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1.
Anim Biosci ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38665081

RESUMO

Objective: Increasing breast meat production is one of the primary goals of the broiler industry. Over the past few decades, tremendous progress has been made in genetic selection and the identification of candidate genes for improving the breast muscle mass. However, the molecular network contributing to muscle production traits in chickens still needs to be further illuminated. Methods: A total of 150 1-day-old male 817 broilers were reared in a floor litter system. At the market age of 50 d, eighteen healthy 817 broilers were slaughtered and the left pectoralis major muscle sample from each bird was collected for RNA-seq sequencing. The birds were then plucked and eviscerated and the whole breast muscle was removed and weighed. Breast muscle yield was calculated as the ratio of the breast muscle weight to the eviscerated weight. To identify the co-expression networks and hub genes contributing to breast muscle yield in chickens, we performed weighted gene co-expression network analysis (WGCNA) based on the 18 transcriptome datasets of pectoralis major muscle from eighteen 817 broilers. Results: The WGCNA analysis classified all co-expressed genes in the pectoral muscle of 817 broilers into 44 modules. Among these modules, the turquoise and skyblue3 modules were found to be most significantly positively (r=0.78, p=1e-04) and negatively (r=-0.57, p=0.01) associated with breast meat yield, respectively. Further analysis identified several hub genes (e.g., DLX3, SH3RF2, TPM1, CAV3, MYF6, and CFL2) that involved in muscle structure and muscle development were identified as potential regulators of breast meat production. Conclusion: The present study has advanced our understanding of the molecular regulatory networks contributing to muscle growth and breast muscle production and will contribute to the molecular breeding of chickens in the future.

2.
Cell Death Differ ; 31(5): 592-604, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38514847

RESUMO

RB transcriptional corepressor 1 (RB) deletion is the most important genomic factor associated with the prognosis of castration-resistant prostate cancer (CRPC) patients receiving androgen receptor (AR) signaling inhibitor therapy. Loss of RB could support prostate cancer cell growth in a hormone-independent manner, but the underlying mechanism by which RB regulates tumor progression extends far beyond the cell cycle pathway. A previous study indicated that RB inactivates AKT signaling but has no effect on mTOR signaling in cancer cells. Here, we found that the S249/T252 site in RB is key to regulating the transcriptional activity of the tumor-promoting factor TRIM24 in CRPC, as identified through FXXXV mapping. The RB/TRIM24 complex functions through DUSP2, which serves as an intermediate bridge, to activate the mTOR pathway and promote prostate cancer progression. Accordingly, we designed RB-linker-proteolysis-targeting chimera (PROTAC) molecules, which decreased TRIM24 protein levels and inactivated the mTOR signaling pathway, thereby inhibiting prostate cancer. Therefore, this study not only elucidates the novel function of RB but also provides a theoretical basis for the development of new drugs for treating prostate cancer.


Assuntos
Transdução de Sinais , Serina-Treonina Quinases TOR , Masculino , Humanos , Serina-Treonina Quinases TOR/metabolismo , Linhagem Celular Tumoral , Animais , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Neoplasias da Próstata/genética , Proteína do Retinoblastoma/metabolismo , Proteínas de Transporte/metabolismo , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/genética , Camundongos , Camundongos Nus , Proliferação de Células
3.
Water Res ; 254: 121391, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38452528

RESUMO

Elemental sulfur-based denitrification (ESDeN) technology is known as a cost-saving alternative to its heterotrophic counterpart for nutrient removal from organic-deficient water. However, the traditional fixed-bed reactor (FixBR), as an extensively used process, suffers from a low denitrification rate and even performance deterioration during long-term operation. Herein, we proposed a novel elemental sulfur-based denitrifying moving-bed reactor (ESDeN-MovBR), in which a screw rotator was employed to drive the filled sulfur particles to be microfluidized vertically (a state of vertical-loop movement). Our results showed that the ESDeN-MovBR realized much superior and more stable denitrification performance compared to the ESDeN-FixBR, as indicated by 3.09-fold higher denitrification rate and over one order of magnitude lower intermediates (NO2- and N2O) yield, which could last for over 100 days. Further research revealed that the microfluidization of sulfur particles facilitated the expelling of nitrogen bubbles and excessive biomass, resulting in the prolongation of actual hydraulic retention time by over 80 % and could partially explain the higher denitrification rate in ESDeN-MovBR. The remaining contribution to the improvement of denitrification rate was suggested to be result from changes in biofilm properties, in which the biofilm thickness of ESDeN-MovBR was found to be 3.29 times thinner yet enriched with 2.52 times more autotrophic denitrifiers. This study offered a completely new solution to boost up the denitrification performance of ESDeN technology and provided in-depth evidence for the necessity of biofilm thickness control in such technology.


Assuntos
Reatores Biológicos , Desnitrificação , Enxofre , Processos Autotróficos , Nitrogênio , Nitratos
4.
Antioxidants (Basel) ; 13(2)2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38397774

RESUMO

Beyond its well-established role in diabetes management, metformin has gained attention as a promising therapeutic for inflammation-related diseases, largely due to its antioxidant capabilities. However, the mechanistic underpinnings of this effect remain elusive. Using in vivo zebrafish models of inflammation, we explored the impact of metformin on neutrophil recruitment and the underlying mechanisms involved. Our data indicate that metformin reduces histone (H3K18) lactylation, leading to the decreased production of reactive oxygen species (ROS) and a muted neutrophil response to both caudal fin injury and otic vesicle inflammation. To investigate the precise mechanisms through which metformin modulates neutrophil migration via ROS and H3K18 lactylation, we meticulously established the correlation between metformin-induced suppression of H3K18 lactylation and ROS levels. Through supplementary experiments involving the restoration of lactate and ROS, our findings demonstrated that elevated levels of both lactate and ROS significantly promoted the inflammatory response in zebrafish. Collectively, our study illuminates previously unexplored avenues of metformin's antioxidant and anti-inflammatory actions through the downregulation of H3K18 lactylation and ROS production, highlighting the crucial role of epigenetic regulation in inflammation and pointing to metformin's potential in treating inflammation-associated conditions.

5.
J Clin Neurosci ; 119: 70-75, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37988975

RESUMO

BACKGROUND: Patients with myasthenia gravis (MG) lose part of their working or living ability due to illness, and bring burden to caregivers. The purpose of this study was to explore the factors related to caregivers' disease family burden for MG patients in Northwest China. METHODS: The study utilized our Myasthenia Gravis database and distributed online questionnaires to both MG patients and their caregivers. The questionnaires included a general data collection form, the Patient Health Questionnaire-9 (PHQ-9) scale, and the Caregivers' Family Burden Scale of Disease (FBSD). Univariate analysis and multivariate linear regression analysis were run, with FBSD as the outcome variable for separate analyses. RESULTS: 178 MG patients were eligible for inclusion in the analysis, of whom 80 patients' caregivers had a positive family burden of MG. The daily activity burden of the family and the economic burden of the family were the heaviest among the six dimensions of the caregivers' family disease burdens. The factors independently associated with FBSD were depression symptom level, MG severity classification and family's monthly per capita income (p < 0.05). CONCLUSIONS: Depression symptom level, MG severity classification and family's monthly per capita income are independent factors related to the caregivers' disease family burden for MG patients.


Assuntos
Miastenia Gravis , Qualidade de Vida , Humanos , Estudos Transversais , Cuidadores , Efeitos Psicossociais da Doença , China/epidemiologia , Miastenia Gravis/epidemiologia , Inquéritos e Questionários
6.
Food Technol Biotechnol ; 61(3): 283-293, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38022876

RESUMO

Research background: Chilling injury is a major disorder affecting the quality of tropical and subtropical vegetables during low temperature storage. Snap bean (Phaseolus vulgaris L.) is sensitive to chilling injury. The main purpose of the present study is to investigate the alleviating effects of 1-methylcyclopropene (1-MCP) on chilling injury of snap bean. In addition, the related mechanisms were also detected from the perspective of the changes of antioxidant defense system. Experimental approach: Snap beans were exposed to different volume fractions of 1-MCP. After 24 h of treatment, snap beans were stored at 4 °C for up to 14 days. Chilling injury index, electrolyte leakage, titratable acidity and total soluble solids were determined. Contents of chlorophyll, ascorbic acid and malondialdehyde were assessed. The total antioxidant capacity, Fe(II) ion chelating capacity, scavenging capacities on free radicals and activities of antioxidant enzymes were detected. Total phenol content and activities of related metabolic enzymes were also determined. Results and conclusions: 1-MCP treatment reduced chilling injury index, electrolyte leakage rate and malondialdehyde content of snap beans. The amounts of total soluble solids, titratable acid, ascorbic acid and total chlorophyll in 1-MCP-treated snap beans were significantly higher than those of control. The snap beans treated with 1-MCP showed stronger total antioxidant capacity and metal chelating activity. The 1-MCP treatment enhanced scavenging effects of snap beans on superoxide, hydroxyl and 1,1-diphenyl-2-trinitrophenylhydrazine radicals. The activities of peroxidase, ascorbate peroxidase, superoxide dismutase and catalase in 1-MCP-treated group were higher than of control. The treatment also enhanced the accumulation of phenolic compounds in snap beans by regulating the activities of phenol-metabolizing enzymes such as shikimate dehydrogenase, phenylalanine ammonia lyase enzyme, cinnamic acid 4-hydroxylase and polyphenol oxidase. In conclusion, with the mechanism that involves the activation of enzymatic and non-enzymatic antioxidant systems, 1-MCP has the ability to avoid chilling injury of snap bean. Novelty and scientific contribution: This study gives insights into whether 1-MCP can regulate postharvest cold resistance in vegetables by enhancing the enzymatic antioxidant system and inducing the accumulation of non-enzymatic antioxidants. Considering the results, 1-MCP treatment could be an effective method to alleviate postharvest chilling injury of snap beans during low temperature storage.

8.
Neuroimage ; 282: 120398, 2023 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-37778420

RESUMO

Magnetic Resonance Imaging (MRI) is widely applied in medical diagnosis due to its excellent non-invasiveness. With the increasing intensity of static magnetic field (SMF), the safety assessment of MRI has been ongoing. In this study, zebrafish larvae were exposed to SMFs of 0.4, 3.0, and 9.4 T for 2 h (h), and we found that there was no significant difference in the number of spontaneous tail swings, heart rate, and body length of zebrafish larvae in the treatment groups. The expression of development-related genes shha, pygo1, mylz3 and runx2b in the three SMF groups was almost not significantly different from the control group. Behavior tests unveiled a notable reduction in both the average speed and duration of high-speed movements in zebrafish larvae across all three SMF groups. In addition, the 0.4 and 3.0 T SMFs increased the migration of neutrophils in caudal fin injury, and the expression of pro-inflammatory cytokines was also increased. To explore the mechanism of SMFs on zebrafish immune function, this study utilized aanat2-/- mutant fish to demonstrate the effect of melatonin (MT) involvement in SMFs on zebrafish immune function. This study provides experimental data for understanding the effects of SMFs on organisms, and also provides a new insight for exploring the relationship between magnetic fields and immune function.


Assuntos
Campos Magnéticos , Peixe-Zebra , Animais , Imunidade
9.
Artigo em Inglês | MEDLINE | ID: mdl-37788187

RESUMO

Text generative models trained via maximum likelihood estimation (MLE) suffer from the notorious exposure bias problem, and generative adversarial networks (GANs) are shown to have potential to tackle this problem. The existing language GANs adopt estimators, such as REINFORCE or continuous relaxations to model word probabilities. The inherent limitations of such estimators lead current models to rely on pretraining techniques (MLE pretraining or pretrained embeddings). Representation modeling methods (RMMs), which are free from those limitations, however, are seldomly explored because of their poor performance in previous attempts. Our analyses reveal that invalid sampling methods and unhealthy gradients are the main contributors to such unsatisfactory performance. In this work, we present two techniques to tackle these problems: dropout sampling and fully normalized long short-term memory network (LSTM). Based on these two techniques, we propose InitialGAN whose parameters are randomly initialized in full. Besides, we introduce a new evaluation metric, least coverage rate (LCR), to better evaluate the quality of generated samples. The experimental results demonstrate that the InitialGAN outperforms both MLE and other compared models. To the best of our knowledge, it is the first time a language GAN can outperform MLE without using any pretraining techniques.

10.
Cell Rep ; 42(10): 113179, 2023 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-37756160

RESUMO

Neutrophil recruitment to inflammatory sites appears to be an evolutionarily conserved strategy to fight against exogenous insults. However, the rhythmic characteristics and underlying mechanisms of neutrophil migration on a 24-h timescale are largely unknown. Using the advantage of in vivo imaging of zebrafish, this study explored how the circadian gene clock1a dynamically regulates the rhythmic recruitment of neutrophils to inflammatory challenges. We generated a clock1a mutant and found that neutrophil migration is significantly increased in caudal fin injury and lipopolysaccharide (LPS) injection. Transcriptome sequencing, chromatin immunoprecipitation (ChIP), and dual-luciferase reporting experiments suggest that the clock1a gene regulates neutrophil migration by coordinating the rhythmic expression of nfe212a and duox genes to control the reactive oxygen species (ROS) level. This study ultimately provides a visual model to expand the understanding of the rhythmic mechanisms of neutrophil recruitment on a circadian timescale in a diurnal organism from the perspective of ROS.


Assuntos
Ritmo Circadiano , Peixe-Zebra , Animais , Ritmo Circadiano/genética , Infiltração de Neutrófilos , Espécies Reativas de Oxigênio/metabolismo , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
11.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 48(5): 782-788, 2023 May 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-37539581

RESUMO

Leiomyosarcoma of urinary bladder (LMS-UB) is a highly malignant mesenchymal tumor, accounting for less than 0.5% of all bladder malignancies, with a predominant clinical presentation of hematuria. Here we report a case of low-grade LMS-UB. A 44-year-old male patient was admitted to the hospital with urodynia for 2 weeks. The patient's pelvis CT showed a mass on the right part of the bladder. For this reason, he was initially diagnosed with bladder cancer. We performed a robot-assisted laparoscopic enucleation of the bladder tumor and low-grade LMS-UB was diagnosed with the histopathological examination. He underwent 5 cycles of adjuvant chemotherapy after surgery. At 19months postoperative follow-up, the patient had no symptoms, recurrence, or distant metastasis. There is no report on the treatment of LMS-UB with minimally invasive enucleation worldwide. This case provides a new comprehensive treatment method of enucleation combined with adjuvant chemotherapy for early low-grade LMS-UB to reduce complications and improve patients' quality of life after surgery.


Assuntos
Laparoscopia , Leiomiossarcoma , Robótica , Neoplasias da Bexiga Urinária , Masculino , Humanos , Adulto , Bexiga Urinária/cirurgia , Leiomiossarcoma/cirurgia , Leiomiossarcoma/diagnóstico , Leiomiossarcoma/secundário , Qualidade de Vida , Pelve/patologia , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia , Laparoscopia/métodos
12.
Tissue Cell ; 82: 102096, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37201439

RESUMO

Chemoresistance is one of the dominant causes for tumor progression and recurrence of bladder cancer (BC). This paper investigated the effects of transcription factor c-MYC through promoting MMS19 expression on proliferation, metastasis and cisplatin (DDP) resistance in BC cells. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database were applied to acquire the needed BC gene data. The mRNA and protein levels of c-MYC and MMS19 were verified with q-PCR or Western blot assay. MTT and Transwell assays were utilized to detect cell viability and metastasis. Chromatin Immunoprecipitation (ChIP) assay and Luciferase reporter assay were exerted to confirm the relationship between c-MYC and MMS19. TCGA and GEO BC datasets results implied MMS19 could be an independent indicator for BC patients' prognosis. MMS19 expression was dramatically augmented in BC cell lines. Overexpression of MMS19 conduced to accelerate BC cells proliferation, metastasis and increase DDP resistance. c-MYC was positively correlated with MMS19 and acted as a transcription activator for MMS19 in BC cell lines and activated MMS19 expression. Overexpression of c-MYC facilitated BC cells proliferation, metastasis and DDP resistance. In conclusions, c-MYC gene was a transcriptional regulator of MMS19. Up-regulation of c-MYC facilitated BC cells proliferation, metastasis and DDP resistance by motivating MMS19 expression. This molecular mechanism between c-MYC and MMS19 exerts a crucial mission in BC tumorigenesis and DDP resistance, and may contribute to the diagnosis and therapy of BC for the time to come.


Assuntos
MicroRNAs , Neoplasias da Bexiga Urinária , Humanos , Linhagem Celular Tumoral , Proliferação de Células/genética , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Regulação para Cima , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética
13.
Front Immunol ; 14: 1141983, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37223097

RESUMO

Background: The safety of COVID-19 vaccines has been clarified in clinical trials; however, some immunocompromised patients, such as myasthenia gravis (MG) patients, are still hesitant to receive vaccines. Whether COVID-19 vaccination increases the risk of disease worsening in these patients remains unknown. This study aims to evaluate the risk of disease exacerbation in COVID-19-vaccinated MG patients. Methods: The data in this study were collected from the MG database at Tangdu Hospital, the Fourth Military Medical University, and the Tertiary Referral Diagnostic Center at Huashan Hospital, Fudan University, from 1 April 2022 to 31 October 2022. A self-controlled case series method was applied, and the incidence rate ratios were calculated in the prespecified risk period using conditional Poisson regression. Results: Inactivated COVID-19 vaccines did not increase the risk of disease exacerbation in MG patients with stable disease status. A few patients experienced transient disease worsening, but the symptoms were mild. It is noted that more attention should be paid to thymoma-related MG, especially within 1 week after COVID-19 vaccination. Conclusion: COVID-19 vaccination has no long-term impact on MG relapse.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Miastenia Gravis , Neoplasias do Timo , Humanos , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/efeitos adversos , Projetos de Pesquisa , Centros de Atenção Terciária
14.
Tissue Cell ; 82: 102078, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37060745

RESUMO

Prostate cancer (PCa) is a prevalent cause of morbidity and mortality. DHRS2-modified human umbilical cord mesenchymal stem cells-derived exosomes (hUC-MSCs-derived exos) function in PCa. We explored the mechanism of DHRS2-modified hUC-MSCs-derived exos in PCa cell malignant behaviors. DHRS2 expression levels in WPMY-1 cells and 4 PCa cell lines were detected by RT-qPCR and Western blot. 22Rv1/DU145 cells with high/low DHRS2 expression were selected to establish the low/high DHRS2 expression models by transfection. Cell proliferation and apoptosis were detected by CCK-8, colony formation assays, and flow cytometry. hUC-MSCs were identified by oil red O, alizarin staining, and flow cytometry. Exos were extracted from hUC-MSCs by ultracentrifugation and identified by transmission electron microscopy, Nano series-Nano-ZS, and Western blot. DU145 cells were selected for in vitro study to further study the effects of DHRS2-modified exos on cell proliferation and apoptosis. The effect of DHRS2-modified exos on cell cycle distribution was detected by flow cytometry. DHRS2 was repressed in PCa cells. DHRS2 overexpression suppressed PCa cell proliferation and promoted apoptosis. Exos were successfully isolated from hUC-MSC. DHRS2-modified hUC-MSCs-derived exos carried DHRS2 into PCa cells and blocked malignant behaviors. Briefly, DHRS2 was repressed in PCa cells. DHRS2-modified hUC-MSCs-derived exos blocked PCa cell proliferation and enhanced apoptosis.


Assuntos
Exossomos , Células-Tronco Mesenquimais , Neoplasias da Próstata , Masculino , Humanos , Exossomos/metabolismo , Apoptose/genética , Proliferação de Células/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Cordão Umbilical , Carbonil Redutase (NADPH)/metabolismo
15.
Nat Protoc ; 18(4): 1056-1089, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36526726

RESUMO

The multi-attribute method (MAM) is a liquid chromatography-mass spectrometry (LC-MS)-based method that is used to directly characterize and monitor numerous product quality attributes (PQAs) at the amino acid level of a biopharmaceutical product. MAM enables identity testing based on primary sequence verification, detection and quantitation of post-translational modifications and impurities. This ability to simultaneously and directly determine PQAs of therapeutic proteins makes MAM a more informative, streamlined and productive workflow than conventional chromatographic and electrophoretic assays. MAM relies on proteolytic digestion of the sample followed by reversed-phase chromatographic separation and high-resolution LC-MS analysis in two phases. First, a discovery study to determine quality attributes for monitoring is followed by the creation of a targeted library based on high-resolution retention time plus accurate mass analysis. The second aspect of MAM is the monitoring phase based on the target peptide library and new peak detection using differential analysis of the data to determine the presence, absence or change of any species that might affect the activity or stability of the biotherapeutic. The sample preparation process takes between 90 and 120 min, whereas the time spent on instrumental and data analyses might vary from one to several days for different sample sizes, depending on the complexity of the molecule, the number of attributes to be monitored and the information to be detailed in the final report. MAM is developed to be used throughout the product life cycle, from process development through upstream and downstream processes to quality control release or under current good manufacturing practices regulations enforced by regulatory agencies.


Assuntos
Anticorpos Monoclonais , Processamento de Proteína Pós-Traducional , Fluxo de Trabalho , Anticorpos Monoclonais/química , Cromatografia Líquida/métodos , Espectrometria de Massas/métodos
16.
Neural Regen Res ; 18(3): 577-581, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36018180

RESUMO

Axon regeneration of central neurons is a complex process that is tightly regulated by multiple extrinsic and intrinsic factors. The expression levels of distinct genes are changed after central neural system (CNS) injury and affect axon regeneration. A previous study identified dusp2 as an upregulated gene in zebrafish with spinal cord injury. Here, we found that dual specificity phosphatase 2 (DUSP2) is a negative regulator of axon regeneration of the Mauthner cell (M-cell). DUSP2 is a phosphatase that mediates the dephosphorylation of JNK. In this study, we knocked out dusp2 by CRISPR/Cas9 and found that M-cell axons of dusp2-/- zebrafish had a better regeneration at the early stage after birth (within 8 days after birth), while those of dusp2+/- zebrafish did not. Overexpression of DUSP2 in Tg (Tol 056) zebrafish by single-cell electroporation retarded the regeneration of M-cell axons. Western blotting results showed that DUSP2 knockout slightly increased the levels of phosphorylated JNK. These findings suggest that knocking out DUSP2 promoted the regeneration of zebrafish M-cell axons, possibly through enhancing JNK phosphorylation.

17.
J Am Soc Mass Spectrom ; 33(9): 1659-1677, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36018776

RESUMO

The multi-attribute method (MAM) was conceived as a single assay to potentially replace multiple single-attribute assays that have long been used in process development and quality control (QC) for protein therapeutics. MAM is rooted in traditional peptide mapping methods; it leverages mass spectrometry (MS) detection for confident identification and quantitation of many types of protein attributes that may be targeted for monitoring. While MAM has been widely explored across the industry, it has yet to gain a strong foothold within QC laboratories as a replacement method for established orthogonal platforms. Members of the MAM consortium recently undertook an interlaboratory study to evaluate the industry-wide status of MAM. Here we present the results of this study as they pertain to the targeted attribute analytics component of MAM, including investigation into the sources of variability between laboratories and comparison of MAM data to orthogonal methods. These results are made available with an eye toward aiding the community in further optimizing the method to enable its more frequent use in the QC environment.


Assuntos
Benchmarking , Proteínas , Espectrometria de Massas/métodos , Mapeamento de Peptídeos/métodos , Controle de Qualidade
18.
Front Oncol ; 12: 957892, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35965573

RESUMO

Background: This study aimed to analyze the pathological characteristics and predictive factors of prostate biopsy in men with PSA levels below 4.0 ng/ml. Patients and methods: We retrospectively analyzed 158 patients who underwent prostate biopsy with PSA levels below 4.0 ng/ml. Pathological results were statistically analyzed. The logistic regression analysis was used to determine the predictive factors for malignant outcomes. Subgroup analysis was performed on patients who received surgery and the postoperative pathological upgrading was counted. Results: A total of 143 patients were enrolled. The tumor detection rate was 20.3%. Among these patients, most of them (79.3%) had prostate adenocarcinoma, but rare malignant tumors also accounted for 20.7%. Logistic regression analysis indicated that the only independent predictive factor for a positive prostate biopsy was the PI-RADS score. For prostate adenocarcinoma cases, 95.7% of them were organ localized and 47.8% of cases were clinically significant. Subgroup analysis was performed on 14 patients who received surgical treatment. 28.6% of patients were upgraded to clinically significant prostate cancer, while 64.3% of patients had an upgrade in tumor stage. Conclusion: Our study indicated that 20.3% of men with PSA levels between 0 and 4.0 ng/ml were diagnosed with prostate malignancies. Among these patients, most of them (79.3%) were diagnosed with prostate adenocarcinoma, and several uncommon types of malignancies were also detected in 20.7% of patients. The only risk factor for a positive biopsy in patients with a low PSA concentration was the PI-RADS score. It should be emphasized that the invasiveness of PCa patients diagnosed by biopsy may be underestimated as more than half of patients will upgrade their Gleason score or clinical stages after surgery. Thus, clinicians should pay more attention to patients with PSA levels between 0 and 4.0 ng/ml.

19.
Biomed Pharmacother ; 153: 113268, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35777221

RESUMO

Fluoxetine (FLX), a selective serotonin reuptake inhibitor (SSRI), increases the serotonin levels in the brain to treat depression. Antidepressants have been demonstrated to modulate circadian rhythm, but the underlying mechanisms by which antidepressants regulate circadian rhythm require more research. This study aimed to investigate the role of FLX on circadian rhythm by analyzing the movement behavior and internal circadian oscillations in zebrafish. The results showed that the expression of clock genes clock1a and bmal1b was significantly down-regulated, and the amplitude reduction and phase shift were observed after FLX treatment. Furthermore, FLX exposure inhibited the expression of aanat2, which led to a decrease in nocturnal melatonin secretion. aanat2-/- larvae showed disrupted circadian rhythm. These findings may help reveal the effect of FLX exposure on the circadian rhythm and locomotor activity. It may provide theoretical data for the clinical application of FLX.


Assuntos
Fluoxetina , Melatonina , Animais , Antidepressivos/farmacologia , Ritmo Circadiano/genética , Fluoxetina/farmacologia , Melatonina/metabolismo , Melatonina/farmacologia , Peixe-Zebra/metabolismo
20.
Chronobiol Int ; 39(10): 1307-1319, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35880245

RESUMO

A variety of devices used in daily life and biomedical field will generate magnetic fields with different parameters, raising concern about their influences on people's physiological functions. Multiple experimental works have been devoted to the influences of magnetic fields on circadian rhythms, yet the findings were not always consistent due to the differences in magnetic field parameters and experimental organisms. Also, clear regulatory mechanisms have not been found. By systematizing the major achievements in research on magnetic and circadian rhythms based on magnetic flux density and analyzing the potential mechanisms of the magnetic fields affecting circadian rhythms, this review sheds light on the effects of magnetic fields on circadian rhythms and the potential applications in biomedicine.


Assuntos
Ritmo Circadiano , Campos Magnéticos , Ritmo Circadiano/fisiologia , Humanos
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