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1.
Sci Rep ; 11(1): 3382, 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33564088

RESUMO

To construct and validate a nomogram to predict the overall survival (OS) of colorectal signet ring cell carcinoma (SRCC). The potentially eligible cases were obtained against the SEER database from 2004 to 2015. Log-rank test and Cox analysis were conducted to identify the independent prognostic factors for predicting OS. The identified prognostic factors were later integrated for the construction of an OS prediction nomogram. Altogether 2904 eligible cases were identified, and the median survival time was 18 (range: 0-155) months. As suggested by multivariate analysis, age, primary site, grade, tumor size, T stage, N stage, M stage, surgery, lymph node dissection and chemotherapy were identified as the independent factors for predicting OS. Afterwards, the above variables were incorporated into the nomogram. The C-index indicated better discriminatory ability of the nomogram than AJCC 8th TNM staging and SEER summary stage systems (both P < 0.001). Calibration plots further showed good consistency between the nomogram prediction and actual observation. The time independent area under the curves (tAUCs) for 3-year and 5-year OS in nomogram were larger than AJCC and SEER summary stage system. The constructed nomogram could potentially predict the survival of colorectal SRCC individuals.

2.
Int Immunopharmacol ; 93: 107165, 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33578182

RESUMO

We previously reported that helicid, an active plant monomer of Helicid nilgirica Bedd, had good antidepressant pharmacological activities. However, the potential mechanism of action remains unknown. Current investigation showed the antidepressant-like effects of helicid and its effects on the neurocalcin delta (NCALD) gene, and its mechanism of action through a depression model in rats exposed to chronic unpredictable mild stress (CUMS). We evaluated depression symptoms using the sucrose preference test (SPT), open field test (OFT), and forced swimming test (FST). By silencing NCALD and using rescue experiments, the IL-6, iNOS, IL-1ß, COX-2, and TNF-α levels in the hippocampus or peripheral blood were determined using western blotting and ELISAs. The expression of IKKß, p-IкBα, p-IKKß, NF-кB p65, and IкBα were tested using western blots of the cytoplasmic or nuclear samples. Helicid and silencing NCALD relieved the CUMS-irritated depressive-like actions of rats, which were shown by increased consumption of sucrose, numbers of rearings, total running distance, zone crossings, and reduced immobility times. Helicid or silencing NCALD reversed the CUMS-induced high levels of IL-1ß, COX-2, IL-6, TNF-α, and iNOS in the hippocampus or peripheral blood. Helicid or silencing NCALD also reduced the expressions of p-IκBα and p-IKKß in the cytoplasm and the expression of nuclear NF-κB p 65 in hippocampus, and simultaneously elevated cytoplasmic expressions of IκBα, IKKß, and NF-κB p65 in the hippocampus. Notably, after NCALD overexpression, the biochemical indices of rat helicid administration were reversed. In conclusion, the antidepressant action of helicid was mediated through NCALD in rats of CUMS by repressing hippocampal neuro-inflammation and abating the activation of the IKK/IκBα/NF-κB pathway.

3.
Expert Rev Clin Pharmacol ; : 1-12, 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33618586

RESUMO

Introduction: Nilotinib is a second-generation tyrosine kinase inhibitor (TKI) targeting BCR/ABL, which is used for the first-line treatment of newly diagnosed chronic myeloid leukemia (CML) patients and the second-line treatment of most CML patients who are resistant or intolerant to prior therapy that includes imatinib. In addition to common adverse reactions, long-term use of nilotinib shows some toxicities that are different from those of occurring during other BCR/ABL TKI treatments, such as cardiovascular toxicity. It is life-threatening, which would affect not only the choice of initial treatment of CML patients but also the safety of long-term medication.Areas covered: Through searching literature and reports from PubMed and clinical trials, here we review a profile of the adverse effects induced by nilotinib. We also discuss the potential molecular toxicological mechanisms and clinical management, which may provide strategies to prevent or intervene the toxicity associated with nilotinib.Expert opinion: Severe adverse effects associated with nilotinib limit its long-term clinical application. However, the exact mechanisms underlying these toxicities remain unclear. Future research should focus on the developing strategies to reduce the toxicities of nilotinib as well as to avoid similar toxicity in the development of new drugs.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33554891

RESUMO

OBJECTIVE: Here we examined the influence of methane-rich saline treatment (MS) on the whole transcriptome of the skin flaps during the ischemia/reperfusion (I/R) injuryusing RNA-sequence (RNA-seq). METHODS: The rats were divided into three groups: the sham surgery group (SH),the I/R surgery group treated with physiological saline (I/R-P) or the I/R surgery group treated with the methane-rich saline (I/R-M) respectively. On the 72 hours after operation, the perfusion and the distribution of micro-circulatoryblood flow in skin flaps were observed by laser doppler flowmeters. The whole transcriptome alteration of the skin flaps was examined using RNA-seq. Moreover, the responses of the skin flaps to MRS treatment were examined using bio-informatic and q-PCR approaches after I/R injury. RESULTS: The methane-rich saline (MS) treatment could expand survival area and improve the blood perfusion of the skin flaps after l/R injury. Compared to the I/R-P group, 474 genes significantly altered in the I/R-M group. These genes were mainly associated the development, the cell adhesion and migration. In addition, the PI3K-Akt signal pathway was meaningfully related to regulation of MS treatment. Q-PCR results confirmed that MS treatment positively regulated PI3K-Akt signal pathway relative genes and inhibited the cell adhesion relative genes. CONCLUSION: These results proved that methane-rich saline may alleviate I/R injury and improve flap survival rate by regulating cell adhesion and PI3K-Akt signal pathway.

5.
IEEE Trans Biomed Eng ; PP2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33606624

RESUMO

OBJECTIVE: Biopsies are the gold standard for clinical diagnosis. However, a discrepancy between the biopsy sample and target tissue because of misplacement of the biopsy spoon can lead to errors in the diagnosis and subsequent treatment. Thus, correctly determining whether the needle tip is in the tumor is crucial for accurate biopsy results. METHODS: A biopsy needle system was designed with a steerable, flexible, and superelastic concentric tube; electrodes to monitor the electrical resistivity; and load cells to monitor the insertion force. The degrees of freedom were analyzed for two working modes: straight-line and deflection. RESULTS: Experimental results showed that the system could perceive the tissue type in real-time based on the electrical resistivity. In addition, changes in the insertion force indicated transitions between the interfaces of adjacent tissue layers. CONCLUSION: The two monitoring methods guarantee that the biopsy spoon is at the desired position inside the tumor during an operation. SIGNIFICANCE: The proposed biopsy needle system can be integrated into an autonomous robotic biopsy system.

6.
J Sci Food Agric ; 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33543481

RESUMO

BACKGROUND: Aspergillus ochraceus causes food spoilage and produces mycotoxin ochratoxin A (OTA) during storage of agricultural commodities. In this study, citral was used to inhibit A. ochraceus growth and OTA accumulation, proteomic analysis was employed to verify the mechanism of citral. RESULTS: Citral was found to significantly inhibit fungal growth and mycotoxin production in A. ochraceus. Specifically, 75, 125, 150 and 200 µL L-1 citral suppressed mycelial growth by 33%, 46%, 50% and 100%, respectively. Additionally, 75 µL L-1 citral inhibited OTA accumulation by 25%. Proteomic analysis was performed to elucidate the inhibitory mechanism of citral on mycelial growth and OTA production at subinhibitory concentrations (75 µL L-1 ). Proteomics analysis identified 2646 proteins in A. ochraceus fc-1, of which 218 were differentially expressed between control and 75 µL L-1 citral treatment samples. Differentially expressed proteins were identified by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of biological process, cellular component and molecular function terms. Potential factors affecting mycelial growth and OTA production were analysed, and OTA production was revealed to be a complex process involving many associated factors related to various processes including nutrient intake, sterol biosynthesis, ribosome biogenesis, energy metabolism, oxidative stress and amino acid metabolism. In addition, citral at 75 µL L-1 down-regulated OTA biosynthetic genes including pks and nrps, but slightly up-regulated the global regulatory factors veA, velB and laeA. CONCLUSION: The findings further demonstrate the potential of citral for the preservation of grains and other agricultural products, and provide new insight into its antifungal mechanisms at subinhibitory concentrations. © 2021 Society of Chemical Industry.

7.
Opt Lett ; 46(3): 536-539, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33528403

RESUMO

We systematically studied femtosecond laser-inscribed self-organized nanogratings and geometric phase elements such as a polarization diffraction focusing lens and Q-plate in sapphire crystal. Besides the void structures observed in the focus, nanogratings with periods of 150~300 nm were observed, depending on a nanoslit that took the role of a seeding effect by localized light field enhancement. The non-polarized refractive index change and birefringence were measured with values around 1∼2×10-3 and 6×10-4, respectively. Based on the laser-inscribed form birefringence, a geometric phase lens and Q-plate were successfully demonstrated in sapphire with high imaging and a focusing effect. We expect that our findings may promote the understanding of laser-induced nanogratings in bulk and potential applications in geometric phase elements.

8.
Toxins (Basel) ; 13(1)2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33450861

RESUMO

Dry-cured meat products are worldwide food with high-salt content, and filamentous fungi are beneficial to the maturation process. However, some salt-tolerant strains of Aspergillus and Penicillium produce ochratoxin A (OTA) on these products and thus threaten food safety. In our study, proteomic analysis was performed to reveal the mechanism of adaptability to high-salt environment by Aspergillus ochraceus. Twenty g/L and 70 g/L NaCl substrates were used to provide medium- and high-NaCl content environments, respectively. The NaCl addition could induce fungal growth, but only 20 g/L NaCl addition could induce spore production while 70 g/L repressed it. Proteomics analysis identified 2646 proteins in A. ochraceus fc-1, of which 237 and 251 were differentially expressed with 20 g/L and 70 g/L NaCl addition, respectively. Potential factors affecting fungal growth and development were identified by GO and KEGG analyses of biological process, cellular component, and molecular function terms. The results revealed that ergosterol synthesis pathway was significantly upregulated with 20 g/L and 70 g/L NaCl addition. However, fungal growth and development including OTA production were complex processes associated with many factors including nutrient uptake, cell membrane integrity, cell cycle, energy metabolism, intracellular redox homeostasis, protein synthesis and processing, autophagy, and secondary metabolism. Reactive oxygen species may be an important window to understand the mechanism that medium-salt content was conducive to intracellular signal transduction while high-salt content caused oxidative stress. The findings would help to improve the processes and storage conditions of dry-cured meat products.

9.
Biochem Pharmacol ; 185: 114407, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33421376

RESUMO

The tumor suppressor protein p53 participates in the control of key biological functions such as cell death, metabolic homeostasis and immune function, which are closely related to various diseases such as tumors, metabolic disorders, infection and neurodegeneration. The p53 gene is also mutated in approximately 50% of human cancer cells. Mutant p53 proteins escape from the ubiquitination-dependent degradation, gain oncogenic function and promote the carcinogenesis, malignant progression, metastasis and chemoresistance. Therefore, the stability of both wild type and mutant p53 needs to be precisely regulated to maintain normal functions and targeting the p53 stability is one of the therapeutic strategies against cancer. Here, we focus on compound-induced degradation of p53 by both the ubiquitination-dependent proteasome and autophagy-lysosome degradation pathways. We also review other posttranslational modifications which control the stability of p53 and the biological functions involved in these processes. This review provides the current theoretical basis for the regulation of p53 abundance and its possible applications in different diseases.

10.
J Environ Sci (China) ; 101: 36-48, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33334530

RESUMO

Cu-Co multiple-oxides modified on HNO3-pretreated activated coke (ACN) were optimized for the simultaneous removal of gaseous CO and elemental mercury (Hg0) at low temperature (< 200 °C). It was found that 2%CuOx-10%CoOx/ACN catalyst calcined at 400°C resulted in the coexistence of complex oxides including CuO, Cu2O, Co3O4, Co2O3 and CoO phases, which might be good for the simultaneous catalytic oxidation of CO by Co-species and removal of Hg0 by Cu-species, benefiting from the synergistic catalysis during the electro-interaction between Co and Cu cations (CoO ⇌ Co3O4 and Cu2O ⇌ CuO). The catalysis removal of CO oxidation was obviously depended on the reaction temperature obtaining 94.7% at 200 °C, while no obvious promoting effect on the Hg0 removal (68.3%-78.7%). These materials were very substitute for the removal of CO and Hg° from the flue gas with the conditions of 8-20 vol.% O2 and flue-gas temperature below 200 °C. The removal of Hg° followed the combination processes of adsorption and catalytic oxidation reaction via Langmuir-Hinshelwood mechanism, while the catalysis of CO abided by the Mars-van Krevelen mechanism with lattice oxygen species.


Assuntos
Coque , Mercúrio , Adsorção , Catálise , Gases , Oxirredução , Temperatura
11.
J Infect Chemother ; 27(2): 323-328, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33309627

RESUMO

PURPOSE: We aimed to compare the efficacy of percutaneous nephrostomy (PCN) versus retrograde ureteric stent (RUS) for acute upper urinary tract obstruction with urosepsis. MATERIALS AND METHODS: We performed a random study, comparing PCN to RUS, for the treatment of patients requiring emergency drainage due to acute upper urinary tract obstruction with urosepsis between January 2019 to March 2020. Data collected included patient characteristics, stone material, microbiological characteristics, and laboratory data. Statistical analysis was performed by the student's t-test or Mann-Whitney U test or chi-squared test and Fisher exact test. RESULTS: At first, a total of 75 patients were eligibly assessed for enrollment. Among them, 3 cases were excluded for declining to participate and 7 cases were failed treated with RUS. At last, 35 PCN (53.85%) and 30 RUS (46.15%) patients were analyzed. There were 24 (36.92%) men and 41 (63.08%) women. The median age was 65 years. Emergency decompression was achieved by PCN in 35 (53.85%) patients and by RUS in 30 (46.15%). Urine culture was positive in 32 (49.23%) patients, of which 17 (53.13%) had E. coli. Postoperative C-reactive protein value and normal temperature recovery time in the PCN group were significantly lower than in the RUS group(P < .05). CONCLUSION: PCN had a better outcome than RUS in emergency drainage with urosepsis, especially for patients with severe inflammation and fever.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33259305

RESUMO

Molecular communication (MC) is a promising paradigm, which conveys messages at the nano- or micro- scale for information exchange by using molecules or particles as signal carriers. Clock synchronization between transmitters and receivers in MC systems plays an important role in information exchange and nanodevices' collaboration. The current research about the synchronization mainly focuses on fixed MC systems. However, the movements of transmitters and receivers commonly exist in MC systems. In this paper, two clock synchronization schemes, the least square method and the peak time method, are proposed to estimate the clock offset between a mobile transmitter and a mobile receiver in mobile MC systems. The synthesis time of information molecules is also taken into consideration in the proposed schemes, and by using different types of molecules, the influence of the synthesis time of molecules can be solved. The effects of the movement of receiver on the received signal are discussed. The performance of the proposed schemes is evaluated by simulations and discussed.

13.
JAMA Psychiatry ; 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33263727

RESUMO

Importance: The genetic basis of bipolar disorder (BD) in Han Chinese individuals is not fully understood. Objective: To explore the genetic basis of BD in the Han Chinese population. Design, Setting, and Participants: A genome-wide association study (GWAS), followed by independent replication, was conducted to identify BD risk loci in Han Chinese individuals. Individuals with BD were diagnosed based on DSM-IV criteria and had no history of schizophrenia, mental retardation, or substance dependence; individuals without any personal or family history of mental illnesses, including BD, were included as control participants. In total, discovery samples from 1822 patients and 4650 control participants passed quality control for the GWAS analysis. Replication analyses of samples from 958 patients and 2050 control participants were conducted. Summary statistics from the European Psychiatric Genomics Consortium 2 (PGC2) BD GWAS (20 352 cases and 31 358 controls) were used for the trans-ancestry genetic correlation analysis, polygenetic risk score analysis, and meta-analysis to compare BD genetic risk between Han Chinese and European individuals. The study was performed in February 2020. Main Outcomes and Measures: Single-nucleotide variations with P < 5.00 × 10-8 were considered to show genome-wide significance of statistical association. Results: The Han Chinese discovery GWAS sample included 1822 cases (mean [SD] age, 35.43 [14.12] years; 838 [46%] male) and 4650 controls (mean [SD] age, 27.48 [5.97] years; 2465 [53%] male), and the replication sample included 958 cases (mean [SD] age, 37.82 [15.54] years; 412 [43%] male) and 2050 controls (mean [SD] age, 27.50 [6.00] years; 1189 [58%] male). A novel BD risk locus in Han Chinese individuals was found near the gene encoding transmembrane protein 108 (TMEM108, rs9863544; P = 2.49 × 10-8; odds ratio [OR], 0.650; 95% CI, 0.559-0.756), which is required for dendritic spine development and glutamatergic transmission in the dentate gyrus. Trans-ancestry genetic correlation estimation (ρge = 0.652, SE = 0.106; P = 7.30 × 10-10) and polygenetic risk score analyses (maximum liability-scaled Nagelkerke pseudo R2 = 1.27%; P = 1.30 × 10-19) showed evidence of shared BD genetic risk between Han Chinese and European populations, and meta-analysis identified 2 new GWAS risk loci near VRK2 (rs41335055; P = 4.98 × 10-9; OR, 0.849; 95% CI, 0.804-0.897) and RHEBL1 (rs7969091; P = 3.12 × 10-8; OR, 0.932; 95% CI, 0.909-0.956). Conclusions and Relevance: This GWAS study identified several loci and genes involved in the heritable risk of BD, providing insights into its genetic architecture and biological basis.

14.
J Biochem Mol Toxicol ; : e22672, 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33270355

RESUMO

Brahma-related gene 1 (Brg-1) is perceived as a cytoprotective protein due to its role in alleviating oxidative stress and apoptosis. Our study aimed to explore the role and mechanism of Brg-1 in high glucose (HG)-stimulated podocytes. The HG exposure downregulated Brg-1 and inactivated the protein kinase B (Akt) pathway in podocytes. Restoration of Brg-1 inhibited HG-induced viability reduction of podocytes. The HG-induced increase of reactive oxygen species and malondialdehyde levels and decrease of superoxide dismutase activity in podocytes were reversed by the Brg-1 overexpression. The Brg-1 overexpression terminated the HG-induced production of fibronectin, collagen IV, transforming growth factor-ß1, and connective tissue growth factor. In addition, the Brg-1 overexpression activated Akt-dependent nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling in HG-stimulated podocytes. However, inhibition of the Akt pathway or Nrf2 silencing counteracted the protective effects of Brg-1 in HG-stimulated podocytes. In conclusion, the Brg-1 overexpression suppressed HG-induced oxidative stress and extracellular matrix accumulation by activation of Akt-dependent Nrf2/ARE signaling in podocytes.

15.
ACS Nano ; 2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33332092

RESUMO

A bulk-heterojunction (BHJ) structure of organic semiconductor blend is widely used in photon-to-electron converting devices such as organic photodetectors (OPD) and photovoltaics (OPV). However, the impact of the molecular structure on the interfacial electronic states and optoelectronic properties of the constituent organic semiconductors is still unclear, limiting further development of these devices for commercialization. Herein, the critical role of donor molecular structure on OPD performance is identified in highly intermixed BHJ blends containing a small-molecule donor and C60 acceptor. Blending introduces a twisted structure in the donor molecule and a strong coupling between donor and acceptor molecules. This results in ultrafast exciton separation (<1 ps), producing bound (binding energy ∼135 meV), localized (∼0.9 nm), and highly emissive interfacial charge transfer (CT) states. These interfacial CT states undergo efficient dissociation under an applied electric field, leading to highly efficient OPDs in reverse bias but poor OPVs. Further structural twisting and molecular-scale aggregation of the donor molecules occur in blends upon thermal annealing just above the transition temperature of 150 °C at which donor molecules start to reorganize themselves without any apparent macroscopic phase-segregation. These subtle structural changes lead to significant improvements in charge transport and OPD performance, yielding ultralow dark currents (∼10-10 A cm-2), 2-fold faster charge extraction (in µs), and nearly an order of magnitude increase in effective carrier mobility. Our results provide molecular insights into high-performance OPDs by identifying the role of subtle molecular structural changes on device performance and highlight key differences in the design of BHJ blends for OPD and OPV devices.

16.
Expert Opin Drug Saf ; : 1-14, 2020 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-33356646

RESUMO

Introduction: Given their importance in cellular processes and association with numerous diseases, protein kinases have emerged as promising targets for drugs. The FDA has approved greater than fifty small molecule kinase inhibitors (SMKIs) since 2001. Nevertheless, severe hepatotoxicity and related fatal cases have grown as a potential challenge in the advancement of these drugs, and the identification and diagnosis of drug-induced liver injury (DILI) are thorny problems for clinicians. Areas covered: This article summarizes the progression and analyzes the significant features in the study of SMKI hepatotoxicity, including clinical observations and investigations of the underlying mechanisms. Expert opinion: The understanding of SMKI-associated hepatotoxicity relies on the development of preclinical models and improvement of clinical assessment. With a full understanding of the role of inflammation in DILI and the mediating role of cytokines in inflammation, cytokines are promising candidates as sensitive and specific biomarkers for DILI. The emergence of three-dimensional spheroid models demonstrates potential use in providing clinically relevant data and predicting hepatotoxicity of SMKIs.

17.
Autophagy ; : 1-17, 2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33315519

RESUMO

Liver dysfunction is an outstanding dose-limiting toxicity of gefitinib, an EGFR (epidermal growth factor receptor)-tyrosine kinase inhibitor (TKI), in the treatment of EGFR mutation-positive non-small cell lung cancer (NSCLC). We aimed to elucidate the mechanisms underlying gefitinib-induced hepatotoxicity, and provide potentially effective intervention strategy. We discovered that gefitinib could sequentially activate macroautophagy/autophagy and apoptosis in hepatocytes. The inhibition of autophagy alleviated gefitinib-induced apoptosis, whereas the suppression of apoptosis failed to lessen gefitinib-induced autophagy. Moreover, liver-specific Atg7 +/- heterozygous mice showed less severe liver injury than vehicle, suggesting that autophagy is involved in the gefitinib-promoted hepatotoxicity. Mechanistically, gefitinib selectively degrades the important anti-apoptosis factor COX6A1 (cytochrome c oxidase subunit 6A1) in the autophagy-lysosome pathway. The gefitinib-induced COX6A1 reduction impairs mitochondrial respiratory chain complex IV (RCC IV) function, which in turn activates apoptosis, hence causing liver injury. Notably, this autophagy-promoted apoptosis is dependent on PLK1 (polo like kinase 1). Both AAV8-mediated Plk1 knockdown and PLK1 inhibitor BI-2536 could mitigate the gefitinib-induced hepatotoxicity in vivo by abrogating the autophagic degradation of the COX6A1 protein. In addition, PLK1 inhibition could not compromise the anti-cancer activity of gefitinib. In conclusion, our findings reveal the gefitinib-hepatotoxicity pathway, wherein autophagy promotes apoptosis through COX6A1 degradation, and highlight pharmacological inhibition of PLK1 as an attractive therapeutic approach toward improving the safety of gefitinib-based cancer therapy. Abbreviations: 3-MA: 3-methyladenine; AAV8: adeno-associated virus serotype 8; ATG5: autophagy related 5; ATG7: autophagy related 7; B2M: beta-2-microglobulin; CCCP: carbonyl cyanide m-chlorophenylhydrazone; CHX: cycloheximide; COX6A1: cytochrome c oxidase subunit 6A1; c-PARP: cleaved poly(ADP-ribose) polymerase; CQ: chloroquine; GOT1/AST: glutamic-oxaloacetic transaminase 1, soluble; GPT/ALT: glutamic pyruvic transaminase, soluble; HBSS: Hanks´ balanced salt solution; H&E: hematoxylin and eosin; MAP1LC3/LC3: microtubule associated proteins 1 light chain 3; PLK1: polo like kinase 1; RCC IV: respiratory chain complex IV; ROS: reactive oxygen species; TUBB8: tubulin beta 8 class VIII.

18.
J Cell Physiol ; 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33230843

RESUMO

Intestinal mucosal injury is one of the most significant complications of burns. In our previous study, it was found that autophagy could alleviate burn-induced intestinal injury, but the underlying mechanisms are still unclear. Irregular expression of long noncoding RNAs (lncRNAs) is present in many diseases, including burns. However, the relationship between lncRNAs and intestinal mucosal injury requires further elucidation. In this study, we established a burn mice model and detected the expression level of autophagy-related proteins. Then, H19 content after autophagy intervention was tested in vitro and in vivo. The interaction of H19 with Let-7g and that of Let-7g with epidermal growth factor (EGF) were verified by dual-luciferase reporter assays. We found that the expression of the autophagy-associated proteins LC3-II and Beclin-1 was raised in the intestinal tract of the burn mice model. Similarly, the transfection of H19 raised autophagy levels. H19 was elevated after autophagy intervention in vitro and in vivo. H19 overexpression was able to promote IEC-6 cell migration and proliferation. Let-7g was suppressed by the overexpression of H19 and the combination of Let-7g mimic was able to abolish the physiological effect of H19. Moreover, the suppression of Let-7g increased the expression of EGF protein, which heightened IEC-6 cell migration and proliferation. Besides this, dual-luciferase assays revealed that Let-7g was a direct target of H19 as well as the EGF gene. Taken together, autophagy-mediated H19 increases in mouse intestinal tract after severe burn and functions as a sponge to Let-7g to regulate EGF, which suggests that H19 serves as a potential therapeutic target and biomarker for intestinal mucosal injury after burns.

19.
Int J Biol Macromol ; 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33188814

RESUMO

Efficient resource utilization plays a central role in the high productivity of domesticated plants and animals. Whether artificial selection acts on digestive enzymes in the domesticated silkworm (Bombyx mori), which is larger than its wild ancestor, Bombyx mandarina (B. mandarina), remains unknown. In this study, we present the characteristics of a novel alpha-amylase, BmAmy1, in B. mori. The activity of recombinant BmAmy1 was maximal at 35 °C and pH 9.0, and could be suppressed by amylase inhibitors from mulberry, the exclusive food source of silkworms. Three different transposable element fragments, which were independently inserted in the 5'-upstream regulatory region, might be responsible for the enhanced expression of BmAmy1 in different domesticated silkworm strains as revealed by dual-luciferase reporter assay. The BmAmy1 overexpression increased the weight of female and male B. mori by 11.9% and 6.8%, respectively, compared with non-transgenic controls. Our results emphasize that, by exploring the genetic mechanisms of human-selected traits, the domestication process could be further accelerated through genetic engineering and targeted breeding.

20.
Org Lett ; 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33170713

RESUMO

We report a DNA-compatible photoredox decarboxylative coupling of α-amino acids with carbonyl compounds to access DNA-encoded sp3-rich 1,2-amino alcohols. The reaction proceeds efficiently for a wide range of DNA-conjugated aldehydes and ketones and provides the desired 1,2-amino alcohols with conversions generally >50%. Additional utility of the developed protocol is demonstrated by one-pot cyclization of DNA-conjugated 1,2-amino alcohols into oxazolidiones and morpholinones. Lastly, qPCR and sequencing data analysis indicates no significant DNA damage upon photoredox decarboxylative coupling.

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