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1.
Int J Biol Macromol ; 202: 234-240, 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35051495

RESUMO

Bioconversion of the C1 compounds into value-added products is one of the CO2-reducing strategies. In particular, because CO2 can be easily converted into formate, the efficient and direct bioconversion of CO2 through formate assimilation is attracting attention. The tetrahydrofolate (THF) cycle is the highly efficient reconstructed formate assimilation pathway, and 5,10-methenyltetrahydrofolate cyclohydrolase (FchA) is an essential enzyme involved in the THF cycle. In this study, a kinetic analysis of FchA from Methylobacterium extorquens AM1 (MeFchA) was performed and revealed that the enzyme has much higher cyclization than hydrolyzation activity, making it an optimal enzyme for formate assimilation. The crystal structure of MeFchA in the apo- and the THF-complexed forms was also determined, revealing that the substrate-binding site of the enzyme has three differently charged regions to stabilize the three differently charged moieties of the formyl-THF substrate. The residues involved in the substrate binding were also verified through site-directed mutagenesis. This study provides a biochemical and structural basis for the molecular mechanism underlying formate assimilation.

2.
Clin Transl Immunology ; 11(1): e1364, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35003748

RESUMO

Objectives: AXL-mediated activation of aberrant tyrosine kinase drives various oncogenic processes and facilitates an immunosuppressive microenvironment. We evaluated the anti-tumor and anti-metastatic activities of SKI-G-801, a small-molecule inhibitor of AXL, alone and in combination with anti-PD-1 therapy. Methods: In vitro pAXL inhibition by SKI-G-801 was performed in both human and mouse cancer cell lines. Immunocompetent mouse models of tumor were established to measure anti-metastatic potential of SKI-G-801. Furthermore, SKI-G-801, anti-PD-1 or their combination was administered as an adjuvant or neoadjuvant in the 4T1 tumor model to assess their potential for clinical application. Results: SKI-G-801 robustly inhibited pAXL expression in various cell lines. SKI-G-801 alone or in combination with anti-PD-1 potently inhibited metastasis in B16F10 melanoma, CT26 colon and 4T1 breast models. SKI-G-801 inhibited the growth of B16F10 and 4T1 tumor-bearing mice but not immune-deficient mice. An antibody depletion assay revealed that CD8+ T cells significantly contributed to SKI-G-801-mediated survival. Anti-PD-1 and combination group were observed the increased CD8+Ki67+ and effector T cells and M1 macrophage and decreased M2 macrophage, and granulocytic myeloid-derived suppressor cell (G-MDSC) compared to the control group. The neoadjuvant combination of SKI-G-801 and anti-PD-1 therapy achieved superior survival benefits by inducing more profound T-cell responses in the 4T1 syngeneic mouse model. Conclusion: SKI-G-801 significantly suppressed tumor metastasis and growth by enhancing anti-tumor immune responses. Our results suggest that SKI-G-801 has the potential to overcome anti-PD-1 therapy resistance and allow more patients to benefit from anti-PD-1 therapy.

3.
BMC Complement Med Ther ; 22(1): 6, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983480

RESUMO

BACKGROUND: Quercus acuta Thunb. (Fagaceae) or Japanese evergreen oak is cultivated as an ornamental plant in South Korea, China, Japan, and Taiwan and used in traditional medicine. The acorn or fruit of Quercus acuta Thunb. (QAF) is the main ingredient of acorn jelly, a traditional food in Korea. Its leaf was recently shown to have potent xanthine oxidase inhibitory and anti-hyperuricemic activities; however, there have been no studies on the biological activity of QAF extracts. Solar ultraviolet light triggers photoaging of the skin, which increases the production of reactive oxygen species (ROS) and expression of matrix metalloproteinase (MMPs), and destroys collagen fibers, consequently inducing wrinkle formation. The aim of this study was to investigate the effect of water extracts of QAF against UVB-induced skin photoaging and to elucidate the underlying molecular mechanisms in human keratinocytes (HaCaT). METHODS: In this study, we used HPLC to identify the major active components of QAF water extracts. Anti-photoaging effects of QAF extracts were evaluated by analyzing ROS procollagen type I in UVB-irradiated HaCaT keratinocytes. Antiradical activity was determined using 2,2-diphenyl-1-picrylhydrazyl and 2,20-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) assays. The expression of MMP-1 was tested by western blotting and ELISA kits. QAF effects on phosphorylation of the MAPK (p38, JNK, and ERK) pathway and transcription factor AP-1, which enhances the expression of MMPs, were analyzed by western blots. RESULTS: We identified two major active components in QAF water extracts, gallotannic acid and ellagic acid. The QAF aqueous extracts recovered UVB-induced cell toxicity and reduced oxidative stress by inhibiting intracellular ROS generation in HaCaT cells. QAF rescued UVB-induced collagen degradation by suppressing MMP-1 expression. The anti-photoaging activities of QAF were associated with the inhibition of UVB-induced phosphorylation of extracellular signal-regulated kinase (ERK) and activator protein 1 (AP-1). Our findings indicated that QAF prevents UVB-induced skin damage due to collagen degradation and MMP-1 activation via inactivation of the ERK/AP-1 signaling pathway. Overall, this study strongly suggests that QAF exerts anti-skin-aging effects and is a potential natural biomaterial that inhibits UVB-induced photoaging. CONCLUSION: These results show that QAF water extract effectively prevents skin photoaging by enhancing collagen deposition and inhibiting MMP-1 via the ERK/AP-1 signaling pathway.


Assuntos
MAP Quinases Reguladas por Sinal Extracelular/farmacologia , Queratinócitos/efeitos dos fármacos , Quercus/metabolismo , Transdução de Sinais , Envelhecimento da Pele/efeitos dos fármacos , Fator de Transcrição AP-1/farmacologia , Raios Ultravioleta/efeitos adversos , Humanos , Extratos Vegetais/farmacologia
4.
Yonsei Med J ; 63(1): 42-55, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34913283

RESUMO

PURPOSE: Agonists of the stimulator of interferon genes (STING) play a key role in activating the STING pathway by promoting the production of cytokines. In this study, we investigated the antitumor effects and activation of the systemic immune response of treatment with DMXAA (5,6-dimethylxanthenone-4-acetic acid), a STING agonist, in EML4-ALK lung cancer and CT26 colon cancer. MATERIALS AND METHODS: The abscopal effects of DMXAA in the treatment of metastatic skin nodules were assessed. EML4-ALK lung cancer and CT26 colon cancer models were used to evaluate these effects after DMXAA treatment. To evaluate the expression of macrophages and T cells, we sacrificed the tumor-bearing mice after DMXAA treatment and obtained the formalin-fixed paraffin-embedded (FFPE) tissue and tumor cells. Immunohistochemistry and flow cytometry were performed to analyze the expression of each FFPE and tumor cell. RESULTS: We observed that highly infiltrating immune cells downstream of the STING pathway had increased levels of chemokines after DMXAA treatment. In addition, the levels of CD80 and CD86 in antigen-presenting cells were significantly increased after STING activation. Furthermore, innate immune activation altered the systemic T cell-mediated immune responses, induced proliferation of macrophages, inhibited tumor growth, and increased numbers of cytotoxic memory T cells. Tumor-specific lymphocytes also increased in number after treatment with DMXAA. CONCLUSION: The abscopal effect of DMXAA treatment on the skin strongly reduced the spread of EML4-ALK lung cancer and CT26 colon cancer through the STING pathway and induced the presentation of antigens.


Assuntos
Neoplasias Cutâneas , Animais , Imunoterapia , Macrófagos , Proteínas de Membrana/genética , Camundongos
5.
Bioorg Med Chem ; 53: 116550, 2021 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-34890995

RESUMO

Under certain conditions, numerous soluble proteins possess an inherent tendency to convert into insoluble amyloid aggregates, which are associated with several sporadic and genetic human diseases. Transthyretin (TTR) is one of the more than 30 human amyloidogenic proteins involved in conditions such as senile systemic amyloidosis, familial amyloid polyneuropathy, and familial amyloid cardiomyopathy. Considerable effort has been focused on identifying the native tetrameric TTR stabilizers to inhibit rate-limiting tetramer dissociation and, consequently, ameliorate TTR amyloidogenesis. Here, we describe the design and synthesis of quinolin-2(1H)-one derivatives that could be structurally complementary to the thyroxine-binding site within tetrameric TTR. Among these quinolin-2(1H)-one derivatives, compound 7a allowed 16.7% of V30M-TTR (3.6 µM) fibril formation at the same concentration and 49.6% at a concentration of 1.8 µM. Compound 7a exhibited much greater potency in complex biological samples like human plasma than that observed with tafamidis, the drug approved for the treatment of TTR amyloid cardiomyopathy for wild-type or hereditary TTR-mediated amyloidosis. Furthermore, the unique spectral properties of compound 7a demonstrated its high potential for TTR quantification, imaging sensors, and fluorescent tools to study the mechanism of TTR amyloidogenesis.

6.
Ann Vasc Surg ; 2021 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-34788706

RESUMO

BACKGROUND: A radiocephalic arteriovenous fistula (RCAVF) is associated with better long-term patency and fewer complications. However, RCAVF have lower maturation rate for hemodialysis compared with upper AVF or arteriovenous graft. We performed this study to determine the effect of the radiocephalic (RC) anastomotic length on the AVF maturation. METHODS: We reviewed the patients who underwent RCAVF creation with a side-to-end manner from March 2015 to December 2018. AVF maturation was defined as successful hemodialysis (HD) in at least two consecutive sessions. We compared the possible factors including the RC anastomotic length between the initial HD success group and initial HD failure group. RESULTS: A total of 114 patients underwent RCAVF creation: 72 males and 42 females (63.2% and 36.8%, respectively). The mean preoperative arteriotomy length of the AVF was 14.1 mm (range 11.0-16.0 mm). Out of 114 patients, initial HD was executed successfully in 83 patients (72.8%). Among the 31 patients with initial HD failure (27.2%) balloon angioplasty was successfully performed in 17 patients, failed in 4 patients, and not performed in 10 patients. The secondary success rate after balloon angioplasty was 87.7%. After factor analysis, pre-emptive AVF (P = 0.01), vein diameter (P < 0.001), and flow rate (P < 0.001) were revealed significant factors for initial HD success, but not RC anastomotic length of AVF (P = 0.55). CONCLUSION: The length of the radiocephalic anastomosis does not affect the RCAVF maturation rate statistically. However, lengthening of arteriotomy on the radial artery may increase the initial success rate of HD.

7.
Biochem Biophys Res Commun ; 585: 169-176, 2021 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-34808500

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is frequently associated with obesity, insulin resistance, and endoplasmic reticulum (ER) stress. Elevated circulating levels of the hepatokine leukocyte cell-derived chemotaxin-2 (LECT2) have also been noted in NAFLD; however, the mechanism underlying this association is unclear. To investigate a possible link between ER stress/unfolded protein response (UPR) signaling and LECT2 secretion, HepG2 cells were incubated with ER stress inducers with or without an ER stress-reducing chemical chaperone. Additionally, UPR pathway genes were knocked down and overexpressed, and a ChIP assay was performed. In diet-induced obese mice, hepatic expression of LECT2 and activating transcription factor 4 (ATF4) was measured. In HepG2 cells, LECT2 expression was increased by ER stressors, an effect blocked by the chemical chaperone. Among UPR pathway proteins, only knockdown of ATF4 suppressed ER stress-induced LECT2 expression, while overexpression of ATF4 enhanced LECT2 expression. The ChIP assay revealed that ATF4 binds to three putative binding sites on the LECT2 promoter and binding is promoted by an ER stress inducer. In steatotic livers of obese mice, LECT2 and ATF4 expression was concomitantly elevated. Our data indicate that activation of ER stress/UPR signaling induces LECT2 expression in steatotic liver; specifically, ATF4 appears to mediate upregulation of LECT2 transcription.

8.
J Nanobiotechnology ; 19(1): 372, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34789265

RESUMO

BACKGROUND: Extracellular vesicles (EVs) are recognized as novel cell-free therapeutics. Non-alcoholic steatohepatitis (NASH) remains a critical health problem. Herein, we show that EVs from pan peroxisome proliferator-activated receptor agonist-primed induced mesenchymal stem cell (pan PPAR-iMSC-EVs) has unique cargo protein signatures, and demonstrate its therapeutic function in NASH. RESULTS: A unique protein signatures were identified in pan PPAR-iMSC-EVs against those from non-stimulated iMSC-EVs. NASH mice receiving pan PPAR-iMSC-EVs showed reduced steatotic changes and ameliorated ER stress and mitochondiral oxidative stress induced by inflammation. Moreover, pan PPAR-iMSC-EVs promoted liver regeneration via inhibiting apoptosis and enhancing proliferation. CONCLUSIONS: We conclude that our strategy for enriching unique cargo proteins in EVs may facilitate the development of novel therapeutic option for NASH.

9.
Invest Radiol ; 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34839305

RESUMO

OBJECTIVES: This study aimed to evaluate the usefulness of deep learning-based image conversion to improve the reproducibility of computed tomography (CT) radiomics features. MATERIALS AND METHODS: This study was conducted using an abdominal phantom with liver nodules. We developed an image conversion algorithm using a residual feature aggregation network to reproduce radiomics features with CT images under various CT protocols and reconstruction kernels. External validation was performed using images from different scanners, consisting of 8 different protocols. To evaluate the variability of radiomics features, regions of interest (ROIs) were drawn by targeting the liver parenchyma, vessels, paraspinal area, and liver nodules. We extracted 18 first-order, 68 second-order, and 688 wavelet radiomics features. Measurement variability was assessed using the concordance correlation coefficient (CCC), compared with the ground-truth image. RESULTS: In the ROI-based analysis, there was an 83.3% improvement of CCC (80/96; 4 ROIs with 3 categories of radiomics features and 8 protocols) in synthetic images compared with the original images. Among them, the 56 CCC pairs showed a significant increase after image synthesis. In the radiomics feature-based analysis, 62.0% (3838 of 6192; 774 radiomics features with 8 protocols) features showed increased CCC after image synthesis, and a significant increase was noted in 26.9% (1663 of 6192) features. In particular, the first-order feature (79.9%, 115/144) showed better improvement in terms of the reproducibility of radiomics feature than the second-order (59.9%, 326/544) or wavelet feature (61.7%, 3397/5504). CONCLUSIONS: Our study demonstrated that a deep learning model for image conversion can improve the reproducibility of radiomics features across various CT protocols, reconstruction kernels, and CT scanners.

10.
Ultrasonography ; 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34674454

RESUMO

PURPOSE: This study aimed to assess the feasibility of shear-wave elastography (SWE) for assessing the testicular involvement of hematologic malignancies in children and young adults. METHODS: Eight patients (mean age, 11.0 years; range, 0.8 to 20 years) with biopsy-confirmed testicular involvement of hematologic malignancy between January 2018 and December 2020 were retrospectively evaluated. Multiparametric ultrasound examinations, including grayscale, color Doppler ultrasonography (CDUS), and SWE, were performed. Stiffness was measured in the involved testicular area and contralateral normal parenchyma. If there was bilateral testicular involvement, the stiffness of the involved area and the adjacent normal echoic parenchyma was measured on one testis. The Mann-Whitney U test was used to compare stiffness values. RESULTS: On grayscale, the testicular lesions were noted as a solitary mass in one patient, multiple lesions in four patients, and diffuse involvement in three patients. On CDUS and SWE, all patients demonstrated increased vascularity, and the stiffness of the involved area was higher than the values of normal parenchyma (the involved area vs. normal parenchyma, 11.6 kPa [3.9-20.2 kPa] vs. 2.9 kPa [1.1-3.7 kPa], P=0.003). The ratio of stiffness between the involved area and normal parenchyma was 3.4, ranging from 1.9 to 5.1. One patient showed decreased stiffness on follow-up SWE after treatment (affected testis vs. normal testis: initial, 13.8 vs. 3.2 kPa; 1 year later, 2.2 vs. 2.4 kPa). CONCLUSION: Increased testicular stiffness on SWE in children and young adults with hematologic malignancies suggests the possibility of testicular involvement.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34718616

RESUMO

CONTEXT: The up-regulation of TRIB3, a stress-inducible gene encoding a pseudokinase, has been implicated in the development of insulin resistance in the skeletal muscle and liver of patients with obesity and type 2 diabetes. However, there is little information regarding TRIB3 expression in human adipose tissue. OBJECTIVES: To investigate whether TRIB3 expression is dysregulated in human adipose tissue in the context of obesity and type 2 diabetes and whether TRIB3 expression in adipose tissues is associated with insulin resistance. METHODS: We measured metabolic parameters and TRIB3 expression in the abdominal subcutaneous and visceral adipose tissue in obese (with or without type 2 diabetes) and normal-weight women. Regulation of TRIB3 expression was studied in human adipocytes. RESULTS: TRIB3 expression in both fat depots was higher in patients with obesity and/or type 2 diabetes; in addition, the expression level was significantly associated with insulin resistance. Incubating adipocytes under the conditions mimicking the microenvironment of obese adipose tissue, including increased endoplasmic reticulum (ER) stress, induced TRIB3 expression. In human adipocytes, the overexpression of TRIB3 impaired the insulin-stimulated AKT phosphorylation and caused dysregulation of the transcription of genes encoding the bioactive molecules released from adipocytes, such as proinflammatory cytokines, adiponectin, and leptin. Pioglitazone, an insulin-sensitizing agent, reduced both these effects of TRIB3 and the ER stressor-induced expression of TRB3. CONCLUSIONS: Our data indicate that TRIB3 expression in adipose tissue is enhanced in patients with obesity and suggest that the increased TRIB3 dysregulates adipocyte function, which may contribute to the development of insulin resistance.

12.
Sci Rep ; 11(1): 20403, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34650076

RESUMO

This study aimed to evaluate a deep learning model for generating synthetic contrast-enhanced CT (sCECT) from non-contrast chest CT (NCCT). A deep learning model was applied to generate sCECT from NCCT. We collected three separate data sets, the development set (n = 25) for model training and tuning, test set 1 (n = 25) for technical evaluation, and test set 2 (n = 12) for clinical utility evaluation. In test set 1, image similarity metrics were calculated. In test set 2, the lesion contrast-to-noise ratio of the mediastinal lymph nodes was measured, and an observer study was conducted to compare lesion conspicuity. Comparisons were performed using the paired t-test or Wilcoxon signed-rank test. In test set 1, sCECT showed a lower mean absolute error (41.72 vs 48.74; P < .001), higher peak signal-to-noise ratio (17.44 vs 15.97; P < .001), higher multiscale structural similarity index measurement (0.84 vs 0.81; P < .001), and lower learned perceptual image patch similarity metric (0.14 vs 0.15; P < .001) than NCCT. In test set 2, the contrast-to-noise ratio of the mediastinal lymph nodes was higher in the sCECT group than in the NCCT group (6.15 ± 5.18 vs 0.74 ± 0.69; P < .001). The observer study showed for all reviewers higher lesion conspicuity in NCCT with sCECT than in NCCT alone (P ≤ .001). Synthetic CECT generated from NCCT improves the depiction of mediastinal lymph nodes.

13.
Polymers (Basel) ; 13(19)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34641126

RESUMO

Bisphenol A diglycidyl ether (DGEBA) was blended with polyetherimide (PEI) as a thermoplastic toughener for thermal stability and mechanical properties as a function of PEI contents. The thermal stability and mechanical properties were investigated using a thermogravimetric analyzer (TGA) and a universal test machine, respectively. The TGA results indicate that PEI addition enhanced the thermal stability of the epoxy resins in terms of the integral procedural decomposition temperature (IPDT) and pyrolysis activation energy (Et). The IPDT and Et values of the DGEBA/PEI blends containing 2 wt% of PEI increased by 2% and 22%, respectively, compared to those of neat DGEBA. Moreover, the critical stress intensity factor and critical strain energy release rate for the DGEBA/PEI blends containing 2 wt% of PEI increased by 83% and 194%, respectively, compared to those of neat DGEBA. These results demonstrate that PEI plays a key role in enhancing the flexural strength and fracture toughness of epoxy blends. This can be attributed to the newly formed semi-interpenetrating polymer networks (semi-IPNs) composed of the epoxy network and linear PEI.

14.
Front Nutr ; 8: 722866, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513905

RESUMO

Background: Oat and its compounds have been found to have anti-inflammatory effects. Through this systematic review and meta-analysis, we aimed to determine an evidence-based link between oat consumption and inflammatory markers. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. By the end of April 2021, we included randomized controlled trials (RCTs) that investigated the anti-inflammatory effect of oat and oat-related products through screening PubMed, Embase, Web of Science, ClinicalTrial.gov, and CENTRAL. Meta-analysis was conducted with a random-effect model on the standardized mean difference (SMD) of the change scores of inflammatory markers, including C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8). Subgroup analyses were conducted to stratify confounding variables. The risk of bias was evaluated using the Cochrane risk of bias tool and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was applied to report the quality of evidence. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42021245844). Results: Systematic screening of five databases yielded 4,119 studies, of which 23 RCTs were finally selected. For the four systemic inflammatory markers analyzed, no significant alterations were found after oat consumption. However, oat intake was found to significantly decrease CRP levels in subjects with one or more health complications (SMD: -0.18; 95% CI: -0.36, 0.00; P = 0.05; I 2 = 10%). Furthermore, IL-6 levels were significantly decreased in subjects with dyslipidemia (SMD = -0.34; 95% CI: -0.59, -0.10; P = 0.006; I 2 = 0%). These beneficial effects might be attributed to the effects of avenanthramide and ß-glucan. Conclusions: Overall evidence supporting the alleviation of inflammatory response by oat intake was poor, calling for future studies including a larger sample size to confirm the findings.

15.
Talanta ; 235: 122801, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34517659

RESUMO

With COVID-19 widespread worldwide, people are still struggling to develop faster and more accurate diagnostic methods. Here we demonstrated the label-free detection of SARS-CoV-2 spike protein by employing a SARS-CoV-2 spike antibody-conjugated phase-shifted long-period fiber grating (PS-LPFG) inscribed with a CO2 laser. At a specific cladding mode, the wavelength separation (λD) between the two split dips of a PS-LPFG varies with the external refractive index, although it is virtually insensitive to ambient temperature variations. To detect SARS-CoV-2 spike protein, SARS-CoV-2 spike antibodies were immobilized on the fiber surface of the fabricated PS-LPFG functionalized through chemical modification. When exposed to SARS-CoV-2 spike protein with different concentrations, the antibody-immobilized PS-LPFG exhibited the variation of λD according to the protein concentration, which was caused by bioaffinity binding-induced local changes in the refractive index at its surface. In particular, we also confirmed the potential of our sensor for clinical application by detecting SARS-CoV-2 spike protein in virus transport medium. Moreover, our sensor could distinguish SARS-CoV-2 spike protein from those of MERS-CoV and offer efficient properties such as reusability and storage stability. Hence, we have successfully fabricated a promising optical transducer for the detection of SARS-CoV-2 spike protein, which can be unperturbed by external temperature disturbances.


Assuntos
Técnicas Biossensoriais , COVID-19 , Humanos , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus
16.
Biomol Ther (Seoul) ; 29(6): 582-595, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34565718

RESUMO

Researchers have endeavored to identify the etiology of inflammatory bowel diseases, including Crohn's disease and ulcerative colitis. Though the pathogenesis of inflammatory bowel diseases remains unknown, dysregulation of the immune system in the host gastrointestinal tract is believed to be the major causative factor. Omics is a powerful methodological tool that can reveal biochemical information stored in clinical samples. Lipidomics is a subset of omics that explores the lipid classes associated with inflammation. One objective of the present systematic review was to facilitate the identification of biochemical targets for use in future lipidomic studies on inflammatory bowel diseases. The use of high-resolution mass spectrometry to observe alterations in global lipidomics might help elucidate the immunoregulatory mechanisms involved in inflammatory bowel diseases and discover novel biomarkers for them. Assessment of the characteristics of previous clinical trials on inflammatory bowel diseases could help researchers design and establish patient selection and analytical method criteria for future studies on these conditions. In this study, we curated literature exclusively from four databases and extracted lipidomics-related data from literature, considering criteria. This paper suggests that the lipidomics approach toward research in inflammatory bowel diseases can clarify their pathogenesis and identify clinically valuable biomarkers to predict and monitor their progression.

17.
Chem Commun (Camb) ; 57(85): 11165-11168, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34570149

RESUMO

Here we report a simple synthesis strategy for Pt-WOx hybrid nanostructures using a metal-dissolution-based electrodeposition technique. The hybrid nanostructures demonstrate an excellent catalytic hydrogen evolution reaction performance with an approximately 17 times higher Pt mass activity and a 7.4 times higher turnover frequency than those of commercial Pt catalysts. The enhanced electrocatalytic performance is related to the creation of Pt-WOx interfacial sites.

18.
Int J Mol Sci ; 22(17)2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34502316

RESUMO

Farrerol (FA) is a flavanone isolated from the Chinese herbal medicine "Man-shan-hong" (Rhododendron dauricum L.). In the present study, FA decreased the viability of SKOV3 cells in a dose- and time-dependent manner, and it induced G2/M cell cycle arrest and cell apoptosis. Cell cycle distribution analysis via flow cytometry showed that FA decreased G1 populations and increased G2/M populations in SKOV3 cells. Additionally, Western blotting confirmed an increase in the expression level of proteins involved in the cell cycle, e.g., CDK and cyclins. FA-induced apoptosis in SKOV3 cells was also investigated using a TUNEL assay, and increased expression levels of proapoptotic factors, including Caspase-3 and poly ADP ribose polymerase (PARP), through the Extracellular signal-regulated kinase (ERK)/MAPK pathway were investigated. Proinflammatory cytokines (e.g., IL-6, TNF-α, and IL-1) have been identified as a driver of the pathological mechanisms underlying involuntary weight loss and impaired physical function, i.e., cachexia, during cancer; in the present study, we showed that farrerol attenuates TNF-α-induced lipolysis and increases adipogenic differentiation in 3T3-L1 cells. Thus, farrerol could potentially be used as an anticancer agent or anticachetic drug.


Assuntos
Cromonas/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Lipólise/efeitos dos fármacos , Neoplasias Ovarianas/tratamento farmacológico , Fator de Necrose Tumoral alfa/farmacologia , Apoptose , Ciclo Celular , Proliferação de Células , Feminino , Humanos , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Células Tumorais Cultivadas
19.
Int J Med Sci ; 18(15): 3395-3402, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34522166

RESUMO

Computed tomography (CT) of the chest is one of the main diagnositic tools for coronavirus disease 2019 (COVID-19) infection. To document the chest CT findings in patients with confirmed COVID-19 and their association with the clinical severity, we searched related literatures through PubMed, MEDLINE, Embase, Web of Science (inception to May 4, 2020) and reviewed reference lists of previous systematic reviews. A total of 31 case reports (3768 patients) on CT findings of COVID-19 were included. The most common comorbid conditions were hypertension (18.4%) and diabetes mellitus (8.3%). The most common symptom was fever (78.7%), followed by cough (60.2%). It took an average of 5.6 days from symptom onset to admission. The most common chest CT finding was vascular enlargement (84.8%), followed by ground-glass opacity (GGO) (60.1%), air-bronchogram (47.8%), and consolidation (41.4%). Most lung lesions were located in the lung periphery (72.2%) and involved bilateral lung (76%). Most patients showed normal range of laboratory findings such as white blood cell count (96.4%) and lymphocyte (87.2%). Compared to previous published meta-analyses, our study is the first to summarize the different radiologic characteristics of chest CT in a total of 3768 COVID-19 patients by compiling case series studies. A comprehensive diagnostic approach should be adopted for patients with known COVID-19, suspected cases, and for exposed individuals.


Assuntos
COVID-19/diagnóstico por imagem , Radiografia Torácica/métodos , Tomografia Computadorizada por Raios X/métodos , COVID-19/sangue , Humanos , Pulmão/diagnóstico por imagem , Pneumopatias/diagnóstico por imagem , Contagem de Linfócitos , Oxigênio/uso terapêutico , Prognóstico
20.
Microbiol Immunol ; 65(12): 566-574, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34516008

RESUMO

The performance of the ASTA MicroIDSys system (ASTA), a new matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) system, was evaluated for the identification of viridans group streptococci (VGS) and compared with the results obtained with the Bruker Biotyper system (Bruker Daltonics). A total of 106 Streptococcus reference strains belonging to 24 species from the bacterial strain bank was analyzed using the two MALDI-TOF MS systems. Of the 106 reference strains tested, ASTA MicroIDSys and Bruker Biotyper correctly identified 84.9% and 81.1% at the species level, 100% and 97.2% at the group level and 100% and 98.1% at the genus level, respectively. The difference between the two systems was not statistically significant (P = 0.289). Out of 24 species, 13 species were accurately identified to the species level with 100% accurate identification rates with both systems. The accurate identification rates at the species level of ASTA MicroIDSys and Bruker Biotyper were 100% and 87.5% for the S. anginosus group; 78.4% and 73.5% for the S. mitis group; 91.7% and 91.7% for the S. mutans group; and 100% and 100% for the S. salivarius group, respectively. The ASTA MicroIDSys showed an identification performance equivalent to that of the Bruker Biotyper for VGS. Therefore, it would be useful for the identification of VGS strains in clinical microbiology laboratories.

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