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Glia are essential to protecting and enabling nervous system function and a key glial function is the formation of the glial sheath around peripheral axons. Each peripheral nerve in the Drosophila larva is ensheathed by three glial layers, which structurally support and insulate the peripheral axons. How peripheral glia communicate with each other and between layers is not well established and we investigated the role of Innexins in mediating glial function in the Drosophila periphery. Of the eight Drosophila Innexins, we found two (Inx1 and Inx2) are important for peripheral glia development. In particular loss of Inx1 and Inx2 resulted in defects in the wrapping glia leading to disruption of the glia wrap. Of interest loss of Inx2 in the subperineurial glia also resulted in defects in the neighboring wrapping glia. Inx plaques were observed between the subperineurial glia and the wrapping glia suggesting that gap junctions link these two glial cell types. We found Inx2 is key to Ca2+ pulses in the peripheral subperineurial glia but not in the wrapping glia, and we found no evidence of gap junction communication between subperineurial and wrapping glia. Rather we have clear evidence that Inx2 plays an adhesive and channel-independent role between the subperineurial and wrapping glia to ensure the integrity of the glial wrap.SIGNIFICANCE STATEMENT Gap junctions are critical for glia communication and formation of myelin in myelinating glia. However, the role of gap junctions in non-myelinating glia is not well studied, yet non-myelinating glia are critical for peripheral nerve function. We found the Innexin gap junction proteins are present between different classes of peripheral glia in Drosophila. Here Innexins form junctions to facilitate adhesion between the different glia but do so in a channel-independent manner. Loss of adhesion leads to disruption of the glial wrap around axons and leads to fragmentation of the wrapping glia membranes. Our work points to an important role for gap junction proteins in mediating insulation by non-myelinating glia.
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Proteínas de Drosophila , Animales , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Neuroglía/metabolismo , Sistema Nervioso Periférico/metabolismo , Drosophila/metabolismo , Axones/metabolismo , Conexinas/genética , Conexinas/metabolismoRESUMEN
BACKGROUND: Circular RNA (circRNA) plays a crucial role in the pathogenesis and progression of colorectal cancer (CRC). However, the current understanding of the emerging function and mechanism of circ-RAPGEF5 in CRC remains poorly understood. METHODS: We first evaluated the expression level of circ-RAPGEF5 in CRC tissues and cells by quantitative real-time polymerase chain reaction (qRT-PCR). Then, we analyzed cell proliferation (EdU and colony formation assay), migration (cell wound healing assay), invasion (transwell assay), and apoptosis (flow cytometry assay). To further elucidate the mechanism of circ-RAPGEF5 in CRC, bioinformatics tools, Dual-luciferase reporter assay, Ago2 RNA immunoprecipitation assay, and RNA pull-down assay were employed. Moreover, we established a CRC transplantation tumor model to evaluate the effect of circ-RAPGEF5 on tumor growth in vivo. RESULTS: circ-RAPGEF5 was significantly upregulated in CRC tissues and CRC cells. Furthermore, the downregulation of circ-RAPGEF5 restrained CRC cell proliferation, migration, and invasion, and promoted cell apoptosis in vitro. Mechanistically, circ-RAPGEF5 accelerated the malignant behaviors of CRC cells by sponging miR-545-5p, which targeted polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3). In addition, we revealed that circ-RAPGEF5 silence curbed tumor growth in vivo. CONCLUSION: These findings revealed that circ-RAPGEF5 played an oncogenic role through the miR-545-5p/GALNT3 axis in CRC progression, providing potential therapeutic targets for the treatment of CRC.
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Neoplasias Colorrectales , Regulación hacia Abajo , N-Acetilgalactosaminiltransferasas , ARN Circular , Animales , Humanos , Masculino , Ratones , Apoptosis , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/genética , MicroARNs/metabolismo , N-Acetilgalactosaminiltransferasas/genética , N-Acetilgalactosaminiltransferasas/metabolismo , Polipéptido N-Acetilgalactosaminiltransferasa , ARN Circular/genética , ARN Circular/metabolismoRESUMEN
Immunodeficiency secondary to anti-interferon-gamma (anti-IFN-γ) autoantibodies was first described in 2004 as an acquired defect in the IFN-γ pathway leading to susceptibility to multiple opportunistic infections, including dimorphic fungi, parasites, and bacteria, especially tuberculosis and non-tuberculous mycobacterium (NTM) species. It has so far only been described in adult patients. We present 2 cases of disseminated NTM infections in otherwise immunocompetent children. A 16-year-old girl with Sweet's syndrome-like neutrophilic dermatosis developed recurrent fever and cervical lymphadenitis secondary to Mycobacterium abscessus. A 10-year-old boy with a history of prolonged fever, aseptic meningitis, aortitis, and arteritis in multiple blood vessels developed thoracic vertebral osteomyelitis secondary to Mycobacterium avium complex. Both patients were found to have positive serum neutralizing anti-IFNγ autoantibodies. Testing for anti-IFNγ autoantibodies should be considered in otherwise healthy immunocompetent hosts with recurrent or disseminated NTM infection. This represents a phenocopy of primary immunodeficiency which has been recently described only in adults. We report the first two cases of this phenomenon to affect children.
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Autoanticuerpos/sangre , Síndromes de Inmunodeficiencia/sangre , Interferón gamma/inmunología , Infecciones por Mycobacterium no Tuberculosas/sangre , Infecciones Oportunistas/sangre , Adolescente , Autoanticuerpos/inmunología , Niño , Femenino , Humanos , Síndromes de Inmunodeficiencia/complicaciones , Síndromes de Inmunodeficiencia/inmunología , Masculino , Infecciones por Mycobacterium no Tuberculosas/complicaciones , Infecciones por Mycobacterium no Tuberculosas/inmunología , Infecciones Oportunistas/complicaciones , Infecciones Oportunistas/inmunologíaRESUMEN
BACKGROUND: Osteoporosis (OP) is the result of bone mass reduction and bone structure disorder. Bone marrow mesenchymal stem cells (BMSCs) are the main source of osteogenic precursor cells involved in adult bone remodeling. The involvement of the deubiquitinating enzyme CYLD in OP has recently been discovered. However, the detailed role and mechanism of CYLD remain unknown. METHODS: The OP mouse model was established by performing ovariectomy (OVX) on mice. Hematoxylin and eosin staining, Masson and Immunohistochemical staining were used to assess pathologic changes. Real-time quantitative PCR, Western blot, and immunofluorescence were employed to assess the expression levels of CYLD, WNK1, NLRP3 and osteogenesis-related molecules. The binding relationship between CYLD and WNK1 was validated through a co-immunoprecipitation assay. The osteogenic capacity of BMSCs was determined using Alkaline phosphatase (ALP) and alizarin red staining (ARS). Protein ubiquitination was evaluated by a ubiquitination assay. RESULTS: The levels of both CYLD and WNK1 were decreased in bone tissues and BMSCs of OVX mice. Overexpression of CYLD or WNK1 induced osteogenic differentiation in BMSCs. Additionally, NLRP3 inflammation was activated in OVX mice, but its activation was attenuated upon overexpression of CYLD or WNK1. CYLD was observed to reduce the ubiquitination of WNK1, thereby enhancing its protein stability and leading to the inactivation of NLRP3 inflammation. However, the protective effects of CYLD on osteogenic differentiation and NLRP3 inflammation inactivation were diminished upon silencing of WNK1. CONCLUSION: CYLD mitigates NLRP3 inflammasome-triggered pyroptosis in osteoporosis through its deubiquitination of WNK1.
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Enfermedades Óseas , Osteoporosis , Animales , Femenino , Ratones , Diferenciación Celular , Células Cultivadas , Enzima Desubiquitinante CYLD , Inflamasomas , Inflamación , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Osteogénesis , Osteoporosis/metabolismo , PiroptosisRESUMEN
ABSTRACT: Asthma is a major chronic disease affecting children, and children with difficult-to-treat asthma account for a disproportionate share of resource utilisation and healthcare costs. This review presents a comprehensive and up-to-date overview of the treatment strategies in difficult-to-treat paediatric asthma. Mimickers of asthma must first be ruled out, and the diagnosis confirmed with objective tests whenever possible. The effect of comorbid conditions such as obesity, smoking, other atopic conditions and psychosocial factors on asthma control and severity should be considered. Treatment can then be optimised by implementing personalised strategies, including the use of appropriate drug delivery devices and adherence monitoring. Biologics can be an alternative treatment option for selected patients but should not be a substitute for addressing poor adherence. Many patients with difficult-to-treat asthma may not have severe asthma, and the physician should work with patients and families to achieve good asthma control via an individualised approach.
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Designing artificial nano-enzymes for scavenging reactive oxygen species (ROS) in chondrocytes (CHOs) is considered the most feasible pathway for the treatment of osteoarthritis (OA). However, the accumulation of ROS due to the amount of nano-enzymatic catalytic site exposure and insufficient oxygen supply seriously threatens the clinical application of this therapy. Although metal-organic framework (MOF) immobilization of artificial nano-enzymes to enhance active site exposure has been extensively studied, artificial nano-enzymes/MOFs for ROS scavenging in OA treatment are still lacking. In this study, a biocompatible lubricating hydrogel-loaded iron-doped zeolitic imidazolate framework-8 (Fe/ZIF-8/Gel) centrase was engineered to scavenge endogenous overexpressed ROS synergistically generating dissolved oxygen and enhancing sustained lubrication for CHOs as a ternary artificial nano-enzyme. This property enabled the nano-enzymatic hydrogels to mitigate OA hypoxia and inhibit oxidative stress damage successfully. Ternary strategy-based therapies show excellent cartilage repair in vivo. The experimental results suggest that nano-enzyme-enhanced lubricating hydrogels are a potentially effective OA treatment and a novel strategy.
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Condrocitos , Hidrogeles , Especies Reactivas de Oxígeno , Hidrogeles/química , Hidrogeles/farmacología , Animales , Condrocitos/metabolismo , Condrocitos/efectos de los fármacos , Condrocitos/citología , Especies Reactivas de Oxígeno/metabolismo , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Osteoartritis/tratamiento farmacológico , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Cartílago/efectos de los fármacos , Cartílago/metabolismo , Tamaño de la Partícula , Humanos , Zeolitas/químicaRESUMEN
Without treatment, familial adenomatous polyposis (FAP) patients will inevitably develop colorectal cancer (CRC) during lifetime. Yet, surgical trauma is a high risk of desmoid tumor (DT), one of the main causes of death in FAP patients. So far, the timing for colectomy is primarily based on the clinician's experience and the patient's preference; most patients undergo surgery at mid-20's. In this study, we analyzed the germline mutation distribution in 35 FAP patients from different families, 16 of them diagnosed with DTs. We also investigated the association between the molecular alterations and the clinicopathological features. Capture-based targeted sequencing using a panel of 520 genes was performed on tumor tissue and paired normal mucosa or white blood cells from 18 FAP probands who were initially diagnosed with CRC. Of all 35 FAP patients, 30 (85.7%) of them harbored germline APC mutations scattered from codon 161 to 1578. The mutations in the 16 DT patients scattered from codon 457 to 1578. All three patients with the mutation at the 3' of 1444 codon were diagnosed with DT. The percentage of high-risk DT (stage III or IV) harboring mutations at the 5' of 1062 or 1062-1578 was 14.3% and 77.8%, respectively, and all three patients with 3' of 1399 codon mutation had high risk. In addition, by using public database, we compared 140 FAP patients with DT to all 1880 FAP patients on the Leiden Open Variation Database and found that the odd ratio of DT in codon 159 to 495 was 0.34, while in codon 1310 to 2011 was 2.36. Compared to sporadic CRCs, the somatic spectrum of FAP CRCs was similar to the early onset CRCs, with higher TP53 (94.1%) and lower somatic APC mutations (65.7%), but the KRAS mutation rate was the highest (58.5%). One of the 18 FAP CRCs was identified as microsatellite instability-high (MSI-H), with tumor mutation burden (TMB) of 115.65 mut/Mb. Given that no TP53 mutations were detected in the low- and high-grade adenomas, ctDNA TP53 sequencing might be used for the close monitoring before FAP colectomy. In conclusion, except mutations at the 5' end of APC (5' to 495), all FAP patients need to consider the risk of DT after colectomy. The chance of life-threating DTs was higher in patients with 3' 1062 codon mutation and peaked in patients with 3' 1399 codon mutation. Scheduled monitoring of TP53 ctDNA is proposed to be a novel tool for optimizing the operation time.
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Understanding the ultrafine substructure in freshly formed Fe-C martensite is the key point to reveal the real martensitic transformation mechanism. As-quenched martensite, whose transformation temperature is close to room temperature, has been investigated in detail by means of transmission electron microscopy (TEM) in this study. The observation results revealed that the freshly formed martensite after quenching is actually composed of ultrafine crystallites with a grain size of 1−2 nm. The present observation result matches well with the suggestion based on X-ray studies carried out one hundred years ago. Such nanocrystals are distributed throughout the entire martensite. The whole martensite shows a uniform contrast under both bright and dark field observation modes, irrespective of what observation directions are chosen. No defect contrast can be observed inside each nanocrystal. However, a body-centered cubic {112}<111>-type twinning relationship exists among the ultrafine α-Fe grains. Such ultrafine α-Fe grains or crystallites are the root cause of the fine microstructure formed in martensitic steels and high hardness after martensitic transformation. The formation mechanism of the ultrafine α-Fe grains in the freshly formed martensite will be discussed based on a new γ â α phase transformation mechanism.
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BACKGROUND: Chronic liver diseases can interfere with hepatic metabolism of lipoproteins, apolipoproteins. Hepatitis B virus (HBV) is a major etiological agent causing acute and chronic liver diseases. Apolipoprotein M (ApoM) is a high-density lipoprotein (HDL) apolipoprotein and exclusively expressed in the liver parenchyma cells and in the tubular cells of the kidney. This study was to determine the correlation between HBV infection and ApoM expression. MATERIALS AND METHODS: Serum ApoM levels in patients with HBV infection and in healthy individuals were measured by ELISA, ApoM mRNA expression were determined by RT-PCR, and the expression of S and E proteins of HBV, as well as the synthesis of viral DNA were measured by ELISA and real-time PCR. RESULTS: The levels of serum ApoM was significantly elevated in patients as compared to healthy individuals (P < 0.001), ApoM promoter activity, mRNA and protein expression were all stimulated in cells transfected with infectious HBV clone. In addition, ApoM decreases the expression of S and E proteins of HBV and the synthesis of viral DNA. CONCLUSION: Raised ApoM levels in HBV infection may in turn suppress HBV replication, one of the protective mechanisms of nature.
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Apolipoproteínas/sangre , Virus de la Hepatitis B/fisiología , Hepatitis B Crónica/sangre , Lipocalinas/sangre , Replicación Viral , Apolipoproteínas/genética , Apolipoproteínas M , Estudios de Casos y Controles , Expresión Génica , Regulación Viral de la Expresión Génica , Genes Reporteros , Células Hep G2 , Humanos , Lipocalinas/genética , Luciferasas de Renilla/biosíntesis , Luciferasas de Renilla/genética , Regiones Promotoras Genéticas , Proteínas Virales/genéticaRESUMEN
As a selective estrogen receptor ß agonist, the natural flavonoid liquiritigenin reportedly inhibits invasiveness of breast cancer cells, but its specific role and mechanism remain largely unclear. In this study, cells from the triple negative breast cancer lines MDA-MB-231 and BT549 were incubated with different concentrations of liquiritigenin. The results indicated that low concentrations had no significant cytotoxic effect, whereas high concentrations decreased viability of both MDA-MB-231 and BT549 cells. Liquiritigenin treatment also resulted in increased apoptosis and enhanced Caspase3 activity. After liquiritigenin treatment, we observed decreased invasive and migratory capacities of cells, as well as upregulated E-cadherin and downregulated N-cadherin, vimentin, and MMP9. Interestingly, liquiritigenin increased the mRNA and protein expression of breast cancer 1 (BRCA1). It also increased p21 and growth arrest and DNA-damage-inducible 45 alpha (GADD45A) levels, accompanied by decreased cellular DNA methyltransferase (DNMT) activity and downregulation of DNMT1, DNMT3a, and DNMT3b. These findings suggest that liquiritigenin can inhibit malignant behavior of triple negative breast cancer cells by inhibiting DNMT activity and increasing BRCA1 expression and its transcriptional activity. Liquiritigenin thus may be a promising candidate for the treatment of breast cancer.
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Proteína BRCA1/genética , Carcinogénesis/patología , ADN (Citosina-5-)-Metiltransferasas/metabolismo , Flavanonas/farmacología , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología , Apoptosis/efectos de los fármacos , Apoptosis/genética , Proteína BRCA1/metabolismo , Carcinogénesis/efectos de los fármacos , Carcinogénesis/genética , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Metilación de ADN/efectos de los fármacos , Metilación de ADN/genética , Transición Epitelial-Mesenquimal/efectos de los fármacos , Transición Epitelial-Mesenquimal/genética , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Invasividad Neoplásica , Regiones Promotoras Genéticas/genética , Transcripción Genética/efectos de los fármacosRESUMEN
AIM: Our previous study has shown that leucine-rich repeat containing GPCR-4 (LGR4, or GPR48) LGR4 plays a role in cell migration, invasion, proliferation and apoptosis of prostate cancer (PCa). In this study, we aimed to explore whether LGR4 would affect radiation response in PCa. MATERIALS AND METHODS: LGR4 expression was silenced by shRNA transfection. qRT-PCR was employed to determine mRNA expression of LGR4 and DNA damage repair genes. Western blot was used to evaluate protein expression of LGR4, RSPO1-4, androgen receptor (AR), cyclic AMP response-element binding protein (CREB1), γH2A.X, and H2A.X. Cell proliferation was detected by CCK-8 assay and apoptosis was assayed by flow cytometry. Additionally, a xenograft model was also established to validate the role of LGR4 in PCa cells after radiation. KEY FINDINGS: LGR4 expression was enhanced in PCa cells by radiation treatment in dose- and time-dependent means. RSPO1-4 were also upregulated post-radiation. Furthermore, LGR4 knockdown exacerbated apoptosis, reduced cell viabilities and strengthened nuclear γH2A.X staining in AR positive PCa cells but not in AR negative cells in the presence of radiation. Likewise, LGR4 ablation diminished AR and CREB1 expression induced by radiation. In contrast, RSPO1 stimulation augmented cell viabilities, promoted AR and CREB1 expression, and upregulated DNA repair gene expression, which could be reversed by enzalutamide, except for AR expression. Additionally, LGR4 knockdown further suppressed tumor growth and AR/CREB1 expression but enhanced γH2A.X expression in xenografts. SIGNIFICANCE: In all, our study suggested that LGR4 might serve as an important regulator of radiation sensitivity in PCa.
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Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/radioterapia , Receptores Acoplados a Proteínas G/metabolismo , Apoptosis/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Humanos , Masculino , Próstata/patología , Neoplasias de la Próstata/patología , Tolerancia a Radiación , Receptores Androgénicos/genética , Receptores Acoplados a Proteínas G/genética , Transducción de Señal/genética , Activación TranscripcionalRESUMEN
MicroRNAs (miRs) serve an integral role in prostate cancer. The present study aimed to investigate the effects and mechanisms of miR137 in hypoxiamediated migration and epithelialmesenchymal transition (EMT). PC3 and DU145 prostate cancer cells were exposed to hypoxia for 24 h, after which the expression of miR137 was determined by reverse transcriptionquantitative PCR (RTqPCR). The cells were transfected with a miR137 mimic or inhibitor, followed by hypoxia exposure. The results demonstrated that hypoxia reduced miR137 expression. Further results from the Cell Counting Kit8, Cell Death Detection ELISA plus kit, Transwell assay, RTqPCR and western blotting assays revealed that the miR137 mimic prevented cell proliferation, facilitated apoptosis and repressed cell migration, invasiveness, and expression of Ncadherin, vimentin and matrix metalloproteinase 2; the miR137 inhibitor exerted the opposite effects. A dual-luciferase reporter assay determined that miR137 directly targeted leucinerich repeatcontaining G proteincoupled receptor 4 (LGR4). Additionally, miR137 negatively regulated the epidermal growth factor receptor/extracellular signal-regulated kinase (EGFR/ERK) signaling pathway by targeting LGR4. LGR4 silencing or EGFR/ERK inhibition abolished the effects of miR137 inhibitor on cell migration and EMT. In conclusion, by targeting LGR4 via the EGFR/ERK signaling pathway, miR137 inhibited prostate cancer cell migration and EMT.
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Sistema de Señalización de MAP Quinasas/genética , MicroARNs/metabolismo , Neoplasias de la Próstata/genética , Receptores Acoplados a Proteínas G/genética , Apoptosis/efectos de los fármacos , Apoptosis/genética , Hipoxia de la Célula , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Transición Epitelial-Mesenquimal/efectos de los fármacos , Transición Epitelial-Mesenquimal/genética , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/metabolismo , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , MicroARNs/agonistas , MicroARNs/antagonistas & inhibidores , Neoplasias de la Próstata/patologíaRESUMEN
Objective: To review the published literature reporting on the incidence of myocardial fibrosis (MF) in high-intensity endurance athletes measured by late gadolinium enhancement (LGE) with cardiac magnetic resonance imaging (CMR). Methods: Five databases (PubMed, Cochrane Controlled Trials Register, EMBASE, Web of Science, and SPORTDiscus) were searched to obtain case cohort studies published before November 10, 2019. From 96 abstracts or reports extracted, 18 full-text articles were reviewed. The incidence of LGE was reported as outcome measures. Subgroup analysis was performed by age (under or above 50 years). Pooled estimates were obtained using a fixed-effects model. Results: After a full-text assessment, 12 studies involving 1,359 participants were included for analysis. Among them, 163/772 participants in the endurance athletes group showed LGE positive, compared with 19/587 participants in the comparison group. The results of the meta-analysis suggested that the prevalence of LGE was higher in the athletes group with long-term endurance exercise (OR 7.20;95%CI: 4.51-11.49). In addition, the same conclusion was drawn after the stratification of age. Conclusions: The available evidence demonstrates that high-intensity endurance athletes is associated with an increased incidence of LGE positive.
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BACKGROUND: Mushroom exposure is a global health issue. The manifestations of mushroom poisoning (MP) may vary. Some species have been reported as rhabdomyolytic, hallucinogenic, or gastrointestinal poisons. Critical or even fatal MPs are mostly attributable to Amanita phalloides, with the development of severe liver or renal failure. Myocardial injury and even cases mimicking ST-segment elevation myocardial infarction (STEMI) have been previously reported, while cardiac arrhythmia or cardiac arrest is not commonly seen. CASE SUMMARY: We report a 68-year-old woman with MP who suffered from delirium, seizure, long QT syndrome on electrocardiogram (ECG), severe cardiac arrhythmias of multiple origins, and cardiac arrest. She was intubated and put on blood perfusion. Her kidney and liver functions were intact; creatine kinase-MB was mildly elevated, and then fell within normal range during her hospital stay. We sent the mushrooms she left for translation elongation factor subunit 1α, ribosomal RNA gene sequence, and internal transcribed spacer sequence analyses. There were four kinds of mushrooms identified, two of which were found to be toxic. CONCLUSION: This is the first time that we found cardiac toxicity caused by Panaeolus subbalteatus and Conocybe lactea, which were believed to be toxic to the liver, kidney, and brain. We suggest that intensive monitoring and ECG follow-up are essential to diagnose prolonged QT interval and different forms of tachycardia in MP patients, even without the development of severe liver or renal failure. The mechanisms need to be further investigated and clarified based on animal experiments and molecular signal pathways.
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Human trophoblast cell surface antigen 2 (TROP2) has been noted to serve an important role in the proliferation and migration of various types of human cancers. However, the potential role and the molecular mechanisms of TROP2 in osteosarcoma (OS) remain largely unclear. In the present study, high expression of TROP2 in human OS tissues and cell lines was observed. Overexpression of TROP2 promoted the proliferation and migration of OS cell lines, while TROP2 knockdown markedly decreased cell growth and migration. Furthermore, it was revealed that TROP2 overexpression significantly activated the phosphoinositide 3kinase/protein kinase B (PI3K/AKT) signaling pathway. Collectively, these results suggested that TROP2 may promote OS cell proliferation and migration via PI3K/AKT signaling and may serve as a novel treatment target for OS.
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Antígenos de Neoplasias/genética , Moléculas de Adhesión Celular/genética , Movimiento Celular/genética , Proliferación Celular/genética , Osteosarcoma/genética , Adolescente , Adulto , Niño , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Masculino , Persona de Mediana Edad , Proteína Oncogénica v-akt/genética , Osteosarcoma/patología , Fosfatidilinositol 3-Quinasas/genética , Transducción de Señal/genética , Adulto JovenRESUMEN
Hepatitis B virus (HBV) infection is one of the major causes of hepatocellular carcinoma (HCC). Kinesin family member 4A (KIF4A) is a microtubulebased motor protein, which is upregulated in cervical and lung cancer. However, the expression of KIF4A in HBVassociated HCC, and the effect of HBV on the expression of KIF4A remain to be elucidated. In the present study, the expression profiles of KIF4A were examined in cancerous tissues and paracancerous tissues from patients with HCC, who presented with histories of chronic HBV infection, and the role of HBV in the induction of the expression of KIF4A was investigated. HepG2 cells were transfected with the pHBV1.3, HBV infectious clone and a construct, which contained the luciferase gene under the control of the KIF4A gene promoter. The results demonstrated that the expression of KIF4A was significantly higher in the HCC tissues than in the paracancerous tissues. HBV activated the KIF4A gene promoter and upregulated the mRNA and protein expression of KIF4A. Furthermore, activation of the gene expression of KIF4A increased in a pHBV1.3 concentrationdependent manner. These results provide novel insights into the understanding of HCC oncogenesis caused by HBV.