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1.
Brain Behav Immun ; 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33932528

RESUMO

In depression, continual activation of the hypothalamic-pituitary-adrenal (HPA) axis with excess cortisol release leads to impair sensitivity of the glucocorticoid receptor (GR) and increase activity of the pro-inflammatory immune responses. Aberrant expression of GR has been associated with inflammation in patients with major depressive disorder (MDD). Our previous studies showed that the aberrant expression of TNFAIP3 gene, which encodes the NF-κB regulatory protein A20, TNFAIP3-associated proteins and Toll-like receptors (TLRs) are involved in inflammation-associated depression. However, the link between desensitization of GR actions and negative regulation of the TLRs-mediated inflammatory pathway in MDD is yet to be established. Here, we examined the association of depression severity, measured via the 17-item Hamilton Depression Rating Scale (HAMD-17), with the mRNA expression profiling of GRα, GRß, TNFAIP3-interacting proteins (TNIP), including TNIP1, TNIP2, and TNIP3, and TNFAIP3-like proteins, such as cezanne1, cezanne2, trabid, and valosin-containing protein p97/p47 complex-interacting protein p135 (VCIP135), in monocytes from 69 patients with MDD and 42 healthy controls. Herein we found the mRNA expressions of GRß and TNIP2 were significantly higher in monocytes from patients with MDD. Notably, TNIP2 level was positively correlated with the GRß expression and severity of depression, as determined via Pearson's correlation analysis. Mechanistically, we demonstrated that overexpression of GRß promotes the mRNA levels of TNIP2 and tumor necrosis factor alpha (TNF-α) in human monocytes. The promoting effect of GRß on TNF-α expression was partially attenuated upon depletion of TNIP2, suggesting that TNIP2 was required for GRß-mediated enhancement of TNF-α levels. Together, these results suggest that activation of GRß/TNIP2/TNF-α axis may induce inflammation in MDD patients and targeting this newly identified pathway may help in the development of better therapeutic approaches to reduce the development of MDD.

2.
Taiwan J Obstet Gynecol ; 60(2): 335-340, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33678338

RESUMO

OBJECTIVE: We present prenatal diagnosis of a 15q11.2-q14 deletion of paternal origin associated with increased nuchal translucency (NT), mosaicism for de novo multiple unbalanced translocations involving 15q11-q14, 5qter, 15qter, 17pter and 3qter, and Prader-Willi syndrome (PWS). CASE REPORT: A 32-year-old, primigravid woman underwent amniocentesis at 18 weeks of gestation because of an increased NT thickness of 5.6 mm and abnormal maternal serum screening results in the first trimester. The pregnancy was conceived by in vitro fertilization and embryo transfer. Amniocentesis revealed a karyotype of 45,XX,der(5)t(5;15)(q35;q14),-15 [16]/45,XX,-15,der(17)t(15;17)(q14;p13)[3]/45,XX,der(15)t(15;15)(q35;q14),-15[2]. The parental karyotypes were normal. Prenatal ultrasound findings were unremarkable. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from cultured amniocytes revealed the result of arr 15q11.2q14 (22,765,628-38,651,755) × 1.0 [GRCh37 (hg19)] with a 15.886-Mb 15q11.2-q14 deletion encompassing TUBGCP5, CYFIP1, NIPA2, NIPA1, SNRPN, SNURF, SNORD116-1, IPW, UBE3A, ACTC1 and MEIS2. The pregnancy was subsequently terminated, and a malformed fetus with facial dysmorphism was delivered. The cord blood had a karyotype of 45,XX,der(5)t(5;15)(q35;q14),-15[46]/45,XX,der(3)t(3;15) (q29;q14),-15[2]/45,XX,-15,der(17)t(15;17)(q14;p13)[2]. The placenta had a karyotype of 45,XX,der(5) t(5;15)(q35;q14),-15. Polymorphic DNA marker analysis confirmed a paternal origin of the proximal 15q deletion. CONCLUSION: Increased NT and abnormal maternal serum screening results may prenatally be associated with PWS. Chromosome 15 rearrangements in PWS include mosaicism for de novo multiple unbalanced translocations.

3.
Taiwan J Obstet Gynecol ; 59(5): 754-757, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32917331

RESUMO

OBJECTIVE: We present perinatal molecular cytogenetic analysis of low-level mosaicism for trisomy 21 in a pregnancy with maternal uniparental disomy (UPD) of chromosome 21 in the fetus. CASE REPORT: A 39-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XX,+21[6]/46,XX[25]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed arr (21) × 2-3, (X) × 2 with about 18% gene dosage increase in chromosome 21 consistent with mosaic trisomy 21. Cordocentesis was performed at 20 weeks of gestation, and the cord blood lymphocytes had a karyotype of 47,XX,+21[3]/46,XX[72]. Prenatal ultrasound findings were unremarkable. After genetic counseling, the parents decided to continue the pregnancy. At 39 weeks of gestation, a 3,494-g phenotypically normal female baby was delivered without phenotypic features of Down syndrome. There was no dysplasia of middle phalanx of the fifth fingers of both hands. The cord blood had a karyotype of 47,XX,+21[2]/46,XX[48]. The placenta had a karyotype of 47,XX,+21[37]/46,XX[3]. The umbilical cord had a karyotype of 47,XX,+21[1]/46,XX[39]. aCGH analysis on the DNA extracted from cord blood revealed no genomic imbalance. Polymorphic DNA marker analysis on the DNAs extracted from cord blood and parental bloods revealed maternal uniparental heterodisomy 21 in the baby. Interphase fluorescence in situ hybridization analysis on buccal mucosal cells revealed trisomy 21 signals in 15/101 (14.9%) buccal cells at birth and in 1/122 (0.82%) buccal cells at age 45 days. CONCLUSION: Low-level mosaicism for trisomy 21 at amniocentesis associated with maternal UPD 21 in the fetus can have a favorable outcome.

4.
J Med Internet Res ; 22(5): e16443, 2020 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-32348254

RESUMO

BACKGROUND: Continuous photoplethysmography (PPG) monitoring with a wearable device may aid the early detection of atrial fibrillation (AF). OBJECTIVE: We aimed to evaluate the diagnostic performance of a ring-type wearable device (CardioTracker, CART), which can detect AF using deep learning analysis of PPG signals. METHODS: Patients with persistent AF who underwent cardioversion were recruited prospectively. We recorded PPG signals at the finger with CART and a conventional pulse oximeter before and after cardioversion over a period of 15 min (each instrument). Cardiologists validated the PPG rhythms with simultaneous single-lead electrocardiography. The PPG data were transmitted to a smartphone wirelessly and analyzed with a deep learning algorithm. We also validated the deep learning algorithm in 20 healthy subjects with sinus rhythm (SR). RESULTS: In 100 study participants, CART generated a total of 13,038 30-s PPG samples (5850 for SR and 7188 for AF). Using the deep learning algorithm, the diagnostic accuracy, sensitivity, specificity, positive-predictive value, and negative-predictive value were 96.9%, 99.0%, 94.3%, 95.6%, and 98.7%, respectively. Although the diagnostic accuracy decreased with shorter sample lengths, the accuracy was maintained at 94.7% with 10-s measurements. For SR, the specificity decreased with higher variability of peak-to-peak intervals. However, for AF, CART maintained consistent sensitivity regardless of variability. Pulse rates had a lower impact on sensitivity than on specificity. The performance of CART was comparable to that of the conventional device when using a proper threshold. External validation showed that 94.99% (16,529/17,400) of the PPG samples from the control group were correctly identified with SR. CONCLUSIONS: A ring-type wearable device with deep learning analysis of PPG signals could accurately diagnose AF without relying on electrocardiography. With this device, continuous monitoring for AF may be promising in high-risk populations. TRIAL REGISTRATION: ClinicalTrials.gov NCT04023188; https://clinicaltrials.gov/ct2/show/NCT04023188.


Assuntos
Fibrilação Atrial/diagnóstico , Aprendizado Profundo/normas , Fotopletismografia/métodos , Dispositivos Eletrônicos Vestíveis/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudo de Prova de Conceito , Estudos Prospectivos
5.
J Nutr Biochem ; 77: 108305, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31926453

RESUMO

Obese women have an approximately twofold higher risk to deliver an infant with neural tube defects (NTDs) despite folate supplementation. Placental transfer of folate is mediated by folate receptor alpha (FR-α), proton coupled folate transporter (PCFT), and reduced folate carrier (RFC). Decreased placental transport may contribute to NTDs in obese women. Serum folate levels were measured and placental tissue was collected from 13 women with normal BMI (21.9±1.9) and 11 obese women (BMI 33.1±2.8) undergoing elective termination at 8-22 weeks of gestation. The syncytiotrophoblast microvillous plasma membranes (MVM) were isolated using homogenization, magnesium precipitation, and differential centrifugation. MVM expression of FR-α, PCFT and RFC was determined by western blot. Folate transport capacity was assessed using radiolabeled methyl-tetrahydrofolate and rapid filtration techniques. Differences in expression and transport capacity were adjusted for gestational age and maternal age in multivariable regression models. P<.05 was considered statistically significant. Serum folate levels were not significantly different between groups. Placental MVM folate transporter expression did not change with gestational age. MVM RFC (-19%) and FR-α (-17%) expression was significantly reduced in placentas from obese women (P<.05). MVM folate transporter activity was reduced by-52% (P<.05) in obese women. These differences remained after adjustment for gestational age. There was no difference in mTOR signaling between groups. In conclusion, RFC and FR alpha expression and transporter activity in the placental MVM are significantly reduced in obese women in early pregnancy. These results may explain the higher incidence of NTDs in infants of obese women with adequate serum folate.

6.
Int J Mol Sci ; 20(23)2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31766662

RESUMO

This study was conducted to elucidate whether microRNA-29a (miR-29a) and/or together with transplantation of mesenchymal stem cells isolated from umbilical cord Wharton's jelly (uMSCs) could aid in skeletal muscle healing and putative molecular mechanisms. We established a skeletal muscle ischemic injury model by injection of a myotoxin bupivacaine (BPVC) into gastrocnemius muscle of C57BL/6 mice. Throughout the angiogenic and fibrotic phases of muscle healing, miR-29a was considerably downregulated in BPVC-injured gastrocnemius muscle. Overexpressed miR-29a efficaciously promoted human umbilical vein endothelial cells proliferation and capillary-like tube formation in vitro, crucial steps for neoangiogenesis, whereas knockdown of miR-29a notably suppressed those endothelial functions. Remarkably, overexpressed miR-29a profitably elicited limbic flow perfusion and estimated by Laser Dopple. MicroRNA-29a motivated perfusion recovery through abolishing the tissue inhibitor of metalloproteinase (TIMP)-2, led great numbers of pro-angiogenic matrix metalloproteinases (MMPs) to be liberated from bondage of TIMP, thus reinforced vascular development. Furthermore, engrafted uMSCs also illustrated comparable effect to restore the flow perfusion and augmented vascular endothelial growth factors-A, -B, and -C expression. Notably, the combination of miR29a and the uMSCs treatments revealed the utmost renovation of limbic flow perfusion. Amplified miR-29a also adequately diminished the collagen deposition and suppressed broad-wide miR-29a targeted extracellular matrix components expression. Consistently, miR-29a administration intensified the relevance of uMSCs to abridge BPVC-aggravated fibrosis. Our data support that miR-29a is a promising pro-angiogenic and anti-fibrotic microRNA which delivers numerous advantages to endorse angiogenesis, perfusion recovery, and protect against fibrosis post injury. Amalgamation of nucleic acid-based strategy (miR-29a) together with the stem cell-based strategy (uMSCs) may be an innovative and eminent strategy to accelerate the healing process post skeletal muscle injury.


Assuntos
Isquemia/metabolismo , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/metabolismo , Músculo Esquelético , Doenças Musculares , Neovascularização Fisiológica , Cordão Umbilical/metabolismo , Animais , Fibrose , Xenoenxertos , Humanos , Isquemia/genética , Isquemia/patologia , Isquemia/terapia , Masculino , Células-Tronco Mesenquimais/patologia , Camundongos , MicroRNAs/genética , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Doenças Musculares/genética , Doenças Musculares/metabolismo , Doenças Musculares/patologia , Doenças Musculares/terapia , Cordão Umbilical/patologia
7.
Taiwan J Obstet Gynecol ; 58(6): 859-863, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31759543

RESUMO

OBJECTIVE: We present detection of a familial 1q21.1 microdeletion and concomitant CHD1L mutation in a fetus with oligohydramnios and bilateral renal dysplasia on prenatal ultrasound. CASE REPORT: A 37-year-old, primigravid woman was referred for level II ultrasound examination at 16 weeks of gestation because of oligohydramnios. The parents were phenotypically normal, and there were no congenital malformations in the family. Prenatal ultrasound at 17 weeks of gestation revealed a fetus with fetal growth biometry equivalent to 16 weeks, oligohydramnios with an amniotic fluid index (AFI) of 1.4 cm and bilateral renal dysplasia without sonographic demonstration of bilateral renal arteries. The pregnancy was subsequently terminated, and a 137-g fetus was delivered without characteristic facial dysmorphism. Postnatal cytogenetic analysis of the umbilical cord and parental bloods revealed normal karyotypes. However, array comparative genomic hybridization (aCGH) analysis on the DNA extracted from the umbilical cord revealed a 2.038-Mb microdeletion of 1q21.1-q21.2 encompassing 11 [Online Mendelian Inheritance in Man (OMIM)] genes of PRKAB2, FMO5, CHD1L, BCL9, ACP6, GJA5, GJA8, GPR89B, NBPF14, TRN-GTT2-1 and NBPF20. The mother was found to carry the same microdeletion. A missense mutation of c.2353T > G, p.Ser785Ala in CHD1L was detected in the umbilical cord. The father was found to carry a heterozygous mutation of c.2353T > G, p.Ser785Ala in CHD1L. CONCLUSION: Fetuses with a 1q21.1 microdeletion and concomitant CHD1L mutation may present oligohydramnios and bilateral renal dysplasia on prenatal ultrasound.


Assuntos
Anormalidades Múltiplas/diagnóstico , DNA Helicases/genética , Proteínas de Ligação a DNA/genética , Túbulos Renais Proximais/anormalidades , Megalencefalia/diagnóstico , Mutação de Sentido Incorreto , Oligo-Hidrâmnio/diagnóstico , Ultrassonografia Pré-Natal/métodos , Anormalidades Urogenitais/diagnóstico , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/metabolismo , Adulto , Deleção Cromossômica , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 1/metabolismo , DNA/genética , DNA Helicases/metabolismo , Análise Mutacional de DNA , Proteínas de Ligação a DNA/metabolismo , Feminino , Humanos , Megalencefalia/genética , Megalencefalia/metabolismo , Oligo-Hidrâmnio/genética , Gravidez , Anormalidades Urogenitais/genética
8.
Cells ; 8(9)2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31480771

RESUMO

While androgen receptor (AR) and stress may influence the development of the major depressive disorder (MDD), the detailed relationship, however, remains unclear. Here we found loss of AR accelerated development of depressive-like behaviors in mice under chronic mild stress (CMS). Mechanism dissection indicated that AR might function via altering the expression of miR-204-5p to modulate the brain-derived neurotrophic factor (BDNF) expression to influence the depressive-like behaviors in the mice under the CMS. Adding the antiandrogen flutamide with the stress hormone corticosterone can additively decrease BDNF mRNA in mouse hippocampus mHippoE-14 cells, which can then be reversed via down-regulating the miR-204-5p expression. Importantly, targeting this newly identified AR-mediated miR-204-5p/BDNF/AKT/MAPK signaling with small molecules including 7,8-DHF and fluoxetine, all led to alter the depressive-like behavior in AR knockout mice under CMS exposure. Together, results from these preclinical studies conclude that decreased AR may accelerate the stress-induced MDD via altering miR-204-5p/BDNF/AKT/MAPK signaling, and targeting this newly identified signaling may help in the development of better therapeutic approaches to reduce the development of MDD.


Assuntos
Depressão/genética , Receptores Androgênicos/genética , Estresse Psicológico/genética , Antagonistas de Androgênios/farmacologia , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Corticosterona/sangue , Depressão/etiologia , Feminino , Flutamida/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/metabolismo , Receptores Androgênicos/deficiência , Estresse Psicológico/complicações
9.
Neuroimmunomodulation ; 26(3): 153-158, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31307045

RESUMO

OBJECTIVE: Elevated levels of pro-inflammatory cytokines, in particular tumor necrotic factor alpha (TNF-α), and abnormalities in negative regulation in Toll-like receptor (TLR) signaling pathways are associated with major depressive disorder (MDD). Previous research by our group disclosed lower expression of TNF-α-induced protein 3 (TNFAIP3), one of the negative regulators of the TLR4 signaling pathway, in depressive patients than in healthy controls. METHODS: In this study, we assessed the mRNA levels of TNFAIP3, TNFAIP3-interacting proteins (TNIP), including TNIP1, TNIP2, and TNIP3, and TNFAIP3-like proteins, such as cezanne1, cezanne2, trabid, and VCIP135, in TNF-α-secreting cells and examined their association with severity of depression using the 17-item Hamilton Depression Rating Scale (HAMD-17) scores from 30 MDD patients and 30 healthy controls. Twenty-six patients received a second assessment after treatment with antidepressants for 4 weeks. RESULTS: TNF-α-secreting cells displayed higher TNIP3 mRNA expression in MDD patients than in healthy controls before treatment, which was marginally decreased after antidepressant treatment. In addition, the TNIP2 level could be effectively applied to predict changes in HAMD scores after linear regression analysis. CONCLUSION: Our collective findings suggest that molecules associated with negative regulation of innate immunity are aberrantly expressed in patients with MDD and present potential therapeutic targets.


Assuntos
Transtorno Depressivo Maior/imunologia , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adulto , Idoso , Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/imunologia , Adulto Jovem
10.
JMIR Mhealth Uhealth ; 7(6): e12770, 2019 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-31199302

RESUMO

BACKGROUND: Wearable devices have evolved as screening tools for atrial fibrillation (AF). A photoplethysmographic (PPG) AF detection algorithm was developed and applied to a convenient smartphone-based device with good accuracy. However, patients with paroxysmal AF frequently exhibit premature atrial complexes (PACs), which result in poor unmanned AF detection, mainly because of rule-based or handcrafted machine learning techniques that are limited in terms of diagnostic accuracy and reliability. OBJECTIVE: This study aimed to develop deep learning (DL) classifiers using PPG data to detect AF from the sinus rhythm (SR) in the presence of PACs after successful cardioversion. METHODS: We examined 75 patients with AF who underwent successful elective direct-current cardioversion (DCC). Electrocardiogram and pulse oximetry data over a 15-min period were obtained before and after DCC and labeled as AF or SR. A 1-dimensional convolutional neural network (1D-CNN) and recurrent neural network (RNN) were chosen as the 2 DL architectures. The PAC indicator estimated the burden of PACs on the PPG dataset. We defined a metric called the confidence level (CL) of AF or SR diagnosis and compared the CLs of true and false diagnoses. We also compared the diagnostic performance of 1D-CNN and RNN with previously developed AF detectors (support vector machine with root-mean-square of successive difference of RR intervals and Shannon entropy, autocorrelation, and ensemble by combining 2 previous methods) using 10 5-fold cross-validation processes. RESULTS: Among the 14,298 training samples containing PPG data, 7157 samples were obtained during the post-DCC period. The PAC indicator estimated 29.79% (2132/7157) of post-DCC samples had PACs. The diagnostic accuracy of AF versus SR was 99.32% (70,925/71,410) versus 95.85% (68,602/71,570) in 1D-CNN and 98.27% (70,176/71,410) versus 96.04% (68,736/71,570) in RNN methods. The area under receiver operating characteristic curves of the 2 DL classifiers was 0.998 (95% CI 0.995-1.000) for 1D-CNN and 0.996 (95% CI 0.993-0.998) for RNN, which were significantly higher than other AF detectors (P<.001). If we assumed that the dataset could emulate a sufficient number of patients in training, both DL classifiers improved their diagnostic performances even further especially for the samples with a high burden of PACs. The average CLs for true versus false classification were 98.56% versus 78.75% for 1D-CNN and 98.37% versus 82.57% for RNN (P<.001 for all cases). CONCLUSIONS: New DL classifiers could detect AF using PPG monitoring signals with high diagnostic accuracy even with frequent PACs and could outperform previously developed AF detectors. Although diagnostic performance decreased as the burden of PACs increased, performance improved when samples from more patients were trained. Moreover, the reliability of the diagnosis could be indicated by the CL. Wearable devices sensing PPG signals with DL classifiers should be validated as tools to screen for AF.


Assuntos
Algoritmos , Fibrilação Atrial/diagnóstico , Aprendizado Profundo/tendências , Fotopletismografia/normas , Idoso , Fibrilação Atrial/fisiopatologia , Eletrocardiografia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fotopletismografia/instrumentação , Fotopletismografia/métodos , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Seul
11.
Cells ; 8(7)2019 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-31252530

RESUMO

Chronic inflammation and abnormalities in Toll-like receptor (TLR) signaling pathways are associated with major depressive disorder (MDD). Our previous work reported that impaired negative regulators for the TLR pathways are associated with MDD. This study aimed to assess the association between the severity of depression and the intracellular microRNAs that regulate TLR4 signaling in both peripheral blood mononuclear cells (PBMCs) and monocytes from MDD patients. The severity of MDD before and after antidepressant treatment was determined by the 17-item Hamilton Depression Rating Scale, and quantitative RT-PCR was used to measure the levels of intracellular regulatory microRNAs, including let-7e, miR-21-5p miR-145, miR-223, miR-146a, and miR-155, in PBMCs and monocytes isolated from 43 healthy controls and 84 patients with MDD before and after treatment with antidepressants. Assays of PBMCs showed that the levels of let-7e, miR-146a, and miR-155 were lower in MDD patients than in healthy controls and were significantly higher after than before treatment in the 69 patients who completed treatment with antidepressants for four weeks. Levels of miR-146a and miR-155 in monocytes were lower in MDD patients than in controls and were increased in the former after antidepressant treatment. Multiple linear regression analyses found that let-7e and miR-146a expression before treatment was inversely correlated with severity of depression, whereas miR-155 before treatment was directly correlated with severity of depression. These findings suggest that intracellular regulatory microRNAs which regulate TLR4 signaling are aberrantly expressed in patients with MDD and that these levels are ameliorated by antidepressant treatment.


Assuntos
Antidepressivos/farmacologia , Transtorno Depressivo Maior/genética , MicroRNAs/metabolismo , Adulto , Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/tratamento farmacológico , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Voluntários Saudáveis , Humanos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Monócitos/metabolismo , Escalas de Graduação Psiquiátrica , Índice de Gravidade de Doença , Transdução de Sinais/genética , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
12.
Int J Biol Macromol ; 131: 167-175, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30771390

RESUMO

Chitosan (300 kDa) was degraded by cellulase to chitosans with molecular weights (MWs) of 156, 72, 7.1, and 3.3 kDa and a chitooligosaccharide mixture (COS). Effects of these on NO secretion, cytokine production, and mitogen-activated protein kinase pathways in lipopolysaccharide (LPS)-induced murine RAW 264.7 macrophages were investigated. Larger chitosans (300, 156, 72 kDa) significantly inhibited NO production, whereas smaller chitosans (7.1 & 3.3 kDa, COS) increased NO production. The 156 and 72 kDa chitosans significantly inhibited TNF-α and IL-6 production, whereas the 7.1 kDa chitosan and COS significantly induced their production. The 156 and 72 kDa chitosans inhibited NF-κB activation and iNOS expression by binding to the CR3 (for 156 kDa chitosan), or CR3 and TLR4 receptor (for 72 kDa chitosan). The smaller chitosans (e.g. 7.1 kDa chitosan and COS) activated NF-κB and enhanced iNOS expression by binding to CD14, TLR4, and CR3 receptors to activate JNK signaling proteins.


Assuntos
Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Quitosana/química , Quitosana/farmacologia , Macrófagos/efeitos dos fármacos , Peso Molecular , Animais , Biomarcadores , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/imunologia , Ativação de Macrófagos/efeitos dos fármacos , Ativação de Macrófagos/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Modelos Biológicos , NF-kappa B/metabolismo , Óxido Nítrico/biossíntese , Fosforilação , Células RAW 264.7
13.
Taiwan J Obstet Gynecol ; 57(5): 636-643, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30342642

RESUMO

The presence of pelvic lymph node metastases is without doubt the most significant prognostic factor that determines recurrences and survival of women with early-stage cervical cancer. To avoid the underdiagnosis of lymph node metastasis, pelvic lymphadenectomy procedure is routinely performed with radical hysterectomy procedure. However, the pelvic lymphadenectomy procedure may not be necessary in most of these women due to the relatively low incidence of pelvic lymph node metastasis. The removal of large numbers of pelvic lymph nodes could also render non-metastatic irreversible damages for these women, including vessel, nerve, or ureteral injuries; formation of lymphocysts; and lymphedema. Over the past decades, the concept of sentinel lymph node biopsy has emerged as a popular and widespread surgical technique for the evaluation of the pelvic lymph node status in gynecologic malignancies. The histological status of sentinel lymph node should be representative for all other lymph nodes in the regional drainage area. If metastasis is non-existent in the sentinel lymph node, the likelihood of metastatic spread in the remaining regional lymph nodes is very low. Further lymphadenectomy is therefore not necessary for a patient with negative sentinel lymph nodes. Since the uterine cervix has several lymphatic drainage pathways, it is a challenging task to assess the distribution pattern of sentinel lymph nodes in women with early-stage cervical cancer. This review article will adapt the methodology proposed in these studies to systematically review sentinel lymphatic mapping among women with early-stage cervical cancer.


Assuntos
Linfonodos/patologia , Metástase Linfática/patologia , Biópsia de Linfonodo Sentinela , Neoplasias do Colo do Útero/patologia , Colo do Útero/patologia , Reações Falso-Negativas , Feminino , Humanos , Excisão de Linfonodo/efeitos adversos , Excisão de Linfonodo/métodos , Linfedema/etiologia , Estadiamento de Neoplasias , Pelve , Sensibilidade e Especificidade , Biópsia de Linfonodo Sentinela/métodos
14.
J Nutr Biochem ; 59: 136-141, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29986308

RESUMO

Folate deficiency in pregnancy is associated with neural tube defects, restricted fetal growth and fetal programming of diseases later in life. Fetal folate availability is dependent on maternal folate levels and placental folate transport capacity, mediated by two key transporters, Folate Receptor-α and Reduced Folate Carrier (RFC). We tested the hypothesis that intrauterine growth restriction (IUGR) is associated with decreased folate transporter expression and activity in isolated syncytiotrophoblast microvillous plasma membranes (MVM). Women with pregnancies complicated by IUGR (birth weight <3rd percentile, mean birth weight 1804±110 g, gestational age 35.7±0.61 weeks, n=25) and women delivering an appropriately-for gestational age infant (control group, birth weight 25th-75th centile, mean birth weight 2493±216 g, gestational age 33.9±0.95 weeks, n=19) were recruited and placentas were collected at delivery. MVM was isolated and folate transporter protein expression was measured using Western blot and transporter activity was determined using radiolabelled methyltetrahydrofolic acid and rapid filtration. Whereas the expression of FR-α was unaffected, MVM RFC protein expression was significantly decreased in the IUGR group (-34%, P<.05). IUGR MVM had a significantly lower folate uptake compared to the control group (-38%, P<.05). In conclusion, placental folate transport capacity is decreased in IUGR, which may contribute to the restricted fetal growth and intrauterine programming of childhood and adult disease. These findings suggest that continuation of folate supplementation in the second and third trimester is of particular importance in pregnancies complicated by IUGR.


Assuntos
Retardo do Crescimento Fetal/metabolismo , Receptor 1 de Folato/metabolismo , Placenta/citologia , Proteína Carregadora de Folato Reduzido/metabolismo , Adulto , Peso ao Nascer , Estudos de Casos e Controles , Membrana Celular/metabolismo , Regulação para Baixo , Feminino , Humanos , Recém-Nascido , Microvilosidades/efeitos dos fármacos , Microvilosidades/metabolismo , Placenta/metabolismo , Gravidez , Tetra-Hidrofolatos/farmacocinética , Trofoblastos/metabolismo
15.
Neuroimmunomodulation ; 25(1): 42-48, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29898456

RESUMO

OBJECTIVE: Changes in the brain's inflammatory status can lead to psychopathological responses, especially depression. Using animal models, recent studies have revealed that this pathology is due, in part, to innate immune responses of monocytes. METHODS: We focus on the involvement of Toll-like receptors (TLRs) and expression of genes encoding their negative regulators, SOCS1, TOLLIP, SIGIRR, MyD88s, NOD2, and TNFAIP3, in CD14+ monocytes from 34 patients with major depressive disorder (MDD) and 33 healthy controls before and after treatment with antidepressants. We also seek to investigate their association with depression severity, measured by the 17-item Hamilton Depression Rating Scale (HAMD-17). RESULTS: mRNA expression of all TLRs, except TLR3 and -5, was significantly higher in monocytes from patients with MDD than in those from controls. Conversely, the "brakes" in TLR signaling, including TOLLIP, MyD88s, NOD2, and TNFAIP3, were downregulated. In clinical findings, the remission group showed higher baseline TLR4 and lower baseline IRAK3 mRNA levels but only baseline elevated SOCS1 mRNA levels, which were inversely correlated with HAMD-17 scores, predicting worsened outcome in MDD patients. In addition, TNFAIP3 mRNA levels were increased by antidepressant treatment. CONCLUSION: Collectively, our findings suggest a role for dysregulation of TLR signaling in monocytes in MDD and identify a balancing effect of antidepressants on this dysregulation.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/tratamento farmacológico , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Receptores Toll-Like/fisiologia , Adulto , Antidepressivos/farmacologia , Transtorno Depressivo Maior/imunologia , Feminino , Seguimentos , Humanos , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/efeitos dos fármacos , Monócitos/imunologia , Monócitos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
16.
Biomedicine (Taipei) ; 8(1): 6, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29480801

RESUMO

Biliopleural fistula (BF) and formation of biliopleural effusion is a rare complication following percutaneous transhepatic biliary drainage (PTBD). It occurs when the pleura is traversed by the catheter before entering the bile duct. Biliopleural fistula should be suspected when right side pleural effusion develops following the PTBD procedure. The diagnosis of biliopleural fistula is made when greenish pleural fluid with high concentration of bilirubin is aspirated. Here we present a case where a patient develops a biliopleural fistula following PTBD due to obstructive jaundice caused by neuroendocrine tumor of pancreas. Biliopleural fistula was disclosed after a scheduled catheter replacement procedure. Treatments of biliopleural fistula include thoracentesis with drainage tube installation into pleural space. In addition, a drainage tube was installed through percutaneous transhepatic gallbladder drainage (PTGBD) to reduce the bile induced pressure. Surgical repair of fistula was performed after the conservative treatment was unsuccessful. The patient expired 5 days after surgery due to respiratory failure.

17.
Taiwan J Obstet Gynecol ; 56(6): 836-839, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29241930

RESUMO

OBJECTIVE: We present prenatal diagnosis of low-level mosaicism for tetrasomy 18p at amniocentesis in a pregnancy with a favorable outcome. CASE REPORT: A 40-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a de novo supernumerary isochromosome 18p in eight of 39 colonies of cultured amniocytes. The karyotype was 47,XX,+i(18)(p10)[8]/46,XX[31]. Array comparative genomic hybridization (aCGH) analysis using uncultured amniocytes revealed arr 18p11.32p11.21 [hg 19] (148,963-14,081,887) × 2-3. Repeat amniocentesis was performed at 20 weeks of gestation. Interphase fluorescence in situ hybridization (FISH) analysis showed four 18p11.22-specific probe (RP11-918F20) signals in 11.7% (12/103 cells) of uncultured amniocytes. aCGH analysis on uncultured amniocytes did not detect genomic imbalance in chromosome 18. The parental karyotypes were normal. Polymorphic DNA marker analysis excluded uniparental disomy 18. Cytogenetic analysis of cultured amniocytes at repeat amniocentesis revealed a karyotype of 47,XX,+i(18)(p10)[2]/46,XX[12]. Prenatal ultrasound was unremarkable. The pregnancy was carried to 38 weeks of gestation, and a 2742-g phenotypically normal female baby was delivered with a cord blood karyotype of 46,XX. When examined at 8 months of age, the infant was normal in growth and psychomotor development. Interphase FISH analysis on 21 uncultured urinary cells revealed normal signals in all cells and no mosaic tetrasomy 18p. CONCLUSION: Low-level mosaic tetrasomy 18p at amniocentesis without ultrasound abnormalities can be associated with a favorable outcome.


Assuntos
Amniocentese/métodos , Transtornos Cromossômicos/diagnóstico , Mosaicismo/embriologia , Adulto , Aneuploidia , Transtornos Cromossômicos/embriologia , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 18/genética , Hibridização Genômica Comparativa/métodos , Análise Citogenética/métodos , Feminino , Humanos , Hibridização in Situ Fluorescente/métodos , Recém-Nascido , Cariótipo , Nascimento Vivo , Idade Materna , Gravidez
18.
PLoS One ; 12(10): e0187156, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29073246

RESUMO

OBJECTIVE: Anti-N-methyl-D-aspartate receptor (NMDAR) antibody was thought to be the cause of anti-NMDAR encephalitis, with manifestations similar to catatonia and schizophrenia. Anti-NMDAR antibody in neuropsychiatric patients who had catatonia before were investigated in a follow-up evaluation. The intensity of antibody immunofluorescence was quantified and compared with healthy controls. METHOD: Nineteen patients (eight males and eleven females) agreed to be followed-up. Thirteen had the diagnosis of schizophrenia, two had the diagnosis of major depressive disorder, two had bipolar disorder, one had postpartum depression, and one had herpes simplex encephalitis. No patient had catatonia during the follow-up. Nineteen sex-matched healthy controls were recruited. RESULTS: Using Mann-Whitney U test, patients had greater intensity of anti-NMDAR antibody immunofluorescence than the healthy controls (121,979 ± 86,526 vs. 47,692 ± 26,102, p = 0.003). No correlation was found between immunofluorescence intensity and catatonia scales or symptom severity scores. Neuropsychiatric patients with past catatonia showed greater anti-NMDAR antibody response than the healthy controls. CONCLUSION: NMDAR dysfunction might play a role in the mechanism underlying catatonia. Further studies are needed to confirm this finding.


Assuntos
Autoanticorpos/sangue , Catatonia/imunologia , Transtornos Mentais/imunologia , Receptores de N-Metil-D-Aspartato/imunologia , Adulto , Estudos de Casos e Controles , Catatonia/sangue , Feminino , Humanos , Masculino , Transtornos Mentais/sangue , Pessoa de Meia-Idade
19.
Medicine (Baltimore) ; 96(22): e7089, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28562580

RESUMO

Increased prevalence of metabolic syndrome was found in patients with schizophrenia. Brain-derived neurotrophic factor (BDNF) was involved in energy metabolism and the pathophysiology of schizophrenia, but differently in males and females. We aimed to investigate the serum BDNF levels in patients with schizophrenia with and without metabolic syndrome.Patients with schizophrenia were recruited. Their demographic data were collected. Metabolic profiles and serum BDNF levels were measured. Clinical symptoms were evaluated with Positive and Negative Syndrome Scale. Metabolic syndrome was determined with the criteria provided by Ministry of Health and Welfare of Taiwan. Framingham Risk Score (FRS) for estimate of 10-year risk for coronary heart disease was provided by National Institutes of Health.Of the 81 participants, 40.7% had metabolic syndrome. Those with metabolic syndrome had higher FRS. Using analysis of covariance adjusted for age and body mass index, male patients with schizophrenia with metabolic syndrome had higher serum BDNF levels than those without (4.6 ±â€Š4.7 vs 3.3 ±â€Š3.8 ng/mL, P = .022). No statistical difference was found between female patients with and without metabolic syndrome.Significant differences of serum BDNF levels were found between male patients with schizophrenia with and without metabolic syndrome, but not in females. This finding suggested the gender difference behind the mechanism of BDNF in metabolic syndrome in schizophrenia.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/sangue , Síndrome Metabólica/sangue , Síndrome Metabólica/complicações , Esquizofrenia/sangue , Esquizofrenia/complicações , Adulto , Fatores Etários , Idoso , Análise de Variância , Biomarcadores/sangue , Análise Química do Sangue , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Índice de Gravidade de Doença , Fatores Sexuais , Adulto Jovem
20.
PLoS One ; 12(1): e0170452, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28114315

RESUMO

OBJECTIVE: The lorazepam-diazepam protocol had been proved to rapidly and effectively relieve catatonia in patients with schizophrenia or mood disorder. This study aims to investigate the efficacy of lorazepam-diazepam protocol in catatonia due to general medical conditions (GMC) and substance. METHOD: Patients with catatonia that required psychiatric intervention in various settings of a medical center were included. The lorazepam-diazepam protocol had been used to treat the catatonia due to GMC or substance according to DSM-IV criteria. The treatment response had been assessed by two psychiatrists. RESULTS: Eighteen (85.7%) of 21 catatonic patients due to GMC or substance became free of catatonia after the lorazepam-diazepam protocol. Five (23.8%) of the 21 patients had passed away with various causes of death and wide range of time periods after catatonia. CONCLUSION: Our results showed that the lorazepam-diazepam protocol could rapidly and effectively relieve catatonia due to GMC and substance.


Assuntos
Catatonia/tratamento farmacológico , Diazepam/administração & dosagem , Lorazepam/administração & dosagem , Adulto , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
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