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1.
Proc Natl Acad Sci U S A ; 120(2): e2214492120, 2023 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-36595698

RESUMEN

Reproductive systems of flowering plants are evolutionarily fluid, with mating patterns changing in response to shifts in abiotic conditions, pollination systems, and population characteristics. Changes in mating should be particularly evident in species with sexual polymorphisms that become ecologically destabilized, promoting transitions to alternative reproductive systems. Here, we decompose female mating portfolios (incidence of selfing, outcross mate number, and intermorph mating) in eight populations of Primula oreodoxa, a self-compatible insect-pollinated herb. This species is ancestrally distylous, with populations subdivided into two floral morphs that usually mate with each other (disassortative mating). Stages in the breakdown of polymorphism also occur, including "mixed" populations of distylous and homostylous (self-pollinating) morphs and purely homostylous populations. Population morph ratios vary with elevation in association with differences in pollinator availability, providing an unusual opportunity to investigate changes in mating patterns accompanying transitions in reproductive systems. Unexpectedly, individuals mostly outcrossed randomly, with substantial disassortative mating in at most two distylous populations. As predicted, mixed populations had higher selfing rates than distylous populations, within mixed populations, homostyles selfed almost twice as much as the distylous morphs, and homostylous populations exhibited the highest selfing rates. Populations with homostyles outcrossed with fewer mates and mate number varied negatively with population selfing rates. These differences indicate maintenance of distyly at low elevation, transition to monomorphic selfing at high elevation, and uncertain, possibly variable fates at intermediate elevation. By quantifying the earliest changes in mating that initiate reproductive transitions, our study highlights the key role of mating in promoting evolutionary divergence.


Asunto(s)
Flores , Reproducción , Humanos , Flores/genética , Reproducción/genética , Polinización/genética , Polimorfismo Genético , Evolución Biológica
2.
Appl Microbiol Biotechnol ; 108(1): 99, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38204135

RESUMEN

Ectomycorrhizal fungi (EMF) can form symbiotic relationships with plants, aiding in plant growth by providing access to nutrients and defense against phytopathogenic fungi. In this context, factors such as plant assemblages and soil properties can impact the interaction between EMF and phytopathogenic fungi in forest soil. However, there is little understanding of how these fungal interactions evolve as forests move through succession stages. In this study, we used high-throughput sequencing to investigate fungal communities in young, intermediate, and old subtropical forests. At the genus level, EMF communities were dominated by Sebacina, Russula, and Lactarius, while Mycena was the most abundant genus in pathogenic fungal communities. The relative abundances of EMF and phytopathogenic fungi in different stages showed no significant difference with the regulation of different factors. We discovered that interactions between phytopathogenic fungi and EMF maintained a dynamic balance under the influence of the differences in soil quality attributed to each forest successional stage. The community composition of phytopathogenic fungi is one of the strong drivers in shaping EMF communities over successions. In addition, the EMF diversity was significantly related to plant diversity, and these relationships varied among successional stages. Despite the regulation of various factors, the positive relationship between the diversity of phytopathogenic fungi and EMF remained unchanged. However, there is no significant difference in the ratio of the abundance of EMF and phytopathogenic fungi over the course of successions. These results will advance our understanding of the biodiversity-ecosystem functioning during forest succession. KEY POINTS: •Community composition of both EMF and phytopathogenic fungi changed significantly over forest succession. •Phytopathogenic fungi is a key driver in shaping EMF community. •The effect of plant Shannon's diversity on EMF communities changed during the forest aging process.


Asunto(s)
Agaricales , Micobioma , Micorrizas , Ecosistema , Bosques , Suelo
3.
Acta Neuropathol ; 145(6): 717-731, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36964213

RESUMEN

Cerebral amyloid-ß (Aß) accumulation due to impaired Aß clearance is a pivotal event in the pathogenesis of Alzheimer's disease (AD). Considerable brain-derived Aß is cleared via transporting to the periphery. The liver is the largest organ responsible for the clearance of metabolites in the periphery. Whether the liver physiologically clears circulating Aß and its therapeutic potential for AD remains unclear. Here, we found that about 13.9% of Aß42 and 8.9% of Aß40 were removed from the blood when flowing through the liver, and this capacity was decreased with Aß receptor LRP-1 expression down-regulated in hepatocytes in the aged animals. Partial blockage of hepatic blood flow increased Aß levels in both blood and brain interstitial fluid. The chronic decline in hepatic Aß clearance via LRP-1 knockdown specific in hepatocytes aggravated cerebral Aß burden and cognitive deficits, while enhancing hepatic Aß clearance via LRP-1 overexpression attenuated cerebral Aß deposition and cognitive impairments in APP/PS1 mice. Our findings demonstrate that the liver physiologically clears blood Aß and regulates brain Aß levels, suggesting that a decline of hepatic Aß clearance during aging could be involved in AD development, and hepatic Aß clearance is a novel therapeutic approach for AD.


Asunto(s)
Enfermedad de Alzheimer , Ratones , Animales , Enfermedad de Alzheimer/patología , Precursor de Proteína beta-Amiloide/metabolismo , Péptidos beta-Amiloides/metabolismo , Encéfalo/patología , Hígado/metabolismo , Hígado/patología , Ratones Transgénicos , Modelos Animales de Enfermedad
4.
J Neurochem ; 161(3): 293-307, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35244207

RESUMEN

The role of α1 adrenergic receptors (α1-ARs) signaling pathway in the pathogenesis of Alzheimer's disease (AD) has rarely been investigated. Clarifying the pathophysiological functions of α1-ARs in the AD brain is helpful for better understanding the pathogenesis and screening novel therapeutic targets of AD. This study included 2 arms of in vivo investigations: 1) 6-month-old female APPswe/PS1 mice were intravenously treated with AAV-PHP.eB-shRNA (α1-ARs)-GFP or AAV-PHP.eB-GFP for 3 months. 2) 3-month-old female APPswe/PS1 mice were daily treated with 0.5 mg/kg terazosin or an equal volume of saline for 6 months. SH-SY5Y cell lines bearing human amyloid precursor protein were treated with terazosin or saline for investigating possible mechanisms. α1-ARs knockdown mice exhibited improved behavioral performances in comparison with control mice. α1-ARs knockdown mice had significantly lower brain amyloid burden, as reflected by soluble Aß species, compact and total Aß plaques, than control mice. α1-ARs inhibitor terazosin substantially reduced Aß deposition, attenuated downstream pathologies including tau hyperphosphorylation, glial activation, neuronal loss, synaptic dysfunction et al., and rescued behavioral deficits in APPswe/PS1 mice. In vitro investigation demonstrated that α1-ARs inhibition down-regulated BACE1 expression, and promoted ser9 phosphorylation of GSK-3ß, thus reducing Aß production. This study indicates that inhibition of α1-ARs signaling pathway might represent a promising therapeutic strategy for AD.


Asunto(s)
Enfermedad de Alzheimer , Enfermedad de Alzheimer/metabolismo , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Péptidos beta-Amiloides/metabolismo , Animales , Ácido Aspártico Endopeptidasas/metabolismo , Modelos Animales de Enfermedad , Femenino , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Ratones , Ratones Transgénicos , Receptores Adrenérgicos/uso terapéutico , Transducción de Señal
5.
Mol Psychiatry ; 26(10): 6074-6082, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-33828237

RESUMEN

Amyloid-ß (Aß) accumulation in the brain is a pivotal event in the pathogenesis of Alzheimer's disease (AD), and its clearance from the brain is impaired in sporadic AD. Previous studies suggest that approximately half of the Aß produced in the brain is cleared by transport into the periphery. However, the mechanism and pathophysiological significance of peripheral Aß clearance remain largely unknown. The kidney is thought to be responsible for Aß clearance, but direct evidence is lacking. In this study, we investigated the impact of unilateral nephrectomy on the dynamic changes in Aß in the blood and brain in both humans and animals and on behavioural deficits and AD pathologies in animals. Furthermore, the therapeutic effects of the diuretic furosemide on Aß clearance via the kidney were assessed. We detected Aß in the kidneys and urine of both humans and animals and found that the Aß level in the blood of the renal artery was higher than that in the blood of the renal vein. Unilateral nephrectomy increased brain Aß deposition; aggravated AD pathologies, including Tau hyperphosphorylation, glial activation, neuroinflammation, and neuronal loss; and aggravated cognitive deficits in APP/PS1 mice. In addition, chronic furosemide treatment reduced blood and brain Aß levels and attenuated AD pathologies and cognitive deficits in APP/PS1 mice. Our findings demonstrate that the kidney physiologically clears Aß from the blood, suggesting that facilitation of Aß clearance via the kidney represents a novel potential therapeutic approach for AD.


Asunto(s)
Enfermedad de Alzheimer , Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animales , Encéfalo/metabolismo , Modelos Animales de Enfermedad , Riñón/metabolismo , Ratones , Ratones Transgénicos , Presenilina-1/metabolismo
6.
Opt Express ; 29(11): 16249-16260, 2021 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-34154192

RESUMEN

A bidirectional planar-displacement waveguide tracker was devised to replace the traditional two-axis tracking system for high-concentration photovoltaics, with improved module thickness, optical field uniformity, and current matching. The concentrating magnification reaches 725 times, and the sun tracking angle is more than 170°, which is equivalent to 11.3 tracking hours per day. The module thickness is only 6.16 cm. This design enabled us to place the module flat on the ground, in which swing was not required. This will greatly improve the mechanical strength and the lifetime of the module and solve the development dilemma faced by III-V multijunction solar cells.

7.
Sleep Breath ; 25(4): 1969-1976, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-33619665

RESUMEN

BACKGROUND: Sleep deprivation (SD) has become a serious concern worldwide. This study aimed to identify key modules and candidate hub genes correlated with diseases caused by SD, using co-expression analysis. METHODS: The weighted gene co-expression network analysis was performed to construct a co-expression network of hub genes correlated with SD. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to search for signaling pathways. The protein-protein interaction network analysis of central genes was performed to recognize the interactions among central genes. Molecular Complex Detection, a plugin in Cytoscape, was used to discover the hub gene clusters involved in SD. RESULTS: A total of 564 genes in the yellow module were identified based on the results of topological overlap measure-based clustering. The yellow module showed a pivotal correlation with SD. Six hub gene clusters prominently associated with SD were identified. Heat shock protein family and circadian clock genes among them may be the hub genes involved in SD. CONCLUSIONS: These genes and pathways might become therapeutic targets with clinical usefulness in the future.


Asunto(s)
Perfilación de la Expresión Génica , Redes Reguladoras de Genes/genética , Transducción de Señal/genética , Privación de Sueño/genética , Humanos
8.
Acta Neuropathol ; 136(4): 525-536, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30074071

RESUMEN

Accumulation of pathological tau is the hallmark of Alzheimer's disease and other tauopathies and is closely correlated with cognitive decline. Clearance of pathological tau from the brain is a major therapeutic strategy for tauopathies. The physiological capacity of the periphery to clear brain-derived tau and its therapeutic potential remain largely unknown. Here, we found that cisterna magna injected 131I-labelled synthetic tau dynamically effluxed from the brain and was mainly cleared from the kidney, blood, and liver in mice; we also found that plasma tau levels in inferior vena cava were lower than those in femoral artery in humans. These findings suggest that tau proteins can efflux out of the brain and be cleared in the periphery under physiological conditions. Next, we showed that lowering blood tau levels via peritoneal dialysis could reduce interstitial fluid (ISF) tau levels in the brain, and tau levels in the blood and ISF were dynamically correlated; furthermore, tau efflux from the brain was accelerated after the addition of another set of peripheral system in a parabiosis model. Finally, we established parabiosis mouse models using tau transgenic mice and their wild-type littermates and found that brain tau levels and related pathologies in parabiotic transgenic mice were significantly reduced after parabiosis, suggesting that chronic enhancement of peripheral tau clearance alleviates pathological tau accumulation and neurodegeneration in the brain. Our study provides the first evidence of physiological clearance of brain-derived pathological tau in the periphery, suggesting that enhancing peripheral tau clearance is a potential therapeutic strategy for tauopathies.


Asunto(s)
Sistema Nervioso Periférico/metabolismo , Tauopatías/metabolismo , Tauopatías/terapia , Proteínas tau/metabolismo , Adulto , Anciano , Animales , Química Encefálica , Cisterna Magna/metabolismo , Líquido Extracelular/metabolismo , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Persona de Mediana Edad , Parabiosis , Diálisis Peritoneal , Distribución Tisular , Vena Cava Inferior/metabolismo , Proteínas tau/genética
9.
Proc Natl Acad Sci U S A ; 112(16): 5225-30, 2015 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-25847999

RESUMEN

Alzheimer's disease (AD) is one of most devastating diseases affecting elderly people. Amyloid-ß (Aß) accumulation and the downstream pathological events such as oxidative stress play critical roles in pathogenesis of AD. Lessons from failures of current clinical trials suggest that targeting multiple key pathways of the AD pathogenesis is necessary to halt the disease progression. Here we show that Edaravone, a free radical scavenger that is marketed for acute ischemic stroke, has a potent capacity of inhibiting Aß aggregation and attenuating Aß-induced oxidation in vitro. When given before or after the onset of Aß deposition via i.p. injection, Edaravone substantially reduces Aß deposition, alleviates oxidative stress, attenuates the downstream pathologies including Tau hyperphosphorylation, glial activation, neuroinflammation, neuronal loss, synaptic dysfunction, and rescues the behavioral deficits of APPswe/PS1 mice. Oral administration of Edaravone also ameliorates the AD-like pathologies and memory deficits of the mice. These findings suggest that Edaravone holds a promise as a therapeutic agent for AD by targeting multiple key pathways of the disease pathogenesis.


Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Antipirina/análogos & derivados , Trastornos del Conocimiento/tratamiento farmacológico , Administración Oral , Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/patología , Amiloide/metabolismo , Péptidos beta-Amiloides/toxicidad , Animales , Antipirina/administración & dosificación , Antipirina/química , Antipirina/farmacología , Antipirina/uso terapéutico , Conducta Animal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/patología , Línea Celular , Trastornos del Conocimiento/complicaciones , Trastornos del Conocimiento/patología , Dendritas/efectos de los fármacos , Dendritas/patología , Edaravona , Humanos , Inflamación/patología , Ratones Transgénicos , Neurotoxinas/toxicidad , Estrés Oxidativo/efectos de los fármacos , Fosforilación/efectos de los fármacos , Presenilina-1/metabolismo , Agregación Patológica de Proteínas/complicaciones , Agregación Patológica de Proteínas/tratamiento farmacológico , Procesamiento Proteico-Postraduccional/efectos de los fármacos , Proteínas tau/metabolismo
10.
Biomed Environ Sci ; 31(11): 816-828, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30558702

RESUMEN

OBJECTIVE: To evaluate the efficacy of cis-2-dodecenoic acid (BDSF) in the treatment and prevention of vaginal candidiasis in vivo. METHODS: The activities of different concentrations of BDSF against the virulence factors of Candida albicans (C. albicans) were determined in vitro. An experimental mouse model of Candida vaginitis was treated with 250 µmol/L BDSF. Treatment efficiency was evaluated in accordance with vaginal fungal burden and inflammation symptoms. RESULTS: In vitro experiments indicated that BDSF attenuated the adhesion and damage of C. albicans to epithelial cells by decreasing phospholipase secretion and blocking filament formation. Treatment with 30 µmol/L BDSF reduced the adhesion and damage of C. albicans to epithelial cells by 36.9% and 42.3%, respectively. Treatment with 200 µmol/L BDSF completely inhibited phospholipase activity. In vivo mouse experiments demonstrated that BDSF could effectively eliminate vaginal infection and relieve inflammatory symptoms. Four days of treatment with 250 µmol/L BDSF reduced vaginal fungal loads by 6-fold and depressed inflammation. Moreover, BDSF treatment decreased the expression levels of the inflammatory chemokine-associated genes MCP-1 and IGFBP3 by 2.5- and 2-fold, respectively. CONCLUSION: BDSF is a novel alternative drug that can efficiently control vaginal candidiasis by inhibiting the virulence factors of C. albicans.


Asunto(s)
Candida albicans/efectos de los fármacos , Candidiasis Vulvovaginal/tratamiento farmacológico , Ácidos Grasos Monoinsaturados/administración & dosificación , Animales , Candida albicans/metabolismo , Candida albicans/patogenicidad , Candida albicans/fisiología , Candidiasis Vulvovaginal/genética , Candidiasis Vulvovaginal/inmunología , Candidiasis Vulvovaginal/microbiología , Quimiocina CCL2/genética , Quimiocina CCL2/inmunología , Modelos Animales de Enfermedad , Femenino , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Humanos , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/inmunología , Ratones , Virulencia/efectos de los fármacos , Factores de Virulencia/genética , Factores de Virulencia/metabolismo
11.
World J Surg ; 41(1): 129-135, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27541032

RESUMEN

BACKGROUND: The decision to perform a total thyroidectomy (TT) for unilateral papillary thyroid microcarcinoma (PTMC) with nodules in the contralateral lobe remains controversial. The aim of this study was to investigate the rate of contralateral carcinomas that are preoperatively misdiagnosed as benign. METHODS: From October 2011 to October 2015, a total of 347 patients with unilateral PTMC and contralateral benign nodules who were treated with a TT at a single institution were enrolled. All patients underwent preoperative fine needle aspiration and ultrasonography (US). Clinicopathological features such as age, sex, laterality, tumor size, central lymph node metastases, capsular invasion, TgAb and TPOAb levels, Hashimoto's thyroiditis, nodule number in both lobes according to preoperative US, and primary carcinoma number in the final postoperative pathology report were all analyzed to investigate the rate and predictive factors of contralateral carcinoma. RESULTS: A total of 100 patients (28.9 %) were diagnosed with papillary thyroid carcinoma in the contralateral lobe. A multivariate analysis showed that tumor size, nodule number in the contralateral lobe, and multifocality of the primary tumor were all independent predictive factors of contralateral carcinoma in patients with unilateral PTMC and contralateral benign nodules. CONCLUSIONS: According to our findings, the rate at which contralateral carcinomas are preoperatively misdiagnosed as benign is 28.9 %. A TT is essential for unilateral PTMC with a primary tumor size >5 mm, multifocal primary carcinomas or multifocal benign nodules in the contralateral lobe.


Asunto(s)
Carcinoma Papilar/diagnóstico , Cuidados Preoperatorios , Neoplasias de la Tiroides/diagnóstico , Tiroidectomía , Adulto , Anciano , Biopsia con Aguja Fina , Carcinoma Papilar/epidemiología , Carcinoma Papilar/patología , Carcinoma Papilar/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Neoplasias de la Tiroides/epidemiología , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugía , Ultrasonografía
12.
Planta Med ; 82(1-2): 70-5, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26393941

RESUMEN

The mammalian target of rapamycin is critical in hypoxia-triggered angiogenesis. Cardamonin inhibits proliferation of various cancer cells through suppressing the mammalian target of rapamycin. In this study, the antiangiogenic effect of cardamonin on CoCl2-mimicked hypoxic SKOV3 cells was investigated. Cardamonin exhibited an antiproliferative effect on normal and CoCl2-mimicked hypoxic SKOV3 cells. Messenger RNA expression of vascular endothelial growth factor was inhibited with cardamonin and rapamycin in SKOV3 cells under both conditions. However, cardamonin had little effect on the messenger RNA expression of hypoxia-inducible factor-α. Cardamonin inhibited the protein expression of hypoxia-inducible factor-1α, hypoxia inducible factor-2α, vascular endothelial growth factor, and the phosphorylation of mammalian target of rapamycin and ribosomal S6 kinase 1. Furthermore, angiogenesis induced by a medium of SKOV3 cells was reduced by cardamonin in a chicken embryo allantois membrane model. These findings suggest that cardamonin inhibits protein expression of hypoxia-inducible factor-α, and vascular endothelial growth factor, which was induced by CoCl2-mimicked hypoxia and this effect partially correlates with the mammalian target of rapamycin inhibition. Cardamonin might be a potential angiogenesis inhibitor for ovarian cancer therapy.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Chalconas/química , Neovascularización Patológica/prevención & control , Serina-Treonina Quinasas TOR/metabolismo , Animales , Línea Celular Tumoral , Embrión de Pollo , Regulación hacia Abajo/efectos de los fármacos , Humanos
13.
Zhongguo Zhong Yao Za Zhi ; 40(15): 3053-8, 2015 Aug.
Artículo en Zh | MEDLINE | ID: mdl-26677710

RESUMEN

This study aims to analyze and compare the effect of cell wall-broken decoction pieces, conventional decoction pieces and conventional powder of Rhodiolae Crenulatae Radix et Rhizoma on the intestinal flora of normal mice. The conventional bacterial culture and PCR-DGGE (polymerase chain reaction-denaturing gradient gel electrophoresis) were adopted for the mice after the oral administration for 14 days. According to the bacterial culture results, the 1/8 dose cell wall-broken decoction pieces group showed fewer Enterococcus and Escherichia coli bacillus but more Lactobacillus and Bifidobacterium than the conventional decoction pieces group and the traditional powder group (P <0.05). Meanwhile, on the basis of the PCR-DGGE results, the 1/8 dose cell wall-broken decoction pieces group revealed the highest Shannon-Wiener index (H) and species richness (S) among the seven groups, with extremely significant differences compared with the normal group (P <0.01), significant differences compared with the conventional decoction pieces group and the conventional powder group (P <0.05) and a high intra-group similarity. In conclusion, the long-term intake of 1/8 dose Rhodiolae Crenulatae Radix et Rhizoma cell wall-broken decoction pieces showed a certain effect in regulating intestinal tract by promoting the growth of Lactobacillus and Bifidobacterium. Furthermore, the intestinal flora community will become more stable.


Asunto(s)
Intestinos/microbiología , Rhodiola , Animales , Bifidobacterium/efectos de los fármacos , Bifidobacterium/genética , Bifidobacterium/crecimiento & desarrollo , Pared Celular , Electroforesis en Gel de Gradiente Desnaturalizante , Lactobacillus/efectos de los fármacos , Lactobacillus/genética , Lactobacillus/crecimiento & desarrollo , Ratones , Ratones Endogámicos C57BL , Reacción en Cadena de la Polimerasa , Rizoma
14.
Sci Adv ; 10(22): eadl1123, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38809977

RESUMEN

Immunosenescence contributes to systematic aging and plays a role in the pathogenesis of Alzheimer's disease (AD). Therefore, the objective of this study was to investigate the potential of immune rejuvenation as a therapeutic strategy for AD. To achieve this, the immune systems of aged APP/PS1 mice were rejuvenated through young bone marrow transplantation (BMT). Single-cell RNA sequencing revealed that young BMT restored the expression of aging- and AD-related genes in multiple cell types within blood immune cells. The level of circulating senescence-associated secretory phenotype proteins was decreased following young BMT. Notably, young BMT resulted in a significant reduction in cerebral Aß plaque burden, neuronal degeneration, neuroinflammation, and improvement of behavioral deficits in aged APP/PS1 mice. The ameliorated cerebral amyloidosis was associated with an enhanced Aß clearance of peripheral monocytes. In conclusion, our study provides evidence that immune system rejuvenation represents a promising therapeutic approach for AD.


Asunto(s)
Enfermedad de Alzheimer , Modelos Animales de Enfermedad , Rejuvenecimiento , Animales , Enfermedad de Alzheimer/terapia , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/inmunología , Ratones , Ratones Transgénicos , Trasplante de Médula Ósea , Conducta Animal , Péptidos beta-Amiloides/metabolismo , Monocitos/inmunología , Monocitos/metabolismo , Placa Amiloide/patología , Placa Amiloide/metabolismo , Envejecimiento/inmunología , Humanos
15.
World J Surg Oncol ; 11: 143, 2013 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-23782473

RESUMEN

BACKGROUND: Gallbladder cancer (GBC) is a relatively uncommon carcinoma among gastrointestinal cancers and usually has a rather poor prognosis. The most common subtype of GBC is adenocarcinoma (AC), which accounts for about 90% of GBC. Squamous carcinoma/adenosquamous carcinoma (SC/ASC) are comparatively rare histopathological subtypes of GBC. The clinicopathological features and biological behaviors of SC/ASC have not been well-characterized. No molecular biomarkers are currently available for predicting the progression, metastasis, and prognosis of the SC/ASC subtype of GBC. METHODS: We examined the expression levels of CCT2 and PDIA3 by immunohistochemistry (IHC) staining in human GBC tissue samples collected from 46 patients with SC/ASC and evaluated the clinicopathological significance of both CCT2 and PDIA3 expression in the SC/ASC subtypes of GBC by Kaplan-Meier analysis and multivariate Cox regression analysis. For comparison, we included specimens from 80 AC patients in our study to investigate the specificity of CCT2 and PDIA3 expression in GBC subtypes. RESULTS: We found that the positive expression of CCT2 and PDIA3 was significantly associated with clinicopathological features of both SC/ASC and AC specimens, including high TNM stage and lymph node metastasis. Univariate analysis revealed that the two-year survival rate was significantly lower for patients with positive expression of CCT2 and PDIA3 than for those with negative expression. Multivariate analysis also indicated that the positive expression of CCT2 and PDIA3 was negatively correlated with poor postoperative patient survival and positively correlated with high mortality. CONCLUSIONS: Our study suggests that positive expression of CCT2 or PDIA3 is associated with tumor progression and the clinical behavior of gallbladder carcinoma. Therefore, CCT2 and PDIA3 could be potentially important diagnostic and prognostic biomarkers for both SC/ASC and AC subtypes of GBC.


Asunto(s)
Adenocarcinoma/secundario , Biomarcadores de Tumor/metabolismo , Carcinoma Adenoescamoso/secundario , Carcinoma de Células Escamosas/secundario , Chaperonina con TCP-1/metabolismo , Neoplasias de la Vesícula Biliar/patología , Proteína Disulfuro Isomerasas/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Adenoescamoso/metabolismo , Carcinoma Adenoescamoso/mortalidad , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidad , Femenino , Estudios de Seguimiento , Neoplasias de la Vesícula Biliar/metabolismo , Neoplasias de la Vesícula Biliar/mortalidad , Humanos , Técnicas para Inmunoenzimas , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , Tasa de Supervivencia
16.
Int J Numer Method Biomed Eng ; 39(12): e3776, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37776042

RESUMEN

Acupuncture points have a positive effect on the auxiliary prevention and treatment of diseases, so medical devices such as acupuncture robots often need to combine acupuncture points to improve the treatment effect when working, however, intelligent acupoint selection technology is not yet mature, the automatic rapid and accurate positioning of acupoints is still challenging. Therefore, this paper proposes a method of back acupoint location and an evaluation index of acupoint location. First, we propose an improved Keypoint RCNN network for the preliminary location of back acupoints and introduce a channel and spatial attention mechanism module (CBAM) to improve the performance of the model. Then, we set up a posterior median line positioning method to improve the accuracy of acupoint positioning. Finally, expand and locate other acupoints according to the prior information of acupoints. According to the experimental results, the accuracy of acupoint positioning was 87.32%. After the correction of acupoint positioning, the accuracy was increased by 2.8%, which was 90.12%. In this paper, the application of depth learning in automatic location of back acupoints is realized for the first time. Only one image can be used to locate the back acupoints, with an accuracy of 90.12%.


Asunto(s)
Terapia por Acupuntura , Aprendizaje Profundo , Meridianos , Puntos de Acupuntura
17.
Neurochem Int ; 169: 105589, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37543308

RESUMEN

As a ubiquitous RNA-binding protein, heterogeneous nuclear ribonucleoprotein K (hnRNPK) interacts with numerous nucleic acids and proteins and is involved in various cellular functions. Available literature indicates that it can regulate dendritic spine density through the extracellular signal-regulating kinase (ERK) - brain-derived neurotrophic factor (BDNF) pathway, which is crucial to retain the synaptic plasticity in patients with major depressive disorder (MDD) and mouse depression models. However, ERK upstream regulatory kinase has not been fully elucidated. Furthermore, it remains unexplored whether hnRNPK may impact the depressive condition via the ERK pathway. The present study addressed this issue by integrating approaches of genetics, molecular biology, behavioral testing. We found that hnRNPK in the brain was mainly distributed in the hippocampal neurons; that it was significantly downregulated in mice that displayed stress-induced depression-like behaviors; and that the level of hnRNPK markedly decreased in MDD patients from the GEO database. Further in vivo and in vitro analyses revealed that the changes in the expressions of BDNF and PSD95 and in the phosphorylation of ERK (Thr202/Tyr204) paralleled the variation of hnRNPK levels in the ventral hippocampal neurons in mice with depression-like behaviors. Finally, esketamine treatment significantly increased the level of hnRNPK in mice. These findings evidence that hnRNPK involved in the pathogenesis of depression via the ERK-BDNF pathway, pinpointing hnRNPK as a potential therapeutic target in treating MDD patients.


Asunto(s)
Depresión , Trastorno Depresivo Mayor , Animales , Ratones , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Depresión/tratamiento farmacológico , Ribonucleoproteína Heterogénea-Nuclear Grupo K/genética , Ribonucleoproteína Heterogénea-Nuclear Grupo K/metabolismo , Hipocampo/metabolismo , Transducción de Señal , Sistema de Señalización de MAP Quinasas
18.
J Alzheimers Dis ; 94(2): 537-546, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37334604

RESUMEN

BACKGROUND: The profile of naturally occurring antibodies to amyloid-ß (NAbs-Aß) is altered in patients with Alzheimer's disease (AD). However, the diagnostic potential of NAbs-Aß for AD is not clear yet. OBJECTIVE: This study aims to investigate the diagnostic capacities of NAbs-Aß for AD. METHODS: A total of 40 AD patients and 40 cognitively normal (CN) controls were enrolled in this study. Levels of NAbs-Aß were detected by ELISA. The correlations of NAbs-Aß levels with cognitive function and AD-associated biomarkers were examined by Spearman correlation analysis. Diagnostic abilities of NAbs-Aß were evaluated by the receiver operating characteristic (ROC) curve analyses. The integrative diagnostic models were established by logistic regression models. RESULTS: We found that NAbs-Aß7-18 had the highest diagnostic capability (AUC = 0.72) among all single NAbs-Aß. The combined model (NAbs-Aß7-18, NAbs-Aß19-30, and NAbs-Aß25-36) had a noticeable improvement (AUC = 0.84) in the diagnostic capacity compared with each single NAbs-Aß. CONCLUSION: NAbs-Aßs are promising in the diagnosis of AD. Further investigations are needed to confirm the translational potential of this diagnostic strategy.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Enfermedad de Alzheimer/diagnóstico , Autoanticuerpos , Péptidos beta-Amiloides , Cognición , Ensayo de Inmunoadsorción Enzimática , Biomarcadores
19.
J Oncol ; 2023: 9432073, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36793375

RESUMEN

Objective: This research intends to investigate the clinical efficacy of radiofrequency ablation and electrocautery in treating grade I or II vaginal intraepithelial neoplasia (VaIN). Methods: This is a single-center retrospective study, which collected the clinical data of 100 patients with VaIN diagnosed by colposcopy and pathological biopsy in the Gynecology and Cervical Center of Xiangzhu Branch of the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region between January 2020 and June 2021. Patients were divided into the study group (radiofrequency ablation treatment) and the control group (electrocautery) according to differences in treatment approaches. 6- and 12-month follow-ups were performed on all patients. Gynecological examination results, liquid-based thin-layer cytology (TCT), negative conversion of human papillomavirus (HPV), curative effects, and prognosis were recorded. Results: All patients completed regular follow-ups that lasted for 6 and 12 months. The 6- and 12-month cure rates of the study group were 76.0% and 92.0%, respectively, and the data in the control group were 70.0% and 82.0%, respectively. In terms of the 6- and 12-month negative conversion rates of HPV, the data in the study group were 68.0% and 78.0%, versus 60% and 68% in the control group, respectively. The lesion duration rate showed no statistical significance between the study group (8.0%) and the control group (P > 0.05). The analysis of postoperative follow-up complications revealed that the study group had a statistically lower overall incidence of vaginal bleeding, excessive vaginal discharge, vaginal burning sensation, and decreased vaginal elasticity than the control group (8.0% vs. 24.0% P < 0.05). Conclusion: Both radiofrequency ablation and electrocautery have obvious clinical effects in patients with grade I or II VaIN, but the former contributed to fewer operative complications and a good prognosis, which deserves clinical promotion.

20.
Mol Neurobiol ; 60(9): 5343-5351, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37310581

RESUMEN

Amyloid ß (Aß) and tau play pivotal roles in the pathogenesis of Alzheimer's disease (AD). Previous studies have shown that brain-derived Aß and tau can be cleared through transport into the periphery, and the kidneys may be vital organs involved in the clearance of Aß and tau. However, the effects of deficiency in the clearance of Aß and tau by the kidneys on brain AD-type pathologies in humans remain largely unknown. In this study, we first recruited 41 patients with chronic kidney disease (CKD) and 40 age- and sex-matched controls with normal renal function to analyze the associations of the estimated glomerular filtration rate (eGFR) with plasma Aß and tau levels. To analyze the associations of eGFR with cerebrospinal fluid (CSF) AD biomarkers, we recruited 42 cognitively normal CKD patients and 150 cognitively normal controls with CSF samples. Compared with controls with normal renal function, CKD patients had higher plasma levels of Aß40, Aß42 and total tau (T-tau), lower CSF levels of Aß40 and Aß42 and higher levels of CSF T-tau/Aß42 and phosphorylated tau (P-tau)/Aß42. Plasma Aß40, Aß42, and T-tau levels were negatively correlated with eGFR. In addition, eGFR was negatively correlated with CSF levels of T-tau, T-tau/Aß42, and P-tau/Aß42 but positively correlated with Mini-Mental State Examination (MMSE) scores. Thus, this study showed that the decline in renal function was correlated with abnormal AD biomarkers and cognitive decline, which provides human evidence that renal function may be involved in the pathogenesis of AD.


Asunto(s)
Enfermedad de Alzheimer , Insuficiencia Renal Crónica , Humanos , Péptidos beta-Amiloides , Enfermedad de Alzheimer/patología , Proteínas tau/líquido cefalorraquídeo , Biomarcadores , Fragmentos de Péptidos , Riñón/fisiología , Riñón/patología
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