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1.
J Affect Disord ; 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38705527

RESUMEN

BACKGROUND: Glaucoma, a progressive neurodegenerative disorder leading to irreversible blindness, is associated with heightened rates of generalized anxiety and depression. This study aims to comprehensively investigate brain morphological changes in glaucoma patients, extending beyond visual processing areas, and explores potential overlaps with alterations observed in anxiety and depression. METHODS: A comparative meta-analysis was conducted, using case-control studies of brain structural integrity in glaucoma patients. We aimed to identify regions with gray matter volume (GMV) changes, examine their role within distinct large-scale networks, and assess overlap with generalized anxiety disorder (GAD) and major depressive disorder (MDD). RESULTS: Glaucoma patients exhibited significant GMV reductions in visual processing regions (lingual gyrus, thalamus). Notably, volumetric reductions extended beyond visual systems, encompassing the left putamen and insula. Behavioral and functional network decoding revealed distinct large-scale networks, implicating visual, motivational, and affective domains. The insular region, linked to pain and affective processes, displayed reductions overlapping with alterations observed in GAD. LIMITATIONS: While the study identified significant VBM changes, the inclusion of studies from both the glaucoma and GAD cohorts is limited due to the lack of independent studies meeting our inclusion criteria. CONCLUSION: The study proposes a tripartite brain model for glaucoma, connecting visual processing changes to the lingual gyrus and suggesting additional alterations in the putamen and insular regions tied to emotional or motivational functions. These neuroanatomical changes extend beyond the visual system, implying broader implications for brain structure and potential pathological developments, providing insights into the overall neurological consequences of this visually focused disorder.

2.
JPRAS Open ; 40: 245-252, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38694441

RESUMEN

Background: The fingertip amputation is an amputation type of the finger beyond the proximal nail fold. There is no vein available for anastomoses on the dorsal side of the finger, and the palmar vein of the finger is small and tightly attached to the skin. Therefore, it is relatively difficult to implement surgical anastomoses, which poses challenges to the clinical treatment of fingertip amputations. Case report: A 29-year-old male was admitted to the hospital due to "the amputation of the fingertips of the right index, middle, and ring fingers caused by a heavy object compression 3 h ago". The admission examination revealed that the right index, middle, and ring fingers were completely severed at the 1/2 plane of the nail bed, with irregular sections, severe contusion, and pollution. The X-ray examination showed comminuted fractures of the distal phalanges of the right index, middle, and ring fingers. Based on these findings, the patient was diagnosed with multiple severed fingertips of the right hand (Tamai Zone 1). The patient underwent debridement, vascular exploration, and replantation of the right index, middle, and ring fingertips under emergency general anesthesia. After surgery, anti-inflammatory, spasmolytic, and anticoagulant treatment and regular dressing changes were conducted. The patient did not receive a blood transfusion, and all three fingers survived. The appearance of these fingers was favorable 3 months after surgery, and the flexion and extension of these fingers were normal. Eventually, the patient achieved excellent Chen's hand function scores. Conclusions: To the best of our knowledge, this may be the first successful case regarding the replantation of three fingertips after amputations in Tamai Zone 1 with favorable outcomes. It can be maintained that super microsurgery can be used for the replantation of multiple fingertip amputations.

3.
Dev Cell ; 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38723629

RESUMEN

In mice, skin-resident type 2 innate lymphoid cells (ILC2s) exhibit some ILC3-like characteristics. However, the underlying mechanism remains elusive. Here, we observed lower expression of the ILC2 master regulator GATA3 specifically in cutaneous ILC2s (cILC2s) compared with canonical ILC2s, in line with its functionally divergent role in transcriptional control in cILC2s. Decreased levels of GATA3 enabled the expansion of RORγt fate-mapped (RORγtfm+) cILC2s after postnatal days, displaying certain similarities to ILC3s. Single-cell trajectory analysis showed a sequential promotion of the RORγtfm+ cILC2 divergency by RORγt and GATA3. Notably, during hair follicle recycling, these RORγtfm+ cILC2s accumulated around the hair follicle dermal papilla (DP) region to facilitate the process. Mechanistically, we found that GATA3-mediated integrin α3ß1 upregulation on RORγtfm+ cILC2s was required for their positioning around the DP. Overall, our study demonstrates a distinct regulatory role of GATA3 in cILC2s, particularly in promoting the divergence of RORγtfm+ cILC2s to facilitate hair follicle recycling.

4.
Nano Lett ; 24(15): 4580-4587, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38573804

RESUMEN

Photon upconverison has attracted a substantial amount of interest in diverse fields due to its characteristic anti-Stokes emissions. However, obtaining intense emission under low-power laser irradiation has remained a challenge. Here we report a mechanistic design of activator-sensitizer alloyed nanoparticles to achieve bright upconversion under weak infrared irradiation. This design allows a nearest sensitizer-activator separation to facilitate efficient energy transfer that results in remarkably enhanced upconversion (>2 orders of magnitude) under 0.26 W cm-2 irradiation compared to that of the Er sublattice, and the upconversion quantum yield also shows a 20-fold increase. Interestingly, the alloyed nanoparticles exhibit a gradual change in emission color with an increase in Yb3+ content, and moreover, their emission colors can be dynamically controlled by simply modulating the excitation laser power and pulse widths. Such alloyed nanoparticles show great promise for application in a near-infrared photodetector.

5.
Open Med (Wars) ; 19(1): 20240926, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38584830

RESUMEN

Ex vivo liver resection combined with autologous liver transplantation offers the opportunity to treat otherwise unresectable hepatobiliary malignancies and has been applied in clinic. The implementation of enhanced recovery after surgery (ERAS) program improves the outcome of surgical procedures. This is a retrospective single-center study including 11 cases of patients with liver cancer that underwent autologous liver transplantation and received ERAS: cholangiocarcinoma of the hilar region (n = 5), intrahepatic cholangiocarcinoma (n = 3), gallbladder cancer (n = 1), liver metastasis from colorectal cancer (n = 1), and liver metastasis from gastrointestinal mesenchymal tumor (n = 1). There were no deaths within 30 days and major complications occurred in two patients, and four patients were readmitted upon the first month after the surgery. Median hospital stay was 20 days (range 13-44) and median open diet was Day 4 (range 2-9) after surgery and median early post-operative activity was Day 5 (range 2-9) after surgery. In conclusion, autologous liver transplantation is feasible in the treatment of otherwise unresectable hepatobiliary malignancies, and our study showed favorable results with autologous liver transplantation in ERAS modality. ERAS modality provides a good option for some patients whose tumors cannot be resected in situ and offers a chance for rapid recovery.

6.
BMC Psychiatry ; 24(1): 269, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38600448

RESUMEN

OBJECTIVE: The purpose of this study was to investigate the effects of escitalopram on the peripheral expression of hypothalamic-pituitary-adrenal (HPA) axis-related genes (FKBP51, HSP90, NR3C1 and POMC) and HPA-axis hormones in patients with panic disorder (PD). METHODS: Seventy-seven patients with PD were treated with escitalopram for 12 weeks. All participants were assessed for the severity of panic symptoms using the Panic Disorder Severity Scale (PDSS). The expression of HPA-axis genes was measured using real-time quantitative fluorescent PCR, and ACTH and cortisol levels were measured using chemiluminescence at baseline and after 12 weeks of treatment. RESULTS: At baseline, patients with PD had elevated levels of ACTH and cortisol, and FKBP51 expression in comparison to healthy controls (all p < 0.01). Correlation analysis revealed that FKBP51 expression levels were significantly positively related to cortisol levels and the severity of PD (all p < 0.01). Furthermore, baseline ACTH and cortisol levels, and FKBP51 expression levels were significantly reduced after 12 weeks of treatment, and the change in the PDSS score from baseline to post-treatment was significantly and positively related to the change in cortisol (p < 0.01). CONCLUSIONS: The results suggest that PD may be associated with elevated levels of ACTH and cortisol, and FKBP51 expression, and that all three biomarkers are substantially decreased in patients who have received escitalopram treatment.


Asunto(s)
Trastorno de Pánico , Humanos , Trastorno de Pánico/tratamiento farmacológico , Trastorno de Pánico/genética , Trastorno de Pánico/diagnóstico , Hormona Adrenocorticotrópica/metabolismo , Hormona Adrenocorticotrópica/farmacología , Hidrocortisona/metabolismo , Escitalopram , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipófiso-Suprarrenal/metabolismo , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , ARN Mensajero
7.
Food Microbiol ; 121: 104499, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38637070

RESUMEN

In this study, we investigated the impact of microbial interactions on Monascus pigment (MP) production. We established diverse microbial consortia involving Monascus purpureus and Lactobacillus fermentum. The addition of Lactobacillus fermentum (4% at 48 h) to the submerged fermentation of M. purpureus resulted in a significantly higher MP production compared to that achieved using the single-fermentation system. Co-cultivation with immobilized L. fermentum led to a remarkable increase of 59.18% in extracellular MP production, while mixed fermentation with free L. fermentum caused a significant decrease of 66.93% in intracellular MPs, contrasting with a marginal increase of 4.52% observed during co-cultivation with immobilized L. fermentum and the control group respectively. The findings indicate an evident enhancement in cell membrane permeability of M. purpureus when co-cultivated with immobilized L. fementum. Moreover, integrated transcriptomic and metabolomic analyses were conducted to elucidate the regulatory mechanisms underlying MP biosynthesis and secretion following inoculation with immobilized L. fementum, with specific emphasis on glycolysis, steroid biosynthesis, fatty acid biosynthesis, and energy metabolism.


Asunto(s)
Monascus , Fermentación , Monascus/genética , Monascus/metabolismo , Pigmentos Biológicos/metabolismo , Consorcios Microbianos , Glucólisis
8.
Front Surg ; 11: 1378529, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38650659

RESUMEN

Background: Head and neck cancer is the 6th most common malignancy worldwide, and its incidence is still on the rise. The salvage surgery has been considered as an important treatment strategy for persistent or recurrent head and neck cancer. Therefore, we conducted a bibliometric analysis of salvage surgery for head and neck cancer since the 21st century. Methods: The literature about salvage surgery of head and neck cancer in Web of Science was searched. CiteSpace and VOSviewer were used to analyze main countries, institutions, authors, journals, subject hotspots, trends, frontiers, etc. Results: A total of 987 papers have been published since the 21st century. These publications were written by 705 authors from 425 institutions in 54 countries. The United States published 311 papers in this field and ranked first. Head & Neck was the most widely published journal. The main keyword clustering included terms such as #0 stereotactic radiotherapy (2012); #1 randomized multicenter (2007); #2 salvage surgery (2004); #3 functional outcomes (2014); #4 transoral robotic surgery (2013); #5 neck high-resolution computed tomography (2010); #6 complications (2008); #7 image guidance (2019). The current research frontiers that have been sustained are "recurrent", "risk factors", and "reirradiation". Conclusion: The current situation of the salvage surgery for head and neck cancer in clinical treatments and basic scientific research were summarized, providing new perspectives for the development of salvage surgery for head and neck cancer in the future.

9.
Sci Rep ; 14(1): 9338, 2024 04 23.
Artículo en Inglés | MEDLINE | ID: mdl-38654120

RESUMEN

Induced resistance is considered an eco-friendly disease control strategy, which can enhance plant disease resistance by inducing the plant's immune system to activate the defense response. In recent years, studies have shown that lactic acid can play a role in plant defense against biological stress; however, whether lactic acid can improve tobacco resistance to Phytophthora nicotianae, and its molecular mechanism remains unclear. In our study, the mycelial growth and sporangium production of P. nicotianae were inhibited by lactic acid in vitro in a dose-dependent manner. Application of lactic acid could reduce the disease index, and the contents of total phenol, salicylic acid (SA), jasmonic acid (JA), lignin and H2O2, catalase (CAT) and phenylalanine ammonia-lyase (PAL) activities were significantly increased. To explore this lactic acid-induced protective mechanism for tobacco disease resistance, RNA-Seq analysis was used. Lactic acid enhances tobacco disease resistance by activating Ca2+, reactive oxygen species (ROS) signal transduction, regulating antioxidant enzymes, SA, JA, abscisic acid (ABA) and indole-3-acetic acid (IAA) signaling pathways, and up-regulating flavonoid biosynthesis-related genes. This study demonstrated that lactic acid might play a role in inducing resistance to tobacco black shank disease; the mechanism by which lactic acid induces disease resistance includes direct antifungal activity and inducing the host to produce direct and primed defenses. In conclusion, this study provided a theoretical basis for lactic acid-induced resistance and a new perspective for preventing and treating tobacco black shank disease.


Asunto(s)
Resistencia a la Enfermedad , Ácido Láctico , Nicotiana , Oxilipinas , Phytophthora , Enfermedades de las Plantas , Phytophthora/patogenicidad , Phytophthora/fisiología , Nicotiana/microbiología , Nicotiana/inmunología , Nicotiana/genética , Nicotiana/metabolismo , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/inmunología , Enfermedades de las Plantas/prevención & control , Oxilipinas/metabolismo , Ácido Láctico/metabolismo , Ciclopentanos/metabolismo , Ácido Salicílico/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Regulación de la Expresión Génica de las Plantas , Ácido Abscísico/metabolismo , Fenilanina Amoníaco-Liasa/metabolismo , Transducción de Señal , Peróxido de Hidrógeno/metabolismo
10.
Enzyme Microb Technol ; 178: 110447, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38626534

RESUMEN

Clostridium butyricum (C. butyricum) represents a new generation of probiotics, which is beneficial because of its good tolerance and ability to produce beneficial metabolites, such as short-chain fatty acids and enzymes; however, its low enzyme activity limits its probiotic efficacy. In this study, a mutant strain, C. butyricum FZM 240 was obtained using carbon ion beam irradiation, which exhibited greatly improved enzyme production and tolerance. The highest filter paper, endoglucanase, and amylase activities produced by C. butyricum FZM 240 were 125.69 U/mL, 225.82 U/ mL, and 252.28 U/mL, which were 2.58, 1.95, and 2.21-fold higher, respectively, than those of the original strain. The survival rate of the strain increased by 11.40 % and 5.60 % after incubation at 90 °C for 5 min and with simulated gastric fluid at pH 2.5 for 2 h, respectively, compared with that of the original strain. Whole-genome resequencing and quantitative real-time PCR(qRT-PCR) analysis showed that the expression of genes related to enzyme synthesis (GE000348, GE001963 and GE003123) and tolerance (GE001114) was significantly up-regulated, while that of genes related to acid metabolism (GE003450) was significantly down-regulated. On this basis, homology modeling and functional prediction of the proteins encoded by the mutated genes were performed. According to the results, the properties related to the efficacy of C. butyricum as a probiotic were significantly enhanced by carbon ion beam irradiation, which is a novel strategy for the application of Clostridium spp. as feed additives.

11.
BMC Psychiatry ; 24(1): 290, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38632560

RESUMEN

BACKGROUND: The diagnosis of adolescent Depressive Disorder (DD) lacks specific biomarkers, posing significant challenges. This study investigates the potential of Niacin Skin Flush Response (NSFR) as a biomarker for identifying and assessing the severity of adolescent Depressive Disorder, as well as distinguishing it from Behavioral and Emotional Disorders typically emerging in childhood and adolescence(BED). METHODS: In a case-control study involving 196 adolescents, including 128 Depressive Disorder, 32 Behavioral and Emotional Disorders, and 36 healthy controls (HCs), NSFR was assessed. Depressive symptoms were measured using the Patient Health Questionnaire-9 (PHQ-9) and anxious symptoms with the Generalized Anxiety Disorder 7-item scale (GAD-7). Pearson correlation analysis determined the relationships between NSFR and the severity of depression in DD patients. Receiver Operating Characteristic (ROC) was used to identify DD from BED integrating NSFR data with clinical symptom measures. RESULTS: The adolescent Depressive Disorder group exhibited a higher rate of severe blunted NSFR (21.4%) compared to BED (12.5%) and HC ( 8.3%). Adolescent Depressive Disorder with psychotic symptoms showed a significant increase in blunted NSFR (p = 0.016). NSFR had negative correlations with depressive (r = -0.240, p = 0.006) and anxious (r = -0.2, p = 0.023) symptoms in adolescent Depressive Disorder. Integrating NSFR with three clinical scales improved the differentiation between adolescent Depressive Disorder and BED (AUC increased from 0.694 to 0.712). CONCLUSION: The NSFR demonstrates potential as an objective biomarker for adolescent Depressive Disorder, aiding in screening, assessing severity, and enhancing insights into its pathophysiology and diagnostic precision.


Asunto(s)
Niacina , Humanos , Adolescente , Depresión , Trastornos de Ansiedad/psicología , Estudios de Casos y Controles , Biomarcadores
12.
Med Image Anal ; 95: 103180, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38657423

RESUMEN

The high noise level of dynamic Positron Emission Tomography (PET) images degrades the quality of parametric images. In this study, we aim to improve the quality and quantitative accuracy of Ki images by utilizing deep learning techniques to reduce the noise in dynamic PET images. We propose a novel denoising technique, Population-based Deep Image Prior (PDIP), which integrates population-based prior information into the optimization process of Deep Image Prior (DIP). Specifically, the population-based prior image is generated from a supervised denoising model that is trained on a prompts-matched static PET dataset comprising 100 clinical studies. The 3D U-Net architecture is employed for both the supervised model and the following DIP optimization process. We evaluated the efficacy of PDIP for noise reduction in 25%-count and 100%-count dynamic PET images from 23 patients by comparing with two other baseline techniques: the Prompts-matched Supervised model (PS) and a conditional DIP (CDIP) model that employs the mean static PET image as the prior. Both the PS and CDIP models show effective noise reduction but result in smoothing and removal of small lesions. In addition, the utilization of a single static image as the prior in the CDIP model also introduces a similar tracer distribution to the denoised dynamic frames, leading to lower Ki in general as well as incorrect Ki in the descending aorta. By contrast, as the proposed PDIP model utilizes intrinsic image features from the dynamic dataset and a large clinical static dataset, it not only achieves comparable noise reduction as the supervised and CDIP models but also improves lesion Ki predictions.

13.
Br J Cancer ; 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38658783

RESUMEN

BACKGROUND: There is a need for diagnostic tests for screening, triaging and staging of epithelial ovarian cancer (EOC). Glycoproteomics of blood samples has shown promise for biomarker discovery. METHODS: We applied glycoproteomics to serum of people with EOC or benign pelvic masses and healthy controls. A total of 653 analytes were quantified and assessed in multivariable models, which were tested in an independent cohort. Additionally, we analyzed glycosylation patterns in serum markers and in tissues. RESULTS: We identified a biomarker panel that distinguished benign lesions from EOC with sensitivity and specificity of 83.5% and 90.1% in the training set, and of 86.7 and 86.7% in the test set, respectively. ROC analysis demonstrated strong performance across a range of cutoffs. Fucosylated multi-antennary glycopeptide markers were higher in late-stage than in early-stage EOC. A comparable pattern was found in late-stage EOC tissues. CONCLUSIONS: Blood glycopeptide biomarkers have the potential to distinguish benign from malignant pelvic masses, and early- from late-stage EOC. Glycosylation of circulating and tumor tissue proteins may be related. This study supports the hypothesis that blood glycoproteomic profiling can be used for EOC diagnosis and staging and it warrants further clinical evaluation.

14.
IEEE Trans Med Imaging ; PP2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38578853

RESUMEN

Single-Photon Emission Computed Tomography (SPECT) is widely applied for the diagnosis of coronary artery diseases. Low-dose (LD) SPECT aims to minimize radiation exposure but leads to increased image noise. Limited-view (LV) SPECT, such as the latest GE MyoSPECT ES system, enables accelerated scanning and reduces hardware expenses but degrades reconstruction accuracy. Additionally, Computed Tomography (CT) is commonly used to derive attenuation maps (µ-maps) for attenuation correction (AC) of cardiac SPECT, but it will introduce additional radiation exposure and SPECT-CT misalignments. Although various methods have been developed to solely focus on LD denoising, LV reconstruction, or CT-free AC in SPECT, the solution for simultaneously addressing these tasks remains challenging and under-explored. Furthermore, it is essential to explore the potential of fusing cross-domain and cross-modality information across these interrelated tasks to further enhance the accuracy of each task. Thus, we propose a Dual-Domain Coarse-to-Fine Progressive Network (DuDoCFNet), a multi-task learning method for simultaneous LD denoising, LV reconstruction, and CT-free µ-map generation of cardiac SPECT. Paired dual-domain networks in DuDoCFNet are cascaded using a multi-layer fusion mechanism for cross-domain and cross-modality feature fusion. Two-stage progressive learning strategies are applied in both projection and image domains to achieve coarse-to-fine estimations of SPECT projections and CT-derived µ-maps. Our experiments demonstrate DuDoCFNet's superior accuracy in estimating projections, generating µ-maps, and AC reconstructions compared to existing single- or multi-task learning methods, under various iterations and LD levels. The source code of this work is available at https://github.com/XiongchaoChen/DuDoCFNet-MultiTask.

15.
Acta Neuropsychiatr ; : 1-13, 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38571295

RESUMEN

BACKGROUND: Persistent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), reactivation of dormant viruses, and immune-oxidative responses are involved in long COVID. OBJECTIVES: To investigate whether long COVID and depressive, anxiety, and chronic fatigue syndrome (CFS) symptoms are associated with IgA/IgM/IgG to SARS-CoV-2, human herpesvirus type 6 (HHV-6), Epstein-Barr Virus (EBV), and immune-oxidative biomarkers. METHODS: We examined 90 long COVID patients and ninety healthy controls. We measured serum IgA/IgM/IgG against HHV-6 and EBV and their deoxyuridine 5'-triphosphate nucleotidohydrolase (duTPase), SARS-CoV-2, and activin-A, C-reactive protein (CRP), advanced oxidation protein products (AOPP), and insulin resistance (HOMA2-IR). RESULTS: Long COVID patients showed significant elevations in IgG/IgM-SARS-CoV-2, IgG/IgM-HHV-6, and HHV-6-duTPase, IgA/IgM-activin-A, CRP, AOPP, and HOMA2-IR. Neural network analysis yielded a highly significant predictive accuracy of 80.6% for the long COVID diagnosis (sensitivity: 78.9%, specificity: 81.8%, area under the ROC curve = 0.876); the topmost predictors were as follows: IGA-activin-A, IgG-HHV-6, IgM-HHV-6-duTPase, IgG-SARS-CoV-2, and IgM-HHV-6 (all positively) and a factor extracted from all IgA levels to all viral antigens (inversely). The top 5 predictors of affective symptoms due to long COVID were IgM-HHV-6-duTPase, IgG-HHV-6, CRP, education, IgA-activin-A (predictive accuracy of r = 0.636). The top 5 predictors of CFS due to long COVID were in descending order: CRP, IgG-HHV-6-duTPase, IgM-activin-A, IgM-SARS-CoV-2, and IgA-activin-A (predictive accuracy: r = 0.709). CONCLUSION: Reactivation of HHV-6, SARS-CoV-2 persistence, and autoimmune reactions to activin-A combined with activated immune-oxidative pathways play a major role in the pathophysiology of long COVID as well as the severity of its affective symptoms and CFS.

16.
Transl Neurodegener ; 13(1): 24, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38671492

RESUMEN

BACKGROUND: Adult neurogenesis occurs in the subventricular zone (SVZ) and the subgranular zone of the dentate gyrus in the hippocampus. The neuronal stem cells in these two neurogenic niches respond differently to various physiological and pathological stimuli. Recently, we have found that the decrement of carboxypeptidase E (CPE) with aging impairs the maturation of brain-derived neurotrophic factor (BDNF) and neurogenesis in the SVZ. However, it remains unknown whether these events occur in the hippocampus, and what the role of CPE is in the adult hippocampal neurogenesis in the context of Alzheimer's disease (AD). METHODS: In vivo screening was performed to search for miRNA mimics capable of upregulating CPE expression and promoting neurogenesis in both neurogenic niches. Among these, two agomirs were further assessed for their effects on hippocampal neurogenesis in the context of AD. We also explored whether these two agomirs could ameliorate behavioral symptoms and AD pathology in mice, using direct intracerebroventricular injection or by non-invasive intranasal instillation. RESULTS: Restoration of CPE expression in the hippocampus improved BDNF maturation and boosted adult hippocampal neurogenesis. By screening the miRNA mimics targeting the 5'UTR region of Cpe gene, we developed two agomirs that were capable of upregulating CPE expression. The two agomirs significantly rescued adult neurogenesis and cognition, showing multiple beneficial effects against the AD-associated pathologies in APP/PS1 mice. Of note, noninvasive approach via intranasal delivery of these agomirs improved the behavioral and neurocognitive functions of APP/PS1 mice. CONCLUSIONS: CPE may regulate adult hippocampal neurogenesis via the CPE-BDNF-TrkB signaling pathway. This study supports the prospect of developing miRNA agomirs targeting CPE as biopharmaceuticals to counteract aging- and disease-related neurological decline in human brains.


Asunto(s)
Enfermedad de Alzheimer , Carboxipeptidasa H , Hipocampo , Trastornos de la Memoria , Neurogénesis , Regulación hacia Arriba , Animales , Neurogénesis/efectos de los fármacos , Neurogénesis/fisiología , Enfermedad de Alzheimer/genética , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Carboxipeptidasa H/genética , Carboxipeptidasa H/biosíntesis , Ratones , Trastornos de la Memoria/genética , Trastornos de la Memoria/etiología , Factor Neurotrófico Derivado del Encéfalo/biosíntesis , Factor Neurotrófico Derivado del Encéfalo/genética , Factor Neurotrófico Derivado del Encéfalo/metabolismo , MicroARNs/genética , MicroARNs/biosíntesis , Masculino , Ratones Transgénicos , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad
17.
Biomolecules ; 14(4)2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38672450

RESUMEN

Motilin is a gastrointestinal hormone that is mainly produced in the duodenum of mammals, and it is responsible for regulating appetite. However, the role and expression of motilin are poorly understood during starvation and the weaning stage, which is of great importance in the seeding cultivation of fish. In this study, the sequences of Yangtze sturgeon (Acipenser dabryanus Motilin (AdMotilin)) motilin receptor (AdMotilinR) were cloned and characterized. The results of tissue expression showed that by contrast with mammals, AdMotilin mRNA was richly expressed in the brain, whereas AdMotilinR was highly expressed in the stomach, duodenum, and brain. Weaning from a natural diet of T. Limnodrilus to commercial feed significantly promoted the expression of AdMotilin in the brain during the period from day 1 to day 10, and after re-feeding with T. Limnodrilus the change in expression of AdMotilin was partially reversed. Similarly, it was revealed that fasting increased the expression of AdMotilin in the brain (3 h, 6 h) and duodenum (3 h), and the expression of AdMotilinR in the brain (1 h) in a time-dependent manner. Furthermore, it was observed that peripheral injection of motilin-NH2 increased food intake and the filling index of the digestive tract in the Yangtze sturgeon, which was accompanied by the changes of AdMotilinR and appetite factors expression in the brain (POMC, CART, AGRP, NPY and CCK) and stomach (CCK). These results indicate that motilin acts as an indicator of nutritional status, and also serves as a novel orexigenic factor that stimulates food intake in Acipenser dabryanus. This study lays a strong foundation for the application of motilin as a biomarker in the estimation of hunger in juvenile Acipenser dabryanu during the weaning phase, and enhances the understanding of the role of motilin as a novel regulator of feeding in fish.


Asunto(s)
Peces , Motilina , Animales , Motilina/metabolismo , Peces/metabolismo , Peces/genética , Peces/fisiología , Receptores de la Hormona Gastrointestinal/metabolismo , Receptores de la Hormona Gastrointestinal/genética , Receptores de Neuropéptido/metabolismo , Receptores de Neuropéptido/genética , Conducta Alimentaria , Proteínas de Peces/metabolismo , Proteínas de Peces/genética , Encéfalo/metabolismo
18.
Sci Total Environ ; : 172742, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38679098

RESUMEN

Wastewater monitoring may be a valuable early surveillance tool for studying mpox virus (MPXV) circulation in China, a country with high population density and very few mpox patients. To evaluate the effectiveness of wastewater monitoring for MPXV in detecting local hidden transmission of the epidemic in the early period, the Chinese Center for Disease Control and Prevention initiated a wastewater monitoring program for MPXV in China in July 2023. To enhance the monitoring sensitivity of the program, an MPXV monitoring point was established in a gathering place of high-risk mpox population. Three different concentration methods, PEG precipitation, ultrafiltration, and magnetic beads method were evaluated and compared. Due to its high recovery efficiency, low limit of detection, and high degree of automation, the magnetic beads method was selected for the daily surveillance of MPXV in wastewater. On September 5, 2023, MPXV DNA was detected at the MPXV monitoring point in Zibo City, marking the first instance of MPXV detection of MPXV in wastewater in China. Next-generation sequencing was conducted on the MPXV genome obtained from the positive wastewater, positive environmental samples, and the single case of mpox in Zibo in September. The results showed that the genotypes of these three genomes were different but all belong to the IIb branch of the C.1 lineage, indicating a probably hidden transmission of mpox. Wastewater monitoring is potentially an effective early surveillance tool for tracking the spread of MPXV in areas with high population density and very few mpox patients.

19.
Nat Prod Res ; : 1-8, 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38683975

RESUMEN

A new labdane diterpene (1), two new norsesquiterpenoids (2-3), as well as eight known terpenoids (4-11) were isolated from the seeds of Alpinia galanga (Zingiberaceae). Their structures and absolute configurations were elucidated by 1D, 2D NMR, MS, and comparison of their experimental and calculated electronic circular dichroism (ECD). The acetylcholinesterase (AChE) inhibitory activities of all the isolated compounds (1-11) were evaluated and the result showed that compounds 6 and 9 had inhibitory activity against AChE, with IC50 values at 295.70 and 183.91 µM, whereas other compounds did not show any inhibitory activity.

20.
Org Lett ; 26(18): 3861-3866, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38679881

RESUMEN

Catalytic cyclization of enynes is an efficient approach for the preparation of cyclic compounds, and a large variety of four- to six-membered rings could be synthesized using this method. However, it has been rarely employed for the construction of medium- and large-sized rings. Herein, we describe a copper-catalyzed cycloisomerization of ene-ynamides through a [2 + 2] cyclization/electrocyclic ring opening cascade, leading to the atom-economical assembly of indole-fused medium- and large-sized rings in moderate to excellent yields under mild reaction conditions. Importantly, the synthetic utility of this reaction was demonstrated by the convenient synthesis of iprindole.

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