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Distant metastasis is the primary reason for treatment failure in patients with nasopharyngeal carcinoma (NPC). In this study, we investigated the effect of ulinastatin (UTI) on NPC metastasis and its underlying mechanism. Highly-metastatic NPC cell lines S18 and 58F were treated with UTI and the effect on cell proliferation, migration, and invasion were determined by MTS and Transwell assays. S18 cells with luciferase-expressing (S18-1C3) were injected into the left hind footpad of nude mice to establish a model of spontaneous metastasis from the footpad to popliteal lymph node (LN). The luciferase messenger RNA (mRNA) was measured by quantitative polymerase chain reaction (qPCR), and the metastasis inhibition rate was calculated. Key molecular members of the UTI-related uPA, uPAR, and JAT/STAT3 signaling pathways were detected by qPCR and immunoblotting. UTI suppressed the migration and infiltration of S18 and 5-8F cells and suppressed the metastasis of S18 cells in vivo without affecting cell proliferation. uPAR expression decreased from 24 to 48 h after UTI treatment. The antimetastatic effect of UTI is partly due to the suppression of uPA and uPAR. UTI partially suppresses NPC metastasis by downregulating the expression of uPA and uPAR.
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Neoplasias Nasofaríngeas , Animales , Ratones , Humanos , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patología , Ratones Desnudos , Línea Celular Tumoral , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/patología , Luciferasas , Movimiento Celular , Invasividad Neoplásica , Metástasis de la NeoplasiaRESUMEN
Charcot-Marie-Tooth disease type 2 (CMT2) is a clinically and genetically heterogeneous inherited neuropathy. Although new causative and disease-associated genes have been identified for CMT2 in recent years, molecular diagnoses are still lacking for a majority of patients. We here studied a cohort of 35 CMT2 patients of Chinese descent, using whole exome sequencing to investigate gene mutations and then explored relationships among genotypes, clinical features, and mitochondrial DNA levels in blood as assessed by droplet digital PCR. We identified pathogenic variants in 57% of CMT2 patients. The most common genetic causes in the cohort were MFN2 mutations. Two patients with typical CMT phenotype and neuromyotonia were detected to harbor compound heterozygous variations in the HINT1 gene. In conclusion, our work supports that the molecular diagnostic rate of CMT2 patients can be increased via whole exome sequencing, and our data suggest that assessment of possible HINT1 mutations should be undertaken for CMT2 patients with neuromyotonia.
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Enfermedad de Charcot-Marie-Tooth/genética , Mutación , Pueblo Asiatico/genética , China , Femenino , GTP Fosfohidrolasas/genética , Genotipo , Humanos , Masculino , Proteínas Mitocondriales/genética , Proteínas del Tejido Nervioso/genética , Secuenciación del ExomaRESUMEN
Nasopharyngeal carcinoma (NPC) is relatively sensitive to ionizing radiation, and radiotherapy is the main treatment modality for non-metastatic NPC. Radiation therapy generates overproduction of reactive oxygen species (ROS), which can cause DNA damage and induce apoptosis in tumors, thereby killing the malignant cells. Although dietary antioxidant supplementation reduces oxidative stress and promotes tumor progression, the effects of antioxidants on the NPC cells upon radiation have not been reported. In the present study, we showed that antioxidants (ß-Carotene, NAC, GSH) played an anti-apoptotic role in response to radiation via decreasing ROS production and inhibiting MAPK pathway in NPC cells. Based on that, we conclude that the use of supplemental antioxidants during radiotherapy should be avoided because of the possibility of tumor protection and reduced treatment efficacy.
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Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Línea Celular Tumoral , Humanos , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
OBJECTIVE: Thoracic aortic dissection (TAD) is associated with matrix changes, biochemical changes, and inflammatory markers like interleukin-1 beta (IL-1ß). However, the exact mechanism remains unknown. This study aimed to investigate the role of IL-1ß, matrix metalloproteinase (MMP)-2, MMP-9, smooth muscle cell apoptosis, and elastic fibre fracture in the development of TAD in a rat model. METHODS: The TAD rat model was induced by ß-aminopropionitrile (BAPN). TAD was investigated in 112 male Sprague-Dawley rats, which were equally divided into four groups of 28 rats (Control, BAPN, BAPN + IL-1ß, and BAPN + IL-1ß antibody). Systolic blood pressure, survival, and the development of TAD were measured after six weeks. Expression of IL-1ß, MMP-2, and MMP-9 was measured by Western blot. Apoptosis, aortic elastin concentration, and biomechanical characteristics were measured by the TdT mediated dUTP nick end labelling assay, Victoria blue staining, and in vitro testing. RESULTS: During six weeks, the mortality was 0% (0/28) in the control group, 53.6% (15/28) in the BAPN group (p < .001 compared with the control group), 75.0% (21/28) in the BAPN + IL-1ß group (p = .007 compared with the BAPN group), and 35.7% (10/28) in the BAPN + IL-1ß antibody group (p = .023 compared with BAPN group and p < .001 compared with the BAPN + IL-1ß group). IL-1ß treatment deteriorates BAPN induced mortality and aneurysm expansion, which were attenuated by anti-IL-1ß treatment. In BAPN + IL-1ß group, stress and strain parameters were decreased by 13.5%-53.5% and elastin content was decreased by 14%, and IL-1ß, MMP-2, and MMP-9 were expressed higher by 117%, 108%, and 75% when compared with the rats in the BAPN group. Contrarily, in the BAPN + IL-1ß antibody group, the above changes could be completely (strain, elastin content, and expression of MMP-2) or partly (elasticity modulus, stress, and expression of MMP-9) blocked by anti-IL-1ß treatment. CONCLUSION: IL-1ß plays a critical role in TAD formation by altering the expression of MMP-2 and MMP-9, degrading the aortic wall matrix, causing elastic fibre rupture, and changing the stress or strain of the aortic wall. Anti-IL-1ß reduces the later effects and could be one of the molecular targets for prognosis and drug treatment of TAD in the future.
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Aneurisma de la Aorta Torácica/metabolismo , Disección Aórtica/metabolismo , Interleucina-1beta/metabolismo , Aminopropionitrilo , Disección Aórtica/inducido químicamente , Disección Aórtica/patología , Animales , Anticuerpos/farmacología , Aorta Torácica/patología , Aneurisma de la Aorta Torácica/inducido químicamente , Aneurisma de la Aorta Torácica/patología , Apoptosis , Modelos Animales de Enfermedad , Elastina/metabolismo , Interleucina-1beta/antagonistas & inhibidores , Interleucina-1beta/inmunología , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Ratas , Ratas Sprague-Dawley , Tasa de SupervivenciaRESUMEN
La(2)Zr(2)O(7) powder was prepared with combustion method with La(2)O(3), Zr(NO(3))(4) and glycine as raw materials. La(2)Zr(2)O(7) powders were characterized with ICP-AES, EDAX, XRD, IR and TG-DTA techniques, respectively. Effects of heat treatment temperature on the XRD spectra and IR spectra of La(2)Zr(2)O(7) powders were studied. The X-ray diffraction pattern of La(2)Zr(2)O(7) powder after heat treatment at 600 â has one diffraction peak, and the diffraction peak is quite broad, therefore, the crystal structure of the La(2)Zr(2)O(7) powder is semi-crystal structure. With the increase of heat treatment temperature, diffraction peaks become gradually sharp and increase. The crystal structure of the La(2)Zr(2)O(7) powders after heat treatment in 750ï½800 â are pyrochlore structure. Analysis results of IR spectra of La(2)Zr(2)O(7) powders after heat treatment in 650ï½750 â show that the crystal structure of the La(2)Zr(2)O(7) powders after heat treatment at 750 â is pyrochlore structure, and the analysis results of XRD and IR are the same. Analysis results of TG-DTG of La(2)Zr(2)O(7) powders show that the crystal structure of the La(2)Zr(2)O(7) powders are stability in 120ï½1 600 â.
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OBJECTIVE: To construct a recombinant eukaryotic expression plasmid containing ROP18-ROP12 (encoding rhoptry protein 18 and 12) complex gene of Toxoplasma gondii, and examine its expression in eukaryotic cells. METHODS: Recombinant plasmids pVAX1-ROP18 and pVAX1-ROP12 were digested by restriction enzymes BamH I and Xba I . ROP12 gene was cloned into pVAX1-ROP18 to construct the eukaryotic expression plasmid pVAX1-ROP18- ROP12. After colony PCR, enzyme digestion and sequencing, the correct recombinant plasmid pVAX1-ROP18-ROP12 was transfected into HeLa cells. Along with it were groups of empty plasmid, pVAX1-ROP18 and pVAX1-ROP12. Total RNA was extracted from HeLa cells and reverse-transcribed to cDNA. RT-PCR was performed to evaluate mRNA expression of the housekeeping gene ß-actin and ROP18-ROP12 complex gene. Immunofluorescence assay and Western blotting were performed to determine the protein levels of ROP18-ROP12 fusion protein. RESULTS: Colony PCR in recombinant plasmid pVAX1-ROP18-ROP12 showed a specific band at about 2 373 bp, consistent with expectation. The extracted recombinant plasmids were confirmed by Hind III, BamH I and Xba I digestion. Sequencing results showed that the sequence of pVAX1-ROP18-ROP12 was 100% identical to that of T. gondii RH strain ROP18 gene (Accession No. AM075204.1) and 99% identical to that of T. gondii RH strain ROP12 gene (Accession No. DQ096559.1). Further, RT-PCR showed amplification products at 613 bp for ß-actin in all the groups, while only the pVAX1-ROP18-ROP12 transfection group showed amplification products for the ROP18-ROP12 complex at 2,373 bp. In addition, the indirect immunofluorescence assay showed yellow-green fluorescence in HeLa cells transfected with pVAX1-ROP18-ROP12, but not in control cells. Western blotting showed that the ROP18-ROP12 fusion protein was expressed in HeLa cells transfected with recombinant plasmid pVAX1-ROP18-ROP12. CONCLUSIONS: The recombinant eukaryotic plasmid pVAX1-ROP18-ROP-2 is constructed and can be expressed in eukaryotic system.
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Toxoplasma , Actinas , Western Blotting , Vectores Genéticos , Células HeLa , Humanos , Plásmidos , Reacción en Cadena de la Polimerasa , Proteínas Recombinantes , TransfecciónRESUMEN
BACKGROUND: Heterotopic pancreas (HP) refers to pancreatic tissue located in areas with no vascular or anatomical connection to the pancreas. HP occurs mostly in the stomach, duodenum, and colon, and rarely in the gallbladder. CASE SUMMARY: A 57-year-old woman was referred to our hospital complaining of right upper quadrant discomfort for 3 years. An abdominal computed tomography scan revealed adenomyomatosis with a thickened fundus of the gallbladder. The patient underwent a laparoscopic cholecystectomy, and pathological examination unexpectedly showed heterotopic pancreatic tissue in the gallbladder. The patient had a favorable recovery and was discharged on postoperative day 3. She did not report any symptoms or complications at the 6-mo postoperative follow-up. Pathologists should pay close attention to such pancreatic tissue and carefully examine it for dysplasia or malignancy. CONCLUSION: This case provides more information about HP in the gallbladder, a rare occurrence.
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BACKGROUND: The clinical incidence of spinal infection is gradually increasing, and its onset is insidious, easily leading to missed diagnosis and misdiagnosis, which may lead to serious complications such as nervous system dysfunction, spinal instability and/or deformity, and cause a huge burden on society and families. Early identification of the causative agent and precision medicine will greatly reduce the suffering of patients. At present, the main pathogenic bacteria that cause spinal infection are Staphylococcus aureus, Streptococcus, Pneumococcus, Escherichia coli, and Klebsiella. There are no reports of spinal infection caused by Pseudomonas fluorescens. CASE SUMMARY: We report a 32-year-old female patient with spinal infection. She presented with flank pain, initially thought to be bone metastases or bone tuberculosis, and had a family background of tumors. Her clinical features and changes in imaging and laboratory tests led to the suspicion of thoracic spine infection. Histopathology of the lesion showed inflammation, tissue culture of the lesion was negative several times, and the possible pathogen - Pseudomonas fluorescens was found after gene sequencing of the lesion. The patient recovered completely after a full course of antibiotic treatment. CONCLUSION: This report increases the range of pathogens involved in spinal infections, highlights the unique advantages of gene sequencing technology in difficult-to-diagnose diseases, and validates conservative treatment with a full course of antibiotics for spinal infections without complications.
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BACKGROUND: Venovenous extracorporeal membrane oxygenation (V-V ECMO) has become an important treatment for severe pneumonia, but there are various complications during the treatment. This article describes a case with severe pneumonia successfully treated by V-V ECMO, but during treatment, the retrovenous catheter, which was supposed to be in the right internal vein, entered the superior vena cava directly in the mediastinum. The ECMO was safely withdrawn after multidisciplinary consultation. Our experience with this case is expected to provide a reference for colleagues who will encounter similar situations. CASE SUMMARY: A 64-year-old man had severe pulmonary infection and respiratory failure. He was admitted to our hospital and was given ventilation support (fraction of inspired oxygen 100%). The respiratory failure was not improved and he was treated by V-V ECMO, during which the venous return catheter, which was supposed to be in the right internal vein, entered the superior vena cava directly in the mediastinum. There was a risk of massive mediastinal bleeding if the catheter was removed directly when the ECMO was withdrawn. Finally, the patient underwent vena cava angiography + balloon attachment + ECMO withdrawal in the operating room (prepared for conversion to thoracotomy for vascular exploration and repair at any time during surgery) after multidisciplinary consultation. ECMO was safely withdrawn, and the patient recovered and was discharged. CONCLUSION: Patients may have different vascular conditions. Multidisciplinary cooperation can ensure patient safety. Our experience will provide a reference for similar cases.
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Nasopharyngeal carcinoma (NPC) originates in the epithelial cells of the nasopharynx and is a common malignant tumor in southern China and Southeast Asia. Metastasis of NPC remains the main cause of death for NPC patients even though the tumor is sensitive to radiotherapy and chemotherapy. Here, we found that the transmembrane protein tetraspanin1 (TSPAN1) potently inhibited the in vitro migration and invasion, as well as, the in vivo metastasis of NPC cells via interacting with the IKBB protein. In addition, TSPAN1 was essential in preventing the overactivation of the NF-kB pathway in TSPAN1 overexpressing NPC cells. Furthermore, reduced TSPAN1 expression was associated with NPC metastasis and the poor prognosis of NPC patients. These results uncovered the suppressive role of TSPAN1 against NF-kB signaling in NPC cells for preventing NPC metastasis. Its therapeutic value warrants further investigation.
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Carcinoma , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/patología , FN-kappa B/genética , FN-kappa B/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Línea Celular Tumoral , Transducción de Señal , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica , Tetraspaninas/genética , Tetraspaninas/metabolismoRESUMEN
BACKGROUND: Metastasis is one of the main obstacles impeding the survival of nasopharyngeal carcinoma (NPC) patients, with the molecular mechanism underlying NPC metastasis still unclear. RESULTS: In this study, Cystatin A (CSTA) was found downregulated in NPC tissues with metastasis compared with those without metastasis. Shorter overall survival and distant metastasis-free survival were found in NPC patients with lower CSTA expression. Using functional assays, we found that CSTA prevented both the in vitro motility of NPC cells and their ability to metastasize in vivo. Transcriptome sequencing and western blot analysis revealed that CSTA inhibited the phosphorylation of AKT. Moreover, activating AKT using AKT agonist SG79 rescued the motility of CSTA-overexpressing NPC cells, whereas, treatment with AKT inhibitor MK2206 inhibited the motility of CSTA-knockdown NPC cells. Mechanically, immunoprecipitation coupled mass spectrometry found that CSTA interacted with the N6-adenosine-methyltransferase subunit METTL3 and promoted its ubiquitin-proteasome-mediated degradation following the upregulation of NKX3-1 and LHPP, which are negative regulators of AKT. Furthermore, knock-down of NKX3-1 and LHPP enhanced the motility of CSTA-overexpressing NPC cells. CONCLUSIONS: The inhibitory effect of CSTA upon NPC metastasis mainly depended on suppressing AKT signaling by the upregulation of NKX3-1 and LHPP expression resulting from the binding between CSTA and METLL3. Our study suggests that the CSTA-METLL3-NKX3-1/LHPP-AKT axis could be of therapeutic value for inhibiting NPC metastasis.
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Carcinoma , Neoplasias Nasofaríngeas , Humanos , Carcinoma/patología , Cistatina A , Transición Epitelial-Mesenquimal , Metiltransferasas , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patología , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
Nasopharyngeal carcinoma (NPC) originates in the nasopharyngeal epithelium and has the highest metastatic rate among head and neck cancers. Distant metastasis is the main reason for treatment failure with the underlying mechanisms remaining unclear. By comparing the expression profiling of NPCs versus non-cancerous nasopharyngeal tissues, we found LACTB was highly expressed in the tumor tissues. We found that elevated expression of the LACTB protein in primary NPCs correlated with poorer patient survival. LACTB is known to be a serine protease and a ubiquitous mitochondrial protein localized in the intermembrane space. Its role in tumor biology remains controversial. We found that the different methylation pattern of LACTB promoter led to its differential expression in NPC cells. Overexpressing LACTB in NPC cells promoted their motility in vitro and metastasis in vivo. While knocking down LACTB reduced the metastasis capability of NPC cells. However, LACTB did not influence cellular proliferation. We further found the role of LACTB in promoting NPC metastasis depended on the activation of ERBB3/EGFR-ERK signaling, which in turn, affected the stability and the following acetylation of histone H3. These findings may shed light on unveiling the mechanisms of NPC metastasis.
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Sistema de Señalización de MAP Quinasas/genética , Proteínas de la Membrana/genética , Proteínas Mitocondriales/genética , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Metástasis de la Neoplasia/genética , Receptor ErbB-3/genética , Transducción de Señal/genética , beta-Lactamasas/genética , Animales , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Receptores ErbB/genética , Femenino , Humanos , Ratones , Ratones Desnudos , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/patología , Metástasis de la Neoplasia/patología , Regiones Promotoras Genéticas/genéticaRESUMEN
Neuraminidase (NA) is an important target for current research on anti-influenza drugs. The acylhydrazone derivatives containing the -CONHN=CH- framework have been shown to have good NA inhibitory activity. In this paper, a series of novel acylhydrazone NA inhibitors (9a-9n) were designed and synthesized, and the inhibitory activities against NA were evaluated in vitro. The NA inhibition results showed that compound 9j has the most potent inhibitory activity (IC50 = 0.6 µM) against NA, which is significantly lower than that of the positive control oseltamivir carboxylic acid (OSC) (IC50 = 17.00 µM). Molecular docking analysis indicates that the acylhydrazone group plays an important role in compound 9j, which can bind well to the residues Arg371 and Arg292 in the S1 subsite of NA. The good potency of 9j may be also ascribed to the extending of morpholinyl ring into the 430-cavity. The results of this work may contribute to the development of more potent NA inhibitors to against mutant influenza viruses.
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Pituitary stalk interruption syndrome (PSIS) is a rare congenital defect manifesting as various degrees of anterior pituitary hormone deficiency. Scattered familial cases have been found, revealing some genetic variants. However, most of the previous research studies involved an affected sibling, and the gene spectra of the patients' entire family have rarely been reported. We conducted a study of a family consisting of a PSIS patient with his unaffected sibling and healthy parents of Han Chinese background using whole-genome sequencing. Bioinformatic analysis was carried out, and mutations related to PSIS, single-nucleotide variants (SNVs), insertion-deletion (InDELs), and structural variations (SVs) in all the four samples were filtered. After Sanger sequencing, we confirmed the variants obtained and selected three candidate genes for functional verification. The gene variations in this boy with PSIS and his lineal relatives are reported herein; de novo sequencing revealed that the NBPF9 gene may be involved in the pathogenesis of PSIS.
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OBJECTIVE: To explore the clinical therapeutic effect of light and heat of moxibustion for knee osteoarthritis (KOA). METHODS: A total of 216 patients with KOA were randomized into a traditional moxibustion group (72 cases, 8 cases dropped off), a moxibustion light group (72 cases, 9 cases dropped off) and a moxibustion heat group (72 cases, 10 cases dropped off).The special light-heat separation moxibustion cup was applied, the patients in the traditional moxibustion group received the treatment of moxibustion, the patients in the moxibustion light group received the treatment of moxibustion light and the patients in the moxibustion heat group received the treatment of moxibustion heat. The acupoint selection of the three groups was Neixiyan (EX-LE 4), Dubi (ST 35) and Zusanli (ST 36), the treatment was given 20 min each time, 3 times a week, 4 weeks were required totally, and the follow-up surveys were made 4 and 8 weeks after treatment. The scores of Western Ontario and McMaster University osteoarthritis index (WOMAC) and visual analogue scale (VAS) were observed before treatment, after 2 and 4 weeks of treatment, 4 and 8 weeks after treatment. The therapeutic effects were evaluated according to the criterion of patient global assessment (PGA) after 4 weeks of treatment and 8 weeks after treatment. RESULTS: Compared with before treatment, the pain scores, stiffness scores, physical function scores and total scores of WOMAC were reduced after 2, 4 weeks of treatment and 4 weeks after treatment in the three groups (P<0.05). The pain scores, stiffness scores, physical function scores and total scores of WOMAC were reduced 8 weeks after treatment in the traditional moxibustion group and the moxibustion heat group (P<0.05). The stiffness score, physical function score and total score of WOMAC were reduced 8 weeks after treatment in the moxibustion light group (P<0.05). The pain score, physical function score and total score of WOMAC in the traditional moxibustion group after 4 weeks of treatment were lower than the moxibustion light group (P<0.05). Compared with before treatment, the VAS scores were reduced after 2, 4 weeks of treatment and 4 , 8 weeks after treatment in the three groups (P<0.05). The improvement rates in the traditional moxibustion group and the moxibustion heat group after 4 weeks of treatment and 8 weeks after treatment were superior to the moxibustion light group (P<0.05). CONCLUSION: The light and heat of moxibustion have therapeutic effect for KOA, and the therapeutic effect of moxibustion heat is superior to moxibustion light.
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Calor , Luz , Moxibustión , Osteoartritis de la Rodilla/terapia , Puntos de Acupuntura , Humanos , Resultado del TratamientoRESUMEN
Nasopharyngeal carcinoma (NPC) is a unique head and neck cancer with highly aggressive and metastatic potential in which distant metastasis is the main reason for treatment failure. Till present, the underlying molecular mechanisms of NPC metastasis remains poorly understood. Here, we identified S100 calcium-binding protein A14 (S100A14) as a functional regulator suppressing NPC metastasis by inhibiting the NF-kB signaling pathway and reversing the epithelial-mesenchymal transition (EMT). S100A14 was found to be downregulated in highly metastatic NPC cells and tissues. Immunohistochemical staining of 202 NPC samples revealed that lower S100A14 expression was significantly correlated with shorter patient overall survival (OS) and distant metastasis-free survival (DMFS). S100A14 was also found as an independent prognostic factor for favorable survival. Gain- and loss-of-function studies confirmed that S100A14 suppressed the in vitro and in vivo motility of NPC cells. Mechanistically, S100A14 promoted the ubiquitin-proteasome-mediated degradation of interleukin-1 receptor-associated kinase 1 (IRAK1) to suppress NPC cellular migration. Moreover, S100A14 and IRAK1 established a feedback loop that could be disrupted by the IRAK1 inhibitor T2457. Overall, our findings showed that the S100A14-IRAK1 feedback loop could be a promising therapeutic target for NPC metastasis.
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Proteínas de Unión al Calcio/genética , Quinasas Asociadas a Receptores de Interleucina-1/genética , Neoplasias Pulmonares/genética , FN-kappa B/genética , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Animales , Proteínas de Unión al Calcio/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Transición Epitelial-Mesenquimal/genética , Retroalimentación Fisiológica , Regulación Neoplásica de la Expresión Génica , Xenoinjertos , Humanos , Quinasas Asociadas a Receptores de Interleucina-1/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Ratones Desnudos , FN-kappa B/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patología , Complejo de la Endopetidasa Proteasomal/metabolismo , Interferencia de ARN , Transducción de Señal/genética , Análisis de SupervivenciaRESUMEN
OBJECTIVE: Pituitary stalk interruption syndrome (PSIS) is a rare congenital disease which results in hypopituitarism. Patients with PSIS often exhibit short stature due to their deficiency of growth hormone (GH). CASE PRESENTATION: Here, we present two rare cases of adults males with PSIS, in which the patients were of normal height and did not take any GH supplements. Sterility and multiple hormone deficiencies including GH were seen in both of them. Through whole exome sequencing of their DNA, we found novel mutations they shared, three in MUC4 (c.7815G>T, c.3548C>T, c.3399C>G) and one in NBPF10 (c.536C>A). CONCLUSION: The present cases suggest that there are exceptions in GH deficient patients where a select few can attain normal heights without GH therapy. Genetic screening can be a predictor for prognoses of rare types of hypopituitarism.
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Estatura/fisiología , Trastornos del Crecimiento/metabolismo , Hipogonadismo/metabolismo , Hipopituitarismo/metabolismo , Hipófisis/anomalías , Adolescente , Adulto , Trastornos del Crecimiento/fisiopatología , Humanos , Hipogonadismo/tratamiento farmacológico , Hipogonadismo/fisiopatología , Hipopituitarismo/tratamiento farmacológico , Hipopituitarismo/fisiopatología , Hipotiroidismo/tratamiento farmacológico , Hipotiroidismo/metabolismo , Imagen por Resonancia Magnética , Masculino , Mucina 4/genética , Hipófisis/diagnóstico por imagenRESUMEN
OBJECTIVES: Our goal was to examine whether interleukin-1 beta (IL-1ß) originates locally and its possible relationship with matrix metalloproteinases (MMPs), apoptosis, elastin fibres and biomechanics in aortic dissecting aneurysms (DAs). METHODS: Aortic DAs were induced in 24 rats with ß-aminopropionitrile (BAPN); another 12 rats without BAPN were designated as controls. Then IL-1ß levels were measured both in the circulation and in local aortic specimens. The expression of MMP-2 and MMP-9 and Victoria blue and TUNEL staining were also detected. Biomechanical parameters such as the elasticity modulus were used to detect the biomechanical changes in the aortic wall. The correlation of IL-1ß, MMP-2, MMP-9, apoptosis and biomechanical properties was analysed. RESULTS: Seventeen rats (17/24, 71%) in the BAPN-treated group died of DA rupture. IL-1ß levels were dramatically increased in the DA specimens but not in the circulation. Victoria blue staining confirmed the formation of the DA and the reduction of elastin content after induction by BAPN. The extent of apoptosis in the aortic media was dramatically higher in rats with BAPN-induced DA than that in the control group and that in rats treated with BAPN but without DA. MMP-2 and MMP-9 levels were significantly increased in BAPN-treated rats compared to the controls, but no statistical significance was found between rats with and without DA. There were significant differences in biomechanical parameters, such as the elasticity modulus. Among the 3 groups, IL-1ß was positively correlated with MMP-2 and MMP-9 levels and with the elasticity modulus but not with apoptosis. CONCLUSIONS: Local IL-1ß might participate in the formation of aortic DA through the upregulation of MMP-2 and MMP-9 and the breakage of elastin fibres, which finally weakens the biomechanical properties of the aortic wall.
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Aorta Torácica/metabolismo , Aneurisma de la Aorta Torácica/metabolismo , Disección Aórtica/metabolismo , Interleucina-1beta/biosíntesis , Metaloproteinasa 2 de la Matriz/biosíntesis , Metaloproteinasa 9 de la Matriz/biosíntesis , Regulación hacia Arriba , Disección Aórtica/patología , Disección Aórtica/fisiopatología , Animales , Aorta Torácica/patología , Aorta Torácica/fisiopatología , Aneurisma de la Aorta Torácica/patología , Aneurisma de la Aorta Torácica/fisiopatología , Apoptosis , Fenómenos Biomecánicos , Western Blotting , Modelos Animales de Enfermedad , Inmunohistoquímica , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
The use of constructed wetlands in combination with microbial fuel cells (CW-MFC) to treat saline wastewater may enhance electricity production by increasing the ionic strength, reducing internal resistance and stimulating microbes to accelerate electron transfer. In this study, salinity did not significantly inhibit the removal of TP and COD, but TN and NH4+-N removal efficiencies during saline wastewater treatment (ST) were significantly lower than during non-saline wastewater treatment (NT). However, salinity significantly increased the power density (16.4â¯mWâ¯m-2 in ST and 3.9â¯mWâ¯m-2 in NT, a 4-fold enhancement) by increasing the electron transfer rate and reducing internal resistance (140.29â¯Ω in ST and 415.21â¯Ω in NT). The peptides in extracellular polymeric substances (EPS) acted as electron shuttles to promote the migration of electrons and protons in ST. From start-up to stable operation, though the microorganisms in ST were reduced in diversity relative to NT, the proportion of electrochemically active bacteria (EAB), such as Ochrobactrum, significantly increased (pâ¯<â¯0.05) and gradually predominated in the microbial community.