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1.
Front Oncol ; 12: 976224, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36185176

RESUMO

Background: Several studies have reported an association between the occurrence of immune-related adverse events (irAEs) and prognosis in patients with melanoma treated with immune checkpoint inhibitors (ICIs), but the results remain controversial. We conducted a systematic review and meta-analysis to investigate the association between irAEs and survival in patients with melanoma treated with ICIs. Methods: We searched the PubMed, Web of Science, and China National Knowledge Infrastructure databases through May 5, 2022 for clinical studies evaluating the association between irAEs and in melanoma patients treated with ICIs. Combined hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were calculated using fixed- or random-effects models based on heterogeneity. Results: A total of 60 articles were included, with 16,520 patients. In patients with melanoma treated with ICIs, the occurrence of irAEs was significantly associated with better OS (HR, 0.58; 95% confidence interval [CI], 0.51-0.66; P<0.00001) and PFS (HR, 0.61; 95%CI, 0.51-0.72; P<0.00001). Endocrine irAEs (OS, HR, 0.81; 95%CI, 0.72-0.92; P=0.001; PFS: HR, 0.84; 95%CI, 0.73-0.96, P=0.009), skin irAEs (OS, HR, 0.59; 95%CI, 0.41-0.85; P=0.004; PFS: HR, 0.43; 95%CI, 0.36-0.52; P<0.00001), vitiligo (OS, HR, 0.22; 95%CI, 0.15-0.31; P<0.00001; PFS, HR, 0.33; 95%CI, 0.25-0.44; P<0.00001), and grade 1-2 irAEs (OS, HR, 0.67; 95%CI, 0.58-0.78; P<0.00001; PFS, HR, 0.62; 95%CI, 0.51-0.76; P<0.00001) showed similar results. However, thyroid, lung, gastrointestinal, liver, and grade 3-4 irAEs were not significantly associated with OS and PFS. The occurrence of non-thyroid endocrine irAEs was significantly associated with better OS (HR, 0.22; 95%CI, 0.15-0.31; P<0.00001). In patients with melanoma treated with anti-programmed cell death protein 1 (OS, HR, 0.61; 95%CI, 0.51-0.72; P<0.00001; PFS, HR, 0.59; 95%CI, 0.47-0.74; P<0.00001), the association between irAEs and clinical benefit was clearer than in patients treated with anti-cytotoxic T-lymphocyte-associated protein 4 (OS, HR, 0.68; 95%CI, 0.52-0.89; P=0.005; PFS, HR, 0.93; 95%CI, 0.49-1.78; P=0.83). Conclusion: Among patients with melanoma treated with ICIs, those who developed non-thyroid endocrine irAEs and cutaneous irAEs have better prognosis. This suggests that non-thyroid endocrine irAEs and cutaneous irAEs may be a prognostic biomarker for patients with melanoma treated with ICIs. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022338308.

2.
Int J Gen Med ; 15: 7459-7466, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36187160

RESUMO

Purpose: To assess the relationship between the duration of systemic corticosteroid therapy and blood eosinophil counts in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD). Patients and Methods: This study included 292 patients with acute COPD exacerbations treated with daily intravenous injections of 40 mg/day methylprednisolone at the Department of Respiratory Medicine, Anhui No.2 Provincial People's Hospital, Hefei, China. The study subjects were divided into two groups - (1) a low-dose group (n = 136) that included patients treated with methylprednisolone for less than or equal to 5 days and (2) a high-dose group (n = 156) that included patients treated with methylprednisolone for more than 5 days. The blood eosinophil counts were analyzed for both the patient groups, and an optimal cut-off value was calculated to distinguish between the two groups. The study endpoints were readmission or deaths within 30 days or 180 days and re-infections within 90 days after hospital discharge. Results: The mean blood eosinophil counts in the low- and high-dose groups were 0.15 × 109/L (0.11-0.23 × 109/L) and 0.08 × 109/L (0.04-0.12 × 109/L), respectively (P < 0.01). Receiver operating characteristic (ROC) curve analysis showed that the cut-off value for the blood eosinophils to distinguish the two patient groups was 0.115 × 109/L with a sensitivity and specificity of 72.8% and 72.4%, respectively. The number of readmissions between the two groups at 30 days and 180 days after hospital discharge did not show any significant differences (P = 0.292, P = 0.398). The follow-up data showed significantly higher rate of re-infections in the high-dose group (24/136) within 90 days after hospital discharge compared to the low-dose group (9/156) (P = 0.018). Conclusion: In patients with acute exacerbations of COPD, blood eosinophil counts of ≥0.115 × 109/L were associated with effective response to corticosteroid therapy in ≤5 days.

3.
Front Vet Sci ; 9: 1005899, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36187840

RESUMO

Avian pathogenic E. coli (APEC), one of the widespread zoonotic-pathogen, can cause a series of diseases collectively known as colibacillosis. This disease can cause thousands of million dollars economic loss each year in poultry industry and threaten to human health via meat or egg contamination. However, the detailed molecular mechanism underlying APEC infection is still not fully understood. Circular RNAs, a new type of endogenous noncoding RNA, have been demonstrated to involve in various biological processes. However, it is still not clear whether the circRNAs participate in host response against APEC infection. Herein, we utilized the high-throughput sequence technology to identify the circRNA expression profiles in APEC infected HD11 cells. A total of 49 differentially expressed (DE) circRNAs were detected in the comparison of APEC infected HD11 cells vs. wild type HD11 cells, which were involved in MAPK signaling pathway, Endocytosis, Focal adhesion, mTOR signaling pathway, and VEGF signaling pathway. Specifically, the source genes (BRAF, PPP3CB, BCL2L13, RAB11A, and TSC2) and their corresponding DE circRNAs may play a significant role in APEC infection. Moreover, based on ceRNA regulation, we constructed the circRNA-miRNA network and identified a couple of important regulatory relationship pairs related to APEC infection, including circRAB11A-gga-miR-125b-3p, circRAB11A-gga-miR-1696, and circTSC2-gga-miR-1649-5p. Results indicate that the aforementioned specific circRNAs and circRNA-miRNA network might have important role in regulating host immune response against APEC infection. This study is the first time to investigate the circRNAs expression profile and the biological function of the source genes of the identified DE circRNAs after APEC infection of chicken HD11 cells. These results would contribute to a better understanding of the molecular mechanisms in host response against APEC infection.

4.
Artigo em Inglês | MEDLINE | ID: mdl-36151600

RESUMO

Photoaffinity labeling is a powerful technique to interrogate drug-protein interactions in native cellular environments. Photo-cross-linkers are instrumental for this technique. However, the introduction of unnatural photo-cross-linkers may significantly reduce the bioactivity of the drug, thus impairing the chemoproteomic outcomes. Herein, we developed a common pharmacophore, isoxazole, into a natively embedded photo-cross-linker for chemoproteomics, which minimally perturbs the drug structure. The photo-cross-linking reactions of the isoxazole were thoroughly investigated for the first time. Functionalized isoxazoles were then designed and applied to protein labeling, demonstrating the superior photo-cross-linking efficiency. Subsequently, two isoxazole-based drugs, Danazol and Luminespib, were employed in chemoproteomic studies, revealing their potential cellular targets. These results provide valuable strategies for future chemoproteomic study and drug development.

5.
Eur Radiol ; 2022 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-36166086

RESUMO

OBJECTIVES: To compare the diagnostic and staging efficacy of PET/diagnostic-level CT (PET/DxCT) and PET/low-dose CT (PET/LDCT) in pretreatment pediatric lymphoma patients and to estimate the reduction of the CT effective dose in the PET/CT scan. METHODS: One hundred and five pediatric patients who underwent total-body PET/CT examination were enrolled and divided into the DxCT group (n = 47) and LDCT group (n = 58) according to their dose levels. The sensitivity, specificity, PPV, and NPV of PET/DxCT and PET/LDCT for detecting the involvement of lymph node, spleen, bone marrow, and other extranodal organs in pretreatment lymphoma were compared. ROC analysis was performed to evaluate the integral efficiency. The staging accuracies based on PET/DxCT and PET/LDCT were also evaluated. Dosimetry was calculated for DxCT and LDCT, and the reduction in the effective dose was estimated. RESULTS: In the diagnosis of nodal, splenic, bone marrow, and other extranodal involvement, the differences in sensitivity, specificity, PPV, and NPV between PET/LDCT and PET/DxCT were not significant (all p values ∈ [0.332, 1.000]). Both modalities had accuracies above 90% and the ROC analysis indicated good or high efficiency in diagnosing all patterns of lymphoma involvement. PET/LDCT and PET/DxCT each had a staging accuracy of 89.7% and 89.4%, respectively. LDCT had a comparable image quality score with DxCT, with a significant increase in noise (p < 0.001) and a 66.1% reduction in effective dose. CONCLUSIONS: PET/LDCT allowed for a 66.1% CT effective dose reduction compared to PET/DxCT in pediatric lymphoma patients without compromising the diagnostic and staging efficacy. KEY POINTS: • Pediatric lymphoma patients can benefit from a reduced effective dose of PET/CT. • This retrospective study showed that the diagnostic and staging efficacies of PET/low-dose CT are comparable to those of PET/diagnostic-level CT, both with satisfactory efficiency in diagnosing all patterns of lymphoma involvement. • PET/low-dose CT allowed for a 66.1% CT effective dose reduction compared to PET/diagnostic-level CT.

6.
BMC Psychiatry ; 22(1): 531, 2022 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-35931995

RESUMO

BACKGROUND: Interleukin-18 (IL-18) may participate in the development of major depressive disorder, but the specific mechanism remains unclear. This study aimed to explore whether IL-18 correlates with areas of the brain associated with depression. METHODS: Using a case-control design, 68 subjects (34 patients and 34 healthy controls) underwent clinical assessment, blood sampling, and resting-state functional Magnetic Resonance Imaging (fMRI). The total Hamilton depression-17 (HAMD-17) score was used to assess depression severity. Enzyme-linked immunosorbent assay (ELISA) was used to detect IL-18 levels. Rest-state fMRI was conducted to explore spontaneous brain activity. RESULTS: The level of IL-18 was higher in patients with depression in comparison with healthy controls. IL-18 was negatively correlated with degree centrality of the left posterior cingulate gyrus in the depression patient group, but no correlation was found in the healthy control group. CONCLUSION: This study suggests the involvement of IL-18 in the pathophysiological mechanism for depression and interference with brain activity.


Assuntos
Transtorno Depressivo Maior , Interleucina-18/metabolismo , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/fisiopatologia , Humanos , Interleucina-18/sangue , Imageamento por Ressonância Magnética/métodos
7.
Chem Commun (Camb) ; 58(67): 9425-9428, 2022 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-35916476

RESUMO

Herein, two mitochondria-targeting photosensitizers (PSs, CCVJ-Mito-1 and CCVJ-Mito-2) that exhibit a turn-on fluorescence response towards increasing viscosity are reported. Notably, CCVJ-Mito-2 exhibits absorption in the near-infrared (NIR) region, and can be employed as a NIR PS targeting mitochondria and a fluorescent probe for tracking mitochondrial viscosity changes during photodynamic therapy (PDT). This dual functional PS can help to shed light on the dynamic changes of the cellular microenvironment during PDT and further guide the PDT process.


Assuntos
Fotoquimioterapia , Fármacos Fotossensibilizantes , Mitocôndrias , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Triazenos , Viscosidade
8.
J Nanobiotechnology ; 20(1): 364, 2022 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-35933359

RESUMO

BACKGROUND: Magnetosomes (BMPs) are organelles of magnetotactic bacteria (MTB) that are responsible for mineralizing iron to form magnetite. In addition, BMP is an ideal biomaterial that is widely used in bio- and nano-technological applications, such as drug delivery, tumor detection and therapy, and immunodetection. The use of BMPs to create multifunctional nanocomposites would further expand the range of their applications. RESULTS: In this study, we firstly demonstrate that the extracted BMP can remineralize in vitro when it is exposed to AgNO3 solution, the silver ions (Ag+) were transported into the BMP biomembrane (MM) and mineralized into a silver crystal on one crystal plane of Fe3O4. Resulting in the rapid synthesis of an Ag-Fe3O4 hybrid BMP (BMP-Ag). The synergy between the biomembrane, Fe3O4 crystal, and unmineralized iron enabled the remineralization of BMPs at an Ag+ concentration ≥ 1.0 mg mL-1. The BMP-Ag displayed good biocompatibility and antibacterial activity. At a concentration of 2.0 mg/mL, the BMP-Ag and biomembrane removed Ag-Fe3O4 NPs inhibited the growth of gram-negative and gram-positive bacteria. Thus using BMP-Ag as a wound dressing can effectively enhance the contraction of infected wounds. CONCLUSIONS: This study represents the first successful attempt to remineralize organelles ex vivo, realizing the biosynthesis of hybrid BMP and providing an important advancement in the synthesis technology of multifunctional biological nanocomposites.


Assuntos
Magnetossomos , Óxido Ferroso-Férrico/química , Bactérias Gram-Negativas , Ferro/química , Magnetossomos/química , Prata/química
9.
Comput Struct Biotechnol J ; 20: 3522-3532, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35860402

RESUMO

Post-translational modifications (PTMs) are closely linked to numerous diseases, playing a significant role in regulating protein structures, activities, and functions. Therefore, the identification of PTMs is crucial for understanding the mechanisms of cell biology and diseases therapy. Compared to traditional machine learning methods, the deep learning approaches for PTM prediction provide accurate and rapid screening, guiding the downstream wet experiments to leverage the screened information for focused studies. In this paper, we reviewed the recent works in deep learning to identify phosphorylation, acetylation, ubiquitination, and other PTM types. In addition, we summarized PTM databases and discussed future directions with critical insights.

10.
J Transl Med ; 20(1): 330, 2022 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-35869517

RESUMO

BACKGROUND: Glutamine is the most abundant amino acid in the body and plays a vital role in colorectal cancer (CRC) cell metabolism. However, limited studies have investigated the clinical and prognostic significance of preoperative serum glutamine levels in patients with colorectal cancer, and the underlying mechanism has not been explored. METHODS: A total of 121 newly diagnosed CRC patients between 2012 and 2016 were enrolled in this study. Serum glutamine levels were detected, and their associations with clinicopathological characteristics, systemic inflammation markers, carcinoembryonic antigen (CEA) and prognosis were analysed. In addition, the effect of glutamine depletion on recurrence and metastasis was examined in SW480 and DLD1 human CRC cell lines, and epithelial-mesenchymal transition (EMT)-related markers were detected to reveal the possible mechanism. RESULTS: A decreased preoperative serum level of glutamine was associated with a higher T-class and lymph node metastasis (P < 0.05). A higher serum level of glutamine correlated with a lower CEA level (r = - 0.25, P = 0.02). Low glutamine levels were correlated with shorter overall survival (OS) and disease-free survival (DFS). Multivariate Cox regression analysis showed that serum glutamine was an independent prognostic factor for DFS (P = 0.018), and a nomogram predicting the probability of 1-, 3- and 5-year DFS after radical surgery was built. In addition, glutamine deficiency promoted the migration and invasion of CRC cells. E-cadherin, a vital marker of EMT, was decreased, and EMT transcription factors, including zeb1and zeb2, were upregulated in this process. CONCLUSIONS: This study elucidated that preoperative serum glutamine is an independent prognostic biomarker to predict CRC progression and suggested that glutamine deprivation might promote migration and invasion in CRC cells by inducing the EMT process.


Assuntos
Neoplasias Colorretais , Transição Epitelial-Mesenquimal , Antígeno Carcinoembrionário , Neoplasias Colorretais/patologia , Glutamina , Humanos , Prognóstico
11.
J Med Chem ; 65(15): 10408-10418, 2022 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-35880853

RESUMO

Covalent inhibitors with an electrophilic warhead have received considerable attention due to their remarkable pharmacological properties. However, the electrophilic warhead in covalent drugs is often an α, ß-unsaturated amide, and the targets are mainly cysteine or lysine residues. Thus, the development of novel electrophiles that can target other amino acids is highly desirable. Ynamide, a useful and versatile building block, is commonly employed in the construction of various compounds in organic synthesis. The performance of this functional group in a proteome-wide environment has been studied here for the first time, and it has been shown that it can efficiently modify carboxyl residues in situ and in vitro. Upon incorporation of this ynamide warhead into the pharmacophores of kinase inhibitors, the resulting compound showed moderate inhibition against the EGFR L858R mutant but not against EGFR WT. This novel electrophilic group can be used in the development of new types of covalent inhibitors.


Assuntos
Cisteína , Proteoma , Aminoácidos , Cisteína/química , Receptores ErbB , Lisina/química , Proteoma/metabolismo
12.
Eur J Med Chem ; 240: 114594, 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-35853430

RESUMO

In contrast to other sirtuins (NAD+-dependent class III lysine deacylases), inhibition of Sirt5 is poorly investigated, yet. Our present work is based on the recently identified Sirt5 inhibitor balsalazide, an approved drug with negligible bioavailability after oral administration. After gaining first insights into its structure-activity relationship in previous work, we were able to now develop heteroaryl-triaryls as a novel chemotype of drug-like, potent and subtype-selective Sirt5 inhibitors. The unfavourable azo group of the lead structure was modified in a systematic and comprehensive manner, leading us to a few open-chained and, most importantly, five-membered heteroaromatic substitutes (isoxazole CG_209, triazole CG_220, pyrazole CG_232) with very encouraging in vitro activities (IC50 on Sirt5 in the low micromolar range, <10 µM). These advanced inhibitors were free of cytotoxicity and showed favourable pharmacokinetic properties, as confirmed by permeability into mitochondria using live cell imaging experiments. Furthermore, results from calculations of the relative free binding affinities of the analogues compared to balsalazide as reference compound agreed well with the trends for inhibitory activities obtained in the in vitro experiments. Therefore, this method can be used to predict the affinity of closely related future potential Sirt5 inhibitors. Encouraged by our findings, we employed chemoproteomic selectivity profiling to confirm Sirt5 as main target of balsalazide and one of its improved analogues. An immobilised balsalazide-analogue specifically pulled down Sirt5 from whole cell lysates and competition experiments identified glutaryl-CoA dehydrogenase (GCDH) and nucleotide diphosphate kinase (NME4) as potential off-targets, once again confirming the selectivity of the novel balsalazide-derived Sirt5 inhibitors. In summary, a combination of targeted chemical synthesis, biological work, and computational studies led to a new generation of tailored Sirt5 inhibitors, which represent valuable chemical tools for the investigation of the physiological role of Sirt5, but could also serve as advanced lead structures for drug candidates for systemic use.


Assuntos
Sirtuínas , Lisina , Mitocôndrias/metabolismo , Sirtuínas/metabolismo , Relação Estrutura-Atividade
13.
Biomed Opt Express ; 13(5): 2605-2615, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35774311

RESUMO

Terahertz (THz) spectroscopy provides multifaceted capabilities for observing low-energy responses of macromolecules, cells and tissues, understanding THz biophysical effects, and expecting to realize the application of THz technology in biomedicine. However, its high-frequency characteristics of limited penetration depth and strong absorption of water in the body comparable to microwaves are impeding the proliferation of THz spectroscopy. Here we show that THz spectroscopy makes possible the observation of THz anisotropy phenomena for the first time in fascia and lean tissue. Through optical microscopy, we infer that the microscopic mechanism of THz anisotropy comes from the periodic stripe structure of the biological tissue. The above related experimental findings may be expected to promote the application of THz technology in biomedicine.

14.
Int J Ophthalmol ; 15(6): 1015-1019, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35814882

RESUMO

AIM: To identify the disease-causing mutation in a four-generation Chinese family diagnosed with Nance-Horan syndrome (NHS). METHODS: A Chinese family, including four affected patients and four healthy siblings, was recruited. All family members received ophthalmic examinations with medical histories provided. Targeted next-generation sequencing approach was conducted on the two affected males to screen for their disease-causing mutations. RESULTS: Two male family members diagnosed with NHS manifested bilateral congenital cataracts microcornea, strabismus and subtle facial and dental abnormalities, while female carriers presented posterior Y-sutural cataracts. A novel frameshift mutation (c.3916_3919del) in the NHS gene was identified. This deletion was predicted to alter the reading frame and generate a premature termination codon after a new reading frame. CONCLUSION: The study discovers a new frameshift mutation in a Chinese family with NHS. The findings broaden the spectrum of NHS mutations that can cause NHS in Chinese patients.

15.
Eur J Nucl Med Mol Imaging ; 49(12): 4145-4155, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35788704

RESUMO

PURPOSE: To explore the impact of a true half dose of [18F]-FDG on image quality in pediatric oncological patients undergoing total-body PET/CT and investigate short acquisition times with half-dose injected activity. METHODS: One hundred pediatric oncological patients who underwent total-body PET/CT using the uEXPLORER scanner after receiving a true half dose of [18F]-FDG (1.85 MBq/kg) were retrospectively enrolled. The PET images were first reconstructed using complete 600-s data and then split into 300-s, 180-s, 60-s, 40-s, and 20-s duration groups (G600 to G20). The subjective analysis was performed using 5-point Likert scales. Objective quantitative metrics included the maximum standard uptake value (SUVmax), SUVmean, standard deviation (SD), signal-to-noise ratio (SNR), and SNRnorm of the background. The variabilities in lesion SUVmean, SUVmax, and tumor-to-background ratio (TBR) were also calculated. RESULTS: The overall image quality scores in the G600, G300, G180, and G60 groups were 4.9 ± 0.2, 4.9 ± 0.3, 4.4 ± 0.5, and 3.5 ± 0.5 points, respectively. All the lesions identified in the half-dose images were localized in the G60 images, while 56% of the lesions could be clearly identified in the G20 images. With reduced acquisition time, the SUVmax and SD of the backgrounds were gradually increased, while the TBR values showed no statistically significant differences among the groups (all p > 0.1). Using the half-dose images as a reference, the variability in the lesion SUVmax gradually increased from the G180 to G20 images, while the lesion SUVmean remained stable across all age groups. SNRnorm was highly negatively correlated with age. CONCLUSION: Total-body PET/CT with a half dose of [18F]-FDG (1.85 MBq/kg, estimated whole-body effective dose: 1.76-2.57 mSv) achieved good performance in pediatric patients, with sufficient image quality and good lesion conspicuity. Sufficient image quality and lesion conspicuity could be maintained at a fast scanning time of 60 s with half-dose activity.


Assuntos
Fluordesoxiglucose F18 , Neoplasias , Criança , Humanos , Neoplasias/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos , Estudos Retrospectivos
16.
Int J Mol Sci ; 23(13)2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35806321

RESUMO

Colibacillosis is an acute and chronic avian disease caused by avian pathogenic E. coli (APEC). Previous studies have demonstrated that RIP2 plays a significant role in APEC infection. Moreover, increasing evidence indicates that microRNAs (miRNAs) are involved in host-pathogen interactions and the immune response. However, the role of miRNAs in the host against APEC infection remains unclear. Herein, we attempted to reveal new miRNAs potentially involved in the regulation of the immune and inflammatory response against APEC infection, with a particular focus on those possibly correlated with RIP2 expression, via miRNA-seq, RT-qPCR, Western blotting, dual-luciferase reporter assay, and CCK-8. The results showed that a total of 93 and 148 differentially expressed (DE) miRNAs were identified in the knockdown of RIP2 cells following APEC infection (shRIP2+APEC) vs. knockdown of RIP2 cells (shRIP2) and shRIP2 vs. wild-type cells (WT), respectively. Among those identified DE miRNAs, the biological function of gga-miR-455-5p was investigated. It was found that gga-miR-455-5p regulated by RIP2 was involved in the immune and inflammatory response against APEC infection via targeting of IRF2 to modulate the expression of type I interferons. Additionally, RIP2 could directly regulate the production of the type I interferons. Altogether, these findings highlighted the crucial role of miRNAs, especially gga-miR-455-5p, in host defense against APEC infection.


Assuntos
Infecções por Escherichia coli , Interferon Tipo I , MicroRNAs , Doenças das Aves Domésticas , Animais , Galinhas/genética , Escherichia coli/metabolismo , Infecções por Escherichia coli/genética , Infecções por Escherichia coli/veterinária , MicroRNAs/genética , MicroRNAs/metabolismo , Doenças das Aves Domésticas/genética
17.
J Vis Exp ; (184)2022 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-35723473

RESUMO

As a classical model system of embryo biology, the chicken embryo has been used to investigate embryonic development and differentiation. Delivering exogenous materials into chicken embryos has a great advantage for studying gene function, transgenic breeding, and chimera preparation during embryonic development. Here we show the method of in ovo intravascular injection whereby exogenous materials such as plasmid vectors or modified primordial germ cells (PGCs) can be transferred into donor chicken embryos at early developmental stages. The results show that the intravascular injection through the dorsal aorta and head allows injected materials to diffuse into the whole embryo through the blood circulatory system. In the presented protocol, the efficacy of exogenous plasmid and lentiviral vector introduction, and the colonization of injected exogenous PGCs in the recipient gonad, were determined by observing fluorescence in the embryos. This article describes detailed procedures of this method, thereby providing an excellent approach to studying gene function, embryo and developmental biology, and gonad-chimeric chicken production. In conclusion, this article will allow researchers to perform in ovo intravascular injection of exogenous materials into chicken embryos with great success and reproducibility.


Assuntos
Galinhas , Células Germinativas , Animais , Animais Geneticamente Modificados , Embrião de Galinha , Galinhas/genética , Quimera , Reprodutibilidade dos Testes
18.
Comput Intell Neurosci ; 2022: 2005188, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35747718

RESUMO

As a serious emergency in 2020, COVID-19 had a great impact on people's lives. In this paper, short-term and long-term response to emergency supplies needs after the outbreak of COVID-19 in a region is studied. Firstly, a comparative study of different regional resource coordination options in the early stages of COVID-19 is conducted using a multiobjective decision-making approach to arrive at the optimal solution. Then, a system dynamics model is established for the follow-up development of the epidemic, to predict the long-term development trend of the epidemic, and to study the urgency of the needs of different materials in different periods. The results show that time and satisfaction are the two most important indicators in the decision-making of the material deployment programme in the early stages of an outbreak. In the long-term control of the epidemic, the number of patients with minor illnesses generally peaks around 20 days, while the number of patients with severe illnesses generally peaks around 40 days, providing a focus for the supply of supplies at different times in the actual development of the epidemic, in order to better and more effectively control the epidemic and reduce inefficient consumption of supplies.


Assuntos
COVID-19 , COVID-19/epidemiologia , Surtos de Doenças , Seguimentos , Humanos , SARS-CoV-2
19.
Cytotechnology ; 74(3): 371-383, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35733702

RESUMO

OCT4, SOX2 and NANOG (OSN) are the key factors of cell reprogramming, which are involved in the maintenance of stem cell pluripotency. Recently, it has been found that glycolysis plays an important role in the process of somatic-cell-induced reprogramming; however, the synergistic effect of OSN on glycolysis has rarely been reported. In this study, chicken embryonic fibroblasts (CEF) was reprogrammed into induced pluripotent stem cells (iPSCs) by OCT4, SOX2, NANOG and LIN28 reprogramming strategy. RNA-seq showed that chicken iPSCs highly expressed pluripotent genes and the expression of the key genes of glycolysis, such as Hk1, Pfkp and Ldha, was also at a high level, while CEF was much lower. Glycolysis gene expression, glucose uptake and lactate production of CEF and iPSCs were also detected. The results showed that the glycolysis level of iPSCs was higher than that of CEF. ChIP-qPCR showed that SOX2 and NANOG transcription factors were significantly enriched in the promoter regions of Hk1, Pfkp and Ldha, while OCT4 was not. The above results indicated that OCT4, SOX2 and NANOG coordinately regulate glycolysis and participate in somatic-cell-induced reprogramming, thus setting a good foundation for further research on the molecular mechanism of somatic-cell-induced reprogramming. Supplementary Information: The online version contains supplementary material available at 10.1007/s10616-022-00530-6.

20.
Crit Rev Eukaryot Gene Expr ; 32(3): 21-30, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35695607

RESUMO

Malignant melanoma is one of the most aggressive types of skin cancer. Thus, efficient diagnosis and treatment methods are crucial for advanced melanoma. Circular RNAs (circRNAs) have been regarded as a 'splicing noise' in the past decades. However, several circRNAs have been recently reported to be differentially expressed in melanoma, and the cell or tissue-specific expression makes these suitable candidate diagnostic or therapeutic biomarkers. In addition, emerging studies have confirmed that circular RNAs play pivotal roles in the proliferation, invasion, metastasis, and migration of malignant melanoma. However, specific pathogenic mechanisms between melanoma and circRNAs remain unclear. In the present study, it was summarized that circRNAs are associated with the pathogenesis of melanoma, including hsa_circ_0083444, hsa_circ_0005320, hsa_circ_0067531, hsa_circ_0084043, hsa_circ_0000082, hsa_circ_0016418, hsa_circ_0085533 and hsa_circ_0025039, hsa_circ_0001946, hsa_circ_0002770, hsa_circ_0079593, hsa_circ_0027247, hsa_circ_0017247, hsa_circ_0020710. These can provide potential diagnosis, treatment, and prognostication biomarkers for advanced melanoma in clinical applications.


Assuntos
Melanoma , Neoplasias Cutâneas , Biomarcadores/metabolismo , Humanos , Melanoma/genética , RNA Circular/genética , Neoplasias Cutâneas/genética
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