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1.
Front Neurosci ; 18: 1402996, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38975245

RESUMEN

Huntingtin-associated protein 1 (HAP1) was the first protein discovered to interact with huntingtin. Besides brain, HAP1 is also expressed in the spinal cord, dorsal root ganglion, endocrine, and digestive systems. HAP1 has diverse functions involving in vesicular transport, receptor recycling, gene transcription, and signal transduction. HAP1 is strongly linked to several neurological diseases, including Huntington's disease, Alzheimer's disease, epilepsy, ischemic stroke, and depression. In addition, HAP1 has been proved to participate in cancers and diabetes mellitus. This article provides an overview of HAP1 regarding the tissue distribution, cell localization, functions, and offers fresh perspectives to investigate its role in diseases.

2.
J Hepatocell Carcinoma ; 11: 813-838, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38737383

RESUMEN

Purpose: Hepatocellular carcinoma is the most common primary liver cancer, with poor prognosis. Complex immune microenvironment of the liver is linked to the development of HCC. PVALB is a calcium-binding protein which has been described as a cancer suppressor gene in thyroid cancer and glioma. Nevertheless, the role of PVALB in HCC is unknown. Materials and Methods: We obtained data from TCGA and GSE54236 datasets. MCP-counter, WGCNA and LASSO model were applied to identify PVALB. With UALCAN, MethSurv, and other websites, we probed the expression, methylation and survival of PVALB. LinkedOmics and GSEA were adopted for functional analysis, while TIMER, TISIDB, Kaplan-Meier plotter, TIDE databases were utilized to evaluate the relevance of PVALB to the tumor immune microenvironment and predict immunotherapy efficacy. TargetScan, DIANA, LncRNASNP2 databases and relevant experiments were employed to construct ceRNA network. Finally, molecular docking and drug sensitivity of PVALB were characterized by GeneMANIA, CTD, and so on. Results: PVALB was recognized as a gene associated with HCC and NK cell. Its expression was down-regulated in HCC tissue, which lead to adverse prognosis. Besides, the hypomethylation of PVALB was related to its reduced expression. Notably, PVALB was tightly linked to immune, and its reduced expression attenuated the anticancer effect of NK cells via the Fas/FasL pathway, leading to a adverse outcome. The lnc-YY1AP1-3/hsa-miR-6735-5p/PVALB axis may regulate the PVALB expression. Finally, we found immunotherapy might be a viable treatment option. Conclusion: In a word, PVALB is a prognostic indicator, whose low expression facilitates HCC progression by impacting NK cell infiltration.

3.
Nat Commun ; 15(1): 4035, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38740742

RESUMEN

Rapid and accurate detection of respiratory virus aerosols is highlighted for virus surveillance and infection control. Here, we report a wireless immunoassay technology for fast (within 10 min), on-site (wireless and battery-free), and sensitive (limit of detection down to fg/L) detection of virus antigens in aerosols. The wireless immunoassay leverages the immuno-responsive hydrogel-modulated radio frequency resonant sensor to capture and amplify the recognition of virus antigen, and flexible readout network to transduce the immuno bindings into electrical signals. The wireless immunoassay achieves simultaneous detection of respiratory viruses such as severe acute respiratory syndrome coronavirus 2, influenza A H1N1 virus, and respiratory syncytial virus for community infection surveillance. Direct detection of unpretreated clinical samples further demonstrates high accuracy for diagnosis of respiratory virus infection. This work provides a sensitive and accurate immunoassay technology for on-site virus detection and disease diagnosis compatible with wearable integration.


Asunto(s)
Hidrogeles , Subtipo H1N1 del Virus de la Influenza A , SARS-CoV-2 , Tecnología Inalámbrica , Inmunoensayo/métodos , Inmunoensayo/instrumentación , Humanos , Hidrogeles/química , SARS-CoV-2/inmunología , SARS-CoV-2/aislamiento & purificación , Tecnología Inalámbrica/instrumentación , Subtipo H1N1 del Virus de la Influenza A/inmunología , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Aerosoles , COVID-19/diagnóstico , COVID-19/virología , COVID-19/inmunología , Antígenos Virales/inmunología , Antígenos Virales/análisis , Virus Sincitiales Respiratorios/inmunología , Virus Sincitiales Respiratorios/aislamiento & purificación , Límite de Detección
4.
Biosens Bioelectron ; 259: 116404, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38772248

RESUMEN

Periodontitis, a chronic disease, can result in irreversible tooth loss and diminished quality of life, highlighting the significance of timely periodontitis monitoring and treatment. Meanwhile, hydrogen sulfide (H2S) in saliva, produced by pathogenic bacteria of periodontitis, is an important marker for periodontitis monitoring. However, the easy volatility and chemical instability of the molecule pose challenges to oral H2S sensing. Here, we report a wearable hydrogel-based radio frequency (RF) sensor capable of in situ H2S detection and antibacterial treatment. The RF sensor comprises an agarose hydrogel containing conjugated silver nanoparticles-chlorhexidine (AG-AgNPs-CHL hydrogel) integrated with split-ring resonators. Adhered to a tooth, the hydrogel-based RF sensor enables wireless transmission of sensing signals to a mobile terminal and a concurrent release of the broad-spectrum antibacterial agent chlorhexidine without complex circuits. With the selective binding of the AgNPs to the sulfidion, the RF sensor demonstrates good sensitivity, a wide detection range (2-30 µM), and a low limit of detection (1.2 µM). Compared with standard H2S measurement, the wireless H2S sensor can distinguish periodontitis patients from healthy individuals in saliva sample tests. The hydrogel-based wearable sensor will benefit patients with periodontitis by detecting disease-related biomarkers for practical oral health management.


Asunto(s)
Antibacterianos , Técnicas Biosensibles , Hidrogeles , Sulfuro de Hidrógeno , Nanopartículas del Metal , Periodontitis , Ondas de Radio , Saliva , Plata , Humanos , Sulfuro de Hidrógeno/análisis , Periodontitis/microbiología , Periodontitis/tratamiento farmacológico , Plata/química , Técnicas Biosensibles/métodos , Hidrogeles/química , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Saliva/química , Saliva/microbiología , Nanopartículas del Metal/química , Clorhexidina , Dispositivos Electrónicos Vestibles , Límite de Detección
5.
Aging (Albany NY) ; 16(8): 6954-6989, 2024 04 12.
Artículo en Inglés | MEDLINE | ID: mdl-38613802

RESUMEN

BACKGROUND: Glioma, a highly invasive and deadly form of human neoplasm, presents a pressing need for the exploration of potential therapeutic targets. While the lysosomal protein transmembrane 4A (LATPM4A) has been identified as a risk factor in pancreatic cancer patients, its role in glioma remains unexplored. METHODS: The analysis of differentially expressed genes (DEG) was conducted from The Cancer Genome Atlas (TCGA) glioma dataset and the Genotype Tissue Expression (GTEx) dataset. Through weighted gene co-expression network analysis (WGCNA), the key glioma-related genes were identified. Among these, by using Kaplan-Meier (KM) analysis and univariate/multivariate COX methods, LAPTM4A emerged as the most influential gene. Moreover, the bioinformatics methods and experimental verification were employed to analyze its relationships with diagnosis, clinical parameters, epithelial-mesenchymal transition (EMT), metastasis, immune cell infiltration, immunotherapy, drug sensitivity, and ceRNA network. RESULTS: Our findings revealed that LAPTM4A was up-regulated in gliomas and was associated with clinicopathological features, leading to poor prognosis. Furthermore, functional enrichment analysis demonstrated that LATPM4A played a role in the immune system and cancer progression. In vitro experiments indicated that LAPTM4A may influence metastasis through the EMT pathway in glioma. Additionally, we found that LAPTM4A was associated with the tumor microenvironment (TME) and immunotherapy. Notably, drug sensitivity analysis revealed that patients with high LAPTM4A expression were sensitive to doxorubicin, which contributed to a reduction in LAPTM4A expression. Finally, we uncovered the FGD5-AS1-hsa-miR-103a-3p-LAPTM4A axis as a facilitator of glioma progression. CONCLUSIONS: In conclusion, our study identifies LATPM4A as a promising biomarker for prognosis and immune characteristics in glioma.


Asunto(s)
Biomarcadores de Tumor , Neoplasias Encefálicas , Biología Computacional , Glioma , Proteínas de la Membrana , Femenino , Humanos , Masculino , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Línea Celular Tumoral , Transición Epitelial-Mesenquimal/genética , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Glioma/genética , Glioma/patología , Glioma/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Pronóstico
6.
Mol Plant ; 17(5): 788-806, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38615195

RESUMEN

During maize endosperm filling, sucrose not only serves as a source of carbon skeletons for storage-reserve synthesis but also acts as a stimulus to promote this process. However, the molecular mechanisms underlying sucrose and endosperm filling are poorly understood. In this study, we found that sucrose promotes the expression of endosperm-filling hub gene Opaque2 (O2), coordinating with storage-reserve accumulation. We showed that the protein kinase SnRK1a1 can attenuate O2-mediated transactivation, but sucrose can release this suppression. Biochemical assays revealed that SnRK1a1 phosphorylates O2 at serine 41 (S41), negatively affecting its protein stability and transactivation ability. We observed that mutation of SnRK1a1 results in larger seeds with increased kernel weight and storage reserves, while overexpression of SnRK1a1 causes the opposite effect. Overexpression of the native O2 (O2-OE), phospho-dead (O2-SA), and phospho-mimetic (O2-SD) variants all increased 100-kernel weight. Although O2-SA seeds exhibit smaller kernel size, they have higher accumulation of starch and proteins, resulting in larger vitreous endosperm and increased test weight. O2-SD seeds display larger kernel size but unchanged levels of storage reserves and test weight. O2-OE seeds show elevated kernel dimensions and nutrient storage, like a mixture of O2-SA and O2-SD seeds. Collectively, our study discovers a novel regulatory mechanism of maize endosperm filling. Identification of S41 as a SnRK1-mediated phosphorylation site in O2 offers a potential engineering target for enhancing storage-reserve accumulation and yield in maize.


Asunto(s)
Endospermo , Proteínas de Plantas , Sacarosa , Zea mays , Zea mays/metabolismo , Zea mays/genética , Endospermo/metabolismo , Fosforilación , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Sacarosa/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Semillas/metabolismo , Semillas/genética , Semillas/crecimiento & desarrollo
7.
Aging (Albany NY) ; 16(1): 714-745, 2024 01 11.
Artículo en Inglés | MEDLINE | ID: mdl-38217544

RESUMEN

BACKGROUND: Uterine corpus endometrial carcinoma (UCEC) is one of the most common gynecological malignancies and its incidence and mortality continue apace. Lysosome-associated membrane protein 3 (LAMP3) is the third member of the LAMP family and its overexpression has been described to be involved in the progression of breast, ovarian and cervical cancers, but there has been an absence of research focusing on its role in UCEC. METHODS: WGCNA, TIMER, LinkedOmics, GSEA, Cytoscape, Kaplan-Meier plotter, GDC, GeneMANIA, cBioPortal, PDB, RNAinter, miRNet were applied in this research. RESULTS: Our study uncovers that LAMP3 possesses higher expression levels in UCEC compared to normal tissues, and this differential expression profile is tightly aligned with clinical and pathological features, and patients demonstrating high LAMP3 expression tend to have a shorter survival expectancy. The high expression of LAMP3 is modulated by the designated ceRNA network. LAMP3 is engaged in UCEC progression by functioning in a variety of biological roles of relevance to immunity. Furthermore, we predicted several prospering drugs based on drug sensitivity. Finally, we also constructed possible docking patterns of LAMP3 with ABCA3, RAB9A, and SGTB. CONCLUSIONS: LAMP3 is a formidable biomarker for UCEC and could be a prospective candidate for the diagnosis, treatment and prognostic assessment of UCEC.


Asunto(s)
Mama , Carcinoma Endometrioide , Humanos , Femenino , Pronóstico , Proteínas de Neoplasias , Proteína 3 de la Membrana Asociada a Lisosoma
8.
Pharmaceuticals (Basel) ; 16(10)2023 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-37895837

RESUMEN

Chronic pain is an unpleasant experience associated with actual or potential tissue damage. Inflammatory pain alerts the body to inflammation and promotes healing; however, unresolved inflammation can lead to chronic pain. Conversely, neuropathic pain, due to somatosensory damage, can be a disease in itself. However, inflammation plays a considerable role in the progression of both types of pain. Resolvins, derived from omega-3 fatty acids, actively suppress pro-inflammatory mediators and aid in the resolution of inflammation. Resolvins alleviate various inflammatory and neuropathic pain models by reducing hypersensitivity and regulating inflammatory cytokines and glial activation in the spinal cord and dorsal root ganglia. Thus, resolvins are a promising alternative for pain management with the potential to reduce the side effects associated with conventional medications. Continued research is crucial to unlock the therapeutic potential of resolvins and integrate them into effective clinical pain management strategies. This review aimed to evaluate the literature surrounding the resolvins in inflammatory and neuropathic pain.

9.
Aging (Albany NY) ; 15(16): 8155-8184, 2023 08 18.
Artículo en Inglés | MEDLINE | ID: mdl-37602882

RESUMEN

Glioma is the most common primary intracranial tumor in the central nervous system, with a high degree of malignancy and poor prognosis, easy to recur, difficult to cure. The mutation of Retinitis Pigmentosa 2 (RP2) can cause retinitis pigmentosa, it is a prognostic factor of osteosarcoma, however, its role in glioma remains unclear. Based on the data from TCGA and GTEx, we identified RP2 as the most related gene for glioma by WGCNA, and used a series of bioinformatics analyses including LinkedOmics, GSCA, CTD, and so on, to explore the expression of RP2 in glioma and the biological functions it is involved in. The results showed that RP2 was highly expressed in glioma, and its overexpression could lead to poor prognosis. In addition, the results of enrichment analysis showed that RP2 was highly correlated with cell proliferation and immune response. And then, we found significant enrichment of Macrophages among immune cells. Furthermore, our experiments have confirmed that Macrophages can promote the development of glioma by secreting or influencing the secretion of some cytokines. Moreover, we investigated the influence of RP2 on the immunotherapy of glioma and the role of m6A modification in the influence of RP2 on glioma. Ultimately, we determined that RP2 is an independent prognostic factor that is mainly closely related to immune for glioma.


Asunto(s)
Neoplasias Óseas , Glioma , Retinitis Pigmentosa , Humanos , Pronóstico , Biomarcadores , Proteínas de la Membrana , Proteínas de Unión al GTP
10.
Front Aging Neurosci ; 15: 1190563, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37484692

RESUMEN

Pain is common and frequent in many neurodegenerative diseases, although it has not received much attention. In Huntington's disease (HD), pain is often ignored and under-researched because attention is more focused on motor and cognitive decline than psychiatric symptoms. In HD progression, pain symptoms are complex and involved in multiple etiologies, particularly mental issues such as apathy, anxiety and irritability. Because of psychiatric issues, HD patients rarely complain of pain, although their bodies show severe pain symptoms, ultimately resulting in insufficient awareness and lack of research. In HD, few studies have focused on pain and pain-related features. A detailed and systemic pain history is crucial to assess and explore pain pathophysiology in HD. This review provides an overview concentrating on pain-related factors in HD, including neuropathology, frequency, features, affecting factors and mechanisms. More attention and studies are still needed in this interesting field in the future.

12.
Aging (Albany NY) ; 15(7): 2631-2666, 2023 04 05.
Artículo en Inglés | MEDLINE | ID: mdl-37059586

RESUMEN

Hepatocellular carcinoma (HCC) is the most common subtype of liver cancer, with a high morbidity and low survival rate. Rho GTPase activating protein 39 (ARHGAP39) is a crucial activating protein of Rho GTPases, a novel target in cancer therapy, and it was identified as a hub gene for gastric cancer. However, the expression and role of ARHGAP39 in hepatocellular carcinoma remain unclear. Accordingly, the cancer genome atlas (TCGA) data were used to analyze the expression and clinical value of ARHGAP39 in hepatocellular carcinoma. Further, the LinkedOmics tool suggested functional enrichment pathways for ARHGAP39. To investigate in depth the possible role of ARHGAP39 on immune infiltration, we analyzed the relationship between ARHGAP39 and chemokines in HCCLM3 cells. Finally, the GSCA website was used to explore drug resistance in patients with high ARHGAP39 expression. Studies have shown that ARHGAP39 is highly expressed in hepatocellular carcinoma and relevant to clinicopathological features. In addition, the overexpression of ARHGAP39 leads to a poor prognosis. Besides, co-expressed genes and enrichment analysis showed a correlation with the cell cycle. Notably, ARHGAP39 may worsen the survival of hepatocellular carcinoma patients by increasing the level of immune infiltration through chemokines. Moreover, N6-methyladenosine (m6A) modification-related factors and drug sensitivity were also found to be associated with ARHGAP39. In brief, ARHGAP39 is a promising prognostic factor for hepatocellular carcinoma patients that is closely related to cell cycle, immune infiltration, m6A modification, and drug resistance.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Biomarcadores , Carcinoma Hepatocelular/genética , Ciclo Celular , Neoplasias Hepáticas/genética , Pronóstico
13.
Aging (Albany NY) ; 15(8): 2937-2969, 2023 04 03.
Artículo en Inglés | MEDLINE | ID: mdl-37074800

RESUMEN

PURPOSE: Hepatocellular carcinoma (HCC) is a prevalent tumor with high morbidity, and an unfavourable prognosis. FARSB is an aminoacyl tRNA synthase, and plays a key role in protein synthesis in cells. Furthermore, previous reports have indicated that FARSB is overexpressed in gastric tumor tissues and is associated with a poor prognosis and tumorigenesis. However, the function of FARSB in HCC has not been studied. RESULTS: The results showed that FARSB mRNA and protein levels were upregulated in HCC and were closely related to many clinicopathological characteristics. Besides, according to multivariate Cox analysis, high FARSB expression was linked with a shorter survival time in HCC and may be an independent prognostic factor. In addition, the FARSB promoter methylation level was negatively associated with the expression of FARSB. Furthermore, enrichment analysis showed that FARSB was related to the cell cycle. And TIMER analysis revealed that the FARSB expression was closely linked to tumor purity and immune cell infiltration. The TCGA and ICGC data analysis suggested that FARSB expression is greatly related to m6A modifier related genes. Potential FARSB-related ceRNA regulatory networks were also constructed. What's more, based on the FARSB-protein interaction network, molecular docking models of FARSB and RPLP1 were constructed. Finally, drug susceptibility testing revealed that FARSB was susceptible to 38 different drugs or small molecules. CONCLUSIONS: FARSB can serve as a prognostic biomarker for HCC and provide clues about immune infiltration, and m6A modification.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Mycobacterium tuberculosis , Humanos , Carcinoma Hepatocelular/genética , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Pronóstico , Neoplasias Hepáticas/genética , Biomarcadores
14.
Small ; 19(24): e2207889, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36899491

RESUMEN

Printed flexible electronics have emerged as versatile functional components of wearable intelligent devices that bridge the digital information networks with biointerfaces. Recent endeavors in plant wearable sensors provide real-time and in situ insights to study phenotyping traits of crops, whereas monitoring of ethylene, the fundamental phytohormone, remains challenging due to the lack of flexible and scalable manufacturing of plant wearable ethylene sensors. Here the all-MXene-printed flexible radio frequency (RF) resonators are presented as plant wearable sensors for wireless ethylene detection. The facile formation of additive-free MXene ink enables rapid, scalable manufacturing of printed electronics, demonstrating decent printing resolution (2.5% variation), ≈30000 S m-1 conductivity and mechanical robustness. Incorporation of MXene-reduced palladium nanoparticles (MXene@PdNPs) facilitates 1.16% ethylene response at 1 ppm with 0.084 ppm limit of detection. The wireless sensor tags are attached on plant organ surfaces for in situ and continuously profiling of plant ethylene emission to inform the key transition of plant biochemistry, potentially extending the application of printed MXene electronics to enable real-time plant hormone monitoring for precision agriculture and food industrial management.


Asunto(s)
Nanopartículas del Metal , Dispositivos Electrónicos Vestibles , Paladio , Productos Agrícolas , Etilenos
15.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 39(1): 34-40, 2023 Jan.
Artículo en Chino | MEDLINE | ID: mdl-36631013

RESUMEN

Objective To examine the effects of Coxsackie virus B3 (CVB3) on the NLR family, pyrin domain containing protein 3 (NLPR3) of mouse macrophages and its mechanisms. Methods RAW264.7 cells, primary mouse macrophages (bone marrow-derived macrophages or peritoneal macrophages), and short hairpin RNA (shRNA)-NLRP3 lentivirus infected RAW264.7 cells were stimulated by different dosages of CVB3. The transcript levels of NLRP3 and IL-1ß were measured by quantitative real-time PCR. IL-1ß in the supernatants of cell cultures was determined by ELISA. The protein level of NLRP3 was tested by Western blot analysis and the interacting proteins of NLRP3 were detected by co-immunoprecipitation (Co-IP). Results The transcript levels of NLRP3 and IL-1ß were significantly up-regulated in the CVB3 stimulated RAW264.7 cells and primary mouse macrophages (bone marrow-derived macrophages or peritoneal macrophages). The expression level of NLRP3 presented CVB3-dose dependence and demonstrated the highest expression level at 6 hours after CVB3 treatment. The transcript level of IL-1ß significantly increased the most at 6 hours after CVB3 treatment, while the protein level of IL-1ß peaked at 24 hours after CVB3 treatment. In the GFP-shRNA-NLRP3 lentivirus infected RAW264.7 cells, NLRP3 was obviously inhibited, and with CVB3 stimulation, IL-1ß in the supernatants of cell cultures decreased significantly. Moreover, NLRP3 antibody was used for Co-IP experiment, in which the resultant protein complex was then stained with silver nitrate. The differential protein band between different groups was identified as nicotinamide adenine dinucleotide kinase 2 (NADK2) by mass spectrometry. This result demonstrated that CVB3 induced the interaction between NADK2 and NLRP3. Conclusion CVB3 stimulation promotes the activation of NLRP3 in macrophages, thereby enhancing the expression and secretion of pro-inflammatory cytokine IL-1ß by activating NADK2.


Asunto(s)
Enterovirus , Macrófagos , NAD , Proteína con Dominio Pirina 3 de la Familia NLR , Fosfotransferasas (Aceptor de Grupo Alcohol) , Animales , Ratones , Enterovirus/metabolismo , Infecciones por Enterovirus/metabolismo , Inflamasomas/metabolismo , Interleucina-1beta/metabolismo , Macrófagos/metabolismo , NAD/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , ARN Interferente Pequeño/metabolismo
16.
Pain ; 164(6): e286-e302, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-36508175

RESUMEN

ABSTRACT: Although pain dysfunction is increasingly observed in Huntington disease, the underlying mechanisms still unknown. As a crucial Huntington-associated protein, Huntington-associated protein 1 (HAP1) is enriched in normal spinal dorsal horn and dorsal root ganglia (DRG) which are regarded as "primary sensory center," indicating its potential functions in pain process. Here, we discovered that HAP1 level was greatly increased in the dorsal horn and DRG under acute and chronic pain conditions. Lack of HAP1 obviously suppressed mechanical allodynia and hyperalgesia in spared nerve injury (SNI)-induced and chronic constriction injury-induced pain. Its deficiency also greatly inhibited the excitability of nociceptive neurons. Interestingly, we found that suppressing HAP1 level diminished the membrane expression of the L-type calcium channel (Cav1.2), which can regulate Ca 2+ influx and then influence brain-derived neurotrophic factor (BDNF) synthesis and release. Furthermore, SNI-induced activation of astrocytes and microglia notably decreased in HAP1-deficient mice. These results indicate that HAP1 deficiency might attenuate pain responses. Collectively, our results suggest that HAP1 in dorsal horn and DRG neurons regulates Cav1.2 surface expression, which in turn reduces neuronal excitability, BDNF secretion, and inflammatory responses and ultimately influences neuropathic pain progression.


Asunto(s)
Neuralgia , Animales , Ratones , Ratas , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Ganglios Espinales/metabolismo , Hiperalgesia , Neuralgia/metabolismo , Ratas Sprague-Dawley , Asta Dorsal de la Médula Espinal/metabolismo
17.
Biosens Bioelectron ; 222: 114945, 2023 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-36462428

RESUMEN

Breath acetone (BrAC) detection presents a promising scheme for noninvasive monitoring of metabolic health due to its close correlation to diets and exercise-regulated lipolysis. Herein, we report a Ti3C2Tx MXene-based wireless facemask for on-body BrAC detection and real-time tracking of lipid metabolism, where Ti3C2Tx MXene serves as a versatile nanoplatform for not only acetone detection but also breath interference filtration. The incorporation of in situ grown TiO2 and short peptides with Ti3C2Tx MXene further improves the acetone sensitivity and selectivity, while TiO2-MXene interfaces facilitate light-assisted response calibration. To further realize wearable breath monitoring, a miniaturized flexible detection tag has been integrated with a commercially available facemask, which enables facile BrAC detection and wireless data transmission. Through the hierarchically designed filtration-detection-calibration-transmission system, we realize BrAC detection down to 0.31 ppm (part per million) in breath. On-body breath tests validate the facemask in dynamically monitoring of lipid metabolism, which could guide dieter, athletes, and fitness enthusiasts to arrange diets and exercise activities. The proposed wearable platform opens up new possibility toward the practice of breath analysis as well as daily lipid metabolic management.


Asunto(s)
Técnicas Biosensibles , Dispositivos Electrónicos Vestibles , Humanos , Acetona/análisis , Acetona/metabolismo , Máscaras , Pruebas Respiratorias , Lípidos
18.
Neural Regen Res ; 18(2): 396-403, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35900436

RESUMEN

After spinal cord injury (SCI), a fibroblast- and microglia-mediated fibrotic scar is formed in the lesion core, and a glial scar is formed around the fibrotic scar as a result of the activation and proliferation of astrocytes. Simultaneously, a large number of neurons are lost in the injured area. Regulating the dense glial scar and replenishing neurons in the injured area are essential for SCI repair. Polypyrimidine tract binding protein (PTB), known as an RNA-binding protein, plays a key role in neurogenesis. Here, we utilized short hairpin RNAs (shRNAs) and antisense oligonucleotides (ASOs) to knock down PTB expression. We found that reactive spinal astrocytes from mice were directly reprogrammed into motoneuron-like cells by PTB downregulation in vitro. In a mouse model of compression-induced SCI, adeno-associated viral shRNA-mediated PTB knockdown replenished motoneuron-like cells around the injured area. Basso Mouse Scale scores and forced swim, inclined plate, cold allodynia, and hot plate tests showed that PTB knockdown promoted motor function recovery in mice but did not improve sensory perception after SCI. Furthermore, ASO-mediated PTB knockdown improved motor function restoration by not only replenishing motoneuron-like cells around the injured area but also by modestly reducing the density of the glial scar without disrupting its overall structure. Together, these findings suggest that PTB knockdown may be a promising therapeutic strategy to promote motor function recovery during spinal cord repair.

19.
Aging (Albany NY) ; 14(23): 9550-9578, 2022 12 03.
Artículo en Inglés | MEDLINE | ID: mdl-36462500

RESUMEN

Hepatocellular carcinoma (HCC) is a common tumor across the globe with a high mortality rate. ZSCAN20 is a ZNF transcription factor, a key determinant of gene expression. Nonetheless, the mechanism of ZSCAN20 as a potential clinical biomarker and therapeutic target for HCC is not understood. Here, TIMER, TCGA, ICGC databases and immunohistochemical (IHC) and Western Blot found ZSCAN20 mRNA and protein levels were upregulated. Additionally, Kaplan-Meier Plotter, GEPIA and TCGA databases showed high ZSCAN20 expression was related to the short survival time of HCC patients. Multivariate Cox analysis exposed that ZSCAN20 can act as an independent prognostic factor. We observed methylation level of ZSCAN20 was associated with the clinicopathological characteristics and prognosis of HCC patients through UALCAN. Furthermore, enrichment examination exposed functional association between ZSCAN20 and cell cycle, immune infiltration. Functional experiments showed that interference with ZSCAN20 significantly reduced the invasion, migration and proliferation abilities of HCC cells. An immune infiltration analysis showed that ZSCAN20 was associated with immune cells, particularly T cells. The expression of ZSCAN20 was correlated with poor prognosis in the Regulatory T-cell. And Real-Time RT-PCR analysis found interference with ZSCAN20 significantly reduced the expression of some chemokines. Finally, the TCGA and ICGC data analysis suggested that the ZSCAN20 expression was greatly related to m6A modifier related genes. In conclusion, ZSCAN20 can serve as a prognostic biomarker for HCC and provide clues about cell cycle, immune infiltration, and m6A modification.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Pronóstico , Neoplasias Hepáticas/genética , Ciclo Celular , Biomarcadores , Biomarcadores de Tumor/genética
20.
Front Cell Neurosci ; 16: 1005399, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36467604

RESUMEN

Spinal cord injury (SCI) is a serious neurological trauma that is challenging to treat. After SCI, many neurons in the injured area die due to necrosis or apoptosis, and astrocytes, oligodendrocytes, microglia and other non-neuronal cells become dysfunctional, hindering the repair of the injured spinal cord. Corrective surgery and biological, physical and pharmacological therapies are commonly used treatment modalities for SCI; however, no current therapeutic strategies can achieve complete recovery. Somatic cell reprogramming is a promising technology that has gradually become a feasible therapeutic approach for repairing the injured spinal cord. This revolutionary technology can reprogram fibroblasts, astrocytes, NG2 cells and neural progenitor cells into neurons or oligodendrocytes for spinal cord repair. In this review, we provide an overview of the transcription factors, genes, microRNAs (miRNAs), small molecules and combinations of these factors that can mediate somatic cell reprogramming to repair the injured spinal cord. Although many challenges and questions related to this technique remain, we believe that the beneficial effect of somatic cell reprogramming provides new ideas for achieving functional recovery after SCI and a direction for the development of treatments for SCI.

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