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Daurian ground squirrels (Spermophilus dauricus) experience various stress states during winter hibernation, but the impact on testicular function remains unclear. This study focused on the effects of changes in testicular autophagy, apoptosis, and mitochondrial homeostasis signaling pathways at various stages on the testes of Daurian ground squirrels. Results indicated that: (1) During winter hibernation, there was a significant increase in seminiferous tubule diameter and seminiferous epithelium thickness compared to summer. Spermatogonia number and testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels were higher during inter-bout arousal, suggesting that the testes remained stable during hibernation. (2) An increased number of mitochondria with intact morphology were observed during hibernation, indicating that mitochondrial homeostasis may contribute to testicular stability. (3) DNA fragmentation was evident in the testes during the hibernation and inter-bout arousal stages, with the highest level of caspase3 enzyme activity detected during inter-bout arousal, together with elevated levels of Bax/Bcl-2 and Lc3 II/Lc3 I, indicating an up-regulation of apoptosis and autophagy signaling pathways during hibernation. (4) The abundance of DRP1, MFF, OPA1, and MFN2 proteins was increased, suggesting an up-regulation of mitochondrial dynamics-related pathways. Overall, testicular autophagy, apoptosis, and mitochondrial homeostasis-related signaling pathways were notably active in the extreme winter environment. The well-maintained mitochondrial morphology may favor the production of reproductive hormones and support stable testicular morphology.
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CONTEXT: Coix [Coix lacryma-jobi L. var. mayuen (Roman.) Stapf (Poaceae)], a crop of medicinal and edible significance, contains coixol, which has demonstrated anticancer properties. However, the limited solubility of coixol restricts its potential therapeutic applications. OBJECTIVE: This study prepared a water-soluble coixol-ß-cyclodextrin polymer (CDP) inclusion compound and evaluated its anticancer effect. MATERIALS AND METHODS: The coixol-CDP compound was synthesized through a solvent-stirring and freeze-drying technique. Its coixol content was quantified using HPLC, and its stability was tested under various conditions. The anticancer effects of the coixol-CDP compound (4.129, 8.259, 16.518, and 33.035 mg/L for 24, 48, and 72 h) on the proliferation of non-small cell lung cancer (NSCLC) A549 cells were evaluated using an MTT assay; cell morphology was examined by Hoechst nuclear staining; apoptosis and cell cycle was detected by flow cytometry; and the expression of apoptosis-related proteins was assessed by Western blots. RESULTS: The water-soluble coixol-CDP inclusion compound was successfully prepared with an inclusion ratio of 86.6% and an inclusion yield rate of 84.1%. The coixol content of the compound was 5.63% and the compound remained stable under various conditions. Compared to coixol alone, all 24, 48, and 72 h administrations with the coixol-CDP compound exhibited lower IC50 values (33.93 ± 2.28, 16.80 ± 1.46, and 6.93 ± 0.83 mg/L) in A549 cells; the compound also showed stronger regulatory effects on apoptosis-related proteins. DISCUSSION AND CONCLUSIONS: These findings offer a new perspective for the potential clinical application of Coix in NSCLC therapy and its future research.
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Carcinoma Pulmonar de Células não Pequenas , Coix , Neoplasias Pulmonares , beta-Ciclodextrinas , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Polímeros/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , beta-Ciclodextrinas/farmacologia , ÁguaRESUMO
Long-term weightlessness in animals can cause changes in myocardial structure and function, in which mitochondria play an important role. Here, a tail suspension (TS) Kunming mouse (Mus musculus) model was used to simulate the effects of weightlessness on the heart. We investigated the effects of 2 and 4 weeks of TS (TS2 and TS4) on myocardial mitochondrial ultrastructure and oxidative respiratory function and on the molecular mechanisms of apoptosis and mitochondrial fission, autophagy and fusion-related signalling. Our study revealed significant changes in the ultrastructural features of cardiomyocytes in response to TS. The results showed: (1) mitochondrial swelling and disruption of cristae in TS2, but mitochondrial recovery and denser cristae in TS4; (2) an increase in the total number of mitochondria and number of sub-mitochondria in TS4; (3) no significant changes in the nuclear ultrastructure or DNA fragmentation among the two TS groups and the control group; (4) an increase in the bax/bcl-2 protein levels in the two TS groups, indicating increased activation of the bax-mediated apoptosis pathway; (5) no change in the phosphorylation ratio of dynamin-related protein 1 in the two TS groups; (6) an increase in the protein levels of optic atrophy 1 and mitofusin 2 in the two TS groups; and (7) in comparison to the TS2 group, an increase in the phosphorylation ratio of parkin and the ratio of LC3II to LC3I in TS4, suggesting an increase in autophagy. Taken together, these findings suggest that mitochondrial autophagy and fusion levels increased after 4 weeks of TS, leading to a restoration of the bax-mediated myocardial apoptosis pathway observed after 2 weeks of TS. NEW FINDINGS: What is the central question of this study? What are the effects of 2 and 4 weeks of tail suspension on myocardial mitochondrial ultrastructure and oxidative respiratory function and on the molecular mechanisms of apoptosis and mitochondrial fission, autophagy and fusion-related signalling? What is the main finding and its importance? Increased mitochondrial autophagy and fusion levels after 4 weeks of tail suspension help to reshape the morphology and increase the number of myocardial mitochondria.
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Elevação dos Membros Posteriores , Mitocôndrias Cardíacas , Camundongos , Animais , Mitocôndrias Cardíacas/metabolismo , Dinâmica Mitocondrial/genética , Proteína X Associada a bcl-2/metabolismo , Apoptose/fisiologia , Autofagia , Miócitos Cardíacos/metabolismoRESUMO
BACKGROUND: This study aims to investigate the association of lipid ratios with intracranial atherosclerotic stenosis (ICAS) in a Chinese population. METHODS: This cross-sectional study included 658 consecutive patients with ischemic stroke. Intracranial and extracranial arteries were evaluated for atherosclerotic stenosis using digital subtraction angiography or computed tomography angiography. Lipid ratios [total cholesterol (TC)/high-density lipoprotein-cholesterol (HDL-C), triglycerides (TG)/HDL-C, low-density lipoprotein-cholesterol (LDL-C)/HDL-C, non-high-density lipoprotein-cholesterol (non-HDL-C)/HDL-C, remnant cholesterol (RC)/HDL-C, apolipoprotein B (apo B)/apolipoprotein A-I (apo A-I), and apo B/HDL-C] were calculated. RESULTS: The TC/HDL-C, LDL-C/HDL-C, RC/HDL-C, non-HDL-C/HDL-C, apo B/HDL-C and apo B/apo A-I ratios (all P < 0.05) were significantly associated with ICAS but not with extracranial atherosclerotic stenosis after adjustment for confounding factors. Receiver operating characteristic (ROC) curves analysis revealed that the apo B/apo A-I ratio had the largest area under the ROC curve (AUC) among lipid levels alone and for lipid ratios (AUC = 0.588). Lipid ratios had higher AUC values than those for lipid levels alone for the identification of ICAS. CONCLUSION: The TC/HDL-C, LDL-C/HDL-C, RC/HDL-C, non-HDL-C/HDL-C apo B/HDL-C, and apo B/apo A-I ratios were significantly related to ICAS risk. Compared with the other variables tested, the apo B/apo A-I ratio appeared to be a better discriminator for identifying ICAS risk in stroke patients.
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Arteriosclerose Intracraniana/sangue , AVC Isquêmico/complicações , Lipídeos/sangue , Idoso , Apolipoproteína A-I/sangue , Apolipoproteína B-100/sangue , Povo Asiático , Biomarcadores/sangue , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Constrição Patológica , Estudos Transversais , Feminino , Humanos , Arteriosclerose Intracraniana/etiologia , AVC Isquêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Curva ROCRESUMO
BACKGROUND: In spontaneous intracerebral hemorrhage (ICH), black hole sign has been proposed as a promising imaging marker that predicts hematoma expansion in patients with ICH. The aim of our study was to investigate whether admission CT black hole sign predicts hematoma growth in patients with ICH. METHODS: From July 2011 till February 2016, patients with spontaneous ICH who underwent baseline CT scan within 6 h of symptoms onset and follow-up CT scan were recruited into the study. The presence of black hole sign on admission non-enhanced CT was independently assessed by 2 readers. The functional outcome was assessed using the modified Rankin Scale (mRS) at 90 days. Univariate and multivariable logistic regression analyses were performed to assess the association between the presence of the black hole sign and functional outcome. RESULTS: A total of 225 patients (67.6% male, mean age 60.3 years) were included in our study. Black hole sign was identified in 32 of 225 (14.2%) patients on admission CT scan. The multivariate logistic regression analysis demonstrated that age, intraventricular hemorrhage, baseline ICH volume, admission Glasgow Coma Scale score, and presence of black hole sign on baseline CT independently predict poor functional outcome at 90 days. There are significantly more patients with a poor functional outcome (defined as mRS ≥4) among patients with black hole sign than those without (84.4 vs. 32.1%, p < 0.001; OR 8.19, p = 0.001). CONCLUSIONS: The CT black hole sign independently predicts poor outcome in patients with ICH. Early identification of black hole sign is useful in prognostic stratification and may serve as a potential therapeutic target for anti-expansion clinical trials.
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Hemorragia Cerebral/diagnóstico por imagem , Hematoma/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Idoso , Hemorragia Cerebral/epidemiologia , Hemorragia Cerebral/fisiopatologia , China/epidemiologia , Avaliação da Deficiência , Progressão da Doença , Diagnóstico Precoce , Feminino , Hematoma/epidemiologia , Hematoma/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Prognóstico , Estudos Prospectivos , Fatores de Risco , Fatores de TempoRESUMO
BACKGROUND Early hematoma growth is associated with poor outcome in patients with spontaneous intracerebral hemorrhage (ICH). The swirl sign (SS) and the black hole sign (BHS) are imaging markers in ICH patients. The aim of this study was to compare the predictive value of these 2 signs for early hematoma growth. MATERIAL AND METHODS ICH patients were screened for the appearance of the 2 signs within 6 h after onset of symptoms. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the 2 signs in predicting early hematoma growth were assessed. The accuracy of the 2 signs in predicting early hematoma growth was analyzed by receiver-operator analysis. RESULTS A total of 200 patients were enrolled in this study. BHS was found in 30 (15%) patients, and SS was found in 70 (35%) patients. Of the 71 patients with early hematoma growth, BHS was found on initial computed tomography scans in 24 (33.8%) and SS in 33 (46.5%). The sensitivity, specificity, PPV, and NPV of BHS for predicting early hematoma growth were 33.8%, 95.3%, 80.0%, and 72.0%, respectively. The sensitivity, specificity, PPV, and NPV of SS were 46.5%, 71.3%, 47.0%, and 71.0%, respectively. The area under the curve was 0.646 for BHS and 0.589 for SS (P=0.08). Multivariate logistic regression showed that presence of BHS is an independent predictor of early hematoma growth. CONCLUSIONS The Black hole sign seems to be good predictor for hematoma growth. The presence of swirl sign on admission CT does not independently predict hematoma growth in patients with ICH.
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Hemorragia Cerebral/complicações , Hemorragia Cerebral/diagnóstico por imagem , Hematoma/complicações , Hematoma/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Curva ROCRESUMO
BACKGROUND: Midline shift (MLS) has been associated with unfavorable outcome in patients with intracerebral hemorrhage (ICH). However, the optimal criteria to define the MLS measurements that indicate future outcome in ICH patients are absent, and the quantitative threshold of MLS that differentiates favorable and poor clinical outcome should be further explored. METHODS: We enrolled patients with ICH who underwent admission computed tomography (CT) within 6 h after onset of symptoms. We assessed MLS at several locations, including the pineal gland, septum pellucidum, and cerebral falx. MLS(max) was defined as the maximum midline shift among these locations. Functional outcomes were assessed with the Modified Rankin Scale (mRS) at 3 months. We performed multivariate logistic regression analysis to investigate the MLS locations for predicting poor outcome. ROC curve analysis was used to establish whether MLS values were predictive of 90-day poor outcome. RESULTS: In 199 patients with ICH, 78 (39.2%) patients had poor functional outcome at 3-month follow-up. Pineal gland shift, septum pellucidum shift, cerebral falx shift, and MLS(max) all showed a significant difference between poor outcome and favorable outcome (p < 0.001). After adjustment for age, baseline Glasgow Coma Scale score, ICH location, time to initial CT, baseline ICH volume, and intraventricular hemorrhage, the MLS(max) was independently associated with poor outcome (p = 0.032). MLS(max) > 4 mm (our proposed optimal threshold) was more likely to have poorer outcomes than those without (p < 0.001). CONCLUSIONS: MLS(max) can be a good independent predictor of clinical outcome, and MLS(max) > 4 mm is an optimal threshold associated with poor outcome in patients with ICH.
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Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/patologia , Avaliação de Resultados em Cuidados de Saúde/métodos , Índice de Gravidade de Doença , Adulto , Idoso , Hemorragia Cerebral/terapia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND AND PURPOSE: The aim of the study was to investigate the usefulness of the computed tomography (CT) island sign for predicting early hematoma growth and poor functional outcome. METHODS: We included patients with spontaneous intracerebral hemorrhage (ICH) who had undergone baseline CT within 6 hours after ICH symptom onset in our hospital between July 2011 and September 2016. Two readers independently assessed the presence of the island sign on the admission noncontrast CT scan. Multivariable logistic regression analysis was used to analyze the association between the presence of the island sign on noncontrast admission CT and early hematoma growth and functional outcome. RESULTS: A total of 252 patients who met the inclusion criteria were analyzed. Among them, 41 (16.3%) patients had the island sign on baseline noncontrast CT scans. In addition, the island sign was observed in 38 of 85 patients (44.7%) with hematoma growth. Multivariate logistic regression analysis demonstrated that the time to baseline CT scan, initial hematoma volume, and the presence of the island sign on baseline CT scan independently predicted early hematoma growth. The sensitivity of the island sign for predicting hematoma expansion was 44.7%, specificity 98.2%, positive predictive value 92.7%, and negative predictive value 77.7%. After adjusting for the patients' age, baseline Glasgow Coma Scale score, presence of intraventricular hemorrhage, presence of subarachnoid hemorrhage, admission systolic blood pressure, baseline ICH volume, and infratentorial location, the presence of the island sign (odds ratio, 3.51; 95% confidence interval, 1.26-9.81; P=0.017) remained an independent predictor of poor outcome in patients with ICH. CONCLUSIONS: The island sign is a reliable CT imaging marker that independently predicts hematoma expansion and poor outcome in patients with ICH. The noncontrast CT island sign may serve as a potential marker for therapeutic intervention.
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Pressão Sanguínea , Hematoma Subdural Intracraniano , Tomografia Computadorizada por Raios X , Idoso , Biomarcadores , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/mortalidade , Hemorragia Cerebral/fisiopatologia , Feminino , Seguimentos , Hematoma Subdural Intracraniano/diagnóstico por imagem , Hematoma Subdural Intracraniano/mortalidade , Hematoma Subdural Intracraniano/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos ProspectivosRESUMO
BACKGROUND AND PURPOSE: Early hematoma growth is a devastating neurological complication after intracerebral hemorrhage. We aim to report and evaluate the usefulness of computed tomography (CT) black hole sign in predicting hematoma growth in patients with intracerebral hemorrhage. METHODS: Patients with intracerebral hemorrhage were screened for the presence of CT black hole sign on admission head CT performed within 6 hours after onset of symptoms. The black hole sign was defined as hypoattenuatting area encapsulated within the hyperattenuating hematoma with a clearly defined border. The sensitivity, specificity, and positive and negative predictive values of CT black hole sign in predicting hematoma expansion were calculated. Logistic regression analyses were used to assess the presence of the black hole sign and early hematoma growth. RESULTS: A total of 206 patients were enrolled. Black hole sign was found in 30 (14.6%) of 206 patients on the baseline CT scan. The black hole sign was more common in patients with hematoma growth (31.9%) than those without hematoma growth (5.8%; P<0.001). The sensitivity, specificity, positive predictive value, and negative predictive value of back hole sign in predicting early hematoma growth were 31.9%, 94.1%, 73.3%, and 73.2%, respectively. The time-to-admission CT scan, baseline hematoma volume, and the presence of black hole sign on admission CT independently predict hematoma growth in multivariate model. CONCLUSIONS: The CT black hole sign could be used as a simple and easy-to-use predictor for early hematoma growth in patients with intracerebral hemorrhage.
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Hemorragia Cerebral/diagnóstico por imagem , Hematoma/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Neuroimagem , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To explore the correlation between the recurrence of cerebral infarction and aspirin resistance (AR)/Chinese medical (CM) constitutions. METHODS: Totally 413 cerebral infarction patients took Aspirin Enteric-coated Tablet (100 mg per day) while receiving routine therapy, 5 days at least in a week. They were followed-up for 12 months. Aspirin sensitivity (AS) was determined using turbidimetry. CM constitutions among patients with different AS were compared. Ratios of AR patients and AS patients of different CM constitutions in cerebral infarction recurrent patients were compared. Platelet membrane glycoproteins (GP) II b HPA-3 gene polymorphism was detected by polymerase chain reaction (PCR) method. Correlation between recurrence of cerebral infarction and AR, bb genotypes, CM constitutions times AS were analyzed by Logistic regression. RESULTS: Totally 11 patients dropped out, 101 (25.12%)with recurrent cerebral infarction and 301 (74.88%) without recurrent cerebral infarction. There were 152 (37.81%) AR patients and 250 (62.19%) AS patients. AR accounted for 26.6% (80/ 301) and AS accounted for 73.4% (221/301) in non-recurrent cerebral infarction patients. AR accounted for 71.3% (72/101) and AS accounted for 28.7% (29/101) in recurrent cerebral infarction patients. There was statistical difference in AR and AS ratios (χ2 = 64.287, P = 0.000). The proportion of yin deficiency constitution (YDC) was the largest [28.3% (43/152)] in AR patients. The proportion of blood stasis constitution (BSC) was the largest [23.6% (59/250)] in AS patients. There was statistical difference in CM constitutions between AR patients and AS patients (χ2 = 21.574, P < 0.01). The former 4 recurrent rates occurred in AR patients of YDC, BSC, damp-phlegm constitution (DPC), qi deficiency constitution (QDC). YDC occupied the first place [22.4% (34/152)]. The former 4 recurrent rates occurred in AS patients of BSC, QDC, DPC, damp-heat constitution (DHC). BSC occupied the first place [3.2% (2/250)]. Compared with non-recurrent cerebral infarction patients and AS patients, bb gene occurred most often, but aa gene and ab gene occurred obviously lesser in non-recurrent cerebral infarction patients and AR patients (χ2 = 20.171, χ2 = 55.139, P < 0.01). AR and bb gene were positively correlated with recurrent cerebral infarction (OR = 18.423, P = 0.000; OR = 1.304, P = 0.028). Body constitutions interacted with AS (OR = 0.707, P = 0.000). CONCLUSIONS: Recurrent cerebral infarction was closely related to AR and constitutional types. The recurrence rate was higher in AR patients of YDC. GP I b HPA-3 bb genotype might be a risk factor for AR and recurrent cerebral infarction.
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Aspirina/uso terapêutico , Infarto Cerebral , Resistência a Medicamentos , Medicina Tradicional Chinesa , Constituição Corporal , Humanos , Neoplasias , Recidiva , Deficiência da Energia YinRESUMO
Essential tremor (ET) and Parkinson's disease (PD) are common chronic movement disorders that can cause a substantial degree of disability. However, the etiology underlying these two conditions remains poorly understood. In the present study, Whole-exome sequencing of peripheral blood samples from the proband and Sanger sequencing of the other 18 family members, and pedigree analysis of four generations of 29 individuals with both ET and PD in a nonconsanguineous Chinese family were performed. Specifically, family members who had available medical information, including historical documentation and physical examination records, were included. A novel c.1909A>T (p.Ser637Cys) missense mutation was identified in the eukaryotic translation initiation factor 4γ1 (EIF4G1) gene as the candidate likely responsible for both conditions. In total, 9 family members exhibited tremor of the bilateral upper limbs and/or head starting from ages of ≥40 years, 3 of whom began showing evidence of PD in their 70s. Eukaryotic initiation factor 4 (eIF4)G1, a component of the translation initiation complex eIF4F, serves as a scaffold protein that interacts with many initiation factors and then binds to the 40S ribosomal subunit. The EIF4G1 (p.Ser637Cys) might inhibit the recruitment of the mRNA to the ribosome. In conclusion, the results from the present study suggested that EIF4G1 may be responsible for the hereditary PD with 'antecedent ET' reported in the family assessed.
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Hereditary spastic paraplegia (HSP) comprises a group of hereditary and neurodegenerative diseases that are characterized by axonal degeneration or demyelination of bilateral corticospinal tracts in the spinal cord; affected patients exhibit progressive spasticity and weakness in the lower limbs. The most common manifestation of HSP is spastic paraplegia type 4 (SPG4), which is caused by mutations in the spastin (SPAST) gene. The present study reports the clinical characteristics of affected individuals and sequencing analysis of a mutation that caused SPG4 in a family. All affected family members exhibited spasticity and weakness of the lower limbs and, notably, only male members of the family were affected. Wholeexome sequencing revealed that all affected individuals had a novel c.1785C>A (p. Ser595Arg) missense mutation in SPAST. Bioinformatics analysis revealed changes in both secondary and tertiary structures of the mutated protein. The novel missense mutation in SPAST supported the diagnosis of SPG4 in this family and expands the spectrum of pathogenic mutations that cause SPG4. Analysis of SPAST sequences revealed that most pathogenic mutations occurred in the AAA domain of the protein, which may have a close relationship with SPG4 pathogenesis.
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Paraplegia Espástica Hereditária , Humanos , Masculino , Paraplegia Espástica Hereditária/genética , Paraplegia Espástica Hereditária/diagnóstico , Paraplegia Espástica Hereditária/patologia , Mutação de Sentido Incorreto , Espastina/genética , MutaçãoRESUMO
BACKGROUND: Spinocerebellar ataxia recessive type 7 (SCAR7) is a rare clinical manifestation beginning in childhood or adolescence. SCAR7 is caused by tripeptidyl peptidase 1 (TPP1) gene mutations, and presents with cerebellar ataxia, pyramidal signs, neurocognitive impairment, deep paresthesia, and cerebellar atrophy. CASE SUMMARY: Here, we describe a 25-year-old female patient in China who presented with increasing difficulty walking, falling easily, shaking limbs, instability holding items, slurred speech, coughing when drinking, palpitations, and frequent hunger and overeating. Magnetic resonance imaging showed cerebellar atrophy. Whole exome sequencing detected two compound heterozygous mutations in the TPP1 gene: c.1468G>A p.Glu490Lys and c.1417G>A p.Gly473Arg. Considering the patient's clinical presentation and genetic test results, we hypothesized that complex heterozygous mutations cause TPP1 enzyme deficiency, which may lead to SCAR7. CONCLUSION: We report the first case of SCAR7 from China. We also identify novel compound heterozygous mutations in the TPP1 gene associated with SCAR7, expanding the range of known disease-causing mutations for SCAR7.
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BACKGROUND: Adenylosuccinate lyase (ADSL) deficiency is a rare autosomal-recessive defect of purine metabolism caused by mutation of the ADSL gene. It can cause severe neurological impairment and diverse clinical manifestations, including epilepsy. CASE SUMMARY: Here, we describe a 3-year-old Chinese boy who had both psychomotor retardation and refractory epilepsy. Magnetic resonance imaging showed myelin hypoplasia. Electroencephalography findings supported a diagnosis of epilepsy. Whole-exon sequencing revealed the presence of a novel complex heterozygous mutation in the ADSL gene: The splicing mutation c.154-3C>G and the missense mutation c.71C>T (p. Pro24Leu). Considering the patient's clinical presentation and genetic test results, the complex heterozygous mutation was predicted to prevent both ADSL alleles from producing normal ADSL, which may have led to ADSL deficiency. Finally, the child was diagnosed with ADSL deficiency. CONCLUSION: We identified a novel complex heterozygous mutation in the ADSL gene associated with ADSL deficiency, thus expanding the known spectrum of pathogenic mutations that cause ADSL deficiency. Additionally, we describe epilepsy that occurs in patients with ADSL deficiency.
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ABSTRACT Objectives: The effects of weightlessness on the liver were studied using a tail suspension (TS) male mouse model. Methods: The effects of 0-, 2- and 4-week TS (CON, TS2 and TS4 groups) on glycogen and lipid content, as well as on the molecular processes of the synthesis and degradation pathways, were examined. Results: (1) The number of glycogenosomes under ultrastructure and the glycogen content were considerably larger in the TS4 group than in the other two groups. (2) In the TS4 group, glycogen synthase activity remained constant while glycogen phosphorylase activity dropped, indicating that glycogen breakdown was reduced. (3) The livers of the TS2 group had the highest lipid and triglyceride content, indicating lipid buildup in the liver at this time. (4) In the TS2 group, the activities of the fatty acid synthesis-related factors acetyl-CoA carboxylase and fatty acid synthase increased, while hepatic lipase decreased, indicating that lipid synthesis increased, while decomposition decreased. (5) In the TS2 group, the protein expression of glucose transporters 1 and 2 increased. Conclusions: From TS2 weeks to TS4 weeks, the main energy consumption mode in the livers of mice transitioned from glucose metabolism to lipid metabolism as glucose use decreased. Level of evidence II; Comparative prospective study.
RESUMEN Objetivos: Se estudiaron los efectos de la antigravedad en el hígado utilizando un modelo de ratón macho en prueba de suspensión de la cola (TS, tail suspension). Métodos: Se examinaron los efectos de la TS a las 0, 2 y 4 semanas (grupos CON, TS2 y TS4) sobre el contenido de glucógeno y lípidos, así como sobre los procesos moleculares de las vías de síntesis y degradación. Resultados: (1) El número de glucogenosomas ultraestructurales y el contenido de glucógeno fueron expresivamente más altos en el grupo TS4 que en los otros dos grupos. (2) En el grupo TS4, la actividad de la glucógeno sintasa se mantuvo constante, mientras que la actividad de la glucógeno fosforilasa disminuyó, lo que indica que la degradación del glucógeno se redujo. (3) Los hígados del grupo TS2 presentaron el mayor contenido de lípidos y triglicéridos, lo que indica la acumulación de lípidos en el hígado en ese momento. (4) En el grupo TS2, la actividad de los factores relacionados con la síntesis de ácidos grasos acetil-CoA carboxilasa y ácido graso sintasa aumentó, mientras que la lipasa hepática disminuyó, indicando que la síntesis de lípidos aumentó mientras que la descomposición disminuyó. (5) En el grupo TS2, la expresión proteica de los transportadores de glucosa 1 y 2 aumentó. Conclusiones: Desde la semana TS2 hasta la semana TS4, el principal modo de consumo de energía en el hígado de los ratones pasó del metabolismo de la glucosa al metabolismo de los lípidos a medida que disminuía el uso de la glucosa. Nivel de Evidencia II, Estudio retrospectivo comparativo.
RESUMO Objetivos: Os efeitos da antigravidade no fígado foram estudados usando um modelo de camundongo macho com a suspensão pela cauda (TS, tail suspension). Métodos: Foram examinados os efeitos da TS em 0, 2 e 4 semanas (grupos CON, TS2 e TS4) sobre o conteúdo de glicogênio e lipídios, bem como nos processos moleculares das vias de síntese e degradação. Resultados: (1) O número de glicogenossomos ultraestruturais e o teor de glicogênio foram expressivamente maiores no grupo TS4 do que nos outros dois grupos. (2) No grupo TS4, a atividade de glicogênio sintase permaneceu constante, enquanto a atividade de glicogênio fosforilase caiu, indicando que a degradação do glicogênio foi reduzida. (3) Os fígados do grupo TS2 tiveram o maior teor lipídico e de triglicérides, indicando acúmulo de lipídios no fígado no momento. (4) No grupo TS2, a atividade dos fatores relacionados com a síntese de ácidos graxos acetil-CoA carboxilase e ácido graxo sintase aumentaram, enquanto a lipase hepática diminuiu, indicando que a síntese de lipídios aumentou, enquanto a decomposição diminuiu. (5) No grupo TS2, a expressão proteica dos transportadores de glicose 1 e 2 aumentou. Conclusões: De TS2 semanas para TS4 semanas, o principal modo de consumo de energia no fígado de camundongos passou do metabolismo da glicose para o metabolismo lipídico, à medida que o uso de glicose diminuiu. Nível de evidência II, Estudo retrospectivo comparativo.
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To improve the aroma profile of Ecolly dry white wine, the simultaneous and sequential inoculations of selected Rhodotorula mucilaginosa and Saccharomyces cerevisiae were performed in wine making of this work. The two yeasts were mixed in various ratios for making the mixed inoculum. The amount of volatiles and aroma characteristics were determined the following year. Mixed fermentation improved both the varietal and fermentative aroma compound composition, especially that of (Z)-3-hexene-1-ol, nerol oxide, certain acetates and ethyls group compounds. Citrus, sweet fruit, acid fruit, berry, and floral aroma traits were enhanced by mixed fermentation; however, an animal note was introduced upon using higher amounts of R. mucilaginosa. Aroma traits were regressed with volatiles as observed by the partial least-square regression method. Analysis of correlation coefficients revealed that the aroma traits were the multiple interactions of volatile compounds, with the fermentative volatiles having more impact on aroma than varietal compounds.
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Frutas/química , Rhodotorula/química , Saccharomyces cerevisiae/química , Vinho/análise , Fermentação , OdorantesRESUMO
BACKGROUND: The novel water-soluble inclusion complex of Brucea javanica oil (BJO) by ß-cyclodextrin polymers (CDP) was prepared by saturated aqueous method and characterized by SEM, FT-IR and 1H NMR. Compared with BJO, the aqueous solubility of BJO-CDP (77.76%) greatly enhanced due to the water-soluble CDP host. RESULTS: In the acute toxicity test, the value of LD50 of BJO-CDP was 11.94 g/kg, suggesting the lower toxicity of BJO-CDP. Moreover, the pharmacodynamics of BJO-CDP was investigated by evaluating its inhibition effects on human hepatoma SMMC-7721 cells and mice transplantable colon cancer CT- 26 cells. CONCLUSION: It has been revealed that BJO-CDP significantly decreased the toxicity of BJO and enhanced its anti-tumor activity. In conclusion, BJO-CDP could be a new and improved clinical formulation of BJO with higher water solubility, lower toxicity and enhanced anti-tumor activity.
Assuntos
Apoptose/efeitos dos fármacos , Brucea/química , Óleos de Plantas , beta-Ciclodextrinas/química , Animais , Linhagem Celular Tumoral , Humanos , Dose Letal Mediana , Camundongos , Camundongos Endogâmicos ICR , Óleos de Plantas/isolamento & purificação , Óleos de Plantas/farmacologia , Óleos de Plantas/toxicidade , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Testes de Toxicidade AgudaRESUMO
INTRODUCTION: Blend sign has been recently described as a novel imaging marker that predicts hematoma expansion. The purpose of our study was to investigate the prognostic value of CT blend sign in patients with ICH. OBJECTIVES AND METHODS: Patients with intracerebral hemorrhage who underwent baseline CT scan within 6 hours were included. The presence of blend sign on admission nonenhanced CT was independently assessed by two readers. The functional outcome was assessed by using the modified Rankin Scale (mRS) at 90 days. RESULTS: Blend sign was identified in 40 of 238 (16.8%) patients on admission CT scan. The proportion of patients with a poor functional outcome was significantly higher in patients with blend sign than those without blend sign (75.0% versus 47.5%, P = 0.001). The multivariate logistic regression analysis demonstrated that age, intraventricular hemorrhage, admission GCS score, baseline hematoma volume and presence of blend sign on baseline CT independently predict poor functional outcome at 90 days. The CT blend sign independently predicts poor outcome in patients with ICH (odds ratio 3.61, 95% confidence interval [1.47-8.89];p = 0.005). CONCLUSIONS: Early identification of blend sign is useful in prognostic stratification and may serve as a potential therapeutic target for prospective interventional studies.
Assuntos
Hemorragia Cerebral/diagnóstico por imagem , Idoso , Hemorragia Cerebral/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Tomografia Computadorizada por Raios XRESUMO
The aim of the present study was to investigate the changes in the levels of serotonin (5-HT), dopamine (DA), norepinephrine (NE) and fibroblast growth factor-2 (FGF-2) in the brains of rats with post-stroke depression (PSD). A rat model of stroke was established by middle cerebral artery occlusion and the rats were randomly divided into two groups: Control and modification groups. The rats in the modification group had PSD, while the rats in the control group had experienced a stroke only. The PSD model was established by applying chronic mild stress to the individually housed rats. High-performance liquid chromatography was used to detect the levels of 5-HT, DA and NE, while western blotting was used to detect the FGF-2 protein expression levels in the frontal lobe and hippocampus. Quantitative polymerase chain reaction was also used to determine the mRNA expression levels of FGF-2 in the frontal lobes of the two groups. The levels of 5-HT, DA and NE in the frontal lobe and hippocampus of the rats in the PSD group were significantly lower than the levels observed in the rats in the stroke group (P<0.01). In addition, protein expression levels of FGF-2 in the frontal lobe of the rats in the PSD group were significantly lower when compared with the control group rats (P<0.01), however, the protein expression levels of FGF-2 in the hippocampus did not exhibit a statistically significant difference (P>0.05). The mRNA expression levels of FGF-2 in the frontal lobe of the rats in the modification group were significantly lower than the levels in the control group rats (P<0.01). Therefore, reduced levels of monoamine neurotransmitters and FGF-2 expression in the brains of rats with PSD are associated with the incidence of PSD.