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1.
Nat Commun ; 13(1): 5540, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36130959

RESUMO

Threat and extinction memories are crucial for organisms' survival in changing environments. These memories are believed to be encoded by separate ensembles of neurons in the brain, but their whereabouts remain elusive. Using an auditory fear-conditioning and extinction paradigm in male mice, here we discovered that two distinct projection neuron subpopulations in physical proximity within the insular cortex (IC), targeting the central amygdala (CeA) and nucleus accumbens (NAc), respectively, to encode fear and extinction memories. Reciprocal intracortical inhibition of these two IC subpopulations gates the emergence of either fear or extinction memory. Using rabies-virus-assisted tracing, we found IC-NAc projection neurons to be preferentially innervated by intercortical inputs from the orbitofrontal cortex (OFC), specifically enhancing extinction to override fear memory. These results demonstrate that IC serves as an operation node harboring distinct projection neurons that decipher fear or extinction memory under the top-down executive control from OFC.


Assuntos
Extinção Psicológica , Medo , Animais , Extinção Psicológica/fisiologia , Medo/fisiologia , Masculino , Camundongos , Neurônios/fisiologia , Núcleo Accumbens/fisiologia , Córtex Pré-Frontal/fisiologia
2.
Acta Pharmacol Sin ; 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36100766

RESUMO

Establishing a stoke experimental model, which is better in line with the physiology and function of human brain, is the bottleneck for the development of effective anti-stroke drugs. A three-dimensional cerebral organoids (COs) from human pluripotent stem cells can mimic cell composition, cortical structure, brain neural connectivity and epigenetic genomics of in-vivo human brain, which provides a promising application in establishing humanized ischemic stroke model. COs have been used for modeling low oxygen condition-induced hypoxic injury, but there is no report on the changes of COs in response to in vitro oxygen-glucose deprivation (OGD)-induced damage of ischemic stroke as well as its application in testing anti-stroke drugs. In this study we compared the cell composition of COs at different culture time and explored the cell types, cell ratios and volume size of COs at 85 days (85 d-CO). The 85 d-CO with diameter more than 2 mm was chosen for establishing humanized ischemic stroke model of OGD. By determining the time-injury relationship of the model, we observed aggravated ischemic injury of COs with OGD exposure time, obtaining first-hand evidence for the damage degree of COs under different OGD condition. The sensitivity of the model to ischemic injury and related treatment was validated by the proven pan-Caspase inhibitor Z-VAD-FMK (20 µM) and Bcl-2 inhibitor navitoclax (0.5 µM). Neuroprotective agents edaravone, butylphthalide, P7C3-A20 and ZL006 (10 µM for each) exerted similar beneficial effects in this model. Taken together, this study establishes a humanized ischemic stroke model based on COs, and provides evidence as a new research platform for anti-stroke drug development.

3.
Nutr J ; 21(1): 56, 2022 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-36114539

RESUMO

BACKGROUND: Nutritional risk is prevalent in various diseases, but its association with contrast-induced acute kidney injury (CI-AKI) remains unclear. This study aimed to explore this association in patients undergoing coronary angiography (CAG). METHODS: In this retrospective cross-sectional study, 4386 patients undergoing CAG were enrolled. Nutritional risks were estimated by nutritional risk screening 2002 (NRS-2002), controlling nutritional status (CONUT), prognostic nutritional index (PNI), and geriatric nutritional risk index (GNRI), respectively. CI-AKI was determined by the elevation of serum creatinine (Scr). Multivariable logistic regression analyses and receiver operator characteristic (ROC) analyses were conducted. Subgroup analyses were performed according to age (< 70/≥70 years), gender (male/female), percutaneous coronary intervention (with/without), and estimated glomerular filtration rate (< 60/≥60 ml/min/1.73m2). RESULTS: Overall, 787 (17.9%) patients were diagnosed with CI-AKI. The median score of NRS-2002, CONUT, PNI, and GNRI was 1.0, 3.0, 45.8, and 98.6, respectively. Nutritional risk was proven to be associated with CI-AKI when four different nutritional tools were employed, including NRS-2002 ([3-7 vs. 0]: odds ratio [95% confidence interval], OR [95%CI] = 4.026 [2.732 to 5.932], P < 0.001), CONUT ([6-12 vs. 0-1]: OR [95%CI] = 2.230 [1.586 to 3.136], P < 0.001), PNI ([< 38 vs. ≥52]: OR [95%CI] = 2.349 [1.529 to 3.610], P < 0.001), and GNRI ([< 90 vs. ≥104]: OR [95%CI] = 1.822 [1.229 to 2.702], P = 0.003). This is consistent when subgroup analyses were performed. Furthermore, nutritional scores were proved to be accurate in predicting CI-AKI (area under ROC curve: NRS-2002, 0.625; CONUT, 0.609; PNI, 0.629; and GNRI, 0.603). CONCLUSIONS: Nutritional risks (high scores of NRS-2002 and CONUT; low scores of PNI and GNRI) were associated with CI-AKI in patients undergoing CAG.


Assuntos
Injúria Renal Aguda , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Idoso , Angiografia Coronária/efeitos adversos , Creatinina , Estudos Transversais , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco
4.
World J Clin Cases ; 10(20): 7105-7115, 2022 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-36051147

RESUMO

BACKGROUND: Lynch syndrome (LS) is an autosomal dominant hereditary disorder because of germline mutations in DNA mismatch repair genes, such as MutL homolog 1 (MLH1), PMS1 homolog 2, MutS homolog 2, and MutS homolog 6. Gene mutations could make individuals and their families more susceptible to experiencing various malignant tumors. In Chinese, MLH1 germline mutation c.(453+1_454-1)_(545+1_546-1)del-related LS has been infrequently reported. Therefore, we report a rare LS patient with colorectal and endometrioid adenocarcinoma and describe her pedigree characteristics. CASE SUMMARY: A 57-year-old female patient complained of irregular postmenopausal vaginal bleeding for 6 mo. She was diagnosed with LS, colonic malignancy, endometrioid adenocarcinoma, secondary fallopian tube malignancy, and intermyometrial leiomyomas. Then, she was treated by abdominal hysterectomy, bilateral oviduct oophorectomy, and sentinel lymph node resection. Genetic testing was performed using next-generation sequencing technology to detect the causative genetic mutations. Moreover, all her family members were offered a free genetic test, but no one accepted it. CONCLUSION: No tumor relapse or metastasis was found in the patient during the 30-mo follow-up period. The genetic panel sequencing showed a novel pathogenic germline mutation in MLH1, c.(453+1_454-1)_(545+1_546-1)del, for LS. Moreover, cancer genetic counseling and testing are still in the initial development state in China, and maybe face numerous challenges in the further.

5.
Front Genet ; 13: 868540, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36092936

RESUMO

The olive complex, comprising six subspecies, is a valuable plant for global trade, human health, and food safety. However, only one subspecies (Olea europaea subsp. europaea, OE) and its wild relative (Olea europaea subsp. europaea var. sylvestris, OS) have genomic references, hindering our understanding of the evolution of this species. Using a hybrid approach by incorporating Illumina, MGI, Nanopore, and Hi-C technologies, we obtained a 1.20-Gb genome assembly for the olive subspecies, Olea europaea subsp. cuspidate (OC), with contig and scaffold N50 values of 5.33 and 50.46 Mb, respectively. A total of 43,511 protein-coding genes were predicted from the genome. Interestingly, we observed a large region (37.5 Mb) of "gene-desert" also called "LTR-hotspot" on chromosome 17. The gene origination analyses revealed a substantial outburst (19.5%) of gene transposition events in the common ancestor of olive subspecies, suggesting the importance of olive speciation in shaping the new gene evolution of OC subspecies. The divergence time between OC and the last common ancestor of OE and OS was estimated to be 4.39 Mya (95% CI: 2.58-6.23 Mya). The pathways of positively selected genes of OC are related to the metabolism of cofactors and vitamins, indicating the potential medical and economic values of OC for further research and utilization. In summary, we constructed the de novo genome assembly and protein-coding gene pool for Olea europaea subsp. cuspidate (OC) in this study, which may facilitate breeding applications of improved olive varieties from this widely distributed olive close relative.

6.
Artigo em Inglês | MEDLINE | ID: mdl-36148947

RESUMO

Egg granuloma formation in the liver is the main pathological lesion caused by Schistosoma japonicum infection, which generally results in liver fibrosis and may lead to death in advanced patients. MicroRNAs (miRNAs) regulate the process of liver fibrosis, but the putative function of miRNAs in liver fibrosis induced by S. japonicum infection is largely unclear. Here, we detect a new miRNA, miR-182-5p, which shows significantly decreased expression in mouse livers after stimulation by soluble egg antigen (SEA) of S. japonicum or S. japonicum infection. Knockdown or overexpression of miR-182-5p in vitro causes increased or decreased expression of tristetraprolin (TTP), an important immunosuppressive protein in the process of liver fibrosis. Furthermore, knockdown of miR-182-5p in vivo upregulates TTP expression and significantly alleviates S. japonicum-induced hepatic fibrosis. Our data demonstrate that downregulation of miR-182-5p increases the expression of TTP in mouse livers following schistosome infection, which leads to destabilization of inflammatory factor mRNAs and attenuates liver fibrosis. Our results uncover fine-tuning of liver inflammatory reactions related to liver fibrosis caused by S. japonicum infection and provide new insights into the regulation of schistosomiasis-induced hepatic fibrosis.

7.
Front Cardiovasc Med ; 9: 833522, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36110418

RESUMO

Objective: The prognostic significance of troponin elevation following percutaneous coronary intervention (PCI) remains debated. This study aimed to evaluate the association between different thresholds of post-PCI cardiac troponin I (cTnI) and mortality. Methods: From January 2012 to July 2017, 5,218 consecutive patients undergoing elective PCI with pre-PCI cTnI < 99th percentile of the upper reference limit (URL) were included. Levels of cTnI were measured before PCI and every 8 h for 24 h after procedural. The outcomes were 3-year cardiac mortality. Results: Patients had a mean age of 66.2 years, 27.6% were women, 67.0% had hypertension, and 26.2% had diabetes mellitus. During the 3 years of follow-up, cardiac death occurred in 0.86%, 1.46%, 1.69%, 2.36%, and 2.86% of patients with cTnI < 1, ≥ 1 to < 5, ≥ 5 to < 35, ≥ 35 to < 70, and ≥ 70 times URL. The cardiac mortality rate was moderately increased with higher peak cTnI values, but the Kaplan-Meier curve demonstrated no significant association between any increment of cTnI and either cardiac or non-cardiac mortality. Isolated cTnI increment of ≥ 5 × URL, ≥ 35 × URL, and ≥ 70 × URL was occurred in 1,379 (26.4%), 197 (3.8%), and 70 (1.3%) patients, respectively. In multivariate Cox regression analysis and Fine-Gray model, none of the above cTnI thresholds was significantly associated with an increased risk of cardiac death. Conclusion: In patients who underwent elective PCI, post-PCI cTnI elevation is not independently associated with cardiac mortality.

8.
J Am Heart Assoc ; 11(18): e026263, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36102255

RESUMO

Background To evaluate the prognostic value of plasma YKL-40 (human cartilage glycoprotein-39) for acute ischemic stroke. Methods and Results We measured plasma YKL-40 levels in 3377 participants from CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). Study outcome data on death, major disability (modified Rankin Scale score ≥3), and vascular diseases were collected at 3 months after stroke onset. The primary outcome was defined as a combination of death and major disability. During the 3-month follow-up, 828 participants (24.5%) experienced major disability or died. After multivariate adjustment, the highest YKL-40 quartile was associated with an increased risk of the primary outcome (odds ratio, 1.426 [95% CI, 1.105-1.839]; Ptrend=0.01) compared with the lowest quartile. Each SD increase in log-transformed YKL-40 level was associated with a 15.5% (95% CI, 5.6-26.3%) increased risk of the primary outcome. The multivariable-adjusted spline regression models showed a linear dose-response relationship between YKL-40 and clinical outcomes. Adding YKL-40 to a model containing conventional risk factors significantly improved the reclassification power for the primary outcome (net reclassification improvement: 15.61%, P<0.001; integrated discrimination index: 0.37%, P=0.004) and marginally significantly improved the discriminatory power for the primary outcome (area under the receiver operating characteristic curve improved by 0.003, P=0.099). Conclusions A higher YKL-40 level in the acute phase of ischemic stroke was associated with an increased risk of mortality and major disability at 3 months after stroke, indicating that YKL-40 may play an important role as a prognostic marker of ischemic stroke. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01840072.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Anti-Hipertensivos , Biomarcadores , Proteína 1 Semelhante à Quitinase-3 , Humanos , Prognóstico
9.
Neuron ; 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36070748

RESUMO

The use of body-focused repetitive behaviors (BFRBs) is conceptualized as a means of coping with stress. However, the neurological mechanism by which repetitive behaviors affect anxiety regulation is unclear. Here, we identify that the excitatory somatostatin-positive neurons in the medial paralemniscal nucleus (MPLSST neurons) in mice promote self-grooming and encode reward. MPLSST neurons display prominent grooming-related neuronal activity. Loss of function of MPLSST neurons impairs both self-grooming and post-stress anxiety alleviation. Activation of MPLSST neurons is rewarding and sufficient to drive reinforcement by activating dopamine (DA) neurons in the ventral tegmental area (VTA) and eliciting dopamine release. The neuropeptide SST facilitates the rewarding impact of MPLSST neurons. MPLSST neuron-mediated self-grooming is triggered by the input from the central amygdala (CeA). Our study reveals a dual role of CeA-MPLSST-VTADA circuit in self-grooming and post-stress anxiety regulation and conceptualizes MPLSST neurons as an interface linking the stress and reward systems in mice.

10.
Int Heart J ; 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36104241

RESUMO

Although the use of iodinated contrast for percutaneous coronary intervention (PCI) has known toxicity issues, the association between the contrast volume-to-creatinine clearance (V/CrCl) ratio and perioperative myocardial infarction (PMI) is unclear. The present study is aimed to investigate the predictive value of V/CrCl ratio on the incidence of PMI, and to determine a relatively safe contrast media V/CrCl ratio cut-off value to prevent PMI undergoing elective PCI. The V/CrCl ratio were obtained from 5970 patients undergoing elective PCI for single-vessel lesions. Cardiac troponin I (cTnI) were measured at baseline, 8, 16, and 24 hours after PCI. PMI was defined as postprocedural > 5 × upper limit of normal. Receiver operating characteristic (ROC) curves were performed to identify the optimal sensitivity for the V/CrCl range. Multivariate regression model were used to assess the association between V/CrCl ratios and PMI. Eight hundred and ninety-seven patients (15.0%) developed PMI. There was a significant association between higher V/CrCl ratio and the development of PMI (P < 0.001 for the trend). ROC curve analysis indicated that V/CrCl ratio of 2.05 was a discriminator for PMI (area under the curve = 0.674). After adjusting for other potential risk factors, V/CrCl ratio > 2.05 remained significant associated with PMI (odds ratio, 1.921; 95% confidence interval, 1.311-2.815; P = 0.001). The finding of this study suggests the importance of minimizing the contrast media dose to avoid PMI development. Use of a contrast media dose based on renal function with a V/CrCl value < 2.05 might be valuable in preventing PMI.

11.
Front Endocrinol (Lausanne) ; 13: 956646, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36060934

RESUMO

Objective: The aim of this study was to fully describe the clinical and genetic characteristics, including clinical manifestations, intact fibroblast growth factor 23 (iFGF23) levels, and presence of PHEX gene mutations, of 22 and 7 patients with familial and sporadic X-linked dominant hypophosphatemia (XLH), respectively. Methods: Demographic data, clinical features, biochemical indicators, and imaging data of 29 patients were collected. All 22 exons and exon-intron boundaries of the PHEX gene were amplified by polymerase chain reaction (PCR) and directly sequenced. The serum level of iFGF23 was measured in 15 of the patients. Results: Twenty-nine patients (male/female: 13:16, juvenile/adult: 15:14) with XLH were included. The main symptoms were bowed lower extremities (89.7%), abnormal gait (89.7%), and short stature/growth retardation (78.6%). Hypophosphatemia with a high alkaline phosphatase level was the main biochemical feature and the median value of serum iFGF23 was 55.7 pg/ml (reference range: 16.1-42.2 pg/ml). Eight novel mutations in the PHEX gene were identified by Sanger sequencing, including two missense mutations (p. Gln682Leu and p. Phe312Ser), two deletions (c.350_356del and c.755_761del), one insertion (c.1985_1986insTGAC), and three splice mutations (c.1700+5G>C, c.1966-1G>T, and c.350-14_350-1del). Additionally, the recurrence rate after the first orthopedic surgery was 77.8% (7/9), and five of them had their first surgery before puberty. Conclusion: Our study expanded the clinical phenotypes and gene mutation spectrum of XLH and provided a reference for the optimal timing of orthopedic surgeries.


Assuntos
Raquitismo Hipofosfatêmico Familiar , Hipofosfatemia , China/epidemiologia , Raquitismo Hipofosfatêmico Familiar/genética , Feminino , Humanos , Masculino , Endopeptidase Neutra Reguladora de Fosfato PHEX/genética , Maturidade Sexual
12.
Hypertension ; 79(10): 2336-2345, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35950501

RESUMO

BACKGROUND: Increased blood pressure (BP) variability is positively associated with the risks of cerebral small-vessel disease, cardiovascular events and death. However, no large clinical trials have been published to demonstrate the effect of BP fluctuations during hospitalization on clinical outcomes after ischemic stroke. METHODS: A total of 3972 patients with acute ischemic stroke from 26 participating hospitals were included in this study, and BP fluctuations were calculated using BP data collected during the hospitalization. The primary outcome was composite outcome of death or major disability (modified Rankin Scale score ≥3) within 3 months and secondary outcomes included death, vascular events, and composite outcomes (death or vascular events). RESULTS: Compared with the lowest quartile of systolic BP fluctuations, the adjusted odds ratio associated with the highest quartile was 1.33 ([95% CI, 1.05-1.68]; Ptrend=0.011) for primary outcome; the adjusted hazard ratios were 2.89 ([95% CI, 1.58-5.32]; Ptrend<0.001) for death, 1.48 ([95% CI, 0.83-2.65]; Ptrend=0.071) for vascular events, and 2.06 ([95% CI, 1.32-3.23]; Ptrend<0.001) for composite outcome. Similar results were found for diastolic BP. Multivariable adjusted restricted cubic spline analysis showed a linear relationship between systolic BP fluctuations and the primary outcome (P for linearity=0.0009). CONCLUSIONS: Larger BP fluctuations during hospitalization were associated with an increased risk of adverse outcomes at 3 months after ischemic stroke onset, independent of mean BP. These findings suggested that BP fluctuation should be a risk factor of adverse outcomes after ischemic stroke, which provided a new insight for BP management strategy.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Pressão Sanguínea , Isquemia Encefálica/diagnóstico , Hospitalização , Humanos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia
13.
Atherosclerosis ; 356: 1-8, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35939981

RESUMO

BACKGROUND AND AIMS: We aimed to explore the dynamic natural morphologies and main components of nonculprit subclinical atherosclerotic changes underlying lesion regression (LR) or lesion progression (LP) in patients with acute coronary syndrome. METHODS: The primary endpoints were changes in percent atheroma volume (ΔPAV), normalized total atheroma volume (ΔTAVn) and each component in nonculprit subclinical atherosclerosis from baseline to 1 year measured by optical flow ratio (OFR) software. LR or LP was defined by an increase or decrease in PAV. Secondary endpoints included the correlation between changes in the lipid profile and ΔPAV/ΔTAVn and major adverse cardiac events (MACEs) related to nonculprit subclinical atherosclerosis at 3 years. RESULTS: This was a subgroup analysis of our previous randomized trial with a total of 161 nonculprit lesions analysed. In the LR (approximately 55.3% of the lesions) group, ΔTAVn was positively correlated only with lipid ΔTAVn (r = 0.482, p < 0.001) but not fibrous and calcium ΔTAVn, and ΔPAV was positively correlated with lipid ΔPAV (r = 0.315, p = 0.003) but not fibrous and calcium ΔPAV. The percent reduction in low-density lipoprotein cholesterol (LDL-C) was an independent predictor of LR in multivariate logistic regression analysis (OR = 3.574, 95% CI: 1.125-11.347, p = 0.031). The incidence of MACEs related to nonculprit lesions at 3 years was higher in the LP group than the LR group (9.9% vs. 2.2%, p = 0.040). CONCLUSIONS: LR of nonculprit subclinical atherosclerosis at 1-year follow-up was mainly caused by regression of the lipid component, which was correlated with the degree of LDL-C reduction and fewer MACEs at 3-year follow-up.


Assuntos
Síndrome Coronariana Aguda , Aterosclerose , Doença da Artéria Coronariana , Placa Aterosclerótica , Síndrome Coronariana Aguda/complicações , Aterosclerose/complicações , Cálcio , LDL-Colesterol , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Seguimentos , Humanos , Placa Aterosclerótica/complicações
14.
Behav Res Methods ; 2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-36002623

RESUMO

The ability to rapidly recognize words and link them to referents is central to children's early language development. This ability, often called word recognition in the developmental literature, is typically studied in the looking-while-listening paradigm, which measures infants' fixation on a target object (vs. a distractor) after hearing a target label. We present a large-scale, open database of infant and toddler eye-tracking data from looking-while-listening tasks. The goal of this effort is to address theoretical and methodological challenges in measuring vocabulary development. We first present how we created the database, its features and structure, and associated tools for processing and accessing infant eye-tracking datasets. Using these tools, we then work through two illustrative examples to show how researchers can use Peekbank to interrogate theoretical and methodological questions about children's developing word recognition ability.

15.
Clin Chem Lab Med ; 60(10): 1675-1682, 2022 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-35938913

RESUMO

OBJECTIVES: The prognostic role of baseline platelet count (PLT) in acute ischemic stroke patients with large vessel occlusion undergoing endovascular thrombectomy is unclear. Whether PLT modifies alteplase treatment effect on clinical outcome in those patients is also uncertain. METHODS: We derived data from a multicenter randomized clinical trial (DIRECT-MT) comparing intravenous alteplase before endovascular treatment vs. endovascular treatment only. The 654 patients with available PLT data were included. Primary outcome was the ordinal modified Rankin Scale (mRS) score evaluated at 90 days. We also assessed various secondary and safety outcomes. RESULTS: After adjusting for confounding factors, patients in the top tertile of PLT had a significantly lower risk of a worse shift in the distribution of mRS score (Odds Ratio: 0.671, 95% Confidence Interval: 0.473-0.953, p for trend=0.025), major disability and death (Odds Ratio: 0.617, 95% Confidence Interval: 0.393-0.97, p for trend=0.037) as well as death (Odds Ratio: 0.544, 95% Confidence Interval: 0.313-0.947, p for trend=0.031), respectively, compared with the bottom one. Among patients in the bottom tertile of PLT, combination therapy was associated with a better imaging outcome of eTICI score of 2b, 2c or 3 on final angiogram (Odds Ratio: 3.23, 95% Confidence Interval: 1.49-7.002) with a marginally significant interaction effect. CONCLUSIONS: Participants with higher baseline PLT had a decreased risk of poor functional outcomes. Low baseline PLT modified alteplase treatment effect on the eTICI score on final angiogram. Combination therapy was beneficial for patients with low baseline PLT to have a better reperfusion status.


Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Contagem de Plaquetas , Trombectomia , Ativador de Plasminogênio Tecidual , Resultado do Tratamento
16.
Oxid Med Cell Longev ; 2022: 5098358, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36035220

RESUMO

Bone metabolism occurs in the entire life of an individual and is required for maintaining skeletal homeostasis. The imbalance between osteogenesis and osteoclastogenesis eventually leads to osteoporosis. Oxidative stress is considered a major cause of bone homeostasis disorder, and relieving excessive oxidative stress in bone mesenchymal stem cells (BMSCs) is a potential treatment strategy for osteoporosis. Carbon monoxide releasing molecule-3 (CORM-3), the classical donor of carbon monoxide (CO), possesses antioxidation, antiapoptosis, and anti-inflammatory properties. In our study, we found that CORM-3 could reduce reactive oxygen species (ROS) accumulation and prevent mitochondrial dysfunction thereby restoring the osteogenic potential of the BMSCs disrupted by hydrogen peroxide (H2O2) exposure. The action of CORM-3 was preliminarily considered the consequence of Nrf2/HO-1 axis activation. In addition, CORM-3 inhibited osteoclast formation in mouse primary bone marrow monocytes (BMMs) by inhibiting H2O2-induced polarization of M1 macrophages and endowing macrophages with M2 polarizating ability. Rat models further demonstrated that CORM-3 treatment could restore bone mass and enhance the expression of Nrf2 and osteogenic markers in the distal femurs. In summary, CORM-3 is a potential therapeutic agent for the treatment of osteoporosis.


Assuntos
Heme Oxigenase-1 , Fator 2 Relacionado a NF-E2 , Compostos Organometálicos , Osteoporose , Animais , Monóxido de Carbono , Heme Oxigenase-1/metabolismo , Peróxido de Hidrogênio , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Compostos Organometálicos/metabolismo , Estresse Oxidativo , Ratos , Transdução de Sinais
17.
Chemosphere ; 307(Pt 1): 135687, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35842050

RESUMO

Anaerobic ammonia oxidation (anammox) is an environmental-friendly biological nitrogen removal process, which has been developed as a promising technology in industrial wastewater treatment. However, anammox nitrogen removal under high saline conditions still faces many challenges. This study investigated the performance of anammox sludge under saline short-term shock and the strategy of rapid recovery. Salinity concentration, saline exposure time, and NaCl/Na2SO4 ratio were selected as three critical factors for short-term shock. The activity inhibition of anammox sludge were tested by using response surface methodology (RSM). Our results showed that, compared with the NaCl/Na2SO4 ratio, the salinity concentration and saline exposure time were the significant factor causing the anammox inhibition. The addition of glycine betaine (GB) in moderate amounts (0.1-5 mM) was found to help anammox to resist in relative low saline shock intensities (e.g., IC25 and IC50), with the activity retention rate of 94.7%. However, glycine betaine was not worked effectively under relatively high saline shock intensities (e.g., complete inhibition condition). Microbial community analysis revealed that Brocadiaceae accounted for only about 7.6%-13.2% at inhibited conditions. Interestingly, 16S rRNA analysis showed that the abundance of activated Brocadiaceae remarkably decreased with time after high-level saline shock. This tendency was consistent with the results of qPCR targeted hzsA gene. Finally, based on quorum sensing, the anammox activity was recovered to 93.5% of original sludge by adding 30% original sludge. The study realized the rapid recovery of anammox activity under complete inhibition, promoting the development and operation of salt-tolerant anammox process.

18.
Artigo em Inglês | MEDLINE | ID: mdl-35841386

RESUMO

OBJECTIVE: To predict risk factors for Bakri balloon tamponade (BBT) failure in the management of postpartum hemorrhage(PPH). METHODS: The data of 599 patients who underwent BBT were retrospectively analyzed from January 1, 2017 to Dec 31, 2021 in a tertiary hospital in Shanghai, East China. The patients were divided into the failure group and the success group.Failure was defined as the inability to control bleeding, which required surgical interventions .Maternal characteristics,PPH characteristics,PPH management approaches, and maternal complications were compared between the groups.The independent predictors of BBT failure were analyzed by logistic regression analysis. RESULTS: The overall success rate of BBT was 83.0% (497/599). The blood loss before and after balloon insertion in the failure group was significantly greater than that in the success group. Of the 102 failures, B-Lynch suture was performed in one patients, uterine artery embolization were performed in 99 patients(with one failure) and total hysterectomy was performed three patients. Some risk factors, including twin gestation(OR=9.68),placenta previa(PP) with/without placenta accreta spectrum(PAS) (OR=4.45),estimated blood loss ≥ 1,135mL at balloon insertion (OR=3.35),multiparous(OR=2.72)and in vitro fertilization-embryo transfer(IVF-ET)(OR=2.00) were strongly associated with BBT failure. CONCLUSION: BBT seemed to be a less effective tool in the management of PPH due to placenta previa with/without PAS and twin gestation.

19.
Mol Psychiatry ; 2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35804093

RESUMO

Fear extinction allows for adaptive control of learned fear responses but often fails, resulting in a renewal or spontaneous recovery of the extinguished fear, i.e., forgetting of the extinction memory readily occurs. Using an activity-dependent neuronal labeling strategy, we demonstrate that engram neurons for fear extinction memory are dynamically positioned in the medial prefrontal cortex (mPFC), basolateral amygdala (BLA), and ventral hippocampus (vHPC), which constitute an engram construct in the term of directional engram synaptic connectivity from the BLA or vHPC to mPFC, but not that in the opposite direction, for retrieval of extinction memory. Fear renewal or spontaneous recovery switches the extinction engram construct from an accessible to inaccessible state, whereas additional extinction learning or optogenetic induction of long-term potentiation restores the directional engram connectivity and prevents the return of fear. Thus, the plasticity of engram construct underlies forgetting of extinction memory.

20.
Front Genet ; 13: 927519, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35812748

RESUMO

Recent studies have identified DNA methylation signatures in the white blood cells as potential biomarkers for breast cancer (BC) in the European population. Here, we investigated the association between BC and blood-based methylation of cluster of differentiation 160 (CD160), inositol-3-phosphate synthase 1 (ISYNA1) and RAD51 paralog B (RAD51B) genes in the Chinese population. Peripheral blood samples were collected from two independent case-control studies with a total of 272 sporadic early-stage BC cases (76.5% at stage I&II) and 272 cancer-free female controls. Mass spectrometry was applied to quantitatively measure the levels of DNA methylation. The logistic regression and non-parametric tests were used for the statistical analyses. In contrast to the protective effects reported in European women, we reported the blood-based hypomethylation in CD160, ISYNA1 and RAD51B as risk factors for BC in the Chinese population (CD160_CpG_3, CD160_CpG_4/cg20975414, ISYNA1_CpG_2, RAD51B_CpG_3 and RAD51B_CpG_4; odds ratios (ORs) per -10% methylation ranging from 1.08 to 1.67, p < 0.05 for all). Moreover, hypomethylation of CD160, ISYNA1 and RAD51B was significantly correlated with age, BC subtypes including estrogen receptor (ER)-negative BC tumors, triple negative tumors, BC cases with larger size, advanced stages and more lymph node involvement. Our results supported the report in European women that BC is associated with altered methylation of CD160, ISYNA1 and RAD51B in the peripheral blood, although the effects are opposite in the Chinese population. The difference between the two populations may be due to variant genetic background or life styles, implicating that the validations of epigenetic biomarkers in variant ethnic groups are warranted.

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