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1.
Poult Sci ; 101(7): 101916, 2022 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-35523032

RESUMO

Cecal epithelial cell damage is a key factor in host injure during the development of E. tenella. The intracellular free Ca2+ of the host cell is closely related to the invasion, development and proliferation of intracellular parasites, and cell damage. To determine the relationship between Ca2+ and host cell damage in the schizogenic stage of E. tenella, we established a chick embryo cecal epithelial cells model of E. tenella infection. Fluorescence staining, flow cytometry, transmission electron microscopy, inhibition and blocking experiments were used to detect the damage effect and mechanism of host cells during the schizogenic stage of E. tenella. The results showed that the host cells cytoskeletal remodeling, cell and organelle structure was destroyed, and apoptosis and necrosis were increased during the schizont stage of E. tenella. Furthermore, the above-mentioned effects of the schizogenic stage of E. tenella on cells can be alleviated by reducing the intracellular Ca2+ concentration in the host cells. These observations indicate that the effect of host cell injury was closely related to Ca2+ during schizont stage of E. tenella.

2.
Clin Lab ; 68(4)2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35443581

RESUMO

BACKGROUND: The goal of the study was to analyze the clinical characteristics of Legionella cases caused by Legionella micdadei and explore the diagnosis and treatment. METHODS: The pathogen was identified by routine isolation and culture, biochemical identification, serum agglutination test, mass spectrometry identification, and routine PCR. Combined with the related literature review, the clinical diagnosis and treatment of Legionella micdadei were analyzed. RESULTS: The patient suffered from pulmonary infection caused by Legionella micdadei. After treatment with moxi-floxacin for 2 weeks, the body temperature dropped and the shadow of the lung was completely absorbed after 2 months. Combined with literature analysis, 8 cases of Legionella micetidis, including 7 males and 1 female, aged from 27 to 57 years old, 6 cases with basic diseases, which were treated with azithromycin, erythromycin or levofloxacin, and all of them achieved good therapeutic effect. CONCLUSIONS: The detection of Legionella should be strengthened in patients with pneumonia whose symptoms have no obvious improvement after antibiotic treatment. Azithromycin, erythromycin or levofloxacin are effective in the treatment of Legionella spp.


Assuntos
Legionella , Legionelose , Pneumonia , Adulto , Azitromicina/farmacologia , Azitromicina/uso terapêutico , Eritromicina/farmacologia , Feminino , Humanos , Legionellaceae , Legionelose/complicações , Legionelose/diagnóstico , Legionelose/tratamento farmacológico , Levofloxacino/farmacologia , Levofloxacino/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pneumonia/diagnóstico
3.
Oxid Med Cell Longev ; 2022: 7531788, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35450408

RESUMO

Intervertebral disc (IVD) degeneration (IDD), the leading cause of low back pain (LBP), remains intractable due to a lack of effective therapeutic strategies. Several lines of studies have documented that nucleus pulposus cell (NPC) death induced by excessive oxidative stress is a crucial contributor to IDD. However, the concrete role and regulation mechanisms have not been fully clarified. Selenium (Se), a vital prosthetic group of antioxidant enzymes, is indispensable for maintaining redox homeostasis and promoting cell survival. However, no light was shed on the role of Se on IDD progression, especially regulation on mitochondrial dynamics and homeostasis. To fill this research gap, the current study focuses on the effects of Se, including sodium selenite (SS) and selenomethionine (Se-Met), on IDD progression and the underlying mechanisms. In vitro, we found that both SS and Se-Met alleviated tert-butyl hydroperoxide- (TBHP-) induced oxidative stress, protected mitochondrial function, and inhibited apoptosis of NPCs. Further experiments indicated that Se suppressed TBHP-induced mitochondrial fission and rescued the imbalance of mitochondrial dynamics. Promoting mitochondrial fission by carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP) partially counteracted the cytoprotective effects of Se. Moreover, blocking nuclear factor erythroid 2-related factor 2 (Nrf2) with ML385 proved that the effect of Se on regulating mitochondrial dynamics was attributed to the activation of the Nrf2 pathway. In the puncture-induced rat IDD model, a supplement of Se-Met ameliorated degenerative manifestations. Taken together, our results demonstrated that Se suppressed TBHP-induced oxidative stress and mitochondrial fission by activating the Nrf2 pathway, thereby inhibiting the apoptosis of NPCs and ameliorating IDD. Regulation of mitochondrial dynamics by Se may have a potential application value in attenuating the pathological process of IDD.


Assuntos
Degeneração do Disco Intervertebral , Núcleo Pulposo , Selênio , Animais , Antioxidantes/metabolismo , Apoptose , Degeneração do Disco Intervertebral/patologia , Dinâmica Mitocondrial , Fator 2 Relacionado a NF-E2/metabolismo , Núcleo Pulposo/patologia , Ratos , Selênio/uso terapêutico
4.
Int J Oncol ; 60(4)2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35244192

RESUMO

Pyruvate kinase M2 (PKM2) plays an important role in the consumption of glucose and the production of lactic acid, the striking feature of cancer metabolism. The association of PKM2 with osteosarcoma (OS) has been reported but its role in OS has yet to be elucidated. To study this, PKM2­bound RNAs in HeLa cells, a type of cancer cells widely used in the study of molecular function and mechanism, were obtained. Peak calling analysis revealed that PKM2 binds to long noncoding RNAs (lncRNAs), which are associated with cancer pathogenesis and development. Validation of the PKM2­lncRNA interaction in the human OS cell line revealed that lncRNA colon cancer associated transcript­1 (lncCCAT1) interacted with PKM2, which upregulated the phosphorylation of sterol regulatory element­binding protein 2 (SREBP2). These factors promoted the Warburg effect, lipogenesis, and OS cell growth. PKM2 appears to be a key regulator in OS by binding to lncCCAT1. This further extends the biological functions of PKM2 in tumorigenesis and makes it a novel potential therapeutic for OS.


Assuntos
Proteínas de Transporte/metabolismo , Proteínas de Membrana/metabolismo , Osteossarcoma/genética , Proteína de Ligação a Elemento Regulador de Esterol 2/efeitos dos fármacos , Hormônios Tireóideos/metabolismo , Carcinogênese/genética , Carcinogênese/metabolismo , Proteínas de Transporte/efeitos dos fármacos , Proteínas de Transporte/genética , Linhagem Celular Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral/metabolismo , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Humanos , Lipogênese/efeitos dos fármacos , Lipogênese/genética , Proteínas de Membrana/efeitos dos fármacos , Proteínas de Membrana/genética , Osteossarcoma/metabolismo , Fosforilação/efeitos dos fármacos , Fosforilação/genética , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Hormônios Tireóideos/genética , Efeito Warburg em Oncologia/efeitos dos fármacos
5.
Exp Mol Med ; 54(3): 309-323, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35338257

RESUMO

Compression-induced apoptosis of nucleus pulposus (NP) cells plays a pivotal role in the pathogenesis of intervertebral disc degeneration (IVDD). Recent studies have shown that the dysregulation of mitochondrial fission and fusion is implicated in the pathogenesis of a variety of diseases. However, its role in and regulatory effects on compression-induced apoptosis of NP cells have not yet been fully elucidated. Heat shock protein 70 (HSP70) is a major cytoprotective heat shock protein, but its physiological role in IVDD, especially its effect on mitochondrial fission and fusion, is still unknown. Herein, we found that compression could induce mitochondrial fission, which ultimately trigger apoptosis of NP cells via the mitochondrial apoptotic pathway. In addition, we identified the cytoprotective effects of HSP70 on NP cells, and we found that promoting the expression of HSP70 could protect NP cells from abnormal mechanical loading in vitro and in vivo. Finally, we showed that HSP70 inhibited compression-induced mitochondrial fission by promoting SIRT3 expression, thereby attenuating mitochondrial dysfunction and the production of reactive oxygen species and ultimately inhibiting the mitochondrial apoptotic pathway in NP cells. In conclusion, our results demonstrated that HSP70 could attenuate compression-induced apoptosis of NP cells by suppressing mitochondrial fission via upregulating SIRT3 expression. Promoting the expression of HSP70 might be a novel strategy for the treatment of IVDD.


Assuntos
Núcleo Pulposo , Sirtuína 3 , Apoptose , Proteínas de Choque Térmico HSP70/genética , Dinâmica Mitocondrial , Núcleo Pulposo/metabolismo , Sirtuína 3/genética , Sirtuína 3/metabolismo
6.
Int J Biol Sci ; 18(5): 1829-1843, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35342359

RESUMO

Ferroptosis is a novel form of programmed cell death, and it is characterized by iron-dependent oxidative damage, lipid peroxidation and reactive oxygen species accumulation. Notable studies have revealed that ferroptosis plays vital roles in tumor occurrence and that abundant ferroptosis in cells can inhibit tumor progression. Recently, some noncoding RNAs (ncRNAs), particularly microRNAs, long noncoding RNAs, and circular RNAs, have been shown to be involved in biological processes of ferroptosis, thus affecting cancer growth. However, the definite regulatory mechanism of this phenomenon is still unclear. To clarify this issue, increasing studies have focused on the regulatory roles of ncRNAs in the initiation and development of ferroptosis and the role of ferroptosis in progression of various cancers, such as lung, liver, and breast cancers. In this review, we systematically summarized the relationship between ferroptosis-associated ncRNAs and cancer progression. Moreover, additional evidence is needed to identify the role of ferroptosis-related ncRNAs in cancer progression. This review will help us to understand the roles of ncRNAs in ferroptosis and cancer progression and may provide new ideas for exploring novel diagnostic and therapeutic biomarkers for cancer in the future.


Assuntos
Neoplasias da Mama , Ferroptose , RNA Longo não Codificante , Feminino , Ferroptose/genética , Humanos , RNA Circular/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA não Traduzido/genética , RNA não Traduzido/metabolismo
7.
Acta Pharmacol Sin ; 2022 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-35241769

RESUMO

Platelet hyperactivity is essential for thrombus formation in coronary artery diseases (CAD). Dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) in patients with cystic fibrosis elevates intracellular Cl- levels ([Cl-]i) and enhanced platelet hyperactivity. In this study, we explored whether alteration of [Cl-]i has a pathological role in regulating platelet hyperactivity and arterial thrombosis formation. CFTR expression was significantly decreased, while [Cl-]i was increased in platelets from CAD patients. In a FeCl3-induced mouse mesenteric arteriole thrombosis model, platelet-specific Cftr-knockout and/or pre-administration of ion channel inhibitor CFTRinh-172 increased platelet [Cl-]i, which accelerated thrombus formation, enhanced platelet aggregation and ATP release, and increased P2Y12 and PAR4 expression in platelets. Conversely, Cftr-overexpressing platelets resulted in subnormal [Cl-]i, thereby decreasing thrombosis formation. Our results showed that clamping [Cl-]i at high levels or Cftr deficiency-induced [Cl-]i increasement dramatically augmented phosphorylation (Ser422) of serum and glucocorticoid-regulated kinase (SGK1), subsequently upregulated P2Y12 and PAR4 expression via NF-κB signaling. Constitutively active mutant S422D SGK1 markedly increased P2Y12 and PAR4 expression. The specific SGK1 inhibitor GSK-650394 decreased platelet aggregation in wildtype and platelet-specific Cftr knockout mice, and platelet SGK1 phosphorylation was observed in line with increased [Cl-]i and decreased CFTR expression in CAD patients. Co-transfection of S422D SGK1 and adenovirus-induced CFTR overexpression in MEG-01 cells restored platelet activation signaling cascade. Our results suggest that [Cl-]i is a novel positive regulator of platelet activation and arterial thrombus formation via the activation of a [Cl-]i-sensitive SGK1 signaling pathway. Therefore, [Cl-]i in platelets is a novel potential biomarker for platelet hyperactivity, and CFTR may be a potential therapeutic target for platelet activation in CAD.

9.
Genes Dis ; 9(2): 347-357, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35224151

RESUMO

The treatment of cancer mainly involves surgical excision supplemented by radiotherapy and chemotherapy. Chemotherapy drugs act by interfering with tumor growth and inducing the death of cancer cells. Anti-tumor drugs were developed to induce apoptosis, but some patient's show apoptosis escape and chemotherapy resistance. Therefore, other forms of cell death that can overcome the resistance of tumor cells are important in the context of cancer treatment. Ferroptosis is a newly discovered iron-dependent, non-apoptotic type of cell death that is highly negatively correlated with cancer development. Ferroptosis is mainly caused by the abnormal increase in iron-dependent lipid reactive oxygen species and the imbalance of redox homeostasis. This review summarizes the progression and regulatory mechanism of ferroptosis in cancer and discusses its possible clinical applications in cancer diagnosis and treatment.

10.
Cancer Cell Int ; 22(1): 64, 2022 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-35135529

RESUMO

BACKGROUND: Osteosarcoma (OS) is a tumour with a high malignancy level and a poor prognosis. First-line chemotherapy for OS has not been improved for many decades. Bromodomain and extraterminal domain (BET) and histone deacetylases (HDACs) regulate histone acetylation in tandem, and BET and HDACs have emerged as potential cancer therapeutic targets. METHODS: Cell proliferation, migration, invasion, colony formation, and sphere-forming assays were performed with the two inhibitors alone or in combination to evaluate their suppressive effect on the malignant properties of OS cells. Apoptosis and the cell cycle profile were measured by flow cytometry. The synergistic inhibitory effect of OTX015/WT-161 on tumours was also examined in a nude mouse xenograft model. RESULTS: The combined therapy of OTX015/WT-161 synergistically inhibited growth, migration, and invasion and induced apoptosis, resulting in G1/S arrest of OS cells. Additionally, OTX015/WT-161 inhibited the self-renewal ability of OS stem cells (OSCs) in a synergistic manner. Further mechanistic exploration revealed that the synergistic downregulation of ß-catenin by OTX015-mediated suppression of FZD2 and WT-161-mediated upregulation of PTEN may be critical for the synergistic effect. Finally, the results of an in vivo assay showed that tumour xenografts were significantly decreased after treatment with the OTX015/WT-161 combination compared with OTX015 or WT-161 alone. CONCLUSIONS: Our findings in this study demonstrated that OTX015 and WT-161 had synergistic anticancer efficacy against OS, and their combination might be a promising therapeutic strategy for OS.

11.
Phytochemistry ; 198: 113126, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35167886

RESUMO

Five previously undescribed oblongolides, namely phomaones A-E, along with four known compounds, were isolated from the endophytic fungus Phoma bellidis Neerg.. Their structures and absolute configurations were determined by extensive experimental spectroscopic methods as well as single crystal X-ray diffractions, ECD calculations and GIAO 13C NMR calculations. Phomaone A represent the first example of oblongolides with glycol directly linked by two C-C bonds, and its biosynthetic pathway were proposed. The cytotoxicity of obtained compounds was evaluated against human cancer cell lines MCF-7, DU145, and SW480. All compounds except phomaone A showed the cytotoxicity against MCF-7 with IC50 value ranging from 12.45 to 49.84 µM.


Assuntos
Ascomicetos , Liliaceae , Ascomicetos/química
12.
Hypertension ; 79(4): e73-e85, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35144478

RESUMO

BACKGROUND: Low serum chloride (Cl-) level is considered an independent predictor of cardiovascular mortality associated with chronic hypertension. However, the underlying mechanisms are unknown. ClC-5, a member of the Cl- channel family, is sensitive to changes in intracellular and extracellular Cl- concentration and conducts outwardly rectifying Cl- currents. The aims of this study were to determine if ClC-5 is regulated by low extracellular Cl-, clarify its putative roles in hypertension-induced cerebrovascular remodeling, and elucidate the associated underlying mechanisms. METHODS: Whole-cell patch technique, intracellular Cl- concentration measurements, flow cytometry, Western blot, Clcn5 knockdown (Clcn5-/y), and adenovirus-mediated ClC-5 overexpression mice, 2-kidney, 2-clip, and angiotensin II infusion-induced hypertensive models were used. RESULTS: We found that low extracellular Cl- evoked a ClC-5-dependent Cl- current that was abolished by ClC-5 depletion in basilar artery smooth muscle cells (BASMCs). ClC-5 was upregulated in the arterial tissues of rats and patients with hypertension. Low Cl--induced current and ClC-5 protein expression positively correlated with basilar artery remodeling during hypertension. ClC-5 knockdown ameliorated hypertension-induced cerebrovascular remodeling and smooth muscle cell proliferation, whereas ClC-5 overexpression mice exhibited the opposite phenotype. ClC-5-dependent Cl- efflux induced by low extracellular Cl- activated WNK1 (lysine-deficient protein kinase 1) which, in turn, activated AKT (protein kinase B), and culminated in BASMC proliferation and vascular remodeling. CONCLUSIONS: ClC-5 mediates low extracellular Cl-induced Cl- currents in BASMCs and regulates hypertension-induced cerebrovascular remodeling by promoting BASMC proliferation via the WNK1/AKT signaling pathway.


Assuntos
Hipertensão , Proteínas Proto-Oncogênicas c-akt , Animais , Proliferação de Células , Canais de Cloreto/genética , Canais de Cloreto/metabolismo , Cloretos/metabolismo , Humanos , Camundongos , Miócitos de Músculo Liso/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos
13.
Neurol Sci ; 2022 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-35138478

RESUMO

BACKGROUND: GNE myopathy is the most common distal myopathy in China. We summarized the clinical, genetic, and pathological characteristics of 125 Chinese patients with GNE myopathy. METHODS: We collected clinical data of 21 patients diagnosed at our hospital and 104 patients from previous reports. Clinical, genetic, and pathological characteristics were summarized. According to the location of mutations, patients were classified into groups to analyze genotype-phenotype correlation. We reviewed the pathological features and studied the expressions of neural cell adhesion molecule. RESULTS: The severity of involvement of lower limb muscles was in the following order: tibialis anterior > biceps femoris > gastrocnemius > iliopsoas > quadriceps femoris. Mutation p.D207V was the most common variant in China. Patients carrying p.D207V tended to show later disease onset. In the epimerase/epimerase group, men had earlier disease onset than women (p < 0.05). In other groups, age at disease onset in females was earlier than that in males. Protein analysis showed decreased sialylation of NCAM and upregulation of LC3 in patients with different mutations. CONCLUSIONS: Mutation p.D207V is the most common GNE variant in China. Involvement of flexor muscles in lower limbs was more obvious than extensor muscles. NCAM expression in patients with various mutations may be a useful diagnostic biomarker in GNE myopathy.

14.
Sci Transl Med ; 14(626): eabf0992, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34985967

RESUMO

High CD8+ T cell infiltration in colorectal cancer (CRC) should suggest a favorable prognosis and a satisfactory response to immunotherapy; however, the vast majority of patients with CRC do not benefit from immunotherapy due to poor T cell infiltration. Therefore, a better understanding of the mechanisms for T cell exclusion from CRC tumors is needed. Tribbles homolog 3 (TRIB3) has been implicated as an oncoprotein, but its role in regulating antitumor immune responses has not been defined. Here, we demonstrated that TRIB3 inhibits CD8+ T cell infiltration in various CRC mouse models. We showed that TRIB3 was acetylated by acetyltransferase P300, which inhibited ubiquitination and subsequent proteasomal degradation of TRIB3. Ectopically expressed TRIB3 inhibited signal transducer and activator of transcription 1 (STAT1) activation and STAT1-mediated CXCL10 transcription by enhancing the epidermal growth factor receptor signaling pathway, causing a reduction in tumor-infiltrating T cells. Genetic ablation of Trib3 or pharmacological acceleration of TRIB3 degradation with a P300 inhibitor increased T cell recruitment and sensitized CRCs to immune checkpoint blockade therapy. These findings identified TRIB3 as a negative modulator of CD8+ T cell infiltration in CRCs, highlighting a potential therapeutic target for treating immunologically "cold" CRCs.


Assuntos
Proteínas de Ciclo Celular , Neoplasias Colorretais , Evasão da Resposta Imune , Proteínas Repressoras , Animais , Linfócitos T CD8-Positivos , Proteínas de Ciclo Celular/metabolismo , Quimiocina CXCL10/metabolismo , Neoplasias Colorretais/patologia , Humanos , Imunoterapia , Camundongos , Proteínas Repressoras/metabolismo , Fator de Transcrição STAT1/metabolismo , Transdução de Sinais
15.
Lipids Health Dis ; 21(1): 13, 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-35057794

RESUMO

BACKGROUND: Benzo [a] pyrene (BaP), a potent carcinogen, has been proved that it has toxicological effects via activation the aryl hydrocarbon receptor (AhR) pathway. AhR can participate in regulating lipogenesis and lipolysis. This topic will verify whether BaP regulates lipid metabolism via AhR. METHODS: (1) C57BL/6 mice were gavaged with BaP for 12 weeks to detect serum lipids, glucose tolerance, and insulin resistance. Morphological changes in white adipose tissue (WAT) were detected by Hematoxylin and Eosin staining. The mRNA expression levels of adipogenesis-related factors included recombinant human CCAAT/enhancer binding protein alpha (C/EBPα), peroxisome proliferator-activated receptor gamma (PPARγ), and fatty acid binding protein 4 (FABP4) and inflammatory factors included nuclear factor kappa-B (NF-κB), monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor alpha (TNF-α) were detected using PCR. (2) Neutral lipid content changes in differentiated 3 T3-L1 adipocytes treated with BaP with and w/o AhR inhibitor were detected by Oil red staining. The protein expression levels of adipogenesis- and decomposition-related factors included PPARγ coactivator-1 alpha (PGC-1α), and peroxisome proliferation-activated receptor alpha (PPARα) were detected using western blotting. The mRNA expression levels of inflammatory factors were detected using PCR. RESULTS: (1) BaP inhibited body weight gain, decreased lipid content, increased lipid levels, and decreased glucose tolerance and insulin tolerance in mice; (2) BaP reduced the expressions of C/EBPα, PPARγ, FABP4, PGC-1α, and PPARα and increased the expressions of NF-κB, MCP-1, and TNF-α by activating AhR. CONCLUSION: BaP inhibit fat synthesis and oxidation while inducing inflammation by activating AhR, leading to WAT dysfunction and causing metabolic complications.


Assuntos
Benzo(a)pireno/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Receptores de Hidrocarboneto Arílico/metabolismo , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Tecido Adiposo Branco/anatomia & histologia , Tecido Adiposo Branco/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Teste de Tolerância a Glucose , Resistência à Insulina , Lipídeos/sangue , Camundongos , Camundongos Endogâmicos C57BL , Receptores de Hidrocarboneto Arílico/efeitos dos fármacos
16.
Sci Rep ; 12(1): 412, 2022 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013490

RESUMO

The endometrium plays a critical role in embryo implantation and pregnancy, and a thin uterus is recognized as a key factor in embryo implantation failure. Umbilical cord mesenchymal stem cells (UC-MSCs) have attracted interest for the repair of intrauterine adhesions. The current study investigated the repair of thin endometrium in rats using the UC-MSCs and the mechanisms involved. Rats were injected with 95% ethanol to establish a model of thin endometrium. The rats were randomly divided into normal, sham, model, and UC-MSCs groups. Endometrial morphological alterations were observed by hematoxylin-eosin staining and Masson staining, and functional restoration was assessed by testing embryo implantation. The interaction between UC-MSCs and rat endometrial stromal cells (ESCs) was evaluated using a transwell 3D model and immunocytochemistry. Microarray mRNA and miRNA platforms were used for miRNA-mRNA expression profiling. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses were performed to identify the biological processes, molecular functions, cellular components, and pathways of endometrial injury and UC-MSCs transplantation repair and real-time quantitative reverse transcription PCR (qRT-PCR) was performed to further identify the expression changes of key molecules in the pathways. Endometrium thickness, number of glands, and the embryo implantation numbers were improved, and the degree of fibrosis was significantly alleviated by UC-MSCs treatment in the rat model of thin endometrium. In vitro cell experiments showed that UC-MSCs migrated to injured ESCs and enhanced their proliferation. miRNA microarray chip results showed that expression of 45 miRNAs was downregulated in the injured endometrium and upregulated after UC-MSCs transplantation. Likewise, expression of 39 miRNAs was upregulated in the injured endometrium and downregulated after UC-MSCs transplantation. The miRNA-mRNA interactions showed the changes in the miRNA and mRNA network during the processes of endometrial injury and repair. GO and KEGG analyses showed that the process of endometrial injury was mainly attributed to the decomposition of the extracellular matrix (ECM), protein degradation and absorption, and accompanying inflammation. The process of UC-MSCs transplantation and repair were accompanied by the reconstruction of the ECM, regulation of chemokines and inflammation, and cell proliferation and apoptosis. The key molecules involved in ECM-receptor interaction pathways were further verified by qRT-PCR. Itga1 and Thbs expression decreased in the model group and increased by UC-MSCs transplantation, while Laminin and Collagen expression increased in both the model group and MSCs group, with greater expression observed in the latter. This study showed that UC-MSCs transplantation could promote recovery of thin endometrial morphology and function. Furthermore, it revealed the expression changes of miRNA and mRNA after endometrial injury and UC-MSCs transplantation repair processed, and signaling pathways that may be involved in endometrial injury and repair.


Assuntos
Proliferação de Células , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Endométrio/patologia , Matriz Extracelular/patologia , Regeneração , Doenças Uterinas/cirurgia , Animais , Comunicação Celular , Células Cultivadas , Modelos Animais de Doenças , Endométrio/metabolismo , Endométrio/fisiopatologia , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Feminino , Sangue Fetal/citologia , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais , Transcriptoma , Doenças Uterinas/metabolismo , Doenças Uterinas/patologia , Doenças Uterinas/fisiopatologia
17.
Heart Lung ; 51: 59-66, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34731699

RESUMO

BACKGROUND: Lung cancer stigma is a widespread psychosocial problem. We developed a short form of the Cataldo lung cancer stigma scale for Chinese people with lung cancer (CLCSS-C-SF) and compared its psychometric properties with those of the full and short versions. METHODS: This was a secondary analysis using data from the full CLCSS-C, distress thermometer and perceived social support of Chinese people with lung cancer (N = 394). Exploratory and confirmatory factor analysis (CFA) were used to identify factor structure and assess construct validity. The internal consistency and concurrent and known-group validity were evaluated. RESULTS: The 22-item CLCSS-C-SF comprised four factors. The convergent validity evaluated using average variance extracted and discriminant validity were acceptable. Cronbach's alphas, concurrent and known-group validity were satisfactory for three versions. Only the four-factor model proposed was validated by CFA. CONCLUSION: The CLCSS-C-SF is reliable and valid and can be used in Chinese lung cancer populations.


Assuntos
Neoplasias Pulmonares , Estigma Social , China , Humanos , Neoplasias Pulmonares/psicologia , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários
18.
Mol Cell Biol ; 42(1): e0016321, 2022 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-34780286

RESUMO

EF24, a curcumin analog, exerts a potent antitumor effect on various cancers. However, whether EF24 retards the progression of triple-negative breast cancer (TNBC) remains unclear. In this study, we explored the role of EF24 in TNBC and clarified the underlying mechanism. In a mouse model of TNBC xenograft, EF24 administration reduced the tumor volume, suppressed cell proliferation, promoted cell apoptosis, and downregulated long noncoding RNA human leukocyte antigen complex group 11 (HCG11) expression. In TNBC cell lines, EF24 administration reduced cell viability, suppressed cell invasion, and downregulated HCG11 expression. HCG11 overexpression reenhanced the proliferation and invasion of TNBC cell lines suppressed by EF24. The following mechanism research revealed that HCG11 overexpression elevated Sp1 transcription factor (Sp1) expression by reducing its ubiquitination, thereby enhanced Sp1-mediated cell survival and invasion in the TNBC cell line. Finally, the in vivo study showed that HCG11-overexpressed TNBC xenografts exhibited lower responsiveness in response to EF24 treatment. In conclusion, EF24 treatment reduced HCG11 expression, resulting in the degradation of Sp1 expression, thereby inhibiting the proliferation and invasion of TNBC cells.


Assuntos
Compostos de Benzilideno/farmacologia , Proliferação de Células/efeitos dos fármacos , Piperidonas/farmacologia , RNA Longo não Codificante/genética , Fator de Transcrição Sp1/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/metabolismo , Animais , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , MicroRNAs/genética , RNA Longo não Codificante/efeitos dos fármacos , Fator de Transcrição Sp1/genética , Fator de Transcrição Sp1/metabolismo , Neoplasias de Mama Triplo Negativas/genética , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Orthop Surg ; 14(2): 254-263, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34914206

RESUMO

OBJECTIVE: To describe the application of reversed contralateral distal femoral locking compression plate (DF-LCP) inserted through a progressive and intermittent drilling procedure in the treatment of osteopetrotic subtrochanteric fracture (OSF). METHODS: Three patients (one male and two females with an average age of 45.33 ± 11.09 years) with OSF hospitalized between September 2015 and September 2020, were included in this present study. Lateral approach was applied in all patients who accepted open reduction and internal fixation (ORIF) with a reversed contralateral DF-LCP inserted through a progressive and intermittent drilling procedure. The operation time and intraoperative blood loss were recorded to evaluate the efficiency of this surgical method. Physical examination and imaging examination of the fracture site were used to evaluate the fracture union status, the position and stability of the implant, and the alignment of the injured limb at 1, 3, 6, and 12 months after operation, then a subsequent visit was conducted at least once a year. Harris Hip Score (HHS) was used to evaluate the hip joint function at 6 and 12 months after operation. RESULTS: The average operation time was 140 ± 21.60 min (110, 160, and 150 min); The average intraoperative blood loss was about 333.33 ± 23.57 ml (300, 350, and 350 ml). The average follow-up time was 22.33 ± 7.41 months (29, 26, and 12 months). All patients achieved bone union with an average time of 6.67 ± 0.94 months (6, 8, and 6 months). At the time of 6 months after operation, case 1 and 3 were almost pain-free and could walk with full weight bearing while case 2 could walk only with partial weight bearing using a crutch. The HHS scores of cases 1, 2, and 3 were 84/100, 74/100, and 92/100, respectively. At the follow-up at 12 months after operation, the HHS score improved to 91/100, 81/100, and 96/100, respectively. The contralateral incomplete old subtrochanteric fracture was deteriorated in case 1 at 26 months after operation. After 3 months of limited weight bearing using a crutch, bone union was verified in radiograph imaging. Fresh contralateral subtrochanteric fracture occurred in case 2 at 26 months after operation, which was treated using a similar surgical approach, and its clinical outcome is under follow-up. Moreover, no perioperative complications including operation-related death, vascular/nerve injury, deep venous thrombosis, pulmonary embolism, and incision infection, and long-term complications involving malunion, nonunion, implant failure, ankylosis, heterotopic ossification, osteonecrosis, and osteomyelitis were identified. CONCLUSION: The application of reversed contralateral DF-LCP in OSF is practicable and reliable. Progressive and intermittent drilling is a safe and efficient method for implant insertion in this complicated situation.


Assuntos
Fraturas do Quadril , Osteopetrose , Adulto , Placas Ósseas , Feminino , Fixação Interna de Fraturas/métodos , Fraturas do Quadril/diagnóstico por imagem , Fraturas do Quadril/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Redução Aberta , Estudos Retrospectivos , Resultado do Tratamento
20.
Cancer Nurs ; 45(1): E59-E67, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-32541209

RESUMO

BACKGROUND: Patients with lung cancer suffer from significant psychological distress. The underlying theoretical model that may explain what predicts or mediates the degree of psychological distress has not been elucidated. OBJECTIVES: To describe the incidence of psychological distress in patients with lung cancer and to test a predictive theoretical model of psychological distress based on symptom burden, type D personality, social support, and intrusive thoughts. METHODS: Three hundred eighty-nine patients with stages I to IV lung cancer were recruited. Participants completed a battery of scales, including measures of psychological distress, symptom burden, type D personality, perceived social support, intrusive thoughts, and demographic and clinical characteristics. The predictive theoretical model was tested using structural equation modeling. RESULTS: Experiencing clinically significant psychological distress was reported by 63.75% of participants. Consistent with the social cognitive processing model, symptom burden, type D personality, social support, and intrusive thoughts all significantly and directly predicted the level of psychological distress in patients with lung cancer. Moreover, intrusive thoughts mediated the effects of type D personality and symptom burden on psychological distress; social support and symptom burden mediated the effects of type D personality on psychological distress. CONCLUSIONS: The majority of the participants experienced psychological distress at a clinically significant level. Intrusive thoughts and social support mediated the effects of type D personality and symptom burden on psychological distress. IMPLICATIONS FOR PRACTICE: Patients with type D personality and symptom burden should be identified. Interventions for targeting social support and intrusive thoughts might ultimately reduce their psychological distress.


Assuntos
Neoplasias Pulmonares , Angústia Psicológica , Ansiedade , Estudos Transversais , Humanos , Neoplasias Pulmonares/complicações , Apoio Social , Estresse Psicológico/epidemiologia
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