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1.
Front Mol Neurosci ; 17: 1405532, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39165718

RESUMEN

Introduction: The cingulate cortex, with its subregions ACC, MCC, and RSC, is key in pain processing. However, the detailed interactions among these regions in modulating pain sensation have remained unclear. Methods: In this study, chemogenetic tools were employed to selectively activate or inhibit neuronal activity in the MCC and RSC of rodents to elucidate their roles in pain regulation.Results: Our results showed that chemogenetic activation in both the RSC and MCC heightened pain sensitivity. Suppression of MCC activity disrupted the RSC's regulation of both mechanical and thermal pain, while RSC inhibition specifically affected the MCC's regulation of thermal pain. Discussion: The findings indicate a complex interplay between the MCC and RSC, with the MCC potentially governing the RSC's pain regulatory mechanisms. The RSC, in turn, is crucial for the MCC's control over thermal sensation, revealing a collaborative mechanism in pain processing. Conclusion: This study provides evidence for the MCC and RSC's collaborative roles in pain regulation, highlighting the importance of their interactions for thermal and mechanical pain sensitivity. Understanding these mechanisms could aid in developing targeted therapies for pain disorders.

2.
World Neurosurg ; 189: 228-247, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38901485

RESUMEN

Full-endoscopic lumbar interbody fusion (FELIF) is a critical yet challenging procedure. However, extensive analyses of discectomy and cartilage endplate preparation techniques are limited. This can be attributed to the lack of universal protocols owing to diverse surgical practices and equipment preferences. Therefore, this narrative review presents a comprehensive overview of discectomy and cartilage endplate preparation techniques in FELIF. A literature search of the PubMed, Embase, and Google Scholar databases in December 2023 retrieved 490 studies, of which 53 met the predefined inclusion criteria, and 1373 patients were included in the analyses. Spinal endoscopic disc and cartilage endplate removal can be categorized into 2 main types: removal under direct endoscopic visualization and removal under radiographic guidance with the protection of a working sheath following the endoscope's removal. Removal under direct visualization ensures the safety and precision of the procedure. Radiographic guidance can enhance the efficiency of the removal process. Specially designed instruments can be utilized through the narrow working channels of spinal endoscopes for the scraping surgery. Moreover, many traditional spinal endoscopic instruments, through specific techniques and manipulations, can also aid in cartilage removal. The approaches and techniques vary significantly among physicians, but overall, these instruments and techniques aim to achieve a safe and efficient disc-scraping outcome. Thus, this review may offer a comprehensive guidance to surgeons in selecting the most efficient practices for FELIF. Uniform procedural protocols are needed to ensure broader adoption and standardized practice.

3.
Cancer Lett ; 598: 217094, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-38945204

RESUMEN

Recent therapeutic strategies for the treatment of triple-negative breast cancer (TNBC) have shifted the focus from vascular growth factors to endothelial cell metabolism. This study highlights the underexplored therapeutic potential of peri-tumoral electroacupuncture, a globally accepted non-pharmacological intervention for TNBC, and molecular mechanisms. Our study showed that peri-tumoral electroacupuncture effectively reduced the density of microvasculature and enhanced vascular functionality in 4T1 breast cancer xenografts, with optimal effects on day 3 post-acupuncture. The timely integration of peri-tumoral electroacupuncture amplified the anti-tumor efficacy of paclitaxel. Multi-omics analysis revealed Glyoxalase 1 (Glo1) and the associated methylglyoxal-glycolytic pathway as key mediators of electroacupuncture-induced vascular normalization. Peri-tumoral electroacupuncture notably reduced Glo1 expression in the endothelial cells of 4T1 xenografts. Using an in vivo matrigel plug angiogenesis assay, we demonstrated that either Glo1 knockdown or electroacupuncture inhibited angiogenesis. In contrast, Glo1 overexpression increased blood vessel formation. In vitro pharmacological inhibition and genetic knockdown of Glo1 in human umbilical vein endothelial cells inhibited proliferation and promoted apoptosis via downregulating the methylglyoxal-glycolytic pathway. The study using the Glo1-silenced zebrafish model further supported the role of Glo1 in vascular development. This study underscores the pivotal role of Glo1 in peri-tumoral electroacupuncture, spotlighting a promising avenue for enhancing vascular normalization and improving TNBC treatment outcomes.


Asunto(s)
Electroacupuntura , Glucólisis , Lactoilglutatión Liasa , Neovascularización Patológica , Neoplasias de la Mama Triple Negativas , Animales , Femenino , Humanos , Ratones , Línea Celular Tumoral , Proliferación Celular , Electroacupuntura/métodos , Células Endoteliales/metabolismo , Células Endoteliales de la Vena Umbilical Humana , Lactoilglutatión Liasa/metabolismo , Lactoilglutatión Liasa/genética , Ratones Endogámicos BALB C , Neovascularización Patológica/metabolismo , Paclitaxel/farmacología , Piruvaldehído/metabolismo , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/terapia , Ensayos Antitumor por Modelo de Xenoinjerto , Pez Cebra
4.
J Cell Physiol ; 239(8): e31298, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38764331

RESUMEN

Early-onset preeclampsia, which occurrs before 34 weeks of gestation, is the most dangerous classification of preeclampsia, which is a pregnancy-specific disease that causes 1% of maternal deaths. G protein-coupled receptor 124 (GPR124) is significantly expressed at various stages of the human reproductive process, particularly during embryogenesis and angiogenesis. Our prior investigation demonstrated a notable decrease in GPR124 expression in the placentas of patients with early-onset preeclampsia compared to that in normal pregnancy placentas. However, there is a lack of extensive investigation into the molecular processes that contribute to the role of GPR124 in placenta development. This study aimed to examine the mechanisms by which GPR124 affects the occurrence of early-onset preeclampsia and its function in trophoblast. Proliferative, invasive, migratory, apoptotic, and inflammatory processes were identified in GPR124 knockdown, GPR124 overexpression, and normal HTR8/SVneo cells. The mechanism of GPR124-mediated cell function in GPR124 knockdown HTR8/SVneo cells was examined using inhibitors of the JNK or P38 MAPK pathway. Downregulation of GPR124 was found to significantly inhibit proliferation, invasion and migration, and promote apoptosis of HTR8/SVneo cells when compared to the control and GPR124 overexpression groups. This observation is consistent with the pathological characteristics of preeclampsia. In addition, GPR124 overexpression inhibits the secretion of pro-inflammatory cytokines interleukin (IL)-8 and interferon-γ (IFN-γ) while enhancing the secretion of the anti-inflammatory cytokine interleukin (IL)-4. Furthermore, GPR124 suppresses the activation of P-JNK and P-P38 within the JNK/P38 MAPK pathway. The invasion, apoptosis, and inflammation mediated by GPR124 were partially restored by suppressing the JNK and P38 MAPK pathways in HTR8/SVneo cells. GPR124 plays a crucial role in regulating trophoblast proliferation, invasion, migration, apoptosis, and inflammation via the JNK and P38 MAPK pathways. Furthermore, the effect of GPR124 on trophoblast suggests its involvement in the pathogenesis of early-onset preeclampsia.


Asunto(s)
Apoptosis , Movimiento Celular , Proliferación Celular , Inflamación , Preeclampsia , Receptores Acoplados a Proteínas G , Trofoblastos , Proteínas Quinasas p38 Activadas por Mitógenos , Humanos , Trofoblastos/metabolismo , Trofoblastos/patología , Apoptosis/genética , Proliferación Celular/genética , Femenino , Movimiento Celular/genética , Embarazo , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Preeclampsia/patología , Preeclampsia/genética , Preeclampsia/metabolismo , Inflamación/patología , Inflamación/genética , Inflamación/metabolismo , Sistema de Señalización de MAP Quinasas , Línea Celular , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Placenta/metabolismo , Placenta/patología , Receptores de Estrógenos
5.
J Clin Med ; 13(7)2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38610675

RESUMEN

Background: This study investigates the efficacy of the Cervical Endoscopic Unilateral Laminoforaminotomy for Bilateral Decompression (CE-ULFBD) technique in treating cervical myeloradiculopathy, primarily caused by degenerative spondylosis. Traditionally managed through multisegmental anterior cervical discectomy and fusion (ACDF) or laminoplasty combined with foraminotomy, this condition has recently experienced a promising shift towards minimally invasive approaches, particularly endoscopic spinal decompression. While empirical evidence is still emerging, these techniques show potential for effective treatment. Method: The objective was to evaluate the outcomes of CE-ULFBD in achieving single or multilevel bilateral foraminal and central decompression, emphasizing the reduction of injury to posterior cervical muscles and the associated postoperative neck soreness common in conventional procedures. This paper delineates the surgical procedures involved in CE-ULFBD and presents the clinical outcomes of nine patients diagnosed with myeloradiculopathy due to severe cervical stenosis. Result: Assessments were conducted using the Visual Analogue Scale (VAS) for neck and arm pain and the Modified Japanese Orthopaedic Association scale (mJOA) for the activity measurement of daily living. Results indicated a considerable decrease in pain levels according to the VAS, coupled with significant improvements in functional capacities as measured by the mJOA scale. Additionally, no major postoperative complications were noted during the follow-up period. Conclusion: The study concludes that CE-ULFBD is a safe and effective approach for the treatment of cervical myeloradiculopathy resulting from severe cervical stenosis, offering a viable and less invasive alternative to traditional decompressive surgeries.

6.
Eur Spine J ; 33(2): 417-428, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37389696

RESUMEN

PURPOSE: Full-endoscopic lumbar interbody fusion (FELIF) is a new-generation treatment for spondylolisthesis. However, owing to their unique characteristics, the two main endoscopic fusion trajectories, the trans-Kambin and posterolateral approaches, have important limitations. Herein, we aimed to introduce a new technique called Kambin Torpedo FELIF (KT-FELIF). METHODS: The KT-FELIF technique is based on the trans-Kambin approach. It additionally completes ipsilateral total facetectomy and contralateral direct decompression. Thus, this novel technique combines the advantages of the trans-Kambin and posterolateral approaches. RESULTS: We reported on the indications and technical steps of KT-FELIF and provided intraoperative and animated videos to clarify the procedure. Short-term follow-up based on 3-month postoperative computed tomography and plain films images taken at least 3 months after surgery showed adequate bony decompression, a large bone graft contact area, and good intervertebral trabecular bone growth without radiolucent lines between the graft, cage, and end plate. The clinical results, such as ipsilateral and contralateral visual analog scale and Oswestry disability index values, gradually improved at 1 and 3 months postoperatively. No complications were observed. CONCLUSIONS: KT-FELIF is a promising FELIF technique for achieving bilateral direct decompression through a unilateral approach while accomplishing thorough discectomy and endplate preparation.


Asunto(s)
Endoscopía , Investigación , Humanos , Placas Óseas , Trasplante Óseo , Hueso Esponjoso
7.
Cell Rep ; 42(12): 113551, 2023 12 26.
Artículo en Inglés | MEDLINE | ID: mdl-38048224

RESUMEN

The retrosplenial cortex (RSC) is a vital area for storing remote memory and has recently been found to undergo broad changes after peripheral nerve injury. However, little is known about the role of RSC in pain regulation. Here, we examine the involvement of RSC in the pain of mice with nerve injury. Notably, reducing the activities of calcium-/calmodulin-dependent protein kinase type II-positive splenial neurons chemogenetically increases paw withdrawal threshold and extends thermal withdrawal latency in mice with nerve injury. The single-cell or single-nucleus RNA-sequencing results predict enhanced excitatory synaptic transmissions in RSC induced by nerve injury. Local infusion of 1-naphthyl acetyl spermine into RSC to decrease the excitatory synaptic transmissions relieves pain and induces conditioned place preference. Our data indicate that RSC is critical for regulating physiological and neuropathic pain. The cell type-dependent transcriptomic information would help understand the molecular basis of neuropathic pain.


Asunto(s)
Neuralgia , Traumatismos de los Nervios Periféricos , Ratones , Animales , Giro del Cíngulo/fisiología , Traumatismos de los Nervios Periféricos/genética , Traumatismos de los Nervios Periféricos/metabolismo , Neuronas/metabolismo , Perfilación de la Expresión Génica , Neuralgia/genética , Neuralgia/metabolismo
8.
Mol Psychiatry ; 2023 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-38001337

RESUMEN

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with a complex pathogenesis. Senile plaques composed of the amyloid-ß (Aß) peptide in the brain are the core hallmarks of AD and a promising target for the development of disease-modifying therapies. However, over the past 20 years, the failures of clinical trials directed at Aß clearance have fueled a debate as to whether Aß is the principal pathogenic factor in AD and a valid therapeutic target. The success of the recent phase 3 trials of lecanemab (Clarity AD) and donanemab (Trailblazer Alz2), and lessons from previous Aß clearance trials provide critical evidence to support the role of Aß in AD pathogenesis and suggest that targeting Aß clearance is heading in the right direction for AD treatment. Here, we analyze key questions relating to the efficacy of Aß targeting therapies, and provide perspectives on early intervention, adequate Aß removal, sufficient treatment period, and combinatory therapeutics, which may be required to achieve the best cognitive benefits in future trials in the real world.

9.
J Alzheimers Dis Rep ; 7(1): 1153-1164, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38025803

RESUMEN

Background: As the primary caregivers for people with dementia in China, family caregivers face a significant care burden that can negatively impact their mental and physical health. It is vital to investigate ways to support these caregivers. Objective: To assess the effectiveness of a program led by community nurses to support caregivers of individuals with dementia. Methods: A total of 30 caregivers received nurse-led support in addition to usual care, while 28 caregivers received only usual care. The primary outcome was caregivers' sense of competency in providing dementia care, which was measured using the Short Sense of Competence Questionnaire (SSCQ). Secondary outcomes included caregivers' ability to perform daily activities, behavioral and psychological symptoms of dementia (BPSD) using a neuropsychiatric inventory questionnaire, and quality of life using the short form health survey (SF-36). The trial was registered at the Chinese Clinical Trial Registry (ChiCTR 2300071484). Results: Compared to the control group, the intervention group had significantly higher SSCQ scores and a lower caregiver distress index over time. Physical and mental health-related quality of life also improved significantly among caregivers in the intervention group. However, there was no significant difference between the two groups in terms of activities of daily living and BPSD. Conclusions: The community nurse-led support program significantly improved caregivers' competency in providing dementia care and quality of life and reduced distress. These findings have important implications for dementia care policies, resources, and workforce development in China, including strengthening community dementia care services through collaboration with specialists in hospitals.

10.
Huan Jing Ke Xue ; 44(9): 5176-5185, 2023 Sep 08.
Artículo en Chino | MEDLINE | ID: mdl-37699835

RESUMEN

This study was conducted to explore the fertilization potential of the high-volume straw returning mode in cooperation with Bacillus and other functional flora on desertification soil and to analyze the changing characteristics of soil carbon, nitrogen, and phosphorus components and functional activities of flora, so as to provide a basis for efficiently improving desertification soil fertility. A randomized block experiment was conducted, setting straw not returning to field (CK) and high-volume straw returning of 6.00 kg·m-2 (ST1), 12.00 kg·m-2 (ST2), 24.00 kg·m-2+(ST3), 6.00 kg·m-2+Bacillus (SM1), 12.00 kg·m-2+Bacillus (SM2), and 24.00 kg·m-2+Bacillus (SM3). In this study, we conducted a randomized block experiment to investigate the effect of the treatment for soil microbial and nutrient contents using 16S rRNA high-throughput sequencing and soil biochemical properties analysis. Our results showed that:① the α diversity of the soil bacterial community was significantly reduced by the combination of high-volume straw returning and Bacillus application. ② The single mode of high-volume straw returning significantly enriched Proteobacteria and decreased the relative abundance of Actinobacteriota, and the effect of the combined application of Bacillus on the variability of bacterial community structure was more significant. At the genus level, the relative abundance of beneficial bacteria such as Pseudomonas, Rhodanobacter, and Bacillus increased significantly. ③ The functional prediction based on FAPROTAX found that the high-volume straw returning combined with Bacillus could significantly improve the decomposition potential of soil flora to organic substances and the transformation potential of nitrogen components. ④ Compared with that in the control, the application of Bacillus with high-volume straw returning significantly increased the contents of soil organic matter, total phosphorus, and available phosphorus by 31.20-32.75 g·kg-1, 0.11-0.18 g·kg-1, and 29.69-35.09 mg·kg-1, respectively. In conclusion, the application of Bacillus in the sand-blown area with a high-volume straw returning can notably improve the contents of soil organic matter and phosphorus components, the functional activity of bacteria, and the abundance of beneficial bacteria, which is of great significance to the rapid improvement of soil fertility in the middle- and low-yield fields in arid areas.


Asunto(s)
Bacillus , Suelo , Conservación de los Recursos Naturales , ARN Ribosómico 16S , Bacterias/genética , Nitrógeno , Fósforo
11.
Int J Biol Macromol ; 252: 126480, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-37634770

RESUMEN

LED-related blue-light-induced damage can cause eye diseases. However, drug delivery in patients with ocular diseases is faced with various challenges. In this study, we developed flexible liposomes based on trimethylated chitosan (TMC-Lipo) to deliver resveratrol for the treatment of retinal diseases. Flexible liposomes can easily cross various biological barriers. Chitosan and its derivatives have adhesive properties and are widely used in mucoadhesive drug delivery systems. Therefore, we wrapped flexible liposomes with trimethylated chitosan via electrostatic adsorption. The charge of the flexible liposomes became positive after encapsulation in TMC, and they remained stable in artificial tears. We assessed the safety of TMC-Lipo in cellular and zebrafish experiments and found that it can be safely used. In addition, treatment with TMC-Lipo significantly reduced H2O2-induced damage to ARPE-19 cells, restored mitochondrial membrane potential, and protected the cells. TMC-Lipo more easily reached the posterior ocular segment of the mice than liposome nanoparticles and attenuated blue-light-induced retinal cytopathy. Our study demonstrates that effective eye drop formulations can be developed based on trimethylated chitosan, which provides a promising approach for the treatment of ocular diseases.


Asunto(s)
Quitosano , Enfermedades de la Retina , Humanos , Ratones , Animales , Liposomas , Resveratrol/farmacología , Portadores de Fármacos , Peróxido de Hidrógeno , Pez Cebra , Sistemas de Liberación de Medicamentos
12.
Brain Res Bull ; 202: 110735, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37586425

RESUMEN

Intermittent theta burst stimulation (iTBS), an emerging and highly efficient paradigm of repetitive transcranial magnetic stimulation (rTMS), has been demonstrated to mitigate cognitive impairment in Alzheimer's disease. Previous clinical studies have shown that the cognitive improvement of iTBS could last several weeks after treatment. Nonetheless, it is largely uncertain how the long-term effects of iTBS treatment are sustained. To investigate whether iTBS has a long-term effect on AD-type pathologies, 6-month-old APP/PS1 mice are administrated with 30 consecutive days of iTBS treatment. After a 2-month interval, morphological alterations in the brain are examined by immunohistochemistry and immunofluorescence staining, while levels of associated proteins are assessed by Western blot at the age of 9 months. We find that iTBS treatment significantly diminishes Aß burden in the cerebral cortex and hippocampus of APP/PS1 mice. Moreover, we observe that iTBS treatment inhibits the expression of BACE1 and elevates the level of IDE, suggesting that the reduction of Aß load could be attributed to the inhibition of Aß production and facilitation of Aß degradation. Furthermore, iTBS treatment attenuates neuroinflammation, neuronal apoptosis, and synaptic loss in APP/PS1 mice. Collectively, these data indicate that 1 month of iTBS treatment ameliorates pathologies in the brain of AD mice for at least 2 months. We provide the novel evidence that iTBS may exert after-effects on AD-type pathologies via inhibition of Aß production and facilitation of Aß degradation.


Asunto(s)
Enfermedad de Alzheimer , Ratones , Animales , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Estimulación Magnética Transcraneal , Ratones Transgénicos , Ácido Aspártico Endopeptidasas , Modelos Animales de Enfermedad , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Presenilina-1/genética , Presenilina-1/metabolismo
14.
Front Med (Lausanne) ; 10: 1166429, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37457580

RESUMEN

Purpose: This study aimed to investigate the relationship among changes in corneal topography, retinal vascular density, and retinal thickness in myopic children who underwent orthokeratology for 3 months. Method: Thirty children with myopia wore orthokeratology lenses for 3 months. Using optical coherence tomography angiography (OCTA), the retina was imaged as 6 × 6 mm en-face images at baseline and 3 months after orthokeratology. Cornea data was acquired by topography and analyzed by customer MATLAB software. The cornea was divided into 3 zones and 9 sectors. The relative corneal refractive power shift (RCRPS) was used in this study. Changes in retinal vascular density (RVDC) and retinal thickness change (RTC) were associated with RCRPS by using spearman test. Statistical significance was set at p < 0.05. Result: A significant correlation was observed between the RVDC and the RCRPS in many regions (the r was 0.375 ~ 0.548, all p value <0.05). Significant positive correlations were found between RVDC in inner and outer temple regions with RCRPS at inner and outer nasal sectors. There were no significant correlations between RTC and RCRPS in other sectors except in the central cornea and the outer nasal retina (r:0.501, p:0.006). At baseline and 3 months after wearing the orthokeratology lens, no significant differences in the retinal microvasculature or thickness (p > 0.05) were observed at any regions. Conclusion: The correlation between the cornea and the retina was observed after orthokeratology. Cornea changes may affect regional retinal responses accordingly,which may explain how orthokeratology delays myopia progression partially.

15.
Front Immunol ; 14: 1224892, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37483616

RESUMEN

Activator protein-1 (AP-1) is a transcription factor that consists of a diverse group of members including Jun, Fos, Maf, and ATF. AP-1 involves a number of processes such as proliferation, migration, and invasion in cells. Dysfunctional AP-1 activity is associated with cancer initiation, development, invasion, migration and drug resistance. Therefore, AP-1 is a potential target for cancer targeted therapy. Currently, some small molecule inhibitors targeting AP-1 have been developed and tested, showing some anticancer effects. However, AP-1 is complex and diverse in its structure and function, and different dimers may play different roles in different type of cancers. Therefore, more research is needed to reveal the specific mechanisms of AP-1 in cancer, and how to select appropriate inhibitors and treatment strategies. Ultimately, this review summarizes the potential of combination therapy for cancer.


Asunto(s)
Neoplasias , Factor de Transcripción AP-1 , Humanos , Factor de Transcripción AP-1/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Proteínas Proto-Oncogénicas c-jun/metabolismo , Regulación de la Expresión Génica
16.
Front Mol Neurosci ; 16: 1153870, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37152432

RESUMEN

The deficit of fragile X messenger ribonucleoprotein (FMRP) leads to intellectual disability in human and animal models, which also leads to desensitization of pain after nerve injury. Recently, it was shown that the protein arginine methyltransferases 1 (PRMT1) regulates the phase separation of FMRP. However, the role of PRMT1 in pain regulation has been less investigated. Here we showed that the downregulation of PRMT1 in the anterior cingulate cortex (ACC) contributes to the development of peripheral pain hypersensitivity. We observed that the peripheral nerve injury decreased the expression of PRMT1 in the ACC; knockdown of the PRMT1 via shRNA in the ACC decreased the paw withdrawal thresholds (PWTs) of naïve mice. Moreover, the deficits of FMRP abolished the effects of PRMT1 on pain sensation. Furthermore, overexpression of PRMT1 in the ACC increased the PWTs of mice with nerve injury. These observations indicate that the downregulation of cingulate PRMT1 was necessary and sufficient to develop peripheral hypersensitivity after nerve injury. Thus, we provided evidence that PRMT1 is vital in regulating peripheral pain hypersensitivity after nerve injury via the FMRP.

17.
Front Neurosci ; 17: 1180454, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37179566

RESUMEN

Background: Cerebellar ataxia (CA) is a movement disorder that can affect balance and gait, limb movement, oculomotor control, and cognition. Multiple system atrophy-cerebellar type (MSA-C) and spinocerebellar ataxia type 3 (SCA3) are the most common forms of CA, for which no effective treatment is currently available. Transcranial alternating current stimulation (tACS) is a non-invasive method of brain stimulation supposed to alter cortical excitability and brain electrical activity, modulating functional connectivity within the brain. The cerebellar tACS can modulate the cerebellar outflow and cerebellum-linked behavior and it is a proven safe technique for humans. Therefore, the aim of this study is to 1) examine whether cerebellar tACS improves ataxia severity and various non-motor symptoms in a homogeneous cohort of CA patients consisting of MSA-C and SCA3, 2) explore the time course of these effects, and 3) assess the safety and tolerance of cerebellar tACS in all participants. Methods/design: This is a 2-week, triple-blind, randomised, sham-controlled study. 164 patients (MSA-C: 84, SCA3: 80) will be recruited and randomly assigned to either active cerebellar tACS or sham cerebellar tACS, in a 1:1 ratio. Patients, investigators, and outcome assessors are unaware of treatment allocation. Cerebellar tACS (40 min, 2 mA, ramp-up and down periods of 10s each) will be delivered over 10 sessions, distributed in two groups of five consecutive days with a two-day break in between. Outcomes are assessed after the tenth stimulation (T1), and after 1 month (T2) and 3 months (T3). The primary outcome measure is the difference between the active and sham groups in the proportion of patients with an improvement of 1.5 points in the Scale for the Assessment and Rating of Ataxia (SARA) score after 2 weeks of treatment. In addition, effects on a variety of non-motor symptoms, quality of life, and autonomic nerve dysfunctions are assessed via relative scales. Gait imbalance, dysarthria, and finger dexterity are objectively valued via relative tools. Finally, functional magnetic resonance imaging is performed to explore the possible mechanism of treatment effects. Discussion: The results of this study will inform whether repeated sessions of active cerebellar tACS benefit CA patients and whether this form of non-invasive stimulation might be a novel therapeutic approach to consider in a neuro-rehabilitation setting.Clinical Trial Registration: ClinicalTrials.gov, identifier NCT05557786; https://www.clinicaltrials.gov/ct2/show/NCT05557786.

18.
J Alzheimers Dis ; 94(1): 303-311, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37248901

RESUMEN

BACKGROUND: Leisure activities and sleep duration are correlated and have been linked to cognitive function, but most studies have examined only one of these factors. OBJECTIVE: To investigate the independent and joint associations of leisure activities and sleep duration with cognitive function among older adults. METHODS: We included 7,796 participants aged≥65 years from the Chinese Longitudinal Healthy Longevity Survey during 2008-2018 (waves 5-8). Self-reported leisure activities and sleep duration were assessed at baseline, and cognitive function was measured repeatedly using the Chinese version of the Mini-Mental State Examination (MMSE) at baseline and during follow-up. We used linear mixed models to estimate regression coefficients (ß) and 95% confidence intervals (CI). RESULTS: The median follow-up duration was 5.77 years. After adjusting for each other and potential confounders, both lower leisure activity score (each 1-point decrease ß= -0.33, 95% CI: -0.36 to -0.30) and longer sleep duration (each 1-hour increase ß= -0.17, 95% CI: -0.22 to -0.11) were independently associated with lower MMSE score. Furthermore, we observed an additive interaction between leisure activities and sleep duration (pinteraction < 0.001). A combination of low leisure activity score and long sleep duration was strongly associated with decreased MMSE score (ß= -2.51, 95% CI: -2.85 to -2.16) compared with the group with combined high leisure activity score and normal sleep duration. CONCLUSION: Both leisure activities and sleep duration were independently associated with cognitive function. Moreover, the combination of leisure inactivity and prolonged sleep duration predicted worse cognitive function (a preclinical hallmark of Alzheimer's disease) in an additive manner.


Asunto(s)
Disfunción Cognitiva , Duración del Sueño , Humanos , Anciano , Estudios Prospectivos , Cognición , Actividades Recreativas/psicología , Estudios Longitudinales , Sueño , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/diagnóstico
19.
Front Neurosci ; 17: 1142524, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37123367

RESUMEN

Purpose: To assess changes in optical quality and visual function in children after 3 months of wearing orthokeratology (OK) lenses. Methods: A total of 25 myopic children aged 8-12 years were recruited and completed the follow-up study. Optical quality, visual function and corneal morphology were assessed at baseline and at follow-ups 1 and 3 months after wearing OK lenses. Optical quality parameters mainly included the modulation transfer function (MTF) cutoff, objective scattering index (OSI), Strehl ratio (SR) and the predicted visual acuities (PVAs). Visual function was assessed by visual acuity, monocular contrast sensitivity function (CSF) across five spatial frequencies and the area under the log contrast sensitivity function (AULCSF) that was also computed as an index for overall CSF. Results: The MTF cutoff and SR values both increased after 1 month of wearing the OK lenses (baseline vs. 1 month: P MTF = 0.008 and P SR = 0.049); this improvement plateaued after 3 months of lens wear (1 month vs. 3 months: P MTF = 0.626, P SR = 0.428). The corneal morphology also showed the similar change trend. The OSI showed the opposite change trend (baseline vs. 1 month: P OSI < 0.001; 1 month vs. 3 months: P OSI = 0.720). The mean CSF at 1.5 cpd decreased significantly after 1 month of wearing the lenses (baseline vs. 1 month: p = 0.001) and recovered after 3 months of lens wear (baseline vs. 3 months: p = 0.076). CSF at spatial frequencies of 3, 6, 12 and 18 cpd as well as the AULCSF did not significantly differ between any two timepoints (all Ps > 0.05). Conclusion: After 3 months of wearing OK lenses, the subjects exhibited a decrease in optical quality, similar to corneal morphology, whereas their visual function remained largely unchanged. Thus, the optical quality was more susceptible to OK lenses than visual function in children. The initial month of OK treatment of children is a key period to be paid close attention to deterioration of optical quality and visual function.

20.
Angew Chem Int Ed Engl ; 62(16): e202300815, 2023 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-36825300

RESUMEN

The exploration of deactivation mechanisms for near-infrared(NIR)-emissive organic molecules has been a key issue in chemistry, materials science and molecular biology. In this study, based on transient absorption spectroscopy and transient grating photoluminescence spectroscopy, we demonstrate that the aggregated PtII complex 4H (efficient NIR emitter) exhibits collective out-of-plane motions with a frequency of 32 cm-1 (0.96 THz) in the excited states. Importantly, similar THz characteristics were also observed in analogous PtII complexes with prominent NIR emission efficiency. The conservation of THz motions enables excited-state deactivation to proceed along low-frequency vibrational coordinates, contributing to the suppression of nonradiative decay and remarkable NIR emission. These novel results highlight the significance of excited-state vibrations in nonradiative processes, which serve as a benchmark for improving device performance.

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