: NA inhibits the over-expression of pro-inflammatory factors but it promotes anti-inflammatory cytokines by down-regulating the Akt/IKK/NF-κB and JNK signaling pathways in experimental models. Thus, NA may be a potential candidate for relieving neuroinflammation.


Assuntos
Alcaloides de Amaryllidaceae/farmacologia , Anti-Inflamatórios/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Microglia/efeitos dos fármacos , Fenantridinas/farmacologia , Animais , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Inflamação , Lipopolissacarídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
18.
Int J Mol Med ; 47(5)2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33649781

RESUMO

Glioblastoma (GBM) is the most common aggressive brain tumor and is associated with an extremely poor prognosis, as the current standard of care treatments have limited efficacy. Natural compounds have attracted increasing attention as potential anticancer drugs. Alantolactone (ATL) is a natural small molecule inhibitor, that has antitumor properties. In the present study, U87MG and U251 cells were treated ATL and changes in actin/G­actin/F­actin/cofilin pathway were detected in whole cells, in the cytoplasm and mitochondria by western blot analysis. Immunofluorescence and immunoprecipitation analysis identified changes in the expression levels of target proteins and interactions, respectively. A LIMK enzyme inhibitor was also applied to assess the effects of ATL on the migration and invasion of GBM cells. Flow cytometry was used to detect the levels of apoptosis of GBM cells. The expression of matrix metalloproteinase (MMP)­2/MMP­9, caspase­3/caspase­9/poly(ADP­ribose) polymerase (PARP)/cytochrome c, were determined by western blot analysis to assess the effects of targeting LIMK. The in vitro findings were verified in vivo by characterizing changes in the expression of cofilin/LIMK in xenograft tumors in immunodeficient mice. It was found that ATL activated cofilin through the targeted inhibition of LIMK enzyme activity and it thus upregulated the ratio of G/F actin, and inhibited GBM cell migration and invasion. Conversely, the activation of cofilin and G­actin could be co­transferred to the mitochondria to initiate the mitochondrial­cytochrome c pathway to induce apoptosis. On the whole, the findings of the present study further illustrate the molecular mechanisms through which ATL inhibits the metastatic phenotype of GBM cells and induces apoptosis. Given previous findings, it can be deduced that ATL can function through multiple pathways and has multiple targets in GBM models, highlighting its potential for use in clinical applications.


Assuntos
Fatores de Despolimerização de Actina/metabolismo , Actinas/metabolismo , Apoptose/efeitos dos fármacos , Glioblastoma/metabolismo , Lactonas/farmacologia , Quinases Lim/metabolismo , Proteínas de Neoplasias/metabolismo , Sesquiterpenos de Eudesmano/farmacologia , Fatores de Despolimerização de Actina/genética , Actinas/genética , Linhagem Celular Tumoral , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Glioblastoma/patologia , Humanos , Quinases Lim/genética , Metástase Neoplásica , Proteínas de Neoplasias/genética
19.
Kaohsiung J Med Sci ; 37(4): 268-275, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33336500

RESUMO

Long noncoding RNA (lncRNA) Cancer Susceptibility 2 (CASC2) has been proved to contribute to the development of cancers. However, the mechanism behind the action of CASC2 in thyroid cancer is not quite clear. We demonstrated that CASC2 was downregulated in thyroid cancer. We noted that CASC2 overexpression restrained the growth, migration, and invasion of thyroid cancer cells, whereas CASC2 depletion caused opposite trends. Bioinformatics analysis predicted that hypoxia inducible factor 1 subunit alpha inhibitor (FIH-1) was potentially targeted by miR-18a-5p, which was confirmed by luciferase reporter assay. Upregulation of FIH-1 abrogated the promotive effect of miR-18a-5p on the growth and invasion of thyroid cancer cells. In addition, CASC2 serves as a competing endogenous RNA (ceRNA) and a ''sponge'' for miR-18a-5p, thereby regulating the expression of FIH-1. These data elucidated the CASC2/miR-18a-5p ceRNA network in thyroid cancer pathogenesis.


Assuntos
Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Oxigenases de Função Mista/genética , RNA Longo não Codificante/genética , Proteínas Repressoras/genética , Proteínas Supressoras de Tumor/genética , Pareamento de Bases , Sequência de Bases , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Genes Reporter , Humanos , Luciferases/genética , Luciferases/metabolismo , MicroRNAs/metabolismo , Oxigenases de Função Mista/metabolismo , RNA Longo não Codificante/metabolismo , Proteínas Repressoras/metabolismo , Transdução de Sinais , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , Proteínas Supressoras de Tumor/metabolismo
20.
Mitochondrial DNA B Resour ; 5(1): 667-668, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-33366695

RESUMO

Here, we determined the nearly complete mitochondrial genome (mitogenome) of Chrysochares punctatus (Coleoptera: Chrysomelidae: Eumolpinae), an important insect pest on Apocynum venetum in Northwestern China. This mitogenome was 14,451 bp long, encoding 13 protein-coding genes (PCGs), 21 transfer RNA genes (tRNAs), and 2 ribosomal RNA genes. The C. punctatus mitogenome presented an A + T content of 75.11%, with a positive AT-skew (0.064) and a negative GC-skew (-0.192). Ten PCGs started with a typical ATN codon, whereas the remaining three PCGs started with AAC (cox1) and TTG (nad1 and nad2). All tRNAs had a typical secondary cloverleaf structure, except for trnS1 which lacked the dihydrouridine arm. Bayesian phylogenetic analysis based on the nucleotide sequences of 13 PCGs recovered a phylogeny within Chrysomelidae: (((Chrysomelinae + Galerucinae), (((Eumolpinae, Lamprosomatinae), Cassidinae), Criocerinae)), Bruchinae).

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...