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1.
PLoS One ; 19(5): e0303205, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38809874

RESUMEN

Cannabis-related emergency department visits have increased after legalization of cannabis for medical and recreational use. Accordingly, the incidence of emergency department visits due to cannabinoid hyperemesis syndrome in patients with chronic cannabis use has also increased. The aim of this study was to examine trends of emergency department visit due to cannabinoid hyperemesis syndrome in Nevada and evaluate factors associated with the increased risk for emergency department visit. The State Emergency Department Databases of Nevada between 2013 and 2021 were used for investigating trends of emergency department visits for cannabinoid hyperemesis syndrome. We compared patients visiting the emergency department due to cannabinoid hyperemesis syndrome with those visiting the emergency department due to other causes except cannabinoid hyperemesis and estimated the impact of cannabis commercialization for recreational use. Emergency department visits due to cannabinoid hyperemesis syndrome have continuously increased during the study period. The number of emergency department visits per 100,000 was 1.07 before commercialization for recreational use. It increased to 2.22 per 100,000 (by approximately 1.1 per 100,000) after commercialization in the third quarter of 2017. Those with cannabinoid hyperemesis syndrome were younger with fewer male patients than those without cannabinoid hyperemesis syndrome. A substantial increase in emergency department visits due to cannabinoid hyperemesis syndrome occurred in Nevada, especially after the commercialization of recreational cannabis. Further study is needed to explore factors associated with emergency department visits.


Asunto(s)
Cannabinoides , Servicio de Urgencia en Hospital , Vómitos , Humanos , Servicio de Urgencia en Hospital/estadística & datos numéricos , Masculino , Femenino , Adulto , Vómitos/inducido químicamente , Vómitos/epidemiología , Nevada/epidemiología , Cannabinoides/efectos adversos , Adulto Joven , Persona de Mediana Edad , Adolescente , Síndrome , Incidencia , Síndrome de Hiperemesis Cannabinoide , Visitas a la Sala de Emergencias
2.
Biomark Res ; 12(1): 52, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38816856

RESUMEN

Protein tyrosine kinase 2 (PTK2), epidermal growth factor receptor (EGFR), and toll-like receptor (TLRs) are amplified in non-small cell lung cancer (NSCLC). However, the functional and clinical associations between them have not been elucidated yet in NSCLC. By using microarray data of non-small cell lung cancer (NSCLC) tumor tissues and matched normal tissues of 42 NSCLC patients, the genetic and clinical associations between PTK2, EGFR, and TLRs were analyzed in NSCLC patients. To verify the functional association, we generated PTK2-knockout (PTK2-KO) lung cancer cells by using CRISPR-Cas9 gene editing method, and performed in vitro cancer progression assay, including 3D tumor spheroid assay, and in vivo xenografted NSG (NOD/SCID/IL-2Rγnull) mouse assay. Finally, therapeutic effects targeted to PTK2 in lung cancer in response to EGF and TLR agonists were verified by using its inhibitor (Defactinib). In summary, we identified that up-regulated PTK2 might be a reliable marker for EGFR- or TLRs-induced lung cancer progression in NSCLC patients via the regulation of the cross-talk between EGFR- and TLRs-mediated signaling. This study provides a theoretical basis for the therapeutic intervention of PTK2 targeting EGFR- or TLRs-induced lung cancer progression.

3.
J Neurol ; 271(5): 2684-2693, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38376545

RESUMEN

BACKGROUND: The effectiveness of endovascular treatment for in-hospital stroke remains debatable. We aimed to compare the outcomes between patients with in-hospital stroke and community-onset stroke who received endovascular treatment. METHODS: This prospective registry-based cohort study included consecutive patients who underwent endovascular treatment from January 2013 to December 2022 and were registered in the Selection Criteria in Endovascular Thrombectomy and Thrombolytic Therapy study and Yonsei Stroke Cohort. Functional outcomes at day 90, radiological outcomes, and safety outcomes were compared between the in-hospital and community-onset groups using logistic regression and propensity score-matched analysis. RESULTS: Of 1,219 patients who underwent endovascular treatment, 117 (9.6%) had in-hospital stroke. Patients with in-hospital onset were more likely to have a pre-stroke disability and active cancer than those with community-onset. The interval from the last known well to puncture was shorter in the in-hospital group than in the community-onset group (155 vs. 355 min, p<0.001). No significant differences in successful recanalization or safety outcomes were observed between the groups; however, the in-hospital group exhibited worse functional outcomes and higher mortality at day 90 than the community-onset group (all p<0.05). After propensity score matching including baseline characteristics, functional outcomes after endovascular treatment did not differ between the groups (OR: 1.19, 95% CI 0.78-1.83, p=0.4). Safety outcomes did not significantly differ between the groups. CONCLUSION: Endovascular treatment is a safe and effective treatment for eligible patients with in-hospital stroke. Our results will help physicians in making decisions when planning treatment and counseling caregivers or patients.


Asunto(s)
Procedimientos Endovasculares , Puntaje de Propensión , Sistema de Registros , Accidente Cerebrovascular , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Accidente Cerebrovascular/terapia , Anciano de 80 o más Años , Resultado del Tratamiento , Estudios Prospectivos , Estudios de Cohortes , Hospitalización/estadística & datos numéricos , Terapia Trombolítica , Evaluación de Resultado en la Atención de Salud , Trombectomía/métodos
5.
Haematologica ; 109(1): 209-219, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37439343

RESUMEN

Tenalisib, a selective phosphoinositide-3-kinase δ/γ, and salt-inducible-kinase-3 inhibitor has shown efficacy and was well-tolerated in patients with T-cell lymphoma (TCL). In vitro studies suggest a synergistic anti-tumor potential for the combination of tenalisib with the histone-deacetylase inhibitor, romidepsin. This multicenter, open-label, phase I/II study was designed to characterize the safety, efficacy and pharmacokinetics of oral tenalisib twice-daily and intravenous romidepsin administered on days 1, 8 and 15 in 28-day cycles in adults with relapsed/refractory TCL. Phase I/dose escalation determined the maximum tolerated dose (MTD)/optimal doses of tenalisib and romidepsin. The phase II/dose expansion assessed the safety and anti-tumor activity of the combination at MTD/optimal dose. Overall, 33 patients were enrolled. In dose escalation, no dose-limiting toxicity was identified. Hence, the recommended doses for dose expansion were tenalisib 800 mg twice daily orally, and romidepsin 14 mg/m2 intravenous. Overall treatment-emergent adverse events of any grade reported in >15% of patients were nausea, thrombocytopenia, increased aspartate aminotransferase, increased alanine aminotransferase, decreased appetite, neutropenia, vomiting, fatigue, anemia, dysgeusia, weight loss, diarrhea, and hypokalemia. Twenty-three patients (69.7%) had related grade ≥3 treatment-emergent adverse events. The overall objective response rate in evaluable patients was 63.0% (peripheral TCL: 75% and cutaneous TCL: 53.3%), with a complete response and partial response of 25.9% and 37.0% respectively. The median duration of response was 5.03 months. Co-administration of tenalisib and romidepsin did not significantly alter the pharmacokinetics of romidepsin. Overall, tenalisib and romidepsin combination demonstrated a favorable safety and efficacy profile supporting its further development for relapsed/refractory TCL (clinicaltrials gov. Identifier: NCT03770000).


Asunto(s)
Linfoma de Células T Periférico , Linfoma de Células T , Neoplasias Cutáneas , Adulto , Humanos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Linfoma de Células T/tratamiento farmacológico , Linfoma de Células T Periférico/tratamiento farmacológico , Resultado del Tratamiento
6.
J Hepatol ; 80(1): 20-30, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37734683

RESUMEN

BACKGROUND & AIMS: Recent studies reported that moderate HBV DNA levels are significantly associated with hepatocellular carcinoma (HCC) risk in hepatitis B e antigen (HBeAg)-positive, non-cirrhotic patients with chronic hepatitis B (CHB). We aimed to develop and validate a new risk score to predict HCC development using baseline moderate HBV DNA levels in patients entering into HBeAg-positive CHB from chronic infection. METHODS: This multicenter cohort study recruited 3,585 HBeAg-positive, non-cirrhotic patients who started antiviral treatment with entecavir or tenofovir disoproxil fumarate at phase change into CHB from chronic infection in 23 tertiary university-affiliated hospitals of South Korea (2012-2020). A new HCC risk score (PAGED-B) was developed (training cohort, n = 2,367) based on multivariable Cox models. Internal validation using bootstrap sampling and external validation (validation cohort, n = 1,218) were performed. RESULTS: Sixty (1.7%) patients developed HCC (median follow-up, 5.4 years). In the training cohort, age, gender, platelets, diabetes and moderate HBV DNA levels (5.00-7.99 log10 IU/ml) were independently associated with HCC development; the PAGED-B score (based on these five predictors) showed a time-dependent AUROC of 0.81 for the prediction of HCC development at 5 years. In the validation cohort, the AUROC of PAGED-B was 0.85, significantly higher than for other risk scores (PAGE-B, mPAGE-B, CAMD, and REAL-B). When stratified by the PAGED-B score, the HCC risk was significantly higher in high-risk patients than in low-risk patients (sub-distribution hazard ratio = 8.43 in the training and 11.59 in the validation cohorts, all p <0.001). CONCLUSIONS: The newly established PAGED-B score may enable risk stratification for HCC at the time of transition into HBeAg-positive CHB. IMPACT AND IMPLICATIONS: In this study, we developed and validated a new risk score to predict hepatocellular carcinoma (HCC) development in patients entering into hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) from chronic infection. The newly established PAGED-B score, which included baseline moderate HBV DNA levels (5-8 log10 IU/ml), improved on the predictive performance of prior risk scores. Based on a patient's age, gender, diabetic status, platelet count, and moderate DNA levels (5-8 log10 IU/ml) at the phase change into CHB from chronic infection, the PAGED-B score represents a reliable and easily available risk score to predict HCC development during the first 5 years of antiviral treatment in HBeAg-positive patients entering into CHB. With a scoring range from 0 to 12 points, the PAGED-B score significantly differentiated the 5-year HCC risk: low <7 points and high ≥7 points.


Asunto(s)
Carcinoma Hepatocelular , Hepatitis B Crónica , Neoplasias Hepáticas , Humanos , Preescolar , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/inducido químicamente , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Antígenos e de la Hepatitis B , ADN Viral , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/inducido químicamente , Estudios de Cohortes , Infección Persistente , Antivirales/uso terapéutico , Factores de Riesgo , Virus de la Hepatitis B/genética
7.
Molecules ; 28(21)2023 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-37959720

RESUMEN

Icariin, a major bioactive compound found in the Epimedium genus, has been reported to exert protective effects against neurodegenerative disorders. In the current study, we aimed to investigate the regulatory effect of icariin and its active metabolites (icariside II and icaritin) against prime G-protein-coupled receptor targets, considering their association with neuronal disorders. Icariside II exhibited selective agonist activity towards the dopamine D3 receptor (D3R), with half-maximal effective concentrations of 13.29 µM. Additionally, they effectively inhibited the specific binding of radioligands to D3R. Molecular docking analysis revealed that icariside II potentially exerts its agonistic effect through hydrogen-bonding interaction with Asp110 of the D3R, accompanied by negative binding energy. Conversely, icaritin demonstrated selective antagonist effects on the muscarinic acetylcholine M2 receptor (M2R). Radioligand binding assay and molecular docking analysis identified icaritin as an orthosteric ligand for M2R. Furthermore, all three compounds, icariin and its two metabolites, successfully mitigated MK-801-induced schizophrenia-like symptoms, including deficits in prepulse inhibition and social interaction, in mice. In summary, these findings highlight the potential of icariin and its metabolites as promising lead structures for the discovery of new drugs targeting cognitive and neurodegenerative disorders.


Asunto(s)
Enfermedades Neurodegenerativas , Esquizofrenia , Ratones , Animales , Maleato de Dizocilpina , Simulación del Acoplamiento Molecular , Esquizofrenia/inducido químicamente , Esquizofrenia/tratamiento farmacológico , Flavonoides/farmacología , Flavonoides/metabolismo
8.
Inflamm Bowel Dis ; 2023 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-37672726

RESUMEN

BACKGROUND: Multidisciplinary teams (MDT) aid the diagnosis and management of patients with inflammatory bowel disease (IBD) and improve patient outcomes. The direct impact of a gastrointestinal expert pathologist on MDT care of IBD patients is unknown. METHODS: A retrospective chart review was conducted evaluating all cases (N = 289) discussed at the IBD MDT conference at Carilion Roanoke Memorial Hospital from June 1, 2013, through December 31, 2019. Cases were discussed between 1 and 6 times at the conference. Data collected included demographics, diagnosis before and after conference, reason for diagnostic change, endoscopy findings, medications, surgeries, and clinical follow-up. RESULTS: Approximately 15% to 42% of patients had a change in diagnosis after the first 3 conferences. The majority of diagnostic changes after the first (84%), second (73%), and third (67%) conferences were due to expert pathologist interpretation. Indeterminate colitis was the most frequently changed diagnosis, and Crohn's disease was the most common new diagnosis after conference. Among patients with a diagnostic change, 28.6% to 38.5% of patients had a change in their IBD medication regimen, and 7.7% to 10.9% had a surgical intervention after the first 2 conferences. Approximately 54.2% to 60% of patients reported clinical improvement or remission within 6 months of the first 3 conferences. CONCLUSION: The majority of diagnostic changes made at the multidisciplinary IBD conference were due to histopathologic re-interpretation. A change in diagnosis at times led to significant modifications in medical or surgical management. An expert gastrointestinal pathologist is an essential MDT member for IBD management.


An expert gastrointestinal pathologist plays a critical role in the diagnosis of patients presented at multidisciplinary team inflammatory bowel disease conferences. Their input at these conferences significantly impacts patients' medical and surgical management and clinical outcomes.

9.
Clin Biochem ; 118: 110603, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37355215

RESUMEN

OBJECTIVES: Alzheimer's disease (AD) is an irreversible neurodegenerative disease characterized by progressive long-term memory loss and cognitive dysfunction. Neuroimaging tests for abnormal amyloid-ß (Aß) deposition are considered the most reliable methods for the diagnosis of AD; however, the cost for such testing is very high and generally not covered by national insurance systems. Accordingly, it is only recommended for individuals exhibiting clinical symptoms of AD supported by clinical cognitive assessments. Recently, it was suggested that dysregulated microRNA-485-3p (miRNA-485-3p) in the brain and cerebrospinal fluid is closely related to pathogenesis of AD. However, a relationship between circulating miRNA-485-3p in salivary exosome-enriched extracellular vesicles (EE-EV) and Aß deposition in the brain has not been observed. DESIGN & METHODS: Using quantitative real-time polymerase chain reaction, we analyzed miRNA-485-3p concentration in salivary EE-EV. We used receiver operating characteristic (ROC) curve analysis to evaluate its predictive value for Aß positron emission tomography (Aß-PET) positivity in patients with AD. RESULTS: Our results showed that the miRNA-485-3p concentration in salivary EE-EV isolated from patients with AD was significantly increased compared with that in the healthy controls (p < 0.0001). In the analysis of all participants, the miRNA-485-3p concentration was significantly increased in Aß-PET-positive participants compared to Aß-PET-negative participants (p < 0.0001). Further analysis using only AD patients also showed that the miRNA-485-3p concentration was significantly increased in Aß-PET-positive AD patients vs. Aß-PET-negative AD patients (p = 0.0063). The ROC curve analysis for differentiating Aß-PET-positive and negative participants showed that the area under the curve for miRNA-485-3p was 0.9217. CONCLUSION: These findings suggested that the miRNA-485-3p concentration in salivary EE-EV was closely related to Aß deposition in the brain and had high diagnostic accuracy for predicting Aß-PET positivity.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Exosomas , MicroARNs , Enfermedades Neurodegenerativas , Humanos , Enfermedad de Alzheimer/diagnóstico , Péptidos beta-Amiloides/líquido cefalorraquídeo , Exosomas/genética , Biomarcadores/líquido cefalorraquídeo , Encéfalo/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , MicroARNs/genética
10.
Dermatol Online J ; 29(1)2023 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-37040913

RESUMEN

We present a case of a female patient who presented with a 0.6cm flesh-colored "rubbery" papule on the left thigh. Biopsy revealed a dermal myxoid tumor containing spindled cells, tapered nuclei, indistinct cell borders, and a large number of mast cells. The spindle cells stained negative for S100 protein and Sox10 on immunohistochemistry, excluding myxoid neurofibroma, but positive for epithelial membrane antigen (EMA), and CD34, supporting a diagnosis of myxoid perineurioma. Interestingly, the mast cells showed cytoplasmic and nuclear positivity for microphthalmia transcription factor (MiTF). The lesion was fully excised one year later with identical histopathology and ancillary immunohistochemical profile.


Asunto(s)
Neoplasias de la Vaina del Nervio , Humanos , Femenino , Neoplasias de la Vaina del Nervio/metabolismo , Neoplasias de la Vaina del Nervio/patología , Inmunohistoquímica , Proteínas S100 , Biopsia , Diagnóstico Diferencial
11.
Case Rep Gastrointest Med ; 2023: 8244696, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37009207

RESUMEN

Mucosa-associated lymphoid tissue (MALT) lymphoma is a common cause of gastric lymphoma. Although most cases are associated with an H. pylori infection, approximately 10% are H. pylori-negative. Patients with gastric MALT lymphoma are usually asymptomatic or present with nonspecific symptoms such as abdominal pain, dyspepsia, weight loss, and occult gastrointestinal bleeding. In this report, we describe two patients with H. pylori-negative MALT lymphoma who both presented with acute upper gastrointestinal bleeding that led to hemodynamic instability. After resuscitation, emergent endoscopy was performed. Both patients had the t (11; 18) (q21; q21) translocation, which prompted direct treatment by radiotherapy.

12.
Leuk Lymphoma ; 64(5): 1026-1034, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36960939

RESUMEN

The objective of this multicenter retrospective study was to examine the incidence, patient characteristics, pathology, and outcomes associated with Epstein-Barr virus (EBV)-related CNS lymphoma (CNSL) in older patients. Among 309 CNSL patients aged ≥60, 11.7% had EBV + tumors of which 72.2% were solid organ transplant (SOT)-related post-transplant lymphoproliferative disorders (PTLD). Younger age, SOT or autoimmune disease, and immunosuppressive treatment correlated highly with EBV-positivity. EBV + tumors were associated with absent C-MYC and BCL6 expression. EBV + PTLD was more likely to be associated with the absence of CD5 expression. EBV + non-PTLD had better median OS (not reached) compared to EBV + PTLD (10.8 months) and EBV-negative patients (43 months). Multivariable Cox regression analysis showed that age, performance status, and PTLD were negative predictors of OS. EBV status and immunosuppressive treatment were not correlated with OS. Our findings merit further investigation of EBV + PCNSL tumors and EBV-directed therapies.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Linfoma , Trastornos Linfoproliferativos , Humanos , Anciano , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/epidemiología , Herpesvirus Humano 4 , Estudios Retrospectivos , Incidencia , Linfoma/etiología , Trastornos Linfoproliferativos/etiología , Inmunosupresores
13.
Am J Hematol ; 98(6): 900-912, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36965007

RESUMEN

There is a paucity of large-scale data delineating outcomes and prognostication of older patients with primary central nervous system lymphoma (PCNSL). We retrospectively analyzed 539 newly-diagnosed PCNSL patients ages ≥60 years across 20 U.S. academic centers. The median age was 70 years (range 60-88); at least one geriatric syndrome was present in 46%; the median Cumulative Index Ratings Scale-Geriatrics (CIRS-G) score was 6 (range, 0-27); and 36% had impairment in activities of daily living (ADL). The most common induction regimens were high-dose methotrexate (HD-MTX) ± rituximab; methotrexate, temozolomide, rituximab (MTR); and rituximab, methotrexate, procarbazine, vincristine (R-MPV). Overall, 70% of patients achieved remission, with 14% undergoing consolidative autologous stem cell transplant (ASCT) and 24% receiving maintenance. With 58-month median follow-up, median progression-free survival (PFS) and overall survival (OS) were 17 months (95% CI 13-22 months) and 43 months (95% CI 31-56 months), respectively. Three-year PFS and OS were highest with MTR (55% and 74%, respectively). With single-agent methotrexate ± rituximab, 3-year PFS and OS were 30% (p = .0002) and 47% (p = .0072). On multivariate analysis, increasing age at diagnosis and Cooperative Oncology Group (ECOG) performance status (PS) was associated with inferior PFS; age, hypoalbuminemia, higher CIRS-G score, and ECOG PS adversely affected OS. Among patients receiving maintenance, 3-year PFS was 65% versus 45% without maintenance (p = 0.02), with 3-year OS of 84% versus 61%, respectively (p = .0003). Altogether, outcomes in older PCNSL patients appeared optimized with HD-MTX combination induction regimens and maintenance therapy. Furthermore, several prognostic factors, including geriatric measures, were associated with inferior outcomes.


Asunto(s)
Neoplasias del Sistema Nervioso Central , Linfoma , Humanos , Anciano , Persona de Mediana Edad , Anciano de 80 o más Años , Rituximab/uso terapéutico , Metotrexato/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Citarabina , Actividades Cotidianas , Estudios Retrospectivos , Temozolomida/uso terapéutico , Linfoma/terapia , Sistema Nervioso Central/patología , Neoplasias del Sistema Nervioso Central/patología
14.
Autophagy ; 19(8): 2318-2337, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36843263

RESUMEN

Impaired activities and abnormally enlarged structures of endolysosomes are frequently observed in Alzheimer disease (AD) brains. However, little is known about whether and how endolysosomal dysregulation is triggered and associated with AD. Here, we show that vacuolar ATPase (V-ATPase) is a hub that mediates proteopathy of oligomeric amyloid beta (Aß) and hyperphosphorylated MAPT/Tau (p-MAPT/Tau). Endolysosomal integrity was largely destroyed in Aß-overloaded or p-MAPT/Tau-positive neurons in culture and AD brains, which was a necessary step for triggering neurotoxicity, and treatments with acidic nanoparticles or endocytosis inhibitors rescued the endolysosomal impairment and neurotoxicity. Interestingly, we found that the lumenal ATP6V0C and cytosolic ATP6V1B2 subunits of the V-ATPase complex bound to the internalized Aß and cytosolic PHF-1-reactive MAPT/Tau, respectively. Their interactions disrupted V-ATPase activity and accompanying endolysosomal activity in vitro and induced neurodegeneration. Using a genome-wide functional screen, we isolated a suppressor, HYAL (hyaluronidase), which reversed the endolysosomal dysfunction and proteopathy and alleviated the memory impairment in 3xTg-AD mice. Further, we found that its metabolite hyaluronic acid (HA) and HA receptor CD44 attenuated neurotoxicity in affected neurons via V-ATPase. We propose that endolysosomal V-ATPase is a bona fide proteotoxic receptor that binds to pathogenic proteins and deteriorates endolysosomal function in AD, leading to neurodegeneration in proteopathy.Abbreviations: AAV, adeno-associated virus; Aß, amyloid beta; AD, Alzheimer disease; APP, amyloid beta precursor protein; ATP6V0C, ATPase H+ transporting V0 subunit c; ATP6V1A, ATPase H+ transporting V1 subunit A; ATP6V1B2, ATPase H+ transporting V1 subunit B2; CD44.Fc, CD44-mouse immunoglobulin Fc fusion construct; Co-IP, co-immunoprecipitation; CTSD, cathepsin D; HA, hyaluronic acid; HMWHA, high-molecular-weight hyaluronic acid; HYAL, hyaluronidase; i.c.v, intracerebroventricular; LMWHA, low-molecular-weight hyaluronic acid; NPs, nanoparticles; p-MAPT/Tau, hyperphosphorylated microtubule associated protein tau; PI3K, phosphoinositide 3-kinase; V-ATPase, vacuolar-type H+-translocating ATPase; WT, wild-type.


Asunto(s)
Enfermedad de Alzheimer , ATPasas de Translocación de Protón Vacuolares , Ratones , Animales , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , ATPasas de Translocación de Protón Vacuolares/metabolismo , Hialuronoglucosaminidasa/metabolismo , Ácido Hialurónico , Fosfatidilinositol 3-Quinasas/metabolismo , Autofagia , Proteínas tau/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Proteínas Portadoras , Ratones Transgénicos , Modelos Animales de Enfermedad
15.
Biol Psychiatry ; 93(9): 829-841, 2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-36759256

RESUMEN

BACKGROUND: In tauopathies, brain regions with tau accumulation strongly correlate with clinical symptoms, and spreading of misfolded tau along neural network leads to disease progression. However, the underlying mechanisms by which tau proteins enter neurons during pathological propagation remain unclear. METHODS: To identify membrane receptors responsible for neuronal propagation of tau oligomers, we established a cell-based tau uptake assay and screened complementary DNA expression library. Tau uptake and propagation were analyzed in vitro and in vivo using a microfluidic device and stereotactic injection. The cognitive function of mice was assessed using behavioral tests. RESULTS: From a genome-wide cell-based functional screening, RAGE (receptor for advanced glycation end products) was isolated to stimulate the cellular uptake of tau oligomers. Rage deficiency reduced neuronal uptake of pathological tau prepared from rTg4510 mouse brains or cerebrospinal fluid from patients with Alzheimer's disease and slowed tau propagation between neurons cultured in a 3-chamber microfluidic device. RAGE levels were increased in the brains of rTg4510 mice and tau oligomer-treated neurons. Rage knockout decreased tau transmission in the brains of nontransgenic mice after injection with Alzheimer's disease patient-derived tau and ameliorated memory loss after injection with GFP-P301L-tau-AAV. Treatment of RAGE antagonist FPS-ZM1 blocked transsynaptic tau propagation and inflammatory responses and alleviated cognitive impairment in rTg4510 mice. CONCLUSIONS: These results suggest that in neurons and microglia, RAGE binds to pathological tau and facilitates neuronal tau pathology progression and behavioral deficits in tauopathies.


Asunto(s)
Enfermedad de Alzheimer , Receptor para Productos Finales de Glicación Avanzada , Tauopatías , Proteínas tau , Animales , Ratones , Enfermedad de Alzheimer/metabolismo , Encéfalo/metabolismo , Modelos Animales de Enfermedad , Trastornos de la Memoria/metabolismo , Ratones Transgénicos , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Proteínas tau/metabolismo , Tauopatías/metabolismo
18.
Int J Mol Sci ; 25(1)2023 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-38203574

RESUMEN

Over the last ten years, the discovery of topological materials has opened up new areas in condensed matter physics. These materials are noted for their distinctive electronic properties, unlike conventional insulators and metals. This discovery has not only spurred new research areas but also offered innovative approaches to electronic device design. A key aspect of these materials is now that transforming them into nanostructures enhances the presence of surface or edge states, which are the key components for their unique electronic properties. In this review, we focus on recent synthesis methods, including vapor-liquid-solid (VLS) growth, chemical vapor deposition (CVD), and chemical conversion techniques. Moreover, the scaling down of topological nanomaterials has revealed new electronic and magnetic properties due to quantum confinement. This review covers their synthesis methods and the outcomes of topological nanomaterials and applications, including quantum computing, spintronics, and interconnects. Finally, we address the materials and synthesis challenges that need to be resolved prior to the practical application of topological nanomaterials in advanced electronic devices.


Asunto(s)
Metodologías Computacionales , Nanoestructuras , Teoría Cuántica , Electrónica , Gases
19.
Polymers (Basel) ; 14(23)2022 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-36501724

RESUMEN

In this paper, we present dual responsive one-dimensional (1D) photonic crystal (PC) multilayer films that utilize a high-humidity environment and temperature. Dual responsive 1D PC multilayer films are fabricated on precoated thermochromic film by sequential alternate layer deposition of photo-crosslinkable poly(2-vinylnaphthalene-co-benzophenone acrylate) (P(2VN-co-BPA)) as a high refractive index polymer, and poly(4-vinylpyrollidone-co-benzophenone acrylate) P(4VP-co-BPA) as a low refractive index polymer. The thermochromic film shows a vivid color transition from black to white at 28 °C. Three different colors of thermochromic 1D PC multilayer films are prepared by thickness modulation of P(4VP-co-BPA) layers, and the films on a black background exhibit visible spectrum color only in a high-humidity environment (over 90% relative humidity (RH)). For the three films placed on a hands display, three different composite colors are synthesized by the reflection of light, including yellow, magenta, and cyan, due to the changing of backgrounds from black to white with temperature. Additionally, the films show remarkable color transitions with reliable reversibility. The films can be applied as anti-counterfeiting labels and can be used for smart decoration films. To the best of our knowledge, this is the first report of dual response colorimetric films that change color in various ways depending on temperature and humidity changes, and we believe that it can be applied to various applications.

20.
Front Plant Sci ; 13: 1030140, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36388508

RESUMEN

Climate change-related drought stress is expected to shift carbon partitioning toward volatile organic compound (VOC) biosynthesis. The effect of drought stress on VOC synthesis remains unknown in several tree species. Therefore, we exposed eastern white pine (Pinus strobus) plants to severe drought for 32 days and performed physiological analysis (chlorophyll content, leaf water content, and root/shoot index), biochemical analysis (non-structural carbohydrates, proline, lipid peroxidation, and antioxidant assay), and total root VOC analysis. Drought stress decreased the relative water and soil moisture contents. Root proline accumulation and antioxidant activity increased significantly, whereas leaf chlorophyll synthesis and fresh weight decreased significantly in drought-treated plants. A non-significant increase in sugar accumulation (leaves and roots), proline accumulation (leaves), antioxidant activity (leaves), and lipid peroxidation (leaves and roots) was observed in drought-treated plants. Drought stress caused a non-significant decline in root/shoot ratio and starch accumulation (leaves and roots) and caused a significant increase in root abscisic acid content. Drought-treated plants showed an increase in overall monoterpene synthesis (16%) and decline in total sesquiterpene synthesis (3%). Our findings provide an overall assessment of the different responses of VOC synthesis to severe water deficit that may help unravel the molecular mechanisms underlying drought tolerance in P. strobus.

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