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1.
J Neurosci ; 44(29)2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38886059

RESUMEN

Anxiety-related disorders respond to cognitive behavioral therapies, which involved the medial prefrontal cortex (mPFC). Previous studies have suggested that subregions of the mPFC have different and even opposite roles in regulating innate anxiety. However, the specific causal targets of their descending projections in modulating innate anxiety and stress-induced anxiety have yet to be fully elucidated. Here, we found that among the various downstream pathways of the prelimbic cortex (PL), a subregion of the mPFC, PL-mediodorsal thalamic nucleus (MD) projection, and PL-ventral tegmental area (VTA) projection exhibited antagonistic effects on anxiety-like behavior, while the PL-MD projection but not PL-VTA projection was necessary for the animal to guide anxiety-related behavior. In addition, MD-projecting PL neurons bidirectionally regulated remote but not recent fear memory retrieval. Notably, restraint stress induced high-anxiety state accompanied by strengthening the excitatory inputs onto MD-projecting PL neurons, and inhibiting PL-MD pathway rescued the stress-induced anxiety. Our findings reveal that the activity of PL-MD pathway may be an essential factor to maintain certain level of anxiety, and stress increased the excitability of this pathway, leading to inappropriate emotional expression, and suggests that targeting specific PL circuits may aid the development of therapies for the treatment of stress-related disorders.


Asunto(s)
Ansiedad , Vías Nerviosas , Corteza Prefrontal , Estrés Psicológico , Animales , Ansiedad/psicología , Ansiedad/fisiopatología , Masculino , Estrés Psicológico/psicología , Estrés Psicológico/fisiopatología , Corteza Prefrontal/fisiopatología , Vías Nerviosas/fisiopatología , Vías Nerviosas/fisiología , Ratones , Miedo/fisiología , Miedo/psicología , Ratones Endogámicos C57BL , Área Tegmental Ventral/fisiopatología , Tálamo/fisiopatología , Núcleo Talámico Mediodorsal/fisiología , Núcleo Talámico Mediodorsal/fisiopatología
2.
Glia ; 72(9): 1646-1662, 2024 09.
Artículo en Inglés | MEDLINE | ID: mdl-38801194

RESUMEN

The adult brain retains a high repopulation capacity of astrocytes after deletion, and both mature astrocytes in the neocortex and neural stem cells in neurogenic regions possess the potential to generate astrocytes. However, the origin and the repopulation dynamics of the repopulating astrocytes after deletion remain largely unclear. The number of astrocytes is reduced in the medial prefrontal cortex (mPFC) of patients with depression, and selective elimination of mPFC astrocytes is sufficient to induce depression-like behaviors in rodents. However, whether astrocyte repopulation capacity is impaired in depression is unknown. In this study, we used different transgenic mouse lines to genetically label different cell types and demonstrated that in the mPFC of normal adult mice of both sexes, mature astrocytes were a major source of the repopulating astrocytes after acute deletion induced by an astrocyte-specific toxin, L-alpha-aminoadipic acid (L-AAA), and astrocyte regeneration was accomplished within two weeks accompanied by reversal of depression-like behaviors. Furthermore, re-ablation of mPFC astrocytes post repopulation led to reappearance of depression-like behaviors. In adult male mice subjected to 14-day chronic restraint stress, a well-validated mouse model of depression, the number of mPFC astrocytes was reduced; however, the ability of mPFC astrocytes to repopulate after L-AAA-induced deletion was largely unaltered. Our study highlights a potentially beneficial role for repopulating astrocytes in depression and provides novel therapeutic insights into enhancing local mature astrocyte generation in depression.


Asunto(s)
Astrocitos , Depresión , Ratones Transgénicos , Corteza Prefrontal , Animales , Astrocitos/metabolismo , Corteza Prefrontal/metabolismo , Masculino , Depresión/genética , Depresión/patología , Femenino , Ratones Endogámicos C57BL , Ratones , Modelos Animales de Enfermedad , Restricción Física , Ácido 2-Aminoadípico , Estrés Psicológico/patología , Estrés Psicológico/metabolismo
3.
Artículo en Inglés | MEDLINE | ID: mdl-38331400

RESUMEN

OBJECTIVES: To characterize the effect of upadacitinib 15 mg once daily (UPA15) on enthesitis in patients with psoriatic arthritis from the SELECT-PsA Phase 3 trials. METHODS: Patients with an inadequate response/intolerance to ≥ 1 non-biologic DMARD (SELECT-PsA 1) or ≥ 1 biologic DMARD (SELECT-PsA 2) received UPA15, adalimumab 40 mg every other week or placebo (weeks 0-24) switched to UPA15 (week 24 onward). The Leeds Enthesitis Index (LEI) and Spondyloarthritis Research Consortium of Canada (SPARCC) index were used to assess improvement in enthesitis, enthesitis resolution, maintenance of enthesitis resolution, and protection from enthesitis development through week 56. RESULTS: Data from 639 patients receiving UPA15 and 635 patients receiving placebo (including 317 patients who switched from placebo to UPA15) were analysed. UPA15 led to higher rates of enthesitis resolution vs placebo at week 24 (LEI: 59.8% vs 38.0%; SPARCC index: 50.6% vs 31.5%, respectively) and greater improvements in the LEI (-1.7 vs -1.0) and SPARCC index (-3.4 vs -1.9); improvements were maintained through week 56. Improvements were observed after 12 weeks of UPA15 treatment. Over 90% of patients without enthesitis (LEI = 0) at baseline receiving UPA15 were enthesitis-free at week 56, and UPA15 prevented recurrence of enthesitis at week 56 in > 80% of patients with enthesitis at baseline who achieved resolution (LEI = 0) at week 24. CONCLUSIONS: UPA15 is associated with a comprehensive improvement in enthesitis, with improvements observed after 12 weeks of treatment. Additionally, treatment with UPA15 was associated with maintaining an enthesitis-free state after resolution and protection against new-onset enthesitis. CLINICALTRIALS.GOV IDENTIFIERS: NCT03104400 (SELECT-PsA 1) and NCT03104374 (SELECT-PsA 2).

4.
Pharmacol Res ; 199: 107042, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38142878

RESUMEN

Drugs acting on dopamine D2 receptors are widely used for the treatment of several neuropsychiatric disorders, including schizophrenia and depression. Social deficits are a core symptom of these disorders. Pharmacological manipulation of dopamine D2 receptors (Drd2), a Gi-coupled subtype of dopamine receptors, in the medial prefrontal cortex (mPFC) has shown that Drd2 is implicated in social behaviors. However, the type of neurons expressing Drd2 in the mPFC and the underlying circuit mechanism regulating social behaviors remain largely unknown. Here, we show that Drd2 were mainly expressed in pyramidal neurons in the mPFC and that the activation of the Gi-pathway in Drd2+ pyramidal neurons impaired social behavior in male mice. In contrast, the knockdown of D2R in pyramidal neurons in the mPFC enhanced social approach behaviors in male mice and selectively facilitated the activation of mPFC neurons projecting to the nucleus accumbens (NAc) during social interaction. Remarkably, optogenetic activation of mPFC-to-NAc-projecting neurons mimicked the effects of conditional D2R knockdown on social behaviors. Altogether, these results demonstrate a cell type-specific role for Drd2 in the mPFC in regulating social behavior, which may be mediated by the mPFC-to-NAc pathway.


Asunto(s)
Células Piramidales , Receptores de Dopamina D2 , Ratones , Masculino , Animales , Receptores de Dopamina D2/metabolismo , Células Piramidales/fisiología , Neuronas/metabolismo , Corteza Prefrontal/metabolismo , Núcleo Accumbens/fisiología , Conducta Social
5.
Environ Sci Technol ; 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39150153

RESUMEN

Recent years have witnessed increasing attempts to track trade flows of critical materials across world regions and along the life cycle for renewable energy and the low carbon transition. Previous studies often had limited spatiotemporal coverage, excluded end-use products, and modeled different life cycle stages as single-layer networks. Here, we integrated material flow analysis and complex network analysis into a multilayer framework to characterize the spatiotemporal and multilayer trade network patterns of the global cobalt cycle from 1988 to 2020. We found substantial growth and notable structural changes in global cobalt trade over the past 30 years. China, Germany, and the United States play pivotal roles in different layers and stages of the global cobalt cycle. The interlayer relationships among alloys, batteries, and materials are robust and continually strengthening, indicating a trend toward synergistic trade. However, cobalt ore-exporting countries are highly concentrated and rarely involved in later life cycle stages, resulting in the weakest relationship between the ore layer and other layers. This causes fluctuations and uncertainty in the global cobalt trade. Our model, linking industrial ecology, supply chain analysis, and network analysis, can be extended to other materials that are critical for the future green transition.

6.
J Environ Manage ; 350: 119652, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38016235

RESUMEN

Renewable energy (RE) plays a crucial role in global energy transformation, and a thorough study of the potential impact of RE on regional carbon emissions is of great significance. This is particularly relevant to China, which needs to clarify its path to carbon reduction. Using the sample data of 30 provinces in China from 2000 to 2021, this paper uses the Granger causality test to verify the causal relationship between carbon emission intensity (CEI) and other factors. It builds a mediation effect model on this basis to explore the direct impact effect and indirect transmission path of renewable energy utilization (REU) on CEI. The results show that REU has a one-way causal relationship with CEI. REU can directly and indirectly reduce CEI by improving social wealth and changing the direction of energy investment. In addition, REU indirectly increases CEI through the transmission paths of investment in the energy industry - social affluence and industrial level-social affluence. The CEI is indirectly reduced through the conduction paths of (social affluence-Urbanization rate), (Investment in the energy industry-Urbanization rate), (Industrial level-Urbanization rate), and (Industrial level-Investment in the energy industry). These conclusions will assist policymakers in exploring targeted pathways for low-carbon power development, providing a reference for strategic and sustainable carbon reduction policies.


Asunto(s)
Dióxido de Carbono , Carbono , Carbono/análisis , Dióxido de Carbono/análisis , Urbanización , Energía Renovable , China , Desarrollo Económico
7.
J Environ Manage ; 363: 121314, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38843731

RESUMEN

Pretreatment, the initial step in recycling spent lithium-ion batteries (LIBs), efficiently separates cathode and anode materials to facilitate key element recovery. Despite brief introductions in existing research, a comprehensive evaluation and comparison of processing methods is lacking. This study reviews 346 references on LIBs recycling, analyzing pretreatment stages, treatment conditions, and method effects. Our analysis highlights insufficient attention to discharge voltage safety and environmental impact. Mechanical disassembly, while suitable for industrial production, overlooks electrolyte recovery and complicates LIBs separation. High temperature pyrolysis flotation offers efficient separation of mixed electrode materials, enhancing mineral recovery. We propose four primary pretreatment processes: discharge, electrolyte recovery, crushing and separation, and electrode material recovery, offering simplified, efficient, green, low-cost, and high-purity raw materials for subsequent recovery processes.


Asunto(s)
Suministros de Energía Eléctrica , Litio , Reciclaje , Litio/química , Reciclaje/métodos , Electrodos , Iones
8.
Carcinogenesis ; 44(8-9): 682-694, 2023 12 02.
Artículo en Inglés | MEDLINE | ID: mdl-37294054

RESUMEN

EphB6 belongs to the receptor tyrosine kinase, whose low expression is associated with shorter survival of colorectal cancer (CRC) patients. But the role and mechanism of EphB6 in the progression of CRC need further study. In addition, EphB6 was mainly expressed in intestinal neurons. But how EphB6 is involved in functions of intestinal neurons has not been known. In our study, we constructed a mouse xenograft model of CRC by injecting CMT93 cells into the rectum of EphB6-deficient mice. We found that the deletion of EphB6 in mice promoted tumor growth of CMT93 cells in a xenograft model of CRC, which was independent of changes in the gut microbiota. Interestingly, inhibition of intestinal neurons by injecting botulinum toxin A into rectum of EphB6-deficient mice could eliminate the promotive effect of EphB6 deficiency on tumor growth in the xenograft model of CRC. Mechanically, the deletion of EphB6 in mice promoted the tumor growth in CRC by increasing GABA in the tumor microenvironment. Furthermore, EphB6 deficiency in mice increased the expression of synaptosomal-associated protein 25 in the intestinal myenteric plexus, which mediated the release of GABA. Our study concluded that EphB6 knockout in mice promotes tumor growth of CMT93 cells in a xenograft model of CRC by modulating GABA release. Our study found a new regulating mechanism of EphB6 on the tumor progression in CRC that is dependent on intestinal neurons.


Asunto(s)
Comunicación Celular , Neoplasias Colorrectales , Humanos , Animales , Ratones , Neoplasias Colorrectales/metabolismo , Intestinos/patología , Neuronas/metabolismo , Neuronas/patología , Ácido gamma-Aminobutírico , Microambiente Tumoral
9.
Mol Psychiatry ; 27(2): 873-885, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34642458

RESUMEN

Long-term potentiation (LTP) in the hippocampus is the most studied form of synaptic plasticity. Temporal integration of synaptic inputs is essential in synaptic plasticity and is assumed to be achieved through Ca2+ signaling in neurons and astroglia. However, whether these two cell types play different roles in LTP remain unknown. Here, we found that through the integration of synaptic inputs, astrocyte inositol triphosphate (IP3) receptor type 2 (IP3R2)-dependent Ca2+ signaling was critical for late-phase LTP (L-LTP) but not early-phase LTP (E-LTP). Moreover, this process was mediated by astrocyte-derived brain-derived neurotrophic factor (BDNF). In contrast, neuron-derived BDNF was critical for both E-LTP and L-LTP. Importantly, the dynamic differences in BDNF secretion play a role in modulating distinct forms of LTP. Moreover, astrocyte- and neuron-derived BDNF exhibited different roles in memory. These observations enriched our knowledge of LTP and memory at the cellular level and implied distinct roles of astrocytes and neurons in information integration.


Asunto(s)
Astrocitos , Factor Neurotrófico Derivado del Encéfalo , Astrocitos/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Hipocampo/metabolismo , Potenciación a Largo Plazo/fisiología , Plasticidad Neuronal/fisiología , Neuronas/metabolismo
10.
Mol Psychiatry ; 27(2): 896-906, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34697452

RESUMEN

Neuroplasticity in the medial prefrontal cortex (mPFC) is essential for fear extinction, the process of which forms the basis of the general therapeutic process used to treat human fear disorders. However, the underlying molecules and local circuit elements controlling neuronal activity and concomitant induction of plasticity remain unclear. Here we show that sustained plasticity of the parvalbumin (PV) neuronal network in the infralimbic (IL) mPFC is required for fear extinction in adult male mice and identify the involvement of neuregulin 1-ErbB4 signalling in PV network plasticity-mediated fear extinction. Moreover, regulation of fear extinction by basal medial amygdala (BMA)-projecting IL neurons is dependent on PV network configuration. Together, these results uncover the local molecular circuit mechanisms underlying mPFC-mediated top-down control of fear extinction, suggesting alterative therapeutic approaches to treat fear disorders.


Asunto(s)
Extinción Psicológica , Miedo , Animales , Extinción Psicológica/fisiología , Miedo/fisiología , Masculino , Ratones , Neurregulina-1 , Plasticidad Neuronal/fisiología , Parvalbúminas , Corteza Prefrontal/fisiología , Receptor ErbB-4
11.
Surg Endosc ; 37(11): 8522-8531, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37775601

RESUMEN

BACKGROUND: Posthepatitic cirrhosis is one of the leading risk factors for hepatocellular carcinoma (HCC) worldwide, among which hepatitis B cirrhosis is the dominant one. This study explored whether laparoscopic splenectomy and azygoportal disconnection (LSD) can reduce the risk of HCC among patients with hepatitis B virus (HBV)-related cirrhotic portal hypertension (CPH). METHODS: A total of 383 patients with HBV-related CPH diagnosed as gastroesophageal variceal bleeding and secondary hypersplenism were identified in our hepatobiliary pancreatic center between April 2012 and April 2022, and conducted an 11-year retrospective follow-up. We used inverse probability of treatment weighting (IPTW) to correct for potential confounders, weighted Kaplan-Meier curves, and logistic regression to estimate survival and risk differences. RESULTS: Patients were divided into two groups based on treatment method: LSD (n = 230) and endoscopic therapy (ET; n = 153) groups. Whether it was processed through IPTW or not, LSD group showed a higher survival benefit than ET group according to Kaplan-Meier analysis (P < 0.001). The incidence density of HCC was higher in the ET group compared to LSD group at the end of follow-up [32.1/1000 vs 8.0/1000 person-years; Rate ratio: 3.998, 95% confidence intervals (CI) 1.928-8.293]. Additionally, in logistic regression analyses weighted by IPTW, LSD was an independent protective predictor of HCC incidence compared to ET (odds ratio 0.516, 95% CI 0.343-0.776; P = 0.002). CONCLUSION: Considering the ability of LSD to improve postoperative survival and prevent HCC in HBV-related CPH patients with gastroesophageal variceal bleeding and secondary hypersplenism, it is worth promoting in the context of the shortage of liver donors.


Asunto(s)
Carcinoma Hepatocelular , Várices Esofágicas y Gástricas , Hiperesplenismo , Hipertensión Portal , Laparoscopía , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/complicaciones , Virus de la Hepatitis B , Várices Esofágicas y Gástricas/cirugía , Várices Esofágicas y Gástricas/complicaciones , Estudios Retrospectivos , Hiperesplenismo/cirugía , Hiperesplenismo/complicaciones , Esplenectomía/efectos adversos , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/complicaciones , Hemorragia Gastrointestinal/etiología , Laparoscopía/efectos adversos , Hipertensión Portal/cirugía , Hipertensión Portal/complicaciones , Cirrosis Hepática/complicaciones , Cirrosis Hepática/cirugía
12.
BMC Infect Dis ; 22(1): 181, 2022 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-35197012

RESUMEN

BACKGROUND: Chlamydia abortus is generally considered to cause abortion, stillbirth, and gestational sepsis in pregnant women, but it's rare in bloodstream infection and pneumonia. CASE PRESENTATION: We present details of a patient with bloodstream infection and pneumonia caused by Chlamydia abortus. Both blood next-generation sequencing (NGS) and sputum NGS indicate Chlamydia abortus infection. The patient received intravenous infusion of piperacillin sodium and tazobactam sodium (4.5 g/8 h) and moxifloxacin (0.4 g/d) and oral oseltamivir (75 mg/day). Within one month of follow-up, the patient's clinical symptoms were significantly improved, and all laboratory parameters showed no marked abnormality. However, chest computer tomography (CT) showed the inflammation wasn't completely absorbed. And we are still following up. CONCLUSIONS: Chlamydia abortus can cause pneumonia in humans. NGS has the particular advantage of quickly and accurately identifying the infection of such rare pathogens. Pneumonia is generally not life-threatening, and has a good prognosis with appropriate treatment. However, Chlamydia infection can lead to serious visceral complications which clinicians should pay attention to.


Asunto(s)
Infecciones por Chlamydia , Chlamydia , Neumonía , Sepsis , Infecciones por Chlamydia/diagnóstico , Infecciones por Chlamydia/tratamiento farmacológico , Femenino , Humanos , Embarazo
13.
J Environ Manage ; 318: 115599, 2022 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-35780676

RESUMEN

Owing to its key role in high-tech industry and clean energy technology, cobalt has been regarded as a critical material in many countries. In this paper, material flow analysis was used to quantitatively track cobalt material flows in China throughout the entire life cycle from 2000 to 2021. Based on data pertaining to cobalt commodity trade, cobalt loss during raw material processing, and recovered cobalt, we analysed the actual cobalt consumption in China. During the study period from 2000 to 2021, the main findings were as follows: (1) China's cobalt raw material imports accounted for 84.7% of the total raw materials acquired, while the export of cobalt-containing end products amounted to 32.6% of the total production. (2) China's cumulative net import of all cobalt commodities reached 561 kt, and battery products accounted for 73.3% of the total cobalt consumption. (3) China recovered 77 kt of cobalt from end-of-life products, while 327 kt of cobalt was not recovered. (4) The cumulative cobalt loss during raw material processing reached 288 kt, with the highest loss occurring in refining (51.0%), followed by manufacturing and fabrication (26.5%), beneficiation (12.3%), and ore mining (10.2%). The overall utilization efficiency of cobalt was 73.8% throughout the entire life cycle. (5) China's actual cobalt consumption reached 497 kt, accounting for 51.9% of the apparent cobalt consumption. Moreover, 61.1% of the cobalt products produced in China was consumed domestically, while 38.9% was exported. The massive export of cobalt commodities resulted in China bearing a disproportionate responsibility for carbon emission reduction. The research results can provide a scientific reference for the reasonable adjustment of the trade structure of cobalt commodities and realization of the economic and efficient utilization of cobalt resources in China.


Asunto(s)
Cobalto , Industrias , Animales , Carbono , China , Comercio , Estadios del Ciclo de Vida
14.
Clin Nephrol ; 96(1): 22-28, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33835012

RESUMEN

BACKGROUND: The majority of dialysis patients receive aggressive burdensome treatment near the end of life. Currently, we lack interventions to improve end-of-life care (EoLC) for these patients. We examined the association of palliative care consultation with improving EoLC for critically ill patients with end-stage renal disease (ESRD) who received cardiopulmonary resuscitation (CPR). MATERIALS AND METHODS: In this retrospective study, we included patients with ESRD admitted to a large academic center who received CPR either prior to or during their hospital stay. Over 8 years, 17 out of 403 patients received palliative care consultation during their hospital stay; consultations were not standardized in their content. Main outcomes of interest to operationalize better EoLC were: (1) change in code status from full code to do not resuscitate (DNR) and (2) withdrawal from intensive care. RESULTS: Of the patients studied, 60.5% were African-American and 43.2% were female. Demographic differences between those with palliative care consultation and those with usual care were not statistically significant. Palliative care consultation was associated with higher odds of change in code status to DNR (odds ratio 8.10, 95% confidence interval 2.19 - 29.94) and withdrawal from intensive care (odds ratio 8.82, 95% confidence interval 2.69 - 28.91) in patients with ESRD who had received CPR. Palliative care consultation was not associated with any change in in-hospital mortality. CONCLUSION: Palliative care consultation needs to be considered for hospitalized ESRD patients with limited expected prognoses as it may reduce aggressive and burdensome therapies at the end of life. Furthermore, primary palliative care skills such as communication and decision-making should be taught to nephrologists to improve EoLC for dialysis patients.


Asunto(s)
Reanimación Cardiopulmonar , Fallo Renal Crónico , Cuidados Paliativos , Derivación y Consulta/estadística & datos numéricos , Humanos , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/terapia , Diálisis Renal , Estudios Retrospectivos , Cuidado Terminal
15.
Hepatobiliary Pancreat Dis Int ; 20(4): 330-336, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33637452

RESUMEN

BACKGROUND: Hepatocellular carcinoma (HCC) progresses fast and has a poor prognosis, but the growth rate in different TNM stages is not clear. The present study was to estimate the growth rate of HCC with different TNM stages at diagnosis. METHODS: Baseline demographics and tumor characteristics were analyzed for 10145 patients in Surveillance, Epidemiology, and End Results (SEER) Program-registered HCC. Multiple linear regression models were used for age adjustment with patient race, sex, marital status, and HCC grade. RESULTS: The age at diagnosis was younger in Caucasians and males. The adjusted average age of patients with stage I HCC was 65.26 years. The adjusted age of patients with stage II, IIIA, IIIB, and IIIC was -0.17, -0.25, -0.29, and -0.55 adjusted-year younger compared with patients with stage I HCC (all P < 0.001). The adjusted average age of patients with T1 was 65.26 years. The age adjustment was -0.17, -0.26, and -0.55 respectively (all P < 0.001) for T2, T3 or T4 tumors without distant metastases. CONCLUSIONS: These findings demonstrated that the more advanced the HCC stage at diagnosis, the younger the age at diagnosis and the faster the HCC growth from tumor occurrence.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Anciano , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/patología , Humanos , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/patología , Masculino , Estado Civil , Estadificación de Neoplasias , Pronóstico
16.
Cereb Cortex ; 29(10): 4334-4346, 2019 09 13.
Artículo en Inglés | MEDLINE | ID: mdl-30590426

RESUMEN

erbb4 is a known susceptibility gene for schizophrenia. Chandelier cells (ChCs, also known as axo-axonic cells) are a distinct GABAergic interneuron subtype that exclusively target the axonal initial segment, which is the site of pyramidal neuron action potential initiation. ChCs are a source of ErbB4 expression and alterations in ChC-pyramidal neuron connectivity occur in the medial prefrontal cortex (mPFC) of schizophrenic patients and animal models of schizophrenia. However, the contribution of ErbB4 in mPFC ChCs to the pathogenesis of schizophrenia remains unknown. By conditional deletion or knockdown of ErbB4 from mPFC ChCs, we demonstrated that ErbB4 deficits led to impaired ChC-pyramidal neuron connections and cognitive dysfunctions. Furthermore, the cognitive dysfunctions were normalized by L-838417, an agonist of GABAAα2 receptors enriched in the axonal initial segment. Given that cognitive dysfunctions are a core symptom of schizophrenia, our results may provide a new perspective for understanding the etiology of schizophrenia and suggest that GABAAα2 receptors may be potential pharmacological targets for its treatment.


Asunto(s)
Disfunción Cognitiva/fisiopatología , Neuronas GABAérgicas/fisiología , Interneuronas/fisiología , Corteza Prefrontal/fisiología , Células Piramidales/fisiología , Receptor ErbB-4/fisiología , Esquizofrenia/fisiopatología , Animales , Conducta Animal , Masculino , Potenciales de la Membrana , Ratones Noqueados , Receptor ErbB-4/genética
17.
Carcinogenesis ; 40(5): 680-686, 2019 07 04.
Artículo en Inglés | MEDLINE | ID: mdl-30452622

RESUMEN

Previously we reported that ErbB4 played a protective role in chronic liver injury and hepatocellular carcinoma. Herein, we examined the role of ErbB4 in the development of colitis-associated cancer (CAC) in ErbB4 knockout mice models, in vitro cell lines and clinical samples. We found that ErbB4 deficiency may lead to more severe inflammation, slower recovery and the development of CAC. Further, loss of ErbB4 could activate Kras by upregulating rate-limiting enzymes in cholesterol metabolism pathway through interacting with the transcription factor Srebf1. In clinic samples, ErbB4 is downregulated in colonic tissues from patients with Crohn's disease. And data from The Cancer Genome Atlas also showed significant negative correlation between ErbB4 and several cholesterol metabolic enzymes. In summary, our study uncovers ErbB4 as a protector in the development of CAC, for its loss could activate Kras by upregulating cholesterol metabolism.


Asunto(s)
Colesterol/metabolismo , Colitis/complicaciones , Neoplasias del Colon/etiología , Enfermedad de Crohn/patología , Receptor ErbB-4/metabolismo , Receptor ErbB-4/fisiología , Animales , Apoptosis , Proliferación Celular , Colitis/inducido químicamente , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Enfermedad de Crohn/metabolismo , Sulfato de Dextran , Genoma , Humanos , Ratones , Ratones Noqueados , Pronóstico
18.
Neurobiol Dis ; 124: 67-80, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30447302

RESUMEN

Alzheimer's disease (AD) treatment represents one of the largest unmet medical needs. Developing small molecules targeting Aß aggregation is an effective approach to prevent and treat AD. Here, we show that gallic acid (GA), a naturally occurring polyphenolic small molecule rich in grape seeds and fruits, has the capacity to alleviate cognitive decline of APP/PS1 transgenic mouse through reduction of Aß1-42 aggregation and neurotoxicity. Oral administration of GA not only improved the spatial reference memory and spatial working memory of 4-month-old APP/PS1 mice, but also significantly reduced the more severe deficits developed in the 9-month-old APP/PS1 mice in terms of spatial learning, reference memory, short-term recognition and spatial working memory. The hippocampal long-term-potentiation (LTP) was also significantly elevated in the GA-treated 9-month-old APP/PS1 mice with increased expression of synaptic marker proteins. Evidence from atomic force microscopy (AFM), dynamic light scattering (DLS) and thioflavin T (ThT) fluorescence densitometry analyses showed that GA significantly reduces Aß1-42 aggregation both in vitro and in vivo. Further, pre-incubating GA with oligomeric Aß1-42 reduced Aß1-42-mediated intracellular calcium influx and neurotoxicity. Molecular docking studies identified that the 3,4,5-hydroxyle groups of GA were essential in noncovalently stabilizing GA binding to the Lys28-Ala42 salt bridge and the -COOH group is critical for disrupting the salt bridge of Aß1-42. The predicated covalent interaction through Schiff-base formation between the carbonyl group of the oxidized product and ε-amino group of Lys16 is also critical for the disruption of Aß1-42 S-shaped triple-ß-motif and toxicity. Together, these studies demonstrated that GA can be further developed as a drug to treat AD through disrupting the formation of Aß1-42 aggregation.


Asunto(s)
Enfermedad de Alzheimer/complicaciones , Péptidos beta-Amiloides/metabolismo , Disfunción Cognitiva/tratamiento farmacológico , Ácido Gálico/administración & dosificación , Fragmentos de Péptidos/metabolismo , Precursor de Proteína beta-Amiloide/genética , Animales , Disfunción Cognitiva/etiología , Disfunción Cognitiva/metabolismo , Modelos Animales de Enfermedad , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Potenciación a Largo Plazo/efectos de los fármacos , Ratones Endogámicos C57BL , Ratones Transgénicos , Simulación del Acoplamiento Molecular , Presenilina-1/genética
19.
J Urol ; 201(1): 56-61, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30100402

RESUMEN

PURPOSE: We performed a single center evaluation to compare perioperative, pathological and functional outcomes of robotic partial nephrectomy of T1a renal masses less than vs greater than 2 cm. MATERIALS AND METHODS: Propensity score 1:1 matching of queried patients was performed using the institutional robotic partial nephrectomy database from January 2007 to January 2017. Matching was done by patient age, gender, race, body mass index, the Charlson comorbidity index, smoking status, diabetes, hypertension, hyperlipidemia, ASA® (American Society of Anesthesiologists®) score, estimated glomerular filtration rate, chronic kidney disease stage and R.E.N.A.L. (radius, exophytic/endophytic properties, nearness of tumor to collecting system or sinus, anterior/posterior, location relative to polar line and abutting main renal artery or vein) score. We analyzed the records of 524 patients, including 262 with a renal mass less than 2 cm vs 262 with a renal mass 2 cm or greater. Perioperative, pathological and functional outcomes were evaluated. RESULTS: Smaller renal masses (less than 2 cm) were associated with significantly lower operative time, blood loss, ischemia time (mean ± SD 14.3 ± 9.58 vs 21.5 ± 9.51 minutes, p <0.001) and intraoperative transfusions (0% vs 2.7%, p = 0.015). Moreover, we found superior early renal functional outcomes as assessed by the estimated glomerular filtration rate on postoperative day 1 (mean 83.1 ± 21.3 vs 76.6 ± 22.0 mg/ml/1.73 m, p = 0.001), greater parenchymal preservation (mean 89.9% ± 9.45% vs 83.6% ± 8.20%, p <0.001) and a trend toward a lower rate of postoperative complications (13.5% vs 19.5%, p = 0.080). A higher incidence of malignancy was found in larger tumors (85.9% vs 74.8%, p = 0.002) but no difference was recorded in positive surgical margins. CONCLUSIONS: Robotic partial nephrectomy tends to be a low morbidity treatment modality for renal masses less than 2 cm. Although active surveillance is a common option for such tumors, robotic partial nephrectomy remains an alternative in select patients.


Asunto(s)
Carcinoma de Células Renales/patología , Carcinoma de Células Renales/cirugía , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Nefrectomía/efectos adversos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Anciano , Femenino , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Tempo Operativo , Complicaciones Posoperatorias/epidemiología , Puntaje de Propensión , Recuperación de la Función , Estudios Retrospectivos , Resultado del Tratamiento
20.
J Urol ; 202(2): 309-313, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31026215

RESUMEN

PURPOSE: Kidney stone formers have lower health related quality of life than nonstone formers. The North American Stone Quality of Life Consortium is a multicenter, longitudinal, prospective study of health related quality of life in patients with kidney stones using the WISQOL (Wisconsin Stone Quality of Life Questionnaire) with data on 2,052 patients from a total of 11 centers. This study is a subanalysis of cross-sectional data looking at the association of age, gender and race on health related quality of life of stone formers. MATERIALS AND METHODS: We performed multivariable analyses of ordinal logistic regression analyses to determine the impact of age, gender and race on health related quality of life, adjusting for other baseline covariates. The proportional odds assumption of ordinal logistic regression was checked. Total score and scores on 4 subdomains (social functioning, emotional functioning, stone related impact and vitality) were included. RESULTS: Median total score for all patients was 80.4. On multivariable analysis older patients had a significantly higher total health related quality of life score than younger patients (per 10-year increase OR 1.25, p <0.0001). Male patients had higher scores than females (OR 1.56, p = 0.0003) and nonCaucasian patients had lower health related quality of life than nonLatino Caucasian patients (OR 0.63, p = 0.0045). CONCLUSIONS: Younger and female patients with kidney stones have lower health related quality of life than older and male patients, respectively. NonCaucasian patients with stones also have lower health related quality of life. The clinical impact of these findings might include future implications for patient counseling, including dietary and medical management of stone disease, and potential changes to the paradigm of the surgical management of stones.


Asunto(s)
Cálculos Renales , Calidad de Vida , Adulto , Factores de Edad , Estudios Transversales , Autoevaluación Diagnóstica , Femenino , Humanos , Cálculos Renales/diagnóstico , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores Sexuales
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