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1.
Front Cardiovasc Med ; 9: 799300, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35498036

RESUMO

Background: Non-fasting (i.e., postprandial) lipid detection is recommended in clinical practice. However, the change in blood lipids in Chinese patients with cardiovascular diseases after three daily meals has never been reported yet. Methods: Serum levels of blood lipids were measured or calculated in 77 inpatients (48 men and 29 women) at high or very high risk of atherosclerotic cardiovascular disease (ASCVD) in the fasting state and at 4 h after three meals within a day according to their diet habits. Results: Female patients showed significantly higher level of high-density lipoprotein cholesterol (HDL-C) than male patients, and the gender difference in other lipid parameters did not reach statistical significance at any time-point. Levels of triglyceride (TG) and remnant cholesterol (RC) increased, while that of low-density lipoprotein cholesterol (LDL-C) decreased significantly after three meals (p < 0.05). Levels of HDL-C, total cholesterol (TC), and non-high-density lipoprotein cholesterol (non-HDL-C) showed smaller changes after three meals. Percent reductions in the non-fasting LDL-C levels after lunch and supper were around 20%, which were greater than that after breakfast. The percent reductions in the non-fasting non-HDL-C levels after three meals were smaller than those in the non-fasting LDL-C levels. Patients with TG level ≥ 2.0 mmol/L (177 mg/dL) after lunch had significantly greater absolute reduction of LDL-C level than those with TG level < 2.0 mmol/L (177 mg/dL) after lunch [-0.69 mmol/L (-27 mg/dL) vs. -0.36 mmol/L (-14 mg/dL), p<0.01]. There was a significant and negative correlation between absolute change in LDL-C level and that in TG level (r = -0.32) or RC level (r = -0.67) after lunch (both p<0.01). Conclusion: LDL-C level decreased significantly after three daily meals in Chinese patients at high or very high risk of ASCVD, especially when TG level reached its peak after lunch. Relatively, non-HDL-C level was more stable than LDL-C level postprandially. Therefore, when LDL-C level was measured in the non-fasting state, non-HDL-C level could be evaluated simultaneously to reduce the interference of related factors, such as postprandial hypertriglyceridemia, on detection.

2.
Front Surg ; 9: 814293, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35495750

RESUMO

Background: The postoperative sepsis is a latent fatal complication for both flexible ureteroscopy (fURS) and percutaneous nephrolithotomy (PNL). An effective predictive model constructed by readily available clinical markers is urgently needed to reduce postoperative adverse events caused by infection. This study aims to determine the pre-operative predictors of sepsis in patients with unilateral, solitary, and proximal ureteral stones after fURS and PNL. Methods: We retrospectively enrolled 910 patients with solitary proximal ureteral stone with stone size 10-20 mm who underwent fURS or PNL from Tongji Hospital's database, including 412 fURS cases and 498 PNL cases. We used the least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression analysis to identify the risk factors for sepsis. Finally, a nomogram was assembled utilizing these risk factors. Results: In this study, 49 patients (5.4%) developed sepsis after fURS or PNL surgery. Lasso regression showed postoperative sepsis was associated with gender (female), pre-operative fever, serum albumin (<35 g/L), positive urine culture, serum WBC (≥10,000 cells/ml), serum neutrophil, positive urine nitrite and operation type (fURS). The multivariate logistic analysis indicated that positive urine culture (odds ratio [OR] = 5.9092, 95% CI [2.6425-13.2140], p < 0.0001) and fURS (OR = 1.9348, 95% CI [1.0219-3.6631], p = 0.0427) were independent risk factors of sepsis and albumin ≥ 35g/L (OR = 0.4321, 95% CI [0.2054-0.9089], p = 0.0270) was independent protective factor of sepsis. A nomogram was constructed and exhibited favorable discrimination (area under receiver operating characteristic curve was 0.78), calibration [Hosmer-Lemeshow (HL) test p = 0.904], and net benefits displayed by decision curve analysis (DCA). Conclusions: Patients who underwent fURS compared to PNL or have certain pre-operative characteristics, such as albumin <35 g/L and positive urine culture, are more likely to develop postoperative sepsis. Cautious preoperative evaluation and appropriate operation type are crucial to reducing serious infectious events after surgery, especially for patients with solitary, unilateral, and proximal ureteral stones sized 10-20 mm.

3.
BMC Gastroenterol ; 22(1): 217, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35505284

RESUMO

BACKGROUND: Group A rotavirus (RVA) remains the main causative agent of acute diarrhea among children under five years in countries that have not yet introduced the RVA vaccine worldwide. Long-term and continuous monitoring data on RVA infection in outpatient children were lacking in Shanghai. We investigated the prevalence and distribution of RVA genotypes in outpatient children with acute diarrhea in Shanghai from 2012 to 2018. METHODS: Stool specimens of outpatient children under five years were collected from the Children's Hospital of Fudan University in Shanghai, China. All the samples enrolled in this study were detected and characterized for the P and G genotypes of RVA were determined using the semi-multiplex RT-PCR technique. RESULTS: Of 1814 children enrolled with acute diarrhea and having specimens collected, 246 (13.6%) were infected with RVA. The highest frequency of RVA was observed in children younger than two years old (87.0%, 214/246). Year-round RVA transmission was observed and the RVA detection rate peaked every winter and troughed in summer. In this study, 12 different RVA strains were identified in children. G9P[8] (49.2%, 121/246) was detected as the most prevalent genotype, followed by G-P[8] (22.8%, 56/246), G3P[8] (11.4%, 28/246), and G9P- (4.9%, 12/246). Although RVA strains detected in this study varied with the time, G9P[8] has been the most predominant circulating genotype since 2012. Furthermore, 12.2% (30/246) RVA positive samples were co-infected with other diarrhea viruses. CONCLUSION: The present analysis showed that RVA was still a major cause of children with acute diarrhea in Shanghai from 2012 to 2018. A great diversity of RVA strains circulated in children with acute diarrhea with G9P[8] being the predominant genotype since 2012. Long-term and continuous monitoring of RVA genotypes is therefore indispensable to refine future vaccine strategy in Shanghai.


Assuntos
Infecções por Rotavirus , Rotavirus , Criança , Pré-Escolar , China/epidemiologia , Diarreia/epidemiologia , Fezes , Genótipo , Humanos , Pacientes Ambulatoriais , Prevalência , Rotavirus/genética , Infecções por Rotavirus/epidemiologia
4.
J Pain Res ; 15: 1315-1324, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35546904

RESUMO

Objective: The study objective was to investigate whether Z-guggulsterone can relieve neuropathic pain in sciatic nerve chronic constriction injury (CCI) mice by inhibiting the expression of astrocytes and proinflammatory cytokines in the spinal dorsal horn. Methods: Neuropathic pain was induced and assessed in CCI mice. Z-guggulsterone was administered multiple times via intraperitoneal injection. Pain behaviour assessments were made by conducting paw withdrawal mechanical threshold (PWMT) and thermal withdrawal latency (TWL) tests. The expression level of the glial fibrillary acidic protein (GFAP) in the spinal dorsal horn was observed by immunofluorescence. The levels of the proinflammatory cytokines, IL-1ß, IL-6 and TNF-α in the spinal cord were measured by ELISA. Data were analysed using one-way ANOVA or two-way ANOVA. Results: The PWMT and TWL were higher on the 5th, 7th, 10th and 14th days after CCI, the expression level of GFAP in the spinal dorsal horn was lower, and the levels of IL-1ß, IL-6 and TNF-α in the spinal cord were lower in the CCI+Z-GS-L, CCI+Z-GS-M and CCI+Z-GS-H groups than in the CCI+Veh group in a dose-dependent manner (P < 0.05). Conclusion: Z-guggulsterone can relieve neurological pain in CCI mice, which may be related to the inhibition of astrocytes and proinflammatory cytokines in the spinal dorsal horn.

5.
Artigo em Inglês | MEDLINE | ID: mdl-35569818

RESUMO

Atherosclerosis, characterized by lipid-rich plaques in the arterial wall, is an age-related disorder and a leading cause of mortality worldwide. However, the specific mechanisms remain complex. Recently, emerging evidence has demonstrated that senescence of various types of cells, such as endothelial cells (ECs), vascular smooth muscle cells (VSMCs), macrophages, endothelial progenitor cells (EPCs), and adipose-derived mesenchymal stem cells (AMSCs) contributes to atherosclerosis. Cellular senescence and atherosclerosis share various causative stimuli, in which dyslipidemia has attracted much attention. Dyslipidemia, mainly referred to elevated plasma levels of atherogenic lipids or lipoproteins, or functional impairment of anti-atherogenic lipids or lipoproteins, plays a pivotal role both in cellular senescence and atherosclerosis. In this review, we summarize the current evidence for dyslipidemia-induced cellular senescence during atherosclerosis, with a focus on low-density lipoprotein (LDL) and its modifications, hydrolysate of triglyceride-rich lipoproteins (TRLs), and high-density lipoprotein (HDL), respectively. Furthermore, we describe the underlying mechanisms linking dyslipidemia-induced cellular senescence and atherosclerosis. Finally, we discuss the senescence-related therapeutic strategies for atherosclerosis, with special attention given to the anti-atherosclerotic effects of promising geroprotectors as well as anti-senescence effects of current lipid-lowering drugs.

6.
Front Oncol ; 12: 862743, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35530337

RESUMO

Redox homeostasis is a lifelong pursuit of cancer cells. Depending on the context, reactive oxygen species (ROS) exert paradoxical effects on cancers; an appropriate concentration stimulates tumorigenesis and supports the progression of cancer cells, while an excessive concentration leads to cell death. The upregulated antioxidant system in cancer cells limits ROS to a tumor-promoting level. In cancers, redox regulation interacts with tumor initiation, proliferation, metastasis, programmed cell death, autophagy, metabolic reprogramming, the tumor microenvironment, therapies, and therapeutic resistance to facilitate cancer development. This review discusses redox control and the major hallmarks of cancer.

7.
Zhongguo Zhong Yao Za Zhi ; 47(8): 2090-2098, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35531725

RESUMO

The methods for determining the characteristic chromatogram and index components content of Xuanfu Daizhe Decoction were established to provide a scientific basis for the quality evaluation of substance benchmarks and preparations. Eighteen batches of Xuanfu Daizhe Decoction were prepared with the decoction pieces of different batches and of the same batch were prepared respectively, and the HPLC characteristic chromatograms of these samples were established. The similarities of the chromatographic fingerprints were analyzed. With liquiritin, glycyrrhizic acid, 6-gingerol, ginsenoside Rg_1, and ginsenoside Re as index components, the high performance liquid chromatography was established for content determination with no more than 70%-130% of the mass average as the limit. The results showed that there were 19 characteristic peaks corresponding to the characteristic chromatograms of 18 batches of Xuanfu Daizhe Decoction, including 8 peaks representing liquiritin, 1,5-O-dicaffeoylqunic acid, ginsenoside Rg_1, ginsenoside Re, 1-O-acetyl britannilactone, ginsenoside Rb_1, glycyrrhizic acid, and 6-gingerol, and the fingerprint similarity was greater than 0.97. The contents of liquiritin, glycyrrhizic acid, 6-gingerol, and ginsenosides Rg_1 + Re in the prepared Xuanfu Daizhe Decoction samples were 0.53%-0.86%, 0.61%-1.2%, 0.023%-0.068%, and 0.33%-0.66%, respectively. Except for several batches, most batches of Xuanfu Daizhe Decoction showed stable contents of index components, with no discrete values. The characteristic chromatograms and index components content characterized the information of Inulae Flos, Ginseng Radix et Rhizoma, Glycyrrhizae Radix et Rhizoma, and Zingiberis Rhizoma Recens in Xuanfu Daizhe Decoction. This study provides a scientific basis for the further research on the key chemical properties of substance benchmark and preparations of Xuanfu Daizhe Decoction.


Assuntos
Medicamentos de Ervas Chinesas , Ginsenosídeos , Benchmarking , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Ginsenosídeos/análise , Ácido Glicirrízico/análise , Controle de Qualidade
8.
Mol Med ; 28(1): 55, 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35562651

RESUMO

BACKGROUND: The aim of this study was to draw a comprehensive mutational landscape of nasopharyngeal carcinoma (NPC) tumors and identify the prognostic factors for distant metastasis-free survival (DMFS). METHODS: A total of forty primary nonkeratinizing NPC patients underwent targeted next-generation sequencing of 450 cancer-relevant genes. Analysis of these sequencing and clinical data was performed comprehensively. Univariate Cox regression analysis and multivariate Lasso-Cox regression analyses were performed to identify factors that predict distant metastasis and construct a risk score model, and seventy percent of patients were randomly selected from among the samples as a validation cohort. A receiver operating characteristic (ROC) curve and Harrell's concordance index (C-index) were used to investigate whether the risk score was superior to the TNM stage in predicting the survival of patients. The survival of patients was determined by Kaplan-Meier curves and log-rank tests. RESULTS: The twenty most frequently mutated genes were identified, such as KMT2D, CYLD, and TP53 et al. Their mutation frequencies of them were compared with those of the COSMIC database and cBioPortal database. N stage, tumor mutational burden (TMB), PIK3CA, and SF3B1 were identified as predictors to build the risk score model. The risk score model showed a higher AUC and C-index than the TNM stage model, regardless of the training cohort or validation cohort. Moreover, this study found that patients with tumors harboring PI3K/AKT or RAS pathway mutations have worse DMFS than their wild-type counterparts. CONCLUSIONS: In this study, we drew a mutational landscape of NPC tumors and established a novel four predictor-based prognostic model, which had much better predictive capacity than TNM stage.

9.
Artigo em Inglês | MEDLINE | ID: mdl-35416276

RESUMO

BACKGROUND: Hemifacial microsomia (HFM) is a congenital craniofacial malformation, and its features include hypoplasia and asymmetry in skeletal tissue and soft tissue. These features are usually associated with a difficult airway. Mandibular distraction osteogenesis can achieve mandibular advancement, but its effect on the subsequent laryngoscopic views has not been adequately documented. AIM: The aim of this study was to determine the change in laryngoscopic views after mandibular distraction osteogenesis (MDO) in children with HFM and to examine the radiological changes after MDO by using computed tomography (CT)-based three-dimensional (3-D) airway reconstruction. METHODS: An observational prospective study was carried out in children with HFM undergoing MDO. All children underwent 3-D airway reconstruction preoperatively before the placement and removal of the distractor. The temporomandibular joint lesions in children were classified by the Pruzansky-Kaban classification. The Cormack-Lehane grade was assessed after induction under direct laryngoscopy. The relationship between difficult laryngoscopy and the Pruzansky-Kaban classification was assessed. Changes in the upper pharyngeal airway parameters and laryngoscopic views were analyzed. RESULTS: Forty children (ages ranging from 5 to 16 years, males = 26, females = 14) with HFM underwent 80 anesthesia for MDO. The incidence of difficult laryngoscopy before mandibular distraction was 5/12 (41.7%) in type IIa, 19/24 (79.2%) in type IIb and 1/4 (25%) in type III HFM. The mean difference in the incidence of difficult laryngoscopy before and after MDO was 33.3% (95% CI: -6.7% to 73.3%), 50.0% (95% CI: 8.4% to 91.6%), and 0% for type IIa, type IIb, and type III, respectively. In type IIb, 12/19 cases of difficult laryngoscopy became easy after mandibular distraction: this was associated with an increase in the palatopharyngeal and glossopharyngeal CT parameters (p < .05). In type IIa, 5/5 cases of difficult laryngoscopy became easy after mandibular distraction, and 1/7 cases of easy laryngoscopy became difficult laryngoscopy. However, there were no significant changes in the palatopharyngeal, glossopharyngeal, and hypopharyngeal CT parameters in type IIa and type III HFM (p > .05). CONCLUSIONS: MDO can improve the laryngoscopic views in children with HFM. According to the Pruzansky-Kaban classification, children with type IIb showed the highest incidence of difficult laryngoscopy before MDO. After MDO, the improvement in laryngoscopic views under direct laryngoscopy in type IIb was related to the increase in the palatopharyngeal and glossopharyngeal volume.

10.
Tree Physiol ; 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35451493

RESUMO

Cryptomeria fortunei growth and development are usually affected by low temperatures. Despite the evergreen nature of this species, most needles turn yellowish-brown in cold winters. The underlying discoloration mechanisms that cause this phenomenon in response to cold acclimation remain poorly understood. Here, we measured the pigment content and ultrastructure of normal wild-type (Wt) and evergreen mutant (GM) C. fortunei needles and performed integrated transcriptomic and metabolomic analyses to explore potential discoloration mechanisms. The results showed that the needle chlorophyll content of these two genotypes decreased in winter. Wt needles showed greater decrease in the chlorophyll content and local destruction of chloroplast ultrastructure, and contained larger amounts of flavonoids than GM needles, as shown by metabolomics analysis. We subsequently identified key differentially expressed genes in the flavonoid biosynthesis pathway and observed significantly upregulated flavonol synthase (FLS) expression in Wt needles compared to GM needles, that significantly increased the anthoxanthin (flavones and flavonols) content, which is likely a key factor underlying the difference in needle color between these two genotypes. Therefore, flavonoid metabolism may play important roles in the cold resistance and needle discoloration of C. fortunei, and our results provide an excellent foundation for the molecular mechanism of C. fortunei in response to cold stress.

11.
Medicine (Baltimore) ; 101(10): e29011, 2022 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-35451398

RESUMO

ABSTRACT: To evaluate the feasibility, efficacy, and safety of minimally invasive pedicle screw (MIPS) fixation, including the fractured vertebra, combined with percutaneous vertebroplasty (PVP) for the treatment of acute thoracolumbar osteoporotic compression fracture in middle-age and elderly individuals.Between January 2016 and August 2019, a total of 30 patients, with a mean age of 69.4 years (range, 58-75 years), who experienced thoracic or lumbar fracture without neurological deficits, underwent the MIPS procedure combined with PVP. Preoperative and postoperative pain were assessed using a visual analog scale and Oswestry Disability Index. Cobb angles and anterior column height were measured on lateral radiographs before surgery and at 3 days, 1, 3, and 6 months, and 1 and 2 years at final follow-up after surgery.All patients underwent surgery successfully, with a mean follow-up of 18.2 ±â€Š5.7 months (range, 12-45 months). Mean preoperative visual analog scale score decreased from 7.3 ±â€Š2.2 to 1.4 ±â€Š0.3 at the final follow-up (P < .05). Mean preoperative Oswestry Disability Index decreased from 84.2 ±â€Š10.3 to 18.8 ±â€Š7.5 (P < .05) at the final follow-up. The Kyphosis angle of operative segment was improved from preoperative (21.38 ±â€Š1.68)° to (4.01 ±â€Š1.38)° 3 days postoperatively and (5.02 ±â€Š1.09)° at final follow-up (P < .05). The anterior vertebral height was improved from preoperative (49.86 ±â€Š6.50)% to (94.01 ±â€Š1.79)% 3 days postoperatively and (91.80 ±â€Š1.88)% at final follow-up (P < .05). No significant changes in vertebral body height restoration were observed during 2 years of follow-up after surgery. In addition, there were no instrumentation failures or complications in any of the patients.MIPS, including the fractured vertebra, combined with PVP, was a reliable and safe procedure, with satisfactory clinical and radiological results for the treatment of thoracolumbar osteoporotic compression fracture in patients without neurological deficits.


Assuntos
Fraturas por Compressão , Fraturas por Osteoporose , Parafusos Pediculares , Fraturas da Coluna Vertebral , Vertebroplastia , Idoso , Fixação Interna de Fraturas/efeitos adversos , Fixação Interna de Fraturas/métodos , Fraturas por Compressão/cirurgia , Humanos , Vértebras Lombares/lesões , Vértebras Lombares/cirurgia , Pessoa de Meia-Idade , Fraturas por Osteoporose/cirurgia , Estudos Prospectivos , Fraturas da Coluna Vertebral/cirurgia , Vértebras Torácicas/lesões , Vértebras Torácicas/cirurgia , Resultado do Tratamento , Vertebroplastia/métodos
12.
Oxid Med Cell Longev ; 2022: 5585384, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35450406

RESUMO

Heat shock protein 90 (HSP90) is widely found in brain tissue. HSP90 inhibition has been proven to have neuroprotective effects on ischemic strokes. In order to study the role of HSP90 in traumatic brain injury (TBI), we carried out the present study. A novel inhibitor of the HSP90 protein, 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DA), has been investigated for its function on the blood-brain barrier (BBB) damage after traumatic brain injury (TBI) in mouse models. These C57BL/6 mice were used as a TBI model and received 17-DA (0.1 mg/kg/d, intraperitoneally) until the experiment ended. To find out whether 17-DA may protect against TBI in vitro, bEnd.3 cells belonging to mouse brain microvascular endothelium were used. The HSP90 protein expressions were raised after TBI at the pericontusional area, especially at 3 d. Our study suggested that 17-DA-treated mice improved the recovery ability of neurological deficits and decreased brain edema, Evans blue extravasation, and the loss of tight junction proteins (TJPs) post-TBI. 17-DA significantly promoted cell proliferation and alleviated apoptosis by inhibiting the generation of intracellular reactive oxygen species (ROS) to downregulate cleaved caspase-3, matrix metallopeptidase- (MMP-) 2, MMP-9, and P-P65 in bEnd.3 cells after the injury. As a result, we assumed that the HSP90 protein was activated post-TBI, and inhibition of HSP90 protein reduced the disruption of BBB and improved the neurobehavioral scores in a mouse model of TBI through the action of 17-DA, which inhibited ROS generation and regulated MMP-2, MMP-9, NF-κB, and caspase-associated pathways. Thus, blocking HSP90 protein may be a potential therapeutic strategy for TBI.


Assuntos
Barreira Hematoencefálica , Lesões Encefálicas Traumáticas , Animais , Barreira Hematoencefálica/metabolismo , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/metabolismo , Modelos Animais de Doenças , Proteínas de Choque Térmico HSP90 , Proteínas de Choque Térmico/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio/metabolismo
13.
Artigo em Inglês | MEDLINE | ID: mdl-35482693

RESUMO

The task of cross-modal image retrieval has recently attracted considerable research attention. In real-world scenarios, keyword-based queries issued by users are usually short and have broad semantics. Therefore, semantic diversity is as important as retrieval accuracy in such user-oriented services, which improves user experience. However, most typical cross-modal image retrieval methods based on single point query embedding inevitably result in low semantic diversity, while existing diverse retrieval approaches frequently lead to low accuracy due to a lack of cross-modal understanding. To address this challenge, we introduce an end-to-end solution termed variational multiple instance graph (VMIG), in which a continuous semantic space is learned to capture diverse query semantics, and the retrieval task is formulated as a multiple instance learning problems to connect diverse features across modalities. Specifically, a query-guided variational autoencoder is employed to model the continuous semantic space instead of learning a single-point embedding. Afterward, multiple instances of the image and query are obtained by sampling in the continuous semantic space and applying multihead attention, respectively. Thereafter, an instance graph is constructed to remove noisy instances and align cross-modal semantics. Finally, heterogeneous modalities are robustly fused under multiple losses. Extensive experiments on two real-world datasets have well verified the effectiveness of our proposed solution in both retrieval accuracy and semantic diversity.

14.
Mol Psychiatry ; 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35484242

RESUMO

Salient sensory stimuli are perceived by the brain, which guides both the timing and outcome of behaviors in a context-dependent manner. Light is such a stimulus, which is used in treating mood disorders often associated with a dysregulated hypothalamic-pituitary-adrenal stress axis. Relationships between the emotional valence of light and the hypothalamus, and how they interact to exert brain-wide impacts remain unclear. Employing larval zebrafish with analogous hypothalamic systems to mammals, we show in free-swimming animals that hypothalamic corticotropin releasing factor (CRFHy) neurons promote dark avoidance, and such role is not shared by other hypothalamic peptidergic neurons. Single-neuron projection analyses uncover processes extended by individual CRFHy neurons to multiple targets including sensorimotor and decision-making areas. In vivo calcium imaging uncovers a complex and heterogeneous response of individual CRFHy neurons to the light or dark stimulus, with a reduced overall sum of CRF neuronal activity in the presence of light. Brain-wide calcium imaging under alternating light/dark stimuli further identifies distinct and distributed photic response neuronal types. CRFHy neuronal ablation increases an overall representation of light in the brain and broadly enhances the functional connectivity associated with an exploratory brain state. These findings delineate brain-wide photic perception, uncover a previously unknown role of CRFHy neurons in regulating the perception and emotional valence of light, and suggest that light therapy may alleviate mood disorders through reducing an overall sum of CRF neuronal activity.

15.
Microbiol Spectr ; 10(2): e0220421, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35384719

RESUMO

The rice-crayfish (RC) integrated breeding model is an important and special agricultural ecosystem that provides a unique ecological environment for exploring the microbial diversity, composition, and functional capacity. To date, little is known about the effect of the breeding model on microbiome assembly and breeding model-specific microbiome composition and the association of the microbiome with water quality and crayfish growth. In the present study, we assessed the taxonomic shifts in gut and water microbiomes and their associations with water quality and crayfish growth in the RC and crayfish monoculture (CM) breeding models across six time points of rice growth, including seedling (a), tillering and jointing (b), blooming (c), filling (d), fruiting (e), and rotting of rice residues (f). Dominant bacterial phyla, such as Proteobacteria, Actinobacteria, Bacteroidetes, and Firmicutes, were detected in both gut and water microbiomes across breeding models. Notably, the diversity and structure of the gut and water microbiomes significantly (P < 0.001) differed between the RC and CM models, with higher microbial diversity being noted in the RC model than in the CM model. The taxa enriched in the RC model included Bacillus sp., Streptomyces sp., Lactobacillus sp., Prevotella sp., Rhodobacter sp., Bifidobacterium sp., Akkermansia sp., and Lactococcus sp., some of which are potentially beneficial to animals. However, opportunistic pathogens, such as Citrobacter sp. and Aeromonas sp., were depleted in the RC model. Furthermore, in the RC model, the enriched taxa that formed complex cooccurrence networks showed a significant positive correlation with water quality and crayfish growth, whereas the depleted taxa showed a significant negative correlation with water quality and crayfish growth. These results suggest that the RC model has a better microbiome composition and that RC model-specific microbes could play important roles in improving crayfish growth and water quality. IMPORTANCE The present study comprehensively compared two different breeding models in terms of their microbiome composition and the associations of the microbiomes with crayfish growth and water quality. RC model-specific microbiome composition was identified; these microbes were found to have a positive association with water quality and crayfish growth. These results provide valuable information for guiding microbial isolation and culture and for potentially harnessing the power of the microbiome to improve crayfish production and health and water quality.


Assuntos
Astacoidea , Microbiota , Animais , Bactérias , Melhoramento Vegetal , Qualidade da Água
16.
Pharmaceutics ; 14(4)2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35456636

RESUMO

The cyclin-dependent kinase inhibitor p27 (Kip1) is an important regulator of the G1/S checkpoint. It is degraded by the SCF-SKP2 complex in late G1 thereby allowing cells to progress to the S phase. Here we investigated the role of the E3 ubiquitin ligase RNF6 (Ring Finger Protein 6) in cell cycle progression in prostate cancer cells. Our data demonstrate that RNF6 can promote cell cycle progression by reducing the levels of p27. Knockdown of RNF6 led to an increase in the stability of p27 and to the arrest of cells in the G1 phase. RNF6 interacted with p27 via its KIL domain and this interaction was found to be phosphorylation independent. RNF6 enhanced ubiquitination and subsequent degradation of p27 in the early G0/G1 phase of the cell cycle. Knockdown of RNF6 expression by short hairpin RNA led to inhibition of the CDK2/Cyclin E complex thereby reducing phosphorylation of Retinoblastoma protein (Rb) and to a subsequent decrease in cell cycle progression and proliferation. Our data suggest that RNF6 acts as a negative regulator for p27kip1 leading to its proteasome-dependent degradation in the early G0/G1 phase of the cell cycle.

17.
Trials ; 23(1): 294, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35413886

RESUMO

BACKGROUND: Sepsis and continuous renal replacement therapy (CRRT) are both responsible for the alterations of the pharmacokinetics of antibiotics. For patients with sepsis receiving CRRT, the serum concentrations of meropenem in the early phase (< 48 h) was significantly lower than that in the late phase (> 48 h). This current trial aimed to investigate whether administration of a loading dose of meropenem results in a more likely achievement of the pharmacokinetic (PK)/pharmacodynamics (PD) target (100% fT > 4 × MIC) and better therapeutic results in the patients with sepsis receiving CRRT. METHODS: This is a single-blinded, single-center, randomized, controlled, two-arm, and parallel-group trial. This trial will be carried out in Guangzhou First People's Hospital, School of Medicine, South China University of Technology Guangdong, China. Adult patients (age ≥ 18 years) with critical sepsis or sepsis-related shock receiving CRRT will be included in the study. The subjects will be assigned to the control group and the intervention group (LD group) randomly at a 1:1 ratio, the estimated sample size should be 120 subjects in each group. In the LD group, the patient will receive a loading dose of 1.5-g meropenem resolved in 30-ml saline which is given via central line for 30 min. Afterward, 0.75-g meropenem will be given immediately for 30 min every 8 h. In the control group, the patient will receive 0.75-g meropenem for 30 min every 8 h. The primary objective is the probabilities of PK/PD target (100% fT > 4 × MIC) achieved in the septic patients who receive CRRT in the first 48 h. Secondary objectives include clinical cure rate, bacterial clearance rate, sepsis-related mortality and all-cause mortality, the total dose of meropenem, duration of meropenem treatment, duration of CRRT, Sequential Organ Failure Assessment (SOFA), C-reactive protein levels, procalcitonin levels, white blood cell count, and safety. DISCUSSION: This trial will assess for the first time whether administration of a loading dose of meropenem results in a more likely achievement of the PK/PD target and better therapeutic results in the patients with sepsis receiving CRRT. Since CRRT is an important therapeutic strategy for sepsis patients with hemodynamic instability, the results from this trial may help to provide evidence-based therapy for septic patients receiving CRRT. TRIAL REGISTRATION: Chinese Clinical Trials Registry, ChiCTR2000032865 . Registered on 13 May 2020, http://www.chictr.org.cn/showproj.aspx?proj=53616 .


Assuntos
Sepse , Choque Séptico , Adolescente , Adulto , Antibacterianos , Estado Terminal , Humanos , Meropeném/efeitos adversos , Meropeném/farmacocinética , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sepse/diagnóstico , Sepse/tratamento farmacológico , Choque Séptico/diagnóstico , Choque Séptico/tratamento farmacológico
18.
Front Immunol ; 13: 864156, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35418978

RESUMO

Background: SUMOylation is an important component of post-translational protein modifications (PTMs), and bladder cancer (BCa) is the ninth most common cancer around the world. But the comprehensive role of SUMOylation in shaping tumor microenvironment (TME) and influencing tumor clinicopathological features and also the prognosis of patients remains unclear. Methods: Using the data downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), we comprehensively evaluated the SUMOylation patterns of 570 bladder cancer samples, and systematically correlated these SUMOylation patterns with TME immune cell infiltrating characteristics. The SUMO score was constructed to quantify SUMOylation patterns of individuals using principal component analysis (PCA) algorithms. Results: Two distinct SUMOylation patterns and gene clusters were finally determined. Significant differences in the prognosis of patients were found among two different SUMOylation patterns and gene clusters, so were in the mRNA transcriptome and the landscape of TME immune cell infiltration. We also established a set of scoring system named SUMO score to quantify the SUMOylation pattern of individuals with BCa, which was discovered to be tightly connected with tumor clinicopathological characteristics and could predict the prognosis of patients with BCa. Moreover, SUMO score was a considerable predictive indicator for the survival outcome independent of tumor mutation burden (TMB) and low SUMO score was related to better response to immunotherapy using PD-1 blockade. We also found that there existed a significant relationship between sensitivity to commonly used chemotherapy drugs and SUMO score. Finally, a nomograph based on five features, namely, SUMO score, age, gender, T category, and M category was constructed to predict the survival probability of patients with BCa in 1, 3, and 5 years, respectively. Conclusions: Our work demonstrated and overviewed the complicated regulation mechanisms of SUMOylation in bladder cancer, and better understanding and evaluating SUMOylation patterns could be helpful in guiding clinical therapeutic strategy and improving the prognosis of patients with BCa.


Assuntos
Microambiente Tumoral , Neoplasias da Bexiga Urinária , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Prognóstico , Sumoilação , Microambiente Tumoral/genética , Neoplasias da Bexiga Urinária/patologia
19.
Front Cell Dev Biol ; 10: 832892, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35386202

RESUMO

Background: Ferroptosis is a unique iron-dependent form of cell death and bladder cancer (BCa) is one of the top ten most common cancer types in the world. However, the role of ferroptosis in shaping the tumor microenvironment and influencing tumor clinicopathological features remains unknown. Methods: Using the data downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), we comprehensively evaluated the ferroptosis patterns of 570 BCa samples based on 234 validated ferroptosis genes reported in the FerrDb database and systematically correlated these ferroptosis patterns with tumor microenvironment (TME) cell-infiltrating characteristics. The ferroptosis score was constructed to quantify ferroptosis patterns of individuals using principal component analysis (PCA) algorithms. Results: Four distinct ferroptosis patterns and two gene clusters were finally determined. Significant differences in clinical characteristics and the prognosis of patients were found among different ferroptosis patterns and gene clusters, so were in the mRNA transcriptome and the landscape of TME immune cell infiltration. We also established a set of scoring system to quantify the ferroptosis pattern of individual patients with BCa named the ferroptosis score, which was discovered to tightly interact with clinical signatures such as the TNM category and tumor grade and could predict the prognosis of patients with BCa. Moreover, tumor mutation burden (TMB) was positively correlated to the ferroptosis score, and the low ferroptosis score was related to a better response to immunotherapy using PD-1 blockade. Finally, we also found there existed a positive correlation between the sensitivity to cisplatin chemotherapy and ferroptosis score. Conclusions: Our work demonstrated and interpreted the complicated regulation mechanisms of ferroptosis on the tumor microenvironment and that better understanding and evaluating ferroptosis patterns could be helpful in guiding the clinical therapeutic strategy and improving the prognosis of patients with BCa.

20.
Mol Med Rep ; 25(6)2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35475447

RESUMO

In recent years, circular RNAs (circRNAs/circs) have attracted significant attention due to their potentially important functions in a variety of human cancer types. circ_0067934 is a newly identified circRNA, the role of which in gastric cancer (GC) has yet to be reported, to the best of our knowledge. In the present study, the expression levels of circ_0067934, microRNA (miR)­1301­3p and kinesin family member 23 (KIF23) in GC cells were detected via reverse transcription­quantitative PCR. Cell proliferation was measured using Cell Counting Kit­8 assays and EdU staining. Wound healing and Transwell assays were performed to assess cell migration and invasion, respectively. Western blotting was performed to measure the protein expression levels of Ki67, proliferating cell nuclear antigen, MMP2, MMP9 and KIF23. The starBase database and luciferase reporter assays were used to predict and verify the binding between circ_0067934 and miR­1301­3p, as well as KIF23, in GC cells. The results demonstrated that circ_0067934 expression was upregulated in GC cells, and circ_0067934 silencing significantly inhibited GC cell proliferation, migration and invasion. In addition, miR­1301­3p was regulated by circ_0067934, and miR­1301­3p overexpression suppressed GC cell migration, invasion and proliferation. miR­1301­3p was found to target KIF23, and KIF23 overexpression reversed the effects of circ_0067934 silencing and miR­1301­3p overexpression on cell proliferation, migration and invasion. In conclusion, circ_0067934 may regulate the proliferation, invasion and migration of GC cells via the miR­1301­3p/KIF23 signaling axis, which may represent a novel therapeutic target for GC metastasis.


Assuntos
MicroRNAs , Neoplasias Gástricas , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , RNA Circular/genética , Neoplasias Gástricas/patologia
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