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1.
Cell Rep ; 43(8): 114582, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39096488

RESUMO

Male infertility is a recognized side effect of chemoradiotherapy. Extant spermatogonial stem cells (SSCs) may act as originators for any subsequent recovery. However, which type of SSCs, the mechanism by which they survive and resist toxicity, and how they act to restart spermatogenesis remain largely unknown. Here, we identify a small population of Set domain-containing protein 4 (Setd4)-expressing SSCs that occur in a relatively dormant state in the mouse seminiferous tubule. Extant beyond high-dose chemoradiotherapy, these cells then activate to recover spermatogenesis. Recovery fails when Setd4+ SSCs are deleted. Confirmed to be of fetal origin, these Setd4+ SSCs are shown to facilitate early testicular development and also contribute to steady-state spermatogenesis in adulthood. Upon activation, chromatin remodeling increases their genome-wide accessibility, enabling Notch1 and Aurora activation with corresponding silencing of p21 and p53. Here, Setd4+ SSCs are presented as the originators of both testicular development and spermatogenesis recovery in chemoradiotherapy-induced infertility.


Assuntos
Infertilidade Masculina , Espermatogênese , Masculino , Animais , Espermatogênese/efeitos dos fármacos , Espermatogênese/efeitos da radiação , Infertilidade Masculina/terapia , Camundongos , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Células-Tronco/metabolismo , Células-Tronco/efeitos da radiação , Camundongos Endogâmicos C57BL , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Montagem e Desmontagem da Cromatina/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/metabolismo , Receptor Notch1/metabolismo , Receptor Notch1/genética
3.
World J Gastrointest Oncol ; 16(4): 1192-1203, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38660657

RESUMO

BACKGROUND: Indentifying predictive factors for postoperative recurrence of hepatocellular carcinoma (HCC) has great significance for patient prognosis. AIM: To explore the value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI) combined with clinical features in predicting early recurrence of HCC after resection. METHODS: A total of 161 patients with pathologically confirmed HCC were enrolled. The patients were divided into early recurrence and non-early recurrence group based on the follow-up results. The clinical, laboratory, pathological results and Gd-EOB-DTPA enhanced MRI imaging features were analyzed. RESULTS: Of 161 patients, 73 had early recurrence and 88 were had non-early recurrence. Univariate analysis showed that patient age, gender, serum alpha-fetoprotein level, the Barcelona Clinic Liver Cancer stage, China liver cancer (CNLC) stage, microvascular invasion (MVI), pathological satellite focus, tumor size, tumor number, tumor boundary, tumor capsule, intratumoral necrosis, portal vein tumor thrombus, large vessel invasion, nonperipheral washout, peritumoral enhancement, hepatobiliary phase (HBP)/tumor signal intensity (SI)/peritumoral SI, HBP peritumoral low signal and peritumoral delay enhancement were significantly associated with early recurrence of HCC after operation. Multivariate logistic regression analysis showed that patient age, MVI, CNLC stage, tumor boundary and large vessel invasion were independent predictive factors. External data validation indicated that the area under the curve of the combined predictors was 0.861, suggesting that multivariate logistic regression was a reasonable predictive model for early recurrence of HCC. CONCLUSION: Gd-EOB-DTPA enhanced MRI combined with clinical features would help predicting the early recurrence of HCC after operation.

4.
Stroke Vasc Neurol ; 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38460971

RESUMO

BACKGROUND: The relationship between anterior cerebral artery (ACA) occlusion and moyamoya disease (MMD) has rarely been studied. In this study, we focused on a special type of MMD: isolated ACA-occlusive MMD. We investigated clinical attributes, genotypes and progression risk factors in patients with ACA-occlusive MMD, providing initial insights into the relationship between ACA occlusion and MMD. METHODS: We retrospectively analysed digital subtraction angiography (DSA) from 2486 patients and diagnosed 139 patients with ACA-occlusive MMD. RNF213 p.R4810K (rs112735431) mutation analysis was performed. Patients were categorised into progression and non-progression groups based on whether they progressed to typical MMD. Differences in clinical characteristics, neuropsychological assessment, radiological findings and genotypes were evaluated. Logistic regression analyses identified risk factors for ACA-occlusive MMD progression. RESULTS: The median age of patients with ACA-occlusive MMD was 36 years, and the primary symptom was transient ischaemic attack (TIA). 72.3% of ACA-occlusive MMD patients had cognitive decline. Of 116 patients who underwent RNF213 gene mutation analysis, 90 patients (77.6%) carried the RNF213 p.R4810K GG allele and 26 (22.4%) carried the GA allele. Of 102 patients with follow-up DSA data, 40 patients (39.2%) progressed. Kaplan-Meier curve estimates indicated a higher incidence of ischaemic stroke in the progression group during follow-up (p=0.035). Younger age (p=0.041), RNF213 p.R4810K GA genotype (p=0.037) and poor collateral compensation from the middle cerebral artery (MCA) to ACA (p<0.001) were risk factors of ACA-occlusive MMD progression to typical MMD. CONCLUSIONS: Cognitive decline and TIA might be the main manifestations of ACA-occlusive MMD. Isolated ACA occlusion may be an early signal of MMD. The initial lesion site of MMD is not strictly confined to the terminal portion of the internal carotid artery. Younger patients, patients with RNF213 p.R4810K GA genotype or those with inadequate MCA-to-ACA compensation are more likely to develop typical MMD.

5.
Brain Behav ; 13(12): e3328, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37962021

RESUMO

BACKGROUND: The pathogenesis of moyamoya disease (MMD) is unclear. Inflammation and immune imbalance have been identified as potential factors contributing to the occurrence and progression of MMD. However, the specific proteins and metabolites responsible for triggering this process are yet to be established. The purpose of this study is to identify differentially expressed proteins and metabolites in patients with MMD and perform Kyoto Encyclopedia of Genes and Genomes pathway integration analysis to pinpoint crucial proteins and metabolites involved in the disease. METHODS: We performed untargeted metabolomic and data-independent acquisition proteomic analyses on the serum samples of individuals with MMD and healthy controls (HC). RESULTS: In patients with MMD versus HC, 24 proteins and 60 metabolites, including 21 anionic metabolites and 39 cationic metabolites, which were significantly different, were identified. In patients with MMD, several proteins involved in inflammation and immune metabolism, such as tubulin beta-6 and complement C4, were found to have significantly altered levels. Similarly, many metabolites involved in inflammation and immune metabolisms, such as dimethyl 4-hydroxyisophthalate, beta-nicotinamide mononucleotide, 2-(3-(4-pyridyl)-1H-1,2,4-triazol-5-yl)pyridine, and PC (17:1/18:2), were significantly altered. Intriguingly, these proteins and metabolites are involved in the progression of atherosclerosis through immune and inflammatory pathways, although some have never been reported in MMD. Moreover, integrated proteomics and metabolomics studies were conducted to determine shared pathways involving cholesterol metabolism, vitamin digestion, fat digestion, and absorption pathways of proteins and metabolites, which warrant further investigation. CONCLUSIONS: Significant increases in pro-inflammatory and immunosuppressive abilities have been observed in patients with MMD, accompanied by significant reductions in anti-inflammatory and immune regulation. Various metabolites and proteins implicated in these processes have been identified for the first time. These findings hold immense significance for comprehending the pathogenesis of MMD and for the development of future drug therapies.


Assuntos
Doença de Moyamoya , Humanos , Proteômica , Metabolômica , Inflamação
6.
Gastric Cancer ; 26(6): 918-933, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37676622

RESUMO

BACKGROUND AND AIMS: Specific mechanisms of lymph node (LN) metastasis in early-stage gastric cancer (GC) have not been elucidated. The role of anemia, a vital clinical feature of GC, in LN metastasis is also unclear. Since the number of erythroid progenitor cells (EPCs) is increased in chronic anemia, we investigated its association with LN metastasis in GC. METHODS: Flow cytometry and immunofluorescence analyses were performed to sort and study EPCs from the circulation and tumors of patients with stage I-III GC. The effect of these EPCs on the activation of T and B cells and on the functions of lymphatic endothelial cells (LECs) was determined, and their ability to promote LN metastasis was evaluated using a footpad-popliteal LN metastasis model based on two human adenocarcinoma GC cell lines in nude mice. The prognostic value of EPCs was also analyzed. RESULTS: The proportion of CD45- EPCs was higher in the mononuclear cells in the circulation, tumors, and LNs of GC patients with LN metastasis (N+) than in those of GC patients without LN metastasis (N0). In N+ patients, CD45- EPCs were more abundant in metastatic LNs than in non-metastatic LNs. Lymphatic vessel endothelial hyaluronan receptor 1 immunoreactivity in tumors revealed that CD45- EPCs were positively associated with nodal stages and lymph vessel density. Furthermore, CD45- EPCs increased LEC proliferation and migration through their S100A8/A9 heterodimer-induced hybrid epithelial/mesenchymal (E/M) state; however, they did not influence the invasion and tubulogenesis of LECs or T and B cell proliferation. CD45- EPCs promoted LN metastasis in vivo; the S100A8/A9 heterodimer mimicked this phenomenon. Finally, CD45- EPCs predicted the overall and disease-free survival of stage I-III GC patients after radical resection. CONCLUSIONS: The CD45- EPCs accumulated in GC tissues and metastatic LNs and promoted LN metastasis via the S100A8/9-induced hybrid E/M state of LECs, which was the specific mechanism of LN metastasis in the early stages of GC.


Assuntos
Anemia , Neoplasias Gástricas , Camundongos , Animais , Humanos , Metástase Linfática/patologia , Neoplasias Gástricas/patologia , Células Endoteliais/metabolismo , Células Precursoras Eritroides/metabolismo , Células Precursoras Eritroides/patologia , Camundongos Nus , Linfonodos/patologia , Anemia/patologia
7.
Foods ; 12(8)2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37107522

RESUMO

The drying of compact and biologically active materials presents significant challenges. In this study, we propose using electrostatic field-ultrasonic coupling pretreatment to enhance the drying efficiency of ginkgo fruits. We designed and constructed an experimental device to investigate the effects of ultrasonic power, pretreatment time, hot air drying temperature, and electrostatic field voltage on the moisture content of the fruits. We used the response surface methodology to identify optimal process conditions and further explored the kinetic model for the moisture content of the fruits under the pretreatment. The results showed that the optimal process parameters for electrostatic-ultrasound pretreatment and the drying of ginkgo fruits were: an electrostatic field voltage of 11.252 kV, an ultrasound power of 590.074 W, a pretreatment time of 32.799 min, and a hot air drying temperature of 85 °C. Under the optimized process conditions, the correlation between the moisture content of ginkgo fruits and the two-term drying kinetics model was the highest. After electrostatic-ultrasound coupling pretreatment, the drying rate of ginkgo fruits was significantly improved during hot air drying.

8.
Front Neurol ; 14: 1115909, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36846147

RESUMO

Background and objective: The natural course and risk factors of moyamoya disease (MMD) associated with unruptured intracranial aneurysms involving stenosed parental arteries are scarcely studied. This study aimed to elucidate the natural course of MMD and its associated risk factors in patients with MMD with unruptured aneurysms. Methods: Between September 2006 and October 2021, patients with MMD with intracranial aneurysms at our center were examined. The natural course, clinical features, radiological features, and follow-up outcomes after revascularization were analyzed. Results: This study included 42 patients with MMD with intracranial aneurysms (42 aneurysms). The age distribution of MMD cases ranged from 6 to 69 years, with four children (9.5%) and 38 adults (90.5%). A total of 17 male and 25 female subjects were included (male-to-female ratio: 1:1.47). The first symptom was cerebral ischemia in 28 cases, and cerebral hemorrhage occurred in 14 cases. There were 35 trunk aneurysms and seven peripheral aneurysms. There were 34 small aneurysms (<5 mm) and eight medium aneurysms (5-15 mm). During the average clinical follow-up period of 37.90 ± 32.53 months, there was no rupture or bleeding from aneurysms. Twenty-seven of these patients underwent a cerebral angiography review, in which it was found that one aneurysm had enlarged, 16 had remained unchanged, and 10 had shrunk or disappeared. A correlation exists between the reduction or disappearance of aneurysms and the progression of the Suzuki stages of MMD (P = 0.015). Nineteen patients underwent EDAS on the aneurysm side, and nine aneurysms disappeared, while eight patients did not undergo EDAS on the aneurysm side and one aneurysm disappeared. Conclusion: The risk of rupture and hemorrhage of unruptured intracranial aneurysms is low when the parent artery already has stenotic lesions, thus, direct intervention may not be necessary for such aneurysms. The progression of the Suzuki stage of moyamoya disease may play a role in the shrinkage or disappearance of the aneurysms, thereby decreasing the risk of rupture and hemorrhage. Encephaloduroarteriosynangiosis (EDAS) surgery may also help promote atrophy or even the disappearance of the aneurysm, thus reducing the risk of further rupture and bleeding.

9.
J Invest Dermatol ; 143(6): 913-924.e4, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36535362

RESUMO

Sebaceous glands play an important role in maintaining the skin barrier function by producing lipids. Dysregulated lipid production in these glands may contribute to the pathogenesis of human skin diseases. Galectin-12, a member of the ß-galactoside‒binding lectin family, is preferentially expressed in adipocytes, where it regulates adipogenesis and functions as an intrinsic negative regulator of lipolysis. It is also expressed by sebocytes and contributes to the proliferation of this cell type. In this study, we show the association between galectin-12 expression and sebocyte differentiation. Galectin-12 knockdown in a human sebocyte cell line reduced lipogenesis and decreased the production of cholesteryl esters, triglycerides, free fatty acids, and cholesterol. Metabolomic analysis of skin surface lipids showed that the levels of the lipids mentioned earlier decreased in sebaceous gland‒specific galectin-12‒knockout mice compared with that in wild-type mice. In addition, galectin-12 positively regulated peroxisome proliferator‒activated receptor-γ transcriptional activity in sebocytes stimulated with fatty acids. Downregulating galectin-12 suppressed the expression of peroxisome proliferator‒activated receptor-γ target genes-acetyl-coenzyme A synthetase 2 gene ACS2 and diacylglycerol O-acyltransferase 1 gene DGAT1-that are required for fatty acid activation and cholesterol and triglyceride biosynthesis. In conclusion, galectin-12 is a positive regulator of sebaceous lipid metabolism with a potential role in the maintenance of skin homeostasis.


Assuntos
Metabolismo dos Lipídeos , Glândulas Sebáceas , Humanos , Animais , Camundongos , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Triglicerídeos/metabolismo , Galectinas/genética , Galectinas/metabolismo
10.
Neural Regen Res ; 18(2): 396-403, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35900436

RESUMO

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.

11.
Front Neurol ; 13: 861187, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35599730

RESUMO

Objective: To explore the long-term progression of neoangiogenesis after indirect revascularization for moyamoya disease (MMD). Methods: We enrolled patients who were diagnosed with MMD and treated by encephaloduroarteriosynangiosis (EDAS) surgery at our center from December 2002 through September 2009. A comparative study between short-term (6-12 months) and long-term (duration ≥ 8 years) follow-up angiographies was performed. The development of collateral circulation through EDAS was graded according to the system described by the Matsushima grade system. Results: A total of 78 patients who received indirect EDAS were enrolled in the study. The mean age at the first operation was 26.9 ± 15.0 years. The Matsushima grades of the same hemisphere were higher at the long-term follow-up compared with the short-term follow-up. Importantly, no attenuation was observed in any hemisphere during the long-term follow-up. In total, 51 hemispheres (32.7%) and 26 hemispheres (16.6%) had progression during the short-term and the long-term follow-up, respectively. The ipsilateral Suzuki stage showed a significant negative correlation with progression pace. Furthermore, higher Suzuki stages were significantly correlated with the postsurgical Matsushima grade at both time points. A total of nine strokes (11.5%) occurred in 78 patients was reported at the long-term follow-up. The annual incidence rate of recurrent strokes was higher for the stage progression group than for the stable group. Conclusion: For patients with MMD, postsurgical neoangiogenesis after indirect bypass continuously improved with time. The short-term progression of the internal carotid artery (ICA) might be attributed to cerebral revascularization, while the long-term progression should be attributed to the natural progression of the disease.

12.
Front Neurol ; 13: 861184, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35557620

RESUMO

Background and Purpose: To explore the genetic basis and molecular mechanism of native arteriogenesis and therapeutic synangiosis in moyamoya disease (MMD). Methods: An angiography-based study using patients from a prospective trial of encephaloduroarteriosynangiosis (EDAS) surgery was performed. The spontaneous collaterals grades were evaluated according to the system described by a new grading system. Blood samples were collected from all the recruited patients before EDAS and during the second hospitalization 3 months post-EDAS. We performed Boolean analysis using a combination of specific cell surface markers of CD34briCD133+CD45dimKDR+. Genotyping of p.R4810K was also performed. The correlation of age, sex, initial symptoms at diagnosis, collateral grade, Suzuki stages, the RNF213 genotype, time to peak (TTP), and endothelial progenitor cell (EPC) count with good collateral circulation was evaluated. Results: Eighty-five patients with MMD were included in this study. The mutation rate of RNF213 p.R4810K in our study was 25.9% (22/85). The heterozygous mutations were occurred significantly more frequently in the cases that were presented with infarction, worse neurological status, severe posterior cerebral artery (PCA) stenosis, and longer TTP delay. Further, the heterozygous mutations occurred significantly more frequently in the poor collateral stage group. Lower grades were significantly correlated with severe ischemia symptoms, worse neurological status, and a longer TTP delay. The post-operative angiographic findings showed that a good Matsushima grade was correlated with heterozygous mutations, a lower collateral stage, and a longer TTP delay. The CD34briCD133+CD45dimKDR+ cell count in patients 3 months post-EDAS was significantly higher as compared to the count before EDAS in the good Matsushima grade group. However, this change was not observed in the poor Matsushima grade group. Conclusions: These data imply that mutations of RNF213 p.R4810K affect the establishment of spontaneous collateral circulation, and EPCs are involved in the process of formation of new EDAS collaterals.

13.
World Neurosurg ; 160: e511-e519, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35077892

RESUMO

BACKGROUND: Moyamoya disease (MMD) often presents as ischemic stroke in pediatric patients and hemorrhage in adults. This situation raises questions as to whether the phenotype of moyamoya disease changes with age. OBJECTIVE: We performed self-precontrol and postcontrol observation monitoring until adulthood on abnormal collateral vessels (ACVs) with the potential risk of bleeding to evaluate the chance of further hemorrhage. METHODS: Fifteen pediatric patients with >10 years angiography-based follow-up were analyzed. The Matsushima grades were divided into 2 groups (good group, representing Matsushima stage A; and mild group, representing Matsushima stages B and C) to investigate the relationship between Matsushima grades and ACVs derived from vessels likely to cause intracranial hemorrhage. RESULTS: Four patients (26.7%) had infarction type and 11 (73.3%) patients had transient ischemic attack type. No patient experienced late-onset cerebral hemorrhagic events. One patient experienced recurrent ischemic stroke 6 months after the second surgery and recovered completely after the third surgery. The angiography-based follow-up was conducted at least 10 years after the encephaloduroarteriosynangiosis (EDAS). The good Matsushima group showed a significant positive correlation with the reduction of the anterior choroidal artery (odds ratio, 56.00; P = 0.003), whereas the posterior communicating artery showed no significant decrease before and after the EDAS procedure (odds ratio, 2.00; P = 1.00). CONCLUSIONS: The EDAS procedure can effectively attenuate the dilation and ACVs of the anterior choroidal artery, which may reduce the incidence of further hemorrhage in adulthood.


Assuntos
Revascularização Cerebral , Ataque Isquêmico Transitório , Doença de Moyamoya , Adolescente , Adulto , Angiografia Cerebral , Revascularização Cerebral/métodos , Criança , Humanos , Ataque Isquêmico Transitório/diagnóstico por imagem , Ataque Isquêmico Transitório/etiologia , Doença de Moyamoya/complicações , Doença de Moyamoya/diagnóstico por imagem , Doença de Moyamoya/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
14.
Glycobiology ; 32(1): 73-82, 2022 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-34791227

RESUMO

Enhanced sebocyte proliferation is associated with the pathogenesis of human skin diseases related to sebaceous gland hyperfunction and androgens, which are known to induce sebocyte proliferation, are key mediators of this process. Galectin-12, a member of the ß-galactoside-binding lectin family that is preferentially expressed by adipocytes and functions as an intrinsic negative regulator of lipolysis, has been shown to be expressed by human sebocytes. In this study, we identified galectin-12 as an important intracellular regulator of sebocyte proliferation. Galectin-12 knockdown in the human SZ95 sebocyte line suppressed cell proliferation, and its overexpression promoted cell cycle progression. Inhibition of galectin-12 expression reduced the androgen-induced SZ95 sebocyte proliferation and growth of sebaceous glands in mice, respectively. The mRNA expression of the key cell cycle regulators cyclin A1 (CCNA1) and cyclin-dependent kinase 2CDK2 was reduced in galectin-12 knockdown SZ95 sebocytes, suggesting a pathway of galectin-12 regulation of sebocyte proliferation. Further, galectin-12 enhanced peroxisome proliferator-activated receptor gamma (PPARγ) expression and transcriptional activity in SZ95 sebocytes, consistent with our previous studies in adipocytes. Rosiglitazone, a PPARγ ligand, induced CCNA1 levels, suggesting that galectin-12 may upregulate CCNA1 expression via PPARγ. Our findings suggest the possibility of targeting galectin-12 to treat human sebaceous gland hyperfunction and androgen-associated skin diseases.


Assuntos
Ciclina A1 , Glândulas Sebáceas , Animais , Ciclo Celular/genética , Proliferação de Células , Ciclina A1/metabolismo , Quinase 2 Dependente de Ciclina , Galectinas/genética , Galectinas/metabolismo , Camundongos , Glândulas Sebáceas/metabolismo
15.
Neural Regen Res ; 17(2): 362-369, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34269211

RESUMO

The rapid formation of a glial/fibrotic scar is one of the main factors hampering axon growth after spinal cord injury. The bidirectional EphB2/ephrin-B2 signaling of the fibroblast-astrocyte contact-dependent interaction is a trigger for glial/fibrotic scar formation. In the present study, a new in vitro model was produced by coculture of fibroblasts and astrocytes wounded by scratching to mimic glial/fibrotic scar-like structures using an improved slide system. After treatment with RNAi to downregulate EphB2, changes in glial/fibrotic scar formation and the growth of VSC4.1 motoneuron axons were examined. Following RNAi treatment, fibroblasts and astrocytes dispersed without forming a glial/fibrotic scar-like structure. Furthermore, the expression levels of neurocan, NG2 and collagen I in the coculture were reduced, and the growth of VSC4.1 motoneuron axons was enhanced. These findings suggest that suppression of EphB2 expression by RNAi attenuates the formation of a glial/fibrotic scar and promotes axon growth. This study was approved by the Laboratory Animal Ethics Committee of Jiangsu Province, China (approval No. 2019-0506-002) on May 6, 2019.

16.
Zhongguo Zhong Yao Za Zhi ; 46(13): 3356-3363, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34396755

RESUMO

With Sangtang Yin granule as model drug,and based on the strategy of " unification of medicines and excipients",the feasibility of preparing high drug loading granules with traditional Chinese medicine( TCM) raw powder as carrier was explored. The powder yield,particle size and particle size distribution,fillibility,flowability,hygroscopicity,reconstituability and other key physical properties relating to preparations of 8 herbs( Dioscoreae Rhizoma,Euryales Semen,Atractylodis Macrocephalae Rhizoma,Coicis semen,Poria,Puerariae Lobatae Radix,Puerariae Thomsonii Radix and Coicis Semen by stir-frying with bran) were studied after being smashed,and the feasibility of taking them as excipients of TCM granules was evaluated by co-spray drying,dry granulation and other preparation techniques. According to the results of the physical properties of raw powders,raw powders of Dioscoreae Rhizoma,Euryales Semen and Puerariae Thomsonii Radix had a high powder yield,uniform particle size distribution,good fillibility,poor hygroscopicity and good reconstitutability,with the feature of assisting granule forming. Compared with the prescription of spray dry powder Sangtang Yin without any excipient,the co-sprayed powder had a high yield,good fillibility and compressibility. The yield of dry granules prepared by co-spraying dry powder was increased by more than 10%,and the particles had a uniform color,good fluidity and dissolubility with the drug-loading rate up to 100%. Based on the physical characteristics of TCM raw powder combined with the analysis of the preparation process,Dioscoreae Rhizoma and Puerariae Thomsonii Radix raw powder were selected as the carriers of granule preparations,and Sangtang Yin granule without any excipient was successfully prepared. The findings provide a feasible idea for the preparation of TCM granules with a high drug loading capacity.


Assuntos
Medicina Tradicional Chinesa , Pueraria , Excipientes , Tamanho da Partícula , Pós , Rizoma
18.
Ultrason Sonochem ; 71: 105371, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33360367

RESUMO

A model for a nonspherical bubble in a compressible liquid under the coupling effect of ultrasound and electrostatic field was developed in this study. The following assumptions are made: (1) the bubble undergoes adiabatic oscillation; (2) the gravity of the liquid is negligible; (3) the bubble is insulating. If the speed of sound approaches infinity (c→∞), the equation set is reduced to the equation set for an incompressible liquid. We found that, under ultrasonic irradiation coupled with electric stress, a nonspherical bubble cannot oscillate steadily in the liquid. The bubble is bound to collapse during several cycles. The presence of electric stress reduces the surface tension at the bubble wall, which produces a larger maximum bubble-radius during the rarefaction cycle and a smaller minimum bubble-radius during the compression cycle. Consequently, during the collapse, both the gas pressure and the temperature in the bubble center increase substantially, if the bubble is exposed to both ultrasound and electrostatic field instead of ultrasound alone. In addition, the cavitation threshold of the bubble within an electrostatic field decreases significantly, compared to the bubble without an electrostatic field. In general, bubble cavitation occurs more easily and violently in the liquid after the introduction of an electrostatic field.

19.
Mitochondrial DNA B Resour ; 5(1): 1048-1049, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33366868

RESUMO

In this study, we determined and analyzed the complete mitochondrial genome of the freshwater fairy shrimp Branchinella kugenumaensis Ishikawa 1894 (Crustacea: Anostraca: Thamnocephalidae). The mitogenome is 15,127 bp in length, consisted of 37 genes that participate in protein production and energy metabolism of mitochondria. The gene order of the B. kugenumaensis mtDNA exhibits major rearrangements compared with the pancrustacean ancestral pattern or other known anostracan mitogenomes, representing a novel mitochondrial genomic organization within the Crustacea. A maximum-likelihood phylogenetic analysis based on concatenated nucleotide sequences of protein-coding genes places B. kugenumaensis next to Streptocephalus sirindhornae, inside the Anostraca clade. Our study will provide new evidence to the less sampled anostracan evolution and take a further step to the completion of the Branchiopoda tree of life.

20.
Med Sci Monit ; 26: e926323, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33206632

RESUMO

BACKGROUND Previous studies have implicated reduced brain-derived neurotrophic factor (BDNF) expression and BDNF-TrkB receptor signaling as well as microglial activation and neuroinflammation in poststroke depression (PSD). However, the contributions of microglial BDNF-TrkB signaling to PSD pathogenesis are unclear. MATERIAL AND METHODS We compared depression-like behaviors as well as neuronal and microglial BDNF and TrkB expression levels in the amygdala, a critical mood-relating limbic structure, in rat models of stroke, depression, and PSD. Depression-like behaviors were assessed using the sucrose preference test, open-field test, and weight measurements, while immunofluorescence double staining was employed to estimate BDNF and TrkB expression by CD11b-positive amygdala microglia and NeuN-positive amygdala neuron. Another group of PSD model rats were examined following daily intracerebroventricular injection of proBDNF, tissue plasminogen activator (t-PA), or normal saline (NS) for 7 days starting 4 weeks after chronic unpredictable mild stress (CUMS). RESULTS The numbers of BDNF/CD11b- and TrkB/CD11b-immunofluorescence-positive cells were lowest in the PSD group at 4 and 8 weeks after CUMS (P0.05). Injection of t-PA increased BDNF/CD11b- and TrkB/CD11b-positive cells in the amygdala of PSD rats and normalized behavior compared with NS or proBDNF injection (P<0.05). In contrast, proBDNF injection reduced BDNF and TrkB expression compared with NS (P<0.05). CONCLUSIONS These results suggest that decreased BDNF and TrkB expression by amygdala microglia may contribute to PSD pathogenesis and depression-like behaviors.


Assuntos
Tonsila do Cerebelo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/etiologia , Depressão/metabolismo , Microglia/metabolismo , Receptor trkB/metabolismo , Acidente Vascular Cerebral/complicações , Animais , Comportamento Animal , Antígeno CD11b/metabolismo , Modelos Animais de Doenças , Injeções Intraventriculares , Atividade Motora , Neuraminidase/metabolismo , Ratos Sprague-Dawley , Ativador de Plasminogênio Tecidual/metabolismo
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