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2.
Infect Genet Evol ; : 105602, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38734397

RESUMO

Hepatitis E, caused by the hepatitis E virus (HEV), is a global public health issue. Low similarity between the gene sequences of mouse and human HEV led to the belief that the risk of human infection was low. Recent reports of chronic and acute hepatitis E caused by murine HEV infection in humans in Hong Kong have raised global concerns. Therefore, it is crucial to investigate the epidemiology and prevalence of HEV in China. We comprehensively analyzed different rodent HEV strains to understand rocahepevirus occurrence in Hubei Province, China. The HEV positivity rate for was 6.43% (73/1136). We identified seven near-full-length rocahepevirus strains and detected rat HEV antigens in tissues from different mouse species. HEV has extensive tissue tropism and a high viral load in the liver. We highlight the genetic diversity of HEVs in rodents and underscore the importance of paying attention to their variation and evolution.

3.
Microb Genom ; 10(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38700925

RESUMO

Paramyxoviruses are a group of single-stranded, negative-sense RNA viruses, some of which are responsible for acute human disease, including parainfluenza virus, measles virus, Nipah virus and Hendra virus. In recent years, a large number of novel paramyxoviruses, particularly members of the genus Jeilongvirus, have been discovered in wild mammals, suggesting that the diversity of paramyxoviruses may be underestimated. Here we used hemi-nested reverse transcription PCR to obtain 190 paramyxovirus sequences from 969 small mammals in Hubei Province, Central China. These newly identified paramyxoviruses were classified into four clades: genera Jeilongvirus, Morbillivirus, Henipavirus and Narmovirus, with most of them belonging to the genus Jeilongvirus. Using Illumina sequencing and Sanger sequencing, we successfully recovered six near-full-length genomes with different genomic organizations, revealing the more complex genome content of paramyxoviruses. Co-divergence analysis of jeilongviruses and their known hosts indicates that host-switching occurred more frequently in the evolutionary histories of the genus Jeilongvirus. Together, our findings demonstrate the high prevalence of paramyxoviruses in small mammals, especially jeilongviruses, and highlight the diversity of paramyxoviruses and their genome content, as well as the evolution of jeilongviruses.


Assuntos
Infecções por Paramyxoviridae , Paramyxovirinae , Paramyxovirinae/genética , Infecções por Paramyxoviridae/epidemiologia , Infecções por Paramyxoviridae/veterinária , Mamíferos , China , Filogenia , Genoma Viral , Especificidade de Hospedeiro
4.
Biomed Pharmacother ; 175: 116693, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38701566

RESUMO

Sevoflurane postconditioning has been shown to provide neuroprotection against cerebral hypoxia-ischemia injury, but the mechanisms remain elusive. Microtubule-associated protein 2 (MAP2) is implicated in early neuronal hypoxia-ischemia injury. This study aimed to investigate whether the neuroprotective effects of sevoflurane postconditioning are related to the Akt/GSK-3ß pathway and its downstream target MAP2 in zebrafish hypoxia/reoxygenation (H/R) model. Sevoflurane postconditioning or GSK-3ß inhibitor TDZD-8 were used to treat H/R zebrafish. The cerebral infarction, neuronal apoptosis, and mitochondrial changes were evaluated using TTC staining, TUNEL staining, and transmission electron microscopy, respectively. The distribution of MAP2 in the brain was determined by immunofluorescence imaging. The levels of Akt, p-Akt, GSK-3ß, p-GSK-3ß, and MAP2 proteins were evaluated by Western blotting. The neurobehavioral recovery of zebrafish was assessed based on optokinetic response behavior. Our results indicated that sevoflurane postconditioning and TDZD-8 significantly reduced the cerebral infarction area, suppressed cell apoptosis, and improved mitochondrial integrity in zebrafish subjected to H/R. Furthermore, sevoflurane postconditioning and TDZD-8 elevated the ratios of p-Akt/Akt and p-GSK-3ß/GSK-3ß. However, the neuroprotective effect of sevoflurane postconditioning was effectively abolished upon suppression of MAP2 expression. In conclusion, sevoflurane postconditioning ameliorated cerebral H/R injury and facilitated the restoration of neurobehavioral function through the activation of Akt/GSK-3ß pathway and promotion of MAP2 expression.

5.
Int J Mol Sci ; 25(9)2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38732191

RESUMO

Acacia melanoxylon is highly valued for its commercial applications, with the heartwood exhibiting a range of colors from dark to light among its various clones. The underlying mechanisms contributing to this color variation, however, have not been fully elucidated. In an effort to understand the factors that influence the development of dark heartwood, a comparative analysis was conducted on the microstructure, substance composition, differential gene expression, and metabolite profiles in the sapwood (SW), transition zone (TZ), and heartwood (HW) of two distinct clones, SR14 and SR25. A microscopic examination revealed that heartwood color variations are associated with an increased substance content within the ray parenchyma cells. A substance analysis indicated that the levels of starches, sugars, and lignin were more abundant in SP compared to HW, while the concentrations of phenols, flavonoids, and terpenoids were found to be higher in HW than in SP. Notably, the dark heartwood of the SR25 clone exhibited greater quantities of phenols and flavonoids compared to the SR14 clone, suggesting that these compounds are pivotal to the color distinction of the heartwood. An integrated analysis of transcriptome and metabolomics data uncovered a significant accumulation of sinapyl alcohol, sinapoyl aldehyde, hesperetin, 2', 3, 4, 4', 6'-peptahydroxychalcone 4'-O-glucoside, homoeriodictyol, and (2S)-liquiritigenin in the heartwood of SR25, which correlates with the up-regulated expression of CCRs (evm.TU.Chr3.1751, evm.TU.Chr4.654_667, evm.TU.Chr4.675, evm.TU.Chr4.699, and evm.TU.Chr4.704), COMTs (evm.TU.Chr13.3082, evm.TU.Chr13.3086, and evm.TU.Chr7.1411), CADs (evm.TU.Chr10.2175, evm.TU.Chr1.3453, and evm.TU.Chr8.1600), and HCTs (evm.TU.Chr4.1122, evm.TU.Chr4.1123, evm.TU.Chr8.1758, and evm.TU.Chr9.2960) in the TZ of A. melanoxylon. Furthermore, a marked differential expression of transcription factors (TFs), including MYBs, AP2/ERFs, bHLHs, bZIPs, C2H2s, and WRKYs, were observed to be closely linked to the phenols and flavonoids metabolites, highlighting the potential role of multiple TFs in regulating the biosynthesis of these metabolites and, consequently, influencing the color variation in the heartwood. This study facilitates molecular breeding for the accumulation of metabolites influencing the heartwood color in A. melanoxylon, and offers new insights into the molecular mechanisms underlying heartwood formation in woody plants.


Assuntos
Acacia , Regulação da Expressão Gênica de Plantas , Madeira , Acacia/metabolismo , Acacia/genética , Madeira/metabolismo , Madeira/química , Flavonoides/metabolismo , Lignina/metabolismo , Transcriptoma , Fenóis/metabolismo , Perfilação da Expressão Gênica/métodos , Metabolômica/métodos
6.
Metab Eng ; 83: 172-182, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38648878

RESUMO

Microbial bioengineering is a growing field for producing plant natural products (PNPs) in recent decades, using heterologous metabolic pathways in host cells. Once heterologous metabolic pathways have been introduced into host cells, traditional metabolic engineering techniques are employed to enhance the productivity and yield of PNP biosynthetic routes, as well as to manage competing pathways. The advent of computational biology has marked the beginning of a novel epoch in strain design through in silico methods. These methods utilize genome-scale metabolic models (GEMs) and flux optimization algorithms to facilitate rational design across the entire cellular metabolic network. However, the implementation of in silico strategies can often result in an uneven distribution of metabolic fluxes due to the rigid knocking out of endogenous genes, which can impede cell growth and ultimately impact the accumulation of target products. In this study, we creatively utilized synthetic biology to refine in silico strain design for efficient PNPs production. OptKnock simulation was performed on the GEM of Saccharomyces cerevisiae OA07, an engineered strain for oleanolic acid (OA) bioproduction that has been reported previously. The simulation predicted that the single deletion of fol1, fol2, fol3, abz1, and abz2, or a combined knockout of hfd1, ald2 and ald3 could improve its OA production. Consequently, strains EK1∼EK7 were constructed and cultivated. EK3 (OA07△fol3), EK5 (OA07△abz1), and EK6 (OA07△abz2) had significantly higher OA titers in a batch cultivation compared to the original strain OA07. However, these increases were less pronounced in the fed-batch mode, indicating that gene deletion did not support sustainable OA production. To address this, we designed a negative feedback circuit regulated by malonyl-CoA, a growth-associated intermediate whose synthesis served as a bypass to OA synthesis, at fol3, abz1, abz2, and at acetyl-CoA carboxylase-encoding gene acc1, to dynamically and autonomously regulate the expression of these genes in OA07. The constructed strains R_3A, R_5A and R_6A had significantly higher OA titers than the initial strain and the responding gene-knockout mutants in either batch or fed-batch culture modes. Among them, strain R_3A stand out with the highest OA titer reported to date. Its OA titer doubled that of the initial strain in the flask-level fed-batch cultivation, and achieved at 1.23 ± 0.04 g L-1 in 96 h in the fermenter-level fed-batch mode. This indicated that the integration of optimization algorithm and synthetic biology approaches was efficiently rational for PNP-producing strain design.

8.
BMC Plant Biol ; 24(1): 308, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38644502

RESUMO

Acacia melanoxylon is well known as a valuable commercial tree species owing to its high-quality heartwood (HW) products. However, the metabolism and regulatory mechanism of heartwood during wood development remain largely unclear. In this study, both microscopic observation and content determination proved that total amount of starches decreased and phenolics and flavonoids increased gradually from sapwood (SW) to HW. We also obtained the metabolite profiles of 10 metabolites related to phenolics and flavonoids during HW formation by metabolomics. Additionally, we collected a comprehensive overview of genes associated with the biosynthesis of sugars, terpenoids, phenolics, and flavonoids using RNA-seq. A total of ninety-one genes related to HW formation were identified. The transcripts related to plant hormones, programmed cell death (PCD), and dehydration were increased in transition zone (TZ) than in SW. The results of RT-PCR showed that the relative expression level of genes and transcription factors was also high in the TZ, regardless of the horizontal or vertical direction of the trunk. Therefore, the HW formation took place in the TZ for A. melanoxylon from molecular level, and potentially connected to plant hormones, PCD, and cell dehydration. Besides, the increased expression of sugar and terpenoid biosynthesis-related genes in TZ further confirmed the close connection between terpenoid biosynthesis and carbohydrate metabolites of A. melanoxylon. Furthermore, the integrated analysis of metabolism data and RNA-seq data showed the key transcription factors (TFs) regulating flavonoids and phenolics accumulation in HW, including negative correlation TFs (WRKY, MYB) and positive correlation TFs (AP2, bZIP, CBF, PB1, and TCP). And, the genes and metabolites from phenylpropanoid and flavonoid metabolism and biosynthesis were up-regulated and largely accumulated in TZ and HW, respectively. The findings of this research provide a basis for comprehending the buildup of metabolites and the molecular regulatory processes of HW formation in A. melanoxylon.


Assuntos
Acacia , Flavonoides , Perfilação da Expressão Gênica , Madeira , Acacia/genética , Acacia/metabolismo , Flavonoides/metabolismo , Flavonoides/biossíntese , Madeira/genética , Madeira/metabolismo , Metabolômica , Regulação da Expressão Gênica de Plantas , Transcriptoma , Fenóis/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética
9.
J Orthop Surg Res ; 19(1): 242, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622724

RESUMO

OBJECTIVE: To systematically evaluate the difference in clinical efficacy between two surgical approaches, oblique lateral approach and intervertebral foraminal approach, in the treatment of degenerative lumbar spondylolisthesis. METHODS: English databases, including PubMed, Cochrane, Embase, and Web of Science, were systematically searched using keywords such as "oblique lumbar interbody fusion" and "transforaminal lumbar interbody fusion." Concurrently, Chinese databases, including CNKI, WanFang data, VIP, and CBM, were also queried using corresponding Chinese terms. The search spanned from January 2014 to February 2024, focusing on published studies in both Chinese and English that compared the clinical efficacy of OLIF and TLIF. The literature screening was conducted by reviewing titles, abstracts, and full texts. Literature meeting the inclusion criteria underwent quality assessment, and relevant data were extracted. Statistical analysis and a meta-analysis of the observational data for both surgical groups were performed using Excel and RevMan 5.4 software. Findings revealed a total of 14 studies meeting the inclusion criteria, encompassing 877 patients. Of these, 414 patients were in the OLIF group, while 463 were in the TLIF group. Meta-analysis of the statistical data revealed that compared to TLIF, OLIF had a shorter average surgical duration (P < 0.05), reduced intraoperative bleeding (P < 0.05), shorter average hospital stay (P < 0.05), better improvement in postoperative VAS scores (P < 0.05), superior enhancement in postoperative ODI scores (P < 0.05), more effective restoration of disc height (P < 0.05), and better correction of lumbar lordosis (P < 0.05). However, there were no significant differences between OLIF and TLIF in terms of the incidence of surgical complications (P > 0.05) and fusion rates (P > 0.05). CONCLUSION: When treating degenerative lumbar spondylolisthesis, OLIF demonstrates significant advantages over TLIF in terms of shorter surgical duration, reduced intraoperative bleeding, shorter hospital stay, superior improvement in postoperative VAS and ODI scores, better restoration of disc height, and more effective correction of lumbar lordosis.


Assuntos
Lordose , Fusão Vertebral , Espondilolistese , Humanos , Estudos Retrospectivos , Espondilolistese/cirurgia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Lordose/cirurgia , Fusão Vertebral/efeitos adversos , Resultado do Tratamento , Procedimentos Cirúrgicos Minimamente Invasivos
10.
Bioorg Chem ; 146: 107327, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38579616

RESUMO

Colorectal cancer (CRC) is well known as a prevalent malignancy affecting the digestive tract, yet its precise etiological determinants remain to be elusive. Accordingly, identifying specific molecular targets for colorectal cancer and predicting potential malignant tumor behavior are potential strategies for therapeutic interventions. Of note, apoptosis (type I programmed cell death) has been widely reported to play a pivotal role in tumorigenesis by exerting a suppressive effect on cancer development. Moreover, autophagy-dependent cell death (type II programmed cell death) has been implicated in different types of human cancers. Thus, investigating the molecular mechanisms underlying apoptosis and autophagy-dependent cell death is paramount in treatment modalities of colorectal cancer. In this study, we uncovered that a new small-molecule activator of SIRT3, named MY-13, triggered both autophagy-dependent cell death and apoptosis by modulating the SIRT3/Hsp90/AKT signaling pathway. Consequently, this compound inhibited tumor cell proliferation and migration in RKO and HCT-116 cell lines. Moreover, we further demonstrated that the small-molecule activator significantly suppressed tumor growth in vivo. In conclusion, these findings demonstrate that the novel small-molecule activator of SIRT3 may hold a therapeutic potential as a drug candidate in colorectal cancer.


Assuntos
Morte Celular Autofágica , Neoplasias Colorretais , Sirtuína 3 , Humanos , Neoplasias Colorretais/metabolismo , Autofagia , Proliferação de Células , Apoptose , Linhagem Celular Tumoral
11.
World J Gastrointest Endosc ; 16(3): 108-111, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38577650

RESUMO

In this editorial, we comment on the minireview by Martino A, published in the recent issue of World Journal of Gastrointestinal Endoscopy 2023; 15 (12): 681-689. We focused mainly on the possibility of replacing the hepatic venous pressure gradient (HVPG) and endoscopy with noninvasive methods for predicting esophageal variceal bleeding. The risk factors for bleeding were the size of the varices, the red sign and the Child-Pugh score. The intrinsic core factor that drove these changes was the HVPG. Therefore, the present studies investigating noninvasive methods, including computed tomography, magnetic resonance imaging, elastography, and laboratory tests, are working on correlating imaging or serum marker data with intravenous pressure and clinical outcomes, such as bleeding. A single parameter is usually not enough to construct an efficient model. Therefore, multiple factors were used in most of the studies to construct predictive models. Encouraging results have been obtained, in which bleeding prediction was partly reached. However, these methods are not satisfactory enough to replace invasive methods, due to the many drawbacks of different studies. There is still plenty of room for future improvement. Prediction of the precise timing of bleeding using various models, and extracting the texture of variceal walls using high-definition imaging modalities to predict the red sign are interesting directions to lay investment on.

12.
J Genet Genomics ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38582297

RESUMO

MicroRNAs (miRNAs) play a significant role in axon regeneration following spinal cord injury. However, the functions of numerous miRNAs in axon regeneration within the central nervous system (CNS) remain largely unexplored. Here, we elucidate the positive role of miR-2184 in axon regeneration within zebrafish Mauthner cells (M-cells). The upregulation of miR-2184 in the single M-cells facilitates axon regeneration, while the specific sponge-induced silencing of miR-2184 leads to impeded axon regeneration. We show that syt3, a downstream target of miR-2184, negatively regulates axon regeneration, and the regeneration suppression by syt3 depends on its binding to Ca2+. Furthermore, pharmacological stimulation of the cAMP/PKA pathway suggests that changes in the readily releasable pool may affect axon regeneration. Our data indicate that miR-2184 promotes axon regeneration of M-cells within the CNS by modulating the downstream target syt3, providing valuable insights into potential therapeutic strategies.

13.
World J Gastrointest Endosc ; 16(4): 187-192, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38680200

RESUMO

In this editorial, we comment on the article published in the recent issue of the World Journal of Gastrointestinal Endoscopy. We focused on the understanding of appendiceal disease, and the various options for diagnosis and treatment via endoscopy. Some factors affecting the diagnosis and management of appendiceal diseases are also discussed. The existence of any organ has its natural rationality, and the appendix is such a magical organ. A growing number of experts and scholars have gradually come to a consensus that the appendix is not a useless evolutionary relic. There are many lymphocytes and lymph nodes in the appendix wall, which has a strong immune function, and this function is particularly important for children and adolescents. Many intestinal probiotics in the appendix are very helpful for maintaining the balance of the intestinal flora. With the continuous progress of endoscopic technology, endoscopic treatment involving preservation of the appendix has shown great advantages over surgery. In the diagnosis of appendiceal inflammation and neoplasms, colonoscopy, endoscopic retrograde appendicography and choledochoscopy help assess conditions of the appendix. Endoscopic retrograde appendicitis therapy, abscess drainage under colonoscopy, fenestration of abscess under colonoscopy, and endoscopic or natural orifice transluminal endoscopic surgery resection of appendiceal neoplasms are safe and effective endoscopic treatments for appendiceal disease. New breakthroughs in the application of endoscopy in the appendix are expected to occur in the near future.

15.
Plants (Basel) ; 13(6)2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38592868

RESUMO

Acacia melanoxylon is a fast-growing macrophanerophyte with strong adaptability whose leaf enables heteromorphic development. Light is one of the essential environmental factors that induces the development of the heteroblastic leaf of A. melanoxylon, but its mechanism is unclear. In this study, the seedlings of A. melanoxylon clones were treated with weak light (shading net with 40% of regular light transmittance) and normal light (control) conditions for 90 d and a follow-up observation. The results show that the seedlings' growth and biomass accumulation were inhibited under weak light. After 60 days of treatment, phyllodes were raised under the control condition while the remaining compound was raised under weak light. The balance of root, stem, and leaf biomass changed to 15:11:74 under weak light, while it was 40:15:45 under control conditions. After comparing the anatomical structures of the compound leaves and phyllode, they were shown to have their own strategies for staying hydrated, while phyllodes were more able to control water loss and adapt to intense light. The compound leaves exhibited elevated levels of K, Cu, Ca, and Mg, increased antioxidant enzyme activity and proline content, and higher concentrations of chlorophyll a, carotenoids, ABA, CTK, and GA. However, they displayed a relatively limited photosynthetic capacity. Phyllodes exhibited higher levels of Fe, cellulose, lignin, IAA content, and high photosynthetic capacity with a higher maximum net photosynthetic rate, light compensation point, dark respiration rate, and water use efficiency. The comparative analysis of compound leaves and phyllodes provides a basis for understanding the diverse survival strategies that heteroblastic plants employ to adapt to environmental changes.

16.
World J Gastroenterol ; 30(9): 1257-1260, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38577178

RESUMO

The increasing popularity of endoscopic submucosal dissection (ESD) as a treatment for early gastric cancer has highlighted the importance of quality assessment in achieving curative resections. This article emphasizes the significance of evaluating ESD quality, not only for curative cases but also for non-curative ones. Postoperative assessment relies on the endoscopic curability (eCura) classification, but management strategies for eCuraC-1 tumour with a positive horizontal margin are unclear. Current research primarily focuses on comparing additional surgical procedures in high-risk patients, while studies specifically targeting eCuraC-1 patients are limited. Exploring management strategies and follow-up outcomes for such cases could provide valuable insights. Furthermore, the application of molecular imaging using near-infrared fluorescent tracers holds promise for precise tumour diagnosis and navigation, potentially impacting the management of early-stage gastric cancer patients. Advancing research in these areas is essential for improving the overall efficacy of endoscopic techniques and refining treatment indications.


Assuntos
Ressecção Endoscópica de Mucosa , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Ressecção Endoscópica de Mucosa/efeitos adversos , Ressecção Endoscópica de Mucosa/métodos , Resultado do Tratamento , Estudos Retrospectivos , Mucosa Gástrica/diagnóstico por imagem , Mucosa Gástrica/cirurgia , Mucosa Gástrica/patologia
17.
Am J Gastroenterol ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38619136

RESUMO

INTRODUCTION: Fully covered self-expandable metal stents (FCSEMSs) are commonly placed in patients with biliary stricture during endoscopic retrograde cholangiopancreatography (ERCP). However, up to 40% of migration has been reported, resulting in treatment failure or the requirement for further intervention. Here, we aimed to investigate the effects of metal clip anchoring on preventing the migration of FCSEMS. METHODS: Consecutive patients requiring placement of FCSEMS were included in this multicenter randomized trial. The enrolled patients were randomly assigned in a 1:1 ratio to receive clip anchoring (clip group) or not (control group). The primary outcome was the migration rate at 6 months after stent insertion. The secondary outcomes were the rates of proximal and distal migration and stent-related adverse events. The analysis followed the intention-to-treat principle. RESULTS: From February 2020 to November 2022, 180 patients with biliary stricture were enrolled, with 90 in each group. The baseline characteristics were comparable between the 2 groups. The overall rate of stent migration at 6 months was significantly lower in the clip group compared with the control group (16.7% vs 30.0%, P = 0.030). The proximal and distal migration rates were similar in the 2 groups (2.2% vs 5.6%, P = 0.205; 14.4% vs 22.2%, P = 0.070). Notably, none of the patients (0/8) who received 2 or more clips experienced stent migration. There were no significant differences in stent-related adverse events between the 2 groups. DISCUSSION: Our data suggest that clip-assisted anchoring is an effective and safe method for preventing migration of FCSEMS without increasing the adverse events.

18.
Cancer Lett ; 590: 216870, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38614386

RESUMO

To seed lethal secondary lesions, circulating tumor cells (CTCs) must survive all rate-limiting factors during hematogenous dissemination, including fluid shear stress (FSS) that poses a grand challenge to their survival. We thus hypothesized that CTCs with the ability to survive FSS in vasculature might hold metastasis-initiating competence. This study reported that FSS of physiologic magnitude selected a small subpopulation of suspended tumor cells in vitro with the traits of metastasis-initiating cells, including stemness, migration/invasion potential, cellular plasticity, and biophysical properties. These shear-selected cells generated local and metastatic tumors at the primary and distal sites efficiently, implicating their metastasis competence. Mechanistically, FSS activated the mechanosensitive protein CXCR4 and the downstream PI3K/AKT signaling, which were essential in shear-mediated selection of metastasis-competent CTCs. In summary, these findings conclude that CTCs with metastasis-initiating competence survive FSS during hematogenous dissemination through CXCR4-PI3K/AKT signaling, which may provide new therapeutic targets for the early prevention of tumor metastasis.


Assuntos
Células Neoplásicas Circulantes , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Receptores CXCR4 , Transdução de Sinais , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Receptores CXCR4/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Linhagem Celular Tumoral , Estresse Mecânico , Feminino , Camundongos , Movimento Celular , Metástase Neoplásica
19.
Sci Total Environ ; 930: 172633, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643877

RESUMO

This study aims to evaluate the effects of oxytetracycline (OTC) on detoxification and oxidative defense in the hepatopancreas and intestine of Chinese mitten crab (Eriocheir sinensis) under cadmium (Cd) stress. The crab was exposed to 0.6 µM Cd, 0.6 µM OTC, and 0.6 µM Cd plus 0.6 µM OTC for 42 days. Our results showed that in the intestine, OTC alone enhanced protein carboxylation (PC) and malondialdehyde (MDA) contents, which was associated with the increased OTC accumulation. Compared to Cd alone, Cd plus OTC increased Cd and OTC contents, and reduced detoxification (i.e., glutathione (GSH) content, gene expressions of cytochrome P450 (CYP) isoforms, 7-ethoxyresorufin O-deethylase (EROD) activity, mRNA levels and activities of glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST)), and antioxidant defense (i.e., gene expressions and activities of catalase (CAT) and superoxide dismutase (SOD)) in the intestine, leading to the increased in PC and MDA contents, suggesting that OTC had a synergistic effect on Cd-induced oxidative damage. In the hepatopancreas, although OTC alone increased OTC accumulation, it did not affect PC and MDA contents. Compared to Cd alone, Cd plus OTC reduced MDA content, which was closely related to the improvement of detoxification (i.e., GSH content, mRNA levels of CYP isoforms, EROD activity, gene expressions and activities of GPx, GR and GST), and antioxidant defense (gene expressions and activities of CAT and SOD, metallothionein content). Aryl hydrocarbon receptor (AhR) and nuclear factor E2-related factor 2 (Nrf2) transcriptional expressions were positively correlated with most detoxification- and antioxidant-related gene expressions, respectively, indicating that AhR and Nrf2 were involved in the regulation of these gene expressions. Our results unambiguously demonstrated that OTC had tissue-specific effects on Cd-induced toxicological effect in E. sinensis, which contributed to accurately evaluating Cd toxicity modulated by TCs in crab.


Assuntos
Antioxidantes , Braquiúros , Cádmio , Hepatopâncreas , Oxitetraciclina , Poluentes Químicos da Água , Animais , Braquiúros/efeitos dos fármacos , Braquiúros/fisiologia , Braquiúros/metabolismo , Cádmio/toxicidade , Oxitetraciclina/toxicidade , Hepatopâncreas/metabolismo , Hepatopâncreas/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Antioxidantes/metabolismo , Intestinos/efeitos dos fármacos , Inativação Metabólica , Estresse Oxidativo/efeitos dos fármacos
20.
Am J Med Sci ; 367(6): 375-381, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38467374

RESUMO

BACKGROUND: Our study aimed to assess the clinical and hemodynamic characteristics of pulmonary hypertension (PH) in patients with overlapping obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD), referred to OSA-COPD overlap syndrome (OS). METHODS: We enrolled a total of 116 patients with OS, COPD, or OSA who underwent right heart catheterization (RHC) due to suspected PH. We conducted a retrospective analysis of the clinical and hemodynamic characteristics of these patients. RESULTS: Among the three groups (OS group, n = 26; COPD group, n = 36; OSA group, n = 54), the prevalence of PH was higher in the OS group (n = 17, 65.4%)compared to OSA group (n = 26,48.1%) and COPD group (n = 20,55.6 %). Among three groups with PH, the superior vena cava pressure (CVP) and right ventricular pressure (RAP) were higher in the OS group than in the OSA group (P < 0.05). Patients in the OS and COPD groups had higher pulmonary artery wedge pressure (PAWP) than in the OSA group (14.88 ± 4.79 mmHg, 13.45 ± 3.68 mmHg vs. 11.00 ± 3.51 mmHg, respectively, P < 0.05). OS patients with PH exhibited higher respiratory event index (REI), time spent with SpO2 <90%, oxygen desaturation index (ODI), minimal SpO2 (MinSpO2) and mean SpO2 (MSpO2) compared to OS patients without PH. After adjusting for potential covariates, we found that MinSpO2 (OR 0.937, 95 % CI 0.882-0.994, P = 0.032), MSpO2 (OR 0.805, 95% CI 0.682-0.949, P = 0.010), time spent with SpO2 <90% (OR 1.422, 95% CI 1.137-1.780, P = 0.002), and FEV1 % pred (OR 0.977, 95 % CI 0.962-0.993, P = 0.005) were related to the development of PH. CONCLUSIONS: Patients with OS showed higher prevalence of PH, along with higher PAWP, CVP and RAP. Worse nocturnal hypoxemia was found in OS patients with PH.


Assuntos
Hemodinâmica , Hipertensão Pulmonar , Doença Pulmonar Obstrutiva Crônica , Apneia Obstrutiva do Sono , Humanos , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/etiologia , Masculino , Feminino , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/epidemiologia , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/complicações , Estudos Retrospectivos , Idoso , Cateterismo Cardíaco
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