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1.
Int J Hematol ; 2020 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-32712863

RESUMO

A 66-year-old woman had experienced abnormal bleeding since the age of 7. Thrombocytopenia was not detected until she was 48, and immune thrombocytopenia was diagnosed at age 66. She also reported experiencing hearing disturbance since the age of 30 and acute renal failure since the age of 61 but reported no visual disturbance. Her younger son, who was 40 years old, also experienced abnormal bleeding since the age of 6, but immune thrombocytopenia was diagnosed as late as age 35. He had no other associated disorders. Laboratory examinations of both mother and son revealed a low platelet count (8000 and 29,000 µL, respectively), giant platelets and Döhle body-like granulocyte inclusion bodies. The mother had a high creatinine level (15.4 mg/dL) and normal liver enzyme levels. MYH9 genetic analysis identified a heterozygous mutation, c.101T>A, p.Val34Glu at exon 2 in both patients. These clinical and laboratory findings were consistent with a diagnosis of an MYH9-related disorder with different phenotypes observed in the same family. MYH9-related disorders were recognised in 2003, but were often misdiagnosed as immune thrombocytopenia, and hence, they have rarely been reported in Taiwan.

2.
Dig Dis Sci ; 2020 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-32654086

RESUMO

INTRODUCTION: In hepatitis C (HCV) patients, obesity and/or diabetes may increase the risk of liver-related outcomes. We aimed to determine whether diabetes and/or obesity are associated with adverse outcomes in direct-acting antiviral (DAA)-treated HCV patients. METHODS: We conducted a retrospective study of 33,003 HCV-infected, DAA-treated Veterans between 2013 and 2015. Body mass index was used to categorize patients into underweight (< 18.5 kg/m2), normal weight (18.5 to < 25 kg/m2), overweight (25 to < 30 kg/m2), obesity I (30 to < 35 kg/m2), and obesity II-III (> 35 kg/m2). Diabetes was defined by ICD-9/10 codes in association with hemoglobin A1c > 6.5% or medication prescriptions. Patients were followed from 180 days post-DAA initiation until 2/14/2019 to assess for development of cirrhosis, decompensations, hepatocellular carcinoma (HCC), and death. Multivariable Cox proportional hazards regression models were used to determine the association between diabetes and/or obesity and outcomes. RESULTS: During a mean follow-up of 3 years, 10.1% patients died, 5.0% were newly diagnosed with cirrhosis, 4.7% had a decompensation and 4.0% developed HCC. Diabetes was associated with an increased risk of mortality (AHR = 1.25, 95% CI 1.10-1.42), cirrhosis (AHR = 1.31, 95% CI 1.16-1.48), decompensation (AHR = 1.74, 95% CI 1.31-2.31), and HCC (AHR = 1.32, 95% CI 1.01-1.72) among patients without baseline cirrhosis. Compared to normal-weight persons, obese persons had a higher risk of cirrhosis, but overweight and obese persons had lower risk of mortality and HCC. CONCLUSIONS: In this large DAA-treated Veterans cohort, pre-DAA diabetes increases mortality and liver-related events independent of SVR. Continued vigilance is warranted in patients with diabetes despite SVR. Elevated BMI categories appear to have improved outcomes, although further studies are needed to understand those associations.

3.
Reprod Fertil Dev ; 32(11): 967-975, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32693909

RESUMO

Lipid droplets (LDs) are reservoirs of arachidonoyl lipids for prostaglandin (PG) E2 synthesis, and progesterone can stimulate PGE2 synthesis; however, the relationship between progesterone and LD metabolism in the murine cervix remains unclear. In the present study we examined LD distribution and changes in the expression of proteins involved in lipolysis and autophagy in the murine cervix during pregnancy, and compared the findings with those in dioestrous mice. During mid-pregnancy, LDs were predominantly distributed in the cervical epithelium. Electron microscopy revealed the transfer of numerous LDs from the basal to apical region in the luminal epithelium, marked catabolism of LDs, an elevated number of LDs and autophagosomes and a higher LD:mitochondrion size ratio in murine cervical epithelial cells (P<0.05). In addition, immunohistochemical and western blotting analyses showed significantly higher cAMP-dependent protein kinase, adipose triglyceride lipase and hormone-sensitive lipase expression, and a higher light chain 3 (LC3) II:LC3I ratio in the stroma and smooth muscles and, particularly, in murine cervical epithelial cells, during mid-pregnancy than late dioestrus. In conclusion, these results suggest that the enhanced lipolysis of LDs and autophagy in murine cervical tissues were closely related to pregnancy and were possibly controlled by progesterone because LD catabolism may be necessary for energy provision and PGE2 synthesis to maintain a closed pregnant cervix.

4.
Artif Cells Nanomed Biotechnol ; 48(1): 1047-1054, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32677473

RESUMO

Diabetic nephropathy (DN) is a common chronic complication of diabetes. In this study, we aimed to explore the potential role of lncRNA LINC-00162 in the pathogenic process of DN. LncRNA microarray analysis, real-time PCR, IHC computational analysis and luciferase assay were performed to explore the regulatory relationship among LINC00162, miR-383 and HDAC9. There was an obvious difference between T2D + DN and T2D - DN patients in their levels of eGRF and albuminuria. A significant difference was observed between T2D + DN and T2D - DN groups in terms of their LINC00162 expression. In particular, LINC00162 and HDAC9 were highly expressed, while miR-383 was lowly expressed in tissues derived from the T2D + DN group compared with those in tissues derived from the T2D - DN group. MiR-383 was able to bind to LINC00162, while HDAC9 was a direct downstream target of miR-383 with a complementary miR-383 binding site located in the 3' UTR of HDAC9. LINC00162 reduced miR-383 expression and further up-regulated HDAC9 expression, while miR-383 mimics reduced HDAC9 expression under a dose-dependent manner. In summary, we suggested for the first time that down-regulation of LINC00162 was associated with the development of DN in T2D via the up-regulation of miR-383 expression and reduction of HDAC9 expression.

5.
Gastric Cancer ; 2020 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-32500456

RESUMO

BACKGROUND: Early diagnosis of Peritoneal metastasis (PM) is clinically significant regarding optimal treatment selection and avoidance of unnecessary surgical procedures. Cytopathology plays an important role in early screening of PM. We aimed to develop a deep learning (DL) system to achieve intelligent cytopathology interpretation, especially in ascites cytopathology. METHODS: The original ascites cytopathology image dataset consists of 139 patients' original hematoxylin-eosin (HE) and Papanicolaou (PAP) Staining images. DL system was developed using transfer learning (TL) to achieve cell detection and classification. Pre-trained alexnet, vgg16, goolenet, resnet18 and resnet50 models were studied. Cell detection dataset consists of 176 cropped images with 6573 annotated cell bounding boxes. Cell classification data set consists of 487 cropped images with 18,558 and 6089 annotated malignant and benign cells in total, respectively. RESULTS: We established a novel ascites cytopathology image dataset and achieved automatically cell detection and classification. DetectionNet based on Faster R-CNN using pre-trained resnet18 achieved cell detection with 87.22% of cells' Intersection of Union (IoU) bigger than the threshold of 0.5. The mean average precision (mAP) was 0.8316. The ClassificationNet based on resnet50 achieved the greatest performance in cell classification with AUC = 0.8851, Precision = 96.80%, FNR = 4.73%. The DL system integrating the separately trained DetectionNet and Classificationnet showed great performance in the cytopathology image interpretation. CONCLUSIONS: We demonstrate that the integration of DL can improve the efficiency of healthcare. The DL system we developed using TL techniques achieved accurate cytopathology interpretation, and had great potential to be integrated into clinician workflow.

6.
Ying Yong Sheng Tai Xue Bao ; 31(5): 1496-1504, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32530226

RESUMO

We investigated the characteristics of plant species diversity in tree and shurb layers and the main influencing factors in different slope positions of a shady slope of degraded tiankeng talus. The results showed that there were 21 species in 17 genera and 13 families in the tree layer, and 20 species in 20 genera and 14 families in shrub layer in the south side of the Shenxiantang. Plant communities were subtropical moist coniferous and broad-leaved mixed forest. Micro-climate led to obvious vegetation variation between the pit and the pit slope at the tiankeng. The secondary collapse over the talus with mid-slope could conserve more water, which supported the water-demanding species in a high-quality niche. All the α diversity indices including Margalef (3.58), Shannon (2.47), Simpson (0.79) and Pielou (0.86) reached the maximum at the pit bottom edge with slight variability, and the maximum coefficient of variation was only 0.226. The ß diversity index fluctuated greatly among the pit-pit, slope-pit, bottom edge. The Routledge and Whilson-Shmida indices showed the trends of decrease-increase-decrease, with the maximum values of 15.95 and 1.20, respectively. Species turnover demonstrated the upward trend overall, and the number of co-species was decreased. Plant diversity on each slope position was mainly related to the contents of total nitrogen, total phosphorus, available phosphorus and organic carbon in soil. Soil was the most important factor leading to the difference among slope positions.


Assuntos
Ecossistema , Tálus , China , Florestas , Plantas , Solo
7.
Molecules ; 25(9)2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32353926

RESUMO

Salvia mltiorrhiza Bunge (SMB) is native to China, whose dried root has been used as medicine. A few chromatographic- or spectrometric-based methods have already been used to analyze the lipid-soluble components in SMB. However, the methodology of qNMR on the extracts of fresh SMB root has not been verified so far. The purpose of this study was to establish a fast and simple method to quantify the tanshinone I, tanshinone IIA, dihydrotanshinone, and cryptotanshinone in fresh Salvia Miltiorrhiza Bunge root without any pre-purification steps using 1H-NMR spectroscopy. The process is as follows: first, 70% methanol aqueous extracts of fresh Salvia Miltiorrhiza Bunge roots were quantitatively analyzed for tanshinone I, tanshinone IIA, dihydrotanshinone, and cryptotanshinone using 1H-NMR spectroscopy. Different internal standards were tested and the validated method was compared with HPLC. 3,4,5-trichloropyridine was chosen as the internal standard. Twelve samples of Salvia Miltiorrhiza Bunge were quantitatively analyzed by qNMR and HPLC respectively. Then, the results were analyzed by chemometric approaches. This NMR method offers a fast, stable, and accurate analysis of four ketones: tanshinone I, tanshinone IIA, dihydrotanshinone, and cryptotanshinone in fresh roots of Salvia Miltiorrhiza Bunge.

8.
Bioresour Technol ; 310: 123463, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32387978

RESUMO

This study investigated the effects of operational temperature on cathodic performances of five bioelectrochemical reactors operated in parallel at 25-7 °C, and on the biofilm microbial community at the end of tests. Compared with the anodic biofilm, the cathodic biofilm has high stability subjected to temperature shift in the aspect of cathode potentials, redox activities, and internal resistances. The maximum power density was reduced linearly with temperature at a rate of 1.1 W/m3 °C. The bacterial community at 7 °C cathodic biofilm was dominated by four phyla including Proteobacteria, Actinobacteria, Bacteroidetes and Firmicutes with percentages of 81.7%, 8.9%, 3.3% and 1.3%, and the predominant genera were affiliated with Azoarcus sp. (56.45%), Acidovorax sp. (7.32%), Rhodococcus sp. (5.02%), Halomonas sp. (2.6%). The most vigorous metabolism of cathodic biofilm at low temperature was proposed to be biosynthesis and energy generation. The cathodic biofilm has resilient microbial community to temperature challenges.


Assuntos
Fontes de Energia Bioelétrica , Bactérias , Biofilmes , Eletrodos , Temperatura
10.
J Pharm Sci ; 109(8): 2544-2552, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32446661

RESUMO

Thermo-sensitive polymer-modified liposomes are able to achieve site-specific delivery of drugs. In this work, thermo-sensitive polymers were synthesized by atomic transfer radical polymerization of N-isopropyl acrylamide (NIPAAm) and N,N-dimethyl acrylamide (DMAAm) using bromoisobutyryl distearoyl phosphoethanolamine (DSPE-Br) as initiator. The resulting PNIPAAm-DSPE and P(NIPAAm-DMAAm)-DSPE polymers were characterized using proton nuclear magnetic resonance, Fourier transform infrared, and ultraviolet-visible spectroscopy. PNIPAAm-DSPE and P(NIPAAm-DMAAm)-DSPE exhibit a lower critical solution temperature of 34.0 and 46.9°C in water, and 29.8 and 38.8°C in phosphate buffered saline, respectively. Paclitaxel-loaded thermo-sensitive liposomes were prepared using film hydration method, followed by post-insertion of P(NIPAAm-DMAAm)-DSPE into the liposome bilayer. Drug release of traditional and thermosensitive liposomes was comparatively studied at 37 and 40°C. The total release and release rate of thermosensitive liposomes at 40°C were much higher than those at 37°C. And drug release is higher for thermosensitive liposomes than for traditional liposomes because insertion of thermo-sensitive polymer chains affects the system's stability. MTT assay showed that thermo-sensitive liposomes present no cytotoxicity to L929 cells at the tested concentrations, and paclitaxel-loaded liposomes have significant cytotoxicity against A549 cancer cells. Therefore, it is concluded that P(NIPAAm-DMAAm)-DSPE modified thermo-sensitive liposomes could be promising as nano-carrier of antitumor drugs.

11.
Gut ; 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32229544

RESUMO

OBJECTIVE: Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are first-line agents for the treatment of chronic hepatitis B (CHB). Recent studies have challenged the assumption that these agents are equally effective at preventing hepatocellular carcinoma (HCC). We aimed to determine whether the risk of HCC and mortality differ in patients with CHB treated with ETV and TDF. DESIGN: We performed a retrospective cohort study of Veterans Affairs patients with CHB in the USA who initiated treatment with ETV or TDF between the dates of Food and Drug Administration approval of these medications and 1 January 2017. Multivariable Cox proportional hazards regression was used to determine the association between antiviral therapy and HCC risk as well as the risk of death or liver transplantation. Propensity score adjustment and competing risks analysis were performed. RESULTS: We identified 2193 ETV-treated and 1094 TDF-treated patients who were followed for a mean of 5.4 years. We found no difference in the risk of HCC in ETV-treated versus TDF-treated patients (adjusted HR (aHR) 1.00, 95% CI 0.76 to 1.32). Results were similar in propensity score adjusted and competing risks analysis, and in multiple sensitivity analyses. We also found no difference in the risk of death or liver transplantation (aHR 1.16, 95% CI 0.98 to 1.39). CONCLUSIONS: We found no difference in the risk of HCC between patients with CHB treated with ETV versus TDF. Our results support current guideline recommendations that both agents are appropriate first-line options for the treatment of CHB.

12.
Int J Hematol ; 112(2): 169-175, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32333264

RESUMO

Hereditary coagulation factor XI (FXI) deficiency is a rare bleeding disorder, but information on FXI deficiency in Taiwanese patients remains scarce. We evaluated clinical and genetic features of severe FXI deficiency patients in Taiwan. We collected clinical information and performed coagulation laboratory tests and genetic studies in ten unrelated Taiwanese families with severe FXI deficiency. FXI coagulation activity was assayed using a one-stage method. FXI antigen was determined using enzyme-linked immunosorbent assay. Underlying genetic mutations were evaluated using direct sequencing methods. Ten unrelated Taiwanese patients with hereditary FXI deficiency and variable bleeding tendencies were analyzed. Half of the patients were male. The most common bleeding manifestations were easy bruising (40%), bleeding after dental procedures (40%), and postoperative bleeding (33%). Two patients (20%) were asymptomatic. No correlation was found between bleeding manifestations and baseline FXI levels. Three novel mutations were identified: c.1322delT p.Lys442Cysfs*8, c.599G > C p.Cys200Ser, and IVS4 c.325 + 2del124. Two common mutations, c.1107C > T p.Tyr369* (40%) and c.841C > T p.Gln281* (30%), were also found. No correlation existed between bleeding and FXI activity, highlighting the difficulty in predicting FXI deficiency-related bleeding. Three novel FXI genetic mutations and two common mutations were identified, contributing to the known spectrum of FXI deficiency-related mutations.

13.
Int J Biol Macromol ; 154: 39-47, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32173435

RESUMO

Fully bio-based amphiphilic diblock copolymers were synthesized from hydroxypropyl methyl cellulose (HPMC) and amino-terminated poly(l-lactide) (PLLA) or poly(l-lactide-co-dl-lactide) (PLA) by reductive amination. The resulting HPMC-PLLA and HPMC-PLA copolymers with various hydrophobic block lengths were characterized by NMR, DOSY-NMR and FT-IR. Micelles were obtained by self-assembly of copolymers in aqueous medium. The micelles are spherical in shape, and the micelle size ranges from 150 to 180 nm with narrow distribution. The critical micelle concentration decreases with increasing PLA block length. Paclitaxel was loaded in micelles. Enhanced drug loading is obtained with increase of PLA block length. A biphasic release profile is observed with a burst of 40% followed by slower release up to 80%. MTT assay indicates the good cytocompatibility of HPMC-PLA micelles. SRB assay shows a significant cytotoxicity of paclitaxel-loaded micelles against SK-BR-3cells. It is thus concluded that bio-based HPMC-PLA block copolymers could be promising nano-carrier of anti-tumor drugs.

14.
Molecules ; 25(5)2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32150865

RESUMO

A series of benzimidazole-derived chalcones containing aromatic amide substituent were designed and synthesized. All of the chalcone compounds were tested for their in vitro antitumor activity against human cancer cell lines (HCT116, HepG2, A549, and CRL-5908). The antiproliferative activity of compounds 3, 6, 9, 14, 15, 16 against HCT116 cells was significantly better than that that of 5-Fluorouracil (IC50: 94.63 µM). The antitumor activity of these compounds showed obvious differences between the wild type HCT116 and mutant HCT116 (TP53-/-) cells. A preliminary mechanistic study suggested that these compounds act by upregulating the expression of TP53 protein in tumor cells without inhibiting the MDM2-TP53 interaction.

15.
Medicine (Baltimore) ; 99(11): e19040, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32176031

RESUMO

Traditional high ligation and stripping (THLS) is a routine operation for varicose veins. However, THLS is accompanied with postoperative subcutaneous ecchymosis and pain. In this current study, we aimed to explore the effect of tumescence solution (TS) combined with negative pressure wound therapy (NPWT) on the relief of subcutaneous ecchymosis and pain after THLS of great saphenous vein.A total of 180 patients receiving THLS were enrolled in group A, and 120 patients undergoing THLS and TS combined with NPWT were assigned into group B. The occurrences of subcutaneous ecchymosis and pain were recorded. Moreover, the total area of subcutaneous ecchymosis was estimated by the grid method. Visual analogue scale (VAS) score was used to assess the pain level of both groups.Preoperative characteristics were not significantly different between 2 groups. Postoperative ecchymosis occurred in 112 cases (62.2%) of group A and 41 cases (34.2%) of group B. The area of ecchymosis in group A (66.6 ±â€Š44.5) cm was larger than that in group B (25.2 ±â€Š19.9) cm. The number of patients without obvious pain in group A (57, 31.7%) was significantly less than that in group B (77, 64.2%) after operation. In addition, VAS score in group A (3.1 ±â€Š2.6) was higher than that in group B (2.2 ±â€Š1.9).In conclusion, the application of TS combined with NPWT in THLS can not only alleviate subcutaneous ecchymosis and pain, but also prevent the occurrence of subcutaneous ecchymosis and pain after operation. Therefore, it is conducive to postoperative recovery and is suitable for clinical application.


Assuntos
Equimose/terapia , Epinefrina/uso terapêutico , Tratamento de Ferimentos com Pressão Negativa/métodos , Ropivacaina/uso terapêutico , Veia Safena/cirurgia , Varizes/cirurgia , Adulto , Epinefrina/administração & dosagem , Feminino , Humanos , Masculino , Dor Pós-Operatória/terapia , Complicações Pós-Operatórias/terapia , Estudos Retrospectivos , Ropivacaina/administração & dosagem
16.
Am J Ind Med ; 63(5): 417-428, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32154609

RESUMO

BACKGROUND: Asthma-related health outcomes are known to be associated with indoor moisture and renovations. The objective of this study was to estimate the frequency of these indoor environmental quality (IEQ) factors in healthcare facilities and their association with asthma-related outcomes among workers. METHODS: New York City healthcare workers (n = 2030) were surveyed regarding asthma-related symptoms, and moisture and renovation factors at work and at home during the last 12 months. Questions for workplace moisture addressed water damage (WD), mold growth (MG), and mold odor (MO), while for renovations they addressed painting (P), floor renovations (FR), and wall renovations (WR). Regression models were fit to examine associations between work and home IEQ factors and multiple asthma-related outcomes. RESULTS: Reports of any moisture (n = 728, 36%) and renovations (n = 1412, 70%) at work were common. Workplace risk factors for asthma-related outcomes included the moisture categories of WD by itself, WD with MO (without MG), and WD with MG and MO, and the renovation category with the three factors P, FR, and WR. Reports of home IEQ factors were less frequent and less likely to be associated with health outcomes. Data analyses suggested that MG and/or MO at work and at home had a synergistic effect on the additive scale with a symptom-based algorithm for bronchial hyperresponsiveness. CONCLUSIONS: The current study determined that moisture and renovation factors are common in healthcare facilities, potentially putting workers at risk for asthma-related outcomes. More research is needed to confirm these results, especially prospective studies.

17.
Anticancer Agents Med Chem ; 20(6): 724-733, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32116203

RESUMO

BACKGROUND: The third-generation irreversible Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors (TKIs) inhibit the T790M mutation while sparing EGFRWT. However, the C797S point mutation confers resistance to existing irreversible EGFRT790M inhibitors. OBJECTIVE: Novel EGFRT790M inhibitors were designed through hybridization of quinoline and anilinopyrimidine, and biologically evaluated their antiproliferative activity against Non-Small Cell Lung Cancer (NSCLC) cell lines. METHODS: The target compounds 11a-h were synthesized and structurally characterized with 1H, 13C Nuclear Magnetic Resonance (NMR) spectroscopy and High-Resolution Mass Spectrometry (HRMS). Their inhibitory effects on tumor cell proliferation and EGFR kinase were biologically evaluated. Additionally, molecular docking studies were also performed on the representative typical EGFRT790M inhibitor. RESULTS: Most of the evaluated compounds displayed moderate antiproliferative activity on H1975 cells with EGFRL858R/T790M. However, compound 11a (IC50 = 2.235 ± 0.565µM) showed stronger inhibition than gefitinib (IC50 = 8.830 ± 0.495µM) in concentration- and time-dependent manner. Moreover, compound 11a exhibited weaker inhibitory activities on cells with EGFRWT. Specifically, compound 11a strongly suppressed EGFRL858R/T790M (IC50 = 0.515 ± 0.011µM) relative to EGFRWT (IC50 = 0.913 ± 0.068µM). Furthermore, molecular docking studies demonstrated its strong binding contacts with the EGFRT790M enzyme through hydrogen bonds and other non-bonded interactions. CONCLUSION: Taken together, these results indicate that the hybrid of quinoline and anilinopyrimidine 11a, could be a potential inhibitor of EGFRT790M in NSCLC, which warrants further in-depth studies.

18.
Brain Behav ; 10(3): e01540, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31985135

RESUMO

INTRODUCTION: 18 F-fluorodeoxyglucose (FDG)-PET metabolic patterns of brain differ among autoimmune encephalitis with different neuronal surface antigens. In this case report, we compared the topographical relationship of cerebral glucose metabolism and antigen distribution in the patients with anti-NMDAR and anti-AMPAR encephalitis. Literature review summarized the common features of brain metabolism of autoimmune encephalitis. METHODS: The cerebral glucose metabolism was evaluated by FDG-PET/CT during acute-to-subacute stage of autoimmune encephalitis and after treatment. The stereo and quantitative analysis of cerebral metabolism used standardized z-score and visualized on three-dimensional stereotactic surface projection. To map NMDAR and AMPAR in human brain, we adopted genetic atlases from the Allen Institute and protein atlases from Zilles's receptor densities. RESULTS: The three-dimensional stereotactic surface projection displayed frontal-dominant hypometabolism in a 66-year-old female patient with anti-AMPAR encephalitis and occipital-dominant hypometabolism in a 29-year-old female patient with anti-NMDAR encephalitis. Receptor density maps revealed opposite frontal-occipital gradients of AMPAR and NMDAR, which reflect reduced metabolism in the correspondent encephalitis. FDG-PET hypometabolic areas possibly represent receptor hypofunction with spatial correspondence to receptor distributions of the autoimmune encephalitis. The reversibility of hypometabolism was in line with patients' cognitive improvement. The literature review summarized six features of metabolic anomalies of autoimmune encephalitis: (a) temporal hypermetabolism, (b) frontal hypermetabolism and (c) occipital hypometabolism in anti-NMDAR encephalitis, (d) hypometabolism in association cortices, (e) sparing of unimodal primary motor cortex, and (e) reversibility in recovery. CONCLUSIONS: The distinct cerebral hypometabolic patterns of autoimmune encephalitis were representative for receptor hypofunction and topographical distribution of antigenic receptors. The reversibility of hypometabolism marked the clinical recovery of autoimmune encephalitis and made FDG-PET of brain a valuable diagnostic tool.

19.
Psychopharmacology (Berl) ; 237(4): 1233-1243, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31953648

RESUMO

RATIONALE AND OBJECTIVE: Vortioxetine has been reported to exhibit a variety of neurobiological functions and neuroprotective effects. In the present study, we aimed to investigate the effects of vortioxetine on cognitive performance in a transgenic mouse model of Alzheimer's disease (AD). METHODS: We administered vortioxetine (10 mg/kg, i.p., every day, for approximately 6 weeks), which acts on multiple 5-serotonin (5-HT) receptors, to 3.5-month-old 5×FAD mice. Subsequently, we used the open field (OF) test to detect anxiety-like behavior in the mice. The novel object recognition (NOR) test and Morris water maze (MWM) were used to assess the cognitive states of the 5×FAD mice. We also measured the levels of insoluble amyloid plaques and soluble ß-amyloid (Aß) plaques. Finally, we explored the expression levels of postsynaptic density protein 95 (PSD95), synaptophysin (SYP), and synaptotagmin-1 (SYT1) in the hippocampus of the mice. RESULTS: The administration of vortioxetine effectively reversed the reduction in anxiety-type behaviors in 5×FAD mice and improved the impairment in recognition memory and spatial reference memory. However, we did not find that vortioxetine decreased or delayed the formation of amyloid plaques or Aß. Interestingly, we found a significant increase in the expression levels of PSD95, SYP, and SYT1 in the 5×FAD mice after vortioxetine treatment compared with the control group. CONCLUSION: These results demonstrate that vortioxetine may improve cognitive impairment in 5×FAD mice. The role in cognitive improvement may be related to the beneficial effects of vortioxetine on synaptic function.

20.
Stem Cells ; 38(2): 218-230, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31648394

RESUMO

Huntington's disease (HD) is a neurodegenerative disorder caused by a mutation in the huntingtin (HTT) gene that results in the production of neurotoxic mutant HTT (mHTT) protein. Suppressing HTT production with antisense oligonucleotides (ASOs) is a promising treatment strategy for HD; however, the difficulty of delivering ASOs to deep brain structures is a major barrier for its clinical application. The glymphatic system of astrocytes involving aquaporin 4 (AQP-4) controls the entry of macromolecules from the cerebrospinal fluid into the brain. Mesenchymal stem cells (MSCs) target astrocytes to inhibit neuroinflammation. Here we examined the glymphatic distribution of ASO in the brain and the therapeutic potential of combining intravenously injection of mesenchymal stem cells (IV-MSC) and ASOs for the treatment of HD. Our results show that Cy3-labeled ASOs entered the brain parenchyma via the perivascular space following cisternal injection, but the brain distribution was significantly lower in AQP-4-/- as compared with wild-type mice. Downregulation of the AQP-4 M23 isoform was accompanied by decreased brain levels of ASOs in BACHD mice as well as an increase in astrogliosis and phosphorylation of nuclear factor κB (NF-κB) p65. IV-MSC treatment restored AQP-4 M23 expression, attenuated astrogliosis, and decreased NF-κB p65 phosphorylation; it also increased the brain distribution of ASOs and enhanced the suppression of mHTT in BACHD mice. These results suggest that modulating glymphatic activity using IV-MSC is a novel strategy for improving the potency of ASO in the treatment of HD.

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