Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 130
Filtrar
1.
Commun Biol ; 7(1): 533, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38710747

RESUMO

Insect wing development is a fascinating and intricate process that involves the regulation of wing size through cell proliferation and apoptosis. In this study, we find that Ter94, an AAA-ATPase, is essential for proper wing size dependently on its ATPase activity. Loss of Ter94 enables the suppression of Hippo target genes. When Ter94 is depleted, it results in reduced wing size and increased apoptosis, which can be rescued by inhibiting the Hippo pathway. Biochemical experiments reveal that Ter94 reciprocally binds to Mer, a critical upstream component of the Hippo pathway, and disrupts its interaction with Ex and Kib. This disruption prevents the formation of the Ex-Mer-Kib complex, ultimately leading to the inactivation of the Hippo pathway and promoting proper wing development. Finally, we show that hVCP, the human homolog of Ter94, is able to substitute for Ter94 in modulating Drosophila wing size, underscoring their functional conservation. In conclusion, Ter94 plays a positive role in regulating wing size by interfering with the Ex-Mer-Kib complex, which results in the suppression of the Hippo pathway.


Assuntos
Proteínas de Drosophila , Drosophila melanogaster , Proteínas de Membrana , Proteínas Serina-Treonina Quinases , Transdução de Sinais , Proteínas Supressoras de Tumor , Asas de Animais , Animais , Asas de Animais/crescimento & desenvolvimento , Asas de Animais/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Drosophila melanogaster/genética , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Apoptose , Neurofibromina 2/metabolismo , Neurofibromina 2/genética , Regulação da Expressão Gênica no Desenvolvimento , Adenosina Trifosfatases/metabolismo , Adenosina Trifosfatases/genética , Drosophila/genética , Drosophila/crescimento & desenvolvimento , Drosophila/metabolismo
2.
Open Life Sci ; 19(1): 20220824, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38465339

RESUMO

Trousseau syndrome (TS) is a malignant tumor-mediated complication of the hypercoagulable state with an unknown etiology. Laboratory testing results in patients with TS have indicated elevated D-dimer levels. The imaging analysis in patients who had undergone stroke has shown the presence of several cerebral infarction lesions in multiple regions. Since patients have had malignant tumors for a long time when they suffer from a secondary stroke, the optimum time for radical tumor treatment is usually missed. This study reports a case to improve the early screening and detection of TS and reduce the risk of recurrence of cerebral infarction.

3.
J Agric Food Chem ; 72(14): 7735-7748, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38546111

RESUMO

Reverse chemical ecology has been widely applied for the functional characterization of olfactory proteins in various arthropods, but few related studies have focused on parasitic wasps. Here, the odorant carrier Niemann-Pick C2 protein of Baryscapus dioryctriae (BdioNPC2b) was studied in vitro and in vivo. Ligand binding analysis revealed that BdioNPC2b most strongly bound to 2-butyl-2-octenal and which compound could elicit an EAG response and attracted B. dioryctriae adults. Moreover, this odorant attractant significantly improved the reproductive efficiency of B. dioryctriae compared to that of the control. Then, the relationship between BdioNPC2b and 2-butyl-2-octenal was validated by RNAi, and site-directed mutagenesis revealed the involvement of three key residues of BdioNPC2b in binding to 2-butyl-2-octenal through hydrogen bonding. Our findings provide not only a deeper understanding of the olfactory function of NPC2 in wasps but also useful information for improving the performance of the parasitoid B. dioryctriae as a biological control agent.


Assuntos
Vespas , Animais , Vespas/genética , Aldeídos , Proteínas de Transporte/metabolismo , Olfato
4.
J Chem Inf Model ; 64(3): 575-583, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38265916

RESUMO

Discovery of small-molecule antibiotics with novel chemotypes serves as one of the essential strategies to address antibiotic resistance. Although a considerable number of computational tools committed to molecular design have been reported, there is a deficit in holistic and efficient tools specifically developed for small-molecule antibiotic discovery. To address this issue, we report AutoMolDesigner, a computational modeling software dedicated to small-molecule antibiotic design. It is a generalized framework comprising two functional modules, i.e., generative-deep-learning-enabled molecular generation and automated machine-learning-based antibacterial activity/property prediction, wherein individually trained models and curated datasets are out-of-the-box for whole-cell-based antibiotic screening and design. It is open-source, thus allowing for the incorporation of new features for flexible use. Unlike most software programs based on Linux and command lines, this application equipped with a Qt-based graphical user interface can be run on personal computers with multiple operating systems, making it much easier to use for experimental scientists. The software and related materials are freely available at GitHub (https://github.com/taoshen99/AutoMolDesigner) and Zenodo (https://zenodo.org/record/10097899).


Assuntos
Inteligência Artificial , Software , Simulação por Computador
5.
Insect Sci ; 31(1): 59-78, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37464967

RESUMO

The Indian meal moth, Plodia interpunctella (Lepidoptera: Pyralidae), a globally distributed storage pest, relies on odors that are emitted from stored foods to select a suitable substrate for oviposition. However, the molecular mechanism underlying the chemical communication between P. interpunctella and its host remains elusive. In this study, 130 chemosensory genes were identified from the transcriptomes of 7 P. interpunctella tissues, and the quantitative expression levels of all 56 P. interpunctella odorant receptor genes (PintORs) were validated using real-time quantitative polymerase chain reaction. The functional characteristics of 5 PintORs with female antennae-biased expression were investigated using 2-electrode voltage clamp recordings in Xenopus laevis oocytes. PintOR23 was found to be specifically tuned to acetophenone. Acetophenone could elicit a significant electrophysiological response and only attracted mated females when compared with males and virgin females. In addition, molecular docking predicted that the hydrogen bonding sites, TRP-335 and ALA-167, might play key roles in the binding of PintOR23 to acetophenone. Our study provides valuable insights into the olfactory mechanism of oviposition substrate detection and localization in P. interpunctella and points toward the possibility of developing eco-friendly odorant agents to control pests of stored products.


Assuntos
Mariposas , Masculino , Feminino , Animais , Simulação de Acoplamento Molecular , Mariposas/genética , Olfato , Oviposição , Odorantes
6.
J Am Chem Soc ; 145(48): 26179-26189, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38053496

RESUMO

Porous magnets that undergo a magnetic phase transition in response to gaseous adsorbates are desirable for the development of sustainable sensing and memory devices. Familiar gases such as O2 and CO2 are one class of target adsorbates because of their close association with life sciences and environmental issues; however, it is not easy to develop magnetic devices that respond to these ubiquitous gases. To date, only three examples of gas-responsive magnetic phase transitions have been demonstrated: (i) from a ferrimagnet to an antiferromagnet, (ii) its vice versa (i.e., change of magnetic phase), and (iii) from a ferrimagnet to a paramagnet (i.e., erasure of the magnetic phase). However, the creation of a magnet, meaning the change from a nonmagnet to a magnet by O2 or CO2 gas adsorption and magnetic switching by this phenomenon have not yet been explored. Herein, we report a CO2-induced antiferromagnet modified from a paramagnetic charge-flexible layered compound, [{Ru2(2,4-F2PhCO2)4}2TCNQ(OEt)2] (1; 2,4-F2PhCO2- = 2,4-difluorobenzoate; TCNQ(OEt)2 = 2,5-diethoxy-7,7,8,8-tetracyanoquinodimethane), where three molar equivalents of CO2 was accommodated at a CO2 pressure of 100 kPa. The magnetic change originates from charge fluctuation due to the transfer of electrons moving from the electron-donor to the electron-acceptor unit or vice versa, resulting in a change in the electron distribution induced by CO2 adsorption/desorption in the donor-acceptor-type charge transfer framework. Owing to the reversible electronic state change upon CO2 adsorption/desorption, these magnetic phases are switched, accompanied by modification of the electrical conductivity, which is boosted by the CO2 accommodation. This is the first example of the creation of a CO2-responsive magnet, which is promising for novel molecular multifunctional devices.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38158486

RESUMO

The issue of environmental pollution caused by the widespread presence of microplastics (MPs) in environmental media has garnered significant attention. However, research on MPs pollution has mainly focused on aquatic ecosystems in recent years. The sources and pollution characteristics of MPs in the environment, especially in solid waste, have not been well-described. Additionally, there are few reports on the ecotoxicity of MPs, which highlights the need to fill this gap. This review first summarizes the occurrence characteristics of MPs in water, soil, and marine environments, and then provides an overview of their toxic effects on organisms and the relevant mechanisms. This paper also provides an outlook on the hotspots of research on pollution characterization and ecotoxicity of MPs. Finally, this review aims to provide insights for future ecotoxicity control of MPs. Overall, this paper expands our understanding of the pollution characteristics and ecological toxicity of MPs in current environmental media, providing forward-looking guidance for future research.

8.
Immun Inflamm Dis ; 11(11): e1060, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38018603

RESUMO

Vascular remodeling is a basic pathological process in various diseases characterized by abnormal changes in the morphology, structure, and function of vascular cells, such as migration, proliferation, hypertrophy, and apoptosis. Various growth factors and pathways are involved in the process of vascular remodeling. The transforming growth factor-ß (TGF-ß) signaling pathway, which is mainly mediated by TGF-ß1, is an important factor in vascular wall enhancement during vascular development and regulates the vascular response to injury by promoting the accumulation of intimal tissue. Vascular endothelial growth factor (VEGF) has an important effect on initiating the formation of blood vessels. The Hippo-YAP/TAZ signaling pathway also plays an important role in angiogenesis. In addition, studies have shown that there is a certain interaction between the TGF-ß/Smads signaling pathway, Hippo-YAP/TAZ signaling pathway, and VEGF. Many studies have shown that in the development of atherosclerosis, hypertension, aneurysm, vertebrobasilar dolichoectasia, pulmonary hypertension, restenosis after percutaneous transluminal angioplasty, and other diseases, various inflammatory reactions lead to changes in vascular structure and vascular microenvironment, which leads to vascular remodeling. The occurrence of vascular remodeling changes the morphology of blood vessels and thus changes the hemodynamics, which is the cause of further development of the disease process. Vascular remodeling can cause vascular smooth muscle cell dysfunction and vascular homeostasis regulation. This review aims to explore the mechanisms of the TGF-ß/Smads signaling pathway, Hippo-YAP/TAZ signaling pathway, and vascular endothelial growth factor in vascular remodeling and related diseases. This paper is expected to provide new ideas for research on the occurrence and development of related diseases and provide a new direction for research on the treatment of related diseases.


Assuntos
Via de Sinalização Hippo , Fator A de Crescimento do Endotélio Vascular , Humanos , Transdução de Sinais , Remodelação Vascular , Proteínas de Sinalização YAP
9.
Bioresour Technol ; 387: 129647, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37567350

RESUMO

In light of the characteristics of excessive acidification and low biogas yield during kitchen waste (KW) dry digestion, the impact of the calcium oxide (CaO) on KW mesophilic dry digestion was investigated, and the enhanced mechanism was revealed through metagenomic approach. The results showed that CaO increased the biogas production, when the CaO dosage was 0.07 g/g (based on total solid), the biogas production reached 656.84 mL/g suspended solids (VS), approximately 8.38 times of that in the control. CaO promoted the leaching and hydrolysis of key organic matter in KW. CaO effectively promoted the conversion of volatile fatty acid (VFA) and mitigated over-acidification. Macrogenome analysis revealed that CaO increased the microbial diversity in KW dry digestion and upregulated the abundance of genes related to amino acid and carbohydrates metabolism. This study provides an effective strategy with potential economic benefits to improve the bioconversion efficiency of organic matter in KW.


Assuntos
Biocombustíveis , Ácidos Graxos Voláteis , Anaerobiose , Ácidos Graxos Voláteis/metabolismo , Compostos de Cálcio , Metano/metabolismo , Reatores Biológicos
10.
Adv Sci (Weinh) ; 10(27): e2300759, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37544925

RESUMO

Numerous studies have demonstrated that individual proteins can moonlight. Eukaryotic Initiation translation factor 3, f subunit (eIF3f) is involved in critical biological functions; however, its role independent of protein translation in regulating colorectal cancer (CRC) is not characterized. Here, it is demonstrated that eIF3f is upregulated in CRC tumor tissues and that both Wnt and EGF signaling pathways are participating in eIF3f's oncogenic impact on targeting phosphoglycerate dehydrogenase (PHGDH) during CRC development. Mechanistically, EGF blocks FBXW7ß-mediated PHGDH ubiquitination through GSK3ß deactivation, and eIF3f antagonizes FBXW7ß-mediated PHGDH ubiquitination through its deubiquitinating activity. Additionally, Wnt signals transcriptionally activate the expression of eIF3f, which also exerts its deubiquitinating activity toward MYC, thereby increasing MYC-mediated PHGDH transcription. Thereby, both impacts allow eIF3f to elevate the expression of PHGDH, enhancing Serine-Glycine-One-Carbon (SGOC) signaling pathway to facilitate CRC development. In summary, the study uncovers the intrinsic role and underlying molecular mechanism of eIF3f in SGOC signaling, providing novel insight into the strategies to target eIF3f-PHGDH axis in CRC.


Assuntos
Neoplasias Colorretais , Transdução de Sinais , Humanos , Fator de Crescimento Epidérmico , Serina
11.
Anal Sci ; 39(10): 1643-1660, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37378821

RESUMO

Salmonella is a common intestinal pathogen that can cause food poisoning and intestinal disease. The high prevalence of Salmonella necessitates efficient and sensitive methods for its identification, detection, and monitoring, especially of viable Salmonella. Conventional culture methods need to be more laborious and time-consuming. And they are relatively limited in their ability to detect Salmonella in the viable but non-culturable status if present in the sample to be tested. As a result, there is an increasing need for rapid and accurate techniques to detect viable Salmonella spp. This paper reviewed the status and progress of various methods reported in recent years that can be used to detect viable Salmonella, such as culture-based methods, molecular methods targeting RNAs and DNAs, phage-based methods, biosensors, and some techniques that have the potential for future application. This review can provide researchers with a reference for additional method options and help facilitate the development of rapid and accurate assays. In the future, viable Salmonella detection approaches will become more stable, sensitive, and fast and are expected to play a more significant role in food safety and public health.


Assuntos
Técnicas Biossensoriais , Salmonella , Microbiologia de Alimentos , Técnicas Biossensoriais/métodos , Inocuidade dos Alimentos
12.
Math Biosci Eng ; 20(6): 10090-10134, 2023 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-37322925

RESUMO

The reptile search algorithm (RSA) is a bionic algorithm proposed by Abualigah. et al. in 2020. RSA simulates the whole process of crocodiles encircling and catching prey. Specifically, the encircling stage includes high walking and belly walking, and the hunting stage includes hunting coordination and cooperation. However, in the middle and later stages of the iteration, most search agents will move towards the optimal solution. However, if the optimal solution falls into local optimum, the population will fall into stagnation. Therefore, RSA cannot converge when solving complex problems. To enable RSA to solve more problems, this paper proposes a multi-hunting coordination strategy by combining Lagrange interpolation and teaching-learning-based optimization (TLBO) algorithm's student stage. Multi-hunting cooperation strategy will make multiple search agents coordinate with each other. Compared with the hunting cooperation strategy in the original RSA, the multi-hunting cooperation strategy has been greatly improved RSA's global capability. Moreover, considering RSA's weak ability to jump out of the local optimum in the middle and later stages, this paper adds the Lens pposition-based learning (LOBL) and restart strategy. Based on the above strategy, a modified reptile search algorithm with a multi-hunting coordination strategy (MRSA) is proposed. To verify the above strategies' effectiveness for RSA, 23 benchmark and CEC2020 functions were used to test MRSA's performance. In addition, MRSA's solutions to six engineering problems reflected MRSA's engineering applicability. It can be seen from the experiment that MRSA has better performance in solving test functions and engineering problems.


Assuntos
Algoritmos , Répteis , Animais , Humanos , Engenharia , Aprendizagem
13.
iScience ; 26(4): 106440, 2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37035004

RESUMO

The main cause of high mortality in cancer patients is tumor metastasis. Exploring the underlying mechanism of tumor metastasis is of great significance for clinical treatments. Here, we identify the transcription factor Apt/FSBP is a suppressor for tumor metastasis. In Drosophila wing disc, knockdown of apt is able to trigger cell migration, whereas overexpression of apt hampers scrib-RNAi-induced tumor cell migration. Further studies show that loss of apt promotes cell migration through activating the JNK pathway. To investigate the role of FSBP, the homolog of Apt in mammals, we construct Fsbp liver-specific knockout mice. Knockout of Fsbp in liver does not cause any detectable physiological defects, but predisposes to tumorigenesis on DEN and CCl4 treatment. In addition, loss of Fsbp accelerates tumor metastasis from liver to diaphragm. Taken together, this study uncovers FSBP is a novel tumor suppressor, and provides it as a considerable drug target for tumor treatment.

14.
Hepatol Int ; 17(2): 417-426, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36322301

RESUMO

BACKGROUND AND AIMS: The portal pressure gradient (PPG) measured at the time of transjugular intrahepatic portosystemic shunt (TIPS) completion (immediate PPG) is easily disturbed by many factors. This study aimed to assess the diagnostic value of PPG remeasured 2-4 days after TIPS (delayed PPG) by comparison with immediate PPG. METHODS: We retrospectively analyzed cirrhotic patients aged 18-75 years who received TIPS for preventing variceal rebleeding and pressure measurements at different time points. RESULTS: Of 154 eligible patients, 60 (39.0%), 62 (40.3%), and 32 (20.8%) were categorized into group LL (both immediate and delayed PPG < 12 mmHg), LH (immediate PPG < but delayed PPG ≥ 12 mmHg) and HH (both immediate and delayed PPG ≥ 12 mmHg), respectively. Mean immediate and delayed PPG were 9.2 mmHg and 12.8 mmHg (p < 0.001). During a median follow-up of 22 months, the 1-year probability of variceal rebleeding was significantly lower in group LL (1.7%) compared to LH (9.8%, absolute risk difference [ARD]: - 8.2%, p = 0.028) and HH (12.6%, ARD: - 11.1%, p = 0.014), but was not significantly different between groups LH and HH (ARD: - 2.9%, p = 0.671). Delayed PPG (p < 0.001) was identified as an independent predictor of variceal rebleeding in multivariable Cox regression analysis. The area under curves of delayed and immediate PPG in predicting variceal rebleeding were 0.837 and 0.693 for all patients (p = 0.031), and 0.936 and 0.694 for patients without shunt dysfunction (p < 0.001). CONCLUSIONS: In cirrhotic patients with variceal bleeding, delayed PPG has higher predictive power for variceal rebleeding than immediate PPG.


Assuntos
Varizes Esofágicas e Gástricas , Derivação Portossistêmica Transjugular Intra-Hepática , Humanos , Pressão na Veia Porta , Estudos Retrospectivos , Cirrose Hepática/complicações , Cirrose Hepática/cirurgia , Hemorragia Gastrointestinal/prevenção & controle , Resultado do Tratamento
15.
Microsc Res Tech ; 86(1): 12-27, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36318186

RESUMO

Baryscapus dioryctriae is an endoparasitic wasp in the pupae of many Pyralidae pests, such as Dioryctria mendacella, Ostrinia furnacalis, and Chilo suppressalis. To provide requisite background for our ongoing research on the mechanisms of host location in B. dioryctriae, the morphology, abundance, distribution, and ultrastructure of the antennal sensilla were investigated using scanning and transmission electron microscopy. The geniculate antennae of B. dioryctriae are composed of scape, pedicel, and flagellum. Eight types of sensilla including Böhm sensilla, chaetica, trichodea, basiconic capitate peg, campaniformia, placodea, coeloconica, and sensilla styloconicum with a long hair were identified on both sexes. Sexual dimorphism exists in the antennae of B. dioryctriae. The number of flagellomere in males is over females, and the subtypes and abundance of sensilla are also different between the sexes. Additionally, the possible functions of distinct sensilla were discussed, which varies from olfaction, contact chemoreceptive, mechanoreception to hygro-/thermoreception, especially, the sensilla trichodea and placodea might be involved in olfactory perception in B. dioryctriae. These results provide an essential basis for further study on chemical communication between B. dioryctriae and their hosts, and contribute to the development of B. dioryctriae becoming an effective biocontrol agent against the pests of agriculture and forestry.


Assuntos
Himenópteros , Vespas , Animais , Feminino , Masculino , Himenópteros/ultraestrutura , Sensilas/ultraestrutura , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Caracteres Sexuais , Antenas de Artrópodes/ultraestrutura
16.
Cell Discov ; 8(1): 130, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36473865

RESUMO

Chromodomain helicase DNA binding protein (CHD) family plays critical roles in regulating gene transcription. The family is linked to cancer disease, but the family member's role in tumorigenesis remains largely unknown. Here, we report that CHD6 is highly expressed in colorectal cancer (CRC). CHD6 knockdown inhibited cancer cell proliferation, migration, invasion, and tumorigenesis. Consistently, Villin-specific Chd6 knockout in mice attenuates cancer formation in AOM/DSS model. We found that aberrant EGF signals promoted the stability of CHD6 by diminishing ubiquitin-mediated degradation. EGF signal inhibits GSK3ß activity, which in turn prevents phosphodegron formation of CHD6, thereby hindering E3 ligase FBXW7-mediated CHD6 ubiquitination and degradation. CHD6's chromatin remodeler activity engages in binding Wnt signaling transcription factor TCF4 to facilitate the transcriptional expression of TMEM65, a mitochondrial inner membrane protein involved in ATP production and mitochondrial dynamics. In addition, Wnt signaling is also an upstream regulator of CHD6. CHD6 promoter contains TCF4 and ß-catenin binding site, and CHD6 can be transcriptionally activated by Wnt ligand to facilitate TMEM65 transcription. Thus CHD6-TMEM65 axis can be regulated by both EGF and Wnt signaling pathways through two different mechanisms. We further illustrate that CHD6-TMEM65 axis is deregulated in cancer and that co-administration of Wnt inhibitor LGK974 and the anti-EGFR monoclonal antibody cetuximab largely restricted the growth of patient-derived xenografts of CRC. Targeting CHD6-TMEM65 axis may be effective for cancer intervention.

17.
Pak J Med Sci ; 38(7): 1748-1753, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36246689

RESUMO

Objectives: To study the effects of anisodamine-tirofiban combined therapy on cardiac function and serological expression of serum NGF and ESM-1 in patients with acute myocardial infarction treated with percutaneous coronary intervention (PCI). Methods: Eighty patients with myocardial infarction treated in Cangzhou Medical College, Hebei, China from February 2015 to April 2017 were selected and divided into the control group and the research group according to the principle of random draw, 40 patients per group. The patients in the control group received symptomatic routine treatment, while the patients in the research group received anisodamine-tirofiban combined therapy on the top of symptomatic routine treatment. Differences between the two groups in TIMI flow grades, cardiac function, levels of NGF and ESM-1 and adverse response were observed. Results: The recovery of cardiac function in the research group was statistically significant with P value (p<0.05) and better than the control group in TIMI flow grades, myocardial perfusion capacity and cardiac function. The serological indicators in the research group had a higher level of NGF and a lower level of ESM-1 than the control group, and the differences were statistically significant (p<0.05). In terms of safety, neither group showed significant hepatorenal disorders. Conclusion: The combined treatment of anisodamine-tirofiban in patients with acute myocardial infarction after percutaneous coronary intervention (PCI) can recover NGF and ESM-1 related proteins, improve postoperative myocardial perfusion, and accelerate the recovery of cardiac function. It is worth promoting in clinic.

18.
Dis Markers ; 2022: 8973721, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36148160

RESUMO

This work was aimed at investigating the predictive value on prognosis, response to immunotherapy, and association with the immune landscape of costimulatory molecules in HCC patients. We acquired the clinicopathological information and gene expression of HCC patients from public available database (TCGA and GEO). The prognostic model in TCGA database was established with LASSO regression and Cox regression analysis. Through the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis, the enrichment analysis was implemented for analyzing the biological function and associated pathways. Immune microenvironment, immune escape, immune therapy, and tumor mutation were analyzed between both risk groups. TNFRSF4, the critical costimulatory molecule, was chosen for the in-depth investigation in vitro experiments. A novel risk signature based on 8 costimulatory molecules associated with prognosis was constructed from TCGA and proved in the database of GEO. The ROC and Kaplan-Meier curves confirmed that this risk model has good predictive accuracy. Our functional analysis demonstrated costimulatory molecular genes might associate with immune-related functions and pathways. Statistical differences were not shown between both groups, in the aspect of immune landscape, response to immune therapy, and tumor mutation. Knocking down TNFRSF4 expression significantly reduced the proliferation ability and increased the apoptosis ability. On the basis of the costimulatory molecule expression in HCC, a novel risk model was constructed and had an excellent value to predict prognosis, immune microenvironment, and response to immune therapy. TNFRSF4 was identified as an underlying oncogene in HCC and deserves further exploration.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Prognóstico , Microambiente Tumoral/genética
19.
Arch Biochem Biophys ; 727: 109348, 2022 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-35835230

RESUMO

Fibroblast growth factor 2 (FGF2) plays crucial roles in the growth and development of several tissues. However, its function in bone homeostasis remains controversial. Here, we found that exogenous FGF2 supplementation inhibited the mineralization of bone marrow stromal cells (BMSCs), at least partially, via up-regulating the gene expression of osteoclastogenesis. The FGF receptor (FGFR) allosteric antagonist SSR128129E modestly, whereas the FGFR tyrosine kinase inhibitor AZD4547 significantly antagonized the effects of FGF2. Mechanistically, FGF2 stimulated ERK phosphorylation, and the ERK signaling inhibitor PD325901 strongly blocked FGF2 enhancement of osteoclastogenesis. Moreover, the phosphorylation of CREB was also activated in response to FGF2, thereby potentiating the interaction of p-CREB with the promoter region of Rankl gene. Notably, FGF2-deficient BMSCs exhibited higher mineralization capability and lower osteoclastogenic gene expression. Correspondingly, FGF2-knockout mice showed increased bone mass and attenuated expression of osteoclast-related markers, which were associated with moderate inhibition of the ERK signaling. In conclusion, FGF2 positively regulates osteoclastogenesis via stimulating the ERK-CREB pathway. These findings establish the importance of FGF2 in bone homeostasis, hinting the potential use of FGF2/ERK/CREB specific inhibitors to fight against bone-related disorders, such as osteoporosis.


Assuntos
Fator 2 de Crescimento de Fibroblastos , Osteogênese , Animais , Diferenciação Celular , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Fator 2 de Crescimento de Fibroblastos/metabolismo , Fator 2 de Crescimento de Fibroblastos/farmacologia , Sistema de Sinalização das MAP Quinases , Camundongos , Osteoclastos/metabolismo , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais
20.
Oncogene ; 41(36): 4231-4243, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35906392

RESUMO

Altered expression of Urea Cycle (UC) enzymes occurs in many tumors, resulting a metabolic hallmark termed as UC dysregulation. Polyamines are synthesized from ornithine, and polyamine synthetic genes are elevated in various tumors. However, the underlying deregulations of UC/ polyamine synthesis in cancer remain elusive. Here, we characterized a hypoxia-induced lncRNA LVBU (lncRNA regulation via BCL6/urea cycle) that is highly expressed in colorectal cancer (CRC) and correlates with poor cancer prognosis. Increased LVBU expression promoted CRC cells proliferation, foci formation and tumorigenesis. Further, LVBU regulates urea cycle and polyamine synthesis through BCL6, a negative regulator of p53. Mechanistically, overexpression of LVBU competitively bound miR-10a/miR-34c to protect BCL6 from miR-10a/34c-mediated degradation, which in turn allows BCL6 to block p53-mediated suppression of genes (arginase1 ARG1, ornithine transcarbamylase OTC, ornithine decarboxylase 1 ODC1) involved in UC/polyamine synthesis. Significantly, ODC1 inhibitor attenuated the growth of patient derived xenografts (PDX) that sustain high LVBU levels. Taken together, elevated LVBU can regulate BCL6-p53 signaling axis for systemic UC/polyamine synthesis reprogramming and confers a predilection toward CRC development. Our data demonstrates that further drug development and clinical evaluation of inhibiting UC/polyamine synthesis are warranted for CRC patients with high expression of LVBU.


Assuntos
Neoplasias Colorretais , MicroRNAs , RNA Longo não Codificante , Animais , Neoplasias Colorretais/patologia , Humanos , Poliaminas/metabolismo , RNA Longo não Codificante/genética , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Ureia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA