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1.
Ecotoxicol Environ Saf ; 222: 112471, 2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-34229168

RESUMO

Ammonia is one of major pollutants in aquatic environment that induces severe stress and toxicity to organisms in aquatic system. The intestine acts a major defense line that protects living organisms from biotic and abiotic stresses. In the current study, we examined the effects of ammonia on intestinal histomorphology, transcriptional levels of intestinal barrier functioning genes and intestinal microbiota of Chinese striped-neck turtle (Mauremys sinensis). Thus, the turtles were placed in water with addition of ammonia at 0 (control), 100, 200 mg L-1 for 30 days. Our findings showed that ammonia reduced the villus length and induced the inflammatory cells appearance. In addition, the epithelial tight junction genes, claudin and zonola occludin significantly downregulated in ammonia exposed groups as compared to control group (P < 0.05). Similarly, the mRNA expression levels of MUC-2 gene also significantly decreased in ammonia treated groups (P < 0.05). However, the expression levels of intestinal immune related genes such as IL-10, IL-12, TGF-ß1, TNF-α and IFN-γ significantly increased (P < 0.05). Furthermore, ammonia changed gut microbial diversity variedly. At the phylum levels, Firmicutes increased, whereas Bacteroidota, Desulfobacterota and Synergistota decreased significantly. Likewise, Lachnospiraceae, Bacteroides, Eubacteriaceae, Desulfovibrio, Muribaculaceae, Bilophila, Cloacibacillus, Christensenellaceae, Ruminococcus and Parabacteroides decreased while, Romboutsia and Turicibacter increased in ammonia exposed groups. In conclusion, ammonia at 100 and 200 mg L-1 could alter the intestinal barrier function and change the composition of intestinal microbiota, leading to bad health status in M. sinensis.

2.
Front Immunol ; 12: 685559, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34234783

RESUMO

Post-ischemic acute kidney injury and disease (AKI/AKD) involve acute tubular necrosis and irreversible nephron loss. Mononuclear phagocytes including conventional dendritic cells (cDCs) are present during different phases of injury and repair, but the functional contribution of this subset remains controversial. Transcription factor interferon regulatory factor 8 (IRF8) is required for the development of type I conventional dendritic cells (cDC1s) lineage and helps to define distinct cDC1 subsets. We identified one distinct subset among mononuclear phagocyte subsets according to the expression patterns of CD11b and CD11c in healthy kidney and lymphoid organs, of which IRF8 was significantly expressed in the CD11blowCD11chigh subset that mainly comprised cDC1s. Next, we applied a Irf8-deficient mouse line (Irf8 fl/fl Clec9a cre mice) to specifically target Clec9a-expressing cDC1s in vivo. During post-ischemic AKI/AKD, these mice lacked cDC1s in the kidney without affecting cDC2s. The absence of cDC1s mildly aggravated the loss of living primary tubule and decline of kidney function, which was associated with decreased anti-inflammatory Tregs-related immune responses, but increased T helper type 1 (TH1)-related and pro-inflammatory cytokines, infiltrating neutrophils and acute tubular cell death, while we also observed a reduced number of cytotoxic CD8+ T cells in the kidney when cDC1s were absent. Together, our data show that IRF8 is indispensable for kidney cDC1s. Kidney cDC1s mildly protect against post-ischemic AKI/AKD, probably via suppressing tissue inflammation and damage, which implies an immunoregulatory role for cDC1s.

3.
Acta Biochim Pol ; 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34237204

RESUMO

C-type natriuretic peptide (CNP) is an important regulator of the male reproductive process. Our previous investigations showed that CNP can significantly stimulate the mRNA expression of androgen-binding protein (Abp) and transferrin (Trf) in the rat Sertoli cells, but the pathways responsible for this process remain to be elucidated. We predict that CNP binds the natriuretic peptide receptor B (NPR-B) to regulate expression of ABP and TRF through the intracellular cyclic guanosine monophosphate (cGMP) pathway. To address this question, in this study, we first confirmed the expression and localization of CNP and NPR-B in rat testes by immunohistochemistry and western blotting. Then, ELISA and real-time PCR were performed to investigate the signaling pathway of CNP in Sertoli cells in rat testes. Our results showed that CNP was mainly localized in the germ cells and Leydig cells, and its receptor, NPR-B, was mostly expressed in the Sertoli cells and vascular endothelial cells. CNP supplementation in the Sertoli cell medium was accompanied by an increase in the amount of intracellular cGMP and in the production of Abp and Trf mRNA, whereas inhibition of PKG with KT5823 led to a decrease in the expression of Abp and Trf mRNA. Moreover, Abp and Trf mRNA were no longer elevated when we used liposome-mediated RNA interference technology to silence the NPR-B gene in a mouse Sertoli cell line (TM4). These results suggest that CNP contributes to the regulation of ABP and TRF in the Sertoli cells through the NPR-B/cGMP/PKG signaling pathways.

4.
Chin Med J (Engl) ; 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34238851

RESUMO

BACKGROUND: Globally, colorectal cancer (CRC) imposes a substantial burden on healthcare systems and confers considerable medical expenditures. We aimed to evaluate the global and regional burden in epidemiological trends and factors associated with the incidence and mortality of CRC. METHODS: We used data from the GLOBOCAN database to estimate CRC incidence and mortality in 60 countries in 2020 and their association with the human development index (HDI). Trends of age-standardized rates of incidence and mortality in 60 countries (2000-2019) were evaluated by Joinpoint regression analysis using data of Global Burden of Disease 2019. The association between exposure to country-level lifestyle, metabolic and socioeconomic factors obtained from the World Health Organization Global Health Observatory and World Bank DataBank data and CRC incidence and mortality was determined by multivariable linear regression. RESULTS: CRC incidence and mortality varied greatly in the 60 selected countries, and much higher incidence and mortality were observed in countries with higher HDIs, and vice versa. From 2000 to 2019, significant increases of incidence and mortality were observed for 33 countries (average annual percent changes [AAPCs], 0.24-3.82) and 18 countries (AAPCs, 0.41-2.22), respectively. A stronger increase in incidence was observed among males (AAPCs, 0.36-4.54) and individuals <50 years (AAPCs, 0.56-3.86). Notably, 15 countries showed significant decreases in both incidence (AAPCs, -0.24 to -2.19) and mortality (AAPCs, -0.84 to -2.74). A significant increase of incidence among individuals <50 years was observed in 30 countries (AAPCs, 0.28-3.62). Countries with higher incidence were more likely to have a higher prevalence of alcohol drinking, higher level of cholesterol level, higher level of unemployment, and a poorer healthcare system. CONCLUSIONS: Some high-HDI countries showed decreasing trends in CRC incidence and mortality, whereas developing countries that previously had low disease burden showed significantly increased incidence and mortality trends, especially in males and populations ≥50 years, which require targeted preventive health programs.

5.
Inorg Chem ; 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34232028

RESUMO

The new indium-based organic framework {(Me2NH2)[In(BDPO)]·DMF·2H2O}n (1) was successfully constructed by using the oxalamide group modified ligand N,N'-bis(isophthalic acid)oxalamide (H4BDPO). This framework presents a 2-fold interpenetrating structural characteristic, and the unique polar pore environment leads to a high capture ability for CO2, C2Hn and CH3OH and good separation ability for CO2 and C2Hn over CH4 as well as for CH3OH over C2H5OH, which was further verified by an ideal adsorbed solution theory (IAST) calculation. Theoretical simulations pointed out the possible adsorption sites of different adsorbed gases in 1. In addition, the excellent chemical stability and strong luminescence of 1 give it an effective selective detection ability for 2,6-dichloro-4-nitroaniline (DCN) in water with a low detection limit of 3.85 ppm, and the detection mechanism is discussed in detail.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34236162

RESUMO

Two-dimensional (2D) materials with intrinsic magnetic properties are intensively explored due to their potential applications in low-power-consumption electronics and spintronics. To date, only a handful of intrinsic magnetic 2D materials have been reported. Here, we report a realization of intrinsic ferromagnetic behavior in 2D V2C MXene nanosheets through layer mismatch engineering. The V2C MXene nanosheets with a small-angle twisting show a robust intrinsic ferromagnetic response with a saturation magnetic moment of 0.013 emu/g at room temperature. An in-depth study has been performed by X-ray absorption spectroscopy as well as electron paramagnetic resonance (EPR) and photoelectron spectroscopy analyses. It has been revealed that the symmetry-broken interlayer twisting reduced the degeneracy of V 3d states and the van Hove singularity. This led to a redistribution of the density of electronic states near the Fermi level and consequently activated the Stoner ferromagnetism with improved density of itinerant d electrons. This work highlights V2C MXene as a promising intrinsic room-temperature ferromagnetic material with potential applications in spintronics or spin-based electronics.

7.
JAMA Ophthalmol ; 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34236391

RESUMO

Importance: Interest in teleophthalmology has been growing, especially during the COVID-19 pandemic. The advent of fifth-generation (5G) wireless systems has the potential to revolutionize teleophthalmology, but these systems have not previously been leveraged to conduct therapeutic telemedicine in the ophthalmology field. Objective: To assess the feasibility of 5G real-time laser photocoagulation as a telemedicine-based treatment for diabetic retinopathy (DR). Design, Setting, and Participants: This was a prospective study involving a retinal specialist from the Peking Union Medical College Hospital in Beijing, China, who performed online 5G real-time navigated retinal laser photocoagulation to treat participants with proliferative or severe nonproliferative DR who had been recruited in the Huzhou First People's Hospital in Zhejiang Province, China, located 1200 km from Beijing from October 2019 to July 2020. Interventions: These teleretinal DR and laser management procedures were conducted using a teleophthalmology platform that used the videoconference platform for teleconsultation, after which telelaser planning and intervention were conducted with a laser system and a platform for remote computer control, which were connected via 5G networks. Main Outcomes and Measures: Diabetic eye prognosis and the real-time laser therapy transmission speed were evaluated. Results: A total of 6 participants (9 eyes) were included. Six eyes were treated via panretinal photocoagulation alone, while 1 eye underwent focal/grid photocoagulation and 2 eyes underwent both panretinal photocoagulation and focal/grid photocoagulation. The mean (SD) age was 53.7 (13.6) years (range, 32-67 years). The mean (SD) duration of diabetes was 14.3 (6.4) years (range, 3-20 years). The mean (SD) logMAR at baseline was 0.32 (0.20) (20/30 Snellen equivalent). Retinal telephotocoagulation operations were performed on all eyes without any noticeable delay during treatment. The mean (SD) number of panretinal photocoagulation laser spots per eye in 1 session was 913 (243). Conclusions and Relevance: This study introduces a novel teleophthalmology paradigm to treat DR at a distance. Applying novel technologies may continue to ensure that remote patients with DR and other conditions have access to essential health care. Further studies will be needed to compare this approach with the current standard of care to determine whether visual acuity or safety outcomes differ.

8.
Cell Commun Signal ; 19(1): 69, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193153

RESUMO

BACKGROUND: Intercellular communications are important for maintaining normal physiological processes. An important intercellular communication is mediated by the exchange of membrane-enclosed extracellular vesicles. Among various vesicles, exosomes can be detected in a wide variety of biological systems, but the regulation and biological implication of exosome secretion/uptake remains largely unclear. METHODS: Cellular retinoic acid (RA) binding protein 1 (Crabp1) knockout (CKO) mice were used for in vivo studies. Extracellular exosomes were monitored in CKO mice and relevant cell cultures including embryonic stem cell (CJ7), macrophage (Raw 264.7) and hippocampal cell (HT22) using Western blot and flow cytometry. Receptor Interacting Protein 140 (RIP140) was depleted by Crispr/Cas9-mediated gene editing. Anti-inflammatory maker was analyzed using qRT-PCR. Clinical relevance was accessed by mining multiple clinical datasets. RESULTS: This study uncovers Crabp1 as a negative regulator of exosome secretion from neurons. Specifically, RIP140, a pro-inflammatory regulator, can be transferred from neurons, via Crabp1-regulated exosome secretion, into macrophages to promote their inflammatory polarization. Consistently, CKO mice, defected in the negative control of exosome secretion, have significantly elevated RIP140-containing exosomes in their blood and cerebrospinal fluid, and exhibit an increased vulnerability to systemic inflammation. Clinical relevance of this pathway is supported by patients' data of multiple inflammatory diseases. Further, the action of Crabp1 in regulating exosome secretion involves its ligand and is mediated by its downstream target, the MAPK signaling pathway. CONCLUSIONS: This study presents the first evidence for the regulation of exosome secretion, which mediates intercellular communication, by RA-Crabp1 signaling. This novel mechanism can contribute to the control of systemic inflammation by transferring an inflammatory regulator, RIP140, between cells. This represents a new mechanism of vitamin A action that can modulate the homeostasis of system-wide innate immunity without involving gene regulation. Video Abstract.

9.
Front Public Health ; 9: 663965, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34211951

RESUMO

Objectives: To develop and validate a radiomics model for distinguishing coronavirus disease 2019 (COVID-19) pneumonia from influenza virus pneumonia. Materials and Methods: A radiomics model was developed on the basis of 56 patients with COVID-19 pneumonia and 90 patients with influenza virus pneumonia in this retrospective study. Radiomics features were extracted from CT images. The radiomics features were reduced by the Max-Relevance and Min-Redundancy algorithm and the least absolute shrinkage and selection operator method. The radiomics model was built using the multivariate backward stepwise logistic regression. A nomogram of the radiomics model was established, and the decision curve showed the clinical usefulness of the radiomics nomogram. Results: The radiomics features, consisting of nine selected features, were significantly different between COVID-19 pneumonia and influenza virus pneumonia in both training and validation data sets. The receiver operator characteristic curve of the radiomics model showed good discrimination in the training sample [area under the receiver operating characteristic curve (AUC), 0.909; 95% confidence interval (CI), 0.859-0.958] and in the validation sample (AUC, 0.911; 95% CI, 0.753-1.000). The nomogram was established and had good calibration. Decision curve analysis showed that the radiomics nomogram was clinically useful. Conclusions: The radiomics model has good performance for distinguishing COVID-19 pneumonia from influenza virus pneumonia and may aid in the diagnosis of COVID-19 pneumonia.


Assuntos
COVID-19 , Orthomyxoviridae , Humanos , Estudos Retrospectivos , SARS-CoV-2 , Tomografia Computadorizada por Raios X
10.
Pathol Oncol Res ; 27: 594299, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34257541

RESUMO

Glioblastoma is one of the most aggressive primary brain tumors with few treatment strategies. ß-Elemene is a sesquiterpene known to have broad spectrum antitumor activity against various cancers. However, the signaling pathways involved in ß-elemene induced apoptosis of glioblastoma cells remains poorly understood. In this study, we reported that ß-elemene exhibited antiproliferative activity on U87 and SHG-44 cells, and induced cell death through induction of apoptosis. Incubation of these cells with ß-elemene led to the activation of caspase-3 and generation of reactive oxygen species (ROS). Western blot assay showed that ß-elemene suppressed phosphorylation of STAT3, and subsequently down-regulated the activation of p-JAK2 and p-Src. Moreover, pre-incubation of cells with ROS inhibitor N-acetyl-L-cysteine (NAC) significantly reversed ß-elemene-mediated apoptosis effect and down-regulation of JAK2/Src-STAT3 signaling pathway. Overall, our findings implied that generation of ROS and suppression of STAT3 signaling pathway is critical for the apoptotic activity of ß-elemene in glioblastoma cells.

11.
Comput Math Methods Med ; 2021: 9980459, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34257702

RESUMO

circRNAs (circular RNAs) are a family of noncoding RNAs and have diverse physiological and pathological functions. However, the functions and mechanisms of circRNAs in the development and progression of colorectal cancer (CRC) remain largely unknown. Here, we aimed to explore the functions and roles of circFAT1(e2) in CRC. qRT-PCR revealed that circFAT1(e2) in CRC tumor tissues was upregulated compared with that in adjacent normal tissues and was also upregulated in CRC cell lines. Small interfering RNAs (siRNAs) against circFAT1(e2) were used to decrease the expression of circFAT1(e2) in HCT116 and RKO cells in vitro. The roles of circFAT1(e2) in CRC cell metastasis and proliferation were then determined by transwell and CCK-8 assays. The results showed that circFAT1(e2) silencing markedly suppressed CRC growth. Moreover, we identified circFAT1(e2) as a promoter of CRC metastasis. Knockdown of circFAT1(e2) evidently reduced HCT116 and RKO cell migration and invasion. Furthermore, the regulatory relationship between circFAT1(e2) and its target miRNAs was verified by a luciferase reporter assay. We demonstrated that circFAT1(e2) could sponge miR-30e-5p, which regulated the expression level of integrin α6 (ITGA6), the downstream target gene of miR-30e-5p. Rescue assays demonstrated that knockdown of miR-30e-5p enhanced CRC proliferation and migration via ITGA6. Taken together, our results reveal the novel oncogenic roles of circFAT1(e2) in CRC through the miR-30e-5p/ITGA6 axis.

12.
Zhongguo Zhen Jiu ; 41(7): 781-6, 2021 Jul 12.
Artigo em Chinês | MEDLINE | ID: mdl-34259412

RESUMO

OBJECTIVE: To observe the effect of long-term moxa smoke exposure of different concentrations on olfactory function in rats, and provide experimental basis of safety study of moxa smoke produced by moxibustion. METHODS: Forty SD rats were randomly divided into a normal control group, a low-concentration moxa smoke group, a moderate-concentration moxa smoke group and a high-concentration moxa smoke group, 10 rats in each one. The rats in the moxa smoke groups were put into three plexiglass moxibustion boxes with different moxa smoke concentrations, 4 hours per times, twice a day for 90 days. The general state of rats was evaluated before and during the experiment. After the intervention, the olfactory function was evaluated by two-bottle experiment (TBE); the morphology of nasal mucosa was observed by HE staining; the apoptosis of olfactory epithelial cells in nasal mucosa was detected by TUNEL method; the serum levels of interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected by ELISA method. RESULTS: In the late stage of moxa smoke exposure (45-90 days into intervention), the behavioral activity of rats in the moderate-concentration moxa smoke group and the high-concentration moxa smoke group was weaker than that in the normal control group, and their response to stimulation was strong, and their mental state was worse. After intervention, the drinking rate of vinegar-water mixture in the moderate-concentration moxa smoke group and the high-concentration moxa smoke group was higher than that in the normal control group and the low-concentration moxa smoke group (P<0.01). The hierarchical structure of nasal mucosa in the moderate-concentration moxa smoke group and the high-concentration moxa smoke group was unclear, disordered, necrotic and inflammatory cell infiltration was serious; the number of apoptotic cells in olfactory epithelium of nasal mucosa in the moderate-concentration moxa smoke group and the high-concentration moxa smoke group was more than that in the normal control group and the low-concentration moxa smoke group (P<0.01), that in the high-concentration moxa smoke group was more than the moderate-concentration group (P<0.01). The serum levels of IL-1, IL-6 and TNF-α in the low-concentration moxa smoke group, the moderate-concentration moxa smoke group and the high-concentration moxa smoke group were higher than the normal control group (P<0.01), and those in the moderate-concentration moxa smoke group and the high-concentration moxa smoke group were higher than the low-concentration moxa smoke group (P<0.01), and those in the high-concentration moxa smoke group were higher than moderate-concentration moxa smoke group (P<0.01). CONCLUSION: The long-term exposure to low, moderate and high concentrations of moxa smoke could cause pathological changes in nasal mucosa and increase the serum levels of IL-1, IL-6 and TNF-α; the moderate and high concentrations of moxa smoke exposure could cause a series of damage to olfactory function and reduce olfactory sensitivity in rats.

13.
Tissue Eng Regen Med ; 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34260048

RESUMO

BACKGROUND: We previously found that atorvastatin (ATV) enhanced mesenchymal stem cells (MSCs) migration, by a yet unknown mechanism. CXC chemokine receptor 4 (CXCR4) is critical to cell migration and regulated by microRNA-146a (miR-146a). Therefore, this study aimed to assess whether ATV ameliorates MSCs migration through miR-146a/CXCR4 signaling. METHODS: Expression of CXCR4 was evaluated by flow cytometry. Expression of miR-146a was examined by reverse transcription-quantitative polymerase chain reaction. A transwell system was used to assess the migration ability of MSCs. Recruitment of systematically delivered MSCs to the infarcted heart was evaluated in Sprague-Dawley rats with acute myocardial infarction (AMI). Mimics of miR-146a were used in vitro, and miR-146a overexpression lentivirus was used in vivo, to assess the role of miR-146a in the migration ability of MSCs. RESULTS: The results showed that ATV pretreatment in vitro upregulated CXCR4 and induced MSCs migration. In addition, flow cytometry demonstrated that miR-146a mimics suppressed CXCR4, and ATV pretreatment no longer ameliorated MSCs migration because of decreased CXCR4. In the AMI model, miR-146a-overexpressing MSCs increased infarct size and fibrosis. CONCLUSION: The miR-146a/CXCR4 signaling pathway contributes to MSCs migration and homing induced by ATV pretreatment. miR-146a may be a novel therapeutic target for stimulating MSCs migration to the ischemic tissue for improved repair.

14.
Proc Natl Acad Sci U S A ; 118(29)2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34253615

RESUMO

We investigated the role of mesothelin (Msln) and thymocyte differentiation antigen 1 (Thy1) in the activation of fibroblasts across multiple organs and demonstrated that Msln-/- mice are protected from cholestatic fibrosis caused by Mdr2 (multidrug resistance gene 2) deficiency, bleomycin-induced lung fibrosis, and UUO (unilateral urinary obstruction)-induced kidney fibrosis. On the contrary, Thy1-/- mice are more susceptible to fibrosis, suggesting that a Msln-Thy1 signaling complex is critical for tissue fibroblast activation. A similar mechanism was observed in human activated portal fibroblasts (aPFs). Targeting of human MSLN+ aPFs with two anti-MSLN immunotoxins killed fibroblasts engineered to express human mesothelin and reduced collagen deposition in livers of bile duct ligation (BDL)-injured mice. We provide evidence that antimesothelin-based therapy may be a strategy for treatment of parenchymal organ fibrosis.

15.
Am J Otolaryngol ; 42(6): 103112, 2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34214712

RESUMO

BACKGROUNDS: Platinum-based induction chemotherapy (ICT) confers benefits in suitable patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Additionally, the application of a proper local approach can not only promote the survival quality and alleviate the suffering, but also improve the resectability in patients with advanced malignant tumor. 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a promising minimally invasive therapy and has shown good efficacy in the treatment of patients bearing precancerous lesions and oral squamous cell carcinoma (OSCC). The aim of the study was to evaluate the application of topical ALA-PDT synchronized with ICT in locally advanced OSCC. PATIENTS AND METHODS: This study described the application of topical ALA-PDT combined with TPF (docetaxel, cisplatin, and 5-fluorouracil) ICT in eleven patients treated due to locally advanced in the oral cavity. Patients qualified for this type of local treatment had cancerous lesions located on the surface of the gum or oral mucosa. The efficacy was evaluated based on the clinical response and complications of the patients. RESULTS: All patients were treated with four courses (bi-weekly) of ALA-PDT with three courses of TPF containing ICT. After treatment, the overall response rate was 90.9%. Then ten patients with surgery experienced radical surgery alone or combined with radiotherapy except a patient with serious heart condition. In the follow-up period of 26-43 months (median duration of 34.1 months), no local recurrence was observed in cases. Only one patient (9.1%) died of unrelated myocardial infarction. CONCLUSION: Topical ALA-PDT proved to be a safe treatment in OSCC patients with locally advanced sites, which could be an appropriate addition to ICT. Despite the short observation period and small sample size, it seems justified to conduct prospective studies for the evaluation of the efficacy and safety of topical ALA-PDT synchronized with ICT followed by surgery.

16.
Poult Sci ; 100(8): 101271, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34214748

RESUMO

Occludin is an important component of tight junction proteins and has been extensively studied in animals such as mice, chickens, geese, and pigs. As one of the most important waterfowl species in China, Muscovy duck (Cairina moschata) is an important economic animal for meat. However, research on the occludin gene in Muscovy duck is lacking. In the present study, Muscovy duck occludin cDNA was cloned for the first time. The length of the cDNA was 1,699 bp, and it showed a high sequence similarity with the Anser cygnoides domesticus and Gallus gallus occludin genes. The occludin gene was differentially expressed in the tissues of healthy ducks. The highest and lowest expressions of occludin were observed in the crop and the spleen, respectively. After the oral administration of Clostridium butyricum (CB), the occludin expression in the ileum of 7-day-old Muscovy ducks was significantly upregulated and subsequently showed a decreasing trend in 14-day-old Muscovy ducks. Under the early intervention of CB, no significant difference was observed in the occludin expression of cecum between the control and CB group. Collectively, these results suggest that CB plays an important role in regulating the expression of the occludin gene in Muscovy ducks, and adding CB in feed may maintain the intestinal barrier of ducks by regulating the expression of occludin.

17.
Chem Commun (Camb) ; 57(58): 7067-7082, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34195709

RESUMO

As a paramount factor to restrict the potential action of drugs and biologics, nanoplatforms based on dynamic covalent chemistry have been demonstrated as promising candidates to fulfill the full requirements during the whole delivery process by the virtue of their remarkable features such as adaptiveness, stimuli-responsiveness, specificity, reversibility and feasibility. This contribution summarizes the latest progress in dynamic covalent bond-based nanoplatforms with improved delivery efficiency and therapeutic performance. In addition, major challenges and perspectives in this field are also discussed. We expect that this feature article will provide a valuable and systematic reference for the further development of dynamic covalent bond-based nanoplatforms.

18.
Aquat Toxicol ; 237: 105903, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34229255

RESUMO

Ammonia is a major pollutant in the water environment, which could cause severe harm to aquatic organisms. To explore the pathological and physiological effects of ammonia in Chinese striped-necked turtles (Mauremys sinensis), the individuals (body mass: 218.26 ± 12.65 g) were divided into two groups: control group and ammonia exposed group (6.25 mM total ammonia), then the expression levels of signaling factors involved in the endoplasmic reticulum stress and apoptotic pathways were determined. The results showed that ammonia exposure up-regulated the transcriptional and protein levels of endoplasmic reticulum stress marker gene Bip. Meanwhile, the relative mRNA levels of key genes (PERK, ATF6, eIF2α, ATF4, IRE1α and XBP1) involved in unfolded protein response up-regulated, and the phosphorylation levels of PERK, eIF2α and IRE1α increased correspondingly. In addition, the protein and transcriptional levels of CHOP and JNK related to apoptotic pathway induced by unfolded protein reaction increased under ammonia exposure. Moreover, Bcl-2 mRNA expression levels and protein levels decreased, whereas BAX and caspase-3 showed an opposite trend, and the cleaved protein of caspase-3 appeared when the turtles in the elevated ammonia. Furthermore, the apoptotic cells in liver increased after ammonia exposure. These results suggested ammonia exposure induced endoplasmic reticulum stress, then activated unfolded protein response, followed by apoptosis in M. sinensis. The results will contribute to a better understanding of the toxicity mechanism of ammonia to aquatic turtles.

19.
Oncol Rep ; 46(2)2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34278503

RESUMO

Non­small cell lung cancer (NSCLC), which accounts for ~85% of all lung cancer cases, is commonly diagnosed at an advanced stage and has a high patient mortality rate. Despite the increasing availability of treatment strategies, the prognosis of patients with NSCLC remains poor, with a low 5­year survival rate. This poor prognosis may be associated with the tumor heterogeneity of NSCLC, as well as its acquisition and intrinsic resistance to therapeutic drugs. It has been suggested that combination therapy with telomerase inhibition may be an effective strategy for the treatment of drug­sensitive and drug­resistant types of cancer. Telomerase is the key enzyme for cell survival, and ~90% of human cancers maintain telomeres by activating telomerase, which is driven by the upregulation of telomerase reverse transcriptase (TERT). Several mechanisms of telomerase reactivation have been described in a variety of cancer types, including TERT promoter mutation, epigenetic modifications via a TERT promoter, TERT amplification, and TERT rearrangement. The aim of the present study was to comprehensively review telomerase activity and its association with the clinical characteristics and prognosis of NSCLC, as well as analyze the potential mechanism via which TERT activates telomerase and determine its potential clinical application in NSCLC. More importantly, current treatment strategies targeting TERT in NSCLC have been summarized with the aim to promote discovery of novel strategies for the future treatment of NSCLC.

20.
Artigo em Inglês | MEDLINE | ID: mdl-34278598

RESUMO

BACKGROUND AND AIM: Activated hepatic stellate cells (HSCs) are the most critical cells responsible for liver fibrosis, and platelet-derived growth factor (PDGF) is the most prominent mitogen for HSCs in fibrogenesis. This study aimed to explore the potential of gadolinium (Gd)-labelled cyclic peptides (pPB) targeting PDGF receptor-ß (PDGFR-ß) as a magnetic resonance imaging (MRI) radiotracer to identify the progression of liver fibrosis by imaging hepatic PDGFR-ß expression. METHODS: Mice treated with carbon tetrachloride (CCl4 ) were used to mimic hepatic fibrosis in vivo. The binding activity of FITC-labelled pPB to PDGFR-ß was assessed in cultured human HSCs (HSC-LX2). MRI was performed to visualize hepatic PDGFR-ß expression in mice with different degrees of liver fibrosis after Gd-labelled pPB was injected. RESULTS: Hepatic PDGFR-ß expression level was correlated with the severity of liver fibrosis, and the majority of cells expressing PDGFR-ß were found to be activated HSCs in fibrotic livers. Culture-activated human HSCs expressed abundant PDGFR-ß, and FITC-labelled pPB could bind to these cells in a concentration- and time-dependent manner. With Gd-labelled pPB as a tracer, an MRI modality demonstrated that the relative hepatic T1-weighted MRI signal value progressively increased with the severity of hepatic fibrosis, and reduced with remission. CONCLUSIONS: Hepatic PDGFR-ß expression reflects the progression of hepatic fibrosis, and MRI using Gd-labelled pPB as a tracer exhibits potential for distinguishing liver fibrosis staging in mice.

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