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1.
Mol Med Rep ; 30(3)2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38963039

RESUMO

 The incidence of Alzheimer's disease (AD) is rising globally, yet its treatment and prediction of this condition remain challenging due to the complex pathophysiological mechanisms associated with it. Consequently, the objective of the present study was to analyze and characterize the molecular mechanisms underlying ferroptosis­related genes (FEGs) in the pathogenesis of AD, as well as to construct a prognostic model. The findings will provide new insights for the future diagnosis and treatment of AD. First, the AD dataset GSE33000 from the Gene Expression Omnibus database and the FEGs from FerrDB were obtained. Next, unsupervised cluster analysis was used to obtain the FEGs that were most relevant to AD. Subsequently, enrichment analyses were performed on the FEGs to explore biological functions. Subsequently, the role of these genes in the immune microenvironment was elucidated through CIBERSORT. Then, the optimal machine learning was selected by comparing the performance of different machine learning models. To validate the prediction efficiency, the models were validated using nomograms, calibration curves, decision curve analysis and external datasets. Furthermore, the expression of FEGs between different groups was verified using reverse transcription quantitative PCR and western blot analysis. In AD, alterations in the expression of FEGs affect the aggregation and infiltration of certain immune cells. This indicated that the occurrence of AD is strongly associated with immune infiltration. Finally, the most appropriate machine learning models were selected, and AD diagnostic models and nomograms were built. The present study provided novel insights that enhance understanding with regard to the molecular mechanism of action of FEGs in AD. Moreover, the present study provided biomarkers that may facilitate the diagnosis of AD.


Assuntos
Doença de Alzheimer , Ferroptose , Doença de Alzheimer/genética , Doença de Alzheimer/imunologia , Ferroptose/genética , Humanos , Aprendizado de Máquina , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Biomarcadores , Prognóstico , Regulação da Expressão Gênica , Biologia Computacional/métodos
2.
Sci Data ; 11(1): 735, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38971852

RESUMO

The leaf beetle Ophraella communa LeSage (Coleoptera: Chrysomelidae) is an effective biological control agent of the common ragweed. Here, we assembled a chromosome-level genome of the O. communa by combining Illumina, Nanopore, and Hi-C sequencing technologies. The genome size of the final genome assembly is 733.1 Mb, encompassing 17 chromosomes, with an improved contig N50 of 7.05 Mb compared to the original version. Genome annotation reveals 25,873 protein-coding genes, with functional annotations available for 22,084 genes (85.35%). Non-coding sequence annotation identified 204 rRNAs, 626 tRNAs, and 1791 small RNAs. Repetitive elements occupy 414.41 Mb, constituting 57.76% of the genome. This high-quality genome is fundamental for advancing biological control strategies employing O. communa.


Assuntos
Besouros , Genoma de Inseto , Besouros/genética , Animais , Anotação de Sequência Molecular , Cromossomos de Insetos
3.
Imeta ; 3(2): e180, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38882491

RESUMO

Inflammatory bowel disease (IBD) is a significant global health concern. The gut microbiota plays an essential role in the onset and development of IBD. Sanghuangporus (SH), a traditional Chinese medicinal mushroom, has excellent anti-inflammatory effects and is effective at modulating the gut microbiota. Despite these attributes, the specific anticolitic effects of SH and the mechanisms through which the gut microbiota mediates its benefits remain unclear. Herein, we demonstrated that polyphenol-rich extract from SH effectively alleviated the pathological symptoms of dextran sodium sulfate (DSS)-induced colitis in mice by modulating the gut microbiota. Treatment with SH distinctly enriched Alistipes, especially Alistipes onderdonkii, and its metabolite 5-hydroxyindole-3-acetic acid (5HIAA). Oral gavage of live A. onderdonkii or 5HIAA potently mitigated DSS-induced colitis in mice. Moreover, both 5HIAA and SH significantly activated the aromatic hydrocarbon receptor (AhR), and the administration of an AhR antagonist abrogated their protective effects against colitis. These results underscore the potent efficacy of SH in diminishing DSS-induced colitis through the promotion of A. onderdonkii and 5HIAA, ultimately activating AhR signaling. This study unveils potential avenues for developing therapeutic strategies for colitis based on the interplay between SH and the gut microbiota.

4.
Cancer Lett ; 592: 216937, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38704134

RESUMO

Dysfunctional bone marrow (BM) endothelial progenitor cells (EPCs) with high levels of reactive oxygen species (ROS) are responsible for defective hematopoiesis in poor graft function (PGF) patients with acute leukemia or myelodysplastic neoplasms post-allotransplant. However, the underlying mechanism by which BM EPCs regulate their intracellular ROS levels and the capacity to support hematopoiesis have not been well clarified. Herein, we demonstrated decreased levels of peroxisome proliferator-activated receptor delta (PPARδ), a lipid-activated nuclear receptor, in BM EPCs of PGF patients compared with those with good graft function (GGF). In vitro assays further identified that PPARδ knockdown contributed to reduced and dysfunctional BM EPCs, characterized by the impaired ability to support hematopoiesis, which were restored by PPARδ overexpression. Moreover, GW501516, an agonist of PPARδ, repaired the damaged BM EPCs triggered by 5-fluorouracil (5FU) in vitro and in vivo. Clinically, activation of PPARδ by GW501516 benefited the damaged BM EPCs from PGF patients or acute leukemia patients in complete remission (CR) post-chemotherapy. Mechanistically, we found that increased expression of NADPH oxidases (NOXs), the main ROS-generating enzymes, may lead to elevated ROS level in BM EPCs, and insufficient PPARδ may trigger BM EPC damage via ROS/p53 pathway. Collectively, we found that defective PPARδ contributes to BM EPC dysfunction, whereas activation of PPARδ in BM EPCs improves their hematopoiesis-supporting ability after myelosuppressive therapy, which may provide a potential therapeutic target not only for patients with leukemia but also for those with other cancers.


Assuntos
Células Progenitoras Endoteliais , Hematopoese , PPAR delta , Espécies Reativas de Oxigênio , Adulto , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Adulto Jovem , Células da Medula Óssea/metabolismo , Células da Medula Óssea/efeitos dos fármacos , Células Progenitoras Endoteliais/metabolismo , Células Progenitoras Endoteliais/efeitos dos fármacos , Fluoruracila/farmacologia , Hematopoese/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Síndromes Mielodisplásicas/patologia , Síndromes Mielodisplásicas/metabolismo , Síndromes Mielodisplásicas/tratamento farmacológico , NADPH Oxidases/metabolismo , PPAR delta/metabolismo , PPAR delta/genética , Espécies Reativas de Oxigênio/metabolismo , Tiazóis/farmacologia , Proteína Supressora de Tumor p53/metabolismo
5.
Front Surg ; 11: 1323614, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38567358

RESUMO

Background: A ruptured sinus of Valsalva aneurysm can lead to rapid heart failure and sudden cardiac death. Management of patients who develop severe heart failure and need to be transferred to a specialized hospital for surgical treatment can be challenging. In patients with severe shock due to a ruptured sinus of Valsalva aneurysm into the right atrium, extracorporeal membrane oxygenation (ECMO) transport is an effective means to ensure patient safety, but increases the right cardiac load. We report the experience of veno-arterial (VA) ECMO transport in the treatment of acute cardiogenic shock caused by rupture of a congenital sinus of Valsalva aneurysm. Case presentation: We describe the case of an 18-year-old male who began having acute episodes of chest pain, shortness of breath, palpitations, and dizziness 18 h before presenting to the emergency department. An echocardiogram revealed an acute ruptured sinus of Valsalva aneurysm and a shunt to the right atrium. The patient presented with severe shock. VA-ECMO was administered to ensure safe transport to the cardiac center. The outcome of emergency surgical repair was good. The patient was on ECMO for 8 h. He returned to the general ward after 7 days and was successfully discharged after 40 days. He had good exercise tolerance 2 years after surgery and no evidence of heart failure. Conclusion: Although ECMO transport can increase right cardiac load, it is an effective and safe method to move patients with severe shock caused by a ruptured sinus of Valsalva aneurysm into the right atrium. Methods to decrease right cardiac load, such as decreasing ECMO flow combined with cardiotonic drugs, should be adopted. Successful treatment involves rapid establishment of cardiopulmonary bypass and urgent repair of the ruptured sinus of Valsalva aneurysm.

6.
Acta Psychol (Amst) ; 246: 104277, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38642454

RESUMO

This study examined the impact of brief mindfulness meditation (BMM) training on attention function and dispositional mindfulness in young males. 126 male participants aged 18-26 from the security industry were recruited, with 66 participants (M = 22.84, SD = 2.41) undergoing 4-week mindfulness meditation training and 60 participants (M = 23.07, SD = 2.29) in the active control group. The intervention was integrated into the participants' schedules. Measures included Five Facets Mindfulness Questionnaires (FFMQ), concentration and assignment attention tasks, Attention Network Test (ANT), and saliva cortisol concentration. Findings indicate that brief mindfulness meditation training led to significant improvements in participants' FFMQ scores), with marginally significant enhancements in the executive control network. However, it had no discernible effect on alertness and orientation networks. Additionally, brief mindfulness meditation training enhanced attention allocation to light stimulation and prolonged individual attention. Surprisingly, there was no observed decrease in saliva cortisol concentration among meditation training participants. However, this study did not find a decrease in saliva cortisol concentration in the brief mindfulness meditation group. In conclusion, this study highlights the potential of a 4-week brief mindfulness meditation training program to enhance dispositional mindfulness and specific aspects of attention function in young men, offering practical insights into the benefits of mindfulness meditation practices for this demographic.


Assuntos
Atenção , Hidrocortisona , Meditação , Atenção Plena , Saliva , Humanos , Masculino , Atenção Plena/métodos , Atenção/fisiologia , Adulto Jovem , Hidrocortisona/metabolismo , Adulto , Saliva/metabolismo , Adolescente , Função Executiva/fisiologia
7.
J Chem Ecol ; 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38372833

RESUMO

The melon fly, Zeugodacus cucurbitae (Coquillett), is a major invasive pest, widely distributed in the Asia-Pacific region and some parts of Africa. Melon fly attractants could improve the effectiveness of current pest management measures. Previous studies have shown that some host fruits are attractive to melon flies but few have investigated the chemical compounds responsible for their attraction. In this study, we aimed to identify the volatile compounds from Luffa acutangula L that attract Z. cucurbitae. In headspace trapping, chemical profiling identified 19 compounds from ridge gourds, with 1-pentadecene being the major component. EAG results revealed that seven compounds elicited antennal responses in Z. cucurbitae, and significant differences in antennal responses between male and female Z. cucurbitae adults were recorded to p-xylene, alpha-pinene, and 1-octadecene. Behavioral experiments demonstrated that the EAG-active compounds methyl isovalerate and methyl myristate had either attractive or repellent effects on Z. cucurbitae at different concentrations, and 1-octadecene attracted Z. cucurbitae. Our findings provide a theoretical basis producing repellents or attractants for effective Integrated Pest Management of Z. cucurbitae.

9.
Technol Health Care ; 32(2): 705-718, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37483032

RESUMO

BACKGROUND: With improving living standards, the incidence of cervical spondylotic myelopathy (CSM) has become increasingly high. OBJECTIVE: The study aims to explore the effect of diversified health-promoting models on rehabilitation exercises in patients with CSM after an operation. METHOD: This was a randomized controlled trial, wherein 107 patients with CSM treated by neurosurgery were selected as the subjects. Of those, 52 patients in the control group adopted the conventional health-promoting model, while the remaining 55 patients in the intervention group adopted diversified health-promoting models. The effect of rehabilitation exercises in the two groups was evaluated according to the self-efficacy rehabilitation outcome scale, grip strength measurement of the affected limb, and Barthel index. RESULTS: At Day 3 post-operation and before discharge, the self-efficacy management of rehabilitation exercises in the intervention group was better than that of the control group (P< 0.05). The grip strength measurement of the affected limb, Japanese Orthopedic Association score of the cervical vertebra, and Barthel index of the two groups at Day 3 post-operation were lower than before the intervention and were not statistically significant (P> 0.05). However, these three items before discharge were improved when compared with those of before intervention and were statistically significant (P< 0.05). CONCLUSION: Postoperative rehabilitation exercises guided by the diversified health-promoting models for patients with CSM can improve the patients' self-efficacy management ability in rehabilitation exercises, help improve grip strength, and promote the recovery of cervical vertebra function, thereby improving the patients' quality of life.


Assuntos
Doenças da Medula Espinal , Espondilose , Humanos , Qualidade de Vida , Espondilose/cirurgia , Espondilose/complicações , Doenças da Medula Espinal/cirurgia , Doenças da Medula Espinal/etiologia , Vértebras Cervicais/cirurgia , Resultado do Tratamento , Terapia por Exercício
10.
Surg Innov ; 31(1): 111-122, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38050944

RESUMO

BACKGROUND: In recent years, numerous innovative yet challenging surgeries, such as minimally invasive procedures, have introduced an overwhelming amount of new technologies, increasing the cognitive load for surgeons and potentially diluting their attention. Cognitive support technologies (CSTs) have been in development to reduce surgeons' cognitive load and minimize errors. Despite its huge demands, it still lacks a systematic review. METHODS: Literature was searched up until May 21st, 2021. Pubmed, Web of Science, and IEEExplore. Studies that aimed at reducing the cognitive load of surgeons were included. Additionally, studies that contained an experimental trial with real patients and real surgeons were prioritized, although phantom and animal studies were also included. Major outcomes that were assessed included surgical error, anatomical localization accuracy, total procedural time, and patient outcome. RESULTS: A total of 37 studies were included. Overall, the implementation of CSTs had better surgical performance than the traditional methods. Most studies reported decreased error rate and increased efficiency. In terms of accuracy, most CSTs had over 90% accuracy in identifying anatomical markers with an error margin below 5 mm. Most studies reported a decrease in surgical time, although some were statistically insignificant. DISCUSSION: CSTs have been shown to reduce the mental workload of surgeons. However, the limited ergonomic design of current CSTs has hindered their widespread use in the clinical setting. Overall, more clinical data on actual patients is needed to provide concrete evidence before the ubiquitous implementation of CSTs.


Assuntos
Salas Cirúrgicas , Cirurgiões , Humanos , Carga de Trabalho/psicologia , Cirurgiões/psicologia , Cognição
11.
Anim Nutr ; 16: 34-44, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38131029

RESUMO

Skatole, a strong fecal odor substance, is generated through microbial degradation of tryptophan in the animal hindgut. It easily accumulates in adipose tissue and affects meat quality. In this study, the effect of mulberry leaf supplementation on skatole in finishing pigs was studied. In a 35-day trial, 20 finishing pigs (barrows and gilts) were fed with a basal diet or basal diet with 6% mulberry leaves. Growth performance of the pigs (n = 10) was automatically recorded by a performance-testing feeder system and 8 pigs in each treatment were slaughtered and sampled for the remaining tests. Skatole and short-chain fatty acids were detected using HPLC and gas chromatography, respectively. Fecal microbiota were analyzed using 16S rRNA gene sequencing. The metabolomics analysis of feces and serum was performed with UHPLC-MS/MS. The major cytochrome P450 (CYP) enzymes that catalyze skatole degradation in the liver were tested by using RT-PCR and Western blot. Effects of major bioactive compounds in mulberry leaves on the CYP genes were verified in the hepatic cell line HepG2 in an in vitro test (n = 3). In finishing pigs, mulberry leaf supplementation had no significant effect on the average daily gain, average daily feed intake, and feed conversion ratio (P > 0.05), but reduced skatole levels in feces, serum, and backfat (P < 0.05), and increased acetic acid levels in feces (P = 0.027). Mulberry leaf supplementation decreased the relative abundance of the skatole-producing bacteria Megasphaera and Olsenella (P < 0.05). Indole-3-acetic acid, the intermediate that is essential for skatole production, was significantly reduced in feces by mulberry leaf supplementation (P < 0.05) and was positively correlated with skatole content in feces (P = 0.004). In pigs treated with mulberry leaves, liver CYP1A1 expression was increased (P < 0.05) and was negatively correlated with skatole content in backfat (P = 0.045). The in vitro test demonstrated that mulberry leaf polyphenols and polysaccharides could directly stimulate CYP1A1 expression in hepatic cells. These findings suggest that mulberry leaf supplementation reduces skatole production and deposition in finishing pigs by regulating the gut microbiota and promoting skatole degradation in liver.

12.
Int J Mol Sci ; 24(23)2023 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-38069395

RESUMO

Zn2+-dependent histone deacetylases (HDACs) are enzymes that regulate gene expression by removing acetyl groups from histone proteins. These enzymes are essential in all living systems, playing key roles in cancer treatment and as potential pesticide targets. Previous phylogenetic analyses of HDAC in certain species have been published. However, their classification and evolutionary origins across biological kingdoms remain unclear, which limits our understanding of them. In this study, we collected the HDAC sequences from 1451 organisms and performed analyses. The HDACs are found to diverge into three classes and seven subclasses under divergent selection pressure. Most subclasses show species specificity, indicating that HDACs have evolved with high plasticity and diversification to adapt to different environmental conditions in different species. In contrast, HDAC1 and HDAC3, belonging to the oldest class, are conserved and crucial in major kingdoms of life, especially HDAC1. These findings lay the groundwork for the future application of HDACs.


Assuntos
Histonas , Zinco , Filogenia , Zinco/metabolismo , Histona Desacetilase 1/genética , Histona Desacetilase 1/metabolismo
13.
Sci Data ; 10(1): 848, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-38040744

RESUMO

The fruit fly Zeugodacus tau (Diptera: Tephritidae) is a major pest of melons and other cucurbits in Southeast Asia. In this study, we used Illumina, Nanopore, and Hi-C sequencing technologies to assemble a reference genome of Z. tau at the chromosomal level. The assembled genome was 421.79 Mb and consisted of six chromosomes (one X-chromosome + five autosomes). The contig N50 was 4.23 Mb. We identified 20,922 protein-coding genes, of which 17,251 (82.45%) were functionally annotated. Additionally, we found 247 rRNAs, 435 tRNAs, 67 small nuclear RNAs, and 829 small RNAs in the genome. Repetitive elements accounted for 55.30 Mb (13.15%) of the genome. This high-quality genome assembly is valuable for evolutionary and genetic studies of Z. tau and its relative species.


Assuntos
Genoma de Inseto , Tephritidae , Animais , Cromossomos , Anotação de Sequência Molecular , Filogenia , Sequências Repetitivas de Ácido Nucleico , Tephritidae/genética
14.
Drug Des Devel Ther ; 17: 3151-3167, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37876500

RESUMO

Objective: Traditional Chinese medicine Polygonum cuspidatum (PC) has significant effects on reducing pain. In this study, we investigated the analgesic effects of the alcohol extract of PC on three types of inflammatory pain and explored its mechanism. Methods: Potential targets for the analgesic effects of the main active components of PC alcohol extract were screened by network pharmacology and molecular docking. Three different inflammatory pain mouse models (acetic acid twisting, formalin foot swelling, and xylene ear swelling) were used to study the analgesic effects of PC. The expression of latent signaling pathways in L4-6 spinal cord tissues in formalin foot swelling mice was evaluated using real-time qPCR (RT-qPCR), Western blot (WB), and immunohistochemistry (IHC) analyses. Results: Network pharmacology analysis shows that PC analgesic mechanism is related to the MAPK/ERK signaling pathway. The five main active components of PC have good docking ability with JNK and p38. PC alcohol extract significantly reduced the pain behavior and alleviated inflammatory reactions in three mouse models, inhibited the mRNA and protein phosphorylation levels of JNK, ERK, p38, and CREB in spinal cord tissues. Conclusion: PC alcohol extract can inhibit inflammation and alleviate pain, which is related to its inhibition of the MAPK/ERK signaling pathway in spinal cord. Thus, PC alcohol extract is a promising candidate for pain treatment.


Assuntos
Fallopia japonica , Ratos , Camundongos , Animais , Fallopia japonica/química , Ratos Sprague-Dawley , Simulação de Acoplamento Molecular , Dor/tratamento farmacológico , Transdução de Sinais , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Etanol , Inflamação/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Modelos Animais de Doenças , Formaldeído/farmacologia
15.
Huan Jing Ke Xue ; 44(8): 4637-4646, 2023 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-37694656

RESUMO

A reasonable definition of carbon emission responsibility and inter-provincial carbon compensation is an important approach to promote regional coordinated emission reduction. Here, based on the 2017 multi-regional input-output table, carbon emissions from provinces were decomposed by using the value-added trade decomposition method, the embodied carbon flows between provinces were measured, and a differentiated carbon compensation mechanism based on emission reduction cost was designed, which provides the reference for China to carry out horizontal carbon compensation. The main conclusions were as follows:①the carbon emissions caused by the final demand within the province accounted for 53.56%, whereas the carbon emissions caused by the final demand outside the province accounted for 32.49%. The embodied carbon flows among provinces showed a significant existence. ②The embodied carbon showed a significant flow characteristic of transferring from the northern and central regions to the Beijing-Tianjin region and the southeastern coastal regions. ③From the perspective of producers, consumers, and shared responsibility, the total carbon emissions of provinces and cities were equal, and the distribution idea of shared responsibility reflected the "benefit principle." ④There were differences in carbon emission reduction costs between provinces. In areas with low carbon emission reduction costs, direct carbon emissions were high, and the industries were dominated by heavy industry. In areas with high carbon emission reduction costs, direct carbon emissions were low, and the industries were high-tech industries and service industries. ⑤The amount of compensation to be paid/accepted by provinces varied based on the cost of emission reduction. Among them, Guangdong had the highest amount of compensation to be paid, and Inner Mongolia had the highest amount of compensation to be accepted.

16.
Front Pediatr ; 11: 1172282, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37622084

RESUMO

Objective: The study aimed to monitor fetuses with tetralogy of Fallot (TOF) after prenatal counseling and how it influenced the decision of parents to terminate the pregnancy. Methods: Fetuses with isolated TOF diagnosed between January 2019 and December 2021 were prospectively enrolled. The follow-up period extended until termination or 6 months after the operation. Results: Of the 1,026 fetuses diagnosed with cardiac defects, 129 were identified to have isolated TOF and completed the follow-up. A total of 55 (42.6%) fetuses were terminated, with larger maternal age (odds ratio: 0.893, 95% confidence interval: 0.806-0.989, P = 0.031) as the protective factor. The maternal anxiety score, gestational weeks, and pulmonary-to-aortic-diameter ratio lost significance in multivariate analysis. Subjectively, the two most common reasons for terminating the pregnancy were worries about the prognosis (41.8%) and concerns about the possible suffering of the unborn child (18.2%). The prenatal diagnosis was accurate in 73 of the 74 (98.6%) live births. Out of the 64 live births that underwent surgical repair in our center, 57 (89.1%) received primary repair, with a median age of 104 days, and 49 (76.6%) underwent valve-sparing repair. No perioperative death occurred. Conclusions: Termination for fetuses with TOF remains common in China. Live births with TOF can be safely and effectively managed.

17.
Cell Rep Med ; 4(8): 101133, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37586317

RESUMO

New York esophageal squamous cell carcinoma-1 (NY-ESO-1)-specific T cell receptor (TCR) T cell therapy is effective in tumors with NY-ESO-1 expression, but a safe and effective TCR-T cell therapeutic protocol remains to be improved. Here, we report a phase 1 investigational new drug clinical trial with TCR affinity-enhanced specific T cell therapy (TAEST16001) for targeting NY-ESO-1. Enrolled patients receive TAEST16001 cell infusion after dose-reduced lymphodepletion with cyclophosphamide (15 mg/kg/day × 3 days) combined with fludarabine (20 mg/m2/day × 3 days), and the TCR-T cells are maintained with low doses of interleukin-2 injection post-adoptive transfer. Analysis of 12 patients treated with the regimen demonstrates no treatment-related serious adverse events. The overall response rate is 41.7%. The median progression-free survival is 7.2 months, and the median duration of response is 13.1 months. The protocol of TAEST16001 cells delivers a safe and highly effective treatment for patients with advanced soft tissue sarcoma (ClinicalTrials.gov: NCT04318964).


Assuntos
Imunoterapia Adotiva , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Antígenos HLA-A/metabolismo , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/metabolismo , Sarcoma/metabolismo , Neoplasias de Tecidos Moles/terapia , Linfócitos T
18.
Genes Genomics ; 45(9): 1127-1141, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37438657

RESUMO

BACKGROUND: MIKC type MADS-box transcription factors are one of the largest gene families and play a pivotal role in flowering time and flower development. Chimonanthus salicifolius belongs to the family Calycanthaceae and has a unique flowering time and flowering morphology compared to other Chimonanthus species, but the research on MIKC type MADS-box gene family of C. salicifolius has not been reported. OBJECTIVE: Identification, comprehensive bioinformatic analysis, the expression pattern of MIKC-type MADS-box gene family from different tissues of C. salicifolius. METHODS: Genome-wide investigation and expression pattern under different tissues of the MIKC-type MADS-box gene family in C. salicifolius, and their phylogenetic relationships, evolutionary characteristics, gene structure, motif distribution, promoter cis-acting element were performed. RESULTS: A total of 29 MIKC-type MADS-box genes were identified from the whole genome sequencing. Interspecies synteny analysis revealed more significant collinearity between C. salicifolius and the magnoliids species compared to eudicots and monocots. MIKC-type MADS-box genes from the same subfamily share similar distribution patterns, gene structure, and expression patterns. Compared with Arabidopsis thaliana, Nymphaea colorata, and Chimonanthus praecox, the FLC genes were absent in C. salicifolius, while the AGL6 subfamily was expanded in C. salicifolius. The selectively expanded promoter (AGL6) and lack of repressor (FLC) genes may explain the earlier flowering in C. salicifolius. The loss of the AP3 homologous gene in C. salicifolius is probably the primary cause of the morphological distinction between C. salicifolius and C. praecox. The csAGL6a gene is specifically expressed in the flowering process and indicates the potential function of promoting flowering. CONCLUSION: This study offers a genome-wide identification and expression profiling of the MIKC-types MADS-box genes in the C. salicifolius, and establishes the foundation for screening flowering development genes and understanding the potential function of the MIKC-types MADS-box genes in the C. salicifolius.


Assuntos
Genoma de Planta , Proteínas de Domínio MADS , Proteínas de Domínio MADS/genética , Proteínas de Domínio MADS/metabolismo , Filogenia , Expressão Gênica , Fatores de Transcrição/genética
19.
Sci China Life Sci ; 66(11): 2553-2570, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37289327

RESUMO

Aplastic anemia (AA) is a life-threatening disease characterized by bone marrow (BM) failure and pancytopenia. As an important component of the BM microenvironment, endothelial cells (ECs) play a crucial role in supporting hematopoiesis and regulating immunity. However, whether impaired BM ECs are involved in the occurrence of AA and whether repairing BM ECs could improve hematopoiesis and immune status in AA remain unknown. In this study, a classical AA mouse model and VE-cadherin blocking antibody that could antagonize the function of ECs were used to validate the role of BM ECs in the occurrence of AA. N-acetyl-L-cysteine (NAC, a reactive oxygen species scavenger) or exogenous EC infusion was administered to AA mice. Furthermore, the frequency and functions of BM ECs from AA patients and healthy donors were evaluated. BM ECs from AA patients were treated with NAC in vitro, and then the functions of BM ECs were evaluated. We found that BM ECs were significantly decreased and damaged in AA mice. Hematopoietic failure and immune imbalance became more severe when the function of BM ECs was antagonized, whereas NAC or EC infusion improved hematopoietic and immunological status by repairing BM ECs in AA mice. Consistently, BM ECs in AA patients were decreased and dysfunctional. Furthermore, dysfunctional BM ECs in AA patients led to their impaired ability to support hematopoiesis and dysregulate T cell differentiation toward proinflammatory phenotypes, which could be repaired by NAC in vitro. The reactive oxygen species pathway was activated, and hematopoiesis- and immune-related signaling pathways were enriched in BM ECs of AA patients. In conclusion, our data indicate that dysfunctional BM ECs with impaired hematopoiesis-supporting and immunomodulatory abilities are involved in the occurrence of AA, suggesting that repairing dysfunctional BM ECs may be a potential therapeutic approach for AA patients.


Assuntos
Anemia Aplástica , Humanos , Animais , Camundongos , Anemia Aplástica/terapia , Medula Óssea , Células Endoteliais/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Células da Medula Óssea/metabolismo
20.
Front Cardiovasc Med ; 10: 1200553, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37363099

RESUMO

Introduction: Massive pulmonary embolism (PE) is a life-threatening complication of major surgery with a mortality rate of up to 50%. Extracorporeal membrane oxygenation (ECMO) is primarily used for respiratory and circulatory support. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is used to stabilize patients with acute massive PE. Acute brain injury, vascular disease, and immunosuppression are contraindications to ECMO, as stated in the 2021 Extracorporeal Life Support Organization guidelines. Case summary: We report a case of a patient with craniocerebral trauma whose postoperative course was complicated by massive PE and subsequent cardiac arrest that required urgent VA-ECMO, followed by anticoagulation with heparin. The patient showed hemodynamic improvement and was discharged 68 days after hospitalization. Discussion: ECMO has gradually been accepted for patients with craniocerebral injuries. The safety and effectiveness of ECMO in patients with craniocerebral injury, along with the optimal duration of ECMO and anticoagulation strategies, require further study.

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