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1.
Neural Regen Res ; 18(2): 344-349, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35900428

RESUMO

The current animal models of stroke primarily model a single intracerebral hemorrhage (ICH) attack, and there is a lack of a reliable model of recurrent ICH. In this study, we established 16-month-old C57BL/6 male mouse models of ICH by injecting collagenase VII-S into the left striatum. Twenty-one days later, we injected collagenase VII-S into the right striatum to simulate recurrent ICH. Our results showed that mice subjected to bilateral striatal hemorrhage had poorer neurological function at the early stage of hemorrhage, delayed recovery in locomotor function, motor coordination, and movement speed, and more obvious emotional and cognitive dysfunction than mice subjected to unilateral striatal hemorrhage. These findings indicate that mouse models of bilateral striatal hemorrhage can well simulate clinically common recurrent ICH. These models should be used as a novel tool for investigating the pathogenesis and treatment targets of recurrent ICH.

2.
PeerJ Comput Sci ; 8: e1049, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36092014

RESUMO

Load forecasting is very essential in the analysis and grid planning of power systems. For this reason, we first propose a household load forecasting method based on federated deep learning and non-intrusive load monitoring (NILM). As far as we know, this is the first research on federated learning (FL) in household load forecasting based on NILM. In this method, the integrated power is decomposed into individual device power by non-intrusive load monitoring, and the power of individual appliances is predicted separately using a federated deep learning model. Finally, the predicted power values of individual appliances are aggregated to form the total power prediction. Specifically, by separately predicting the electrical equipment to obtain the predicted power, it avoids the error caused by the strong time dependence in the power signal of a single device. In the federated deep learning prediction model, the household owners with the power data share the parameters of the local model instead of the local power data, guaranteeing the privacy of the household user data. The case results demonstrate that the proposed approach provides a better prediction effect than the traditional methodology that directly predicts the aggregated signal as a whole. In addition, experiments in various federated learning environments are designed and implemented to validate the validity of this methodology.

3.
J Gastrointest Oncol ; 13(4): 1805-1817, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36092341

RESUMO

Background: Although studies have reported that certain sleep characteristics, such as sleep duration and sleep apnea, are linked to the risk of colorectal cancer (CRC), this link remains contentious because of the limited evidence from individual studies. Furthermore, evidence indicated that shift work involving circadian disruption as a probable human carcinogen. This systematic review and meta-analysis aimed to examine the associations between sleep duration, sleep apnea, and shift work with the risk of colorectal neoplasms, including CRC and colorectal adenoma (CRA). Methods: We conducted a comprehensive literature search in PubMed, Embase, and Web of Science databases. The inclusion criteria were determined using PICOS principles. Observational studies reporting associations of sleep duration, sleep apnea, or shift work with risk of CRC or CRA were included. We assessed the risk of bias on the basis of the Newcastle-Ottawa Scale. Results: A total of 18 observational studies were included. Of these studies, nine studies reported the effect of sleep duration on risk of colorectal neoplasms, five reported the effect of sleep apnea, and six reported the effect of shift work. The relative risk (RR) for colorectal neoplasms was 1.06 [95% confidence interval (CI): 0.94, 1.20] in the short sleep duration group compared with the moderate sleep duration group. Long sleep duration was associated with an increased risk of colorectal neoplasms (RR: 1.33, 95% CI: 1.07, 1.65). The pooled results showed that sleep apnea was associated with an increased risk of colorectal neoplasms (RR: 1.75, 95% CI: 1.56, 1.97). Furthermore, results showed that the association between shift work and the risk of colorectal neoplasms was not significant (RR: 1.06, 95% CI: 0.95, 1.17). No publication bias was observed in all the analyses (all P>0.05). The sensitivity analysis showed that no individual study substantially influenced the pooled RRs for colorectal neoplasms and CRC. Conclusions: Our findings suggest the significant positive association of long sleep duration and sleep apnea with risk of colorectal neoplasms and CRC. Given that sleep characteristics may be a potentially modifiable risk factor for colorectal neoplasms, further understanding of its role in carcinogenesis will provide valuable insight for cancer prevention.

4.
Front Aging Neurosci ; 14: 998255, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36092815

RESUMO

Background: Reduced dopamine transporter (DAT) binding in the striatum has been reported in patients with progressive supranuclear palsy (PSP). However, the relationship between striatal dopaminergic lesions and the disease severity of PSP remains to be explored. Objective: To investigate the contributions of striatal dopaminergic lesions to the disease severity of PSP. Methods: One hundred patients with clinically diagnosed PSP were consecutively enrolled in this study. The disease severity was systemically assessed using the PSP rating scale (PSPrs), and the dopaminergic lesions were assessed using the 11C-N-2-carbomethoxy-3-(4-fluorophenyl)-tropane positron emission tomography (11C-CFT PET) imaging. To explore the correlations between striatal DAT bindings and the disease severity, both the region-wise and voxel-wise analysis were adopted. Partial correlations and multiple linear regressions were performed to investigate the contribution of striatal dopaminergic lesions to the disease severity in PSP. Results: Sixty-three patients of PSP with Richardson's syndrome (PSP-RS) and 37 patients with PSP-non-RS were finally included. The disease severity in PSP-RS was much heavier than that in the PSP-non-RS. The DAT bindings in the caudate and anterior putamen correlated significantly with the PSPrs total scores, mainly in the domains of history, mentation, bulbar, and ocular motor symptoms. The striatal DAT bindings (caudate) contributed significantly to the disease severity of PSP, independent of the motor, cognition, emotion and behavioral dysfunctions. Conclusion: Our study highlighted the independent contribution of striatal dopaminergic lesions to the disease severity in PSP.

5.
PLoS One ; 17(9): e0274396, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36108272

RESUMO

Diffusion weighted imaging (DWI) with multiple, high b-values is critical for extracting tissue microstructure measurements; however, high b-value DWI images contain high noise levels that can overwhelm the signal of interest and bias microstructural measurements. Here, we propose a simple denoising method that can be applied to any dataset, provided a low-noise, single-subject dataset is acquired using the same DWI sequence. The denoising method uses a one-dimensional convolutional neural network (1D-CNN) and deep learning to learn from a low-noise dataset, voxel-by-voxel. The trained model can then be applied to high-noise datasets from other subjects. We validated the 1D-CNN denoising method by first demonstrating that 1D-CNN denoising resulted in DWI images that were more similar to the noise-free ground truth than comparable denoising methods, e.g., MP-PCA, using simulated DWI data. Using the same DWI acquisition but reconstructed with two common reconstruction methods, i.e. SENSE1 and sum-of-square, to generate a pair of low-noise and high-noise datasets, we then demonstrated that 1D-CNN denoising of high-noise DWI data collected from human subjects showed promising results in three domains: DWI images, diffusion metrics, and tractography. In particular, the denoised images were very similar to a low-noise reference image of that subject, more than the similarity between repeated low-noise images (i.e. computational reproducibility). Finally, we demonstrated the use of the 1D-CNN method in two practical examples to reduce noise from parallel imaging and simultaneous multi-slice acquisition. We conclude that the 1D-CNN denoising method is a simple, effective denoising method for DWI images that overcomes some of the limitations of current state-of-the-art denoising methods, such as the need for a large number of training subjects and the need to account for the rectified noise floor.


Assuntos
Processamento de Imagem Assistida por Computador , Redes Neurais de Computação , Imagem de Difusão por Ressonância Magnética/métodos , Humanos , Processamento de Imagem Assistida por Computador/métodos , Reprodutibilidade dos Testes , Razão Sinal-Ruído
7.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(9): 1001-1007, 2022.
Artigo em Chinês | MEDLINE | ID: mdl-36111718

RESUMO

OBJECTIVES: To study the association between neonatal discharge preparedness and adverse health events. METHODS: The neonates who were born in hospitals from different regions of Gansu Province in China and their parents were enrolled as subjects, and an investigation was performed for the discharge preparedness. According to the level of discharge preparedness, the subjects were divided into low-, middle-, and high-level groups. The neonates were followed up to observe the incidence rate of adverse health events within one month after discharge. The association between neonatal discharge preparedness and adverse health events was analyzed. RESULTS: The neonates with adverse health events had a significantly lower level of discharge preparedness than those without adverse events (P<0.05). The multivariate logistic regression analysis showed that the incidence rate of adverse health events was reduced by 34.8% in the middle-level group and 78.7% in the high-level group compared with the low-level group (P<0.05). The readmission rate of neonates was 8.1% (35/430), and the neonates readmitted had a significantly lower level of discharge preparedness than those not readmitted (P<0.05). The multivariate logistic regression analysis showed that the readmission rate of neonates was reduced by 67.4% in the middle-level group and 84.2% in the high-level group compared with the low-level group (P<0.05). CONCLUSIONS: Discharge preparedness may affect the incidence of adverse health events and the rate of readmission within one month after discharge. Medical staff should adopt effective intervention measures to improve discharge preparedness, so as to reduce the incidence of adverse health events and the rate of readmission.


Assuntos
Alta do Paciente , Readmissão do Paciente , China , Humanos , Incidência , Recém-Nascido
8.
Cancer Cell ; 40(9): 1044-1059.e8, 2022 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-36099882

RESUMO

Cisplatin-based chemotherapy remains the primary treatment for unresectable and metastatic muscle-invasive bladder cancers (MIBCs). However, tumors frequently develop chemoresistance. Here, we established a primary and orthotopic MIBC mouse model with gene-edited organoids to recapitulate the full course of chemotherapy in patients. We found that partial squamous differentiation, called semi-squamatization, is associated with acquired chemoresistance in both mice and human MIBCs. Multi-omics analyses showed that cathepsin H (CTSH) is correlated with chemoresistance and semi-squamatization. Cathepsin inhibition by E64 treatment induces full squamous differentiation and pyroptosis, and thus specifically restrains chemoresistant MIBCs. Mechanistically, E64 treatment activates the tumor necrosis factor pathway, which is required for the terminal differentiation and pyroptosis of chemoresistant MIBC cells. Our study revealed that semi-squamatization is a type of lineage plasticity associated with chemoresistance, suggesting that differentiation via targeting of CTSH is a potential therapeutic strategy for the treatment of chemoresistant MIBCs.


Assuntos
Carcinoma de Células Escamosas , Neoplasias da Bexiga Urinária , Animais , Carcinoma de Células Escamosas/tratamento farmacológico , Diferenciação Celular , Cisplatino , Humanos , Camundongos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
9.
Int J Ophthalmol ; 15(9): 1423-1430, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36124184

RESUMO

AIM: To identify potential mutations and elucidate the clinical findings of male patients and female carriers of X-linked retinitis pigmentosa (XLRP) in a Chinese family. METHODS: A four generation pedigree was collected that consisted of 20 individuals. Genomic DNA was extracted from peripheral blood, and then the target fragments were amplified by PCR and sequenced directly. In addition, all affected patients and female carriers underwent comprehensively ophthalmic evaluation. RESULTS: A novel mutation c.2865G>A p.W955X in RPGR gene was identified of this family, including four affected individuals and eight carriers. All male patients, aging from 7 to 31y, tended to have more various, even potentially deleterious clinical features of RP. At the same time, individuals with heterozygous mutations (carriers) manifested a wide spectrum of clinical features. Herein, only two male patients and three female carriers manifested pathological myopia (PM). Among the female carriers, half of subjects who harbor poor visual acuity suffered esotropia or exotropia. Additionally, 16.7% and 66.7% of carriers had abnormal electroretinogram (ERG) and fundus, respectively. CONCLUSION: In this study, a novel mutation of the RPGR gene is identified, which broadens the spectrum of RPGR mutations, and elaborates the relationship between genotype and phenotype.

10.
Front Plant Sci ; 13: 976669, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119573

RESUMO

High seedling vigor can improve the ability to compete against weeds and flooding at the seedling stage and is essential for the direct seeding of rice. Early shoot length is an important performance index in seedling vigor evaluation. However, information on the identity of rice germplasm with high seedling vigor, and the genetic basis of seedling vigor are not well understood. In this study, we have conducted a genome-wide association study using 302 international diverse rice accessions from the Rice Diversity Panel 2. Six quantitative trait loci (QTLs) were found to associate with shoot length (SL). The locus qSL2 was further analyzed for candidate gene characterization. We identified OsCPS1, which encodes CDP synthase and functions in GA (Gibberellins) biosynthesis in rice, exhibits differential expression between long and short SL accessions. Using the Nipponbare genome sequence as the reference, we identified a 36 bp deletion in the 5' UTR of OsCPS1 in long SL accessions, which is absent in short SL accessions. GA content analysis showed that the levels of bioactive GA1 and GA4 are considerably higher in long SL accessions than in short SL accessions. Genome-wide gene expression analysis indicated the expression of some photosynthesis genes is higher in long SL accessions than in short SL accessions. In contrast, genes involved in ABA (Abscisic Acid)-activated signal pathway showed lower expression in long SL accessions. Population analysis across wild rice, indica and japonica, suggested that OsCPS1 may be under selection in japonica during domestication. The results suggest that OsCPS1 is a candidate gene underlying qSL2. These data provide a promising source for candidate genetic variation associated with seedling vigor, with practical applications in rice breeding.

11.
Front Pediatr ; 10: 931667, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36120649

RESUMO

SATB1 variants causing developmental delay with dysmorphic facies and dental anomalies have been reported in a small cohort. Most patients present epilepsy as a main clinical feature in neurodevelopmental disorders; however, its treatment is unknown. Here, we present a Chinese patient with a de novo truncating variation in SATB1 who presented with mild developmental delay. We disclose the detailed anti-epileptic pharmacological treatment that enabled a favorable outcome. Our study provides important information that may aid clinicians in the prognosis and treatment of rare neurological developmental disorders caused by gene mutations.

12.
Artigo em Inglês | MEDLINE | ID: mdl-36123446

RESUMO

To investigate the effects of different types of land use and soil depths on the distributions of heavy metals in the soil in mining areas, heavy metals in different soil layers of five types of agricultural land in the Tongguan gold mining area were studied. The results revealed that the land use type had a greater impact than soil layers on the distribution of heavy metals in the soil. Among the five types of agricultural land examined, the risk values were only exceeded for the heavy metals lead(Pb) and mercury(Hg) in the pepper field, indicating combined pollution of Pb and Hg. Furthermore, some of the heavy metals, such as Pb, zinc(Zn), cadmium(Cd) and Hg, were highly significantly and positively correlated with each other. The pepper field should be monitored to prevent pollution from other heavy metals.

13.
Immunopharmacol Immunotoxicol ; : 1-13, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36083020

RESUMO

BACKGROUND: Resistance to chemotherapeutic drugs limits the control of gastric cancer (GC) development. The study intended to probe into the mechanism of aquaporin 3 (AQP3) on the chemoresistance of GC. METHODS: Cisplatin (CDDP)-resistant cells were constructed. Parental AGS and HGC-27 cells and their respective CDDP-resistant cells were transfected with AQP3 overexpression plasmid, AQP3 short hairpin RNA (sh-AQP3) and sh-Kruppel-like factor 5 (shKLF5). The expressions of AQP3 and factors related to autophagy (LC3 I, LC3 II, Atg5, Beclin-1, p62)/epithelial-mesenchymal transition (EMT; E-cadherin and snail) were assessed by Western blot and qRT-PCR. Cell counting kit-8 assay was adopted to test cell viability and half maximal inhibitory concentration (IC 50) was determined. Transwell assay was used for the examination of cell migration and invasion. The regulatory relationship of AQP3 and KLF5 was tested by chromatin immunoprecipitation (ChIP) and dual luciferase reporter assays. RESULTS: AQP3 was highly-expressed in GC cells and its level was even higher in CDDP-resistant GC cells. AQP3 silencing inhibited viability, autophagy and EMT in CDDP-resistant GC cells, while AQP3 overexpression had the opposite effect. KLF5 positively modulated AQP3 in GC cells resistant to CDDP. KLF5 knockdown reversed AQP3-induced autophagy, viability, migration, invasion and EMT in CDDP-resistant GC cells. CONCLUSION: KLF5-modulated AQP3 activated autophagy to facilitate the resistance of GC to CDDP.

14.
Cell Biosci ; 12(1): 158, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36114560

RESUMO

BACKGROUND: Abnormal lipid metabolism is one of the most prominent metabolic changes in cancer. Studies have shown that lipid metabolism also plays an important role in neuroblastoma. We recently discovered that the insulinoma-associated 2 gene (INSM2) could regulate lipid metabolism in neuroblastoma (NB) and is improperly controlled by super enhancers, a mammalian genome region that has been shown to control the expression of NB cell identity genes. However, the specific molecular pathways by which INSM2 leads to NB disease development are unknown. RESULTS: We identified INSM2 as a gene regulated by super enhancers in NB. In addition, INSM2 expression levels were significantly upregulated in NB and correlated with poor prognosis in patients. We found that INSM2 drives the growth of NB cell lines both in vitro and in vivo. Knocking down INSM2 inhibited fatty acid metabolism in NB cells. Mechanistically, INSM2 regulates the expression of SREBP1 by regulating the mTOR signaling pathway, which in turn affects lipid metabolism, thereby mediating the occurrence and development of neuroblastoma. CONCLUSION: INSM2 as a super-enhancer-associated gene could regulates lipid metabolism by modulating mTOR signaling pathway in neuroblastoma.

15.
Nat Commun ; 13(1): 5462, 2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36115848

RESUMO

Generalization is a fundamental cognitive ability of organisms to deal with the uncertainty in real-world situations. Excessive fear generalization and impaired reward generalization are closely related to many psychiatric disorders. However, the neural circuit mechanism for reward generalization and its role in anxiety-like behaviours remain elusive. Here, we found a robust activation of calbindin 1-neurons (Calb 1) in the posterior basolateral amygdala (pBLA), simultaneous with reward generalization to an ambiguous cue after reward conditioning in mice. We identify the infralimbic medial prefrontal cortex (IL) to the pBLACalb1 (Calb 1 neurons in the pBLA) pathway as being involved in reward generalization for the ambiguity. Activating IL-pBLA inputs strengthens reward generalization and reduces chronic unpredictable mild stress-induced anxiety- and depression-like behaviours in a manner dependent on pBLACalb1 neuron activation. These findings suggest that the IL-pBLACalb1 circuit could be a target to promote stress resilience via reward generalization and consequently ameliorate anxiety- and depression-like behaviours.


Assuntos
Complexo Nuclear Basolateral da Amígdala , Animais , Ansiedade , Calbindina 1 , Depressão , Humanos , Camundongos , Neurônios/fisiologia , Córtex Pré-Frontal/fisiologia
16.
Science ; 377(6610): eabp9444, 2022 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-36048929

RESUMO

The molecular mechanism underlying brain regeneration in vertebrates remains elusive. We performed spatial enhanced resolution omics sequencing (Stereo-seq) to capture spatially resolved single-cell transcriptomes of axolotl telencephalon sections during development and regeneration. Annotated cell types exhibited distinct spatial distribution, molecular features, and functions. We identified an injury-induced ependymoglial cell cluster at the wound site as a progenitor cell population for the potential replenishment of lost neurons, through a cell state transition process resembling neurogenesis during development. Transcriptome comparisons indicated that these induced cells may originate from local resident ependymoglial cells. We further uncovered spatially defined neurons at the lesion site that may regress to an immature neuron-like state. Our work establishes spatial transcriptome profiles of an anamniote tetrapod brain and decodes potential neurogenesis from ependymoglial cells for development and regeneration, thus providing mechanistic insights into vertebrate brain regeneration.


Assuntos
Ambystoma mexicanum , Regeneração do Cérebro , Células-Tronco Neurais , Ambystoma mexicanum/fisiologia , Animais , Células-Tronco Neurais/fisiologia , Análise de Célula Única , Telencéfalo/fisiologia , Transcriptoma
17.
Mov Disord ; 37(9): 1807-1816, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36054272

RESUMO

BACKGROUND: The diagnostic criteria for Parkinson's disease (PD) remain complex, which is especially problematic for nonmovement disorder experts. A test is required to establish a diagnosis of PD with improved accuracy and reproducibility. OBJECTIVE: The study aimed to investigate the sensitivity and specificity of tests using sniffer dogs to diagnose PD. METHODS: A prospective, diagnostic case-control study was conducted in four tertiary medical centers in China to evaluate the accuracy of sniffer dogs to distinguish between 109 clinically established medicated patients with PD, 654 subjects without PD, 37 drug-naïve patients with PD, and 185 non-PD controls. The primary outcomes were sensitivity and specificity of sniffer dog's identification. RESULTS: In the study with patients who were medicated, when two or all three sniffer dogs yielded positive detection results in a sample tested, the index test sensitivity, specificity, and positive and negative likelihood ratios were 91% (95% CI: 84%-96%), 95% (95% CI: 93%-97%), and 19.16 (95% CI: 13.52-27.16) and 0.10 (95% CI: 0.05-0.17), respectively. The corresponding sensitivity, specificity, and positive and negative likelihood ratios in patients who were drug-naïve were 89% (95% CI: 75%-96%), 86% (95% CI: 81%-91%), and 6.6 (95% CI: 4.51-9.66) and 0.13 (95% CI: 0.05-0.32), respectively. CONCLUSIONS: Tests using sniffer dogs may be a useful, noninvasive, fast, and cost-effective method to identify patients with PD in community screening and health prevention checkups as well as in neurological practice. © 2022 International Parkinson and Movement Disorder Society.


Assuntos
Doença de Parkinson , Animais , Estudos de Casos e Controles , Cães , Humanos , Doença de Parkinson/diagnóstico , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Cães Trabalhadores
18.
BMC Oral Health ; 22(1): 373, 2022 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-36057573

RESUMO

BACKGROUND: The comparison of the two Willems dental age estimation methods (gender-specific (Willems I) and non-gender-specific (Willems II)) has not been fully investigated. Here we aimed to explore the applicability of the Willems dental age estimation in an Eastern Chinese population, which may cast light on the field of dental age estimation. METHODS: A total of 1211 oral panoramic radiographs (582 boys and 629 girls) of the Chinese Han population aged 11-16 years old were collected. Dental ages (DAs) were calculated using the Willems method. Statistical significance was set at a p-value < 0.05. Age differences between chronological age (CA) and dental age were analyzed by paired t-tests and mean absolute error (MAE). RESULTS: The differences between CA and DA determined by the Willems I method were + 0.44 and + 0.09 years for boys and girls, respectively. When using the Willems II method, these differences were + 0.57 and - 0.09. The MAEs of the Willems I method between DA and CA were 0.95 and 1.00 years in boys and girls, respectively. For Willems II, MAEs were 1.02 and 1.00 years in boys and girls. CONCLUSIONS: This study showed that the Willems I method was more accurate than the Willems II method in the boys' group for predicting age from a whole scale. In comparison, Willems II is more competitive in the girls' group. Neither method may be satisfactory for 11-to-16-year-old teenagers in Eastern China.


Assuntos
Determinação da Idade pelos Dentes , Dente , Adolescente , Determinação da Idade pelos Dentes/métodos , Asiáticos , Criança , China , Feminino , Humanos , Masculino , Radiografia Panorâmica
19.
Signal Transduct Target Ther ; 7(1): 305, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36050306

RESUMO

The current understanding of lactate extends from its origins as a byproduct of glycolysis to its role in tumor metabolism, as identified by studies on the Warburg effect. The lactate shuttle hypothesis suggests that lactate plays an important role as a bridging signaling molecule that coordinates signaling among different cells, organs and tissues. Lactylation is a posttranslational modification initially reported by Professor Yingming Zhao's research group in 2019. Subsequent studies confirmed that lactylation is a vital component of lactate function and is involved in tumor proliferation, neural excitation, inflammation and other biological processes. An indispensable substance for various physiological cellular functions, lactate plays a regulatory role in different aspects of energy metabolism and signal transduction. Therefore, a comprehensive review and summary of lactate is presented to clarify the role of lactate in disease and to provide a reference and direction for future research. This review offers a systematic overview of lactate homeostasis and its roles in physiological and pathological processes, as well as a comprehensive overview of the effects of lactylation in various diseases, particularly inflammation and cancer.


Assuntos
Glicólise , Neoplasias , Glicólise/genética , Homeostase , Humanos , Inflamação/genética , Ácido Láctico/metabolismo , Neoplasias/patologia
20.
Artigo em Inglês | MEDLINE | ID: mdl-36068945

RESUMO

BACKGROUND AND AIM: Considering the limitation of varying acid suppression of proton pump inhibitors, this study was aimed to assess the efficacy, safety, and dose-effect relationship of keverprazan, a novel potassium-competitive acid blocker, in the treatment of duodenal ulcer (DU) compared with lansoprazole. METHODS: A randomized, double-blind, double-dummy, multicenter, low-dose, high-dose, and positive-drug parallel-controlled study was conducted to verify the non-inferiority of keverprazan (20 or 30 mg) to lansoprazole of 30 mg once daily for 4 to 6 weeks and dose-effect relationship of keverprazan in the treatment of patients with active DU confirmed by endoscopy. RESULTS: Of the 180 subjects randomized, including 55 cases in the keverprazan_20 mg group, 61 cases in the keverprazan_30 mg group, and 64 cases in the lansoprazole_30 mg group, 168 subjects (93.33%) completed the study. The proportions of healed DU subjects in the keverprazan_20 mg, keverprazan_30 mg, and lansoprazole_30 mg groups were respectively 87.27%, 90.16%, and 79.69% at week 4 (P = 0.4595) and were respectively 96.36%, 98.36%, and 92.19% at week 6 (P = 0.2577). The incidence of adverse events in the keverprazan_20 mg group was lower than that in the lansoprazole_30 mg (P = 0.0285) and keverprazan_30 mg groups (P = 0.0398). CONCLUSIONS: Keverprazan was effective and non-inferior to lansoprazole in healing DU. Based on the comparable efficacy and safety data, keverprazan of 20 mg once daily is recommended for the follow-up study of acid-related disorders. (Trial registration number: ChiCTR2100043455.).

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