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1.
Stem Cell Res Ther ; 15(1): 143, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38764049

RESUMO

BACKGROUND: Spinal cord injury (SCI) is a debilitating illness in humans that causes permanent loss of movement or sensation. To treat SCI, exosomes, with their unique benefits, can circumvent limitations through direct stem cell transplantation. Therefore, we utilized Gelfoam encapsulated with exosomes derived from human umbilical cord mesenchymal stem cells (HucMSC-EX) in a rat SCI model. METHODS: SCI model was established through hemisection surgery in T9 spinal cord of female Sprague-Dawley rats. Exosome-loaded Gelfoam was implanted into the lesion site. An in vivo uptake assay using labeled exosomes was conducted on day 3 post-implantation. Locomotor functions and gait analyses were assessed using Basso-Beattie-Bresnahan (BBB) locomotor rating scale and DigiGait Imaging System from weeks 1 to 8. Nociceptive responses were evaluated through von Frey filament and noxious radiant heat tests. The therapeutic effects and potential mechanisms were analyzed using Western blotting and immunofluorescence staining at week 8 post-SCI. RESULTS: For the in vivo exosome uptake assay, we observed the uptake of labeled exosomes by NeuN+, Iba1+, GFAP+, and OLIG2+ cells around the injured area. Exosome treatment consistently increased the BBB score from 1 to 8 weeks compared with the Gelfoam-saline and SCI control groups. Additionally, exosome treatment significantly improved gait abnormalities including right-to-left hind paw contact area ratio, stance/stride, stride length, stride frequency, and swing duration, validating motor function recovery. Immunostaining and Western blotting revealed high expression of NF200, MBP, GAP43, synaptophysin, and PSD95 in exosome treatment group, indicating the promotion of nerve regeneration, remyelination, and synapse formation. Interestingly, exosome treatment reduced SCI-induced upregulation of GFAP and CSPG. Furthermore, levels of Bax, p75NTR, Iba1, and iNOS were reduced around the injured area, suggesting anti-inflammatory and anti-apoptotic effects. Moreover, exosome treatment alleviated SCI-induced pain behaviors and reduced pain-associated proteins (BDNF, TRPV1, and Cav3.2). Exosomal miRNA analysis revealed several promising therapeutic miRNAs. The cell culture study also confirmed the neurotrophic effect of HucMSCs-EX. CONCLUSION: Implantation of HucMSCs-EX-encapsulated Gelfoam improves SCI-induced motor dysfunction and neuropathic pain, possibly through its capabilities in nerve regeneration, remyelination, anti-inflammation, and anti-apoptosis. Overall, exosomes could serve as a promising therapeutic alternative for SCI treatment.


Assuntos
Modelos Animais de Doenças , Exossomos , Células-Tronco Mesenquimais , Neuralgia , Ratos Sprague-Dawley , Traumatismos da Medula Espinal , Animais , Traumatismos da Medula Espinal/terapia , Exossomos/metabolismo , Neuralgia/terapia , Neuralgia/metabolismo , Ratos , Feminino , Humanos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Locomoção , Esponja de Gelatina Absorvível , Cordão Umbilical/citologia
2.
SAGE Open Med Case Rep ; 12: 2050313X241252371, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38803359

RESUMO

The occurrence of multiple primary malignancies in a single patient has been relatively rare. We report here the case of a 71-year-old man with three primary tumors of lung cancer, intrahepatic cholangiocarcinoma, and prostate cancer, and a preliminary study of the mechanisms by which multiple primary tumors develop at the genetic level. Because of the late stage of the patient's condition, large tumor burden, and poor physical status, the patient survived only a few months. In the case presented herein, cholangiocarcinoma, lung cancer, and prostate cancer were found simultaneously, and the pathogenic sites are not related. Whole-exome sequencing was performed on the pathological tissues to explore the mechanism that may underlie multiple primary cancers at the genetic level. Several gene mutations were found in this case. They involved cell proliferation, cell cycle regulation, genetic stability, metabolism, cell invasion, angiogenesis, cell apoptosis, and other pathways. It can be preliminarily inferred that the mechanism underlying multiple primary tumors is related to the abnormality of tumor-promoting and suppressing pathways.

3.
Neuron ; 112(7): 1165-1181.e8, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38301648

RESUMO

Physical exercise is known to reduce anxiety, but the underlying brain mechanisms remain unclear. Here, we explore a hypothalamo-cerebello-amygdalar circuit that may mediate motor-dependent alleviation of anxiety. This three-neuron loop, in which the cerebellar dentate nucleus takes center stage, bridges the motor system with the emotional system. Subjecting animals to a constant rotarod engages glutamatergic cerebellar dentate neurons that drive PKCδ+ amygdalar neurons to elicit an anxiolytic effect. Moreover, challenging animals on an accelerated rather than a constant rotarod engages hypothalamic neurons that provide a superimposed anxiolytic effect via an orexinergic projection to the dentate neurons that activate the amygdala. Our findings reveal a cerebello-limbic pathway that may contribute to motor-triggered alleviation of anxiety and that may be optimally exploited during challenging physical exercise.


Assuntos
Ansiolíticos , Animais , Ansiedade/metabolismo , Hipotálamo , Cerebelo , Transtornos de Ansiedade
4.
Genes Genet Syst ; 992024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38417894

RESUMO

Homeostasis is essential for muscle repair and regeneration after skeletal muscle exercise. This study investigated the role of methyltransferase-like 21C (METTL21C) in skeletal muscle of mice after exercise and the potential mechanism. First, muscle samples were collected at 2, 4 and 6 weeks after exercise, and liver glycogen, muscle glycogen, blood lactic acid and triglyceride were assessed. Moreover, the expression levels of autophagy markers and METTL21C in skeletal muscle were analyzed. The results showed that the expression levels of METTL21C and MYH7 in the gastrocnemius muscle of mice in the exercise group were significantly higher after exercise than those in the control group, which suggested that long-term exercise promoted the formation of slow-twitch muscle fibers in mouse skeletal muscle. Likewise, the autophagy capacity was enhanced with the prolongation of exercise in muscles. The findings were confirmed in mouse C2C12 cells. We discovered that knockdown of Mettl21c reduced the expression of MYH7 and the autophagy level in mouse myoblasts. These findings indicate that METTL21C promotes skeletal muscle homeostasis after exercise by enhancing autophagy, and also contributes to myogenic differentiation and the formation of slow muscle fibers.


Assuntos
Autofagia , Metiltransferases , Fibras Musculares de Contração Lenta , Cadeias Pesadas de Miosina , Condicionamento Físico Animal , Animais , Camundongos , Metiltransferases/metabolismo , Metiltransferases/genética , Cadeias Pesadas de Miosina/metabolismo , Cadeias Pesadas de Miosina/genética , Fibras Musculares de Contração Lenta/metabolismo , Masculino , Músculo Esquelético/metabolismo , Mioblastos/metabolismo , Linhagem Celular , Camundongos Endogâmicos C57BL , Desenvolvimento Muscular
5.
Yi Chuan ; 46(1): 3-17, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38230453

RESUMO

As an intraspecific outcrossing mechanism, self-incompatibility (SI) widely adopted by hermaphroditic plants is usually controlled by a polymorphic multi-allelic S locus. Typically, six molecular types of SI have been found, including type-I controlled by the pistil S S-RNase and pollen S SLFs commonly spread in Plantaginaceae, Solanaceae, Rosaceae and Rutaceae, type-II by SRK and SCR in Brassicaceae, type-III by PrsS and PrpS in Papaveraceae, type-IV by CYP-GLO2-KFB-CCM-PUM in Primulaceae, type-V by TsSPH1-TsYUC6-TsBAHD in Turneraceae and type-VI by HPS10-S and DUF247I-S in Poaceae, with type-I characterized as a non-self recognition system but types-II, -III and -VI self ones. Furthermore, remarkable progresses have been made in their origin and evolutionary mechanisms recently. Among them, type-I SI possessed a single origin in the most recent common ancestor of eudicots and types II-V dynamically evolved following its losses, while type-VI SI exclusively existed in monocot Poaceae may be regained after the loss of the ancient type-I. Here, we mainly review the molecular and evolutionary mechanisms of angiosperm SI systems, thus providing a helpful reference for their theoretical research and breeding application.


Assuntos
Magnoliopsida , Autoincompatibilidade em Angiospermas , Magnoliopsida/genética , Autoincompatibilidade em Angiospermas/genética , Melhoramento Vegetal , Evolução Biológica , Pólen , Proteínas de Plantas/genética
6.
Acta Pharmacol Sin ; 45(3): 517-530, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37880339

RESUMO

Malignant ventricular arrhythmia (VA) after myocardial infarction (MI) is mainly caused by myocardial electrophysiological remodeling. Brahma-related gene 1 (BRG1) is an ATPase catalytic subunit that belongs to a family of chromatin remodeling complexes called Switch/Sucrose Non-Fermentable Chromatin (SWI/SNF). BRG1 has been reported as a molecular chaperone, interacting with various transcription factors or proteins to regulate transcription in cardiac diseases. In this study, we investigated the potential role of BRG1 in ion channel remodeling and VA after ischemic infarction. Myocardial infarction (MI) mice were established by ligating the left anterior descending (LAD) coronary artery, and electrocardiogram (ECG) was monitored. Epicardial conduction of MI mouse heart was characterized in Langendorff-perfused hearts using epicardial optical voltage mapping. Patch-clamping analysis was conducted in single ventricular cardiomyocytes isolated from the mice. We showed that BRG1 expression in the border zone was progressively increased in the first week following MI. Cardiac-specific deletion of BRG1 by tail vein injection of AAV9-BRG1-shRNA significantly ameliorated susceptibility to electrical-induced VA and shortened QTc intervals in MI mice. BRG1 knockdown significantly enhanced conduction velocity (CV) and reversed the prolonged action potential duration in MI mouse heart. Moreover, BRG1 knockdown improved the decreased densities of Na+ current (INa) and transient outward potassium current (Ito), as well as the expression of Nav1.5 and Kv4.3 in the border zone of MI mouse hearts and in hypoxia-treated neonatal mouse ventricular cardiomyocytes. We revealed that MI increased the binding among BRG1, T-cell factor 4 (TCF4) and ß-catenin, forming a transcription complex, which suppressed the transcription activity of SCN5A and KCND3, thereby influencing the incidence of VA post-MI.


Assuntos
Infarto do Miocárdio , Camundongos , Animais , Infarto do Miocárdio/metabolismo , Arritmias Cardíacas/genética , Miocárdio/patologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Miócitos Cardíacos/metabolismo
7.
China Pharmacy ; (12): 555-559, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1012572

RESUMO

OBJECTIVE To study the effects of Phellodendron amurense polysaccharides (PAP) on improving gouty nephropathy (GN) in rats, and to investigate its mechanism primarily by interfering the p38 mitogen-activated protein kinase (p38 MAPK)/nuclear factor-κB(NF-κB)/tumor necrosis factor-α(TNF-α). METHODS Sixty rats were randomly divided into normal group (water), model group (water), allopurinol group (positive control, 20 mg/kg), PAP high-dose, medium-dose and low-dose groups (100, 50, 25 mg/kg, by raw material) after being stratified by body weight, with 10 rats in each group. Except for the normal group, the other groups were induced to construct GN model by giving 1 500 mg/kg potassium oxazinate and 100 mg/kg adenine intragastrically for 14 days. After modeling, the rats in each group were given relevant medicine/water intragastrically, once a day, for consecutive 28 days. After the last medication, the levels of biochemical parameters related to renal function [uric acid, creatinine (Cr), blood urea nitrogen (BUN), xanthine oxidase (XOD)] were detected in rats, and the histopathological changes in the rat kidney were observed. The protein expressions of monocyte chemoattractant protein-1(MCP-1),TNF-α and interleukin-6(IL-6) as well as the phosphorylation levels of p38 MAPK and NF-κB p65 protein were determined in renal tissue of rats. RESULTS Compared with the normal group, the model group suffered from the dilatation of renal tubules, structural damage to glomeruli, accompanied by inflammatory infiltration and fibrosis; the contents of uric acid, Cr, BUN and XOD, the protein expressions of MCP-1,TNF-α and IL-6 and the phosphorylation levels of p38 MAPK and NF-κB p65 protein were all increased significantly (P<0.05 or P<0.01). Compared with the model group, the pathological symptoms of renal tissue in rats had been improved to varying degrees in different dose groups of PAP; the contents of uric acid, Cr, BUN and XOD, protein expressions of MCP-1, TNF-α and IL-6, the phosphorylation levels of p38 MAPK and NF-κB p65 protein in PAP high-dose and PAP medium-dose groups were all decreased significantly (P<0.05 or P<0.01). CONCLUSIONS PAP exhibits an anti-GN effect, the mechanism of which may be associated with inhibiting the p38 MAPK/NF-κB/TNF-α signaling pathway.

8.
Heliyon ; 9(9): e19765, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37809742

RESUMO

Sewage sludge (SS) is an environmental issue due to its high organic content and ability to release hazardous substances. Most of the treatments available are biological, thermal hydrolysis, mechanical (ultrasound, high pressure, and lysis), chemical with oxidation (mainly ozonation), and alkali pre-treatments. Other treatment methods include landfill, wet oxidation, composting, drying, stabilization, incineration, pyrolysis, carbonization, liquefaction, gasification, and torrefaction. Some of these SS disposal methods damage the ecosystem and underutilize the potential resource value of SS. These challenges must be overcome with an innovative technique for the improvement of SS's nutritional value, energy content, and usability. This review proposes plasma pyrolysis and anaerobic digestion (AD) as promising SS treatment technologies. Plasma pyrolysis pre-treats SS to make it digestible by AD bacteria and immobilizes the heavy metals. The addition of Char to the upstream AD process increases the quantity and quality of biogas produced while enhancing the nutrients in the digestate. These two processes are integrated at high temperatures, thus creating concerns about their energy demand. These challenges are offset by the generated energy that can run the treatment plant or be sold to the grid, generating additional cash. Plasma pyrolysis wastes can also be converted into biochar, organic fertilizer, or soil conditioner. These combined technologies' financial sustainability depends on the treatment facility's circumstances and location. Plasma pyrolysis and AD can treat SS sustainably and provide nutrients and resources. This paper explains the co-process treatment route's techno-economic prospects, challenges, and recommendations for the future application of SS valorization and resource recovery.

9.
Prog Mol Biol Transl Sci ; 199: 63-107, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37678982

RESUMO

Human pluripotent stem cells (human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs)) have unlimited proliferative potential, whereas adult stem cells such as bone marrow-derived stem cells and adipose-derived stem cells have problems with aging. When hPSCs are intended to be cultured on feeder-free or xeno-free conditions without utilizing mouse embryonic fibroblasts or human fibroblasts, they cannot be cultured on conventional tissue culture polystyrene dishes, as adult stem cells can be cultured but should be cultivated on material surfaces grafted or coated with (a) natural or recombinant extracellular matrix (ECM) proteins, (b) ECM protein-derived peptides and specific synthetic polymer surfaces in xeno-free and/or chemically defined conditions. This review describes current developing cell culture biomaterials for the proliferation of hPSCs while maintaining the pluripotency and differentiation potential of the cells into 3 germ layers. Biomaterials for the cultivation of hPSCs without utilizing a feeder layer are essential to decrease the risk of xenogenic molecules, which contributes to the potential clinical usage of hPSCs. ECM proteins such as human recombinant vitronectin, laminin-511 and laminin-521 have been utilized instead of Matrigel for the feeder-free cultivation of hPSCs. The following biomaterials are also discussed for hPSC cultivation: (a) decellularized ECM, (b) peptide-grafted biomaterials derived from ECM proteins, (c) recombinant E-cadherin-coated surface, (d) polysaccharide-immobilized surface, (e) synthetic polymer surfaces with and without bioactive sites, (f) thermoresponsive polymer surfaces with and without bioactive sites, and (g) synthetic microfibrous scaffolds.


Assuntos
Células-Tronco Adultas , Laminina , Animais , Camundongos , Adulto , Humanos , Laminina/farmacologia , Fibroblastos , Materiais Biocompatíveis/farmacologia , Proliferação de Células
10.
BMC Med ; 21(1): 348, 2023 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-37679672

RESUMO

BACKGROUND: Full-cohort and sibling-comparison designs have yielded inconsistent results about the impacts of caesarean delivery on offspring health outcomes, with the effect estimates from the latter being more likely directed towards the null value. We hypothesized that the seemingly conservative results obtained from the sibling-comparison design might be attributed to inadequate adjustment for non-shared confounders between siblings, particularly maternal age at delivery. METHODS: A systematic review and meta-analysis was first conducted. PubMed, Embase, and the Web of Science were searched from database inception to April 6, 2022. Included studies (1) examined the association of caesarean delivery, whether elective or emergency, with offspring health outcomes; (2) simultaneously conducted full-cohort and sibling-comparison analyses; and (3) reported adjusted effect estimates with 95% confidence intervals (95% CIs). No language restrictions were applied. Data were extracted by 2 reviewers independently. Three-level meta-analytic models were used to calculate the pooled odds ratios (ORs) and 95% CIs for caesarean versus vaginal delivery on multiple offspring health outcomes separately for full-cohort and sibling-comparison designs. Subgroup analyses were performed based on the method of adjustment for maternal age at delivery. A simulation study was then conducted. The simulated datasets were generated with some key parameters derived from the meta-analysis. RESULTS: Eighteen studies involving 21,854,828 individuals were included. The outcomes assessed included mental and behavioral disorders; endocrine, nutritional and metabolic diseases; asthma; cardiorespiratory fitness; and multiple sclerosis. The overall pooled OR for estimates from the full-cohort design was 1.14 (95% CI: 1.11 to 1.17), higher than that for estimates from the sibling-comparison design (OR = 1.08; 95% CI: 1.02 to 1.14). Stratified analyses showed that estimates from the sibling-comparison design varied considerably across studies using different methods to adjust for maternal age at delivery in multivariate analyses, while those from the full-cohort design were rather stable: in studies that did not adjust maternal age at delivery, the pooled OR of full-cohort vs. sibling-comparison design was 1.10 (95% CI: 0.99 to 1.22) vs. 1.06 (95% CI: 0.85 to 1.31), in studies adjusting it as a categorical variable, 1.15 (95% CI: 1.11 to 1.19) vs. 1.07 (95% CI: 1.00 to 1.15), and in studies adjusting it as a continuous variable, 1.12 (95% CI: 1.05 to 1.19) vs. 1.12 (95% CI: 0.98 to 1.29). The severe underestimation bias related to the inadequate adjustment of maternal age at delivery in sibling-comparison analyses was fully replicated in the simulation study. CONCLUSIONS: Sibling-comparison analyses may underestimate the association of caesarean delivery with multiple offspring health outcomes due to inadequate adjustment of non-shared confounders, such as maternal age at delivery. Thus, we should be cautious when interpreting the seemingly conservative results of sibling-comparison analyses in delivery-related studies.


Assuntos
Asma , Irmãos , Feminino , Gravidez , Humanos , Cesárea , Parto Obstétrico , Avaliação de Resultados em Cuidados de Saúde
11.
World J Gastroenterol ; 29(29): 4557-4570, 2023 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-37621756

RESUMO

BACKGROUND: Hydrogen sulfide (H2S) is a recently discovered gaseous neurotransmitter in the nervous and gastrointestinal systems. It exerts its effects through multiple signaling pathways, impacting various physiological activities. The nucleus tractus solitarius (NTS), a vital nucleus involved in visceral sensation, was investigated in this study to understand the role of H2S in regulating gastric function in rats. AIM: To examine whether H2S affects the nuclear factor kappa-B (NF-κB) and transient receptor potential vanilloid 1 pathways and the neurokinin 1 (NK1) receptor in the NTS. METHODS: Immunohistochemical and fluorescent double-labeling techniques were employed to identify cystathionine beta-synthase (CBS) and c-Fos co-expressed positive neurons in the NTS during rat stress. Gastric motility curves were recorded by inserting a pressure-sensing balloon into the pylorus through the stomach fundus. Changes in gastric motility were observed before and after injecting different doses of NaHS (4 nmol and 8 nmol), physiological saline, Capsazepine (4 nmol) + NaHS (4 nmol), pyrrolidine dithiocarbamate (PDTC, 4 nmol) + NaHS (4 nmol), and L703606 (4 nmol) + NaHS (4 nmol). RESULTS: We identified a significant increase in the co-expression of c-Fos and CBS positive neurons in the NTS after 1 h and 3 h of restraint water-immersion stress compared to the expressions observed in the control group. Intra-NTS injection of NaHS at different doses significantly inhibited gastric motility in rats (P < 0.01). However, injection of saline, first injection NF-κB inhibitor PDTC or transient receptor potential vanilloid 1 (TRPV1) antagonist Capsazepine or NK1 receptor blockers L703606 and then injection NaHS did not produce significant changes (P > 0.05). CONCLUSION: NTS contains neurons co-expressing CBS and c-Fos, and the injection of NaHS into the NTS can suppress gastric motility in rats. This effect may be mediated by activating TRPV1 and NK1 receptors via the NF-κB channel.


Assuntos
Sulfeto de Hidrogênio , Animais , Ratos , Sulfeto de Hidrogênio/farmacologia , NF-kappa B , Núcleo Solitário , Desidratação
12.
Pharmacol Res ; 191: 106773, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37068531

RESUMO

Specific medications to combat cerebellar ataxias, a group of debilitating movement disorders characterized by difficulty with walking, balance and coordination, are still lacking. Notably, cerebellar microglial activation appears to be a common feature in different types of ataxic patients and rodent models. However, direct evidence that cerebellar microglial activation in vivo is sufficient to induce ataxia is still lacking. Here, by employing chemogenetic approaches to manipulate cerebellar microglia selectively and directly, we found that specific chemogenetic activation of microglia in the cerebellar vermis directly leads to ataxia symptoms in wild-type mice and aggravated ataxic motor deficits in 3-acetylpyridine (3-AP) mice, a classic mouse model of cerebellar ataxia. Mechanistically, cerebellar microglial proinflammatory activation induced by either chemogenetic M3D(Gq) stimulation or 3-AP modeling hyperexcites Purkinje cells (PCs), which consequently triggers ataxia. Blockade of microglia-derived TNF-α, one of the most important proinflammatory cytokines, attenuates the hyperactivity of PCs driven by microglia. Moreover, chemogenetic inhibition of cerebellar microglial activation or suppression of cerebellar microglial activation by PLX3397 and minocycline reduces the production of proinflammatory cytokines, including TNF-α, to effectively restore the overactivation of PCs and alleviate motor deficits in 3-AP mice. These results suggest that cerebellar microglial activation may aggravate the neuroinflammatory response and subsequently induce dysfunction of PCs, which in turn triggers ataxic motor deficits. Our findings thus reveal a causal relationship between proinflammatory activation of cerebellar microglia and ataxic motor symptoms, which may offer novel evidence for therapeutic intervention for cerebellar ataxias by targeting microglia and microglia-derived inflammatory mediators.


Assuntos
Ataxia Cerebelar , Camundongos , Animais , Ataxia Cerebelar/induzido quimicamente , Células de Purkinje/fisiologia , Microglia , Fator de Necrose Tumoral alfa/farmacologia , Cerebelo , Citocinas
13.
Cerebellum ; 22(5): 888-904, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36040660

RESUMO

The classical motor center cerebellum is one of the most consistent structures of abnormality in autism spectrum disorders (ASD), and neuropeptide oxytocin is increasingly explored as a potential pharmacotherapy for ASD. However, whether oxytocin targets the cerebellum for therapeutic effects remains unclear. Here, we report a localization of oxytocin receptor (OXTR) in Purkinje cells (PCs) of cerebellar lobule Crus I, which is functionally connected with ASD-implicated circuits. OXTR activation neither affects firing activities, intrinsic excitability, and synaptic transmission of normal PCs nor improves abnormal intrinsic excitability and synaptic transmission of PCs in maternal immune activation (MIA) mouse model of autism. Furthermore, blockage of OXTR in Crus I in wild-type mice does not induce autistic-like social, stereotypic, cognitive, and anxiety-like behaviors. These results suggest that oxytocin signaling in Crus I PCs seems to be uninvolved in ASD pathophysiology, and contribute to understanding of targets and mechanisms of oxytocin in ASD treatment.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Camundongos , Animais , Receptores de Ocitocina , Ocitocina , Células de Purkinje
14.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-959036

RESUMO

Objective With the deepening of population aging, sarcopenia has become an important public health problem affecting the health and quality of life of the elderly population. As the end-product of purine metabolism in human body, uric acid has dual effects of anti-oxidation, pro-oxidation and pro-inflammatory reaction , which affects the occurrence and development of sarcopenia to a certain extent. This paper reviews the research progress of serum uric acid and sarcopenia. Methods PubMed database, Web of Science core collection database, Embase database, China National Knowledge Infrastructure (CNKI) and Wanfang database were searched for literatures on the relationship between serum uric acid (SUA) level and sarcopenia up to February 7, 2022, and then reviewed. Results A total of 4 epidemiological studies were found on serum uric acid levels and the risk of sarcopenia. Among them, 3 studies found that SUA within a certain level range was a protective factor for sarcopenia, and 1 study suggested that the risk of sarcopenia increased with the increase of SUA levels. There was a gender difference between serum uric acid level and sarcopenia risk. Conclusion At present, the results of studies on the relationship between serum uric acid levels and the risk of sarcopenia are still controversial, which may be caused by the different effects of uric acid in human body. In the future , more extensive and in-depth studies are needed to investigate the relationship between the two.

15.
Chinese Journal of Hematology ; (12): 838-844, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1012241

RESUMO

Objective: To explore the dynamic changes in serum lipid levels and nutritional status during BCMA-CAR-T-cell therapy in patients with refractory or relapsed multiple myeloma (R/R MM) based on LEGEND-2. Methods: The data of patients with R/R MM who underwent BCMA-CAR-T therapy at our hospital between March 30, 2016, and February 6, 2018, were retrospectively collected. Serum lipid levels, controlled nutritional status (CONUT) score, and other clinical indicators at different time points before and after CAR-T-cell infusion were compared and analyzed. The best cut-off value was determined by using the receiver operator characteristic (ROC) curve. The patients were divided into high-CONUT score (>6.5 points, malnutrition group) and low-CONUT score groups (≤6.5 points, good nutrition group), comparing the progression-free survival (PFS) and total survival (OS) of the two groups using Kaplan-Meier survival analysis. Results: Before the infusion of CAR-T-cells, excluding triglycerides (TG), patients' serum lipid levels were lower than normal on average. At 8-14 d after CAR-T-cell infusion, serum albumin (ALB), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and apolipoprotein A1 (Apo A1) levels dropped to the minimum, whereas CONUT scores reached the maximum. In addition to TG, apolipoprotein B (Apo B) levels increased compared with baseline. After CAR-T-cell therapy, the patients' serum lipid levels significantly increased with well-improved nutritional status. Spearman's related analysis showed that TC, HDL, and ApoA1 levels after CAR-T-cell injection were significantly negatively correlated with the grade of cytokine-release syndrome (CRS) (r=-0.548, P=0.003; r=-0.444, P=0.020; r=-0.589, P=0.001). Furthermore, survival analysis indicated that the CONUT score was unrelated to PFS, and the median OS of patients with R/R MM in the high-CONUT score group was shorter than that in the low-CONUT score group (P=0.046) . Conclusions: During CAR-T-cell therapy, hypolipidemia and poor nutritional status were aggravated, which is possibly related to CRS. The patients' serum lipid levels and nutritional status were significantly improved after CAR-T-cell treatment. The CONUT score affected the median OS in patients treated with CAR-T-cells. Therefore, specific screening and intervention for nutritional status in patients receiving CAR-T-cell therapy are required.


Assuntos
Humanos , Mieloma Múltiplo/tratamento farmacológico , Estado Nutricional , Estudos Retrospectivos , Receptores de Antígenos Quiméricos/uso terapêutico , Antígeno de Maturação de Linfócitos B/uso terapêutico , Terapia Baseada em Transplante de Células e Tecidos , Lipídeos/uso terapêutico
16.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-1010590

RESUMO

Cytomegalovirus (CMV) infection is currently prevalent in populations throughout the world, and 56%‍-94% of the global population is seropositive for CMV. CMV infection mainly affects immunocompromised hosts. In these cases, it can cause significant symptoms, tissue-invasive disease, and many sequelae including death (Dioverti and Razonable, 2016). The vast majority of healthy adults with CMV infection experience an asymptomatic course; when symptomatic, it manifests as a mononucleosis-like syndrome in approximately 10% of patients (Sridhar et al., 2018). The gastrointestinal tract and central nervous system appear to be the most frequent sites of severe CMV infection in immunocompetent individuals (Rafailidis et al., 2008). However, CMV infection is relatively rarely recorded in immunocompetent hosts.


Assuntos
Adulto , Humanos , Linfo-Histiocitose Hemofagocítica/complicações , Infecções por Citomegalovirus/diagnóstico , Trato Gastrointestinal , Progressão da Doença
17.
Chinese Journal of Pediatrics ; (12): 49-55, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-970235

RESUMO

Objective: To investigate the characteristics of duodenal bulbar microbiota in children with duodenal ulcer and Helicobacter pylori (Hp) infection. Methods: This prospective cohort study enrolled 23 children with duodenal ulcers diagnosed by gastroscopy who were admitted to the Children's Hospital of Zhejiang University School of Medicine due to abdominal pain, abdominal distension, and vomiting from January 2018 to August 2018. They were divided into Hp-positive and Hp-negative groups according to the presence or absence of Hp infection. Duodenal bulbar mucosa was sampled to detect the bacterial DNA by high-throughput sequencing. The statistical difference in α diversity and β diversity, and the relative abundance in taxonomic level between the two groups were compared. Microbial functions were predicted using the software PICRUSt. T-test, Rank sum test or χ2 test were used for comparison between the two groups. Results: A total of 23 children diagnosed with duodenal ulcer were enrolled in this study, including 15 cases with Hp infection ((11.2±3.3) years of age, 11 males and 4 females) and 8 cases without Hp infection ((10.1±4.4) years of age, 6 males and 2 females). Compared with Hp-negative group, the Hp-positive group had higher Helicobacter abundance (0.551% (0.258%, 5.368%) vs. 0.143% (0.039%, 0.762%), Z=2.00, P=0.045) and lower abundance of Fusobacterium, Streptococcus and unclassified- Comamonadaceae (0.010% (0.001%, 0.031%) vs. 0.049% (0.011%, 0.310%), Z=-2.24, P=0.025; 0.031% (0.015%, 0.092%) vs. 0.118% (0.046%, 0.410%), Z=-2.10, P=0.036; 0.046% (0.036%, 0.062%) vs. 0.110% (0.045%, 0.176%), Z=-2.01, P=0.045). Linear discriminant analysis (LDA) effect sized showed that at the genus level, only Helicobacter was significantly enriched in Hp-positive group (LDA=4.89, P=0.045), while Streptococcus and Fusobacterium significantly enriched in Hp-negative group (LDA=3.28, 3.11;P=0.036,0.025, respectively). PICRUSt microbial function prediction showed that the expression of oxidative phosphorylation and disease-related pathways (pathways in cancer, renal cell carcinoma, amoebiasis, type 1 diabetes mellitus) in Hp-positive group were significantly higher than that in Hp-negative group (all P<0.05), while the expression of pathways such as energy metabolism and phosphotransferase system pathways were significantly lower than that in Hp-negative group (all P<0.05). Conclusion: In children with Hp-infected duodenal ulcers, the mucosal microbiota of the duodenal bulb is altered, characterized by an increased abundance of Helicobacter and a decreased abundance of Clostridium and Streptococcus, and possibly alters the biological function of the commensal microbiota through specific metabolic pathways.


Assuntos
Masculino , Feminino , Humanos , Criança , Úlcera Duodenal/diagnóstico , Infecções por Helicobacter/complicações , Helicobacter pylori/genética , Estudos Prospectivos , Microbiota
18.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-969938

RESUMO

This paper makes an interpretation of the collection Acupuncture: how to improve the evidence base published by BMJ & BMJ Open. Studies show that the quality of randomized controlled trial (RCT) of acupuncture is low, and multivariable Meta-regression analysis fails to confirm most factors commonly believed to influence the effect of acupuncture. The methodological challenges in design and conduct of RCT in acupuncture were analyzed, and a consensus on how to design high-quality acupuncture RCT was developed. The number of acupuncture systematic reviews was huge but the evidence was underused in clinical practice and health policy, and a large number of western clinical practice guidelines recommended acupuncture therapy, but the usefulness of recommendations needed to be improved. In view of the problems in clinical research on acupuncture mentioned in this collection, combined with the analysis of the purpose of clinical research on acupuncture, perspectives, study types, as well as the relationship between evidence and clinical decision-making, a five-stage study paradigm of clinical research on acupuncture is proposed.


Assuntos
Terapia por Acupuntura , Acupuntura , Projetos de Pesquisa , Consenso
19.
International Eye Science ; (12): 694-699, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-965803

RESUMO

AIM: To analyze the clinical and histopathological composition of orbital tumors and tumor-like lesions.METHODS: Retrospective case-series study. The clinical histopathological data of 699 cases(707 eyes)with orbital tumor and tumor-like lesions who treated in the orbital disease and ophthalmic plastic department of Tianjin Eye Hospital between January 2010 and December 2020 were collected. All the pathology diagnosis results were divided into three categories which were benign tumor, borderline tumor and malignant tumor according to the eighth edition of the American Joint Committee on Cancer staging system and the 2018 World Health Organization Classification of tumors of the eye. All cases were divided into four groups according to age, including 0~17 years old, 18~39 years old, 40~59 years old, 60 years and above. The histological composition of each group was analyzed.RESULTS: Among the 699 cases(707 eyes), 311 patients(316 eyes)were male and 388 patients(391 eyes)were female. The patient's age at diagnosis ranged from 1 to 84 years(mean 39.9±2.2)years. The right orbit was involved in 307 patients, the left orbit in 384 patients, and 8 patients in bilateral orbit. There were 598 patients(604 eyes, 85.6%)with benign tumor and tumor-like lesions, 7 patients(7 eyes, 1.0%)with borderline tumor, and 94 patients(96 eyes, 13.4%)with malignant tumors. The top 5 benign tumor and tumor-like lesions were cavernous hemangioma(110 cases, 15.7%), dermoid cysts(96 cases, 13.7%), pleomorphic adenomas(54 cases, 7.7%), inflammatory pseudotumors(38 cases, 5.4%), and schwannomas(29 cases, 4.1%)respectively. The top 5 borderline and malignant tumors were non-Hodgkin lymphomas(42 cases, 41.6%), solitary fibrous tumors(12 cases, 11.9%), adenoid cystic carcinomas(11 cases, 10.9%), metastatic tumor(9 cases, 8.9%), and rhabdomyosarcoma(8 cases, 7.9%), respectively. Among the common orbital benign tumors and tumor-like lesions, cavernous hemangioma and pleomorphic adenoma showed a female predominance. Among the common borderline and malignant tumors, non-Hodgkin lymphoma and mesenchymal chondrosarcoma showed a male predominance. The most common benign and malignant tumors were dermoid cysts, rhabdomyosarcomas respectively in group under 18 years old. And dermoid cysts and solitary fibrous tumors were the most common benign and malignant tumors respectively in patients between 18 and 39 years old. Cavernous hemangioma and non-Hodgkin lymphomas were the most common benign and malignant tumors respectively in patients between 40 and 59 years old. While cavernous hemangioma and non-Hodgkin lymphomas were the most common benign and malignant tumors respectively in cases over 60 years old.CONCLUSION: Most orbital tumors and tumor-like lesions are benign. The most common benign orbital tumor is cavernous hemangioma, followed by dermoid cyst. Non-Hodgkin lymphoma is the most common malignant orbital tumor.

20.
Chinese Medical Journal ; (24): 1216-1224, 2023.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-980858

RESUMO

BACKGROUND@#Neuroendocrine neoplasms (NENs) are rare tumors characterized by variable biology and delayed diagnosis. However, the nationwide epidemiology of NENs has never been reported in China. We aimed to estimate the incidence and survival statistics of NENs in China, in comparison to those in the United States during the same period.@*METHODS@#Based on the data from 246 population-based cancer registries covering 272.5 million people of China, we calculated age-specific incidence on NENs in 2017 and multiplied by corresponding national population to estimate the nationwide incidence in China. The data of 22 population-based cancer registries were used to estimate the trends of NENs incidence from 2000 to 2017 through the Joinpoint regression model. We used the cohort approach to analyze the 5-year age-standardized relative survival by sex, age group, and urban-rural area between 2008 and 2013, based on data from 176 high-quality cancer registries. We used data from the Surveillance, Epidemiology, and End Results (SEER) 18 program to estimate the comparable incidence and survival of NENs in the United States.@*RESULTS@#The overall age-standardized rate (ASR) of NENs incidence was lower in China (1.14 per 100,000) than in the United States (6.26 per 100,000). The most common primary sites were lungs, pancreas, stomach, and rectum in China. The ASRs of NENs incidence increased by 9.8% and 3.6% per year in China and the United States, respectively. The overall 5-year relative survival in China (36.2%) was lower than in the United States (63.9%). The 5-year relative survival was higher for female patients than male patients, and was higher in urban areas than in rural areas.@*CONCLUSIONS@#The disparities in burden of NENs persist across sex, area, age group, and site in China and the United States. These findings may provide a scientific basis on prevention and control of NENs in the two countries.


Assuntos
Humanos , Masculino , Feminino , Estados Unidos/epidemiologia , Incidência , Tumores Neuroendócrinos/patologia , Neoplasias/epidemiologia , Sistema de Registros , População Urbana , China/epidemiologia
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