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1.
Int J Nanomedicine ; 19: 7817-7830, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39099790

RESUMEN

Background: Photothermal therapy (PTT) guided by photoacoustic imaging (PAI) using nanoplatforms has emerged as a promising strategy for cancer treatment due to its efficiency and accuracy. This study aimed to develop and synthesize novel second near-infrared region (NIR-II) absorption-conjugated polymer acceptor acrylate-substituted thiadiazoloquinoxaline-diketopyrrolopyrrole polymers (PATQ-DPP) designed specifically as photothermal and imaging contrast agents for nasopharyngeal carcinoma (NPC). Methods: The PATQ-DPP nanoparticles were synthesized and characterized for their optical properties, including low optical band gaps. Their potential as PTT agents and imaging contrast agents for NPC was evaluated both in vitro and in vivo. The accumulation of nanoparticles at tumor sites was assessed post-injection, and the efficacy of PTT under near-infrared laser irradiation was investigated in a mouse model of NPC. Results: Experimental results indicated that the PATQ-DPP nanoparticles exhibited significant photoacoustic contrast enhancement and favorable PTT performance. Safety and non-toxicity evaluations confirmed the biocompatibility of these nanoparticles. In vivo studies showed that PATQ-DPP nanoparticles effectively accumulated at NPC tumor sites and demonstrated excellent tumor growth inhibition upon exposure to near-infrared laser irradiation. Notably, complete elimination of nasopharyngeal tumors was observed within 18 days following PTT. Discussion: The findings suggest that PATQ-DPP nanoparticles are a promising theranostic agent for NIR-II PAI and PTT of tumors. This innovative approach utilizing PATQ-DPP nanoparticles provides a powerful tool for the early diagnosis and precise treatment of NPC, offering a new avenue in the management of this challenging malignancy.


Asunto(s)
Nanopartículas , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Técnicas Fotoacústicas , Terapia Fototérmica , Animales , Técnicas Fotoacústicas/métodos , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/diagnóstico por imagen , Terapia Fototérmica/métodos , Ratones , Línea Celular Tumoral , Humanos , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/diagnóstico por imagen , Nanopartículas/química , Rayos Infrarrojos , Ratones Desnudos , Medios de Contraste/química , Ratones Endogámicos BALB C , Polímeros/química , Femenino
2.
Sheng Li Xue Bao ; 76(4): 561-575, 2024 Aug 25.
Artículo en Chino | MEDLINE | ID: mdl-39192789

RESUMEN

As the largest organelle in eukaryotic cells, the endoplasmic reticulum (ER) plays a crucial role in regulating intracellular protein folding, translation and assembly. Multiple quality control mechanisms in the ER ensure accurate modification of proteins in the ER lumen are accurately modified, thus maintaining calcium homeostasis, oxidative stress, cellular senescence and apoptosis. These mechanisms include ER stress (ERS), ER autophagy (ER-phagy, ERPA) and ER-associated degradation (ERAD). Intervertebral disc degeneration (IDD) is an age-related degenerative disease of the spine. Although the pathogenesis of IDD has not been fully elucidated, emerging evidence suggests that the ER quality control system may be involved in its progression. Previous studies have focused on mitochondrial quality control and its related mechanisms in diseases, with limited systematic summaries on the ER quality control system. In this paper, we comprehensively reviewed the molecular mechanisms of the ER quality control system and investigated its association with IDD. In addition, we summarized the potential therapeutic strategies targeting the ER quality control system to attenuate IDD progression, offering new insights into the pathogenesis and regenerative repair strategies of IDD.


Asunto(s)
Autofagia , Estrés del Retículo Endoplásmico , Retículo Endoplásmico , Degeneración del Disco Intervertebral , Humanos , Degeneración del Disco Intervertebral/terapia , Degeneración del Disco Intervertebral/fisiopatología , Retículo Endoplásmico/metabolismo , Retículo Endoplásmico/fisiología , Autofagia/fisiología , Estrés del Retículo Endoplásmico/fisiología , Animales , Degradación Asociada con el Retículo Endoplásmico/fisiología
3.
Phytomedicine ; 132: 155320, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38901285

RESUMEN

BACKGROUND: Metabolic syndrome (MetS), characterized by obesity, hyperglycemia, and abnormal blood lipid levels, is the pathological basis of many cardiovascular diseases. Gualou-Xiebai-Banxia-Tang decoction (GT) was first described in the Synopsis of the Golden Chamber, the earliest traditional Chinese medicine (TCM) monograph on diagnosis and treatment of miscellaneous diseases in China. According to TCM precepts, based on its ability to activate yang to release stagnation, activate qi to reduce depression, remove phlegm, and broaden the chest, GT has been used for more than 2,000 years to treat cardiovascular ailments. However, the molecular bases of its therapeutic mechanisms remain unclear. PURPOSE: The aim of this study was to identify lipid- and glucose-related hepatic genes differentially regulated by GT, and to assess GT impact on gut microbiota composition, in mice with high-fat diet (HFD)-induced MetS. STUDY DESIGN AND METHODS: ApoE-/- mice were fed with an HFD for 24 weeks, with or without concurrent GT supplementation, to induce MetS. At the study's end, body weight, visceral fat weight, blood lipid levels, and insulin sensitivity were measured, and histopathological staining was used to evaluate hepatosteatosis and intestinal barrier integrity. Liver transcriptomics was used for analysis of differentially expressed genes in liver and prediction of relevant regulatory pathways. Hepatic lipid/glucose metabolism-related genes and proteins were detected by RT-qPCR and western blotting. Gut microbial composition was determined by 16S rRNA gene sequencing. RESULTS: GT administration reduced MetS-related liver steatosis and weight gain, promoted insulin sensitivity and lipid metabolism, and beneficially modulated gut microbiota composition by decreasing the relative abundance of g_Lachnospiraceae_NK4A136_group and increasing the relative abundance of g_Alistipes. Liver transcriptomics revealed that GT regulated the expression of genes related to lipid and glucose metabolism (Pparγ, Igf1, Gpnmb, and Trem2) and of genes encoding chemokines/chemokine receptors (e.g. Cxcl9 and Cx3cr1). Significant, positive correlations were found for Ccr2, Ccl4, Ccr1, and Cx3cr1 and the g_Lachnospiraceae_NK4A136_group, and between Cxcl9, Ccr2, Ccl4, and Cx3cr1 and g_Desulfovibrio. GT treatment downregulated the protein expressions of SCD1 and CX3CR1 and upregulated the expression of PCK1 protein. CONCLUSION: GT supplementation alleviates HFD-induced MetS in mice by improving hepatic lipid and glucose metabolism. The anti-metabolic syndrome effects of GT may be related to the regulation of the gut-liver axis.


Asunto(s)
Dieta Alta en Grasa , Medicamentos Herbarios Chinos , Microbioma Gastrointestinal , Hígado , Síndrome Metabólico , Animales , Medicamentos Herbarios Chinos/farmacología , Hígado/efectos de los fármacos , Hígado/metabolismo , Microbioma Gastrointestinal/efectos de los fármacos , Síndrome Metabólico/tratamiento farmacológico , Masculino , Ratones , Metabolismo de los Lípidos/efectos de los fármacos , Ratones Endogámicos C57BL
4.
Angew Chem Int Ed Engl ; 63(15): e202400467, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38273162

RESUMEN

How Nature synthesizes enantiomerically pure substances from achiral or racemic resources remains a mystery. In this study, we aimed to emulate this natural phenomenon by constructing chiral tetrahedral cages through self-assembly, achieved by condensing two achiral compounds-a trisamine and a trisaldehyde. The occurrence of intercomponent CH⋅⋅⋅π interactions among the phenyl building blocks within the cage frameworks results in twisted conformations, imparting planar chirality to the tetrahedrons. In instances where the trisaldehyde precursor features electron-withdrawing ester side chains, we observed that the intermolecular CH⋅⋅⋅π forces are strong enough to prevent racemization. To attain enantioselective self-assembly, a chiral amine was introduced during the imine formation process. The addition of three equivalents of chiral amino mediator to one equivalent of the achiral trisaldehyde precursor formed a trisimino intermediate. This chiral compound was subsequently combined with the achiral trisamino precursor, leading to an imine exchange reaction that releasing the chiral amino mediator and formation of the tetrahedral cage with an enantiomeric excess (ee) of up to 75 %, exclusively composed of achiral building blocks. This experimental observation aligns with theoretical calculations based on the free energies of related cage structures. Moreover, since the chiral amine was not consumed during the imine exchange cycle, it enabled the enantioselective self-assembly of the tetrahedral cage for multiple cycles when new batches of the achiral trisaldehyde and trisamino precursors were successively added.

5.
Molecules ; 28(24)2023 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-38138565

RESUMEN

To investigate the effects of traditional high-temperature cooking and sous-vide cooking on the quality of tilapia fillets, muscle microstructure, texture, lipid oxidation, protein structure, and volatile compounds were analyzed. In comparison with samples subjected to traditional high-temperature cooking, sous-vide-treated samples exhibited less protein denaturation, a secondary structure dominated by α-helices, a stable and compact structure, a significantly higher moisture content, and fewer gaps in muscle fibers. The hardness of the sous-vide-treated samples was higher than that of control samples, and the extent of lipid oxidation was significantly reduced. The sous-vide cooking technique resulted in notable changes in the composition and relative content of volatile compounds, notably leading to an increase in the presence of 1-octen-3-ol, α-pinene, and dimethyl sulfide, and a decrease in the levels of hexanal, D-limonene, and methanethiol. Sous-vide treatment significantly enhanced the structural stability, hardness, and springiness of muscle fibers in tilapia fillets and reduced nutrient loss, enriched flavor, and mitigated effects on taste and fishy odor.


Asunto(s)
Tilapia , Animales , Culinaria/métodos , Lípidos
6.
Zhongguo Zhong Yao Za Zhi ; 48(19): 5294-5303, 2023 Oct.
Artículo en Chino | MEDLINE | ID: mdl-38114119

RESUMEN

This paper aims to investigate the effects and mechanisms of adipose-derived stem cells-exosomes(ADSCs-exos) toge-ther with aucubin in protecting human-derived nucleus pulposus cells(NPCs) from inflammatory injury, senescence, and apoptosis. The tert-butyl hydroperoxide(TBHP)-induced NPCs were assigned into normal, model, aucubin, ADSCs-exos, and aucubin+ADSCs-exos groups. The cell viability was examined by cell counting kit-8(CCK-8), cell proliferation by EdU staining, cell senescence by senescence-associated-ß-galactosidase(SA-ß-Gal), and cell cycle and apoptosis by flow cytometry. Enzyme-linked immunosorbent assay was employed to examine the expression of interleukin-1ß(IL-1ß), IL-10, and tumor necrosis factor-α(TNF-α). Real-time fluorescence quantitative PCR and Western blot were employed to determine the mRNA and protein levels of aggregated proteoglycan(aggrecan), type Ⅱ collagen alpha 1(COL2A1), Toll-like receptor 4(TLR4), and nuclear factor-kappa B(NF-κB). The results showed that compared with the model group, the aucubin or ADSCs-exos group showed enhanced viability and proliferation of NPCs, decreased proportion of G_0/G_1 phase cells, increased proportion of S phase cells, reduced apoptosis and proportion of cells in senescence, lowered IL-1ß and TNF-α levels, elevated IL-10 level, down-regulated mRNA and protein levels of TLR4 and NF-κB, and up-regulated mRNA and protein levels of aggrecan and COL2A1. Compared with the aucubin or ADSCs-exos group, the aucubin+ADSCs-exos combination further increased the viability and proliferation of NPCs, decreased the proportion of G_0/G_1 phase cells, increased the proportion of S phase cells, reduced the apoptosis and proportion of cells in senescence, lowered the IL-1ß and TNF-α levels, elevated the IL-10 level, down-regulated the mRNA and protein levels of TLR4 and NF-κB, and up-regulated the mRNA and protein levels of aggrecan and COL2A1. In summary, both aucubin and ADSCs-exos could exert protective effects by inhibiting inflammatory responses, reducing apoptosis and senescence of NPCs, improving cell viability and proliferation as well as extracellular matrix synthesis, which may be associated with the inhibition of TLR4/NF-κB signaling pathway activation. The combination of both plays a synergistic role in the protective effects.


Asunto(s)
FN-kappa B , Núcleo Pulposo , Humanos , FN-kappa B/genética , FN-kappa B/metabolismo , Interleucina-10 , Núcleo Pulposo/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Agrecanos/metabolismo , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , ARN Mensajero/metabolismo
7.
J Orthop Surg Res ; 18(1): 622, 2023 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-37872583

RESUMEN

OBJECTIVE: To explore the mechanism of psoralen synergized with exosomes (exos)-loaded SPC25 on nucleus pulposus (NP) cell senescence in intervertebral disc degeneration (IVDD). METHODS: IVDD cellular models were established on NP cells by tert-butyl hydroperoxide (TBHP) induction, followed by the treatment of psoralen or/and exos from adipose-derived stem cells (ADSCs) transfected with SPC25 overexpression vector (ADSCs-oe-SPC25-Exos). The viability, cell cycle, apoptosis, and senescence of NP cells were examined, accompanied by the expression measurement of aggrecan, COL2A1, Bcl-2, Bax, CDK2, p16, and p21. RESULTS: After TBHP-induced NP cells were treated with psoralen or ADSCs-oe-SPC25-Exos, cell proliferation and the expression of aggrecan, COL2A1, Bcl-2, and CDK2 were promoted; however, the expression of Bax, p16, p21, and inflammatory factors was decreased, and cell senescence, cycle arrest, and apoptosis were inhibited. Of note, psoralen combined with ADSCs-oe-SPC25-Exos further decelerated NP cell senescence and cycle arrest compared to psoralen or ADSCs-oe-SPC25-Exos alone. CONCLUSION: Combined treatment of psoralen and ADSCs-oe-SPC25-Exos exerted an alleviating effect on NP cell senescence, which may provide an insightful idea for IVDD treatment.


Asunto(s)
Exosomas , Degeneración del Disco Intervertebral , Disco Intervertebral , Núcleo Pulposo , Humanos , Degeneración del Disco Intervertebral/tratamiento farmacológico , Degeneración del Disco Intervertebral/metabolismo , Exosomas/metabolismo , Agrecanos/metabolismo , Ficusina/farmacología , Proteína X Asociada a bcl-2/metabolismo , Disco Intervertebral/metabolismo , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas Asociadas a Microtúbulos/farmacología
8.
Nat Commun ; 14(1): 4627, 2023 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-37532710

RESUMEN

It is considered a more formidable task to precisely control the self-assembled products containing purely covalent components, due to a lack of intrinsic templates such as transition metals to suppress entropy loss during self-assembly. Here, we attempt to tackle this challenge by using directing groups. That is, the self-assembly products of condensing a 1:2 mixture of a tetraformyl and a biamine can be precisely controlled by slightly changing the substituent groups in the aldehyde precursor. This is because different directing groups provide hydrogen bonds with different modes to the adjacent imine units, so that the building blocks are endowed with totally different conformations. Each conformation favors the formation of a specific product that is thus produced selectively, including chiral and achiral cages. These results of using a specific directing group to favor a target product pave the way for accomplishing atom economy in synthesizing purely covalent molecules without relying on toxic transition metal templates.

9.
J Ethnopharmacol ; 316: 116692, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37277086

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Lower back pain (LBP) is a common and frequent clinical condition, and intervertebral disc degeneration (IDD) is recognized as the leading cause of LBP, typically manifested by increased nucleus pulposus cell (NPC) senescence and death. In recent years, the treatment of IDD with stem cell injections has had great potential compared to surgical treatment. Combining the two may achieve better results, as BuShenHuoXueFang (BSHXF) is an herbal formula that improves the survival rate of transplanted stem cells and enhances their efficacy. AIM OF THE STUDY: We aimed to qualitatively and quantitatively analyze BSHXF-medicated serum and investigate the molecular mechanism of BSHXF-mediated serum in promoting the differentiation of adipose mesenchymal stem cells (ADSCs) into NPCs and delaying the senescence of NPCs by regulating the TGF-ß1/Smad pathway. MATERIALS AND METHODS: In this study, an ultrahigh-performance liquid chromatography-quadrupole-time-of-flight mass spectrometer (UPLC-Q-TOF-MS) was used to establish a method for the analysis of rat serum samples to track the active components in vivo; the oxidative damage model of NPCs was induced by T-BHP, and a Transwell chamber was used to construct a coculture system of ADSCs and NPCs. Flow cytometry was used to determine the cell cycle; SA-ß-Gal staining was used to assess cell senescence; ELISA was used to detect IL-1ß, IL-6 inflammatory factors, CXCL-1, CXCL-3, CXCL-10 chemokines, and TGF-ß1 in the supernatants of ADSCs and NPCs. WB was used to detect COL2A1, COL1A1, and Aggrecan in ADSCs to assess the manifestation of NP differentiation in ADSCs, and the WB method was used to detect COL2A1, COL1A1, Aggrecan, p16, p21, p53, and p-p53 protein expression in NPCs to reflect the cellular senescence status and to detect TGF-ß1, Smad2, Smad3, p- Smad2, and p- Smad3 protein expression in NPCs to reflect the pathway condition. RESULTS: We finally identified 70 blood components and their metabolites, including 38 prototypes, from the BSHXF-medicated serum. Compared with that in the nonmedicated serum group, the TGF-ß1/Smad pathway was activated in the medicated serum group, ADSCs moved toward NPC characteristics, the number of NPCs in the S/G2M phase increased, the number of senescent NPCs decreased, IL-1ß and IL-6 inflammatory factors in the Transwell decreased, CXCL-1, CXCL-3, and CXCL-10 chemokines decreased, and the expression of p16, p21, p53 and p-p53 proteins in NPCs was inhibited. CONCLUSION: By regulating the TGF-ß1/Smad pathway, BSHXF-medicated serum promoted ADSCs to NPCs, effectively alleviated the cycle blockage of NPCs after oxidative damage, encouraged the growth and proliferation of NPCs, delayed the aging of NPCs, improved the deteriorating microenvironment around NPCs, and repaired oxidatively damaged NPCs. The combination of BSHXF or its compounds with ADSCs has great potential for the treatment of IDD in the future.


Asunto(s)
Degeneración del Disco Intervertebral , Factor de Crecimiento Transformador beta1 , Ratas , Animales , Factor de Crecimiento Transformador beta1/metabolismo , Proteína p53 Supresora de Tumor , Agrecanos/metabolismo , Interleucina-6/metabolismo , Degeneración del Disco Intervertebral/terapia , Degeneración del Disco Intervertebral/metabolismo
10.
J Ethnopharmacol ; 314: 116532, 2023 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-37149071

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Gardenia jasminoides Ellis is a traditional Chinese medicine that has been used for treatment of various diseases, including atherosclerosis by clearing heat and detoxication. Geniposide is considered as the effective compounds responsible for the therapeutic efficacy of Gardenia jasminoides Ellis against atherosclerosis. AIM OF THE STUDY: To investigate the effect of geniposide on atherosclerosis burden and plaque macrophage polarization, with focus on its potential impact on CXCL14 expression by perivascular adipose tissue (PVAT). MATERIALS AND METHODS: ApoE-/- mice fed a western diet (WD) were used to model atherosclerosis. In vitro cultures of mouse 3T3-L1 preadipocytes and RAW264.7 macrophages were used for molecular assays. RESULTS: The results revealed that geniposide treatment reduced atherosclerotic lesions in ApoE-/- mice, and this effect was correlated with increased M2 and decreased M1 polarization of plaque macrophages. Of note, geniposide increased the expression of CXCL14 in PVAT, and both the anti-atherosclerotic effect of geniposide, as well as its regulatory influence on macrophage polarization, were abrogated upon in vivo CXCL14 knockdown. In line with these findings, exposure to conditioned medium from geniposide-treated 3T3-L1 adipocytes (or to recombinant CXCL14 protein) enhanced M2 polarization in interleukin-4 (IL-4) treated RAW264.7 macrophages, and this effect was negated after CXCL14 silencing in 3T3-L1 cells. CONCLUSION: In summary, our findings suggest that geniposide protects ApoE-/- mice against WD-induced atherosclerosis by inducing M2 polarization of plaque macrophages via enhanced expression of CXCL14 in PVAT. These data provide novel insights into PVAT paracrine function in atherosclerosis and reaffirm geniposide as a therapeutic drug candidate for atherosclerosis treatment.


Asunto(s)
Aterosclerosis , Placa Aterosclerótica , Ratones , Animales , Aterosclerosis/metabolismo , Placa Aterosclerótica/tratamiento farmacológico , Adipocitos/metabolismo , Macrófagos/metabolismo , Apolipoproteínas E/genética , Ratones Endogámicos C57BL , Quimiocinas CXC/metabolismo , Quimiocinas CXC/uso terapéutico
11.
Curr Mol Med ; 23(7): 688-697, 2023 05 30.
Artículo en Inglés | MEDLINE | ID: mdl-35975860

RESUMEN

BACKGROUND: Psoralidin (PL) could affect the differentiation of bone marrow mesenchymal stem cells (BMSCs). The role of PL is still unclear in adipose-derived stem cells (ADSCs). AIMS: This study aimed to investigate the effects of PL on ADSCs differentiation into nucleus pulposus-like cells and the TGF-ß/Smad signaling pathway. METHODS: The proliferation and apoptosis of ADSCs were detected. The nucleus pulposus cell-related markers (CD24, BASP1, KRT19, and Aggrecan) and TGF-ß/Smad signaling pathway indexes were analyzed. RESULTS: The results showed that compared to the control group, the cell activity was increased in the PL group, and the apoptosis rate was decreased. The mRNA and protein levels of nucleus pulposus cells markers (CD24, BASP1, KRT19, Aggrecan, and Collagen Type II) and TGF-ß/Smad signaling pathway-related indexes (TGF-ß, SMAD2, and SMAD3) were increased in PL group. After treatment with PL and TGF-ß silencing, the TGF-ß/Smad signaling pathway-related indicators (TGF-ß, SMAD2, and SMAD3) and nucleus pulposus cells markers (CD24, BASP1, KRT19, Aggrecan, and Collagen Type II) were found to be higher in the sh-TGF-ß +PL group than in the sh-TGF-ß group. CONCLUSION: In conclusion, our study showed that PL might induce the differentiation of ADSCs to nucleus pulposus cells through the TGF-ß/Smad signaling pathway. It might have the potential application value in the treatment of intervertebral disc degeneration.


Asunto(s)
Células Madre Mesenquimatosas , Núcleo Pulposo , Núcleo Pulposo/metabolismo , Agrecanos/genética , Agrecanos/metabolismo , Agrecanos/farmacología , Colágeno Tipo II/metabolismo , Colágeno Tipo II/farmacología , Diferenciación Celular , Factor de Crecimiento Transformador beta/metabolismo , Células Cultivadas
12.
Appl Opt ; 61(27): 7899-7911, 2022 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-36255910

RESUMEN

Rough manual interpretation distance cannot keep up with the intelligent detection and interpretation of sewer pipe defects. We present an automatic location method for the accurate longitudinal distance of the structural defects in sewer pipes via a pinhole-based defect monocular ranging model via image processing of pipe diameters. Then the model verification experiment is undertaken through a comparison with the actual data of the pipe size and the camera parameters. The results of the experiment demonstrate an improved accuracy of this method of defect spatial location and the robustness and stability of the model of the accurate acquisition of the longitudinal distance based on the monocular ranging between the inspection robot and the pipe defect.

13.
Front Oncol ; 12: 970613, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36212461

RESUMEN

Hepatocellular carcinoma (HCC) is a common malignancy worldwide with poor clinical outcomes, and the infection of hepatitis B virus (HBV) is the leading cause of this disease. Mounting evidence shows that RNA binding proteins (RBPs) can modulate the progression of cancers. However, the functions and clinical implications of RBP-related mRNAs in HBV-related HCC remain largely unclear. Therefore, we aim to develop a prognostic model based on the RBP-related mRNAs for HBV-related HCC patients. Firstly, we identified 626 differentially expressed RBP-related mRNAs in the HBV-related HCC through the Pearson correlation analysis. Subsequently, the Kaplan-Meier survival, univariate, Least Absolute Shrinkage and Selection Operator (LASSO), and multivariate Cox regression analyses were used to construct a prognostic model comprised of five RBP-related mRNAs. Furthermore, the patients were categorized into the high- and low-risk groups by the prognostic model and the patients in the high-risk group had a poor prognosis. Additionally, the prognostic model was an independent predictor of prognosis, and the accuracy of the prognostic model was proved by the receiver operator characteristic (ROC) analysis. Furthermore, the functional enrichment analysis revealed that various cancer-promoting processes were enriched in the high-risk group. Taken together, our study may provide the HBV-related HCC biomarkers of prognosis to improve the clinical outcomes of patients.

14.
J Orthop Surg (Hong Kong) ; 30(3): 10225536221135474, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36307202

RESUMEN

PURPOSE: This study aims to explore the potential mechanism of Achyranthoside D (AD) in improving intervertebral disc (IVD) degeneration (IDD). METHODS: The IDD model of SD rats and nucleus pulposus cells (NPCs) was established by lumbar cone annulus puncture and tert-butyl peroxide, respectively. Cell proliferation was detected by CCK8 assay. Apoptosis was detected by flow cytometry and TUNEL staining. IVD tissue injury was observed by HE staining. Alcian blue staining observed the glycoprotein secretion in IVD. Monodansylcadaverin (MDC) staining was used to detect the formation of autophagosomes. The LC3 expression was tested by immunofluorescence. The type II collagen, aggrecan and MMP3 expression were detected by ELISA. RT-qPCR was used to detect the Casp 3, Bax, Bcl2, Acan, Col2a1 and Mmp3 expression. The LC3, P62, type II collagen, aggrecan, Beclin1, Akt, MMP3, p-mTOR, PI3K, mTOR, p-PI3K and p-Akt expression were analyzed by western blot. RESULTS: The IVD tissue damage and apoptosis occurred in the Model group, and the glycoprotein secretion decreased. Compared with Model group, AD-H group alleviated the injury of IVD tissue, inhibited the apoptosis of cells, and increased the secretion of glycoprotein. 40 µg/mL AD restored the proliferation activity of NPCs. Compared to the Normal group, the NPCs apoptosis increased, the Collagen II, aggrecan and Bcl2 expressions were significantly decreased, the MMP3, Bax and Casp 3 expression were significantly increased, and the LC-3 II/I expression in IVD tissues were increased significantly in Model group, all of which was reversed in AD group. AD promoted the p-Akt, p-PI3K, p-mTOR, LC-3 II/I and Beclin1 expression, inhibited the P62 expression to alleviate the damage of nucleus pulporeus cells and the degeneration of IVD. CONCLUSION: AD improved IDD by affecting the PI3K/Akt/mTOR pathway and autophagy.


Asunto(s)
Degeneración del Disco Intervertebral , Ratas , Animales , Degeneración del Disco Intervertebral/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Metaloproteinasa 3 de la Matriz , Agrecanos/metabolismo , Colágeno Tipo II/metabolismo , Beclina-1 , Proteína X Asociada a bcl-2 , Ratas Sprague-Dawley , Autofagia , Serina-Treonina Quinasas TOR/metabolismo , Apoptosis
15.
Genes (Basel) ; 13(6)2022 06 19.
Artículo en Inglés | MEDLINE | ID: mdl-35741856

RESUMEN

LncRNAs have been well known for their multiple functions in the tumorigenesis, development, and relapse of colorectal cancer (CRC). Accumulating studies demonstrated that the expression of lncRNAs can be regulated by ferroptosis, a biological process that has been revealed to suppress CRC progression. However, the functions and clinical implications of ferroptosis-associated lncRNAs in CRC remain largely unknown. We, herein, aim to construct a prognostic signature with ferroptosis-related lncRNAs for the prognostic estimation of CRC patients. Firstly, we identified the lncRNAs related to ferroptosis based on the RNA-Seq data of CRC from the TCGA database. The univariate and multivariate Cox analyses were then performed to establish a prognostic signature composed of eight ferroptosis-related lncRNAs (AL161729.4, AC010973.2, CCDC144NL-AS1, AC009549.1, LINC01857, AP003555.1, AC099850.3, and AC008494.3). Furthermore, we divided the CRC patients into high- and low-risk groups based on the signature and found the overall survival (OS) of patients in the high-risk group was significantly shorter than that in the low-risk group (p = 3.31 × 10-11). Moreover, the patients in the high-risk groups had shorter recurrence-free survival (RFS) (p = 6.5 × 10-3) and disease-free survival (DFS) (p = 4.27 × 10-4), as well as higher tumor recurrence rate. Additionally, we found that the oncogenic pathways were enriched in the high-risk group, whereas the ferroptosis pathway that probably repressed CRC development was enriched in the low-risk group. In summary, our signature may provide a theoretical foundation for not only accurate judgment for prognosis but also evaluation for recurrence and metastasis in CRC patients.


Asunto(s)
Neoplasias Colorrectales , Ferroptosis , ARN Largo no Codificante , Carcinogénesis/genética , Neoplasias Colorrectales/patología , Ferroptosis/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Recurrencia Local de Neoplasia/genética , Pronóstico , ARN Largo no Codificante/metabolismo
16.
Int J Nanomedicine ; 17: 2435-2446, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35656166

RESUMEN

Nasopharyngeal carcinoma (NPC) is a common malignant tumor of the head and neck with a high incidence rate worldwide, especially in southern China. Phototheranostics in combination with nanoparticles is an integrated strategy for enabling simultaneous diagnosis, real-time monitoring, and administration of precision therapy for nasopharyngeal carcinoma (NPC). It has shown great potential in the field of cancer diagnosis and treatment owing to its unique noninvasive advantages. Many Chinese and international research teams have applied nano-targeted drugs to optical diagnosis and treatment technology to conduct multimodal imaging and collaborative treatment of NPC, which has become a hot research topic. In this review, we aimed to introduce the recent developments in phototheranostics of NPC based on a nanoplatform. This study aimed to elaborate on the applications of nanoplatform-based optical imaging strategies and treatment modalities, including fluorescence imaging, photoacoustic imaging, Raman spectroscopy imaging, photodynamic therapy, and photothermal therapy. This study is expected to provide a scientific basis for further research and development of NPC diagnosis and treatment.


Asunto(s)
Neoplasias Nasofaríngeas , Fototerapia , Humanos , Carcinoma Nasofaríngeo/diagnóstico por imagen , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/diagnóstico por imagen , Neoplasias Nasofaríngeas/terapia , Imagen Óptica , Terapia Fototérmica
17.
Nat Commun ; 13(1): 3557, 2022 06 21.
Artículo en Inglés | MEDLINE | ID: mdl-35729153

RESUMEN

The preparation of topologically nontrivial molecules is often assisted by covalent, supramolecular or coordinative templates that provide spatial pre-organization for all components. Herein, we report a trefoil knot that can be self-assembled efficiently in water without involving additional templates. The direct condensation of three equivalents of a tetraformyl precursor and six equivalents of a chiral diamine produces successfully a [3 + 6] trefoil knot whose intrinsic handedness is dictated by the stereochemical configuration of the diamine linkers. Contrary to the conventional wisdom that imine condensation is not amenable to use in water, the multivalent cooperativity between all the imine bonds within the framework makes this trefoil knot robust in the aqueous environment. Furthermore, the presence of water is proven to be essential for the trefoil knot formation. A topologically trivial macrocycle composed of two tetraformyl and four diamino building blocks is obtained when a similar reaction is performed in organic media, indicating that hydrophobic effect is a major driving force behind the scene.


Asunto(s)
Lotus , Diaminas , Iminas , Agua
18.
Genes (Basel) ; 13(2)2022 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-35205391

RESUMEN

Long non-coding RNAs (lncRNAs) have been well known for their multiple functions in the tumorigenesis, development, and prognosis of breast cancer (BC). Mechanistically, their production, function, or stability can be regulated by RNA binding proteins (RBPs), which were also involved in the carcinogenesis and progression of BC. However, the roles and clinical implications of RBP-related lncRNAs in BC remain largely unknown. Therefore, we herein aim to construct a prognostic signature with RBP-relevant lncRNAs for the prognostic evaluation of BC patients. Firstly, based on the RNA sequencing data of female BC patients from The Cancer Genome Atlas (TCGA) database, we screened out 377 differentially expressed lncRNAs related to RBPs. The univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses were then performed to establish a prognostic signature composed of 12-RBP-related lncRNAs. Furthermore, we divided the BC patients into high- and low-risk groups by the prognostic signature and found the overall survival (OS) of patients in the high-risk group was significantly shorter than that of the low-risk group. Moreover, the 12-lncRNA signature exhibited independence in evaluating the prognosis of BC patients. Additionally, a functional enrichment analysis revealed that the prognostic signature was associated with some cancer-relevant pathways, including cell cycle and immunity. In summary, our 12-lncRNA signature may provide a theoretical reference for the prognostic evaluation or clinical treatment of BC patients.


Asunto(s)
Neoplasias de la Mama , ARN Largo no Codificante , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/genética , Femenino , Humanos , Pronóstico , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Proteínas de Unión al ARN/genética
19.
Carbohydr Polym ; 239: 115480, 2020 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-32414433

RESUMEN

In this study, we fabricated a soft, transparent UV-shielding film (Alg-Fe3+-EDTA) by crosslinking sodium alginate with a ferric ion solution containing EDTA. The obtained films were characterized via SEM, ATR-FTIR, XRD, TG and DTG; the results indicated that the synergistic gelation of ferric alginate and alginic acid existed in Alg-Fe3+-EDTA film. The Alg-Fe3+-EDTA film performance to be optimized under the following conditions: 1.6% Fe3+, 0.8% EDTA, and crosslinking duration of 12 min. The Alg-Fe3+-EDTA film had high visible light transmittance, the UV-C (200-280 nm) and UV-B (280-315 nm) shielding rates were 100%, and the UV-A (315-400 nm) shielding rate was 98.37%; the UPF reached 50+; additionally, the tensile strength and elongation-at-break were 56.85 MPa and 10.45%, respectively, and still have ultraviolet shielding effect under water environments or after strong light irradiation. This work provides an efficient method to improve the optical and mechanical ability of ferric alginate films.


Asunto(s)
Alginatos/química , Reactivos de Enlaces Cruzados/química , Compuestos Férricos/química , Rayos Ultravioleta , Conformación de Carbohidratos , Ácido Edético/química , Tamaño de la Partícula , Espectroscopía Infrarroja por Transformada de Fourier , Propiedades de Superficie
20.
Cell Mol Life Sci ; 76(21): 4233-4243, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31270581

RESUMEN

Circular RNAs (circRNAs) are single-stranded and covalently closed back-splicing products of pre-mRNAs. They can be derived from exons, introns, or exons with intron retained between exons of transcripts, as well as antisense transcripts. CircRNAs have been reported to function as microRNA sponges, regulate gene transcription mediated by RNA polymerase II, and modulate the splicing or stability of mRNA. However, emerging studies demonstrate that they affect the behavior of proteins via direct interactions with them. Here, we summarize that by binding directly with proteins; circRNAs can facilitate their nuclear or cytoplasmic localizations, regulate their functions or stability, promote or inhibit the interactions between them, or influence the interactions between them and DNA. Furthermore, these circRNA-binding proteins contain transcription factors, RNA processing proteins, proteases, and some other RNA-binding proteins. As a consequence, circRNAs are involved in the regulation of multiple physiological or pathological processes, including tumorigenesis, atherosclerosis, wound repair, cardiac senescence, myocardial ischemia/reperfusion injury, and so forth. Nonetheless, it is worthwhile to further explore more types of proteins that interact with circRNAs, which would be helpful in revealing other unknown biological functions of circRNAs that guide the variation in behavior of cellular proteins.


Asunto(s)
Proteínas/metabolismo , ARN/fisiología , Animales , Proteínas de Unión al ADN/metabolismo , Regulación de la Expresión Génica/fisiología , Humanos , Unión Proteica , Estabilidad Proteica , Transporte de Proteínas/genética , ARN/metabolismo , ARN Circular , Proteínas de Unión al ARN/metabolismo
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