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1.
J Dent Sci ; 18(1): 157-164, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36643274

RESUMO

Background/purpose: The efficiency of root canal irrigation has an important impact on the prognosis of root canal treatment. Photon-induced photoacoustic streaming (PIPS) and shock wave enhanced emission photoacoustic streaming (SWEEPS) are the special modality of Er: YAG laser, whether can they improve the efficiency of root canal irrigation remains to be studied. Materials and methods: Fifty human teeth with curved root canals were collected and stored in the thymol solution until used in the study. After traditional endodontic cavities preparation, root canals were prepared to size #35 with a 0.04 taper. The final irrigating techniques were as follows: (I) manual dynamic activation (MDA), (II) ultrasonically activated irrigation (UAI), (III) sonically activated irrigation (SAI), (IV) PIPS, and (V) SWEEPS. Fifty teeth were randomly divided into five groups mentioned above. After root canal preparation, the roots were cleaved longitudinally. The dentine surfaces were photographed from the coronal, middle, and apical third of the root by scanning electron microscopy operated at a low vacuum. Two examiners separately graded each image according to the remained smear layer situations. Results: PIPS and SWEEPS groups showed fewer smear layers remaining than the others in the middle and the apical third (P < 0.05) of the root canal. In contrast, in the coronal third, five groups showed no significant difference (P > 0.05). Conclusion: PIPS and SWEEPS showed superior smear layer clearing efficiency than traditional irrigating techniques in curved root canals.

2.
Environ Res ; 220: 115256, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36634892

RESUMO

Metabolism generally transforms xenobiotics into more polar and hydrophilic products, facilitating their elimination from the body. Recently, a new metabolic pathway that transforms phenolic xenobiotics into more lipophilic and bioactive dimer products was discovered. To elucidate the role of cytochrome P450 (CYP) enzymes in mediating this cross-coupling metabolism, we used high-throughput screening to identify the metabolites generated from the coupling of 20 xenobiotics with four endogenous metabolites in liver microsomes. Endogenous vitamin E (VE) was the most reactive metabolite, as VE reacted with seven phenolic xenobiotics containing various structures (e.g., an imidazoline ring or a diphenol group) to generate novel lipophilic ethers such as bakuchiol-O-VE, phentolamine-O-VE, phenylethyl resorcinol-O-VE, 2-propanol-O-VE, and resveratrol-O-VE. Seven recombinant CYP enzymes were successfully expressed and purified in Escherichia coli. Integration of the results of recombinant human CYP incubation and molecular docking identified the central role of CYP3A4 in the cross-coupling metabolic pathway. Structural analysis revealed the π-π interactions, hydrogen bonds, and hydrophobic interactions between reactive xenobiotics and VE in the malleable active sites of CYP3A4. The consistency between the molecular docking results and the in vitro human cytochrome P450 evaluation shows that docking calculations can be used to screen molecules participating in cross-coupling metabolism. The results of this study provide supporting evidence for the overlooked toxicological effects induced by direct reactions between xenobiotics and endogenous metabolites during metabolic processes.

3.
Bioorg Chem ; 132: 106348, 2023 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-36657274

RESUMO

The phytochemical study of Limonium gmelinii roots resulted in the isolation of five lignanamides (1-5). Among them, limoniumins J, K, and M (1, 2, and 4) are undescribed compounds, limoniumin L (3) is a new naturally occurring lignanamide, and limoniumin B (5) is a known compound which showed PTP1B inhibition activity with an IC50 value of 5.05 ± 2.44 µM in our previous work. Spectroscopic data analysis, including 1D and 2D NMR and HRESIMS experiments, established the chemical structures of limoniumins J - M (1-4). Compounds 1-4 showed PTP1B inhibition activity, among which compound 3 showed the most potent PTP1B inhibition with an IC50 value of 2.07 ± 0.05 µM. Compounds 3 and 5 could significantly increase cellular glucose consumption and glucose uptake in L6 muscle cells and could synergize with insulin to promote glucose consumption and glucose uptake in a concentration-dependent manner. The treatment of compound 3 also promoted glycogen synthesis in skeletal muscle cells. Western blot analysis demonstrated that the good hypoglycemic effect of compounds 3 and 5 was achieved by activating PI3K/AKT signaling pathway to promote glucose consumption, glucose uptake, and glycogen synthesis. Furthermore, studies on molecular docking revealed the potent interactions between these bioactive substances and the PTP1B protein.

4.
Foods ; 12(2)2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36673366

RESUMO

Lactobacillus acidophilus (LA) and Astragalus polysaccharides (APS) have each been shown to have anti-osteoporotic activity, and the aim of this study was to further investigate whether the LA fermenting APS was more effective in improving calcium absorption and osteoporosis than the unfermented mixed solution (MS). We found that the fermentation solution (FS) intervention improved the calcium absorption, BMD, and bone microarchitecture in osteoporotic rats and resulted in better inhibition of osteoclast differentiation markers ACP-5 and pro-inflammatory cytokines TNF-α and IL-6 and promotion of osteoblast differentiation marker OCN. This better performance may be due to the improved restoration of the relative abundance of specific bacteria associated with improved calcium absorption and osteoporosis such as Lactobacillus, Allobaculum, and UCG-005. Several key metabolites, including indicaxanthin, chlorogenic acid, and 3-hydroxymelatonin, may also be the key to the better improvement. In conclusion, the LA fermenting APS can better improve calcium absorption and osteoporosis by increasing active metabolites and altering gut microbiota. This finding should become a solid foundation for the development of LA fermenting APS in functional foods.

5.
Sci Rep ; 13(1): 436, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36624121

RESUMO

We aimed to explore whether superfluous sympathetic activity affects myoblast differentiation, fusion, and myofiber types using a continuous single-dose isoprenaline exposure model in vitro and to further confirm the role of distinct NFATs in ISO-mediated effects. Compared with delivery of single and interval single, continuous single-dose ISO most obviously diminished myotube size while postponing myoblast differentiation/fusion in a time- and dose-dependent pattern, accompanied by an apparent decrease in nuclear NFATc1/c2 levels and a slight increase in nuclear NFATc3/c4 levels. Overexpression of NFATc1 or NFATc2, particularly NFATc1, markedly abolished the inhibitory effects of ISO on myoblast differentiation/fusion, myotube size and Myh7 expression, which was attributed to a remarkable increase in the nuclear NFATc1/c2 levels and a reduction in the nuclear NFATc4 levels and the associated increase in the numbers of MyoG and MEF2C positive nuclei within more than 3 nuclei myotubes, especially in MEF2C. Moreover, knockdown of NFATc3 by shRNA did not alter the inhibitory effect of ISO on myoblast differentiation/fusion or myotube size but partially recovered the expression of Myh7, which was related to the slightly increased nuclear levels of NFATc1/c2, MyoG and MEF2C. Knockdown of NFATc4 by shRNA prominently increased the number of MyHC +, MyoG or MEF2C + myoblast cells with 1 ~ 2 nuclei, causing fewer numbers and smaller myotube sizes. However, NFATc4 knockdown further deteriorated the effects of ISO on myoblast fusion and myotube size, with more than 5 nuclei and Myh1/2/4 expression, which was associated with a decrease in nuclear NFATc2/c3 levels. Therefore, ISO inhibited myoblast differentiation/fusion and myotube size through the NFAT-MyoG-MEF2C signaling pathway.


Assuntos
Fibras Musculares Esqueléticas , Transdução de Sinais , Isoproterenol/farmacologia , Isoproterenol/metabolismo , Diferenciação Celular , Fibras Musculares Esqueléticas/metabolismo , Mioblastos/metabolismo , RNA Interferente Pequeno/metabolismo
6.
Appl Opt ; 62(1): 206-210, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36606866

RESUMO

In this work, the intensity noise transfer properties of a two-stage single-frequency fiber amplifier at 1 µm are systematically investigated in the frequency domain. By applying an artificial modulation signal to the driving current of the first- and second-stage pump sources, the pump and signal transfer functions of the second-stage amplifier are experimentally measured from 10 Hz to 100 kHz. By associating the theoretical model, the effects of pump power, the operating wavelength, and the absorption coefficient of the gain fiber on the pump and signal transfer properties are analyzed based on the experimental measurements. It turns out that the gain dynamics of the last-stage amplifier play an important role in determining the noise performances of the final amplified laser. Because the pump and signal transfer functions essentially behave as a low pass and damped high pass filter, the pump intensity noise of the last-stage amplifier dominates the amplifier system's overall noise performance. In addition, the effects of amplified spontaneous emission (ASE) on the intensity noise transfer properties are nontrivial, although it is not included in the theoretical model. It is believed that the current work provides a useful guideline for optimizing the design of high-power single-frequency fiber amplifiers with low-intensity noise.

7.
Integr Med Res ; 12(1): 100915, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36632129

RESUMO

Background: Traditional Medicine (TM) has a wide uptake in most countries. In China, Traditional Chinese Medicine (TCM) is a common kind of primary health because of its beneficial effects. This review aimed to appraise the publication reporting quality of economic evaluations for selective TCM in the National Reimbursement Drug List (NRDL), Version 2020, based on the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. Methods: Electronic databases were searched for economic evaluation that supported the TCM negotiations in NRDL (2020 version) published from 2001 to 2021, including PubMed, Web of Science, Embase, CNKI, WanFang, and SinoMed. The CHEERS statement was used to appraise the reporting quality of included TCM economic evaluations. Results: A total of 360 articles were retrieved, but only 38 economic evaluations met the inclusion criteria. None of the articles reported all items in the CHEERS checklist. The mean score of included articles is low at 10.93±2.62, with an average scoring rate of 51.31±10.53%. The least reported items included: "Characterizing heterogeneity," "Conflicts of interest", "Discount rate," and "Study perspective," with a reporting rate of 0.00%, 5.26%, 7.89%, and 15.79%, respectively. Conclusion: An upward trend occurred in the quantity and quality of the economic evaluation publications of TCM in China. TCM economic evaluations are still at an early stage, with an urgent need for improving reporting quality. It may result from research experiences or different ideas between TCM and Western Medicine. Adhering to reporting guidelines like CHEERS and educating economic evaluation investigators can improve TCM economic evaluations' reporting quality.

8.
Nat Commun ; 14(1): 258, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36650145

RESUMO

Pollen tube guidance within female tissues of flowering plants can be divided into preovular guidance, ovular guidance and a connecting stage called pollen tube emergence. As yet, no female factor has been identified to positively regulate this transition process. In this study, we show that an ovary-expressed bHLH transcription factor Cucumis sativus ALCATRAZ (CsALC) functions in pollen tube emergence in cucumber. CsALC knockout mutants showed diminished pollen tube emergence, extremely reduced entry into ovules, and a 95% reduction in female fertility. Further examination showed two rapid alkalinization factors CsRALF4 and CsRALF19 were less expressed in Csalc ovaries compared to WT. Besides the loss of male fertility derived from precocious pollen tube rupture as in Arabidopsis, Csralf4 Csralf19 double mutants exhibited a 60% decrease in female fertility due to reduced pollen tube distribution and decreased ovule targeting efficiency. In brief, CsALC regulates female fertility and promotes CsRALF4/19 expression in the ovary during pollen tube guidance in cucumber.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Cucumis sativus , Cucumis sativus/genética , Ovário/metabolismo , Tubo Polínico/genética , Tubo Polínico/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Óvulo Vegetal/metabolismo
9.
Dermatology ; : 1-15, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36623489

RESUMO

BACKGROUND: Psoriasis is a chronic recurrent inflammatory skin disease with a high risk of diabetes based on disease severity. OBJECTIVES: The aim of the study was to evaluate the efficacy of different hypoglycemic medications in patients with psoriasis. METHODS: A systematic review and meta-analysis of studies were conducted to evaluate the efficacy of hypoglycemic medications in patients with psoriasis. The primary outcome was of changes in the psoriasis area and severity index (PASI) score, and a 75% improvement in PASI from baseline (PASI75). Subgroup analysis was used to investigate associations among the types of hypoglycemic medicines, combination therapy, patient characteristics, course of treatment, and curative effect. RESULTS: We included 3,286 patients from 19 studies to explore the effects of hypoglycemic medications. Patients randomized to receive hypoglycemic medicines showed a more significant decrease in the PASI score (standard mean difference = -0.55, 95% confidence interval (CI): -0.87 to -0.23, p = 0.0007) and a higher PASI75 ratio (RR: 1.80, 95% CI: 1.20-2.71, p = 0.0046). Patients consuming thiazolidinediones (TZDs) were more likely to reach PASI75 than those consuming glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase 4 inhibitors. The combined use of hypoglycemic medicines had an add-on effect on the standard psoriasis treatment, and the proportion of PASI75 in the combination group was nearly four times that in the noncombination group (p = 0.0216). In addition, hypoglycemic medications can reduce body weight, waist circumference, triglyceride, total cholesterol, low-density lipoprotein, and systolic blood pressure. CONCLUSIONS: Certain hypoglycemic drugs, such as GLP-1 RAs and TZDs, are beneficial for treating psoriasis. Multidisciplinary collaboration is recommended for the management of systemic inflammation in patients with psoriasis and diabetes.

10.
J Appl Oral Sci ; 31: e20220313, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36700591

RESUMO

BACKGROUND: Bone morphogenetic protein 9 (BMP9) tends to be associated with various inflammatory responses of diseases, but its relationship with pulpitis remains unknown. OBJECTIVE: This study aimed to evaluate the effects and mechanisms of BMP9 in pulpitis. METHODOLOGY: A rat model of pulpitis was used to evaluate the expression of BMP9, which was also analysed in Porphyromonas gingivalis lipopolysaccharide (Pg-LPS)-stimulated human dental pulp cells (hDPCs). The effects and mechanism of BMP9 on the regulation of inflammatory factors and matrix metalloproteinase-2 (MMP2) were evaluated using real-time quantitative PCR, western blotting, and immunocytofluorescence. Moreover, the migration ability of THP-1 monocyte-macrophages, treated with inflammatory supernate inhibited by BMP9, was previously tested by a transwell migration assay. Finally, a direct rat pulp capping model was used to evaluate in vivo the influence of the overexpression of BMP9 in pulpitis. RESULTS: The expression of BMP9 decreased after 24 h and increased after 3 and 7 d in rat pulpitis and inflammatory hDPCs. The overexpression of BMP9 inhibited the gene expression of inflammatory factors (IL-6, IL-8, and CCL2) and the secretion of IL-6 and MMP2 in Pg-LPS-stimulated hDPCs. The level of phosphorylated Smad1/5 was upregulated and the levels of phosphorylated ERK and JNK were downregulated. The inflammatory supernate of hDPCs inhibited by BMP9 reduced the migration of THP-1 cells. In rat pulp capping models, overexpressed BMP9 could partially restrain the development of dental pulp inflammation. CONCLUSION: This is the first study to confirm that BMP9 is involved in the occurrence and development of pulpitis and can partially inhibit its severity in the early stage. These findings provided a theoretical reference for future studies on the mechanism of pulpitis and application of bioactive molecules in vital pulp therapy.


Assuntos
Pulpite , Ratos , Humanos , Animais , Pulpite/metabolismo , Metaloproteinase 2 da Matriz , Fator 2 de Diferenciação de Crescimento/farmacologia , Fator 2 de Diferenciação de Crescimento/metabolismo , Polpa Dentária , Interleucina-6 , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo , Inflamação , Células Cultivadas
11.
Chemistry ; 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36715454

RESUMO

The combination of the alkoxyphosphoranes, Ph2P(OR)(O2C6Cl4) and the borane B(C6F5)3 generates the zwitterions 3 which act as FLP to effect the alkylation of several nucleophiles affording C-C, C-N, C-H and C-Cl coupling products. A DFT study shows the reaction proceeds via an FLP activation pathway generating an alkoxyphosphonium intermediate which effects the alkylation of the nucleophiles, akin to the Mitsunobu reaction.

12.
Chem Commun (Camb) ; 59(3): 282-285, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36484802

RESUMO

The aluminum analogue of Piers' borane, [HAl(C6F5)2]31, is prepared on a gram-scale. Density functional theory (DFT) calculations reveal 1 has a higher fluoride ion affinity (FIA) than Piers' borane, while the Al-H moiety proved to be a strong hydride donor, reacting with alcohol and terminal alkyne to give the corresponding dehydrogenative products 3 and 4. Hydroalumination product 5 was prepared via reaction of 1 with aldehyde. In addition, 1 catalyzes the hydrosilylation of alkynes and alkenes.

13.
J Enzyme Inhib Med Chem ; 38(1): 398-404, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36476046

RESUMO

The non-receptor protein tyrosine phosphatase (PTP) SHP2 encoded by the PTPN11 gene is a critical regulator in a number of cellular signalling processes and pathways, including the MAPK and the immune-inhibitory programmed cell death PD-L1/PD-1 pathway. Hyperactivation and inactivation of SHP2 is of great therapeutic interest for its association with multiple developmental disorders and cancer-related diseases. In this work, we characterised a potent SHP2 allosteric inhibitor 2-((3 R,4R)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl)-5-(2,3-dichlorophenyl)-3-methylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (PB17-026-01) by using structure-based design. To study the structure-activity relationship, we compared co-crystal structures of SHP2 bound with PB17-026-01 and its analogue compound PB17-036-01, which is ∼20-fold less active than PB17-026-01, revealing that both of the compounds are bound to SHP2 in the allosteric binding pocket and PB17-026-01 forms more polar contacts with its terminal group. Overall, our results provide new insights into the modes of action of allosteric SHP2 inhibitor and a guide for the design of SHP2 allosteric inhibitor.


Assuntos
Triazinas , Triazinas/farmacologia , Cristalografia por Raios X , Proteína Tirosina Fosfatase não Receptora Tipo 11
14.
Gene ; 854: 147101, 2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36496178

RESUMO

OBJECTIVE: Microscopic polyangiitis (MPA) onset is affected by genetic predisposition. Autophagy plays a certain role in antineutrophil cytoplasmic antibody-associated vasculitis developing. A key factor in autophagy regulating, the genetic polymorphism of MTOR gene is essential. The objective was to explore the associations between MTOR gene polymorphism and MPA susceptibility in a Guangxi population of China. METHODS: A sum of 208 MPA cases and 209 healthy volunteers from Guangxi in this case-control study, four important single nucleotide polymorphism (SNP) loci of MTOR gene including rs3806317, rs1064261, rs1883965 and rs2295080 were examined. Multiplex polymerase chain reaction combined with high-throughput sequencing was performed. Subgroup analysis was evaluated by gender and ethnicity. Linkage disequilibrium and haplotype analysis were tested. Multi-SNPs interaction among mTOR signaling pathway was assessed. RESULTS: For rs2295080, homozygous mutant GG genotype was associated with a decreased susceptibility of MPA in recessive model (OR = 0.38, 95%CI: 0.14-1.00, p = 0.040), particularly in the subgroup of female (OR = 0.16, 95%CI: 0.03-0.74, p = 0.006) and Han population (OR = 0.32, 95%CI: 0.10-1.00, p = 0.034). Individual carrying G allele was linked with decreasing MPA susceptibility in Han population of Guangxi (OR = 0.65, 95%CI: 0.44-0.97, p = 0.036). In haplotype analysis, the haplotype AAT was correlated with increasing susceptibility of MPA (OR = 1.347, 95%CI: 1.004-1.807, p = 0.046). Moreover, in the multi-SNPs interaction analysis, the six-locus model was identified as the best interaction model (p < 0.05). CONCLUSION: These findings suggest that rs2295080 polymorphism of MTOR gene may be associated with MPA susceptibility in a Guangxi population of China and G allele might be an important protective factor.


Assuntos
Poliangiite Microscópica , Humanos , Feminino , Poliangiite Microscópica/genética , Estudos de Casos e Controles , China/epidemiologia , Genótipo , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Haplótipos , Serina-Treonina Quinases TOR/genética , Frequência do Gene
15.
J Cancer Res Clin Oncol ; 149(1): 247-261, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36565319

RESUMO

PURPOSE: The goal of this study was to investigate whether the combined PET/CT radiomic features of the primary tumor and lymph node could predict lymph node metastasis (LNM) of resectable non-small cell lung cancer (NSCLC) in stage T2-4. METHODS: This retrospective study included 192 NSCLC patients who underwent tumor and node dissection between August 2016 and December 2017 and underwent 18F-fluorodeoxyglucose (18F-FDG) PET/CT scanning 1-3 weeks before surgery. In total, 192 primary tumors (> 3 cm) and 462 lymph nodes (LN > 0.5 cm) were analyzed. The pretreatment clinical features of these patients were recorded, and the radiomic features of their primary tumor and lymph node were extracted from PET/CT imaging. The Spearman's relevance combined with the least absolute shrinkage and selection operator was used for radiomic feature selection. Five independent machine learning models (multi-layer perceptron, extreme Gradient Boosting, light gradient boosting machine, gradient boosting decision tree, and support vector machine) were tested as classifiers for model development. We developed the following three models to predict LNM: tumor PET/CT-clinical (TPC), lymph PET/CT-clinical (LPC), and tumor and lymph PET/CT-clinical (TLPC). The performance of the models and the clinical node (cN) staging was evaluated using the ROC curve and confusion matrix analysis. RESULTS: The ROC analysis showed that among the three models, the TLPC model had better predictive clinical utility and efficiency in predicting LNM of NSCLC (AUC = 0.93, accuracy = 85%; sensitivity = 0.93; specificity = 0.75) than both the TPC model (AUC = 0.54, accuracy = 50%; specificity = 0.38; sensitivity = 0.59) and the LPC model (AUC = 0.82, accuracy = 70%; specificity = 0.41; sensitivity = 0.92). The TLPC model also exhibited great potential in predicting the N2 stage in NSCLC (AUC = 0.94, accuracy = 79%; specificity = 0.64; sensitivity = 0.91). CONCLUSION: The combination of CT and PET radiomic features of the primary tumor and lymph node showed great potential for predicting LNM of resectable T2-4 NSCLC. The TLPC model can non-invasively predict lymph node metastasis in NSCLC, which may be helpful for clinicians to develop more rational therapeutic strategies.

16.
Small ; 18(4): e2104341, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34622570

RESUMO

Currently, nucleic acid aptamers are exploited as robust targeting ligands in the biomedical field, due to their specific molecular recognition, little immunogenicity, low cost, ect. Thanks to the facile chemical modification and high hydrophilicity, aptamers can be site-specifically linked with hydrophobic moieties to prepare aptamer-organic amphiphiles (AOAs), which spontaneously assemble into aptamer-organic amphiphile self-assemblies (AOASs). These polyvalent self-assemblies feature with enhanced target-binding ability, increased resistance to nuclease, and efficient cargo-loading, making them powerful platforms for bioapplications, including targeted drug delivery, cell-based cancer therapy, biosensing, and bioimaging. Besides, the morphology of AOASs can be elaborately manipulated for smarter biomedical functions, by regulating the hydrophilicity/hydrophobicity ratio of AOAs. Benefiting from the boom in DNA synthesis technology and nanotechnology, various types of AOASs, including aptamer-polymer amphiphile self-assemblies, aptamer-lipid amphiphile self-assemblies, aptamer-cell self-assemblies, ect, have been constructed with great biomedical potential. Particularly, stimuli-responsive AOASs with transformable structure can realize site-specific drug release, enhanced tumor penetration, and specific target molecule detection. Herein, the general synthesis methods of oligonucleotide-organic amphiphiles are firstly summarized. Then recent progress in different types of AOASs for bioapplications and strategies for morphology control are systematically reviewed. The present challenges and future perspectives of this field are also discussed.


Assuntos
Aptâmeros de Nucleotídeos , Neoplasias , Aptâmeros de Nucleotídeos/química , Sistemas de Liberação de Medicamentos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Nanotecnologia/métodos , Oligonucleotídeos
17.
BMC Health Serv Res ; 22(1): 1475, 2022 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-36463141

RESUMO

PURPOSE: To assess the reporting quality of published economic evaluations of the negotiated oncology drugs listed for China's 2020 National Reimbursement Drug List (NRDL). METHODS: A comprehensive search was conducted to identify economic evaluation studies of negotiated oncology drugs listed in China's 2020 NRDL using the PubMed/MEDLINE, Embase, Web of Science, CNKI, SinoMed, and WanFang Database up to March 31, 2021. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist scored the reporting quality between 0 and 100. A linear regression analysis was employed to examine the influence of various characteristics on the reporting quality scores. RESULTS: Eighty papers were included in the study, with the majority published during the past decade. Furthermore, more than half of the articles (57.5%, or 46 out of 80) were written in English. The average CHEERS score was 74.63 ± 12.75 and ranged from 43.48 to 93.75. The most inadequately reported items included choice of model, characterization of heterogeneity, and discussion, as well as currency, price date and conversion. Higher scores were associated with articles published from 2019 to 2021 and English publications. CONCLUSION: The economic evaluation studies of negotiated oncology drugs listed in 2020 NRDL had moderate reporting quality. The Chinese economic evaluation publications could improve the reporting quality if the CHEERS checklist is consistently implemented. Also, the Chinese journals maybe explore introducing a reporting standard for economic evaluations.


Assuntos
Oncologia , Humanos , Análise Custo-Benefício , Lista de Checagem , China
18.
Food Chem Toxicol ; : 113541, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36464109

RESUMO

Cantharidin (CTD) is a principal bioactive component of traditional Chinese medicine Mylabris used in cancer treatment. However, CTD clinical application is limited due to nephrotoxicity, and the mechanism is unknown. The present study used widely-targeted metabolomics, network pharmacology, and cell experiments to investigate the nephrotoxicity mechanism after CTD exposure. In mice exposed to CTD, serum creatinine and urea nitrogen levels increased with renal injury. Then, 74 differential metabolites were detected, including 51 up-regulated and 23 down-regulated metabolites classified as amino acids, small peptides, fatty acyl, arachidonic acid metabolite, organic acid, and nucleotides. Sixteen metabolic pathways including tyrosine, sulfur, and pyrimidine metabolism were all disrupted in the kidney. Furthermore, network pharmacology revealed that 258 metabolic targets, and pathway enrichment indicated that CTD could activate oxidative phosphorylation and oxidative stress (OS). Subsequently, HK-2 cell experiments demonstrated that CTD could reduce superoxide dismutase while increasing malondialdehyde levels. In conclusion, after CTD exposure, biometabolic processes may be disrupted with renal injury in mice, resulting in oxidative phosphorylation and OS.

19.
Cell Mol Biol Lett ; 27(1): 107, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36474192

RESUMO

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a common head and neck cancer, and the incidence of OSCC is increasing. As the mortality of OSCC keeps increasing, it is crucial to clarify its pathogenesis and develop new therapeutic strategies. METHODS: Confocal laser scanning microscopy was used to evaluate the uptake of nanoparticles (NPs). The potential functions of USP30 were evaluated by cell counting kit (CCK)-8, flow cytometry, biochemical assay, coimmunoprecipitation, qRT-PCR, and immunoblotting. The antitumor effect of NP-loaded USP30 inhibitor MF-094 was evaluated in vitro and in vivo. RESULTS: In this study, increased USP30 expression was found in OSCC specimens and cell lines through qRT-PCR and immunoblotting. CCK-8, flow cytometry, and biochemical assay revealed that the deubiquitylated catalytic activity of USP30 contributed to cell viability and glutamine consumption of OSCC. Subsequently, USP30 inhibitor MF-094 was loaded in ZIF-8-PDA and PEGTK to fabricate ZIF-8-PDA-PEGTK nanoparticles, which exhibited excellent inhibition of cell viability and glutamine consumption of OSCC, both in vitro and in vivo. CONCLUSION: The results indicated the clinical significance of USP30 and showed that nanocomposites provide a targeted drug delivery system for treating OSCC.

20.
Front Immunol ; 13: 1019870, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36466840

RESUMO

Skeletal undifferentiated pleomorphic sarcoma (SUPS) is an invasive pleomorphic soft tissue sarcoma with a high degree of malignancy and poor prognosis. It is prone to recur and metastasize. The tumor microenvironment (TME) and the pathophysiology of SUPS are barely described. Single-cell RNA sequencing (scRNA-seq) provides an opportunity to dissect the landscape of human diseases at an unprecedented resolution, particularly in diseases lacking animal models, such as SUPS. We performed scRNA-seq to analyze tumor tissues and paracancer tissues from a SUPS patient. We identified the cell types and the corresponding marker genes in this SUPS case. We further showed that CD8+ exhausted T cells and Tregs highly expressed PDCD1, CTLA4 and TIGIT. Thus, PDCD1, CTLA4 and TIGIT were identified as potential targets in this case. We applied copy number karyotyping of aneuploid tumors (CopyKAT) to distinguish malignant cells from normal cells in fibroblasts. Our study identified eight malignant fibroblast subsets in SUPS with distinct gene expression profiles. C1-malignant Fibroblast and C6-malignant Fibroblast in the TME play crucial roles in tumor growth, angiogenesis, metastasis and immune response. Hence, targeting malignant fibroblasts could represent a potential strategy for this SUPS therapy. Intervention via tirelizumab enabled disease control, and immune checkpoint inhibitors (ICIs) of PD-1 may be considered as the first-line option in patients with SUPS. Taken together, scRNA-seq analyses provided a powerful basis for this SUPS treatment, improved our understanding of complex human diseases, and may afforded an alternative approach for personalized medicine in the future.


Assuntos
Sarcoma , Microambiente Tumoral , Animais , Humanos , Microambiente Tumoral/genética , Antígeno CTLA-4 , Recidiva Local de Neoplasia , Sarcoma/genética , Inibidores de Checkpoint Imunológico
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