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1.
Artigo em Inglês | MEDLINE | ID: mdl-34523091

RESUMO

Plant diversity is changing in the world; climate variation at annual scale is believed to drive these changes; however, the effects of climate variation at month scale are still unknown. Anxi, West Ordos, Xilingol, and Tumuji grassland nature reserves, located in northern China, have been well protected from human disturbance, are ideal areas to identify the drive forces for plant diversity change. Using Landsat images from 1982 to 2017, we analyzed the evolution of month- and annual-climate variables and spectral plant diversity indices, and explored the effects of the variability of temperature and precipitation on plant diversity and their relationship. The results showed that the diversity of the four grasslands was decreasing. Climate variables, in particular temperature at month scale, significantly related to grassland plant diversity. These results enlarge our understanding in how climate change driving plant diversity during a long term. Measurements coping with plant diversity decreasing may be more effective and earlier based on monthly climate variables.

2.
J Inorg Biochem ; 225: 111616, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34555601

RESUMO

Ruthenium-containing complexes have emerged as good alternative to the currently used platinum-containing drugs for malignant tumor therapy. In this work, cytotoxic effects of recently synthesized ruthenium polypyridyl complexes [Ru(bpy)2(CFPIP)](ClO4)2 (bpy = 2,2'-bipyridine, CFPIP = (E)-2-(4-fluorostyryl)-1H-imidazo[4,5-f][1,10]phenanthroline, Ru(II)-1), [Ru(phen)2(CFPIP)](ClO4)2 (phen = 1,10-phenanthroline, Ru(II)-2) and [Ru(dmb)2(CFPIP)](ClO4)2 (dmb = 4,4'-dimethyl-2,2'-bipyridine, Ru(II)-3) toward different tumor cells were investigated in vitro and compared with cisplatin, the most widely used chemotherapeutic drug against hepatocellular carcinoma (HepG-2). The results demonstrate that target complexes show excellent cytotoxicity against HepG-2 cells with low IC50 value of 21.4 ± 1.5, 18.0 ± 2.1 and 22.3 ± 1.7 µM, respectively. It was important noting that target Ru(II) complexes exhibited better antitumor activity than cisplatin (IC50 = 28.5 ± 2.4 µM) against HepG-2 cells, and has no obvious toxicity to normal cell LO2. DNA binding results suggest that Ru(II)-1, Ru(II)-2 and Ru(II)-3 interact with CT DNA (calf thymus DNA) through intercalative mode. Complexes exerted its antitumor activity through increasing anti-migration and inducing cell cycle arrest at the S phase. In addition, the apoptosis was tested by AO (acridine orange)/EB (ethidium bromide) staining and flow cytometry. Mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and colocalization tests were also evaluated by ImageXpress Micro XLS system. Overall, the results show that the ruthenium polypyridyl complexes induce apoptosis in HepG-2 cells through ROS-mediated mitochondria dysfunction pathway.

3.
J Inorg Biochem ; 225: 111603, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34564032

RESUMO

Two iridium (III) polypyridine complexes [Ir(ppy)2(BIP)]PF6 (ppy = 2-phenylpyridine, BIP = 2-biphenyl-1H-imidazo[4,5-f][1,10]phenanthroline, Ir1), [Ir(piq)2(BIP)]PF6 (piq = 1-phenylisoquinoline, Ir2) and their liposomes Ir1lipo and Ir2lipo were synthesized and characterized. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate cytotoxic activity against several cancer cells (A549, HepG2, SGC-7901, Bel-7402, HeLa) and non-cancer cell (mouse embryonic fibroblast, NIH3T3). The results showed that Ir1lipo displays the high cytotoxicity toward SGC-7901 with IC50 value of 5.8 ± 0.2 µM, while the complexes have no cytotoxicity toward A549, HepG2, Bel-7402 and HeLa cells. The cell colony demonstrated that the iridium (III) complexes-loaded liposomes can inhibit cell proliferation, induce cell cycle arrest at G0/G1 phase. Moreover, they also cause autophagy, induce a decrease of mitochondrial membrane potential and increase intracellular reactive oxygen species (ROS) content. These results suggest that the complexes encapsulated liposomes Ir1lipo and Ir2lipo inhibit the growth of SGC-7901 cells through a ROS-mediated mitochondrial dysfunction and activating the PI3K (phosphoinositide-3 kinase)/ AKT (protein kinase B) signaling pathways.

4.
Cell Metab ; 33(10): 2059-2075.e10, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34536344

RESUMO

Myocardial ischemia-reperfusion (MIR) injury is a major cause of adverse outcomes of revascularization after myocardial infarction. To identify the fundamental regulator of reperfusion injury, we performed metabolomics profiling in plasma of individuals before and after revascularization and identified a marked accumulation of arachidonate 12-lipoxygenase (ALOX12)-dependent 12-HETE following revascularization. The potent induction of 12-HETE proceeded by reperfusion was conserved in post-MIR in mice, pigs, and monkeys. While genetic inhibition of Alox12 protected mouse hearts from reperfusion injury and remodeling, Alox12 overexpression exacerbated MIR injury. Remarkably, pharmacological inhibition of ALOX12 significantly reduced cardiac injury in mice, pigs, and monkeys. Unexpectedly, ALOX12 promotes cardiomyocyte injury beyond its enzymatic activity and production of 12-HETE but also by its suppression of AMPK activity via a direct interaction with its upstream kinase TAK1. Taken together, our study demonstrates that ALOX12 is a novel AMPK upstream regulator in the post-MIR heart and that it represents a conserved therapeutic target for the treatment of myocardial reperfusion injury.

5.
Hepatology ; 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34435375

RESUMO

BACKGROUND & AIMS: Although the prevalence of nonalcoholic fatty liver disease (NAFLD) has risen dramatically to 25% of the adult population worldwide, there are as yet no approved pharmacological interventions for the disease due to uncertainty about the underlying molecular mechanisms. It is known that mitochondrial dysfunction is an important factor in the development of NAFLD. Mitochondrial antiviral signaling protein (MAVS) is a critical signaling adaptor for host defenses against viral infection. However, the role of MAVS in mitochondrial metabolism during NAFLD progression remains largely unknown. APPROACH & RESULTS: Based on expression analysis, we identified a marked downregulation of MAVS in hepatocytes during NAFLD progression. By employing MAVS global knockout and hepatocyte-specific MAVS knockout mice, we found that MAVS is protective against diet-induced NAFLD. MAVS deficiency induces extensive mitochondrial dysfunction during NAFLD pathogenesis which was confirmed as impaired mitochondrial respiratory capacity and membrane potential. Metabolomics data also showed the extensive metabolic disorders after MAVS deletion. Mechanistically, MAVS interacts with the N-terminal stretch of voltage-dependent anion channel 2 (VDAC2), which is required for the ability of MAVS to influence mitochondrial function and hepatic steatosis. CONCLUSIONS: In hepatocytes, MAVS plays an important role in protecting against NAFLD by helping to regulate healthy mitochondrial function. These findings provide new insights regarding the metabolic importance of conventional immune regulators and support the possibility that targeting MAVS may represent a new avenue for treating NAFLD.

6.
Endocr J ; 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34408100

RESUMO

Obesity, closely related to systematic metabolic disorders, has become a major public health problem in recent decades. Here, we aimed to study the function of Parathyroid hormone-related protein (PTHrP) on high fat diet (HFD) induced murine obesity. Male C57BL/6J mice were transduced with adeno-associated virus vector encoding PTHrP (AAV-PTHrP) or adeno-associated virus control vector (AAV-Vehicle), following with HFD for 8 weeks. In addition, mice without transduction were fed on normal diet or HFD, respectively. Histological, metabolic and biochemical changes were detected. At the endpoint of experiment, body weight of mice treated with AAV-PTHrP did not increase as much as mice with AAV-Vehicle, but similar as mice with normal diet. Food efficiency ratio and weight of interscapular brown adipose tissue and epididymal white adipose tissue in mice overexpressed PTHrP were also lower than mice transducted with AAV-Vehicle. Besides, administration of AAV-PTHrP inhibited HFD-induced adipocyte hypertrophy. Protein level of PKA signaling pathway and thermogenic gene in adipose tissue exhibited a significant raise in HFD + AAV-PTHrP group, whereas transcription of inflammatory gene were decreased. Additionally, PTHrP overexpression ameliorated HFD-induced dyslipidemia, hepatic steatosis and insulin sensitivity. In HFD-induced murine obesity model, PTHrP is crucial to maintain metabolic homeostasis. PTHrP drives white adipose tissue browning and inhibits whitening of brown adipose tissue. Most importantly, PTHrP prevented HFD-induced obesity, hepatic steatosis and insulin resistance.

7.
J Inorg Biochem ; 223: 111550, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34311319

RESUMO

The new ligand BBIP (BBIP = 2-(7-bromo-2H-benzo[d]imidazole-4-yl)-1H-imidazo[4,5-f][1,10]phenanthroline) with its iridium(III) complexes: [Ir(ppy)2(BBIP)](PF6) (ppy = 2-phenylpyridine, Ir1), [Ir(bzq)2(BBIP)](PF6) (bzq = benzo[h]quinolone, Ir2) and [Ir(piq)2(BBIP)](PF6) (piq = 1-phenylisoquinoline, Ir3) were synthesized and characterized by elemental analysis, High Resolution Mass Spectrometer (HRMS), 1H NMR and 13C{1H} NMR. The cytotoxicity of the complexes against A549, HepG2, SGC-7901, BEL-7402, HeLa and normal LO2 was evaluated through 3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide (MTT) method. The results show that Ir1 exhibits high cytotoxic activity against A549 cells with a low IC50 value of 4.9 ± 0.5 µM. A series of biological activities such as cell cycle arrest, endoplasmic reticulum localization assay, apoptosis, western blotting, cellular uptake determination and in vivo antitumor activity were investigated. The assays implied that the complexes inhibit cancer cell migration through blocking mitotic progress. Cell cycle distribution stated that the complexes depress cell growth at G0/G1 phase. Additionally, the complexes acted on the endoplasmic reticulum and induce apoptosis through endoplasmic reticulum stress pathway. Especially, the western blotting showed that the complexes activated Bcl-2 (B-cell lymphoma-2) family and decreased PI3K (phosphoinositide-3 kinase) and AKT (protein kinase B), up-regulated the expression of mTOR (mammalian target of rapamycin) and p-mTOR (phosphorylated mammalian target of rapamycin). Therefore, the complexes induce apoptosis through activating PI3K-AKT-mTOR pathway. Antitumor in vivo demonstrated that Ir1 can effectively prevent the tumor growth with an inhibitory rate of 48.89%.

8.
Turk J Gastroenterol ; 32(4): 401-411, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-34231487

RESUMO

BACKGROUND: Double-balloon enteroscopy (DBE) enables the detection of ulcerations in the small bowel. However, determining an etiological diagnosis remains challenging. This study was conducted to investigate the clinical and endoscopic features of ulcerations with isolated involvement of the small bowel (UIISB) to improve diagnostic ability. METHODS: Patients (n = 565) who underwent DBE and presented with ulcerations in the small bowel at Nanfang Hospital from January 2005 to January 2018 were eligible. Medical records were retrospectively examined. Predictors to determine ulceration etiology were identified by logistic regression analysis. RESULTS: After excluding patients with extra-ulcerations in other sites (n = 306) and those without follow-up records (n = 50), 209 patients with UIISB were enrolled. Among them, 59.3% of the ulcers were in the ileum, 26.8% in the jejunum, and 13.4% in the jejunoileum. Initial symptoms included abdominal pain (54.1%) and obscure gastrointestinal bleeding (30.0%). The multiplicity of ulceration was categorized as a single (22.0%) or multiple (78.0%). Cases were diagnosed with Crohn's disease (50.7%), chronic nonspecific inflammation (21.5%), diverticulum (9.1%), lymphoma (6.2%), gastrointestinal stromal tumor (4.3%), intestinal tuberculosis (1.9%), adenocarcinoma (1.4%), infective enteritis (1.4%), hemangioma (1.0%), cryptogenic multifocal ulcerous stenosing enteritis (1.0%), anastomotic ulcer (0.5%), intestinal duplication (0.5%), or neuroendocrine tumor (0.5%). Etiology identification indicated the if patients were aged 40 years or more, or had overt bleeding, single ulceration, and ulcer at jejunum, it as more prone to be neoplastic (P < .05). CONCLUSION: When we manage patients with UIISB, Crohn's disease should be first under consideration. Age≥40, overt bleeding, single ulceration, and ulcer at jejunum were reasonable indications for etiology of neoplasm or non-neoplasm.

10.
Cell Metab ; 33(8): 1640-1654.e8, 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34107313

RESUMO

Obesity is characterized by the excessive accumulation of the white adipose tissue (WAT), but healthy expansion of WAT via adipocyte hyperplasia can offset the negative metabolic effects of obesity. Thus, identification of novel adipogenesis regulators that promote hyperplasia may lead to effective therapies for obesity-induced metabolic disorders. Using transcriptomic approaches, we identified transmembrane BAX inhibitor motif-containing 1 (TMBIM1) as an inhibitor of adipogenesis. Gain or loss of function of TMBIM1 in preadipocytes inhibited or promoted adipogenesis, respectively. In vivo, in response to caloric excess, adipocyte precursor (AP)-specific Tmbim1 knockout (KO) mice displayed WAT hyperplasia and improved systemic metabolic health, while overexpression of Tmbim1 in transgenic mice showed the opposite effects. Moreover, mature adipocyte-specific Tmbim1 KO did not affect WAT cellularity or nutrient homeostasis. Mechanistically, TMBIM1 binds to and promotes the autoubiquitination and degradation of NEDD4, which is an E3 ligase that stabilizes PPARγ. Our data show that TMBIM1 is a potent repressor of adipogenesis and a potential therapeutic target for obesity-related metabolic disease.

11.
J Sci Food Agric ; 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33969883

RESUMO

BACKGROUND: The COVID-19 outbreak caused short-term disruptions in the supply chain of fresh agricultural products (FAPs), which exposed the vulnerability of the existing FAP supply chain. With pandemic control being widely coordinated, the supply chain of FAPs was gradually optimized and improved. However, after the outbreak of COVID-19, achieving an effective supply of FAPs in future pandemics has become a key issue. The present work therefore aimed to construct a three-level supply chain based on the Stackelberg game model, consisting of suppliers, third-party logistics (TPL), and retailers, to guarantee the supply of FAPs. COVID-19 pandemic factors such as virus infection coefficients and pandemic prevention efforts were fully integrated into the model. RESULTS: Compared with the wholesale prices of FAPs, preservation efforts and pandemic prevention efforts have huge impacts on the retail prices of FAPs. When suppliers are in the leading position, the quality assurance effort level is positively correlated with the optimal profit. Compared with this situation, when FAP retailers are in the leading position, TPL providers show higher levels of pandemic prevention effort and FAP preservation effort. With an increase in consumer preference for pandemic prevention, the profits of supply-chain members when FAP retailers are in the leading position will gradually increase. CONCLUSION: This study reveals an effective supply mechanism for FAPs in metropolitan areas during the COVID-19 pandemic and describes the authors' experience of guaranteeing the quality and safety of FAPs for future pandemic cases. © 2021 Society of Chemical Industry.

12.
Free Radic Biol Med ; 172: 33-47, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34029692

RESUMO

Dysfunction in macrophages is involved in the pathogenesis of various diseases, including Crohn's disease (CD). Previously, we found that advanced oxidation protein products (AOPPs) were predominantly deposited in macrophages in the intestinal lamina propria of CD patients. However, whether AOPPs contributes to macrophage dysfunction in CD and the underlying mechanism remains unknown. This study aimed to investigate the effects of AOPPs on macrophages functions in CD. In the present study, we discovered increased AOPPs levels were positively correlated with impaired autophagy in macrophages of CD patients. AOPPs could impair autophagic flux by inducing lysosomal dysfunction in RAW264.7 cell line and macrophages in AOPPs-treated mice, evidenced by increased number of autophagosomes, blocked degradation of autophagy-related proteins (LC3B-II and SQSTM1/p62), and decreased activity of lysosomal proteolytic enzymes after AOPPs challenge. Besides, AOPPs could also promote M1 polarization in RAW264.7 cells and bone marrow derived macrophages (BMDMs) in AOPPs-treated mice. In addition, our study revealed that PI3K-AKT-mTOR-TFEB pathway was activated by AOPPs in macrophages. Inhibition of the PI3K pathway effectively alleviated AOPPs-induced autophagy impairment and M1 polarization both in vitro and in vivo, thus reducing intestinal inflammation in AOPPs-challenged mice. Together, this study demonstrates that AOPPs-induced autophagy impairment in macrophages is crucial for CD progression.


Assuntos
Produtos da Oxidação Avançada de Proteínas , Doença de Crohn , Animais , Autofagia , Humanos , Lisossomos , Macrófagos , Camundongos , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Serina-Treonina Quinases TOR/genética
13.
Inquiry ; 58: 469580211018283, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34027690

RESUMO

This paper discussed the influence of disability and the degree of disability on the intergenerational needs of the elderly in terms of time and economy. The data is from the CLHLS in 2018. And the study discussed from 3 dimensions: nursing time, economic support, and medical cost support provided by children. The results showed that disability had a significant impact on the care time and medical expenses provided by adult children (care time: ß = 45.631, P < .001; medical expenses: ß = 2017.664, P < .01). Compared with the elderly with low degree of disability, the economic intergenerational care needs of the elderly with severe disability increased significantly (ß = 2108.078, P < .01). The results of sub sample regression show that the intergenerational care needs of the elderly in China are restricted by objective factors and have not been met. These findings revealed the current situation of intergenerational support for the disabled in China, and emphasized that the government should establish and improve the social formal care, gradually reduce the burden of care for children with disabled elderly families, and improve the quality of life of the disabled elderly.

14.
Cell Metab ; 33(6): 1171-1186.e9, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33951476

RESUMO

Antihyperglycemic therapy is an important priority for the treatment of type 2 diabetes (T2D). Excessive hepatic glucose production (HGP) is a major cause of fasting hyperglycemia. Therefore, a better understanding of its regulation would be important to develop effective antihyperglycemic therapies. Using a gluconeogenesis-targeted kinome screening approach combined with transcriptome analyses, we uncovered Nemo-like kinase (NLK) as a potent suppressor of HGP. Mechanistically, NLK phosphorylates and promotes nuclear export of CRTC2 and FOXO1, two key regulators of hepatic gluconeogenesis, resulting in the proteasome-dependent degradation of the former and the inhibition of the self-transcriptional activity and expression of the latter. Importantly, the expression of NLK is downregulated in the liver of individuals with diabetes and in diabetic rodent models and restoring NLK expression in the mouse model ameliorates hyperglycemia. Therefore, our findings uncover NLK as a critical player in the gluconeogenic regulatory network and as a potential therapeutic target for T2D.

15.
Environ Sci Pollut Res Int ; 28(33): 44916-44935, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33851296

RESUMO

We investigated the potential impacts of climate change on ecosystem services and their components in two distinct ecosystems: the northern grasslands and southern hills in China. The effects of minimum, average, and maximum temperature, and precipitation at monthly, seasonal, and yearly scales on ecosystem services and their components were studied through stepwise multiple regression analysis. The results showed that in the northern grasslands, an increase in the total ecosystem services value (ESV) was mainly attributed to soil conservation, biodiversity, hydrological regulation, and aesthetic landscape. In the southern hills, an increase in total ESV in each region was mainly attributed to climate regulation, environmental purification, biodiversity, and aesthetic landscape. There were strong correlations between ESVs and fluctuations in temperature and precipitation. In the northern grasslands, temperature was the main driving factor of the values from 11 categories of ecosystem services in Anxi, Tumuji, and Xilingol. However, in West Ordos, precipitation negatively affected the change in ESVs. In the southern hills, ESVs were governed by both precipitation and temperature in Huaying. Precipitation variables were an important factor affecting the ESVs in Cili. There was a stronger correlation between temperature and the majority of ESVs in Danjiangkou, Chongyi, and Lechang than precipitation. This paper provides a basis for a better understanding of the impact of climate change on different ecosystem services, and helps to enhance ESV under climate warming.


Assuntos
Mudança Climática , Ecossistema , Biodiversidade , China , Pradaria
16.
IEEE Trans Cybern ; PP2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33523821

RESUMO

Cross-manifold clustering is an extreme challenge learning problem. Since the low-density hypothesis is not satisfied in cross-manifold problems, many traditional clustering methods failed to discover the cross-manifold structures. In this article, we propose multiple flat projections clustering (MFPC) for cross-manifold clustering. In our MFPC, the given samples are projected into multiple localized flats to discover the global structures of implicit manifolds. Thus, the intersected clusters are distinguished in various projection flats. In MFPC, a series of nonconvex matrix optimization problems is solved by a proposed recursive algorithm. Furthermore, a nonlinear version of MFPC is extended via kernel tricks to deal with a more complex cross-manifold learning situation. The synthetic tests show that our MFPC works on the cross-manifold structures well. Moreover, experimental results on the benchmark datasets and object tracking videos show excellent performance of our MFPC compared with some state-of-the-art manifold clustering methods.

17.
J Hazard Mater ; 413: 125291, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-33588337

RESUMO

Real-time and visual monitoring of pollutants in the air is of great importance since they are usually cannot be seen, smelled, or touched. Lanthanide nano-cluster is a kind of luminescent sensor for various species. However, controlling synthesis of lanthanide nano-cluster remains experimentally challenging. In this work, four series of lanthanide-barium (Ln-Ba) nano-clusters of Dy2Ba (1), Tb2Ba2 (2), Ln4Ba3 (Ln = Tb, 3a; Eu, 3b), Tb4Ba4 (4) were assembled through precisely controlling the pH of the reactant solutions. The work features the first example that the number of cluster's nuclei changes regularly with the pH. Moreover, investigation reveals that nano-cluster 3a is a highly selective and sensitive sensor towards acetylacetone (acac) and aniline. Interestingly, easy-to-use sensing devices of test paper, agarose gel, and five kinds of film on CaCO3, polyfoam, coin, mask, and wall that based on 3a were fabricated by facile methods. The seven sensing devices showed remarkable ability to sense aniline and acac vapors with visibility to the naked eyes. This is the first work on multiple real-time and visual sensing devices based on the lanthanide nano-cluster.

18.
J Biol Inorg Chem ; 26(1): 109-122, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33475857

RESUMO

Iridium(III) complexes have gained great attention in cancer treatment in recent years. In this paper, we designed and synthesized a new iridium(III) complex [Ir(piq)2(DQTT)](PF6) Ir1 (piq = 1-phenylisoquinoline, DQTT = 12-(1,4-dihydroquinoxalin-6-yl)-4,5,9,14-tetraazabenzo[b]triphenylene). The Ir1-loaded PEGylated liposomes (Lipo-Ir1) were prepared using the ethanol injection method. The anticancer activity of the complex and Lipo-Ir1 against SGC-7901 (human gastric adenocarcinoma), A549 (human lung carcinoma), HeLa (human cervical carcinoma), HepG2 (human hepatocellular carcinoma), BEL-7402 (human hepatocellular carcinoma), and normal NIH3T3 (mouse embryonic fibroblasts) was tested by the MTT method. The complex Ir1 shows moderate or low cytotoxicity against the selected cancer cells, whereas the Lipo-Ir1 exhibits high anticancer activity toward the same cancer cells. The apoptosis induced by Lipo-Ir1 was assayed by flow cytometry and Lipo-Ir1 induced apoptosis through increasing intracellular reactive-oxygen species levels, decreasing mitochondrial membrane potential, further promoting cytochrome c release and causing the increase of level of intracellular Ca2+. Western blot was used to detect the changes in Bcl-2 family protein and PI3K/AKT pathway proteins. The cloning experiments demonstrated that the Lipo-Ir1 can effectively inhibit cell proliferation. In vivo experiments, Lipo-Ir1 inhibited tumor growth in xenograft nude mice, and the percentage of tumor growth inhibition in vivo was 75.70%. Overall, the liposomes Lipo-Ir1 exhibits higher anticancer activity than Ir1 under the same conditions. These results indicated that Lipo-Ir1 may be a valuable resource for cancer therapy.


Assuntos
Antineoplásicos/uso terapêutico , Complexos de Coordenação/uso terapêutico , Portadores de Fármacos/química , Lipossomos/química , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/química , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Cálcio/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/química , Complexos de Coordenação/toxicidade , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Hemólise/efeitos dos fármacos , Irídio/química , Irídio/toxicidade , Lipossomos/toxicidade , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Mitocôndrias/efeitos dos fármacos , Células NIH 3T3 , Neoplasias/patologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Mol Med Rep ; 23(2)2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33355370

RESUMO

S100 calcium binding protein A16 (S100A16) is the most recent member of the S100 calcium-binding protein family. The function of S100A16 has been associated with various types of cancer; however, its role in colorectal cancer (CRC) remains unknown. Therefore, the aim of the present study was to investigate the role of S100A16 in CRC progression. The Oncomine dataset used in the current study revealed that the expression of S100A16 was decreased in CRC compared with normal colorectal tissues. Similar results were also determined via immunohistochemistry. In addition, a negative association was identified between S100A16 expression and the prognosis of patients with CRC. Further functional experiments revealed that S100A16 knockdown promoted the proliferation, migration and invasion of HCT116 and SW480 cells, and vice versa in Lovo cells. Epithelial-mesenchymal transition (EMT) was promoted and the JNK/p38 MAPK pathway was activated in HCT116 cells following S100A16 knockdown, as determined via western blotting. Furthermore, S100A16 silencing promoted the migration and invasion of cells. EMT was also reversed when cells were treated with the JNK inhibitor (SP600125) or the p38 inhibitor (SB203580). In summary, the results of the present study demonstrated that S100A16 suppressed the proliferation, migration and invasion of CRC cells partially via the JNK/p38 MAPK signalling pathway and subsequent EMT mediation.


Assuntos
Movimento Celular , Proliferação de Células , Neoplasias Colorretais/metabolismo , MAP Quinase Quinase 4/metabolismo , Sistema de Sinalização das MAP Quinases , Proteínas de Neoplasias/metabolismo , Proteínas S100/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Células HCT116 , Humanos , MAP Quinase Quinase 4/genética , Masculino , Invasividade Neoplásica , Proteínas de Neoplasias/genética , Proteínas S100/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genética
20.
Cancer Cell Int ; 20: 503, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061855

RESUMO

Background: Tumors display a high rate of glucose metabolism and the SLC2A (also known as GLUT) gene family may be central regulators of cellular glucose uptake. However, roles of SLC2A family in mechanism of metabolite communication with immunity in gastric cancer remains unknown. Methods: Bioinformatics analysis and IHC staining were used to reveal the expression of SLC2A3 in gastric cancer and the correlation with survival prognosis. Real-time PCR, western blots, OCR, ECAR, lactate production and glucose uptake assays were applied to determine the effect of SLC2A3 on glycolysis reprogramming. We then investigated the consequences of SLC2A3 upregulation or inhibition on aerobic glycolysis, also explored the underlying mechanism. Bioinformatics analysis and in vitro and in vivo research were used to reveal the role of SLC2A3 in macrophage infiltration and transition. Results: Here, we show that SLC2A3 acts as a tumor promoter and accelerates aerobic glycolysis in GC cells. Mechanistically, the SLC2A3-STAT3-SLC2A3 feedback loop could promote phosphorylation of the STAT3 signaling pathway and downstream glycolytic targeting genes. Moreover, SLC2A3 potentially contributes to M2 subtype transition of macrophage infiltration in the GC microenvironment. Conclusions: SLC2A3 could be used as a prognostic biomarker to determine prognosis and immune infiltration in GC and may provide an intervention strategy for GC therapy.

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