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1.
Environ Pollut ; 349: 123943, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38599271

RESUMO

Aeromonas hydrophila has ability to spread tetracycline resistance (tetR) under stresses of oxytetracycline (OTC), one of the most important antibiotics in aquaculture industry. Even though environmental reservoir of Aeromonas allows it to be at interfaces across One Health components, a robust modelling framework for rigorously assessing health risks is currently lacking. We proposed a One Health-based approach and leveraged recent advances in quantitative microbial risk assessment appraised by available dataset to interpret interactions at the human-animal-environment interfaces in various exposure scenarios. The dose-response models were constructed considering the effects on mortality for aquaculture species and tetR genes transfer for humans. A scenario-specific risk assessment on pond species-associated A. hydrophila infection and human gut-associated tetR genes transfer was examined. Risk-based control strategies were involved to test their effectiveness. We showed that farmed shrimp exposed to tetracycline-resistant A. hydrophila in OTC-contaminated water experienced higher infection risk (relative risk: 1.25-1.34). The tetR genes transfer risk for farmers in shrimp ponds (∼2 × 10-4) and swimmers in coastal areas (∼4 × 10-6) during autumn exceeded acceptable risk (10-6). This cautionary finding underscores the importance of accounting for monitoring, assessing, and mitigating occupational health hazards among workers in shrimp farming sectors within future One Health-based strategies for managing water infection risks. We recommend that OTC emission rate together with A. hydrophila concentration should be reduced by up to 70-99% to protect human, farmed shrimp, and environmental health. Our predictive framework can be adopted for other systems and be used as a "risk detector" for assessing tetR-related health risks that invoke potential risk management on addressing sustainable mitigation on offsetting residual OTC emission and tetR genes spread in a species-human-environmental health system.

2.
J Genet Genomics ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38582298

RESUMO

The phenotypic diversity resulting from artificial or natural selection of sheep has made a significant contribution to human civilization. Hu sheep are a local sheep breed unique to China with high reproductive rates and rapid growth. Genome selection signatures have been widely used to investigate the genetic mechanisms underlying phenotypic variation in livestock. Here, we conduct whole-genome sequencing of 207 Hu sheep and compare them with the wild ancestors of domestic sheep (Asiatic mouflon) to investigate the genetic characteristics and selection signatures of Hu sheep. Based on six signatures of selection approaches, we detect genomic regions containing genes related to reproduction (BMPR1B, BMP2, PGFS, CYP19, CAMK4, GGT5, and GNAQ), vision (ALDH1A2, SAG, and PDE6B), nervous system (NAV1), and immune response (GPR35, SH2B2, PIK3R3, and HRAS). Association analysis with a population of 1299 Hu sheep reveal those missense mutations in the GPR35 (GPR35 g.952651 A>G; GPR35 g.952496 C>T) and NAV1 (NAV1 g.84216190 C>T; NAV1 g.84227412 G>A) genes are significantly associated (P < 0.05) with immune and growth traits in Hu sheep, respectively. This research offers unique insights into the selection characteristics of Hu sheep and facilitates further genetic improvement and molecular investigations.

3.
Immunology ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637948

RESUMO

Immune cell infiltration is a significant pathological process in abdominal aortic aneurysms (AAA). T cells, particularly CD4+ T cells, are essential immune cells responsible for substantial infiltration of the aorta. Regulatory T cells (Tregs) in AAA have been identified as tissue-specific; however, the time, location, and mechanism of acquiring the tissue-specific phenotype are still unknown. Using single-cell RNA sequencing (scRNA-seq) on CD4+ T cells from the AAA aorta and spleen, we discovered heterogeneity among CD4+ T cells and identified activated, proliferating and developed aorta Tregs. These Tregs originate in the peripheral tissues and acquire the tissue-specific phenotype in the aorta. The identification of precursors for Tregs in AAA provides new insight into the pathogenesis of AAA.

5.
Phys Rev E ; 109(3-2): 035204, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38632729

RESUMO

During the ultraintense laser interaction with solids (overdense plasmas), the competition between two possible quantum electrodynamics (QED) mechanisms responsible for e^{±} pair production, i.e., linear and nonlinear Breit-Wheeler (BW) processes, remains to be studied. Here, we have implemented the linear BW process via a Monte Carlo algorithm into the QED particle-in-cell (PIC) code yunic, enabling us to self-consistently investigate both pair production mechanisms in the plasma environment. By a series of two-dimensional QED-PIC simulations, the transition from the linear to the nonlinear BW process is observed with the increase of laser intensities in the typical configuration of a linearly polarized laser interaction with solid targets. A critical normalized laser amplitude about a_{0}∼400-500 is found under a large range of preplasma scale lengths, below which the linear BW process dominates over the nonlinear BW process. This work provides a practicable technique to model linear QED processes via integrated QED-PIC simulations. Moreover, it calls for more attention to be paid to linear BW pair production in near future 10-PW-class laser-solid interactions.

6.
Diabetes Ther ; 15(3): 725-739, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38438707

RESUMO

INTRODUCTION: Insulin degludec (degludec), an ultra-long-acting basal insulin analogue, provides equivalent glycemic control to other basal insulin analogues, with lower risk of hypoglycemia and flexible dosing. Chinese TREsiba AudiT (CN-TREAT) investigated outcomes with degludec in people with type 2 diabetes (T2D) in routine clinical practice in China. METHODS: This was a retrospective chart review study in adults with T2D initiating or switching to degludec at 50 sites in China between January 2020 and July 2021. The primary endpoint was change in glycated hemoglobin (HbA1c) from baseline to end of study (EOS; week 20). Secondary endpoints included change from baseline to EOS in fasting plasma glucose (FPG), self-measured plasma glucose (SMPG), daily insulin dose, and rate of hypoglycemia. RESULTS: Data from 936 participants were included (499 insulin-naïve; 437 insulin-experienced). Mean (95% confidence interval [CI]) HbA1c change from baseline to EOS was - 1.48%-points (- 1.57; - 1.38; P < 0.0001) overall: - 1.95%-points (- 2.08; - 1.81; P < 0.0001) in insulin-naïve participants and - 0.95%-points (- 1.08; - 0.82; P < 0.0001) in insulin-experienced participants. Mean (95% CI) changes in FPG and SMPG were - 2.27 mmol/L (- 2.69; - 1.85; P < 0.0001) and - 2.89 mmol/L (- 3.52; - 2.25; P < 0.0001), respectively, with similar reductions in insulin-naïve and insulin-experienced subgroups. Rate of hypoglycemia did not change statistically significantly from baseline to EOS overall, or in insulin-experienced participants, except when adjusted for baseline hypoglycemia. Basal insulin dose did not change statistically significantly in insulin-experienced participants. CONCLUSION: In routine clinical practice in China, initiation or switching to degludec was associated with improvements in glycemic control in people with T2D, with no increased risk of hypoglycemia. TRIAL REGISTRATION: ClinialTrials.gov, NCT04227431.

7.
Meat Sci ; 212: 109476, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38452564

RESUMO

Because substantial numbers of Chinese consumers are prepared to pay for tender and quality lamb, meat quality traits are becoming more relevant for breeding programs for Chinese sheep breeds. The current study estimated heritabilities and genetic correlations for 13 meat quality traits recorded on lamb loins from Hu sheep. Heritability estimates ranged from 0.04 ± 0.06 for meat redness at 45 min to 0.57 ± 0.10 for drip loss, with most of the meat quality traits having moderate heritabilities. Positive genetic correlations were observed among meat color traits. Intramuscular fat (IMF) was genetically correlated with most meat quality traits, indicating that increasing IMF can favor meat pH, color, and tenderness, but would lead to increased cooking loss. Direct selection to increase IMF of loins is recommended to be included in breeding programs for Hu sheep, as it was more efficient than indirect selection on the other meat quality traits. The genetic parameters presented in this preliminary study provide valuable genetic information needed to design a breeding program aimed at improving the quality of lamb meat from Hu sheep.


Assuntos
Carne , Carne Vermelha , Ovinos/genética , Animais , Carne/análise , Fenótipo , Culinária
8.
Pharmacol Res ; 201: 107091, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38316371

RESUMO

Inhibition of checkpoint kinase 1 (Chk1) has shown to overcome resistance to poly (ADP-ribose) polymerase (PARP) inhibitors and expand the clinical utility of PARP inhibitors in a broad range of human cancers. Pristimerin, a naturally occurring pentacyclic triterpenoid, has been the focus of intensive studies for its anticancer potential. However, it is not yet known whether low dose of pristimerin can be combined with PARP inhibitors by targeting Chk1 signaling pathway. In this study, we investigated the efficacy, safety and molecular mechanisms of the synergistic effect produced by the combination olaparib and pristimerin in TP53-deficient and BRCA-proficient cell models. As a result, an increased expression of Chk1 was correlated with TP53 mutation, and pristimerin preferentially sensitized p53-defective cells to olaparib. The combination of olaparib and pristimerin resulted in a more pronounced abrogation of DNA synthesis and induction of DNA double-strand breaks (DSBs). Moreover, pristimerin disrupted the constitutional levels of Chk1 and DSB repair activities. Mechanistically, pristimerin promoted K48-linked polyubiquitination and proteasomal degradation of Chk1 while not affecting its kinase domain and activity. Importantly, combinatorial therapy led to a higher rate of tumor growth inhibition without apparent hematological toxicities. In addition, pristimerin suppressed olaparib-induced upregulation of Chk1 and enhanced olaparib-induced DSB marker γΗ2ΑΧ in vivo. Taken together, inhibition of Chk1 by pristimerin has been observed to induce DNA repair deficiency, which may expand the application of olaparib in BRCA-proficient cancers harboring TP53 mutations. Thus, pristimerin can be combined for PARP inhibitor-based therapy.


Assuntos
Antineoplásicos , Triterpenos , Humanos , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Quinase 1 do Ponto de Checagem/metabolismo , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Proteína Supressora de Tumor p53/metabolismo , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Triterpenos Pentacíclicos , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/metabolismo , Ubiquitinação , DNA
9.
J Hazard Mater ; 467: 133692, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38341886

RESUMO

Cigarette smoking substantially promotes tumorigenesis and progression of colorectal cancer; however, the underlying molecular mechanism remains unclear. Among 662 colorectal cancer patients, our investigation revealed a significant correlation between cigarette smoking and factors, such as large tumor size, poor differentiation, and high degree of invasion. Among the nicotine-derived nitrosamines, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) emerged as the most critical carcinogen, which significantly promoted the malignant progression of colorectal cancer both in vivo and in vitro. The results of methylated RNA immunoprecipitation and transcriptome sequencing indicated that NNK upregulated transmembrane and ubiquitin-like domain-containing protein 1 (TMUB1) via N6-adenosine methylation, which was regulated by methyltransferase-like 14 (METTL14) and YTH N6-methyladenosine RNA binding protein 2 (YTHDF2). Elevated TMUB1 levels were associated with a higher risk of cancer invasion and metastasis, leading to a high mortality risk in patients with colorectal cancer. Additionally, TMUB1 promoted lysine63-linked ubiquitination of AKT by interacting with AMFR, which led to the induction of malignant proliferation and metastasis in colorectal cancer cells exposed to NNK. In summary, this study provides a new insight, indicating that targeting TMUB1 expression via METTL14/YTHDF2 mediated N6-adenosine methylation may be a potential therapeutic and prognostic target for patients with colorectal cancer who smoke.


Assuntos
Adenina/análogos & derivados , Neoplasias Colorretais , Nicotina , Humanos , Proteínas Proto-Oncogênicas c-akt , Adenosina , Proteínas de Ligação a RNA , Metiltransferases/genética
10.
Cell Metab ; 36(4): 822-838.e8, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38350448

RESUMO

Immunomodulatory effects of long-chain fatty acids (LCFAs) and their activating enzyme, acyl-coenzyme A (CoA) synthetase long-chain family (ACSL), in the tumor microenvironment remain largely unknown. Here, we find that ACSL5 functions as an immune-dependent tumor suppressor. ACSL5 expression sensitizes tumors to PD-1 blockade therapy in vivo and the cytotoxicity mediated by CD8+ T cells in vitro via regulation of major histocompatibility complex class I (MHC-I)-mediated antigen presentation. Through screening potential substrates for ACSL5, we further identify that elaidic acid (EA), a trans LCFA that has long been considered harmful to human health, phenocopies to enhance MHC-I expression. EA supplementation can suppress tumor growth and sensitize PD-1 blockade therapy. Clinically, ACSL5 expression is positively associated with improved survival in patients with lung cancer, and plasma EA level is also predictive for immunotherapy efficiency. Our findings provide a foundation for enhancing immunotherapy through either targeting ACSL5 or metabolic reprogramming of antigen presentation via dietary EA supplementation.


Assuntos
Apresentação de Antígeno , Neoplasias , Ácidos Oleicos , Humanos , Linfócitos T CD8-Positivos/metabolismo , Receptor de Morte Celular Programada 1 , Suplementos Nutricionais , Microambiente Tumoral , Coenzima A Ligases/metabolismo
11.
J Agric Food Chem ; 72(6): 2997-3007, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38300824

RESUMO

Lipid metabolism is closely related to obesity and its complications. Our previous study found that ginsenoside Rk3 (Rk3), a natural bioactive substance derived from ginseng, can effectively alleviate obesity-induced colitis, while its impact on the improvement of the lipid metabolism disorder remains unclear. Here, we demonstrated that Rk3 significantly alleviated inflammation, oxidative stress, and lipid dysregulation in high-fat diet-induced colitis C57BL/6 mice. The potential mechanism by which Rk3 mitigated colon inflammation in the context of obesity may involve the modulation of polyunsaturated fatty acid metabolism with specific attention to n-6 fatty acids, linoleic acid, and arachidonic acid. Rk3 intervention markedly reduced the production of pro-inflammatory factors (PGE2, PGD2, TXB2, HETE, and HODE) by inhibiting cyclooxygenase and lipoxygenase pathways, while enhancing the production of anti-inflammatory factors (EET and diHOME) via cytochrome P450 pathways. Our findings suggest that Rk3 is a potential anti-inflammatory natural drug that can improve obesity-induced intestinal inflammation by regulating lipid metabolism.


Assuntos
Colite , Ginsenosídeos , Metabolismo dos Lipídeos , Camundongos , Animais , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/genética , Inflamação , Colite/tratamento farmacológico , Colite/genética , Anti-Inflamatórios
12.
Adv Sci (Weinh) ; 11(14): e2307143, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38308097

RESUMO

Photodynamic therapy (PDT) is a minimally invasive and controllable local cancer treatment for cholangiocarcinoma (CCA). However, the efficacy of PDT is hindered by intratumoral hypoxia and the presence of an antioxidant microenvironment. To address these limitations, combining PDT with gas therapy may be a promising strategy to enhance tumor oxygenation. Moreover, the augmentation of oxidative damage induced by PDT and gas therapy can be achieved by inhibiting NRF2, a core regulatory molecule involved in the antioxidant response. In this study, an integrated nanotherapeutic platform called CMArg@Lip, incorporating PDT and gas therapies using ROS-responsive liposomes encapsulating the photosensitizer Ce6, the NO gas-generating agent L-arginine, and the NRF2 inhibitor ML385, is successfully developed. The utilization of CMArg@Lip effectively deals with challenges posed by tumor hypoxia and antioxidant microenvironment, resulting in elevated levels of oxidative damage and subsequent induction of ferroptosis in CCA. Additionally, these findings suggest that CMArg@Lip exhibits notable immunomodulatory effects, including the promotion of immunogenic cell death and facilitation of dendritic cell maturation. Furthermore, it contributes to the anti-tumor function of cytotoxic T lymphocytes through the downregulation of PD-L1 expression in tumor cells and the activation of the STING signaling pathway in myeloid-derived suppressor cells, thereby reprogramming the immunosuppressive microenvironment via various mechanisms.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Fotoquimioterapia , Humanos , Fotoquimioterapia/métodos , Fator 2 Relacionado a NF-E2/metabolismo , Antioxidantes/farmacologia , Colangiocarcinoma/tratamento farmacológico , Neoplasias dos Ductos Biliares/tratamento farmacológico , Ductos Biliares Intra-Hepáticos/metabolismo , Microambiente Tumoral
13.
Phys Rev E ; 109(1-2): 015208, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38366504

RESUMO

Quasimonoenergetic GeV-scale protons are predicted to be efficiently generated via radiation pressure acceleration (RPA) when the foil thickness is matched with the laser intensity, e.g., L_{mat} of several nm to 100 nm for 10^{19}-10^{22}Wcm^{-2} available in laboratory. However, nonmonoenergetic protons with much lower energies than predicted were usually observed in RPA experiments because of too small foil thickness which cannot support insufficient laser contrast and foil surface roughness. Besides the technical problems, we here find that there is an upper-limit thickness L_{up} derived from the requirement that the laser energy should dominate over the ion source energy in the effective laser-proton interaction zone, and L_{up} is lower than L_{mat} with the intensity below 10^{22}Wcm^{-2}, which causes inefficient or unsteady RPA. As the intensity is enhanced to ≥10^{23}Wcm^{-2} provided by 10-100 PW laser facilities, L_{up} can significantly exceed L_{mat}, and therefore RPA becomes efficient. In this regime, L_{mat} acts as a lower-limit thickness for efficient RPA, so the matching thickness can be extended to a continuous range from L_{mat} to L_{up}; the range can reach micrometers, within which foil thickness is adjustable. This makes RPA steady and meanwhile the above technical problems can be overcome. Particle-in-cell simulation shows that multi-GeV quasimonoenergetic proton beams can be steadily generated and the fluctuation of the energy peaks and the energy conversation efficiency remains stable although the thickness is taken in a larger range with increasing intensity. This work predicts that near future RPA experiments with 10-100 PW facilities will enter a new regime with a large range of usable foil thicknesses that can be adjusted to the interaction conditions for steady acceleration.

14.
Front Microbiol ; 15: 1348873, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38419634

RESUMO

Fecal scores are crucial for assessing the digestive and gastrointestinal status of animals. The Bristol fecal scoring system is a commonly used method for the subjective evaluation of host feces, there is limited research on fecal scoring standards for fattening Hu sheep. In this study, Hu sheep were collected for rumen, rectum, and colon contents for 16S rDNA sequencing. 514 Hu sheep feces were scored based on the Bristol fecal scoring system, and production performance at each stage was measured. Finally, we developed the scoring standard of the manure of Hu sheep in the fattening period (a total of five grades). The result shows that moisture content significantly increased with higher grades (p < 0.05). We analyzed the relationship between fecal scores and production traits, blood indices, muscle nutrients, and digestive tract microorganisms. The growth traits (body weight, body height, body length, average daily gain (ADG), and average daily feed intake (ADFI) during 80-180 days), body composition traits of the F3 group, and the carcass traits were found to be significantly higher (p < 0.05) than those of the F1 and F2 groups. There was no significant difference in gastrointestinal microflora diversity among all groups (p > 0.05). Significant differences were observed in Aspartate aminotransferase, Glucose, Total bilirubin, and Red Blood Cell Count between groups (p < 0.05). The mutton moisture content in group F4 was significantly higher than in the other groups, and the protein content was also the lowest (p < 0.05). The results of the correlation analysis demonstrated that Actinobacteria, Peptostreptococcaceae, Acidaminococcales, Gammaproteobacteria, and Proteobacteria were the significant bacteria affecting fecal scores. In addition, Muribaculaceae and Oscillospiraceae were identified as the noteworthy flora affecting growth performance and immunity. This study highlights the differences in production traits and blood indicators between fecal assessment groups and the complex relationship between intestinal microbiota and fecal characteristics in Hu sheep, suggesting potential impacts on animal performance and health, which suggest strategies for improved management.

15.
Phys Rev Lett ; 132(6): 065105, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38394557

RESUMO

Stable transport of laser beams in highly overdense plasmas is of significance in the fast ignition of inertial confinement fusion, relativistic electron generation, and powerful electromagnetic emission, but hard to realize. Early in 1996, Harris proposed an electromagnetically induced transparency (EIT) mechanism, analogous to the concept in atomic physics, to transport a low-frequency (LF) laser in overdense plasmas aided by a high-frequency pump laser. However, subsequent investigations show that EIT cannot occur in real plasmas with boundaries. Here, our particle-in-cell simulations show that EIT can occur in the strongly relativistic regime and result in stable propagation of a LF laser in bounded plasmas with tens of its critical density. A relativistic three-wave coupling model is developed, and the criteria and frequency passband for EIT occurrence are presented. The passband is sufficiently wide in the strongly relativistic regime, allowing EIT to work sustainably. Nevertheless, it is narrowed to nearly an isolated point in the weakly relativistic regime, which can explain the quenching of EIT in bounded plasmas found in previous investigations.

16.
FASEB J ; 38(4): e23488, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38358359

RESUMO

Myocardial infarction (MI) is defined as sudden ischemic death of myocardial tissue. Amphiregulin (Areg) regulates cell survival and is crucial for the healing of tissues after damage. However, the functions and mechanisms of Areg after MI remain unclear. Here, we aimed to investigate Areg's impact on myocardial remodeling. Mice model of MI was constructed and Areg-/- mice were used. Expression of Areg was analyzed using western blotting, RT-qPCR, flow cytometry, and immunofluorescence staining. Echocardiographic analysis, Masson's trichrome, and triphenyltetrazolium chloride staining were used to assess cardiac function and structure. RNA sequencing was used for unbiased analysis. Apoptosis and autophagy were determined by western blotting, TUNEL staining, electron microscopy, and mRFP-GFP-LC3 lentivirus. Lysosomal acidity was determined by Lysotracker staining. Areg was elevated in the infarct border zone after MI. It was mostly secreted by macrophages. Areg deficiency aggravated adverse ventricular remodeling, as reflected by worsening cardiac function, a lower survival rate, increased scar size, and interstitial fibrosis. RNA sequencing analyses showed that Areg related to the epidermal growth factor receptor (EGFR), phosphoinositide 3-kinase/protein kinase B (PI3K-Akt), mammalian target of rapamycin (mTOR) signaling pathways, V-ATPase and lysosome pathways. Mechanistically, Areg exerts beneficial effects via increasing lysosomal acidity to promote autophagosome clearance, and activating the EGFR/PI3K/Akt/mTOR signaling pathway, subsequently inhibiting excessive autophagosome formation and apoptosis in cardiomyocytes. This study provides a novel evidence for the role of Areg in inhibiting ventricular remodeling after MI by regulating autophagy and apoptosis and identifies Areg as a potential therapeutic target in ventricular remodeling after MI.


Assuntos
Infarto do Miocárdio , Fosfatidilinositol 3-Quinases , Animais , Camundongos , Anfirregulina/genética , Apoptose , Autofagia , Receptores ErbB , Mamíferos , Proteínas Proto-Oncogênicas c-akt , Serina-Treonina Quinases TOR , Remodelação Ventricular
18.
Glia ; 72(4): 692-707, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38192185

RESUMO

Schwann cells (SCs), the primary glial cells of the peripheral nervous system, which have been identified in many solid tumors, play an important role in cancer development and progression by shaping the tumor immunoenvironment and supporting the development of metastases. Using different cellular, molecular, and genetic approaches with integrated bioinformatics analysis and functional assays, we revealed the role of human SC-derived exosomal miRNAs in lung cancer progression in vitro and in vivo. We found that exosomal miRNA-21 from SCs up-regulated the proliferation, motility, and invasiveness of human lung cancer cells in vitro, which requires functional Rab small GTPases Rab27A and Rab27B in SCs for exosome release. We also revealed that SC exosomal miRNA-21-5p regulated the functional activation of tumor cells by targeting metalloprotease inhibitor RECK in tumor cells. Integrated bioinformatic analyses showed that hsa-miRNA-21-5p is associated with poor prognosis in patients with lung adenocarcinoma and can promote lung cancer progression through multiple signaling pathways including the MAPK, PI3K/Akt, and TNF signaling. Furthermore, in mouse xenograft models, SC exosomes and SC exosomal hsa-miRNA-21-5p augmented human lung cancer cell growth and lymph node metastasis in vivo. Together our data revealed, for the first time, that SC-secreted exosomes and exosomal miRNA-21-5p promoted the proliferation, motility, and spreading of human lung cancer cells in vitro and in vivo. Thus, exosomal miRNA-21 may play an oncogenic role in SC-accelerated progression of lung cancer and this pathway may serve as a new therapeutic target for further evaluation.


Assuntos
Exossomos , Neoplasias Pulmonares , MicroRNAs , Humanos , Camundongos , Animais , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Exossomos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Células de Schwann/metabolismo , Modelos Animais de Doenças , Proliferação de Células/genética , Proteínas Ligadas por GPI/metabolismo
19.
Anim Biotechnol ; 35(1): 2295928, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38174897

RESUMO

Scrotal circumference is an important reproductive index of breeding rams, which has a high genetic correlation with ejaculation volume and semen quality. In this study, the scrotal circumference of 1353 male Hu sheep at different stages of development was measured and descriptive statistical analysis was performed. The results showed that the coefficient of variation of scrotal circumference at each stage was greater than 10%, and its heritability were moderately to high, ranging from 0.318 to 0.719. We used PCR amplification and Sanger sequencing to scan the polymorphisms of the IGFALS gene, and performed association analysis with the circumference of the scrotum at different stages. We identified a synonymous mutation g.918 G > C in exon 1 of the IGFALS gene, and this mutation was significantly associated with scrotal circumference at 100, 120, 140, 160 and 180 days (p < 0.05). Therefore, IGFALS gene polymorphism can be used as a molecular marker affecting scrotal circumference of Hu sheep, which can provide a reference for future molecular marker-assisted selection of scrotal circumference in sheep.


Assuntos
Escroto , Análise do Sêmen , Ovinos/genética , Masculino , Animais , Análise do Sêmen/veterinária , Carneiro Doméstico , Reprodução , Polimorfismo Genético/genética
20.
Talanta ; 271: 125673, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38244311

RESUMO

Photoionization-ion trap mass spectrometry (PI-ITMS) is one of the major directions of mass spectrometer miniaturization because of its great potential for rapid on-site VOCs detection in many cases. Traditionally, PI has always been investigated separately and is restrained by ion transmission structure, so a new structure needs to be designed and investigated for simplifying and improving the ion transmission efficiency. Interestingly, our preliminary experiments found that the signal intensity and mass range can be effectively improved by combing atmospheric pressure photoionization (APPI) and low-pressure photoionization (LPPI). Therefore, in this paper, a new dual photoionization - ion trap mass spectrometry (DPI-ITMS) was developed, explored and used to directly analyze complex VOCs. Compared with traditional single PI configuration, it presents two obvious merits: (1) simplified ion transmission structure, eliminating the need to use deflection electrode to repel ions and avoiding breakdown risk. (2) some missing/weak low m/z ion mass spectral peaks in APPI and some high m/z ion mass spectral peaks in LPPI were improved in DPI detection mode. In addition, by combining multivariate statistical analysis, we preliminary achieved in differentiating fruit types and maturity level. In summary, we concluded that the developed DPI-ITMS has moderate detection sensitivity (limited by the homemade ITMS, 0.1-1 ppmv with RSD of 6.36 %), and the DPI-ITMS configuration can be referenced by future PI-MS, and this study also provides a high-throughput, simple, noninvasive and no chemical contamination solution for analyzing main VOCs in fruit aroma.


Assuntos
Frutas , Odorantes , Cromatografia Gasosa-Espectrometria de Massas , Pressão Atmosférica , Contaminação de Medicamentos
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