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This study aimed to reveal the specific role of early growth response protein 1 (EGR1) and nuclear receptor 4A3 (NR4A3) in nucleus pulposus cells (NPCs) and the related molecular mechanism and to identify a new strategy for treating intervertebral disc degeneration (IVDD). Bioinformatics analysis was used to explore and predict IVDD-related differentially expressed genes, and chromatin immunoprecipitation sequencing (ChIP-seq) revealed NR4A3 as the EGR1 target gene. An in vitro NPC model induced by tributyl hydrogen peroxide (TBHP) and a rat model induced by fibrous ring acupuncture were established. Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemical staining, immunofluorescence staining, and flow cytometry were used to detect the effects of EGR1 and NR4A3 knockdown and overexpression on NPC apoptosis and the expression of extracellular matrix (ECM) anabolism-related proteins. Interactions between EGR1 and NR4A3 were analyzed via ChIP-qPCR and dual luciferase assays. EGR1 and NR4A3 expression levels were significantly higher in severely degenerated discs (SDD) than in mildly degenerated discs (MDD), indicating that these genes are important risk factors in IVDD progression. ChIP-seq and RNA-seq revealed NR4A3 as a direct downstream target of EGR1, and this finding was verified by ChIP-qPCR and dual luciferase reporter experiments. Remarkably, the rescue experiments showed that EGR1 promotes TBHP-induced NPC apoptosis and impairs ECM anabolism, dependent on elevated NR4A3 expression. In summary, the EGR1-NR4A3 axis mediates the progression of NPC apoptosis and ECM impairment and is a potential therapeutic target in IVDD.

Asunto(s)

Apoptosis , Proteína 1 de la Respuesta de Crecimiento Precoz , Degeneración del Disco Intervertebral , Núcleo Pulposo , Estrés Oxidativo , Receptores de Hormona Tiroidea , Adulto , Animales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ratas , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Proteína 1 de la Respuesta de Crecimiento Precoz/metabolismo , Proteína 1 de la Respuesta de Crecimiento Precoz/genética , Degeneración del Disco Intervertebral/metabolismo , Degeneración del Disco Intervertebral/genética , Degeneración del Disco Intervertebral/patología , Proteínas del Tejido Nervioso , Núcleo Pulposo/metabolismo , Núcleo Pulposo/patología , Ratas Sprague-Dawley , Receptores de Esteroides/metabolismo , Receptores de Esteroides/genética , Receptores de Hormona Tiroidea/metabolismo , Receptores de Hormona Tiroidea/genética , Regulación hacia Arriba

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Flavonoids, which contain a benzo-γ-pyrone (C6-C3-C6) skeleton, have been reported to exhibit effective antioxidant ability. This study aimed to compare the antioxidant activities of 7,8-dihydroxyflavone (7,8-DHF) and 7-hydroxyflavone (7-HF) in H2 O2 , lipopolysaccharide (LPS), or tert-butyl hydroperoxide (t-BHP)-induced RAW264.7 cells, respectively. The antioxidant capacities of 7,8-DHF and 7-HF were firstly evaluated by 2,2-azinobis-3-ethyl-benzothiazoline-6-sulphonic acid (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. Then, reactive oxygen species (ROS), super oxide dismutase (SOD), and malondialdehyde (MDA) productions in H2 O2 , LPS, or t-BHP-induced RAW264.7 cells were tested and compared, respectively. Finally, the antioxidant mechanisms of 7-HF and 7,8-DHF were initially investigated by western blot. Our results showed that 7,8-DHF possessed stronger free-radical scavenging capacity than 7-HF. Both 7,8-DHF and 7-HF suppressed MDA production and ROS accumulation, improved the activity of SOD in H2 O2 , LPS, or t-BHP-induced RAW264.7 cells, respectively. And 7,8-DHF exerted a better antioxidant effect than 7-HF, especially in t-BHP-induced oxidative stress. Mechanically, 7,8-DHF prevented the activation of poly ADP-ribosepolymerase and caspase-3, meanwhile markedly upregulated the expression of HO-1 protein in t-BHP-induced oxidative stress. These results suggested that 7,8-DHF might serve as a potential pharmaceutical drug against oxidative stress injury.

Asunto(s)

Antioxidantes , Flavonas , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Antioxidantes/farmacología , Antioxidantes/metabolismo , Caspasa 3/metabolismo , Lipopolisacáridos/toxicidad , Estrés Oxidativo , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismo , Animales , Ratones

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Sesquiterpenes are natural terpenoids with 15 carbon atoms in the basic skeleton, which mainly exist in plant volatile oil and have important physiological and medicinal value. Cytochrome P450 (CYP450) is a kind of monooxygenase encoded by supergene family, which is one of the largest gene families in plants. It is involved in the synthesis and metabolism of terpenoids, alkaloids and other secondary metabolites. In the process of terpene biosynthesis, CYP450 participates in the post-modification stage of terpenes by introducing functional groups such as hydroxyl, carboxyl and carbonyl, which plays an important role in enriching the diversity of terpenes. The CYP450 enzymes involved in sesquiterpene synthesis and their substrate catalytic specificity mechanisms have been partially investigated. In this paper, the biosynthetic pathway of plant sesquiterpenes, the structure and classification of CYP450 enzymes were briefly introduced, and the CYP450 enzymes involved in sesquiterpene biosynthesis were summarized, in order to provide a reference for intensive study of the role of CYP450 enzymes in the synthesis of sesquiterpenoids.

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Five psoralen derivatives were synthesized and the structures of them were characterized by 1 H-NMR, 13 C-NMR, and IR. The antioxidant properties of the compounds were tested by inhibiting the free radical-initiated DNA oxidation and scavenging the radical reaction. The results showed that the effective stoichiometric factors (n) of the compounds V and IV could reach 2.00 and 2.11 in the system of inhibiting the DNA oxidation reaction initiated by 2,2'-Azobis(2-methylpropionamidine) dihydrochloride (AAPH). In the inhibition of ⋅OH-oxidation of the DNA system, compounds I~V showed antioxidant properties. The thiobarbituric acid absorbance (TBARS) percentages of compounds IV and V were 76.19 % and 78.84 %. Compounds I~V could also inhibit Cu2+ /GSH-oxidation of DNA, and all compounds exhibited good antioxidant properties except compound II (94.00 %). All the five compounds were able to trap diammonium 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) salt radical (ABTS+ ⋅), 2,2-diphenyl-1-picrylhydrazyl radical (DPPH⋅) and 2,6-di-tert-butyl-alpha-(3,5-di-tert-butyl-4-oxo-2,5-cyclohexadien-p-tolylox radical (galvinoxyl⋅). The ability of compounds I~V to scavenge those free radicals can be measured by the k values. The k values ranged from 0.07 to 0.82 in scavenging ABTS+ ⋅, galvinoxyl, and DPPH radicals, respectively.

RESUMEN

A series of thioether pleuromutilin derivatives containing 1,2,4-triazole on the side chain of C14 were designed and synthesized. The in vitro antibacterial activities experiments of the synthesized derivatives showed that compounds 72 and 73 displayed superior in vitro antibacterial effect against MRSA minimal inhibitory concentration (MIC = 0.0625 µg/mL) than tiamulin (MIC = 0.5 µg/mL). The results of time-kill study and postantibiotic effect study indicated that compound 72 could inhibit the growth of MRSA quickly (-2.16 log10 CFU/mL) and showed certain postantibiotic effect (PAE) time (exposure to 2 × MIC and 4 × MIC for 2 h, the PAE was 1.30 and 1.35 h) against MRSA. Furthermore, the binding mode between compound 72 and 50S ribosome of MRSA was explored by molecular docking and five hydrogen bonds were formed between compound 72 and 50S ribosome.

Asunto(s)

Antibacterianos , Compuestos Policíclicos , Simulación del Acoplamiento Molecular , Antibacterianos/química , Compuestos Policíclicos/farmacología , Compuestos Policíclicos/química , Pruebas de Sensibilidad Microbiana , Relación Estructura-Actividad , Pleuromutilinas

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Laser corneal refractive surgery is an effective way for the correction of myopia, and its long-term stability is a common concern of surgeons and patients. However, refractive regression is still one of the most common postoperative long-term complications, which has a great impact on postoperative refractive state and visual quality. Refractive regression may be related to many factors, such as the remodeling of corneal epithelium and stroma, and the imbalance between corneal biomechanics and intraocular pressure. Although enhancement surgery could be a useful way to correct refractive regression, there is a risk of corneal ectasia and other complications. Some intraocular pressure lowering medications can be used to rebuild the balance of intraocular pressure and corneal biomechanics, and to prevent postoperative refractive regression by affecting the thickness of corneal epithelium. To a certain extent, the type, the timing and the way of intraocular pressure lowering medications application may have an impact on the prevention and treatment effect of refractive regression.

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Traditional Chinese Medicine (TCM) shows unique advantages in the field of adjuvant treatment of gastric cancer. The main mechanism of TCM in improving gastric cancer includes regulating cell proliferation and apoptosis, reversing cell resistance, reducing the ability of invasion and metastasis and epithelial-mesenchymal transformation, regulating immune function, inhibiting neovascularization, regulating autophagy exosome, and ferroptosis.

RESUMEN

Cytochrome P450 (CYP450) is a kind of superfamily oxidase containing heme, which is distributed in various aerobic organisms. They are widely involved in the biosynthesis of terpenoids, alkaloids, flavonoids, fatty acids, etc. In this study, the full-length cDNA sequence of a P450 was cloned by reverse transcription-PCR (RT-PCR) and rapid amplification of cDNA ends (RACE) technology, with the specific primers that designed according to the sequence of a transcript annotated as P450 from the Aquilaria sinensis (Lour.) Gilg transcriptome database. The tissue expression and subcellular localization were also studied. The full-length cDNA of the cloned P450 gene is 1 920 bp, with 88 bp 5′-untranslated region (UTR), 344 bp 3′-UTR and a 21 bp polyA tail, and 1 488 bp open reading frame (ORF), encoding 495 amino acids. Sequence alignment revealed that the protein belonged to CYP71D family of cytochrome P450 family, and named AsCYP71D1. Tissue expression analysis indicated that AsCYP71D1 was mainly expressed in stem. Further subcellular localization of onion epidermis showed that AsCYP71D1 was expressed in cytoplasm, nucleus and cell membrane. This study will provide a foundation for further research on its function in agarwood sesquiterpene biosynthesis.

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Objective: To analyze the correlation between loss of smell/taste and the number of real confirmed cases of coronavirus disease 2019 (COVID-19) worldwide based on Google Trends data, and to explore the guiding role of smell/taste loss for the COVID-19 prevention and control. Methods: "Loss of smell" and "loss of taste" related keywords were searched in the Google Trends platform, the data were obtained from Jan. 1 2019 to Jul. 11 2021. The daily and newly confirmed COVID-19 case number were collected from World Health Organization (WHO) since Dec. 30 2019. All data were statistically analyzed by SPSS 23.0 software. The correlation was finally tested by Spearman correlation analysis. Results: A total of data from 80 weeks were collected. The retrospective analysis was performed on the new trend of COVID-19 confirmed cases in a total of 186 292 441 cases worldwide. Since the epidemic of COVID-19 was recorded on the WHO website, the relative searches related to loss of smell/taste in the Google Trends platform had been increasing globally. The global relative search volumes of "loss of smell" and "loss of taste" on Google Trends was 10.23±2.58 and 16.33±2.47 before the record of epidemic while 80.25±39.81 and 80.45±40.04 after (t value was 8.67, 14.43, respectively, both P<0.001). In the United States and India, the relative searches for "loss of smell" and "loss of taste" after the record of epidemic were also much higher than before (all P<0.001). The correlation coefficients between the trend of weekly new COVID-19 cases and the Google Trends of "loss of smell" in the global, United States, and India was 0.53, 0.76, and 0.82 respectively (all P<0.001), the correlation coefficients with Google Trends of "loss of taste" was 0.54, 0.78, and 0.82 respectively (all P<0.001). The lowest and highest point of loss of smell/taste search curves of Google Trends in different periods appeared 7 to 14 days earlier than that of the weekly newly COVID-19 confirmed cases curves, respectively. Conclusions: There is a significant positive correlation between the number of newly confirmed cases of COVID-19 worldwide and the amount of keywords, such as "loss of smell" and "loss of taste", retrieved in Google Trends. The trend of big data based on Google Trends might predict the outbreak trend of COVID-19 in advance.

Asunto(s)

Humanos , Ageusia , Macrodatos , COVID-19 , Brotes de Enfermedades , Internet , Estudios Retrospectivos , Olfato , Estados Unidos

RESUMEN

The rapid development of Internet in recent years has led to a proliferation of social media networks as people who can gather online to share information, knowledge, and opinions. However, the network public opinion tends to generate strongly misleading and a large number of messages can cause shocks to the public once major emergencies appear. Therefore, we need to make correct prediction regarding and timely identify a potential crisis in the early warning of network public opinion. In view of this, this study fully considers the features of development and the propagation characteristics, so as to construct a network public opinion early warning index system that includes 4 first-level indicators and 13 second-level indicators. The weight of each indicator is calculated by the "CRITIC" method, so that the comprehensive evaluation value of each time point can be obtained and the early warning level of internet public opinion can be divided. Then, the Back Propagation neural network based on Genetic Algorithm (GA-BP) is used to establish a network public opinion early warning model. Finally, the major public health emergency, COVID-19 pandemic, is taken as a case for empirical analysis. The results show that by comparing with the traditional classification methods, such as BP neural network, decision tree, random forest, support vector machine and naive Bayes, GA-BP neural network has a higher accuracy rate for early warning of network public opinion. Consequently, the index system and early warning model constructed in this study have good feasibility and can provide references for related research on internet public opinion.

RESUMEN

Novel series of pleuromutilin analogs containing substituted 1,2,3-triazole moieties were designed, synthesised and assessed for their in vitro antibacterial activity against Methicillin-resistant Staphylococcus aureus (MRSA). Initially, the in vitro antibacterial activities of these derivatives against 4 strains of S. aureus (MRSA ATCC 43300, ATCC 29213, AD3, and 144) were tested by the broth dilution method. Most of the synthesised pleuromutilin analogs displayed potent activities. Among them, compounds 50, 62, and 64 (MIC = 0.5∼1 µg/mL) showed the most effective antibacterial activity and their anti-MRSA activity were further studied by the time-killing kinetics approach. Binding mode investigations by surface plasmon resonance (SPR) with 50S ribosome revealed that the selected compounds all showed obvious affinity for 50S ribosome (KD = 2.32 × 10-8∼5.10 × 10-5 M). Subsequently, the binding of compounds 50 and 64 to the 50S ribosome was further investigated by molecular modelling. Compound 50 had a superior docking mode with 50S ribosome, and the binding free energy of compound 50 was calculated to be -12.0 kcal/mol.

Asunto(s)

Antibacterianos/farmacología , Diterpenos/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Simulación del Acoplamiento Molecular , Compuestos Policíclicos/farmacología , Resonancia por Plasmón de Superficie , Antibacterianos/síntesis química , Antibacterianos/química , Química Clic , Diterpenos/síntesis química , Diterpenos/química , Relación Dosis-Respuesta a Droga , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Compuestos Policíclicos/síntesis química , Compuestos Policíclicos/química , Pleuromutilinas

RESUMEN

OBJECTIVE: To improve the treatment effect of patients with L5 S1 lumber disc herniation (LDH) with a narrow interlaminar window, we proposed an alternative approach to percutaneous endoscopic interlaminar discectomy (PEID) via the laminoplasty technique. METHODS: Fifteen L5 S1 LDH patients (7 men and 8 women; age range, 22 to 56 years; median age, 34 years; 9 left, 6 right) were enrolled in the present study retrospectively. The interlaminar windows of all patients were narrow (the transverse diameter of the L5 S1 interlaminar window is equal to or less than that of L4-5 ). Percutaneous laminoplasty and endoscopic interlaminar discectomy surgery were undergone by all patients from July 2018 to July 2019. All operations were completed under local anesthesia. The target laminoplasty area was the safety zone, use of which avoids both transverse and exit nerve roots. Under fluoroscopic guidance or clear endoscopic visualization, the trephines were used to enlarge the interlaminar window, which allowed the working cannula to enter the spinal canal but avoid nerve roots and the dural sac. The preoperative/postoperative visual analogue scale (VAS) scores and Oswestry disability index (ODI) were statistically analyzed. The modified MacNab criterion was used to assess the clinical effects. The radiological outcomes were evaluated by MRI and CT. SPSS 19.0 software was used for the statistical evaluation. RESULTS: The operative time ranged from 70 to 120 min, with a median time of 92 min, and the fluoroscopy times ranged from 8 to 12, with a median of 9.7 times. The body mass index (BMI) of patients ranged from 18.10 to 26.06, with a median of 22.04. All patients were followed up in the outpatient department for at least 12 months after surgery. At the last follow up, the average VAS-Back score of the study patients was reduced from 5.33 ± 2.09 to 2.00 ± 1.20 (P < 0.001) and the average VAS-Leg score was reduced from 7.53 ± 1.69 to 1.47 ± 0.92 (P < 0.001). The average ODI scores improved from 47.87 ± 11.41 to 12.93 ± 3.24 (P < 0.01). According to the modified MacNab criteria, 11 cases achieved excellent results and 4 cases achieved good results. All of the operations were successful. There wertr no nerve root injuries, dural tears, or other complications. CONCLUSION: The laminoplasty approach for PEID provides a safe and useful alternative for the treatment of L5-S1 LDH patients with a narrow interlaminar window.

Asunto(s)

Discectomía Percutánea/métodos , Endoscopía/métodos , Degeneración del Disco Intervertebral/cirugía , Desplazamiento del Disco Intervertebral/cirugía , Laminoplastia/métodos , Vértebras Lumbares/cirugía , Adulto , Evaluación de la Discapacidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Estudios Retrospectivos , Adulto Joven

RESUMEN

BACKGROUNDS: Transforaminal percutaneous endoscopic discectomy (TF-PELD) and interlaminar percutaneous endoscopic discectomy (IL-PELD) are the most common alternative treatments of lumbar disc herniation. The aim of this study was to compare the operation time duration and X-ray exposure as well as outcomes of TF-PELD and IL-PELD as indicated by the published clinical evidences within randomized trials. METHODS: We included randomized, controlled studies reporting operation duration and X-ray exposure as well as clinical outcome evaluations, comparing TF-PELD to IL-PELD with a minimum of 10 patients per group. The included data measures were operation duration, X-ray exposure and postoperation evaluations. Data were synthesized and analyzed using ReviewManager version 5.3. Publication bias was evaluated via funnel plot. The Cochran Q test and the degree of inconsistency (I2) were used to assess heterogeneity. Lowly biased and heterogenous dichotomous data were calculated by odds ratio and continuous data were calculated by mean difference (MD) with 95% confidence intervals (CI). RESULTS: Thirteen studies published from January 1970 to March 2018, with a total of 770 lumbar disc herniation patients, including 361 cases of TF-PELD and 409 cases of IL-PELD, were finally included. Meta-analysis of data extracted from these studies revealed that the postoperation outcomes of both surgery methods did not differ significantly, but the surgery duration was significantly shorter in the IL-PELD group than in the TF-PELD group (MD 21.69; 95% CI 12.94-30.27; P = .00001), and the fluoroscopy times demanded in the IL-PELD group was significantly fewer than those in the TF-PELD group (MD 7.57; 95% CI 6.22-8.93; P = .00001). CONCLUSION: The main finding of the study is that IL-PELD approach can decrease radiation exposure as their demanded duration of operation and fluoroscopy times were significantly shorter and fewer in the IL-PELD group, which they achieve similar outcomes comparing to TF-PELD. The study is limited at a lack of samples with lumbar disc herniation levels out of L5/S1. The findings implicate selection of IL-PELD approach over TF-PELD at applicable circumstances for lower lumbar disc herniation. Physicians should consider this data when choosing between TF-PELD and IL-PELD.

Asunto(s)

Discectomía Percutánea/métodos , Desplazamiento del Disco Intervertebral/cirugía , Vértebras Lumbares/cirugía , Fluoroscopía/estadística & datos numéricos , Humanos , Tempo Operativo , Complicaciones Posoperatorias/epidemiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos

RESUMEN

Objective:Through the analysis of the risk factors of clinical scientific research project, risk assessment theory was brought in to develop risk assessment procedures, at the same time, to explore possible applications of risk assessment theories and methodologies in clinical scientific research projects, which might empower the research project administration.Methods:Through literature review and the author's scientific research management daily practice, the characteristics of risks involved in clinical scientific research projects were systematically summarized, relevant standards and models were used for reference to develop relevant working procedures, fatherly, methodologies of project risk assessment were discussed.Results:There are risks at different stages of scientific research project that including compliance, safety, research topic selection, research design, executive ability and risk-control. A proposal regarding to the implementation of project risk assessment covers three main steps which including preliminary preparation, implementation of risk assessment (risk identification, risk analysis and risk assessment) and risk-response proposal.Conclusions:The risk assessment of clinical scientific research projects is crucial. It is necessary to promote the development of risk assessment and improve the capacity building by improving awareness, establishing system, clarifying structure and improving technology.

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Objective:To explore the collaborative development of drug clinical trial institutions and Contract Research Organizations from the perspective of " government-application-industry-academia-research" , and facilitate faster and better conducting of clinical trials.Methods:Based the combination of literature review and the working practice in drug clinical trial management, problems existed during the implementation of clinical trials were summarized, and then the collaborative development of drug clinical trial institutions and Contract Research Organizations were discussed from the perspective of " government-application-industry-academia-research" partnership.Results:Problems identified during the implementation of clinical trials including uneven capacity of CROs, lack of effective supervision department and insufficient cooperation with clinical trial institutions, which resulted difficulties in sharing clinical trial resources and also negatively impacted the quality of clinical trials. Some proposals were offered in this article, including making good use of the " visible hand" of the government to strengthen the supervision of CROs, accelerating the construction of innovation alliance between clinical trial institutions and CROs, establishing the incentive mechanism of collaborative development and the talent team construction, strengthening the personnel professional training.Conclusions:The application of " government-application-industry-academia-research" model in clinical trials would promote the collaboration between drug clinical trial institutions and Contract Research Organizations, which play important roles in the development of clinical trials.

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Objective:By sorting out the occurrence of the risk outcomes of scientific research project in the hospital, conducting root-cause analysis, the risk management theory, process and methodologies are introduced into the management system of hospital scientific research projects to reduce the occurrence of risk outcome of scientific research projects.Methods:Through literature review and the reflection of daily scientific research management practice, the risk characteristics of clinical scientific research projects were systematically summarized, comparative analysis were conducted to explore the effectiveness before and after the introduction of risk management, and the practical experiences of scientific research project risk management were summarized.Results:There are mainly six types of internal and external risks in hospital scientific research projects, which lead to project termination, project modifications, project delays, assessment index adjustments, budget adjustments and other risk issues. By establishing scientific research project risk management environment, standardizing risk management procedures, as well as establishing risk-monitoring and early warning information system, the introduction of risk management system enables more effective control of scientific research project risks in hospitals.Conclusions:The application of risk management in the management of scientific research projects in hospitals has showed positive impact. The risk management of scientific research projects in hospitals has certain practical value and feasibility. The exploration of risk management theories and methods should be continued to promote the high-quality development of hospital scientific research project management.

RESUMEN

Clear cell renal cell carcinoma (ccRCC) remains one of the most common cancer types globally, and while it has been extensively studied, the molecular basis for its pathology remains incompletely understood. Herein, we profiled three previously published datasets (GSE66272, GSE100666, and GSE105261) in a single integrated analysis aimed at identifying disease-associated patterns of gene expression that may offer mechanistic insight into the drivers of this disease. We pooled expression data from 39 normal kidney samples and 39 kidney tumors, leading us to identify 310 differentially expressed genes (DEGs) that were linked to kidney cancer in all three analyzed datasets. Of these genes, 133 and 177 were up- and down-regulated, respectively, in cancer samples. We then incorporated these DEGs into a protein-protein interaction network with the STRING and Cytoscape tools, and we were able to identify signaling pathways significantly enriched for these DEGs. The relationship between DEG expression and ccRCC patient survival was further evaluated using a Kaplan-Meier approach, leading us to identify TIMP1 as an independent prognostic factor in ccRCC patients. When TIMP1 expression was disrupted in ccRCC cell lines, this impaired their migratory and invasive capabilities. In summary, we employed an integrative bioinformatics approach to identify ccRCC-related DEGs and associated signaling pathways. Together these findings offer novel insight into the mechanistic basis for ccRCC, potentially helping to identify novel therapeutic targets for the treatment of this deadly disease.

Asunto(s)

Carcinoma de Células Renales , Neoplasias Renales , Transcriptoma/genética , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/genética , Células HEK293 , Humanos , Riñón/patología , Neoplasias Renales/genética , Neoplasias Renales/metabolismo , Neoplasias Renales/mortalidad , Neoplasias Renales/patología

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This paper was originally published in Aging Advance Online Publications on February 2, 2020. In compliance with Aging's withdrawal policy, the paper was withdrawn in its entirety. It will not appear in Aging internal or any external indexes or archives.

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Proinflammatory cytokine such as interleukin (IL)-1ß causes inflammation of articular cartilage. In this current study, we explored the chondroprotective effects of long noncoding RNA (lncRNA) MALAT-1 on cell proliferation, apoptosis, and matrix metabolism in IL-1ß-induced inflammation in articular chondrocytes. Articular chondrocytes from knee joints of normal rats were isolated and cultured, followed by identification through observation of toluidine blue and COL II immunocytochemical stainings. The proliferation of chondrocytes at passage 2 was detected by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The inflammatory chondrocytes induced by 10 ng/mL IL-1ß were observed and identified by toluidine blue and COL II immunocytochemical stainings. pcDNA 3.1 and pcDNA-MALAT-1 were transfected in the chondrocytes. Ultrastructure of chondrocytes was observed by using a transmission electron microscope. The MTT assay was carried out to evaluate chondrocyte viability. Hoechst 33258 staining and flow cytometry were adopted to assess chondrocyte apoptosis. The chondrocytes at passage 2 with the biological characteristics of chondrocytes were used for subsequent experiments. In IL-1ß-treated chondrocytes, the growth rate of chondrocytes slowed down, the cells became narrow and long, the vacuoles were seen in the cells, and the morphology of the chondrocytes was irregular. The toluidine blue staining and the immunohistochemical staining of COL II became weaker. In response to IL-1ß induction, articular chondrocytes showed reduced MALAT-1 expression; moreover, obvious cartilage injury was observed with decreased chondrocyte viability and Col II expression and elevated chondrocyte apoptosis, MMP-13 expression, and p-JNK expression. With the treatment of pcDNA-MALAT-1, the cartilage injury was alleviated with increased chondrocyte viability and type II collagen (Col II) expression and reduced chondrocyte apoptosis, MMP-13 expression and p-JNK expression. Taken together these results, lncRNA MALAT-1 blocked the activation of the JNK signaling pathway; thereby, IL-1ß-induced inflammation in articular chondrocytes was reduced with enhanced chondrocyte proliferation and suppressed chondrocyte apoptosis and extracellular matrix degradation.

Asunto(s)

Condrocitos/efectos de los fármacos , Interleucina-1beta/farmacología , MAP Quinasa Quinasa 4/genética , Sistema de Señalización de MAP Quinasas/genética , ARN Largo no Codificante/genética , Animales , Animales Recién Nacidos , Apoptosis/efectos de los fármacos , Apoptosis/genética , Cartílago Articular/citología , Cartílago Articular/metabolismo , Proliferación Celular/efectos de los fármacos , Condrocitos/metabolismo , Condrocitos/patología , Colágeno Tipo II/genética , Colágeno Tipo II/metabolismo , Regulación de la Expresión Génica , Inflamación , MAP Quinasa Quinasa 4/metabolismo , Metaloproteinasa 13 de la Matriz/genética , Metaloproteinasa 13 de la Matriz/metabolismo , Modelos Biológicos , Plásmidos/química , Plásmidos/metabolismo , Cultivo Primario de Células , ARN Largo no Codificante/agonistas , ARN Largo no Codificante/metabolismo , Ratas , Transfección

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RATIONALE: Follicular occlusion triad (FOT) is an autosomal recessive inherited disease and no more than 3 variants of the triad have been reported. We give a report in which scrotal elephantiasis is a variant of FOT and further perform a literature review. PATIENT CONCERNS: A 41-year-old man came to us because of a large scrotal cyst and generalized skin lesions that had occurred over the past 10 years. The generalized skin lesions consisted of hidradenitis suppurativa on the perineum and back, acne conglobata in the armpit, and dissecting cellulitis of the scalp. He took antibiotics for a long time but achieved poor effect. Furthermore, he told his father and elder brother also manifested such skin lesions. DIAGNOSES: Magnetic resonance showed a mass in the left scrotum with clear boundaries. A routine blood test showed a high leukocyte level of 12 × 10/L and a hemoglobin content of 78 g/L. C-reactive-protein increased. Series of autoimmune antibody tests were negative. The postoperative pathologic findings showed that the mass was an epidermoid cyst, and hematoxylin and eosin staining showed hyperkeratosis of the skin as well as inflammatory and edematous changes. A diagnosis of a variant of FOT was made. INTERVENTIONS: We removed skin abscesses and lesioned the inner part with hydrogen peroxide. Then we performed an excision of the scrotal lesion. OUTCOME: The patient recovered well and had no evidence of recurrence at a 16-month follow-up. LESSONS: We reported a case in which scrotal elephantiasis was a variant of FOT and surgical intervention played an important role in secondary urologic diseases.

Asunto(s)

Acne Conglobata/complicaciones , Celulitis (Flemón)/complicaciones , Elefantiasis/etiología , Hidradenitis Supurativa/complicaciones , Dermatosis del Cuero Cabelludo/complicaciones , Escroto , Enfermedades Cutáneas Genéticas/complicaciones , Acne Conglobata/genética , Adulto , Celulitis (Flemón)/genética , Elefantiasis/genética , Elefantiasis/patología , Elefantiasis/cirugía , Hidradenitis Supurativa/genética , Humanos , Imagen por Resonancia Magnética , Masculino , Dermatosis del Cuero Cabelludo/genética , Escroto/diagnóstico por imagen , Escroto/patología , Escroto/cirugía , Enfermedades Cutáneas Genéticas/genética