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1.
Ann Anat ; 239: 151847, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34687906

RESUMO

BACKGROUND: To explore the role of the mechanosensitive ion channel Piezo1 in the proliferation and osteogenic differentiation of human dental follicle cells (hDFCs), and its mechanism, so as to provide the basis for the use of hDFCs to achieve bone regeneration. METHODS: hDFCs were obtained from fresh dental follicle tissues by enzymatic digestion, and cell phenotype and multipotential differentiation were identified. Identification of the expression of mechanosensitive ion channel Piezo1 was performed by immunofluorescence and immunohistochemistry. CCK-8 was used to determine the optimal concentration of the Piezo1 agonist, Yoda1. Then, according to the obtained results, Alizarin red staining, RT-PCR quantitative analysis and Western blot were used to further observe the osteogenic differentiation of hDFCs and its probable mechanism via Wnt/ß-catenin signalling. The data were analysed by SPSS 22.0 software. RESULTS: The results of the concentration gradient experiments indicated that 0.5 µM Piezo1 agonist (Yoda1) enhanced the proliferation of hDFCs. Compared with the control group, a considerable number of calcium nodules showed that activating Piezo1 could promote the osteogenic differentiation of hDFCs. The relative mRNA and protein expression of Piezo1, ALP, RUNX2, OCN and BMP2 in the Piezo1 agonist group were higher than that of the control group. Furthermore, the expression of Wnt3a and ß-catenin related to the classical osteogenic pathway were significantly up-regulated in the Piezo1 agonist group. CONCLUSION: Activating mechanosensitive ion channel Piezo1 with an appropriate concentration of Yoda1 has a positive effect on the proliferation and osteogenic differentiation of hDFCs. This mechanism of promoting osteogenic differentiation may be mediated by the Wnt/ß-catenin pathway.


Assuntos
Saco Dentário , Osteogênese , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Humanos , Canais Iônicos/genética
2.
Anal Chim Acta ; 1190: 339175, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34857128

RESUMO

In this work, we developed a new approach for fabricating hollow and porous nitrogen doped carbon nanoballoons loading AuNPs (Au-NC-NBs) with a large specific surface area, a high N and Au content. The surface-enhanced Raman scattering (SERS) aptasensor based on the resulting Au-NC-NBs possess a wider linear range (10 to 107 cells/mL), a lower detection limit (3 cells/mL), better selectivity for detecting bacteria than previously reported sensors. Importantly, Au-NC-NBs SERS aptasensor also exhibits excellent performance for detecting bacteria in the real food and biological samples. This work provides a facile and versatile designing strategy for controlled construction of SERS biosensor by combination of Au nanoparticles and carbon materials, which has a great applied potential in food safety monitoring and clinical diagnosis.

3.
J Neurotrauma ; 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34726508

RESUMO

Excessive activation of voltage-gated sodium channel Nav1.3 has been recently reported in secondary traumatic brain injury (TBI). However, the molecular mechanisms underlying regulating voltage-gated sodium channel (Nav1.3) has not been well understood. The present study used a TBI rat model induced by a fluid percussion device and performed a circRNA microarray (n=3) to profile the altered circRNAs in the hippocampus after TBI. After PCR validation, certain circRNA was selected to investigate the function and mechanism in regulating Nav1.3 in the TBI rat model by intracerebroventricular (ICV) injection with lentivirus. The neurological outcome was evaluated by Morris water maze (MWM) test, modified Neurological Severity Score (mNSS), brain water content measurement, hematoxylin, and eosin (H&E) staining. The related molecular mechanisms were explored with PCR, western blotting, luciferase reporter, chromatin immunoprecipitation (ChIP), and electrophoretic mobility shift assay (EMSA). A total of 347 circRNAs were observed to be differentially expressed (FC ≥1.2 and p < 0.05) after TBI, including 234 up-regulated and 113 down-regulated circRNAs. Among 10 validated circRNAs, we selected circRNA_009194 with the maximized up-regulated fold change (n=5, FC=4.45, p<0.001) for the in vivo functional experiments. Down-regulation of circRNA_009194 resulted in a 27.5% reduced mNSS in rat brain (n=6, p<0.01) after TBI and regulated the expression levels of miR-145-3p, Sp1, and Nav1.3, which was reversed by sh-miR-145-3p or Sp1/Nav1.3 overexpression (n=5, p<0.05). Mechanistically, circRNA_009194 might act as a sponge for miR-145-3p to regulate Sp1-mediated Nav1.3. This study demonstrated that circRNA_009194 knockdown could improve neurological outcomes in TBI in vivo by inhibiting Nav1.3, directly or indirectly (Graphical Summary).

5.
Am J Transl Res ; 13(10): 11316-11328, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34786060

RESUMO

OBJECTIVE: To investigate the effect of long non-coding RNA (LncRNA) PTGS2 on islet ß-cell function via the miR-146a-5p/Retinol binding protein 4 (RBP4) axis and its diagnostic value in type 2 diabetes mellitus (T2DM). METHODS: The Gene Expression Omnibus (GEO) was analyzed and LncRNA PTGS2 was identified as a potential regulator of T2DM. Mouse pancreatic ß cell INS-1 cells were cultured with high glucose, and the relative expression of LncRNA PTGS2 in the serum of T2DM patients and INS-1 cells was detected by Fluorescence Quantitative PCR (qRT-PCR) and its diagnostic value for T2DM was analyzed. The PTGS2/miR-146a-5p/RBP4 axis in INS-1 cells was intervened to observe the changes in cell function. The proliferation of INS-1 cells was detected by CCK8, and the level of insulin secretion was detected by enzyme linked immunosorbent assay (ELISA). The regulatory relationship among LncRNA PTGS2, miR-146a-5p and RBP4 was determined by dual-luciferase reporter assay. RESULTS: The expression of LncRNA PTGS2 in the serum of T2DM patients increased, and the expression of LncRNA PTGS2 was positively correlated with the fasting blood glucose level of patients (R=0.306, P<0.05). Knockdown of LncRNA PTGS2 could promote the proliferation and insulin secretion of INS-1 cells, while overexpression of LncRNA PTGS2 showed the opposite results (all P<0.05). Knockdown of LncRNA PTGS2 could up-regulate the expression of miR-146a-5p. Overexpression of LncRNA PTGS2 inhibited the proliferation and insulin secretion of INS-1 cells, while miR-146a-5p could partially reverse this effect. RBP4 has been identified as a downstream target gene of miR-146a-5p. Overexpression of miR-146a-5p could inhibit the expression of RBP4, which was positively correlated withLncRNA PTGS2 regulation. The effect of RBP4 on INS-1 cells was the same as that of LncRNA PTGS2. CONCLUSION: LncRNA PTGS2 can damage islet ß-cell function by regulation of miR-146a-5p and up-regulation of RBP4. LncRNA PTGS2 has potential value in the diagnosis of T2DM.

6.
BMC Immunol ; 22(1): 67, 2021 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620075

RESUMO

BACKGROUND: Toll-like receptors (TLRs) play central roles in the initiation of innate immune response, and also control adaptive immunity activation. Thus, the aim of the study was to investigate the regulation of TLR activation to CD8+ T cells has not been fully elucidated in gastric cancer (GC). MATERIALS AND METHODS: Thirty-two GC patients and twenty-three healthy controls were enrolled. Expression profile of TLRs in peripheral and tumor-infiltrating CD8+ T cells was investigated. Purified CD8+ T cells were stimulated with Pam3Csk4, an agonist of TLR2, and cytotoxic and co-inhibitory molecules in CD8+ T cells was measured. Direct and indirect contact coculture system between CD8+ T cells and AGS cells was set up. Modulation of TLR2 activation to CD8+ T cells was assessed by measuring lactate dehydrogenase release and cytokine secretion. RESULTS: TLR2 mRNA and TLR2+ cell percentage was down-regulated in GC derived peripheral and tumor-infiltrating CD8+ T cells. CD8+ T cells from GC patients showed exhausted phenotype, which presented as decreased perforin/granzyme B, increased programmed death-1, and reduced cytotoxicity to AGS cells. TLR2 activation by Pam3Csk4 enhanced perforin and granzyme B expression in CD8+ T cells, however, did not affect either proinflammatory cytokine production or co-inhibitory molecules expression. Pam3Csk4 stimulation enhanced cytolytic activation of peripheral and tumor-infiltrating CD8+ T cells from GC, but not those from healthy individuals. CONCLUSION: The present data revealed an important immunomodulatory activity of TLR2 to CD8+ T cells in GC patients.

7.
Plants (Basel) ; 10(10)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34685880

RESUMO

A new steroidal saponin, 26-O-ß-d-glucopyranosyl-(25R)-furost-5-ene-3ß,22α,26-triol 3-O-(1-4)-ß-d-glucopyranosyl-α-l-rhamnopyranosyl-(1-2)-[α-l-rhamnopyranosyl-(1-4)]-ß-d-glucopyranoside [asparacochioside A (1)] was isolated from a hot water extract of the roots of Asparagus cochinchinensis, together with the known steroidal saponins protodioscin (2), methyl protodioscin (3), aspacochioside A (4), aspacochioside C (5), 15-hydroxypseudoprotodioscin (6), and chamaedroside E (7). The structure of the new compound 1 was determined by interpretation of its spectroscopic data (1D- and 2D-NMR and HR-Q-TOF-MS) and sugar analysis. The isolated compounds 1-7 were tested for their in vitro cytotoxicity against human ovarian cancer cell lines (A2780 and SKOV3). Asparacochioside A (1) exhibited a significant cytotoxicity against both A2780 and SKOV3 cells with IC50 values of 5.25 ± 2.2 and 46.82 ± 9.43 µM, respectively. Furthermore, asparacochioside A (1) significantly increased the percentage of Annexin V-positive cells (apoptotic cells), suggesting that asparacochioside A induces ovarian cancer cell death via apoptosis.

8.
PeerJ ; 9: e12147, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616615

RESUMO

Purpose: Breast cancer (BC) is characterized by concealed onset, delayed diagnosis, and high fatality rates making it particularly dangerous to patients' health. The purpose of this study was to use comprehensive bioinformatics analysis and experimental verification to find a new biomarker for BC diagnosis. Methods: We comprehensively analyzed microRNA (miRNA) and mRNA expression profiles from the Gene Expression Omnibus (GEO) and screened out differentially-expressed (DE) miRNAs and mRNAs. We used the miRNet website to predict potential DE-miRNA target genes. Using the Database for Annotation, Visualization and Integrated Discovery (DAVID), we performed Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses on overlapping potential target genes and DE-mRNAs. The protein-protein interaction (PPI) network was then established. The miRNA-mRNA regulatory network was constructed using Cytoscape and the analysis results were visualized. We verified the expression of the most up-regulated DE-miRNA using reverse transcription and a quantitative polymerase chain reaction in BC tissue. The diagnostic value of the most up-regulated DE-miRNA was further explored across three levels: plasma-derived exosomes, cells, and cell exosomes. Results: Our comprehensive bioinformatics analysis and experimental results showed that hsa-miR-21-5p was significantly up-regulated in BC tissue, cells, and exosomes. Our results also revealed that tumor-derived hsa-miR-21-5p could be packaged in exosomes and released into peripheral blood. Additionally, when evaluating the diagnostic value of plasma exosomal hsa-miR-21-5p, we found that it was significantly up-regulated in BC patients. Receiver operating characteristic (ROC) analysis also confirmed that hsa-miR-21-5p could effectively distinguish healthy people from BC patients. The sensitivity and specificity were 86.7% and 93.3%, respectively. Conclusion: This study's results showed that plasma exosomal hsa-miR-21-5p could be used as a biomarker for BC diagnosis.

9.
J Immunother Cancer ; 9(9)2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34593620

RESUMO

BACKGROUND: CD8+ tumor-infiltrating lymphocytes (TILs) comprise phenotypically and functionally heterogeneous subpopulations. Of these, effector memory CD45RA re-expressing CD8+ T cells (Temra) have been discovered and characterized as the most terminally differentiated subset. However, their exact ontogeny and physiological importance in association with tumor progression remain poorly understood. METHODS: We analyzed primary tumors and peripheral blood samples from 26 patients with non-small cell lung cancer and analyzed their phenotypes and functional characteristics using flow cytometry, RNA-sequencing, and bioinformatics. RESULTS: We found that tumor-infiltrating Temra (tilTemra) cells largely differ from peripheral blood Temra (pTemra), with distinct transcriptomes and functional properties. Notably, although majority of the pTemra was CD27-CD28- double-negative (DN), a large fraction of tilTemra population was CD27+CD28+ double-positive (DP), a characteristic of early-stage, less differentiated effector cells. Trajectory analysis revealed that CD8+ TILs undergo a divergent sequence of events for differentiation into either DP or DN tilTemra. Such a differentiation toward DP tilTemra relied on persistent expression of CD27 and CD28 and was associated with weak T cell receptor engagement. Thus, a higher proportion of DP Temra was correlated with lower immunogenicity of tumor antigens and consequently lower accumulation of CD8+ TILs. CONCLUSIONS: These data suggest a complex interplay between CD8+ T cells and tumors and define DP Temra as a unique subset of tumor-specific CD8+ TILs that are produced in patients with relatively low immunogenic cancer types, predicting immunogenicity of tumor antigens and CD8+ TIL counts, a reliable biomarker for successful cancer immunotherapy.

10.
Blood ; 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34665865

RESUMO

The study aimed to compare the efficacy and safety of all-trans retinoic acid (ATRA) plus low-dose rituximab (LD-RTX) with LD-RTX monotherapy in corticosteroid-resistant or relapsed immune thrombocytopenia (ITP) patients. Recruited patients were randomized at a ratio of 2:1 into 2 groups: 112 patients received LD-RTX plus ATRA and 56 patients received LD-RTX monotherapy. Overall response (OR), defined as achieving a platelet count of ≥ 30 × 109/L confirmed on at least two separate occasions (at least 7 days apart), at least a doubling of the baseline platelet count without any other ITP-specific treatment and the absence of bleeding within 1 year after enrollment, was observed in more patients in the LD-RTX plus ATRA group (80%) than in the LD-RTX monotherapy group (59%) (between-group difference, 0.22; 95% CI, 0.07 to 0.36). Sustained response (SR), defined as maintenance of a platelet count > 30 x 109/L, an absence of bleeding, and no requirement for any other ITP-specific treatment for 6 consecutive months after achievement of OR during 1 year following enrollment, was achieved by 68 (61%) patients in the combination group and 23 (41%) patients in the monotherapy group (between-group difference, 0.20; 95% CI, 0.04 to 0.35). The 2 most common AEs for the combination group were dry skin and headache or dizziness. Our findings demonstrated that ATRA plus LD-RTX significantly increased the overall and sustained response, indicating a promising treatment option for corticosteroid-resistant or relapsed adult ITP. This study is registered at www.clinicaltrials.gov as #NCT03304288.

11.
Bioengineered ; 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34709970

RESUMO

Long-chain non-coding RNA ASB16-AS1 has been proven to be an oncogene for many cancer types. However, the relationship between ASB16-AS1 and immunity is still under studied. This study aims to explore the expression and prognostic potential of ASB16-AS1, and to visualize the relationship between ASB16-AS1 expression and immune infiltration in pan-cancer. We clarified ASB16-AS1 expression patterns in pan-cancer and its relationship with prognosis through multi-platform and multi-database sources (TCGA, GEO, GTEx, ArrayExpress, and SRA), and verified the function of ASB16-AS1 in liver hepatocellular carcinoma (LIHC). Then, a variety of immune cell content evaluation methods were used to mutually verify the correlation between ASB16-AS1 and immune infiltration. Finally, the relationships between ASB16-AS1 and some molecular characteristics (immune checkpoints, tumor mutation burden, microsatellite instability, oncogenic signaling pathways) were further explored. In terms of comprehensive analysis, compared with non-tumor tissues, ASB16-AS1 was highly expressed in tumor tissues, and indicated the value of poor prognosis in multiple cancer types. Functional assays, such as CCK8 assay, transwell assay and wound scratch assay, verified that high ASB16-AS1 expression promoted tumor progression in LIHC. ASB16-AS1 was positively correlated with B cells, T cell CD4+ and T cell CD8+ in most cancer types, and negatively correlated with macrophages, dendritic cells and neutrophils in some cancer types, especially in neutrophils. In addition, there were different interaction modes between ASB16-AS1 and molecular features, such as the relationship with oncogenic signaling pathways, showing that the high ASB16-AS1 expression was related to alterations in oncogenic signaling pathways. Our study emphasizes that ASB16-AS1 is a potential pan-cancer prognostic marker, whichs is associated with the immune infiltration in multiple cancer types.

12.
Arch Gerontol Geriatr ; 98: 104544, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34628214

RESUMO

BACKGROUND: Frailty has been proposed as a poor prognostic indicator for elderly patients with coronary artery diseases (CAD). The objective of this meta-analysis was to evaluate the effects of frailty on all-cause mortality in elderly patients with CAD following percutaneous coronary intervention (PCI). METHODS: PubMed, Embase, the Cochrane library, Web of science, and ClinicalTrial.gov were searched for associated studies from their inception to April 30, 2021. Odds ratios (OR) were calculated to estimate the in-hospital and short-term outcomes, whereas the hazard ratios (HR) were pooled for long-term mortality using random-effects by Revman 5.3. RESULTS: A total of nine studies including 2658 elderly participants were included in this meta-analysis. It was identified that the prevalence of frailty ranged from 12.5 to 27.8%. Frailty was associated with increased in-hospital mortality (OR 3.59, 95% CI 2.01 - 6.42; I2 = 35%), short-term mortality (OR 6.61, 95% CI 2.89 - 15.16; I2 = 0%), as well as long-term mortality (HR 3.24, 95% CI 2.04- 5.14; I2 = 70%) in patients undergoing PCI. Besides, we also found that prefrailty was a predictor of all-cause mortality. CONCLUSIONS: Frailty was associated with in-hospital, short-term and long-term mortality in elderly patients with PCI. The results may consolidate the importance of routine frailty screening in risk stratification in elderly patients with CAD who are considered for PCI.

13.
Stem Cells Dev ; 30(22): 1126-1138, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34549601

RESUMO

Urine-derived stem cells (USCs) are adult stem cells isolated from urine with strong proliferative ability and differentiation potentials. Cell transplantation of USCs could partly repair liver injury. It has been reported that the proliferative ability of bone mesenchymal stem cells in patients with chronic liver failure is significantly lower than in patients without liver disease. The aim of this study was therefore to evaluate the biological characteristics of USCs from end-stage liver disease patients (LD-USCs, USCs from patients with liver disease) compared with those from normal healthy individuals (N-USCs, USCs from normal individuals), with a view to determining whether autologous USCs can be applied to the treatment of liver disease. In this study USCs were isolated from urine samples of male patients with end-stage liver disease. Adherent USCs exhibit a spindle- or rice grain-like morphology, and express CD24, CD29, CD73, CD90, and CD146 surface markers, but not CD31, CD34, CD45, and CD105. We observed no differences in cell morphology or cell surface marker profile between LD-USCs and N-USCs. LD-USCs exhibited similar proliferative, colony-forming, apoptotic, and migratory abilities to N-USCs. Both USCs demonstrated similar capacities for osteogenic, adipogenic, and chondrogenic differentiation. When USCs were transplanted into CCl4 treatment-induced acute and chronic liver fibrosis mouse models, we observed a decrease in liver index, recovery of alanine aminotransferase and aspartate aminotransferase levels, alleviation of liver tissue injury, and dramatic improvement of liver tissue structure. USC transplantation can effectively recover liver function and improve liver tissue damage in acute or chronic liver injury mouse models. According to the results, we concluded that the biological characteristics of LD-USCs are not affected by basic liver disease. This study provides further evidence of the stem cell characteristics and liver repair function of LD-USCs, which may serve as a theoretical and experimental foundation for autologous USC transplantation technology in the treatment of liver failure and end-stage liver diseases.

14.
Reprod Toxicol ; 105: 91-100, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34478853

RESUMO

Pulmonary arterial hypertension is a progressive disorder characterized by remodeling and increased small pulmonary arteries resistance. Endothelin-1 (ET-1) was related to PAH and ET-1 receptors were up-regulated selectively in the lung when exposed to toxic factor hypoxia. However, the role of ET-1 signaling in the pathogenesis of prenatal hypoxia-induced pulmonary abnormalities remains to be elucidated. Pregnant rats were divided into prenatal hypoxia (10.5 % O2 from gestational day 4-21) and control group. Their three-month-old offspring male rats were tested for vascular functions and molecular analysis, DNA methylation was assessed for cellular hypoxia. Functional testing showed that ET-1-mediated vasoconstriction was enhanced, and the expressions of endothelin A receptor/B receptor (ETAR/ETBR), inositol 1,4,5-trisphosphate receptor, type 1, and the sensitivity of calcium channels were increased in the small pulmonary arteries following prenatal hypoxia. q-PCR and DHE staining showed that the expressions of NADPH oxidase 1/4 (Nox1/4) were up-regulated, along with the increased production of superoxide anion. Furthermore, superoxide anion promoted ET-1-mediated pulmonary artery contraction. In the pulmonary artery smooth muscle cell experiments, q-PCR, Western Blot, CCK8 and DHE staining showed that the expressions of ETBR, Nox1/4, and superoxide anion were increased by hypoxia, along with promoted cell proliferation. 2,2,6,6-Tetramethyl-1-piperidinyloxy reversed hypoxia-induced cell proliferation. ETBR antagonist BQ788 inhibited hypoxia-increased expressions of Nox1/4, superoxide anion production, and proliferation of cells. Moreover, methylation analysis indicated that hypoxia decreased the methylation levels of the ETBR promoter in the pulmonary artery smooth muscle cells. The results indicated that prenatal toxic factor hypoxia resulted in abnormal ETBR activation, which enhanced ET-1-mediated vasoconstriction of pulmonary arteries and pulmonary artery smooth muscle cell proliferation through ETBR/Nox1/4-derived ROS pathway.

15.
ACS Appl Mater Interfaces ; 13(36): 42917-42926, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34478622

RESUMO

The LiCoO2 cathode undergoes undesirable electrochemical performance when cycled with a high cut-off voltage (≥4.5 V versus Li/Li+). The unstable interface with poor kinetics is one of the main contributors to the performance failure. Hence, a hybrid Li-ion conductor (Li1.5Al0.5Ge1.5P3O12) and electron conductor (Al-doped ZnO) coating layer was built on the LiCoO2 surface. Characterization studies prove that a thick and conductive layer is homogeneously covered on LiCoO2 particles. The coating layer can not only enhance the interfacial ionic and electronic transport kinetics but also act as a protective layer to suppress the side reactions between the cathode and electrolyte. The modified LiCoO2 (HC-LCO) achieves an excellent cycling stability (77.1% capacity retention after 350 cycles at 1C) and rate capability (139.8 mAh g-1 at 10C) at 3.0-4.6 V. Investigations show that the protective layer can inhibit the particle cracks and Co dissolution and stabilize the cathode electrolyte interface (CEI). Furthermore, the irreversible phase transformation is still observed on the HC-LCO surface, indicating the phase transformation of the LiCoO2 surface may not be the main factor for fast performance failure. This work provides new insight of interfacial design for cathodes operating with a high cut-off voltage.

16.
Org Biomol Chem ; 19(39): 8554-8558, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34557883

RESUMO

A concise and environmentally friendly protocol was developed for the synthesis of 6-phenylbenzo[h]quinolines. 6-Phenylbenzo[h]quinolines were obtained in good yields via irradiation of (E)-2-phenyl-3-styrylpyridines with a 254 nm UV light (64 W) in EtOH under an argon atmosphere in the presence of TFA. The reaction is a dehydrogenative annulation reaction that proceeds through 6π-electrocyclization, a [1,5]-H shift, 1,3-enamine tautomerization, and elimination of a hydrogen molecule to afford 6-phenylbenzo[h]quinolines. The described protocol not only avoids the usage of a transition metal catalyst and an oxidant but also has the advantages of high atom efficiency and mild reaction conditions.

17.
Blood Adv ; 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34507352

RESUMO

Transplant-associated thrombotic microangiopathy (TA-TMA) is a potentially life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Information on markers for early prognostication remains limited, and no predictive tools for TA-TMA are available. We attempt to develop and validate a prognostic model for TA-TMA. A total of 507 patients who developed TA-TMA following allo-HSCT were retrospectively identified and separated into a derivation cohort and a validation cohort according to the time of transplantation to perform external temporal validation. Patient age (OR 2.371, 95% CI 1.264-4.445), anemia (OR 2.836, 95% CI 1.566-5.138), severe thrombocytopenia (OR 3.871, 95% CI 2.156-6.950), elevated total bilirubin (OR 2.716, 95% CI 1.489-4.955) and proteinuria (OR 2.289, 95% CI 1.257-4.168) were identified as independent prognostic factors for the 6-month outcome of TA-TMA. A risk score model termed BATAP (Bilirubin, Age, Thrombocytopenia, Anemia, Proteinuria) was then constructed according to the regression coefficients. The validated c-statistics were 0.816 (95% CI 0.766-0.867) and 0.756 (95% CI 0.696-0.817) in the internal and external validation, respectively. Calibration plots indicated that the model-predicted probabilities correlated well with the actual observed frequencies. This predictive model may facilitate the prognostication of TA-TMA and contribute to the early identification of high-risk patients.

18.
J Comput Assist Tomogr ; 45(6): 932-940, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34469904

RESUMO

OBJECTIVE: This study investigated the role of radiomics in evaluating the alterations of oncogenic signaling pathways in head and neck cancer. METHODS: Radiomics features were extracted from 106 enhanced computed tomography images with head and neck squamous cell carcinoma. Support vector machine-recursive feature elimination was used for feature selection. Support vector machine algorithm was used to develop radiomics scores to predict genetic alterations in oncogenic signaling pathways. The performance was evaluated by the area under the curve (AUC) of the receiver operating characteristic curve. RESULTS: The alterations of the Cell Cycle, HIPPO, NOTCH, PI3K, RTK RAS, and TP53 signaling pathways were predicted by radiomics scores. The AUC values of the training cohort were 0.94, 0.91, 0.94, 0.93, 0.87, and 0.93, respectively. The AUC values of the validation cohort were all greater than 0.7. CONCLUSIONS: Radiogenomics is a new method for noninvasive acquisition of tumor molecular information at the genetic level.

19.
Curr Med Chem ; 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34365945

RESUMO

Rifamycins are considered a milestone for tuberculosis (TB) treatment because of their proficient sterilizing ability. Currently, available TB treatments are complicated and need a long duration, which ultimately leads to failure of patient compliance. Some new rifamycin derivatives, i.e., rifametane, TNP-2092 (rifamycin-quinolizinonehybrid), and TNP-2198 (rifamycin-nitromidazole hybrid) are under clinical trials, which are attempting to overcome the problems associated with TB treatment. The undertaken review is intended to compare the pharmacokinetics, pharmacodynamics and safety profiles of these rifamycins, including rifalazil, another derivative terminated in phase II trials, and already approved rifamycins. The emerging resistance of microbes is an imperative consideration associated with antibiotics. Resistance development potential of microbial strains against rifamycins and an overview of chemistry, as well as structure-activity relationship (SAR) of rifamycins, are briefly described. Moreover, issues associated with rifamycins are discussed as well. We expect that newly emerging rifamycins shall appear as potential tools for TB treatment in the near future.

20.
Int J Biol Macromol ; 188: 323-332, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34375661

RESUMO

The demand for biodegradable and renewable UV-shielding materials is ever increasing due to the rising concern for the environment. In this paper, biobased lignin was functionalized by polyhedral oligomeric silsesquioxane (POSS) with an epoxy substituent. Then the POSS decorated lignin (lignin-POSS) was mixed with polylactide (PLA) to act as UV-shielding filler by melt compounding. The SEM observation revealed that the presence of POSS contributed to improving the homogeneous dispersion of lignin-POSS in the PLA matrix with good compatibility when the content of lignin-POSS was lower than 5 wt%. The synergistic effects of lignin and POSS endowed PLA composite films with a good balance of UV-shielding ability and transparency in the visible light region. With the addition of 5 wt% lignin-POSS, the PLA composite film absorbed almost all UV irradiation across the entire UV spectrum. In addition, the presence of lignin-POSS could serve as a nucleating agent to increase the degree of crystallinity of PLA. The dynamical rheological tests revealed that the lignin-POSSS reduced the complex viscosity and storage modulus of PLA composites, improving the flowability of PLA composites. This work presents a viable pathway to prepare biodegradable and renewable UV-shielding materials for potential packaging applications.

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