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1.
Inhal Toxicol ; 36(4): 275-281, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38836332

RESUMO

Multiwalled carbon nanotubes (MWCNTs) have numerous applications in the field of carbon nanomaterials. However, the associated toxicity concerns have increased significantly because of their widespread use. The inhalation of MWCNTs can lead to nanoparticle deposition in the lung tissue, causing inflammation and health risks. In this study, celastrol, a natural plant medicine with potent anti-inflammatory properties, effectively reduced the number of inflammatory cells, including white blood cells, neutrophils, and lymphocytes, and levels of inflammatory cytokines, such as IL-1ß, IL-6, and TNF-α, in mice lungs exposed to MWCNTs. Moreover, celastrol inhibited the activation of the NF-κB-signaling pathway. This study confirmed these findings by demonstrating comparable reductions in inflammation upon exposure to MWCNTs in mice with the deletion of NF-κB (P50-/-). These results indicate the utility of celastrol as a promising pharmacological agent for preventing MWCNT-induced lung tissue inflammation.


Assuntos
Camundongos Endogâmicos C57BL , NF-kappa B , Nanotubos de Carbono , Triterpenos Pentacíclicos , Pneumonia , Transdução de Sinais , Triterpenos , Animais , Triterpenos Pentacíclicos/farmacologia , Nanotubos de Carbono/toxicidade , Transdução de Sinais/efeitos dos fármacos , Triterpenos/farmacologia , Pneumonia/induzido quimicamente , Pneumonia/tratamento farmacológico , Pneumonia/prevenção & controle , Pneumonia/metabolismo , NF-kappa B/metabolismo , Masculino , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Camundongos , Camundongos Knockout , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/química
2.
Carbohydr Polym ; 330: 121812, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38368083

RESUMO

Biomacromolecules based injectable and self-healing hydrogels possessing high mechanical properties have widespread potential in biomedical field. However, dynamic features are usually inversely proportional to toughness. It is challenging to simultaneously endow these properties to the dynamic hydrogels. Here, we fabricated an injectable nanocomposite hydrogel (CS-NPs@OSA-l-Gtn) stimultaneously possessing excellent autonomous self-healing performance and high mechanical strength by doping chitosan nanoparticles (CS-NPs) into dynamic polymer networks of oxidized sodium alginate (OSA) and gelatin (Gtn) in the presence of borax. The synergistic effect of the multiple reversible interactions combining dynamic covalent bonds (i.e., imine bond and borate ester bond) and noncovalent interactions (i.e., electrostatic interaction and hydrogen bond) provide effective energy dissipation to endure high fatigue resistance and cyclic loading. The dynamic hydrogel exhibited excellent mechanical properties like maximum 2.43 MPa compressive strength, 493.91 % fracture strain, and 89.54 kJ/m3 toughness. Moreover, the integrated hydrogel after injection and self-healing could withstand 150 successive compressive cycles. Besides, the bovine serum albumin embedded in CS-NPs could be sustainably released from the nanocomposite hydrogel for 12 days. This study proposes a novel strategy to synthesize an injectable and self-healing hydrogel combined with excellent mechanical properties for designing high-strength natural carriers with sustained protein delivery.


Assuntos
Alginatos , Quitosana , Alginatos/química , Nanogéis , Gelatina/química , Hidrogéis/química , Polímeros , Quitosana/química
3.
Zhen Ci Yan Jiu ; 49(2): 198-207, 2024 Feb 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38413042

RESUMO

OBJECTIVES: To explore the rules of acupoint selection in the treatment of neurogenic bladder (NB) with acupuncture and moxibustion by using data mining. METHODS: The clinical research literatures on acupuncture treatment of NB were collected from PubMed, Embase, Cochrane Library, CNKI, Wanfang Database, VIP Database and China Biology Medicine from retrieved to January 1, 2023. The acupoint prescription database was established using Excel 2019. SPSS Modeler 18.0 and SPSS Statistics 26.0 softwares were used to conduct the frequency, meri-dians, locations, specific acupoints analysis and association rules analysis, factor analysis, cluster analysis, etc., to explore the characteristics and rules of acupoint selection in acupuncture and moxibustion treatment of NB. RESULTS: Totally 313 papers were included, including 110 acupoints with a total frequency of 1 995. The high-frequency acupoints are Zhongji (CV3), Guanyuan (CV4), Sanyinjiao (SP6), etc. The commonly used meridians are the Bladder Meridian of Foot Taiyang and Conception Vessel. The involved acupoints are mostly located in the lumbosacral region and abdomen, and intersection acupoints, mu-front acupoints and back-shu acupoints are the majority in the specific acupoints. The core acupoints group was analyzed, and 17 groups of association rules, 7 factors and 6 effective cluster groups were obtained. CONCLUSIONS: Acupuncture and moxibustion treatment of NB follows the therapeutic principles of toni-fying the kidney, invigorating the spleen, and soothing the liver. The core acupoints group is CV3-CV4-SP6.


Assuntos
Terapia por Acupuntura , Meridianos , Moxibustão , Bexiga Urinaria Neurogênica , Humanos , Pontos de Acupuntura , Mineração de Dados
4.
Carbohydr Polym ; 328: 121711, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38220344

RESUMO

This study was to explore the internal reasons for the changes in oil absorption performance of tigernut starch (TS) by revealing the high-temperature induced variations of structural and functional properties of TS. The results showed that as the temperature increased from 80 °C to 140 °C, the degree of starch gelatinization increased, while the proportion of double helix structures, the total proportion of B1 and B2 chains, the relative crystallinity and the molecular weight decreased, accompanied by the fragmentation and swelling of TS granules. The oxidation of tigernut oil (TNO) led to a decrease in oil density and an increase in total polar component content. These phenomena could result in an increase of oil absorption capacity of TS and starch-lipid complex index. With further increase in temperature from 170 °C to 200 °C, the disruption of the crystalline structure and chain structure increased, resulting in the melting and disintegration of TS granules. This caused a decrease in the starch-oil contact area and capillary absorption of TNO by the TS granules. The results will contribute to revealing the effect of high-temperature induced changes in the structural and functional properties of TS on its oil absorption properties.

5.
Sheng Li Xue Bao ; 75(6): 799-816, 2023 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-38151345

RESUMO

Mitochondria-associated endoplasmic reticulum membranes (MAMs) are the physical connection sites between mitochondria and endoplasmic reticulum (ER). As the compartments controlling substance and information communications between ER and mitochondria, MAMs were involved in the regulation of various pathophysiological processes, such as calcium homeostasis, mitochondrial morphology and function, lipid metabolism and autophagy. In the past decades, accumulating lines of evidence have revealed the pivotal role of MAMs in diverse cardiovascular diseases (CVD). Aging is one of the major independent risk factors for CVD, which causes progressive degeneration of the cardiovascular system, leading to increased morbidity and mortality of CVD. This review aims to summarize the research progress of MAMs in age-related CVD, and explore new targets for its prevention and treatment.


Assuntos
Doenças Cardiovasculares , Membranas Mitocondriais , Humanos , Doenças Cardiovasculares/metabolismo , Sinalização do Cálcio/fisiologia , Mitocôndrias/fisiologia , Retículo Endoplasmático/metabolismo
6.
Curr Med Sci ; 43(6): 1133-1150, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38015361

RESUMO

OBJECTIVE: Pseudogenes are initially regarded as nonfunctional genomic sequences, but some pseudogenes regulate tumor initiation and progression by interacting with other genes to modulate their transcriptional activities. Olfactory receptor family 7 subfamily E member 47 pseudogene (OR7E47P) is expressed broadly in lung tissues and has been identified as a positive regulator in the tumor microenvironment (TME) of lung adenocarcinoma (LUAD). This study aimed to elucidate the correlation between OR7E47P and tumor immunity in lung squamous cell carcinoma (LUSC). METHODS: Clinical and molecular information from The Cancer Genome Atlas (TCGA) LUSC cohort was used to identify OR7E47P-related immune genes (ORIGs) by weighted gene correlation network analysis (WGCNA). Based on the ORIGs, 2 OR7E47P clusters were identified using non-negative matrix factorization (NMF) clustering, and the stability of the clustering was tested by an extreme gradient boosting classifier (XGBoost). LASSO-Cox and stepwise regressions were applied to further select prognostic ORIGs and to construct a predictive model (ORPScore) for immunotherapy. The Botling cohorts and 8 immunotherapy cohorts (the Samstein, Braun, Jung, Gide, IMvigor210, Lauss, Van Allen, and Cho cohorts) were included as independent validation cohorts. RESULTS: OR7E47P expression was positively correlated with immune cell infiltration and enrichment of immune-related pathways in LUSC. A total of 57 ORIGs were identified to classify the patients into 2 OR7E47P clusters (Cluster 1 and Cluster 2) with distinct immune, mutation, and stromal programs. Compared to Cluster 1, Cluster 2 had more infiltration by immune and stromal cells, lower mutation rates of driver genes, and higher expression of immune-related proteins. The clustering performed well in the internal and 5 external validation cohorts. Based on the 7 ORIGs (HOPX, STX2, WFS, DUSP22, SLFN13, GGCT, and CCSER2), the ORPScore was constructed to predict the prognosis and the treatment response. In addition, the ORPScore was a better prognostic factor and correlated positively with the immunotherapeutic response in cancer patients. The area under the curve values ranged from 0.584 to 0.805 in the 6 independent immunotherapy cohorts. CONCLUSION: Our study suggests a significant correlation between OR7E47P and TME modulation in LUSC. ORIGs can be applied to molecularly stratify patients, and the ORPScore may serve as a biomarker for clinical decision-making regarding individualized prognostication and immunotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Pulmão , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Pseudogenes/genética , Microambiente Tumoral/genética
7.
J Appl Microbiol ; 134(10)2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37873659

RESUMO

AIMS: We evaluated whether the randomness of mutation breeding can be regulated through a double-reporter system. We hope that by establishing a new precursor feeding strategy, the production capacity of industrial microorganisms after pilot scale-up can be further improved. METHODS AND RESULTS: In this study, the industrial strain Streptomyces roseosporus L2796 was used as the starter strain for daptomycin production, and a double-reporter system with the kanamycin resistance gene Neo and the chromogenic gene gusA was constructed to screen for high-yield strain L2201 through atmospheric and room temperature plasma (ARTP). Furthermore, the composition of the culture medium and the parameters of precursor replenishment were optimized, resulting in a significant enhancement of the daptomycin yield of the mutant strain L2201(752.67 mg/l). CONCLUSIONS: This study successfully screened a high-yield strain of daptomycin through a double-reporter system combined with ARTP mutation. The expression level of two reporter genes can evaluate the strength of dptEp promoter, which can stimulate the expression level of dptE in the biosynthesis of daptomycin, thus producing more daptomycin. The developed multi-stage feeding rate strategy provides a novel way to increase daptomycin in industrial fermentation.


Assuntos
Daptomicina , Streptomyces , Fermentação , Mutagênese , Mutação , Streptomyces/genética , Streptomyces/metabolismo
8.
Redox Biol ; 68: 102944, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37890359

RESUMO

AIMS: Endothelial dysfunction plays a pivotal role in atherosclerosis, but the detailed mechanism remains incomplete understood. Nogo-B is an endoplasmic reticulum (ER)-localized protein mediating ER-mitochondrial morphology. We previously showed endothelial Nogo-B as a key regulator of endothelial function in the setting of hypertension. Here, we aim to further assess the role of Nogo-B in coronary atherosclerosis in ApoE-/- mice with pressure overload. METHODS AND RESULTS: We generated double knockout (DKO) mouse models of systemically or endothelium-specifically excising Nogo-A/B gene on an ApoE-/- background. After 7 weeks of transverse aortic constriction (TAC) surgery, compared to ApoE-/- mice DKO mice were resistant to the development of coronary atherosclerotic lesions and plaque rapture. Sustained elevation of Nogo-B and adhesion molecules (VCAM-1/ICAM-1), early markers of atherosclerosis, was identified in heart tissues and endothelial cells (ECs) isolated from TAC ApoE-/- mice, changes that were significantly repressed by Nogo-B deficiency. In cultured human umbilical vein endothelial cells (HUVECs) exposure to inflammatory cytokines (TNF-α, IL-1ß), Nogo-B was upregulated and activated reactive oxide species (ROS)-p38-p65 signaling axis. Mitofusin 2 (Mfn2) is a key protein tethering ER to mitochondria in ECs, and we showed that Nogo-B expression positively correlated with Mfn2 protein level. And Nogo-B deletion in ECs or in ApoE-/- mice reduced Mfn2 protein content and increased ER-mitochondria distance, reduced ER-mitochondrial Ca2+ transport and mitochondrial ROS generation, and prevented VCAM-1/ICAM-1 upregulation and EC dysfunction, eventually restrained atherosclerotic lesions development. CONCLUSION: Our study revealed that Nogo-B is a critical modulator in promoting endothelial dysfunction and consequent pathogenesis of coronary atherosclerosis in pressure overloaded hearts of ApoE-/- mice. Nogo-B may hold the promise to be a common therapeutic target in the setting of hypertension.


Assuntos
Aterosclerose , Doença da Artéria Coronariana , Hipertensão , Placa Aterosclerótica , Humanos , Animais , Camundongos , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/metabolismo , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismo , Proteínas Nogo/genética , Proteínas Nogo/metabolismo , Aterosclerose/genética , Aterosclerose/metabolismo , Placa Aterosclerótica/metabolismo , Estresse Oxidativo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Inflamação/metabolismo , Endotélio/metabolismo , Hipertensão/metabolismo , Apolipoproteínas E/genética , Camundongos Knockout , Camundongos Endogâmicos C57BL
9.
Nat Metab ; 5(10): 1726-1746, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37770763

RESUMO

Chronic inflammation due to islet-residing macrophages plays key roles in the development of type 2 diabetes mellitus. By systematically profiling intra-islet lipid-transmembrane receptor signalling in islet-resident macrophages, we identified endogenous 9(S)-hydroxy-10,12-octadecadienoic acid-G-protein-coupled receptor 132 (GPR132)-Gi signalling as a significant contributor to islet macrophage reprogramming and found that GPR132 deficiency in macrophages reversed metabolic disorders in mice fed a high-fat diet. The cryo-electron microscopy structures of GPR132 bound with two endogenous agonists, N-palmitoylglycine and 9(S)-hydroxy-10,12-octadecadienoic acid, enabled us to rationally design both GPR132 agonists and antagonists with high potency and selectivity through stepwise translational approaches. We ultimately identified a selective GPR132 antagonist, NOX-6-18, that modulates macrophage reprogramming within pancreatic islets, decreases weight gain and enhances glucose metabolism in mice fed a high-fat diet. Our study not only illustrates that intra-islet lipid signalling contributes to islet macrophage reprogramming but also provides a broadly applicable strategy for the identification of important G-protein-coupled receptor targets in pathophysiological processes, followed by the rational design of therapeutic leads for refractory diseases such as diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Ilhotas Pancreáticas , Camundongos , Animais , Diabetes Mellitus Tipo 2/metabolismo , Microscopia Crioeletrônica , Ilhotas Pancreáticas/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais
10.
Curr Med Sci ; 43(4): 631-646, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37558863

RESUMO

Cancer treatment has evolved rapidly due to major advances in tumor immunity research. However, due to the complexity, heterogeneity, and immunosuppressive microenvironment of tumors, the overall efficacy of immunotherapy is only 20%. In recent years, nanoparticles have attracted more attention in the field of cancer immunotherapy because of their remarkable advantages in biocompatibility, precise targeting, and controlled drug delivery. However, the clinical application of nanomedicine also faces many problems concerning biological safety, and the synergistic mechanism of nano-drugs with immunity remains to be elucidated. Our study summarizes the functional characteristics and regulatory mechanisms of nanoparticles in the cancer immune microenvironment and how nanoparticles activate and long-term stimulate innate immunity and adaptive immunity. Finally, the current problems and future development trends regarding the application of nanoparticles are fully discussed and prospected to promote the transformation and application of nanomedicine used in cancer treatment.


Assuntos
Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Imunoterapia , Nanomedicina , Sistemas de Liberação de Medicamentos , Imunidade Adaptativa , Microambiente Tumoral
11.
Front Bioeng Biotechnol ; 11: 1169124, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37251573

RESUMO

The proper microenvironment is critical for the storage and transportation of embryonic stem cells (ESCs). To mimic a dynamic 3D microenvironment as it exists in vivo and consider "off-the-shelf" availability reaching the destination, we proposed an alternative approach that allows for facile storage and transportation of stem cells in the form of ESCs-dynamic hydrogel construct (CDHC) under ambient conditions. To form CDHC, mouse embryonic stem cells (mESCs) were in-situ encapsulated within a polysaccharide-based dynamic and self-biodegradable hydrogel. After storing CDHC in a sterile and hermetic environment for 3 days and then transferring to a sealed vessel with fresh medium for another 3 days, the large and compact colonies retained a 90% survival rate and pluripotency. Furthermore, after transporting and arriving at the destination, the encapsulated stem cell could be automatically released from the self-biodegradable hydrogel. After continuous cultivation of 15 generations of retrieved cells, automatically released from the CDHC, the mESCs underwent 3D encapsulation, storage, transportation, release, and continuous long-term subculture; resumed colony forming capacity and pluripotency were revealed by stem cell markers both in protein and mRNA levels. We believe that the dynamic and self-biodegradable hydrogel provides a simple, cost-effective, and valuable tool for storing and transporting "ready-to-use" CDHC under ambient conditions, facilitating "off-the-shelf" availability and widespread applications.

12.
Heliyon ; 9(4): e14823, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37025887

RESUMO

Type 2 diabetes mellitus (T2DM) is characterized by chronic low-grade systemic inflammation. Tissue infiltration by monocyte migration contributes to the pathogenesis of vascular complications in T2DM. We studied the role of intermediate-conductance Ca2+-activated K+ (KCa3.1) channels in the palmitic acid (PA)-induced migration of peripheral blood mononuclear cells (PBMCs) from T2DM patients and the influence of advanced glycation endproducts (AGEs). A total of 49 T2DM patients and 33 healthy subjects was recruited into this study. Using flow cytometry and Western blotting analysis as well as cell migration assay, we found that there was a significant decrease in frequency of T lymphocytes and monocytes in CD45+ leukocyte population. PA at 100 µM stimulated migration of PBMCs from T2DM individuals, which was inhibited by the specific KCa3.1 channel blocker TRAM-34 (1 µM). The PBMC migration was positively correlated with glycosylated hemoglobin A1 chain (HbA1c) level of T2DM patients, an indicator of AGEs, and PBMCs with higher level of HbA1c showed upregulated expression of toll-like receptor (TLR) 2/4 and KCa3.1 channels. In THP-1 cells, AGEs at 200 µg/ml increased protein expression of TLR 2/4 and KCa3.1 channels, and were synergistically involved in PA-induced migration through receptors of AGEs (RAGE)-mediated KCa3.1 upregulation. In conclusion, in PBMCs of T2DM patients, AGEs promotes PA-induced migration via upregulation of TLR2/4 and KCa3.1 channels.

13.
Front Oncol ; 13: 1104447, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36969008

RESUMO

Gastric carcinomas have high morbidity and mortality. It produces no noticeable symptoms in the early stage while causing complex complications in its advanced stage, making treatment difficult. Palliative therapy aims to relieve the symptoms of cancer patients and focuses on improving their quality of life. At present, five palliative therapies for advanced gastric carcinomas are offered: resection, gastrojejunostomy, stenting, chemotherapy, and radiotherapy. In recent years, palliative therapy has been used in the clinical treatment of advanced gastric carcinomas and related complications because of its efficacy in gastric outlet obstruction and gastric bleeding. In the future, multimodal and interdisciplinary palliative therapies can be applied to control general symptoms to improve patients' condition, prolong their lifespan and improve their quality of life.

14.
Arterioscler Thromb Vasc Biol ; 43(5): 726-738, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36951065

RESUMO

BACKGROUND: S1P (sphingosine-1-phosphate) has been reported to possess vasodilatory properties, but the underlying pathways are largely unknown. METHODS: Isolated mouse mesenteric artery and endothelial cell models were used to determine S1P-induced vasodilation, intracellular calcium, membrane potentials, and calcium-activated potassium channels (KCa2.3 and KCa3.1 [endothelial small- and intermediate-conductance calcium-activated potassium channels]). Effect of deletion of endothelial S1PR1 (type 1 S1P receptor) on vasodilation and blood pressure was evaluated. RESULTS: Mesenteric arteries subjected to acute S1P stimulation displayed a dose-dependent vasodilation response, which was attenuated by blocking endothelial KCa2.3 or KCa3.1 channels. In cultured human umbilical vein endothelial cells, S1P stimulated immediate membrane potential hyperpolarization following activation of KCa2.3/KCa3.1 with elevated cytosolic Ca2+. Further, chronic S1P stimulation enhanced expression of KCa2.3 and KCa3.1 in human umbilical vein endothelial cells in dose- and time-dependent manners, which was abolished by disrupting either S1PR1-Ca2+ signaling or downstream Ca2+-activated calcineurin/NFAT (nuclear factor of activated T-cells) signaling. By combination of bioinformatics-based binding site prediction and chromatin immunoprecipitation assay, we revealed in human umbilical vein endothelial cells that chronic activation of S1P/S1PR1 promoted NFATc2 nuclear translocation and binding to promoter regions of KCa2.3 and KCa3.1 genes thus to upregulate transcription of these channels. Deletion of endothelial S1PR1 reduced expression of KCa2.3 and KCa3.1 in mesenteric arteries and exacerbated hypertension in mice with angiotensin II infusion. CONCLUSIONS: This study provides evidence for the mechanistic role of KCa2.3/KCa3.1-activated endothelium-dependent hyperpolarization in vasodilation and blood pressure homeostasis in response to S1P. This mechanistic demonstration would facilitate the development of new therapies for cardiovascular diseases associated with hypertension.


Assuntos
Hipertensão , Vasodilatação , Camundongos , Humanos , Animais , Pressão Sanguínea , Endotélio/metabolismo , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/genética , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Homeostase , Canais de Potássio Ativados por Cálcio de Condutância Baixa/genética , Canais de Potássio Ativados por Cálcio de Condutância Baixa/metabolismo
15.
Oncol Rep ; 48(5)2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36129137

RESUMO

Subsequently to the publication of the above article, the authors have realized that a couple of clerical errors were made when writing the article, and wish to correct these errors in a corrigendum statement. First, in the Materials and methods section on p. 2216, the final sentence of the 'Immunohistochemistry and tissue microarray' subsection, the authors wish to add a further definition, so that the text reads as follows (changes highlighted in bold): 'The positive expression of RET was defined as ≥5% staining of a tumor section; high expression was defined as ≥40% staining of a tumor section, and low expression as <40%'. Secondly, in the Results section, 'Mutation frequency of each gene distributed in 4 biological categories' subsection, p. 2220, right­hand column, second paragraph, line 17, the sentence written here should have read as follows: 'The group with the positive expression of RET included 28.9% (26/90) of the patients, and 4 of these patients were defined as high expression'. The authors are grateful to the Editor of Oncology Reports for allowing them this opportunity to publish a corrigendum, and apologize to the readership of the journal for any inconvenience caused. [Oncology Reports 37: 2215­2226, 2017; DOI: 10.3892/or.2017.5494].

16.
J Cancer Prev ; 27(1): 42-49, 2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35419308

RESUMO

Chaenomeles sinensis is known to inhibit the development and progression of many age-related diseases, but the underlying molecular mechanisms are largely unclear. In the present study, we observed that the ethanol extract of Chaenomeles sinensis scavenged 2,2'-diphenylpicrylhydrazyl and 2,2'-azinobis diammonium radicals in vitro. The ethanol extract of Chaenomeles sinensis activated antioxidant response element-luciferase activity and induced expression of NRF2 target genes in HaCaT cells. The ethanol extract of Chaenomeles sinensis also suppressed LPS-induced expression of COX-2 and iNOS proteins, and mRNA expression of TNF-α and IL-2 in RAW264.7 cells. Finally, the ethanol extract of Chaenomeles sinensis significantly suppressed testosterone propionate-induced benign prostatic hyperplasia in mice. Together, our study provides the evidence that the ethanol extract of Chaenomeles sinensis inhibits the development of benign prostatic hyperplasia by exhibiting anti-oxidant and anti-inflammatory effects.

17.
PLoS Med ; 19(2): e1003900, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35104296

RESUMO

BACKGROUND: Pre-gestational diabetes mellitus (PGDM) has been known to be a risk factor for congenital heart defects (CHDs) for decades. However, the associations between maternal PGDM and gestational diabetes mellitus (GDM) and the risk of specific types of CHDs and congenital anomalies (CAs) in other systems remain under debate. We aimed to investigate type-specific CAs in offspring of women with diabetes and to examine the extent to which types of maternal diabetes are associated with increased risk of CAs in offspring. METHODS AND FINDINGS: We searched PubMed and Embase from database inception to 15 October 2021 for population-based studies reporting on type-specific CAs in offspring born to women with PGDM (combined type 1 and 2) or GDM, with no limitation on language. Reviewers extracted data for relevant outcomes and performed random effects meta-analyses, subgroup analyses, and multivariable meta-regression. Risk of bias appraisal was performed using the Cochrane Risk of Bias Tool. This study was registered in PROSPERO (CRD42021229217). Primary outcomes were overall CAs and CHDs. Secondary outcomes were type-specific CAs. Overall, 59 population-based studies published from 1990 to 2021 with 80,437,056 participants met the inclusion criteria. Of the participants, 2,407,862 (3.0%) women had PGDM and 2,353,205 (2.9%) women had GDM. The meta-analyses showed increased risks of overall CAs/CHDs in offspring born to women with PGDM (for overall CAs, relative risk [RR] = 1.99, 95% CI 1.82 to 2.17, P < 0.001; for CHDs, RR = 3.46, 95% CI 2.77 to 4.32, P < 0.001) or GDM (for overall CAs, RR = 1.18, 95% CI 1.13 to 1.23, P < 0.001; for CHDs, RR = 1.50, 95% CI 1.38 to 1.64, P < 0.001). The results of the meta-regression analyses showed significant differences in RRs of CAs/CHDs in PGDM versus GDM (all P < 0.001). Of the 23 CA categories, excluding CHD-related categories, in offspring, maternal PGDM was associated with a significantly increased risk of CAs in 21 categories; the corresponding RRs ranged from 1.57 (for hypospadias, 95% CI 1.22 to 2.02) to 18.18 (for holoprosencephaly, 95% CI 4.03 to 82.06). Maternal GDM was associated with a small but significant increase in the risk of CAs in 9 categories; the corresponding RRs ranged from 1.14 (for limb reduction, 95% CI 1.06 to 1.23) to 5.70 (for heterotaxia, 95% CI 1.09 to 29.92). The main limitation of our analysis is that some high significant heterogeneity still persisted in both subgroup and sensitivity analyses. CONCLUSIONS: In this study, we observed an increased rate of CAs in offspring of women with diabetes and noted the differences for PGDM versus GDM. The RRs of overall CAs and CHDs in offspring of women with PGDM were higher than those in offspring of women with GDM. Screening for diabetes in pregnant women may enable better glycemic control, and may enable identification of offspring at risk for CAs.


Assuntos
Diabetes Gestacional/epidemiologia , Cardiopatias Congênitas/epidemiologia , Vigilância da População , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Estudos de Casos e Controles , Estudos de Coortes , Estudos Transversais , Diabetes Gestacional/diagnóstico , Feminino , Cardiopatias Congênitas/diagnóstico , Humanos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Fatores de Risco
18.
Front Pharmacol ; 12: 673221, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34211395

RESUMO

As a well-known multimodal-acting antidepressant, vortioxetine is thought to aim at several serotonin (5-HT) receptors and the 5-HT transporter. However, recently more and more proteins besides 5-HT are being reported to participate in the antidepressant mechanism of vortioxetine. As a widely known nuclear hormone receptor, peroxisome proliferator activated receptor α (PPARα) possesses transcriptional activity and is very important in the brain. Several reports have suggested that hippocampal PPARα is implicated in antidepressant responses. Here we speculate that hippocampal PPARα may participate in the antidepressant mechanism of vortioxetine. In this study, chronic unpredictable mild stress (CUMS), chronic social defeat stress (CSDS), behavioral tests, the western blotting and adenovirus associated virus (AAV)-mediated gene knockdown methods were used together. It was found that vortioxetine administration significantly reversed the inhibitory actions of both CUMS and CSDS on the hippocampal PPARα expression. Pharmacological blockade of PPARα notably prevented the antidepressant actions of vortioxetine in the CUMS and CSDS models. Moreover, genetic knockdown of PPARα in the hippocampus also significantly blocked the protecting effects of vortioxetine against both CUMS and CSDS. Therefore, the antidepressant effects of vortioxetine in mice require hippocampal PPARα.

19.
Eur Neurol ; 84(2): 85-95, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33789307

RESUMO

BACKGROUND: CTNNB1 is reported to be related to the pathological process of ischemic stroke (IS) and coronary artery disease (CAD). Polymorphism located in the 3' untranslated region (3'UTR) of a gene might affect gene expression by modifying binding sites for microRNAs (miRNAs). This study aimed to analyze the association between polymorphism rs2953, which locates in the 3'UTR of CTNNB1, and the risk of IS and CAD. METHODS: The CTNNB1 messenger RNA (mRNA) expression level in peripheral venous blood was measured. In total, 533 patients with IS, 500 patients with CAD, and 531 healthy individuals were genotyped by Sequenom Mass-Array technology. The binding of miR-3161 to CTNNB1 was determined by dual-luciferase reporter assay. RESULTS: The CTNNB1 mRNA expression level for the IS group was significantly lower than that for the control group. Rs2953 was significantly associated with both IS risk and CAD risk. Significant association was also found between polymorphism rs2953 and many conventional factors, such as serum lipid level, blood coagulation markers, blood glucose level, and homocysteine level in patients. Rs2953 T allele introduced a binding site to miRNA-3161 and thus decreased luciferase activity. CONCLUSION: Polymorphism rs2953 is associated with the risk of both IS and CAD. Moreover, polymorphism rs2953 (T) introduces a binding site to miRNA-3161 and thus decreases luciferase activity in cell lines.


Assuntos
Isquemia Encefálica , Doença da Artéria Coronariana , AVC Isquêmico , MicroRNAs , Acidente Vascular Cerebral , Regiões 3' não Traduzidas , Estudos de Casos e Controles , China , Doença da Artéria Coronariana/genética , Predisposição Genética para Doença , Humanos , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral/genética , beta Catenina/genética
20.
World Neurosurg ; 127: e155-e161, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30872195

RESUMO

BACKGROUND: Mechanical thrombectomy (MT) has demonstrated benefit in patients with acute ischemic stroke due to proximal large-vessel occlusion. However, it is unclear whether these results can be extrapolated to patients with an occlusion of the second segment (M2) of the middle cerebral artery (MCA). We sought to study outcomes in patients with M2 occlusion treated with MT and to better understand clinical predictors of these outcomes. METHODS: We performed a single-center retrospective analysis of consecutive patients with acute MCA M2 segment occlusion who underwent stent retriever MT. We correlated clinical and radiographic outcomes with demographic, clinical, and technical characteristics. RESULTS: Thirty-seven patients were included in the analysis (median admission National Institutes of Health Stroke Scale [NIHSS] score, 15 [12-19], mean age 74 [67-80] years, 48.6% women). Good clinical outcome at 3 months (modified Rankin Scale ≤2) was achieved in 48.6% of patients. Baseline NIHSS was a predictor of clinical outcomes, based on modified Rankin Scale distribution at 3 months after MT (P = 0.015, odds ratio 1.63, 95% confidence interval 1.01-2.43). CONCLUSIONS: The results of our single-institution experience suggest that MT-based endovascular therapy for M2 occlusions is safe and effective. Baseline NIHSS was a predictor of outcomes in patients treated with MT for M2 segment occlusion of the MCA.


Assuntos
Infarto da Artéria Cerebral Média/terapia , Trombólise Mecânica , Idoso , Idoso de 80 Anos ou mais , Angiografia Cerebral , Terapia Combinada , Comorbidade , Angiografia por Tomografia Computadorizada , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Infarto da Artéria Cerebral Média/tratamento farmacológico , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença , Stents , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/uso terapêutico , Resultado do Tratamento
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