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1.
J Glaucoma ; 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35019875

RESUMO

PRECIS: The annual incidence of glaucoma progression (9.7%) and rates of visual field mean deviation change in progressors (-1.02±0.06▒dB/y) are high in a small cohort of urban Ghanaians. PURPOSE: To report the incidence of glaucoma progression and the rate of visual field deterioration in a small cohort of Ghanaians. METHODS: One hundred and ten subjects (204 eyes) diagnosed with glaucoma at a baseline population-based screening examination were re-examined a mean of 8.3±0.8 years later. Eyes were classified as having progressed if the optic disc alone, visual field alone or both showed significant glaucomatous changes on follow-up. Visual field mean deviation (MD) was used to calculate the rate of visual field progression. RESULTS: Progression was observed in 89 (80.9%, 9.7%/year) subjects (130 eyes). Progression occurred in 32 (31.7%, 3.8%/year) subjects by optic disc alone (46 eyes), 38 (44.7%, 5.4%/year) subjects by visual field alone (58 eyes), and 19 (25.0%, 3.0%/year) subjects by both modalities (26 eyes). The average rate of change in MD differed significantly between progressors (-1.02±1.06▒dB/y) and non-progressors (+0.089±0.49▒dB/y), P=0.001. The rate of visual field worsening was greater among those who were classified as having progressed by both structure and function (-1.29±0.68▒dB/y) and by function alone (-1.21±1.20▒dB/y) than by structure alone (-0.55±0.76▒dB/y). Progression was significantly associated with older age (OR, 1.42; P<0.001) and higher baseline IOP (OR, 1.18; P=0.002). Factors associated with rate of MD change were baseline older age (OR, 1.66; P=0.003), higher IOP (OR, 2.81; P=0.007), better visual field MD (OR, 1.41; P=0.004), and systemic hypertension (OR, 1.15; P=0.029). CONCLUSION: The incidence and rate of visual field progression is high in this longitudinal study of Ghanaian subjects with glaucoma. The findings may have important clinical and public health policy ramifications.

2.
Virchows Arch ; 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34997312

RESUMO

Epstein-Barr virus-infected B cells are found at high frequency in peripheral T cell lymphoma. Herein, we report a case involving excessive EBV-positive B cells accompanying peripheral T cell lymphoma, not otherwise specified in the nasopharynx masquerading as nasopharyngeal extranodal NK/T cell lymphoma. A large number of Epstein-Barr virus-infected B cells infiltrate in between CD3-positive cytotoxic tumor T cells, as if EBV was infecting tumor T cells. After chemotherapy, the T cell lymphoma population decreased, but the B cell population expanded to form EBV-positive diffuse large B cell lymphoma in the tonsils and nasopharynx. At the follow-up, bone marrow biopsy exhibited infiltration of composite peripheral T cell lymphoma, not otherwise specified, and EBV-positive diffuse large B cell lymphoma. Although this condition is rare, the cell lineage of EBV-infected cells must be confirmed when diagnosing extranodal NK/T cell lymphoma to exclude the possibility of misdiagnosis by Epstein-Barr virus-infected B cells.

3.
J Pers Med ; 11(12)2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34945718

RESUMO

A person high in neuroticism is more likely to experience anxiety, stress, worry, fear, anger, and depression. Previous studies have shown that the gut microbiota can influence personality and mental disorders, including stress, anxiety, and depression, through the gut-brain axis. Here, we investigated the correlations between the sub-facet of neuroticism and gut microbiota using the Revised NEO Personality Inventory and the 16S rRNA gene sequencing data 784 adults. We found that the high anxiety and vulnerability group showed significantly lower richness in microbial diversity than a group with low anxiety and vulnerability. In beta diversity, there was a significant difference between the low and high groups of anxiety, self-consciousness, impulsiveness, and vulnerability. In taxonomic compositions, Haemophilus belonging to Gammaproteobacteria was correlated with the Neuroticism domain as well as N1 anxiety and N6 vulnerability facets. The high N1 anxiety and N6 vulnerability group was correlated with a low abundance of Christensenellaceae belonging to Firmicutes Clostridia. High N4 self-consciousness was correlated with a low abundance of Alistipes and Sudoligranulum. N5 impulsiveness was correlated with a low abundance of Oscillospirales. Our findings will contribute to uncovering the potential link between the gut microbiota and neuroticism, and the elucidation of the correlations of the microbiome-gut-brain axis with behavioral changes and psychiatric cases in the general population.

4.
J Pers Med ; 11(12)2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34945854

RESUMO

Animal studies have shown the interaction between androgens and the gut microbiome directly and indirectly; however, limited evidence from human studies is available. To evaluate the association between prostate-specific antigen (PSA) levels within the normal range, reflective of androgen receptor activity, and the gut microbiota composition, a cross-sectional analysis was performed in 759 Korean men aged between 25 and 78 years with normal PSA levels of ≤4.0 ng/mL. We evaluated the biodiversity of gut microbiota as well as the taxonomic and functional signatures associated with PSA levels using 16S rRNA gene sequencing data. PSA levels within the normal range were categorized into three groups: lowest quartile (G1), interquartile range (G2, reference), and highest quartile (G3). The G3 group had higher microbial richness than the G2 group, although it was dominated by a few bacteria. An increase in Escherichia/Shigella abundance and a reduction in Megamonas abundance in the G3 group were also detected. A U-shaped relationship was observed between the three groups across most analyses, including biodiversity, taxonomic composition, and inferred pathways in the gut microbiota. This study showed different microbiota patterns across PSA levels within the normal range. Further studies are required to elucidate the role of microbiota in regulating PSA levels.

5.
J Pathol Transl Med ; 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34775730

RESUMO

Composite lymphoma is very rare and a combination of Hodgkin lymphoma and non-Hodgkin lymphoma and even histiocytic tumors can occur. Because of the unfamiliarity, not only can this cause diagnostic problems, but can also affect treatment plan. We report a case of composite lymphoma in a 40-year-old male. Initial biopsy showed a composite lymphoma of follicular lymphoma grade 1 and classic Hodgkin lymphoma. After chemotherapy, another lymph node was taken because of disease progression, which revealed follicular lymphoma, grade 3a without Hodgkin lymphoma component.

6.
Sci Rep ; 11(1): 22745, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34815492

RESUMO

Although Krüppel-associated box domain-containing zinc-finger proteins (K-ZNFs) may be associated with sophisticated gene regulation in higher organisms, the physiological functions of most K-ZNFs remain unknown. The Zfp212 protein was highly conserved in mammals and abundant in the brain; it was mainly expressed in the cerebellum (Cb). Zfp212 (mouse homolog of human ZNF212) knockout (Zfp212-KO) mice showed a reduction in survival rate compared to wild-type mice after 20 months of age. GABAergic Purkinje cell degeneration in the Cb and aberrant locomotion were observed in adult Zfp212-KO mice. To identify genes related to the ataxia-like phenotype of Zfp212-KO mice, 39 ataxia-associated genes in the Cb were monitored. Substantial alterations in the expression of ataxin 10, protein phosphatase 2 regulatory subunit beta, protein kinase C gamma, and phospholipase D3 (Pld3) were observed. Among them, Pld3 alone was tightly regulated by Flag-tagged ZNF212 overexpression or Zfp212 knockdown in the HT22 cell line. The Cyclic Amplification and Selection of Targets assay identified the TATTTC sequence as a recognition motif of ZNF212, and these motifs occurred in both human and mouse PLD3 gene promoters. Adeno-associated virus-mediated introduction of human ZNF212 into the Cb of 3-week-old Zfp212-KO mice prevented Purkinje cell death and motor behavioral deficits. We confirmed the reduction of Zfp212 and Pld3 in the Cb of an alcohol-induced cerebellar degeneration mouse model, suggesting that the ZNF212-PLD3 relationship is important for Purkinje cell survival.

7.
Cell Immunol ; 371: 104454, 2021 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-34773897

RESUMO

Immune dysregulation is commonly observed in patients with coronavirus disease 2019 (COVID-19). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces severe lung inflammation and innate immune cell dysregulation. However, the precise interaction between SARS-CoV-2 and the innate immune system is currently unknown. To understand the interaction between SARS-CoV-2 and natural killer (NK) cells, several SARS-CoV-2 S protein peptides capable of binding to the NKG2D receptor were screened by in silico analysis. Among them, two peptides, cov1 and cov2, bound to NK cells and NKG2D receptors. These cov peptides increased NK cytotoxicity toward lung cancer cells, stimulated interferon gamma (IFN-γ) production by NK cells, and likely mediated these responses through the phosphorylation of Vav1, a key downstream-signaling molecule of NKG2D and NK activation genes. The direct interaction between SARS-CoV-2 and NK cells is a novel finding, and modulation of this interaction has potential clinical application as a therapeutic target for COVID-19.

8.
Gut Pathog ; 13(1): 65, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34717727

RESUMO

BACKGROUND: Hepatitis B virus (HBV) infection is associated with a reduced risk of developing dyslipidemia and non-alcoholic fatty liver diseases. Given that the gut microbiota plays a significant role in cholesterol metabolism, we compared the differences in gut microbial diversity and composition between HBV-infected and uninfected subjects. RESULTS: A prospective case-control study was designed comprising healthy controls (group A) and HBV-infected individuals (group B) in a 1:1 ratio (57 participants each; total = 114). The patients in group B were divided into two subgroups according to their HBV DNA loads: B1 < 2000 IU/mL (N = 40) and B2 ≥ 2000 IU/mL (N = 17). In a pairwise comparison of HBV-infected individuals and controls, higher alpha diversity was noted in group B, and the difference was significant only in patients in group B1. Alloprevotella and Eubacterium coprostanoligenes were predominant in group B1 compared to the control, whereas the abundance of Bacteroides fragilis and Prevotella 2 was lower. CONCLUSIONS: The gut microbiome in HBV-infected individuals with a low viral load is highly diverse and is dominated by specific taxa involved in fatty acid and lipid metabolism. To our knowledge, this is the first demonstration of a correlation between the presence of certain bacterial taxa and chronic HBV infection depending on the load of HBV DNA.

9.
J Med Virol ; 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34709664

RESUMO

Two messenger RNA (mRNA) vaccines developed by Pfizer-BioNTech and Moderna are being rolled out. Despite the high volume of emerging evidence regarding adverse events (AEs) associated with the COVID-19 mRNA vaccines, previous studies have thus far been largely based on the comparison between vaccinated and unvaccinated control, possibly highlighting the AE risks with COVID-19 mRNA vaccination. Comparing the safety profile of mRNA vaccinated individuals with otherwise vaccinated individuals would enable a more relevant assessment for the safety of mRNA vaccination. We designed a comparative safety study between 18 755 and 27 895 individuals who reported to VigiBase for adverse events following immunization (AEFI) with mRNA COVID-19 and influenza vaccines, respectively, from January 1, 2020, to January 17, 2021. We employed disproportionality analysis to rapidly detect relevant safety signals and compared comparative risks of a diverse span of AEFIs for the vaccines. The safety profile of novel mRNA vaccines was divergent from that of influenza vaccines. The overall pattern suggested that systematic reactions like chill, myalgia, fatigue were more noticeable with the mRNA COVID-19 vaccine, while injection site reactogenicity events were more prevalent with the influenza vaccine. Compared to the influenza vaccine, mRNA COVID-19 vaccines demonstrated a significantly higher risk for a few manageable cardiovascular complications, such as hypertensive crisis (adjusted reporting odds ratio [ROR], 12.72; 95% confidence interval [CI], 2.47-65.54), and supraventricular tachycardia (adjusted ROR, 7.94; 95% CI, 2.62-24.00), but lower risk of neurological complications such as syncope, neuralgia, loss of consciousness, Guillain-Barre syndrome, gait disturbance, visual impairment, and dyskinesia. This study has not identified significant safety concerns regarding mRNA vaccination in real-world settings. The overall safety profile patterned a lower risk of serious AEFI following mRNA vaccines compared to influenza vaccines.

10.
Rheum Dis Clin North Am ; 47(4): 669-690, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635298

RESUMO

Juvenile dermatomyositis (JDM) is a heterogeneous disease with new classification criteria and updates in myositis-specific autoantibody and myositis-associated antibody groups. There are many validated assessment tools for assessing disease activity in JDM. Future studies will optimize these tools and improve feasibility in clinical and research contexts. Genetic and environmental risk factors, mechanisms of muscle pathology, role of interferon, vascular markers, and changes in immune cells provide insights to JDM pathogenesis. Outcomes have improved, but chronic disease, damage, and mortality highlight the need for better outcome predictors and treatments. Increased collaboration of stakeholders may help overcome research barriers and improve JDM treatment.


Assuntos
Dermatomiosite , Miosite , Autoanticorpos , Biomarcadores , Dermatomiosite/diagnóstico , Humanos , Interferons
11.
Subst Abuse Treat Prev Policy ; 16(1): 78, 2021 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663379

RESUMO

BACKGROUND: Expanding access to medications for opioid use disorder (MOUD), such as buprenorphine and extended release (XR) naltrexone, is critical to addressing the US opioid epidemic, but little is known about prescriber satisfaction with delivering these two types of MOUD. The current study describes the satisfaction of prescribers delivering buprenorphine and XR-naltrexone while examining whether satisfaction is associated with current patient census and organizational environment. METHODS: As part of a cluster randomized clinical trial (RCT) focused on expanding access to medication for opioid use disorder, 41 MOUD prescribers in Florida, Ohio, and Wisconsin completed a web-based survey. The survey included measures of prescriber satisfaction with delivering buprenorphine treatment and XR-naltrexone. In addition, the survey measured several prescriber characteristics and their perceptions of the organizational environment. RESULTS: Prescribers were generally satisfied with their work in delivering these two types of MOUD. Prescribers reporting a greater number of patients (r = .46, p = .006), those who would recommend the center to others (r = .56, p < .001), and those reporting positive relationships with staff (r = .56, p < .001) reported significantly greater overall satisfaction with delivering buprenorphine treatment. Prescribers who more strongly endorsed feeling overburdened reported lower overall buprenorphine satisfaction (r = -.37, p = .02). None of the prescriber characteristics or perceptions of the organizational environment were significantly associated with overall satisfaction with delivering XR-naltrexone treatment. CONCLUSIONS: The generally high levels of satisfaction with both types of MOUD is notable given that prescriber dissatisfaction can lead to turnover and impact intentions to leave the profession. Future research should continue to explore the prescriber characteristics and organizational factors associated with satisfaction in providing different types of MOUD. REGISTRATION: ClinicalTrials.gov. NCT02926482. Date of registration: September 9, 2016. https://clinicaltrials.gov/ct2/show/NCT02926482 .


Assuntos
Buprenorfina , Transtornos Relacionados ao Uso de Opioides , Analgésicos Opioides/uso terapêutico , Buprenorfina/uso terapêutico , Humanos , Naltrexona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Satisfação Pessoal
12.
Healthcare (Basel) ; 9(6)2021 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-34199256

RESUMO

The aim of this study was to identify inflammatory cytokines as salivary biomarkers for periodontal disease. The subjects were 33 Korean adults aged 23 to 71 years. Using a multiplexed bead immunoassay called Luminex, the levels of inflammatory cytokines related to periodontal disease were evaluated. Oral examination for periodontal disease and gingival bleeding was conducted. With these two independent variables, differences in inflammatory cytokines were analyzed by an independent t-test and age-adjusted ANCOVA. Among the subjects, 21 had periodontal disease and 12 were healthy subjects. The gingival bleeding status was classified into low and high levels. Among 13 inflammatory cytokines in saliva, IL-1α, IL-1ß, IL-4, IL-8, CCL2/MCP-1, CCL3/MIP-1α, and TNF-α were found to be significant biomarkers within the standard curve. The quantity of IL-1ß was increased in subjects with high levels of gingival bleeding. IL-1α levels were increased in subjects with periodontal disease. After adjusting for age, the significant biomarkers for gingival bleeding and periodontal disease were IL-1ß and IL-1α, respectively. Using the receiver operating characteristic (ROC) curve, IL-1ß was confirmed as a significant biomarker. The sensitivity and specificity of IL-1ß for predicting periodontitis were 88.24% and 62.5%, respectively. Therefore, IL-1 was found to be a significant biomarker for periodontal disease, and it could be used in the diagnosis of periodontal disease using saliva.

13.
Mitochondrial DNA B Resour ; 6(7): 2066-2068, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34212100

RESUMO

We report the complete mitochondrial genome sequence of the endangered Eurasian otter, Lutra lutra. The complete mitochondrial genome is 16,537 bp in length and contains 13 protein-coding genes, 22 transfer RNA, two ribosomal RNA, and one control region. The mitogenome is A + T rich, with a composition of 32.2% A, 27.5% C, 14.5% G, and 25.8% T. Phylogenetic analysis based on 13 protein-coding mitochondrial genes of Mustelidae supports the conventional systematic treatment with eight subfamilies. Lutra lutra is closely related to Lutra sumatrana and the subfamily Lutrinae was closely grouped with the Ictonychinae. This study provides genetic and taxonomic information for future studies of Eurasian otters and the Mustelidae.

14.
Microorganisms ; 9(6)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200249

RESUMO

Patients with COVID-19 have been reported to experience gastrointestinal symptoms as well as respiratory symptoms, but the effects of COVID-19 on the gut microbiota are poorly understood. We explored gut microbiome profiles associated with the respiratory infection of SARS-CoV-2 during the recovery phase in patients with asymptomatic or mild COVID-19. A longitudinal analysis was performed using the same patients to determine whether the gut microbiota changed after recovery from COVID-19. We applied 16S rRNA amplicon sequencing to analyze two paired fecal samples from 12 patients with asymptomatic or mild COVID-19. Fecal samples were selected at two time points: during SARS-CoV-2 infection (infected state) and after negative conversion of the viral RNA (recovered state). We also compared the microbiome data with those from 36 healthy controls. Microbial evenness of the recovered state was significantly increased compared with the infected state. SARS-CoV-2 infection induced the depletion of Bacteroidetes, while an abundance was observed with a tendency to rapidly reverse in the recovered state. The Firmicutes/Bacteroidetes ratio in the infected state was markedly higher than that in the recovered state. Gut dysbiosis was observed after infection even in patients with asymptomatic or mild COVID-19, while the composition of the gut microbiota was recovered after negative conversion of SARS-CoV-2 RNA. Modifying intestinal microbes in response to COVID-19 might be a useful therapeutic alternative.

15.
Sci Transl Med ; 13(604)2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34321320

RESUMO

Accumulation of the parkin-interacting substrate (PARIS; ZNF746), due to inactivation of parkin, contributes to Parkinson's disease (PD) through repression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α; PPARGC1A) activity. Here, we identify farnesol as an inhibitor of PARIS. Farnesol promoted the farnesylation of PARIS, preventing its repression of PGC-1α via decreasing PARIS occupancy on the PPARGC1A promoter. Farnesol prevented dopaminergic neuronal loss and behavioral deficits via farnesylation of PARIS in PARIS transgenic mice, ventral midbrain transduction of AAV-PARIS, adult conditional parkin KO mice, and the α-synuclein preformed fibril model of sporadic PD. PARIS farnesylation is decreased in the substantia nigra of patients with PD, suggesting that reduced farnesylation of PARIS may play a role in PD. Thus, farnesol may be beneficial in the treatment of PD by enhancing the farnesylation of PARIS and restoring PGC-1α activity.


Assuntos
Doença de Parkinson , Animais , Dopamina , Camundongos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Prenilação , Proteínas Repressoras/metabolismo , Substância Negra/metabolismo
16.
Curr Opin Rheumatol ; 33(5): 371-377, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34230439

RESUMO

PURPOSE OF REVIEW: This review provides updates regarding the role of interferon (IFN) in juvenile dermatomyositis (JDM), including comparison to interferonopathies and therapeutic implications. RECENT FINDINGS: Transcriptomic and protein-based studies in different tissues and peripheral IFN-α assessment have demonstrated the importance of the dysregulated IFN pathway in JDM. Additional studies have validated IFN-regulated gene and protein expression correlation with disease activity in blood and muscle, with potential to predict flares. Type I and II IFN both are dysregulated in peripheral blood and muscle, with more type I IFN in skin. Muscle studies connects hypoxia to IFN production and IFN to vascular dysfunction and muscle atrophy. JDM overlaps with interferonopathy phenotype and IFN signature. There are multiple case reports and case series noting decreased IFN markers and clinical improvement in refractory JDM with Janus kinase (JAK) inhibitors. SUMMARY: Studies confirm IFN, particularly type I and II IFN, is an important part of JDM pathogenesis by the level of dysregulation and correlation with disease activity, as well as IFN recapitulating key JDM muscle pathology. Smaller studies indicate there may be differences by myositis-specific autoantibody group, but validation is needed. JAK inhibitors are a promising therapy as they can inhibit IFN signaling, but further study is needed regarding which patients will benefit, dosing, and safety monitoring.


Assuntos
Dermatomiosite , Miosite , Antivirais , Autoanticorpos , Dermatomiosite/tratamento farmacológico , Humanos , Interferons
17.
Int J Mol Sci ; 22(10)2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065515

RESUMO

α-Synuclein (α-syn) is a hallmark amyloidogenic protein component of Lewy bodies in dopaminergic neurons affected by Parkinson's disease (PD). Despite the multi-faceted gene regulation of α-syn in the nucleus, the mechanism underlying α-syn crosstalk in chromatin remodeling in PD pathogenesis remains elusive. Here, we identified transcriptional adapter 2-alpha (TADA2a) as a novel binding partner of α-syn using the BioID system. TADA2a is a component of the p300/CBP-associated factor and is related to histone H3/H4 acetylation. We found that α-syn A53T was more preferentially localized in the nucleus than the α-syn wild-type (WT), leading to a stronger disturbance of TADA2a. Indeed, α-syn A53T significantly reduced the level of histone H3 acetylation in SH-SY5Y cells; its reduction was also evident in the striatum (STR) and substantia nigra (SN) of mice that were stereotaxically injected with α-syn preformed fibrils (PFFs). Interestingly, α-syn PFF injection resulted in a decrease in TADA2a in the STR and SN of α-syn PFF-injected mice. Furthermore, the levels of TADA2a and acetylated histone H3 were significantly decreased in the SN of patients with PD. Therefore, histone modification through α-syn A53T-TADA2a interaction may be associated with α-syn-mediated neurotoxicity in PD pathology.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Histonas/metabolismo , Fatores de Transcrição/metabolismo , alfa-Sinucleína/metabolismo , Acetilação , Animais , Linhagem Celular Tumoral , Corpo Estriado/metabolismo , Modelos Animais de Doenças , Neurônios Dopaminérgicos/metabolismo , Humanos , Corpos de Lewy/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Degeneração Neural/metabolismo , Doença de Parkinson/metabolismo , Substância Negra/metabolismo
18.
Biochem Biophys Res Commun ; 563: 98-104, 2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34062393

RESUMO

Hepatocellular carcinoma (HCC) is the most common primary liver cancer to cause liver cancer related deaths worldwide. Zinc finger protein 746 (ZNF746), initially identified as a Parkin-interacting substrate (PARIS), acts as a transcriptional repressor of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) in Parkinson's disease. As recent studies reported that PARIS is associated with cancer onset, we investigated whether PARIS is associated with HCC. We found an increase in insoluble parkin and PARIS accumulation in the liver of diethylnitrosamine (DEN)-injected mice, leading to the downregulation of PGC-1α and nuclear respiratory factor 1 (NRF1). Interestingly, the occurrence of DEN-induced tumors was significantly alleviated in the livers of DEN-injected PARIS knockout mice compared to DEN-injected wild-type mice, suggesting that PARIS is involved in DEN-induced hepatocellular tumorigenesis. Moreover, H2O2-treated Chang liver cells showed accumulation of PARIS and downregulation of PGC-1α and NRF1. Thus, these results suggest that PARIS upregulation by oncogenic stresses can promote cancer progression by suppressing the transcriptional level of PGC-1α, and the modulation of PARIS can be a promising therapeutic target for HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas Repressoras/metabolismo , Animais , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Repressoras/deficiência , Proteínas Repressoras/genética , Células Tumorais Cultivadas
19.
Artigo em Inglês | MEDLINE | ID: mdl-34067192

RESUMO

Oropharyngeal dysphagia is a condition characterized by swallowing difficulty in the mouth and pharynx, which can be due to various factors. Animal models of oropharyngeal dysphagia are essential to confirm the cause-specific symptoms, pathological findings, and the effect of treatment. Recently, various animal models of dysphagia have been reported. The purpose of this review is to organize the rodent models of oropharyngeal dysphagia reported to date. The articles were obtained from Medline, Embase, and the Cochrane library, and selected following the PRISMA guideline. The animal models in which oropharyngeal dysphagia was induced in rats or mice were selected and classified based on the diseases causing oropharyngeal dysphagia. The animal used, method of inducing dysphagia, and screening methods and results were collected from the selected 37 articles. Various rodent models of oropharyngeal dysphagia provide distinctive information on atypical swallowing. Applying and analyzing the treatment in rodent models of dysphagia induced from various causes is an essential process to develop symptom-specific treatments. Therefore, the results of this study provide fundamental and important data for selecting appropriate animal models to study dysphagia.


Assuntos
Transtornos de Deglutição , Animais , Deglutição , Transtornos de Deglutição/etiologia , Camundongos , Boca , Faringe , Ratos , Roedores
20.
Proc Natl Acad Sci U S A ; 118(27)2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34187898

RESUMO

An acute increase in the circulating concentration of glucocorticoid hormones is essential for the survival of severe somatic stresses. Circulating concentrations of GDF15, a hormone that acts in the brain to reduce food intake, are frequently elevated in stressful states. We now report that GDF15 potently activates the hypothalamic-pituitary-adrenal (HPA) axis in mice and rats. A blocking antibody to the GDNF-family receptor α-like receptor completely prevented the corticosterone response to GDF15 administration. In wild-type mice exposed to a range of stressful stimuli, circulating levels of both corticosterone and GDF15 rose acutely. In the case of Escherichia coli or lipopolysaccharide injections, the vigorous proinflammatory cytokine response elicited was sufficient to produce a near-maximal HPA response, regardless of the presence or absence of GDF15. In contrast, the activation of the HPA axis seen in wild-type mice in response to the administration of genotoxic or endoplasmic reticulum toxins, which do not provoke a marked rise in cytokines, was absent in Gdf15 -/- mice. In conclusion, consistent with its proposed role as a sentinel hormone, endogenous GDF15 is required for the activation of the protective HPA response to toxins that do not induce a substantial cytokine response. In the context of efforts to develop GDF15 as an antiobesity therapeutic, these findings identify a biomarker of target engagement and a previously unrecognized pharmacodynamic effect, which will require monitoring in human studies.

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