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BACKGROUND: Ubiquitin-specific protease 11 (USP11), one of the principal phosphatase and tensin homolog (PTEN) deubiquitinases, can reserve PTEN polyubiquitination to maintain PTEN protein integrity and inhibit PI3K/AKT pathway activation. The aim of the current study was to investigate the associations between immunohistochemical USP11 staining intensities and prognostic indicators in individuals with prostate cancer. METHODS: Tissue microarrays (TMAs) were performed for human prostate cancer and normal tissue (control) samples. Data on patient's age, Gleason score, plasma prostate-specific antigen (PSA) titer, disease stage, and presence of seminal vesicles, lymph nodes, and surgical margin involvement were collected. A pathologist who was blinded to the clinical outcome data scored the TMA for USP11 staining intensity as either positive or negative. RESULTS: Cancerous tissues exhibited lower USP11 staining intensity, whereas the neighboring benign peri-tumoral tissues showed higher USP11 staining intensity. The degree of USP11 staining intensity was lower in patients with a higher PSA titer, higher Gleason score, or more advanced disease stage. Patients who showed positive USP11 staining were more likely to have more optimal clinical and biochemical recurrence-free survival statistics. CONCLUSIONS: USP11 staining intensity in patients with prostate cancer is negatively associated with several prognostic factors such as an elevated PSA titer and a high Gleason score. It also reflects both biochemical and clinical recurrence-free survival in such patients. Thus, USP11 staining is a valuable prognostic factor in patients with prostate cancer.
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BACKGROUND: Adenovirus expresses two non-coding virus-associated (VA) RNAs: VA I RNA and VA II RNA. Adenovirus-expressed VA RNAs interfere with the microRNA (miRNA) pathway by competing with precursor miRNAs. The processing pattern of primary miRNA (pri-miRNA) and factors to affect its processing are not exactly known when using adenovirus for the delivery of pri-miRNA. METHODS: To observe pri-miRNA processing, plasmid construct encoding pri-miRNA was co-transfected with VA I/II RNA expression plasmid, or recombinant adenovirus encoding pri-miRNA was generated and infected. Levels of miRNAs, VA I RNA and VA II RNA were analyzed by a quantitative real-time PCR (RT-PCR). VA I-II full-length RNA was analyzed by a RT-PCR. RNA immunoprecipitation analysis to pull-down the VA I-II full-length RNA binding with Drosha was conducted with Drosha antibody. RESULTS: pri-miRNA was normally processed into mature miRNA when it was expressed in cells using plasmid. However, miRNA maturation was impaired when pri-miRNA was delivered and expressed using adenovirus. Of note, pri-miRNA processing was observed to be blocked by VA RNA expression. Such blocked processing could be recovered by introducing antisense RNA of VA RNA, anti-3'VA RNA. In addition, VA RNAs were transcribed into VA I-II full-length RNA, which was found to bind and sequester Drosha. CONCLUSIONS: Adenovirus infection downregulated the processing of pri-miRNAs in cells, and such downregulation could be derived from VA I-II full-length RNAs in pri-miRNA-like form through competitively binding to Drosha protein. These results indicated that the expression of adenovirus VA RNAs should be inhibited for successful delivery and expression of pri-miRNA or shRNA in cells using adenovirus.
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MicroRNAs , Processamento Pós-Transcricional do RNA , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Viral/genética , RNA Viral/metabolismo , Adenoviridae/genéticaRESUMO
Long-term nationwide atmospheric monitoring of organochlorine pesticides (OCPs) was performed in South Korea during 2008-2017. Their occurrences, seasonal and temporal variability, sources, and effect of ambient temperature were investigated. The OCPs are pronounced with a mean concentration of total OCPs ranging from 5.2 to 256 pg/Sm3. However, a decrease of 54 % was observed in the mean concentration of total OCPs from 2008 to 2017 associated with regulatory actions. OCP concentrations did not show any variations between the different site types, and OCPs were ubiquitously present at all site types. The mean concentration of total OCPs in summer was two-fold higher than in winter. The concentrations of DRINs, DDTs, ENDOs, and HCHs were significantly higher in summer, but the concentrations of chlordane and heptachlor were higher in winter. The diagnostic ratios identified major sources as ongoing sources, past use, and atmospheric transport. Clausius Clapeyron plots strongly suggested the re-emission of α-endosulfan, ß-endosulfan, α-HCH, and ß-HCH, and ΔHsa (enthalpy of surface air exchange) values suggested the influence of the transport and/or new sources on aldrin, dieldrin, and chlordane. The occurrence of OCPs due to re-emissions, ongoing sources, and long-range atmospheric transport could be a challenge towards the complete phase-out of OCPs in South Korea.
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Poluentes Atmosféricos , Hidrocarbonetos Clorados , Praguicidas , Clordano/análise , Poluentes Atmosféricos/análise , Monitoramento Ambiental , Praguicidas/análise , Hidrocarbonetos Clorados/análise , Endossulfano/análise , República da CoreiaRESUMO
PURPOSE: Ubiquitin-conjugating enzyme E2 C (UBE2C) is known to show a causal relationship with cancer development and advancement. The role of UBE2C is to control the mitotic spindle checkpoint. Excess UBE2C has been identified in patients with advanced prostate cancer. The objective of the present study was to examine positive connections between the expression of UBE2C and prognostic factors for prostate cancer. METHODS: Prostate cancer patients' clinical data were analysed. Tissue microarrays (TMAs) were also performed for human prostate cancer tissues (n = 335) and adjacent non-neoplastic tissues (n = 22). TMA slides were incubated with antibodies against UBE2C. Cores were scored by a pathologist who was blind to cancer results. RESULTS: Of 335 prostate cancer patients, 200 could be assessed for biochemical recurrence, clinical recurrence, and overall survival. Human prostate cancer tissues showed higher expression of UBE2C than adjacent non-neoplastic tissues. High expression level of UBE2C showed a strong positive relationship with a high prostate-specific antigen (PSA), Gleason's score, and pathological stage of prostate cancer. Patients with a higher UBE2C grade demonstrated greater lymphatic engagement of prostate cancer than those with a lower UBE2C grade. CONCLUSION: The expression of UBE2C has positive correlations with several prognostic factors for prostate cancer. Thus, investigating the expression level of UBE2C staining is a promising tool for predicting prostate cancer prognosis.
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Neoplasias da Próstata , Enzimas de Conjugação de Ubiquitina , Masculino , Humanos , PrognósticoRESUMO
PURPOSE: Healthy aging is an important concern in an aging society. Although the causal relationship between hypogonadism and erectile dysfunction in elderly men remains unclear, many physicians have achieved positive results after implementing exogenous testosterone supplementation therapy in patients with normal or slightly low blood testosterone. The purpose of this study was to conduct a systematic review and meta-analysis on whether testosterone replacement therapy (TRT) could improve sexual function in the elderly, as reported recently. MATERIALS AND METHODS: As a comprehensive literature search was performed to find articles published in PubMed, Embase, and Cochrane databases by January 2022. The search used keywords of 'aged', 'male', 'sexual behavior', and 'testosterone'. Randomized controlled trials (RCTs) were finally selected. As the main effect variable, results of a questionnaire on sexual function were analyzed and the effects of TRT were compared to those of placebo control. RESULTS: Five RCT studies were included in this meta-analysis. The overall improvement by mean difference of sexual function for testosterone supplementation was 0.082 (95% CI: -0.049 to 0.213). In subgroup analysis, only intramuscular injection of 1,000 mg testosterone significantly improved sexual function of the elderly (0.229, 95% CI: 0.112 to 0.347). There was no significant difference in sexual function according to testosterone dose in meta-ANOVA (p=0.957). The difference was not statistically significant either in the meta-regression test (p=0.310). Egger's regression coefficient test did not indicate a publication bias (p=0.132). CONCLUSIONS: Although our overall effect size (that is, sexual function effect of TRT) did not show a significant improvement, the direction of improvement in erection and motivation was clearly shown. The injection formulation resulted in a significant sexual function improvement. Since only a few RCTs were included in the analysis, more well-designed prospective studies are needed to have a definite conclusion.
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A high rate of Meniere's disease (MD) in patients with osteoporosis has been suggested. This research intended to estimate the bidirectional association of MD with osteoporosis. The ≥40-year-old population in the Korean National Health Insurance Service-Health Screening Cohort 2002-2019 was examined. In study I, 9529 patients with MD and 38,116 control I participants were analyzed for a previous history of osteoporosis. In study II, 65,858 patients with osteoporosis and 65,858 control II participants were analyzed for a previous history of MD. Stratified Cox proportional hazard models were applied to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of MD for osteoporosis in study I and of osteoporosis for MD in study II. The rate of a prior history of osteoporosis was 13.3% for the MD group and 11.3% for the control I group. The patients with MD had a 1.12 times higher HR for previous osteoporosis (95% CI = 1.04-1.20). In study II, the rate or a prior history of MD was 3.7% for patients with osteoporosis and 2.0% for the control II group. The patients with osteoporosis had a 1.50 times higher HR for previous MD (95% CI = 1.40-1.61). Most subgroups according to age, sex, and comorbid conditions demonstrated consistent bidirectional associations between MD and osteoporosis. Adult patients with MD had a greater risk of osteoporosis. In addition, adult patients with osteoporosis also showed a higher risk of MD.
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Doença de Meniere , Osteoporose , Adulto , Humanos , Seguimentos , Doença de Meniere/complicações , Doença de Meniere/epidemiologia , Estudos de Coortes , Osteoporose/complicações , Osteoporose/epidemiologia , Modelos de Riscos ProporcionaisRESUMO
Objective: The coronavirus disease 2019 (COVID-19) pandemic has affected all medical fields, including neurosurgery. Particularly, performing preoperative screening tests has become mandatory, potentially extending the time from admission to the emergency room and operating room, thus possibly affecting patients' prognosis. This study aimed to determine the influence of COVID-19 screening time on patients' postoperative prognosis. Methods: From September 10, 2020, to May 31, 2021, we retrospectively evaluated 54 patients with cerebral hemorrhage who underwent emergency surgery in the emergency room after the screening test. The control group included 89 patients with cerebral hemorrhage who underwent emergency surgery between January 2019 and March 2020, i.e., the period before the COVID-19 pandemic. Prognosis was measured using the Glasgow Coma Scale scores, which were obtained preoperatively, postoperatively, and at discharge, and the modified Rankin Scale (mRS). Additionally, unfavorable outcomes (mRS score 3-6) and in-hospital mortality rates were investigated for postoperative prognostic assessments. Results: No remarkable differences were observed in the time to surgical intervention and prognostic evaluation scores between patients with cerebral hemorrhage who underwent COVID-19 screening tests and subjects in the control group. Conclusion: This study confirmed that patient treatment and prognosis were not significantly affected by additional preoperative screening testing times during the pandemic. We believe that our results are informative for the evaluation and performance of emergency neurosurgery during the pandemic.
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The bdelloid rotifers collected from terrestrial habitats such as leaf litter, mosses and tree barks were studied and three new species were identified: Philodina haejooni n. sp., P. hongcheonensis n. sp. and Philodinavus koreanus n. sp. Philodina haejooni n. sp. is easily distinguished from its congeners by the leaf margin-shaped longitudinal ridges on trunk. The most significant diagnostic characteristic of Philodina hongcheonensis n. sp. is the four dorsal hemispherical processes on anal pseudosegment. Philodinavus koreanus n. sp. is the thirdly described species for the genus. The detailed morphologies of ciliated buccal fields, cheeks and spurs make Philodinavus koreanus n. sp. distinguishable from its two congeners. Here these three new species are described and illustrated. The partial sequences of mitochondrial cytochrome c oxidase subunit 1 gene (mtCOX1) for three new species are presented as well.
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Briófitas , Rotíferos , Animais , Ecossistema , República da CoreiaRESUMO
Organochlorine pesticides in soil samples across urban, suburban, agricultural, and industrial sites were analyzed every year between 2013 and 2016 in South Korea. The study aims to understand the residual status, diminution of occurrence from the South Korean environment, and its risk to humans after three decades of the ban. A general decreasing trend of OCPs has been observed over the years. The OCP concentrations were below the guideline values prescribed for soil pollution. Metabolites like p,p'-DDD and endosulfan sulfate contributed a major portion to the total OCP concentration over the years. The agricultural sites showed higher OCP levels than other site types. Compositional profile and diagnostic ratios suggested that the occurrence of DDT and endosulfan residues were due to historical inputs, but those of HCH and chlordane reflect recent usage in some pockets. The calculated incremental lifetime cancer risk was within the safety limit for all age groups across the genders in the majority of the sites. It is evident that the OCP load on soil is decreasing since the ban on usage. However, regular monitoring with a special focus on metabolites can be an effective control measure to regulate and eliminate the contamination of OCPs.
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Hidrocarbonetos Clorados , Praguicidas , Poluentes do Solo , Agricultura , China , Monitoramento Ambiental , Feminino , Humanos , Hidrocarbonetos Clorados/análise , Masculino , Praguicidas/análise , Solo/química , Poluentes do Solo/análiseRESUMO
Several recent preclinical studies have reported that dynamic changes in miRNA expression contribute to hearing function. This study aims to investigate miRNA expression changes in the cochlear nuclei (CN) of rats following chronic noise exposure. Eight-week-old rats (n = 14) were exposed to noise for 4 weeks. The control rats (n = 14) were raised under identical conditions without noise. Two months after noise exposure, the auditory brainstem response (ABR) was examined, and the cochlea and CN were harvested. In the CN, the expression levels of arc, neurocan, and brevican were measured (n = 6 per group). Furthermore, the expression levels of miRNAs and their predicted target genes were measured in the CN (n = 8 per group). ABR thresholds were elevated after 4 weeks of noise exposure, which were maintained for 3 months. In CN, the protein expression of arc and brevican was higher in the noise-exposed group than in the control group (0.95 [standard deviation (SD) = 0.53] vs. 3.19 [SD = 1.00], p < 0.001 for arc and 1.02 [SD = 0.10] vs. 1.66 [SD = 0.24], p < 0.001 for brevican). The noise-exposed rats exhibited lower expression levels of miR-758-5p, miR-15b-5p, miR-212-3p, miR-199a-5p, and miR-134-3p than the control rats (all p < 0.001). The AMPK signaling pathway was predicted to be regulated by these miRNAs. The predicted target genes AKT3, SIRT1, and PRKAA1 were highly expressed in noise-exposed rats. In CN of noise-exposed rats, the miRNAs of miR-758-5p, miR-15b-5p, miR-212-3p, miR-199a-5p, and miR-134-3p were reduced and related to AMPK signaling including AKT3 and SIRT1 expression. These modulation of signaling pathways could mediate the increased expression of brevican in the CN of noise-exposed rats.
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Núcleo Coclear , MicroRNAs , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Brevicam/metabolismo , Núcleo Coclear/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Ratos , Sirtuína 1/metabolismoRESUMO
This study aimed to estimate the risk of mortality related to the number of missing teeth in a South Korean population. The ≥ 40-year-old population of the Korean National Health Insurance Service-Health Screening Cohort 2002-2003 was analyzed. Participants were selected from a total of 220,189 participants and included in groups of 0 teeth lost, 1-2 teeth lost, and ≥ 3 teeth lost. Among the total population, 17,211 participants were included in no missing teeth, 1-2 missing teeth, and ≥ 3 missing teeth and were randomly matched 1:1:1 for age and sex. Mortality from specific causes and all-cause mortality were compared among the groups. The hazard ratio (HR) of the number of missing teeth for all-cause mortality or each cause of mortality was analyzed using Cox proportional hazard models. According to the cause of death, the HRs for metabolic disease, digestive disease, and trauma were greater in the group with ≥ 3 missing teeth than in the no missing teeth group. The group with ≥ 3 missing teeth indicated a 1.19-fold higher HR for all-cause mortality than the no missing teeth group [95% confidence intervals (95% CIs) = 1.12-1.27, P < 0.001]. The group with 1- 2 missing teeth did not show a higher HR for all-cause mortality. In the group with 1-2 missing teeth, the HRs for mortality from mental disease and digestive disease were higher than those in the no missing teeth group. The group with 1-2 missing teeth did not show a higher HR for all-cause mortality. The number of missing teeth was linked with a higher risk of mortality. For specific causes of mortality, mortality from metabolic disease, digestive disease, and trauma was higher in the participants with the number of missing teeth.
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The effect of statins on aminoglycoside-induced ototoxicity is controversial. This study aimed to explore the role of pravastatin (PV) in kanamycin-induced hearing loss in rats. Adult rats were intraperitoneally treated with 20 mg/kg/day of kanamycin (KM) for 10 days. In the PV- and PV + KM-treated rats, 25 mg/kg/day of PV was intraperitoneally administered for 5 days. The auditory brainstem response (ABR) thresholds were measured before and after drug treatment using a smartEP system at 4, 8, 16, and 32 kHz. Cochlear changes in poly ADP-ribose (PAR) polymerase (PARP), PAR, and caspase 3 were estimated using Western blotting. PV administration did not increase the ABR thresholds. The KM-treated rats showed elevated ABR thresholds at 4, 8, 16, and 32 kHz. The PV + KM-treated rats demonstrated lower ABR thresholds than the KM-treated rats at 4, 8, and 16 kHz. The cochlear outer hair cells and spiral ganglion cells were relatively preserved in the PV + KM-treated rats when compared with that in the KM-treated rats. The cochlear expression levels of PARP, PAR, and caspase 3 were higher in the KM-treated rats. The PV + KM-treated rats showed lower levels of PARP, PAR, and caspase 3 than the KM-treated rats. PV protected cochleae from KM-induced hearing loss in rats. The regulation of autophagy and apoptosis mediated the otoprotective effects of PV.
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Surdez , Perda Auditiva , Animais , Caspase 3/metabolismo , Cóclea/metabolismo , Surdez/metabolismo , Potenciais Evocados Auditivos do Tronco Encefálico , Perda Auditiva/induzido quimicamente , Perda Auditiva/tratamento farmacológico , Perda Auditiva/metabolismo , Canamicina/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Pravastatina/farmacologia , RatosRESUMO
Importance: A connection between Meniere disease (MD) and migraine has been proposed, but the temporal association remains unknown. Objective: To examine the bidirectional association of MD with migraine. Design, Setting, and Participants: This case-control study included participants 40 years or older from the Korean National Health Insurance Service Health Screening Cohort from 2002 to 2015. Main Outcomes and Measures: A total of 6919 patients with MD were matched with 27â¯676 control participants without MD for age, sex, income, region of residence, and index date. The incidence of migraine was analyzed in the MD and matched groups using a stratified Cox proportional hazard regression model. In addition, 35â¯889 patients with migraine were matched with 71â¯778 control participants without migraine. The incidence of MD was analyzed using a stratified Cox proportional hazard regression model. Results: Of 142â¯262 total participants, 94â¯611 (66.5%) were women. Migraine occurred in 695 of 6919 patients with MD (10.0%) and 970 of 27â¯676 matched control participants (3.5%). The MD group demonstrated a 2.22-fold higher risk of migraine than the matched control group (95% CI, 1.99-2.49). Meniere disease was present in 1098 of 35â¯889 patients with migraine (3.1%) and 781 of 71â¯778 matched control participants (1.1%). The migraine group had a 1.95-fold higher risk of MD than the matched control group (95% CI, 1.77-2.15). Conclusions and Relevance: The results of this case-control study suggest that patients with MD had a greater risk of migraine occurrence. Furthermore, patients with migraine had a higher risk of MD. Based on the bidirectional association, therapeutics for migraine could potentially be applied to MD and vice versa.
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Doença de Meniere , Transtornos de Enxaqueca , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Doença de Meniere/complicações , Doença de Meniere/epidemiologia , Transtornos de Enxaqueca/complicações , Transtornos de Enxaqueca/epidemiologia , Fatores de RiscoRESUMO
OBJECTIVE: To investigate the risk of sudden sensorineural hearing loss (SSNHL) in asthma patients. DESIGN: A longitudinal follow-up study using a retrospective cohort SETTING: The 2002-2013 Korean National Health Insurance Service-Health Screening Cohort PARTICIPANTS AND INTERVENTIONS: The ≥40 years old Korean population were enrolled. The asthma patients were 1:1 matched with the control group for age, sex, income and region of residence. MAIN OUTCOME MEASURE: The occurrence of SSNHL was followed in both asthma and control groups. The stratified Cox proportional hazard model was used. Age, sex, income and region of residence were stratified, and Charlson Comorbidity Index scores, obesity, smoking, alcohol consumption and atopic dermatitis histories were adjusted. Subgroup analysis was performed according to age, sex, obesity, smoking and alcohol consumption. RESULTS: The results showed that 1.0% (877/90 564) of the asthma group and 0.8% (706/90,564) of the control group exhibited SSNHL (p<0.001). The asthma group demonstrated a higher HR for SSNHL than the control group (adjusted HR 1.23, 95% CI 1.11 to 1.36, p<0.001). According to age and sex, the female subgroup showed elevated HRs for SSNHL in asthma patients. Both the non-smoker and current smoker groups demonstrated higher HRs for SSNHL in asthma patients than in controls. According to alcohol consumption or obesity, the <1 time a week alcohol consumption group and normal weight and severe obesity groups showed higher HRs for SSNHL in asthma patients than in the controls. CONCLUSIONS: Adult asthma patients had a higher risk of SSNHL than the control participants matched for demographic and socioeconomic factors.
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Asma , Perda Auditiva Neurossensorial , Perda Auditiva Súbita , Adulto , Asma/complicações , Asma/epidemiologia , Estudos de Casos e Controles , Feminino , Seguimentos , Perda Auditiva Neurossensorial/complicações , Perda Auditiva Neurossensorial/etiologia , Perda Auditiva Súbita/complicações , Perda Auditiva Súbita/etiologia , Humanos , Estudos Longitudinais , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVES/HYPOTHESIS: This study aimed to investigate the association between Meniere's disease and prior history of asthma. STUDY DESIGN: A nested case-control study. METHODS: Among the patients aged ≥40 years from the Korean National Health Insurance Service-Health Screening Cohort 2002-2015, 7,734 diagnosed with Meniere's disease between 2004 and 2015 were enrolled in this study. From the 505,834 participants without a prior history of Meniere's disease, 30,936 control participants were selected based on age, sex, income, and region of residence. The presence of a prior history of asthma before the diagnosis of Meniere's disease was compared between the Meniere's disease group and control group using conditional logistic regression with odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Prior history of asthma was associated with 1.30 (1.21-1.39) times higher odds of Meniere's disease (E-value = 1.92 [1.71]). Both allergic asthma and nonallergic asthma patients demonstrated higher odds of Meniere's disease than the control group (adjusted OR = 1.21 [1.08-1.36] and E-value = 1.72 [1.37] for allergic asthma; adjusted OR = 1.26 [1.17-1.36] and E-value = 1.83 [1.60] for nonallergic asthma). CONCLUSIONS: This study is the first to demonstrate a positive relationship between Meniere's disease and prior asthma history in adults. The association between prior asthma history and Meniere's disease was noted in both allergic and nonallergic asthma cases. The potential development of Meniere's disease should be considered when managing the asthma patients with dizziness or vertigo. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:864-872, 2022.
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Asma , Doença de Meniere , Adulto , Asma/complicações , Asma/epidemiologia , Estudos de Casos e Controles , Estudos de Coortes , Humanos , Doença de Meniere/complicações , Doença de Meniere/epidemiologia , Vertigem/complicaçõesRESUMO
Telmisartan (TM) has been proposed to relieve inflammatory responses by modulating peroxisome proliferator activator receptor-γ (PPARγ) signaling. This study aimed to investigate the protective effects of TM on kanamycin(KM)-induced ototoxicity in rats. Forty-eight, 8-week-old female Sprague Dawley rats were divided into four groups: (1) control group, (2) TM group, (3) KM group, and (4) TM + KM group. Auditory brainstem response was measured. The histology of the cochlea was examined. The protein expression levels of angiotensin-converting enzyme 2 (ACE2), HO1, and PPARγ were measured by Western blotting. The auditory threshold shifts at 4, 8, 16, and 32 kHz were lower in the TM + KM group than in the KM group (all p < 0.05). The loss of cochlear outer hair cells and spiral ganglial cells was lower in the TM + KM group than in the KM group. The protein expression levels of ACE2, PPARγ, and HO1 were higher in the KM group than in the control group (all p < 0.05). The TM + KM group showed lower expression levels of PPARγ and HO1 than the KM group.TM protected the cochlea from KM-induced injuries in rats. TM preserved hearing levels and attenuated the increase in PPARγ and HO1 expression levels in KM-exposed rat cochleae.
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Enzima de Conversão de Angiotensina 2/metabolismo , Heme Oxigenase (Desciclizante)/metabolismo , Canamicina/toxicidade , Ototoxicidade/tratamento farmacológico , PPAR gama/metabolismo , Telmisartan/farmacologia , Enzima de Conversão de Angiotensina 2/genética , Animais , Antibacterianos/toxicidade , Anti-Hipertensivos/farmacologia , Limiar Auditivo/efeitos dos fármacos , Cóclea/efeitos dos fármacos , Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos , Feminino , Heme Oxigenase (Desciclizante)/genética , Ototoxicidade/etiologia , Ototoxicidade/metabolismo , Ototoxicidade/patologia , PPAR gama/genética , Ratos , Ratos Sprague-DawleyRESUMO
Although hippocampal changes due to noise-induced hearing loss have been suggested, little is known about the miRNA levels due to these hippocampal changes. Three-week-old Sprague-Dawley rats were divided into noise and control groups (n = 20 per group). The noise group rats were exposed to white Gaussian noise (115 dB SPL, 4 hours per day) for three days. One day after noise exposure, the hippocampi of rats were harvested and miRNA expressions were analyzed using the Affymetrix miRNA 4.0 microarray (n = 6 per group). The predicted target genes of each miRNA were retrieved, and the pathways related to the predicted target genes were analyzed. miR-758-5p, miR-210-5p, miR-370-5p, miR-652-5p, miR-3544, miR-128-1-5p, miR-665, miR-188-5p, and miR-874-5p expression increased in the hippocampal tissue of the noise group compared to that in the control group. The overlapping predicted target genes included Bend4, Creb1, Adcy6, Creb5, Kcnj9, and Pten. The pathways related to these genes were the estrogen signaling pathway, vasopressin-regulated water reabsorption, thyroid hormone synthesis, aldosterone synthesis and secretion, insulin secretion, circadian entrainment, insulin resistance, cholinergic synapse, dopaminergic synapse, cGMP-PKG signaling pathway, cAMP signaling pathway, PI3K-Akt signaling pathway, TNF signaling pathway, and AMPK signaling pathway. miR-448-3p, miR204-5p, and miR-204-3p expression decreased in the hippocampal tissue of the noise group compared to that in the control group. The overlapping predicted target genes of these three miRNAs were Rps6kas, Nfactc3, Rictor, Spred1, Cdh4, Cdh6, Dvl3, and Rcyt1b. Pathway analysis suggested that the Wnt signaling pathway is related to Dvl3 and Nfactc3. Noise-induced hearing loss dysregulates miR-758-5p, miR210-5p, miR370-5p, miR-652-5p, miR-3544, miR-128-1-5p, miR-665, miR-188-5p, miR-874-5p, miR-448-3p, miR-204-5p, miR-204-3p, and miR-140-5p expression in the hippocampus. These miRNAs have been predicted to be associated with hormonal, inflammatory, and synaptic pathways.
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Perda Auditiva Provocada por Ruído/patologia , Hipocampo/metabolismo , MicroRNAs/metabolismo , Animais , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Perda Auditiva Provocada por Ruído/genética , Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Ratos , Ratos Sprague-Dawley , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Proteínas Quinases S6 Ribossômicas 90-kDa/genética , Proteínas Quinases S6 Ribossômicas 90-kDa/metabolismo , Transdução de Sinais/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: The mTOR signaling pathway is inactivated by AMPK's tumor-suppressing function. It is recognized that ubiquitin conjugating enzyme 2O (UBE2O), which directly targets AMPK for ubiquitination and degradation, is intensified in human cancers. METHODS: This study investigated the clinical data about prostate cancer. Examination was also carried out into tissue microarrays (TMA) of human prostate cancer (n = 382) and adjacent non-neoplastic tissues around prostate cancer (n = 61). The TMA slides were incubated with antibodies against UBE2O, and the cores were scored by the pathologist blind to cancer results. RESULTS: Very strong positive correlations were identified between the expression of UBE2O staining and high PSA and pathological stage of prostate cancer. Cox's proportional hazard analysis established correlations between the following: (1) positive surgical margin and biochemical recurrence free survival, (2) PSA grade and clinical recurrence free survival, (3) regional lymph node positive and clinical recurrence free survival, (4) adjuvant treatment and overall survival, and (5) pathological T stage and overall survival. CONCLUSION: There is a positive correlation between the expression of UBE2O staining and prognosis for prostate cancer. Thus, a prostate cancer prognosis can be assessed with the expression of UBE2O staining.
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The association between air pollutants and Meniere's disease has not been explored. The present study investigated the relationship between meteorological factors and air pollutants on Meniere's disease. Participants, aged ≥ 40 years, of the Korean National Health Insurance Service-Health Screening Cohort were included in this study. The 7725 patients with Meniere's disease were matched with 30,900 control participants. The moving average meteorological and air pollution data of the previous 7 days, 1 month, 3 months, and 6 months before the onset of Meniere's disease were compared between the Meniere's disease and control groups using conditional logistic regression analyses. Additional analyses were conducted according to age, sex, income, and residential area. Temperature range; ambient atmospheric pressure; sunshine duration; and levels of SO2, NO2, O3, CO, and PM10 for 1 month and 6 months were associated with Meniere's disease. Adjusted ORs (odds ratios with 95% confidence interval [CI]) for 1 and 6 months of O3 concentration were 1.29 (95% CI 1.23-1.35) and 1.31 (95% CI 1.22-1.42), respectively; that for the 1 and 6 months of CO concentration were 3.34 (95% CI 2.39-4.68) and 4.19 (95% CI 2.79-6.30), respectively. Subgroup analyses indicated a steady relationship of O3 and CO concentrations with Meniere's disease. Meteorological factors and air pollutants were associated with the rate of Meniere's disease. In particular, CO and O3 concentrations were positively related to the occurrence of Meniere's disease.
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Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , Doença de Meniere/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Masculino , Conceitos Meteorológicos , Meteorologia/métodos , Pessoa de Meia-Idade , Ozônio/efeitos adversos , Material Particulado/efeitos adversos , Dióxido de Enxofre/efeitos adversosRESUMO
This study aimed to investigate the association of previous stain use with hearing impairment in an adult population. Data from the ≥ 40-year-old population in the Korean National Health Insurance Service Health Screening Cohort were used. The hearing impairment group was classified based on the national registry of hearing-impaired persons. Control participants were randomly selected and matched for age, sex, income, and region of residence. The number of days of statin prescription during the 2 years before the diagnosis of hearing impairment was compared between the hearing impairment group and the control group using conditional logistic regression analysis. Additional analyses were conducted according to age and sex. The number of days of previous statin use was not different between the hearing impairment group and the control group (adjusted odds ratio [aOR] = 0.94, 95% confidence interval (CI) = 0.86-1.02, P = 0.118). According to age, in the ≥ 70-year-old group, those with hearing impairment had 11% lower rates of previous statin use than those in the control group (aOR = 0.89, 95% CI = 0.80-0.99, P = 0.039). According to sex, in the male group, 12% lower rates of previous statin use were observed among those with hearing impairment than among those in the control group (aOR = 0.88, 95% CI = 0.79-0.99, P = 0.037). Previous statin use might have an effect on reducing the prevalence of hearing impairment in elderly individuals and men.