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1.
J Neurochem ; 167(6): 766-777, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37994169

RESUMO

Angelman syndrome, a severe neurodevelopmental disorder, is primarily caused by mutations or deletions of maternally inherited ubiquitin protein ligase E3A (UBE3A). Activation of the silenced paternal copy of UBE3A can occur with pharmacological perturbation; however, an environmental approach has not been examined. Here, we found Ube3a is highly expressed in embryonic and early neonatal mouse retina and is maternally-, but not paternally-, expressed in ganglion cells, amacrine cells, and horizontal cells. Moreover, we analyzed UBE3A expression in the retina and visual cortex of postnatal day 28 mice (P28) following exposure to light emissions from white compact-fluorescent bulbs or blue light-emitting diodes from postnatal day 0 (P0) to 28 (P28), encompassing a crucial phase of visual system development. We found higher levels of Ube3a RNA and protein in the retina, but not visual cortex compared with tissues from P28 mice exposure to typical lighting (controls). Levels of both paternal- and maternal-UBE3A protein in mouse retina were higher than controls in P28 mice exposed to white or blue light. Moreover, levels of open and repressive chromatin structures, indicated by histone H3 lysine 4 trimethylation (H3K4me3) and histone H3 lysine 27 trimethylation (H3K27me3), respectively, were increased in the Ube3a promoter from mouse retina exposed to white or blue light. Our findings strongly suggest that extended exposure to white or blue light constitutes a substantial environmental factor that can effectively promote UBE3A expression within the central nervous system.


Assuntos
Síndrome de Angelman , Camundongos , Animais , Síndrome de Angelman/genética , Síndrome de Angelman/metabolismo , Histonas , Cromatina , Lisina , Retina/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
2.
Eur J Clin Microbiol Infect Dis ; 42(3): 323-338, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36723755

RESUMO

Patients with chronic kidney disease (CKD) who are being treated with immunosuppressive medications are at risk for developing Pneumocystis jirovecii pneumonia (PCP). We attempted to characterize the clinical aspects of PCP in CKD patients in order to alert high-risk patients with bad prognosis. A retrospective study of CKD patients was conducted from June 2018 to June 2022. Based on PCP diagnostic criteria, these patients were divided into PCP and non-PCP groups. Using univariate and multivariate logistic regression analysis, risk indicators were evaluated, and nomogram and decision tree were developed. Of the CKD patients screened for Pneumocystis carinii nucleic acid, 1512 were included. Two-hundred forty four (16.14%) were diagnosed with PCP. Of the PCP, 88.5% was receiving glucocorticoid (GC) therapy, of which 66.3% received more than 0.5 mg/kg GC. Multivariate analysis showed that membranous nephropathy (OR 2.35, 95% CI 1.45-3.80), immunosuppressive therapy (OR 1.94, 95% CI 1.06-3.69), and ground glass opacity of CT scanning (OR 1.71, 95% CI 1.10-2.65) were associated with increased risk of Pneumocystis carinii infection. The AUC of nomogram based on logistics regression was 0.78 (0.75-0.81). The mortality in patients with PCP was 32.40%. Univariate analysis and decision tree showed that pulmonary insufficiency (PO2: OR 0.98, 95% CI 0.96-1.00), elevated APTT (OR 1.07, 95% CI 1.04-1.11), and reduced hemoglobin (OR 0.97, 95% CI 0.96-0.98) were associated with poor prognosis. PCP is not rare in CKD patients, particularly in those treated with immunosuppressive therapy. Considering the high mortality of the cases, further studies on the prevention and management of these patients are needed.


Assuntos
Pneumocystis carinii , Pneumonia por Pneumocystis , Insuficiência Renal Crônica , Humanos , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/epidemiologia , Pneumonia por Pneumocystis/microbiologia , Estudos Retrospectivos , Fatores de Risco , Insuficiência Renal Crônica/complicações , Medição de Risco
3.
Geriatr Nurs ; 53: 247-254, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37598428

RESUMO

This study aimed to examine the relationship between self-perceived quality of transitional care and functional outcome among patients with stroke and fractures. The Care Transition Measure (CTM-15) was used to survey patient's self-perceived transitional care quality before discharge. General estimating equations were used to investigate the influences of transitional care quality on patient's functional outcomes at before, 1 week after, and 1 or 3 months after discharge. Among stroke patients, higher CTM-15 scores were positively associated with greater outcome in Instrumental Activities of Daily Living (IADL) following discharge. Higher scores for "reader-friendly written care plan," "consideration of patient's preferences," and "understanding of health management" had significantly positive effects on functional recovery in IADL among both patient groups following discharge. These findings suggest that heterogeneity in transitional care needs between medical and surgical patients shall not be overlooked. A one-size-fits-all strategy may be insufficient for ensuring patient care continuity following discharge.


Assuntos
Acidente Vascular Cerebral , Cuidado Transicional , Humanos , Atividades Cotidianas , Taiwan , Alta do Paciente , Acidente Vascular Cerebral/terapia , Percepção
4.
Am J Nephrol ; 52(3): 228-238, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33823527

RESUMO

INTRODUCTION: Increasing evidence has demonstrated that loss of peritubular capillaries plays a critical role in renal interstitial fibrosis. Leucine-rich α2-glycoprotein-1 (LRG1) has been observed promoting angiogenesis in the ocular disease mouse model and myocardial infarction model. We aimed to explore the role of LRG1 in renal interstitial fibrosis. METHODS: We analyzed the expression of LRG1 in the plasma and kidney of CKD patients by ELISA and immunohistochemistry. Relationships between the expression of LRG1 in plasma and kidney and renal fibrosis and inflammation were analyzed. Tube formation assay was used to detect the angiogenesis in the human umbilical vein endothelial cell lines (HUVECs). And real-time PCR was used to detect the mRNA expression of LRG1, inflammatory factors, renal tubular injury indicators, pro-fibrotic cytokines, and CD31. We examined the effects of genetic ablation of LRG1 on renal fibrosis induced by unilateral ureteral obstruction (UUO) mice model at day 7. RESULTS: We demonstrated that the expression of LRG1 in renal tissues and plasma samples was upregulated in CKD patients. And the expression of LRG1 was elevated in human renal tubular epithelial cell line (HK-2) cells in response to the stimulation of TNF-α in vitro, and in kidney after UUO in vivo. The deficiency of the LRG1 gene aggravated renal fibrosis, inflammatory cells infiltration, and capillary rarefaction after UUO. In vitro, LRG1 promoted the tube formation of HUVEC cells. LRG1 inhibits fibronectin secretion induced by TGF-ß1 in HK-2 and overexpression of LRG1 in HK-2 cells decreased fibronectin secretion. CONCLUSION: LRG1 may prevent renal fibrosis by inhibiting the secretion of inflammatory and pro-fibrotic cytokines and promoting angiogenesis.


Assuntos
Citocinas/fisiologia , Glicoproteínas/fisiologia , Nefropatias/etiologia , Rim/patologia , Rarefação Microvascular/etiologia , Adulto , Animais , Feminino , Fibrose/etiologia , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade
5.
BMC Infect Dis ; 21(1): 397, 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33926392

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) has emerged as a major global health threat with a great number of deaths worldwide. Despite abundant data on that many COVID-19 patients also displayed kidney disease, there is limited information available about the recovery of kidney disease after discharge. METHODS: Retrospective and prospective cohort study to patients with new-onset kidney disease during the COVID-19 hospitalization, admitted between January 28 to February 26, 2020. The median follow-up was 4 months after discharge. The follow-up patients were divided into the recovery group and non-recovery group. Descriptive statistics and between-groups comparison were used. RESULTS: In total, 143 discharged patients with new-onset kidney disease during the COVID-19 hospitalization were included. Patients had a median age was 64 (IQR, 51-70) years, and 59.4% of patients were men. During 4-months median follow-up, 91% (130 of 143) patients recovered from kidney disease, and 9% (13 of 143) patients haven't recovered. The median age of patients in the non-recovery group was 72 years, which was significantly higher than the median age of 62 years in the recovery group. Discharge serum creatinine was significantly higher in the non-recovery group than in the recovery group. CONCLUSIONS: Most of the new-onset kidney diseases during hospitalization of COVID-19 patients recovered 4 months after discharge. We recommend that COVID-19 patients with new-onset kidney disease be followed after discharge to assess kidney recovery, especially elderly patients or patients with high discharge creatinine.


Assuntos
COVID-19/etiologia , Creatinina/sangue , Nefropatias/etiologia , Idoso , Antivirais/uso terapêutico , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/terapia , China/epidemiologia , Comorbidade , Feminino , Seguimentos , Taxa de Filtração Glomerular , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Nefropatias/epidemiologia , Nefropatias/terapia , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Estudos Prospectivos , Proteinúria/epidemiologia , Proteinúria/virologia , Respiração Artificial , Estudos Retrospectivos
6.
Am J Nephrol ; 51(11): 919-929, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33207339

RESUMO

BACKGROUND: For patients with CKD, evidence on the optimal dose of physical activity and possible harm with excessive exercise is limited. This study aimed to analyze the dose-response association between leisure-time physical activity (LTPA) and mortality in those with CKD and explore the optimal dose or possible harm associated with increased levels of LTPA. METHODS: 4,604 participants with CKD from the 1999 to 2012 National Health and Nutrition Examination Surveys with linked mortality data obtained through 2015 were classified into 6 groups: 0, 1-149, 150-299, 300-599, 600-899, and ≥900 min/week based on the total duration of the self-reported LTPA. Multivariable-adjusted Cox proportional hazards models were used to examine dose-response associations between LTPA and mortality. RESULTS: During the median follow-up of 114 months, 1,449 (31%) all-cause deaths were recorded. Compared to the inactive group (0 min/week), we observed a 22% lower risk of all-cause mortality (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.63-0.97) among participants who performed 1-149 min per week for LTPA. The corresponding HRs and 95% CIs for all-cause mortality for 150-299 and 300-599 min/week of LTPA were 0.79 (0.64-0.97) and 0.74 (0.56-0.98). The benefit appeared to reach a threshold of a 43% (HR, 0.57; 95% CI, 0.36-0.91) lower risk of all-cause mortality among individuals performing 600-899 min/week for LTPA. Importantly, for ≥900 min/week of LTPA, the continued benefits were observed (HR, 0.62; 95% CI, 0.44-0.87). CONCLUSION: LTPA was associated with lower mortality in those with CKD. The optimal dose was observed at the LTPA level of approximately 600-899 min/week, and there were still benefits rather than the excess risk with LTPA levels as high as ≥900 min/week. Therefore, clinicians should encourage inactive CKD patients to perform LTPA and do not need to discourage CKD patients who already adhere to long-term physical activity.


Assuntos
Atividades de Lazer , Insuficiência Renal Crônica/mortalidade , Comportamento Sedentário , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais/estatística & dados numéricos , Insuficiência Renal Crônica/reabilitação , Medição de Risco/estatística & dados numéricos , Estados Unidos/epidemiologia
7.
RNA Biol ; 15(12): 1487-1498, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30497328

RESUMO

Hypoxia plays a crucial role in the aggressiveness of solid tumors by driving multiple signaling pathways. Recently, long non-coding RNA (lncRNA) has been reported to promote or inhibit tumor aggressiveness by regulating gene expression. Previous studies in our laboratory found that the lncRNA NDRG1-OT1 is significantly up-regulated under hypoxia and inhibits its target gene NDRG1 at both the mRNA and protein levels. At the protein level, NDRG1-OT1 increases NDRG1 degradation via ubiquitin-mediated proteolysis. However, the repressive mechanism of NDRG1 at the RNA level is still unknown. Therefore, the purpose of this study was to study how NDRG1-OT1 transcriptionally regulates its target gene NDRG1. Luciferase reporter assays showed that NDRG1-OT1 decreased NDRG1 promoter activities. Mass spectrometry, bioinformatics tools, genetic manipulation, and immunoblotting were used to identify the interacting proteins. Surprisingly, different fragments of NDRG1-OT1 had opposite effects on NDRG1. The first quarter fragment (1-149 nt) of NDRG1-OT1 had no effect on the NDRG1 promoter; the second quarter fragment (150-263 nt) repressed NDRG1 by increasing the binding affinity of HNRNPA1; the third quarter fragment (264-392 nt) improved NDRG1 promoter activity by recruiting HIF-1α; the fourth quarter fragment (393-508 nt) down-regulated NDRG1 promoter activity via down-regulation of KHSRP under hypoxia. In summary, we have found a novel mechanism by which different fragments of the same lncRNA can cause opposite effects within the same target gene.


Assuntos
Neoplasias da Mama/genética , Proteínas de Ciclo Celular/genética , Hipóxia/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , RNA Longo não Codificante/genética , Transcrição Gênica , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Genes Reporter , Humanos , Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Conformação de Ácido Nucleico , Regiões Promotoras Genéticas , Ligação Proteica , RNA Longo não Codificante/química , Proteínas de Ligação a RNA/genética , Transativadores/genética
8.
Front Med (Lausanne) ; 10: 1135586, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37636568

RESUMO

Background: The aim of this study was to investigate the relationship between pneumonia and chronic kidney disease (CKD), to elucidate potential risk factors, and to develop a new predictive model for the poor prognosis of pneumonia in CKD patients. Method: We conducted a retrospective observational study of CKD patients admitted to Tongji Hospital between June 2012 and June 2022. Demographic information, comorbidities or laboratory tests were collected. Applying univariate and multivariate logistic regression analyses, independent risk factors associated with a poor prognosis (i.e., respiratory failure, shock, combined other organ failure, and/or death during hospitalization) for pneumonia in CKD patients were discovered, with nomogram model subsequently developed. Predictive model was compared with other commonly used pneumonia severity scores. Result: Of 3,193 CKD patients with pneumonia, 1,013 (31.7%) met the primary endpoint during hospitalization. Risk factors predicting poor prognosis of pneumonia in CKD patients were selected on the result of multivariate logistic regression models, including chronic cardiac disease; CKD stage; elevated neutrophil to lymphocyte ratio (NLR) and D-dimer; decreased platelets, PTA, and chloride iron; and significant symptom presence and GGO presentation on CT. The nomogram model outperformed other pneumonia severity indices with AUC of 0.82 (95% CI: 0.80, 0.84) in training set and 0.83 (95% CI: 0.80, 0.86) in testing set. In addition, calibration curve and decision curve analysis (DCA) proved its efficiency and adaptability. Conclusion: We designed a clinical prediction model PNPI (pneumonia in nephropathy patients prognostic index) to assess the risk of poor prognosis in CKD patients with pneumonia, which may be generalized after more external validation.

9.
Lung Cancer ; 178: 198-205, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36871344

RESUMO

INTRODUCTION: Circulating tumor cells (CTCs) and their proliferative ability in lung adenocarcinoma (LUAD) were not well-investigated. We developed a protocol combining an efficient viable CTC isolation and in-vitro cultivation for the CTC enumeration and proliferation to evaluate their clinical significance. METHOD: The peripheral blood of 124 treatment-naïve LUAD patients were processed by a CTC isolation microfluidics, DS platform, followed by in-vitro cultivation. LUAD-specific CTCs were defined by immunostaining of DAPI+/CD45-/(TTF1/CK7)+ and were enumerated upon isolation and after 7-day cultivation. The CTC proliferative ability was evaluated by both the cultured number and the culture index, a ratio of cultured CTC number to the initial CTC number in 2 mL of blood. RESULT: All but two LUAD patients (98.4%) were detected with at least one CTC per 2 mL of blood. Initial CTC numbers did not correlate with metastasis (75 ± 126 for non-metastatic, 87 ± 113 for metastatic groups; P = 0.203). In contrast, both the cultured CTC number (mean: 28, 104, and 185 in stage 0/I, II/III, and IV; P < 0.001), and the culture index (mean: 1.1, 1.7 and 9.3 in stage 0/I, II/III, and IV; P = 0.043) were significantly correlated with the stages. Overall survival analysis within the non-metastatic group (N = 53) showed poor prognosis for patients with elevated cultured counts (cutoff ≥ 30; P = 0.027). CONCLUSION: We implemented a CTC assay in clinical LUAD patients with a high detection rate and cultivation capability. Cultured CTC count and proliferative ability, rather than the crude CTC numbers, highly associated with cancer prognosis.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Células Neoplásicas Circulantes , Humanos , Células Neoplásicas Circulantes/patologia , Prognóstico , Neoplasias Pulmonares/patologia , Análise de Sobrevida , Biomarcadores Tumorais
10.
Clin Kidney J ; 15(4): 718-726, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35371462

RESUMO

Background: The relationship between intake of sugar-sweetened beverages (SSBs) and the risk of death in patients with chronic kidney disease (CKD) is unclear. We evaluated the association between SSB intake and subsequent overall mortality in CKD patients. Methods: We included data from 3996 CKD patients who participated in the 1999-2014 National Health and Nutrition Examination Survey (NHANES). SSB intake was assessed by a 24-h dietary recall, grouped as none, >0 to <1 serving/day, 1 to <2 servings/day and ≥2 servings/day. After adjusting for demographic variables, lifestyle, diet and comorbidities, Cox proportional risk regressions were applied to analyze the associations between the daily intake of SSBs as well as added sugar from beverages and all-cause mortality. Results: In the whole research population, the median age at baseline was 67 years, 22% were Black and 54% were female. A total of 42% had stage 3 CKD. During an average follow-up period of 8.3 years, a sum of 1137 (28%) deaths from all causes was recorded. The confounder-adjusted risk of mortality was associated with an increase of 1 serving/day of SSBs, with all-cause mortality of 1.18 [95% confidence interval (95% CI)1.08-1.28], and intakes of increased 20-g added sugar/1000 kcal of total energy per day were associated with all-cause mortality of 1.14 (1.05-1.24). Equivalently substituting 1 serving/day of SSBs with unsweetened coffee [HR (95% CI) 0.82 (0.74-0.91)], unsweetened tea [HR (95% CI) 0.86 (0.76-0.98)], plain water [HR (95% CI) 0.79 (0.71-0.88)], or non- or low-fat milk [HR (95% CI) 0.75 (0.60-0.93)] were related to a 14-25% reduced risk of all-cause mortality. Conclusion: Findings suggest that in the CKD population, increased SSB intake was associated with a higher risk of mortality and indicated a stratified association with dose. Plain water and unsweetened coffee/tea might be possible alternatives for SSBs to avert untimely deaths.

11.
Front Med (Lausanne) ; 9: 823835, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35372385

RESUMO

Background: Chronic kidney disease (CKD) in women is often accompanied by hormone disorders such as sex hormones, and most women with CKD are in the post-menopausal age group. Due to the close relationship between menopause and sex hormones, we aimed to explore the association between early menopause and CKD in post-menopausal women, and the influence of early menopause on longevity in the CKD population. Methods: Information regarding 4,945 post-menopausal women was extracted from the database of the National Health and Nutrition Examination Survey (NHANES) 1999-2014, and then divided into 4 groups according to the type of menopause (natural or surgical) and early menopause (menopause at age <45) or not. The association between early menopause and CKD prevalence was examined using multivariable logistic regression, while we used multivariable Cox proportional hazards models to investigate the possible relationship between early menopause and all-cause mortality in CKD and non-CKD populations. The differences in the levels of sex hormones between women with and without CKD were also explored. Results: Compared with women with natural menopause at age ≥45, women experiencing early natural menopause had a higher risk of CKD [OR = 1.26 (1.01-1.56)]. Similarly, as compared to women with surgical menopause at age ≥ 45, women in the early surgical menopause group were more likely to have CKD [OR = 1.38 (1.05-1.81)]. In addition, early surgical menopause was associated with higher mortality in the non-CKD group [HR = 1.62 (1.06-2.49)], but not in the CKD group. Women with CKD had a higher level of luteinizing hormone and follicle-stimulating hormone, combined with a lower level of testosterone and estradiol than the non-CKD women. Conclusion: Both early natural and surgical menopause were associated with a higher risk of CKD. Early surgical menopause was a hazard factor for survival in the non-CKD group, but not in the CKD group. Further research is required to understand the mechanisms.

12.
Kidney Dis (Basel) ; 7(5): 391-400, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34604345

RESUMO

BACKGROUND: The relationship between marital status and CKD is rarely studied. We aimed to explore the effect of marital status on the depression and mortality of patients with CKD. METHODS: The data sources came from the NHANES database during 2005-2014 and 3,865 participants were included in this study. We used logistic regression models to examine the relationship between marital status and depression of CKD patients. The Cox proportional hazard models were used to evaluate the association between marital status and mortality of CKD patients. RESULTS: In terms of depression in CKD patients, unmarried patients had a worse situation than married patients. Meanwhile, after adjusting the covariables, unmarried patients had increased risk of depression (OR = 1.26, 95% CI: 1.01-1.57) compared with married CKD patients, especially in males (OR = 1.45, 95% CI: 1.02-2.06) and patients with more than college education level (OR = 12.4, 95% CI: 3.75-41.02). There was a significant relationship between marital status and mortality of general CKD patients (HR = 1.36, 95% CI: 1.17-1.58). Moreover, marriage showed a protective effect against death among male patients, patients with school graduate or less and more than college educational level, patients with high income, and patients in different estimated glomerular filtration rate groups. CONCLUSIONS: The use of large numbers of participants has revealed the effect of marital status on CKD patients. Unmarried ones had a higher risk of depression than married ones among CKD patients. Meanwhile, the risk of death was higher in unmarried ones than married ones among CKD patients in this study.

13.
Front Med (Lausanne) ; 8: 803929, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35211487

RESUMO

BACKGROUND: Tertiary lymphoid organs play an essential role in the inflammation of the kidney. The clinical association between TLOs and membranous nephropathy (MN) is not clear yet. METHODS: Consecutive patients with the histologically confirmed membranous nephropathy in Tongji Hospital from July 19, 2012, to September 26, 2019, were included in this study. TLOs in renal biopsy tissues were detected by periodic acid-Schiff-stained and immunohistochemistry. Logistic regression was performed to evaluate the correlations of TLOs and clinical features of patients with MN. Kaplan-Meier analysis was utilized to examine the relationship between TLOs and remission of proteinuria. RESULTS: A total of 442 patients with MN were included in this study, of which the average age was 46.4 years old, and 58.8% were male. Moreover, 33% of patients with MN had TLOs in this study. The median value of proteinuria among patients with MN with TLOs was 4.9 g/24 h, which was much greater than no-TLOs ones (3.2 g/24 h, p < 0.001). Moreover, the patients with TLOs had higher serum creatinine and lower serum albumin. The severity of clinical features among the patients with MN aggravated with the increase in the grade of TLOs. In addition, the patients who had TLOs were more likely to be positive of anti-phospholipase A2 receptor autoantibodies. Meanwhile, the patients without TLOs showed significantly higher complete remission and total remission of proteinuria. CONCLUSION: In this study, we demonstrated that TLOs were common among patients with MN. Moreover, the patients with MN with TLOs showed a worse clinical manifestation and an outcome compared with the patients without TLOs.

14.
Front Oncol ; 11: 663114, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34141617

RESUMO

Long non-coding RNAs (lncRNAs) have been found to participate in multiple genetic pathways in cancer. Also, mitochondria-associated lncRNAs have been discovered to modulate mitochondrial function and metabolism. Previously, we identified oxygen-responsive lncRNAs in MCF-7 breast cancer cells under different oxygen concentrations. Among them, a novel mitochondria-encoded lncRNA, mitochondrial oxygen-responsive transcript 1 (MTORT1), was chosen for further investigation. Nuclear, cytoplasmic, and mitochondrial fractionation assays were performed to evaluate the endogenous expression levels of MTORT1 in breast cancer cells. In vitro proliferation and migration assays were conducted to investigate the functions of MTORT1 in breast cancer cells by knockdown of MTORT1. RNA immunoprecipitation and luciferase reporter assays were used to examine the physical binding between MTORT1 and microRNAs. Our results showed that MTORT1 had low endogenous expression levels in breast cancer cells and was mainly located in the mitochondria. Knockdown of MTORT1 enhanced cell proliferation and migration, implying a tumor suppressor role of this novel mitochondrial lncRNA. MTORT1 served as sponge of miR-26a-5p to up-regulate its target genes, CREB1 and STK4. Our findings shed some light on the characterization, function, and regulatory mechanism of the novel hypoxia-induced mitochondrial lncRNA MTORT1, which functions as a microRNA sponge and may inhibit breast cancer progression. These data suggest that MTORT1 may be a candidate for therapeutic targeting of breast cancer progression.

15.
Ann Transl Med ; 8(6): 381, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32355825

RESUMO

BACKGROUND: There are few non-invasive biomarkers that have been identified to improve the risk stratification of patients with IgA nephropathy (IgAN). CXCL16 has been shown to play a key role as a chemoattractant, adhesion, and fibrosis factor in inflammatory disease. This study evaluated the potential for CXCL16 plasma as a potential biomarker in patients with IgAN. METHODS: Plasma CXCL16 was measured in 230 patients with renal biopsied IgAN enrolled from 2012 to 2014. The patients were followed for 41.3 months, with a 50% reduction in estimated glomerular filtration rate or end-stage renal disease as endpoints. RESULTS: The plasma CXCL16 levels in IgAN patients were strongly correlated with the uric acid, estimated glomerular filtration rate and tubular atrophy/interstitial fibrosis score in multivariate analysis. Furthermore, counts of CD4+ T cells, CD8+ T cells, and CD20+ B cells in renal biopsies of IgAN patients were significantly correlated with the plasma CXCL16 levels, but not CD68+ macrophage. Lastly, we concluded that patients with higher levels of plasma CXCL16 had an increased risk of poor renal outcome compared to those with lower levels. There was no association between the polymorphisms and clinical parameters of CXCL16, including the levels and prognosis of plasma CXCL16. CONCLUSIONS: Plasma CXCL16 levels were associated with clinical parameters; pathological damage; CD4+ T cell, CD8+ T cell, and CD20+ B cell infiltration in renal tissue; and renal outcome in IgAN patients. Plasma CXCL16 might be a potential prognosis predictor in Chinese IgAN patients.

16.
Psychosomatics ; 50(5): 538-42, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19855041

RESUMO

BACKGROUND: Although rare, psychosis can emerge during interferon (IFN)-alpha therapy and persist after therapy is completed. OBJECTIVE: The authors report the case of a 30-year-old man with hepatitis C infection treated with IFN-alpha and ribavirin who developed acute psychosis with persecutory delusions and auditory hallucinations, resulting in a suicide attempt. METHOD: The patient was treated with amisulpride for 6 weeks and then with risperidone for 6 weeks. RESULTS: There was no improvement in symptoms until the patient was treated with quetiapine; he then had a marked recovery from the psychotic symptoms. The duration of the psychosis was 28 weeks. CONCLUSION: Hepatitis C can be successfully treated with IFN therapy, and the risk of IFN-induced psychosis is low, with psychotic symptoms resolving in most cases after completion of IFN therapy with or without antipsychotic treatment. In prolonged psychosis induced by IFN, quetiapine might also be of benefit.


Assuntos
Antivirais/efeitos adversos , Hepatite C/tratamento farmacológico , Interferon-alfa/efeitos adversos , Psicoses Induzidas por Substâncias/etiologia , Adulto , Antipsicóticos/uso terapêutico , Antivirais/uso terapêutico , Delusões/induzido quimicamente , Delusões/tratamento farmacológico , Dibenzotiazepinas/uso terapêutico , Alucinações/induzido quimicamente , Alucinações/tratamento farmacológico , Humanos , Interferon-alfa/uso terapêutico , Masculino , Psicoses Induzidas por Substâncias/tratamento farmacológico , Fumarato de Quetiapina , Tentativa de Suicídio
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