Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 715
Filtrar
1.
J Thorac Dis ; 13(10): 5964-5972, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34795944

RESUMO

Background: Clinical features of epidermal growth factor receptor (EGFR) mutations have been commonly recognized in variant cancers. The role of EGFR mutations in non-small cell lung cancer (NSCLC) has spurred research and drug development efforts. However, there are still mutations that have not been widely reported, and their influences on NSCLC have not been fully elucidated; EGFR G873R mutation is just one of them. The aim of this study was to investigate the correlation between EGFR G873R mutation and the prognosis of chemotherapy in NSCLC. Methods: A total of 54 patients with NSCLC were enrolled in this study. Immunohistochemical staining was used to detect the expression of EGFR. A DNA extraction kit (GeneRead DNA FFPE Kit) was used to extract total DNA from resected cancer tissues. Genomic DNA targets were amplified by polymerase chain reaction (PCR), and then the amplicons were purified and sequenced. Statistical methods were performed to detect the relationship between EGFR G873R mutation and various clinicopathological features and the effect of EGFR G873R mutation on the prognosis of chemotherapy. Results: EGFR G873R mutation did not show statistical significance, with EGFR high expression identified in 30 cases (P>0.05). Patients with EGFR G873R mutation had a significantly favorable prognosis of docetaxel (P=0.032), and for patients treated with docetaxel, EGFR G873R mutation was significantly correlated with better 5-year disease-free survival (DFS; P=0.026) and overall survival (OS; P=0.026). However, there was no statistical significance found between EGFR G873R mutation and the prognosis of vinorelbine (P>0.05), and for patients treated with vinorelbine, EGFR G873R mutation had no statistical significance with 5-year DFS (P>0.05) and OS (P>0.05). Conclusions: EGFR G873R mutation was remarkably correlated with the prognosis of docetaxel in NSCLC, which indicates that EGFR G873R may be employed as a promising biomarker to identify individuals with better prognosis of docetaxel and as an antitumor target for NSCLC treatment.

2.
J Sci Food Agric ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34761381

RESUMO

BACKGROUND: During the storage and processing of Lilium bulbs, the phenomenon of violet-red colour change in Lilium bulbs which is different from enzymatic browning often exists, but the specific mechanism is not clear. RESULTS: In this study, we chose six-year-old Lilium davidii var. unicolor to study. Bulb scales which were sealed in polyethylene film plastic bags were exposed to room temperature (20 ± 2 °C) treatment for 5 days (12 h of sunshine and 12 h of sun shading). Metabolomics and transcript omics were conducted to elucidate the mechanism of violet-red color change in Lilium bulbs. The results showed that the color of Lilium bulb scales was obvious violet-red in 5 days; chromaticity value measuring showed the a values had the most significant upward trend. Metabolomics analysis showed many metabolites produced from the flavonoid biosynthesis pathway showed an upward trend. Transcriptome revealed that flavonoid biosynthesis pathway was significantly enriched, of which 20 synthesis genes were highly regulated expression. Metabolome and transcriptome co-analysis that up-regulated expression of flavonoids synthesis genes including ten chalcone synthase, two anthocyanidin reductase, and chalcone isomerase, 3'-hydroxylase, 3-hydroxylase, dihydroflavonol 4-reductase, anthocyanin synthase, anthocyanidin 3-O-glucosyltransferase and flavonol synthase were highly positive correlated with epicatechin, rutin and cyanidin 3-rutinoside. CONCLUSION: Phenotypic, metabolomic and transcriptomic analysis indicated that the up-related expression levels of genes and accumulated flavonoids related to flavonoid metabolism contributed greatly to the violet-red colour change in Lilium bulbs. The results of this study will deepen our understanding of the color formation of violet-red Lilium bulbs and provide the basis for future storage and preservation of Lilium bulbs. © 2021 Society of Chemical Industry.

3.
Am J Ophthalmol ; 2021 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-34818515

RESUMO

PURPOSE: To evaluate the diagnostic yield of congenital ectopia lentis (EL) in a Chinese cohort by combining panel-based next-generation sequencing with clinical findings DESIGN: A cohort study. METHODS: In total, 175 patients with congenital EL and their available family members (n = 338) were enrolled. All congenital EL patients underwent genetic testing. Genotype-phenotype analyses were conducted to assess the biometric and structural ocular manifestations of congenital EL. RESULTS: In total, 175 patients with congenital EL and 338 of their relatives were included in this study. In these patients, 92.57% (162/175) of disease-related variants were detected in FBN1 (83.43%), CPAMD8 (1.71%), COL4A5 (0.57%), ADAMTSL4 (3.43%), LTBP2 (1.71%), and CBS (2.29%). Based on genetic and clinical findings, the primary diagnostic rate was increased to 40.57% from 19.43% with the exception of the 91 diagnoses of potential MFS, with a new diagnostic strategy for congenital ectopia lentis thus having been developed. Within this group of patients harboring FBN1 mutations, 16.44% (19/141) probands were diagnosed with ectopia lentis syndrome (ELS) and 2.13% (3/141) were diagnosed with Marfan syndrome (MFS). CONCLUSIONS: The results of this cohort study expand the genomic landscape associated with congenital EL in Chinese cohorts. FBN1 mutations represent the most common cause of congenital EL in this population, and we have developed a new diagnostic strategy for congenital EL subtypes via the use of a well-designed panel-based next-Generation Sequencing (NGS) which can be used to efficiently and precisely diagnose patients with congenital EL in a cost-effective manner.

4.
Ann Transl Med ; 9(18): 1464, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34734016

RESUMO

Background: Esophageal squamous cell carcinoma (ESCC) is the leading cause of cancer-related mortality. While recent studies have documented the presence of extrachromosomal circular DNAs (eccDNAs) in various tumors, to date, there have been no studies examining the distribution and function of eccDNAs in ESCC. Methods: The eccDNAs from three surgically matched ESCC tissue samples were extracted and amplified by rolling circle amplification after removal of linear DNA and mitochondrial circular DNA. High-throughput eccDNA sequencing and bioinformatics analysis was performed to study the distribution pattern and the level of eccDNA expression. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed on the genes associated with the differentially expressed eccDNAs. Five up-regulated and five down-regulated candidate eccDNAs were validated by routine polymerase chain reaction (PCR), TOPO-TA cloning and Sanger sequencing. The nucleotides flanking the eccDNA junctions were analyzed to explore the mechanisms of eccDNA formation. Results: A total of 184,557 eccDNAs was identified. The overall length distribution ranged from 33 to 968,842 base pairs (bp), with the peak at approximately 360 bp. These eccDNAs mainly originated from 5'- and 3'-untranslated regions (UTRs), and rarely from exons, introns, LINE, or Alu repeat regions. The chromosome distribution, length distribution, and genomic annotation of the eccDNAs were comparable between ESCC samples and matched normal epithelium. Nevertheless, 16,031 eccDNAs were found to be differentially expressed between ESCC and matched normal epithelium, including 10,126 up-regulated eccDNAs and 5,905 down-regulated eccDNAs. GO analysis and KEGG pathway analysis showed enriched in cancer pathways, mitogen-activated protein kinase (MAPK) pathway, GTPase-related activity, and cytoskeleton function. PCR, TOPO-TA cloning, and Sanger sequencing validated the junctional sites of five up-regulated candidate eccDNAs and four other unexpected eccDNAs. A repeat nucleotide pattern between the position flanking the start site and that flanking the end site was detected. Conclusions: This study demonstrated the genome-wide presence of eccDNAs, explored the differential expression of eccDNAs, and revealed the potential mechanisms of eccDNAs in ESCC. This work provides further insights into our understanding of genome plasticity, the role of eccDNAs in ESCC, and may contribute to the development of potential clinical therapies.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34719759

RESUMO

Imidacloprid as a widely used neonicotinoid insecticide can cause harmful pesticide residue inevitably. Metal-organic frameworks (MOFs) were innovatively composited to improve the light absorption and degradation performance of Bi2WO6 semiconductor, which expanded the photodegradation application in solving environmental problems. Based on the synergistic effect of Bi2WO6 and NH2-MIL-88B(Fe), a Bi2WO6/NH2-MIL-88B(Fe) (BNM) heterojunction photocatalyst with high-performance of photocatalytic degradation activities was successfully synthesized. The optimized BNM catalyst had a good degradation rate under visible light, which was mainly caused by generation of the active ·OH. Transient photocurrent response and electrochemical impedance tests verified that 1:2 BNM exhibits a highest charge separation and a lowest carrier recombination rate which were favorable to the photocatalytic activity. Cycle experiments show that the composite photocatalyst had good reusability and stability which were very important for potential industry applications.

7.
J Med Chem ; 64(19): 14603-14619, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34596404

RESUMO

Herein, we report the discovery of a novel class of quinazoline carboxamides as dual p70S6k/Akt inhibitors for the treatment of tumors driven by alterations to the PI3K/Akt/mTOR (PAM) pathway. Through the screening of in-house proprietary kinase library, 4-benzylamino-quinazoline-8-carboxylic acid amide 1 stood out, with sub-micromolar p70S6k biochemical activity, as the starting point for a structurally enabled p70S6K/Akt dual inhibitor program that led to the discovery of M2698, a dual p70S6k/Akt inhibitor. M2698 is kinase selective, possesses favorable physical, chemical, and DMPK profiles, is orally available and well tolerated, and displayed tumor control in multiple in vivo studies of PAM pathway-driven tumors.

8.
Ann Thorac Surg ; 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34624264

RESUMO

BACKGROUND: Enhanced recovery after surgery (ERAS) is a perioperative management protocol that aims to accelerate patient recovery. This study aimed to evaluate its benefits in patients with resectable esophageal cancer. METHODS: This retrospective study compared patients before (January 2013 to December 2016) and after (June 2018 to December 2020) ERAS protocol implementation in our hospital. A propensity score-matched (PSM) analysis was used to compare short-term surgical outcomes between ERAS and non-ERAS groups. After PSM, each group included 243 patients. RESULTS: There were significant differences in hospital length of stay after surgery (7.40 vs. 11.17 days, P<.001) and hospitalization cost (¥69380 vs. ¥78075, P<.001) between the ERAS and non-ERAS groups. The time to chest tube removal (4.91 vs. 7.16 days, P<.001) and first bowel movement (2.87 vs. 3.97 days, P<.001) was significantly shorter in the ERAS group. However, there was no significant difference in total postoperative complication morbidity (20.2% vs. 25.1%, P=0.193). The complication of postoperative atelectasis or pneumonia was significantly lower in the ERAS group (P=0.003), but there was no significant difference in occurrence of ≥Grade III complications between the two groups (12.3% vs. 11.5%, P=0.889). CONCLUSIONS: We demonstrated that ERAS could reduce the hospital stay, numerical pain scores, and hospitalization costs without increasing postoperative complication and readmission. Furthermore, subgroup analyses revealed that ERAS was safe for older people (>70 years old).

9.
Reprod Biol Endocrinol ; 19(1): 161, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34686198

RESUMO

BACKGROUND: Endometriosis, the presence of active endometrial tissue outside the lining membrane of the uterine cavity, is a common disease in women of childbearing age. The ectopic endometrium has some characteristics of tumor tissue, including invasive and migratory abilities. In addition, endometriosis is associated with inflammation and reduced cellular apoptosis. METHODS: Western blot analysis, qPCR, immunohistochemistry, immunofluorescence microscopy, Transwell assay, wound healing assay, and TUNEL staining. RESULTS: Interleukin-1ß (IL-1ß) induced WEE1 expression in endometrial stromal cells (ESCs), suggesting that WEE1 may be upregulated during the endometriosis-induced inflammatory response. Overexpression of WEE1 in cultured ESCs promoted ESC migration while inhibiting apoptosis, whereas WEE1 knockdown reduced ESC migration while promoting apoptosis. Inhibition of WEE1 attenuates fibrosis in ESCs and female C57BL/6 J mice. This pro-fibrotic effect of WEE1 was significantly decreased by treatment with the Wnt/ß-catenin inhibitor XAV939, suggesting that WEE1 acts via the Wnt/ß-catenin signaling pathway. CONCLUSION: Our study demonstrates that WEE1 promotes ESC migration and fibrosis via the Wnt/ß-catenin signaling pathway. Thus, WEE1 may serve as a potential therapeutic target for the treatment of endometriosis.

10.
Chin Med J (Engl) ; 134(20): 2430-2437, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34669636

RESUMO

BACKGROUND: Circulating tumor DNA (ctDNA) is a promising biomarker for non-invasive epidermal growth factor receptor mutations (EGFRm) detection in lung cancer patients, but existing methods have limitations in sensitivity and availability. In this study, we used the ΔCt value (mutant cycle threshold [Ct] value-internal control Ct value) generated during the polymerase chain reaction (PCR) assay to convert super-amplification-refractory mutation system (superARMS) from a qualitative method to a semi-quantitative method named reformed-superARMS (R-superARMS), and evaluated its performance in detecting EGFRm in plasma ctDNA in patients with advanced lung adenocarcinoma. METHODS: A total of 41 pairs of tissues and plasma samples were obtained from lung adenocarcinoma patients who had known EGFRm in tumor tissue and were previously untreated. EGFRm in ctDNA was identified by using superARMS. Through making use of ΔCt value generated during the detection process of superARMS, we indirectly transform this qualitative detection method into a semi-quantitative PCR detection method, named R-superARMS. Both qualitative and quantitative analyses of the data were performed. Kaplan-Meier analysis was performed to estimate the progression-free survival (PFS) and overall survival (OS). Fisher exact test was used for categorical variables. RESULTS: The concordance rate of EGFRm in tumor tissues and matched plasma samples was 68.3% (28/41). At baseline, EGFRm-positive patients were divided into two groups according to the cut-off ΔCt value of EGFRm set at 8.11. A significant difference in the median OS (mOS) between the two groups was observed (EGFRm ΔCt ≤8.11 vs. >8.11: not reached vs. 11.0 months; log-rank P = 0.024). Patients were divided into mutation clearance (MC) group and mutation incomplete clearance (MIC) group according to whether the ΔCt value of EGFRm test turned negative after 1 month of treatment. We found that there was also a significant difference in mOS (not reached vs. 10.4 months; log-rank P = 0.021) between MC group and MIC group. Although there was no significant difference in PFS between the two groups, the two curves were separated and the PFS of MC group tended to be higher than the MIC group (not reached vs. 27.5 months; log-rank P = 0.088). Furthermore, EGFRm-positive patients were divided into two groups according to the cut-off of the changes in ΔCt value of EGFRm after 1 month of treatment, which was set at 4.89. A significant difference in the mOS between the two groups was observed (change value of ΔCt >4.89 vs. ≤4.89: not reached vs. 11.0 months; log-rank P = 0.014). CONCLUSIONS: Detecting EGFRm in ctDNA using R-superARMS can identify patients who are more likely sensitive to targeted therapy, reflect the molecular load of patients, and predict the therapeutic efficacy and clinical outcomes of patients.


Assuntos
Adenocarcinoma de Pulmão , DNA Tumoral Circulante , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/genética , DNA Tumoral Circulante/genética , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/genética , Mutação/genética , Inibidores de Proteínas Quinases
11.
Front Oncol ; 11: 738477, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34568075

RESUMO

Background: Ferroptosis is a novel form of regulated cell death involved in tumor progression. The role of ferroptosis-related lncRNAs in hepatocellular carcinoma (HCC) remains unclear. Methods: RNA-seq and clinical data for HCC patients were downloaded from The Cancer Genome Atlas (TCGA) Genomic Data Commons (GDC) portal. Bioinformatics methods, including weighted gene coexpression network analysis (WGCNA), Cox regression, and least absolute shrinkage and selection operator (LASSO) analysis, were used to identify signature markers for diagnosis/prognosis. The tumor microenvironment, immune infiltration and functional enrichment were compared between the low-risk and high-risk groups. Subsequently, small molecule drugs targeting ferroptosis-related signature components were predicted via the L1000FWD and PubChem databases. Results: The prognostic model consisted of 2 ferroptosis-related mRNAs (SLC1A5 and SLC7A11) and 8 ferroptosis-related lncRNAs (AC245297.3, MYLK-AS1, NRAV, SREBF2-AS1, AL031985.3, ZFPM2-AS1, AC015908.3, MSC-AS1). The areas under the curves (AUCs) were 0.830 and 0.806 in the training and test groups, respectively. Decision curve analysis (DCA) revealed that the ferroptosis-related signature performed better than all pathological characteristics. Multivariate Cox regression analysis showed that the risk score was an independent prognostic factor. The survival probability of low- and high-risk patients could be clearly distinguished by the principal component analysis (PCA) plot. The risk score divided HCC patients into two distinct groups in terms of immune status, especially checkpoint gene expression, which was further supported by the Gene Ontology (GO) biological process, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Finally, several small molecule drugs (SIB-1893, geldanamycin and PD-184352, etc) targeting ferroptosis-related signature components were identified for future reference. Conclusion: We constructed a new ferroptosis-related mRNA/lncRNA signature for HCC patients. The model can be used for prognostic prediction and immune evaluation, providing a reference for immunotherapies and targeted therapies.

12.
Innovation (N Y) ; 2(1): 100083, 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-34557738

RESUMO

As one of the most spectacular energy release events in the solar system, solar flares are generally powered by magnetic reconnection in the solar corona. As a result of the re-arrangement of magnetic field topology after the reconnection process, a series of new loop-like magnetic structures are often formed and are known as flare loops. A hot diffuse region, consisting of around 5-10 MK plasma, is also observed above the loops and is called a supra-arcade fan. Often, dark, tadpole-like structures are seen to descend through the bright supra-arcade fans. It remains unclear what role these so-called supra-arcade downflows (SADs) play in heating the flaring coronal plasma. Here we show a unique flare observation, where many SADs collide with the flare loops and strongly heat the loops to a temperature of 10-20 MK. Several of these interactions generate clear signatures of quasi-periodic enhancement in the full-Sun-integrated soft X-ray emission, providing an alternative interpretation for quasi-periodic pulsations that are commonly observed during solar and stellar flares.

13.
Materials (Basel) ; 14(17)2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34501113

RESUMO

The crystal stacking order plays a crucial role in determining the structure and physical properties of 2D layered materials. A variation in the stacking sequence of adjacent 2D building blocks causes drastic changes in their functionalities. In this work, the structural variation of belloite (Cu(OH)Cl), as a function of pressure, is presented. Through in situ synchrotron X-ray diffraction and Raman scattering studies, in combination with first-principles theoretical simulations, a structural transformation from the initial monoclinic phase into an orthorhombic one has been established at 18.7 GPa, featuring variations in the stacking sequence of the tectonic monolayers. In the monoclinic phase, they are arranged in an AAAA sequence. While in the orthorhombic phase, the monolayers are stacked in an ABAB sequence. Such phenomena are similar to those observed in van der Waals 2D materials, with pressure-induced changes in the stacking order between layers. In addition, an isostructural phase transition within the initial monoclinic phase is also observed to occur at 12.9-16 GPa, which is associated with layer-sliding and a change in hydrogen bond configuration. These results show that Cu(OH)Cl, as well as other hydrogen-bonded 2D layered materials, can provide a convenient platform for studying the effects of the crystal stacking order.

14.
BMC Cancer ; 21(1): 1003, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34493236

RESUMO

BACKGROUND: Nasopharyngeal carcinoma (NPC) is one of the most common malignancies in head and neck. Platinum-based chemotherapy is an important treatment for NPC. However, the molecular mechanism of resistance to platinum drug remains unknown. Endoplasmic reticulum resident protein 44(ERp44), an unfolded protein response (UPR)-induced endoplasmic reticulum(ER) protein, is induced during ER stress. This research explored the mechanism of ERp44 in strengthening cisplatin resistance in NPC. METHODS: Western blot and immunohistochemistry were used to investigate the expression of ERp44 and Glucose-Regulated Protein 78(GRP78) in NPC. We took CCK8 to detect the role of ERp44 on cell chemosensitivity. Flow cytometric analysis and western blot were taken to analyze cell apoptosis. We performed differential centrifugation to isolate exosomes from serum or conditioned media of cells and analyzed the impact of exosomal ERp44 on cells cisplatin sensitivity. Finally, the results were confirmed in vivo. RESULTS: We found the increased expression of ERp44 and GRP78 in NPC and ERp44 was highly expressed in ER-stressed tissues. Cell proliferation was inhibited after cisplatin treatment when ERp44 was knocked down and ERp44 strengthened cisplatin resistance by influencing cell apoptosis and pyroptosis. Then we also collected exosomes and cell viability was increased after the addition of NPC-derived-exosomes with cisplatin treatment. More importantly, our results showed under ERS, NPC cells secreted exosomes containing ERp44 and could transfer them to adjacent cells to strengthen chemoresistance. CONCLUSION: Our data suggested that exosomal ERp44 derived from ER-stressed NPC cells took an inevitable role in NPC chemoresistance and might act as a treatment target.


Assuntos
Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Estresse do Retículo Endoplasmático , Exossomos/metabolismo , Proteínas de Membrana/metabolismo , Chaperonas Moleculares/metabolismo , Carcinoma Nasofaríngeo/tratamento farmacológico , Resposta a Proteínas não Dobradas , Animais , Antineoplásicos/farmacologia , Apoptose , Proliferação de Células , Exossomos/genética , Humanos , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Chaperonas Moleculares/genética , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Transdução de Sinais , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Proc Natl Acad Sci U S A ; 118(40)2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34588304

RESUMO

Virtually all of the many active matter systems studied so far are made of units (biofilaments, cells, colloidal particles, robots, animals, etc.) that move even when they are alone or isolated. Their collective properties continue to fascinate, and we now understand better how they are unique to the bulk transduction of energy into work. Here we demonstrate that systems in which isolated but potentially active particles do not move can exhibit specific and remarkable collective properties. Combining experiments, theory, and numerical simulations, we show that such subcritical active matter can be realized with Quincke rollers, that is, dielectric colloidal particles immersed in a conducting fluid subjected to a vertical DC electric field. Working below the threshold field value marking the onset of motion for a single colloid, we find fast activity waves, reminiscent of excitable systems, and stable, arbitrarily large self-standing vortices made of thousands of particles moving at the same speed. Our theoretical model accounts for these phenomena and shows how they can arise in the absence of confining boundaries and individual chirality. We argue that our findings imply that a faithful description of the collective properties of Quincke rollers need to consider the fluid surrounding particles.

16.
Hum Mutat ; 42(12): 1637-1647, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34550612

RESUMO

Mutations of fibrillin-1 (FBN1) have been associated with Marfan syndrome and pleiotropic connective tissue disorders, collectively termed as "type I fibrillinopathy". However, few genotype-phenotype correlations are known in the ocular system. Patients with congenital ectopia lentis (EL) received panel-based next-generation sequencing, complemented with multiplex ligation-dependent probe amplification. In a total of 125 probands, the ocular phenotypes were compared for different types of FBN1 mutations. Premature termination codons were associated with less severe EL and a thinner central corneal thickness (CCT) than the inframe mutations. The eyes of patients with mutations in the C-terminal region had a higher incidence of posterior staphyloma than those in the middle and N-terminal regions. Mutations in the TGF-ß-regulating sequence had larger horizontal corneal diameters (white-to-white [WTW]), higher incidence of posterior staphyloma, but less severe EL than those with mutations in other regions. Mutations in the neonatal region were associated with thinner CCT. Longer axial length (AL) was associated with mutations in the C-terminal region or TGF-ß regulating sequence after adjusting for age, EL severity, and corneal curvature radius. FBN1 genotype-phenotype correlations were established for some ocular features, including EL severity, AL, WTW, CCT, and so forth, providing novel perspectives and directions for further mechanistic studies.

17.
Bioorg Med Chem Lett ; 50: 128352, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34481987

RESUMO

Activation of the PI3K/Akt/mTOR kinase pathway is associated with human cancers. A dual p70S6K/Akt inhibitor is sufficient to inhibit strong tumor growth and to block negative impact of the compensatory Akt feedback loop activation. A scaffold docking strategy based on an existing quinazoline carboxamide series identified 4-aminopyrimidine analog 6, which showed a single-digit nanomolar and a micromolar potencies in p70S6K and Akt enzymatic assays. SAR optimization improved Akt enzymatic and p70S6K cellular potencies, reduced hERG liability, and ultimately discovered the promising candidate 37, which exhibited with a single digit nanomolar value in both p70S6K and Akt biochemical assays, and hERG activities (IC50 = 17.4 µM). This agent demonstrated dose-dependent efficacy in inhibiting mice breast cancer tumor growth and covered more than 90% pS6 inhibition up to 24 h at a dose of 200 mg/kg po.

18.
Future Microbiol ; 16: 1041-1051, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34493087

RESUMO

Aim: To screen novel biomarkers in serum of syphilis patients using a mass spectrometry-based method. Materials & methods: Sera were collected from 18 syphilis patients and divided into three groups. Every six serum samples (before and after treatment) in each group were pooled and detected by mass spectrometry. Results: Twenty-five unique peptides corresponding to 15 Treponema pallidum proteins were discovered. Among them, Tp0369 was discovered as a promising biomarker candidate in this study. Tp0524 and Tp0984 levels decreased 0.38-fold and 0.51-fold after BPG treatment, respectively, which may be related to disease outcomes of syphilis. Conclusion: These findings confirmed the presence of detectable T. pallidum protein in patients' serum, which could promote the development of syphilis diagnostics.

19.
Obes Surg ; 31(12): 5358-5366, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34586568

RESUMO

PURPOSE: Obesity increases the risk of incident chronic kidney disease (CKD) and is one of the strongest risk factors for new-onset CKD even in the absence of metabolic risk factors. Weight loss has been shown to reduce renal hyperfiltration and proteinuria. Metabolic bariatric surgery (MBS) remains an effective treatment for obesity and its metabolic-related complications. However, literature on its impact on renal function remains limited. MATERIALS AND METHODS: This was an observational retrospective study in a tertiary centre in Singapore. MBS cases performed at the centre between 2008 and 2019 were included. The primary outcome measures were estimated glomerular filtration rate (eGFR), calculated using the CKD epidemiology collaboration equation, and albuminuria (defined as urine albumin-creatinine ratio (uACR) > 3.5 mg/mmol) at baseline and 1-year post-MBS. RESULTS: Five hundred fifty-seven patients were included. One-year post-MBS, median eGFR increased from 110.9 mL/min/1.73 m2 (IQR 92.4 to 121.5) to 112.6 mL/min/1.73 m2 (IQR 97.3 to 122.3), p < 0.001. Median uACR decreased from 1.00 mg/mmol (IQR 0.40 to 3.55) to 0.70 mg/mmol (IQR 0.40 to 1.80) 1-year post-MBS (p = 0.001). 12.9% of patients had improved CKD staging. The proportion of patients with albuminuria decreased from 24.8% at baseline to 1.89% 1-year post-MBS (p < 0.001). One-year post-MBS, the subgroup with reduced eGFR had significant increases in eGFR (p < 0.001), with a trend towards a reduction in uACR. CONCLUSIONS: MBS had a positive impact on renal function with modest but statistically significant improvement in eGFR and reduction in albuminuria at 1-year post-surgery. Longer-term data is required to investigate the durability of this impact.

20.
Int J Ophthalmol ; 14(8): 1218-1224, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34414087

RESUMO

AIM: To investigate whether the axial length (AL)/total corneal refractive power (TCRP) ratio is a sensitive and simple factor that can be used for the early diagnosis of Marfan's syndrome (MFS) in children. METHODS: The relationship between the AL/TCRP ratio and the diagnosis of MFS for 192 eyes in 97 children were evaluate. The biological characteristics, including age, sex, AL, and TCRP, were collected from medical records. Receiver operating characteristic (ROC) curve analysis was performed to investigate whether the AL/TCRP ratio effectively distinguishes MFS from other subjects. The Youden index was used to re-divide the whole population into two groups according to an AL/TCRP ratio of 0.59. RESULTS: Of 96 subjects (mean age 7.46±3.28y) evaluated, 56 (110 eyes) had a definite diagnosis of MFS in childhood based on the revised Ghent criteria, 41 (82 eyes) with diagnosis of congenital ectopia lentis (EL) were included as a control group. AL was negatively correlated with TCRP, with a linear regression coefficient of -0.36 (R 2=0.08). A significant correlation was found between age and the AL/TCRP ratio (P=0.023). ROC curve analysis showed that the AL/TCRP ratio distinguished MFS from the other patients at a threshold of 0.59. MFS patients were present in 24/58 (41.38%) patients with an AL/TCRP ratio of ≤0.59 and in 34/39 (87.18%) patients with an AL/TCRP ratio of >0.59. CONCLUSION: An AL/TCRP ratio of >0.59 is significantly associated with the risk of MFS. The AL/TCRP ratio should be measured as a promising marker for the prognosis of children MFS. Changes in the AL/TCRP ratio should be monitored over time.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...