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1.
Bioact Mater ; 21: 267-283, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36157242

RESUMO

Injectable materials show their special merits in regeneration of damaged/degenerated bones in minimally-invasive approach. Injectable calcium phosphate bone cement (CPC) has attracted broad attention for its bioactivity, as compared to non-degradable polymethyl methacrylate cement. However, its brittleness, poor anti-washout property and uncontrollable biodegradability are the main challenges to limit its further clinical application mainly because of its stone-like dense structure and fragile inorganic-salt weakness. Herein, we developed a kind of injectable CPC bone cement with porous structure and improved robustness by incorporating poly(lactide-co-glycolic acid) (PLGA) nanofiber into CPC, with carboxymethyl cellulose (CMC) to offer good injectability as well as anti-wash-out capacity. Furthermore, the introduction of PLGA and CMC also enabled a formation of initial porous structure in the cements, where PLGA nanofiber endowed the cement with a dynamically controllable biodegradability which provided room for cell movement and bone ingrowth. Interestingly, the reinforced biodegradable cement afforded a sustainable provision of Ca2+ bioactive components, together with its porous structure, to improve synergistically new bone formation and osteo-integration in vivo by using a rat model of femur condyle defect. Further study on regenerative mechanisms indicated that the good minimally-invasive bone regeneration may come from the synergistic enhanced osteogenic effect of calcium ion enrichment and the improved revascularization capacity contributed from the porosity as well as the lactic acid released from PLGA nanofiber. These results indicate the injectable bone cement with high strength, anti-washout property and controllable biodegradability is a promising candidate for bone regeneration in a minimally-invasive approach.

2.
BMC Cancer ; 22(1): 1250, 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36460972

RESUMO

INTRODUCTION: Improving the early prediction of neoadjuvant chemotherapy (NAC) efficacy in breast cancer can lead to an improved prediction of the final prognosis of patients, which would be useful for promoting individualized treatment. This study aimed to explore the value of the combination of dynamic contrast-enhanced (DCE)-MRI parameters and apparent diffusion coefficient (ADC) values in the early prediction of pathological complete response (pCR) to NAC for breast cancer. METHODS: A total of 119 (range, 28-69 years) patients with biopsy-proven breast cancer who received two cycles of NAC before breast surgery were retrospectively enrolled from our hospital database. Patients were divided into pCR and non pCR groups according to their pathological responses; a total of 24 patients achieved pCR, while 95 did not. The quantitative (Ktrans; Kep; Ve; IAUC) and semiquantitative parameters (W-in; W-out; TTP) of DCE-MRI that were significantly different between groups were combined with ADC values to explore their value in the early prediction of pCR to NAC for breast cancer. The independent T test was performed to compare the differences in DCE-MRI parameters and ADC values between the two groups. Receiver operating characteristic (ROC) curves were plotted, and the area under the ROC curve (AUC), sensitivity and specificity were calculated to evaluate the performance of the prediction. RESULTS: The Ktrans, Kep, IAUC, ADC, W-in and TTP values were significantly different between the pCR and non pCR groups after NAC. The AUC (0.845) and specificity (95.79%) of the combined Ktrans, Kep, IAUC and ADC values were both higher than those of the individual parameters. The combination of W-in, TTP and ADC values had the highest AUC value (0.886) in predicting pCR, with a sensitivity and specificity of 87.5% and 82.11%, respectively. CONCLUSIONS: The results suggested that the combination of ADC values and quantitative and semiquantitative DCE-MRI parameters, especially the combination of W-in, TTP, and ADC values, may improve the early prediction of pCR in breast cancer.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Estudos Retrospectivos , Imageamento por Ressonância Magnética
3.
J Chromatogr A ; 1686: 463649, 2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36423357

RESUMO

In this study, a strategy based on COSMO-RS (Conductor-like Screening Model for Real Solvents) with a constrained optimization calculation was developed for ab initio calculation based solvent system selection in silico for counter-current chromatography. The separation of resibufogenin glycosylation products was selected as an example to show its practicability. The selected solvent system in silico gave the K values consistent with the experimentally measured data (RMSD=0.2861) and the glycosylation products, namely Resibufogenin-3-O-ß-D-glucoside (R-G) and Resibufogenin-3-O-ß-D-glucosyl (1→2)-ß-D-glucoside (R-2G), were successfully separated by HSCCC.


Assuntos
Distribuição Contracorrente , Glucosídeos , Solventes , Glicosilação
4.
Front Pharmacol ; 13: 1044027, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36339575

RESUMO

Bufadienolide, an essential member of the C-24 steroid family, is characterized by an α-pyrone positioned at C-17. As the predominantly active constituent in traditional Chinese medicine of Chansu, bufadienolide has been prescribed in the treatment of numerous ailments. It is a specifically potent inhibitor of Na+/K+ ATPase with excellent anti-inflammatory activity. However, the severe side effects triggered by unbiased inhibition of the whole-body cells distributed α1-subtype of Na+/K+ ATPase, restrict its future applicability. Thus, researchers have paved the road for the structural alteration of desirable bufadienolide derivatives with minimal adverse effects via biotransformation. In this review, we give priority to the present evidence for structural diversity, MS fragmentation principles, anti-inflammatory efficacy, and structure modification of bufadienolides derived from toads to offer a scientific foundation for future in-depth investigations and views.

5.
Nat Commun ; 13(1): 7047, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36396656

RESUMO

Chemotherapy can eradicate a majority of cancer cells. However, a small population of tumor cells often survives drug treatments through genetic and/or non-genetic mechanisms, leading to tumor recurrence. Here we report a reversible chemoresistance phenotype regulated by the mTOR pathway. Through a genome-wide CRISPR knockout library screen in pancreatic cancer cells treated with chemotherapeutic agents, we have identified the mTOR pathway as a prominent determinant of chemosensitivity. Pharmacological suppression of mTOR activity in cancer cells from diverse tissue origins leads to the persistence of a reversibly resistant population, which is otherwise eliminated by chemotherapeutic agents. Conversely, activation of the mTOR pathway increases chemosensitivity in vitro and in vivo and predicts better survival among various human cancers. Persister cells display a senescence phenotype. Inhibition of mTOR does not induce cellular senescence per se, but rather promotes the survival of senescent cells through regulation of autophagy and G2/M cell cycle arrest, as revealed by a small-molecule chemical library screen. Thus, mTOR plays a causal yet paradoxical role in regulating chemotherapeutic response; inhibition of the mTOR pathway, while suppressing tumor expansion, facilitates the development of a reversible drug-tolerant senescence state.


Assuntos
Neoplasias , Serina-Treonina Quinases TOR , Humanos , Proliferação de Células , Serina-Treonina Quinases TOR/metabolismo , Senescência Celular , Autofagia/fisiologia , Neoplasias/patologia
6.
Front Bioeng Biotechnol ; 10: 1033987, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36394031

RESUMO

Androgenic alopecia (AGA) is a common disease that negatively affects patients' physical and mental health. AGA can be treated with drugs that improve the perifollicular microenvironment, such as 5α-reductase inhibitors (e.g., dutasteride [DUT]), androgen receptor blockers, and minoxidil. However, the efficacy of these treatments is limited. Therefore, this study aimed to show that nanoparticles are effective as stable carriers with high curative benefits and little adverse effects. The in vitro study showed that PLGA-DUT/siAR@DPCM NPs could deliver both DUT and siAR to dermal papilla cells. They could successfully suppress 5α-reductase and knock down androgen receptor, respectively, and thereby promote cell proliferation. In the in vivo study, PLGA-DUT/siAR@DPCM NPs showed a significant therapeutic effect in an AGA mouse model. They successfully penetrated the stratum corneum and showed a clear targeting effect on hair follicles and surrounding tissues. PLGA-DUT/siAR@DPCM NPs could enable the targeted delivery of DUT and siAR through percutaneous penetration, enhancing phagocytosis and decreasing adverse effects. Thus, they have great potential in the clinical treatment of AGA.

7.
IEEE Trans Image Process ; 31: 7165-7178, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36367912

RESUMO

Visible-infrared person re-identification (VI-ReID) is challenging due to the large modality discrepancy between visible and infrared images. Existing methods mainly focus on learning modality-shared representations by embedding images from different modalities into a common feature space, in which some discriminative modality information is discarded. Different from these methods, in this paper, we propose a novel Modality-Specific Memory Network (MSMNet) to complete the missing modality information and aggregate visible and infrared modality features into a unified feature space for the VI-ReID task. The proposed model enjoys several merits. First, it can exploit the missing modality information to alleviate the modality discrepancy when only the single-modality input is provided. To the best of our knowledge, this is the first work to exploit the missing modality information completion and alleviate the modality discrepancy with the memory network. Second, to guide the learning process of the memory network, we design three effective learning strategies, including feature consistency, memory representativeness and structural alignment. By incorporating these learning strategies in a unified model, the memory network can be well learned to propagate identity-related information between modalities and boost the VI-ReID performance. Extensive experimental results on two standard benchmarks (SYSU-MM01 and RegDB) demonstrate that the proposed MSMNet performs favorably against state-of-the-art methods.

8.
J Sep Sci ; 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36337042

RESUMO

The separation of polar compounds is challenging work due to poor retention and insufficient selectivity. In the present study, an efficient strategy for large-scale preparation of five polar polyphenols including three isomers from Phyllanthus emblica Linn has been established by preparative high-speed counter-current chromatography. Macroporous resin column chromatography was used for the enrichment of the polar polyphenols. However, sugar and other ultra-polar impurities were co-washed out with the targets. Liquid-liquid extraction with ethyl acetate/water (1/1, v/v) solvent system was developed to remove the ultra-polar impurities with a clearance rate of 95%. Finally, the targets were introduced to preparative high-speed counter-current chromatography for separation using ethyl acetate/n-butanol/acetic acid/water (2/7/1/10, v/v/v/v) solvent system. As a result, 191 mg of Mucic acid 1,4-lactone 5-O-gallate, 370 mg of ß-Glucogallin, 301 mg of Gallic acid, 195 mg of Mucic acid 1,4-lactone 3-O-gallate and 176 mg of Mucic acid 1,4-lactone 2-O-gallate with purity higher than 98% were obtained from 1.5 g of sample. Mucic acid 1,4-lactone 3-O-gallate, Mucic acid 1,4-lactone 3-O-gallate, and Mucic acid 1,4-lactone 2-O-gallate are isomers. The results showed that high-speed counter-current chromatography could be well developed for the separation of polar compounds from natural products.

9.
Obesity (Silver Spring) ; 30(11): 2213-2221, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36321272

RESUMO

OBJECTIVE: This study explored the relationship between BMI and regional cerebral glucose metabolism and explicitly detected regions with significant differences in cerebral metabolism using positron emission tomography (PET)/magnetic resonance imaging in the resting state. METHODS: Corresponding PET images acquired from 220 participants were sorted into four groups according to Asian BMI standards: underweight, normal weight, overweight, and obesity. Pearson correlation coefficient analysis was performed to assess the association between BMI and standard uptake value. The regional cerebral glucose metabolism was measured in the fasted state. The PET images were analyzed using statistical parameter maps. One-way ANOVA was used to explore differences in the standard uptake value as an indicator of regional cerebral glucose metabolism. RESULTS: This study found that lower cerebral glucose metabolism in reward- and motivation-related regions was accompanied by more severe obesity and that regional cerebral glucose metabolism activities were negatively correlated with BMI. In addition, more severe obesity was accompanied by a larger range of areas with significant differences independent of current dietary status. CONCLUSIONS: These findings suggest that the reward and motivation circuits may be a factor regulating energy balance and influencing the degree of obesity.


Assuntos
Obesidade Mórbida , Compostos Radiofarmacêuticos , Humanos , Compostos Radiofarmacêuticos/metabolismo , Motivação , Índice de Massa Corporal , Obesidade Mórbida/metabolismo , Glucose/metabolismo , Fluordesoxiglucose F18/metabolismo , Tomografia por Emissão de Pósitrons , Recompensa , Encéfalo/metabolismo
10.
Front Plant Sci ; 13: 1010474, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36275564

RESUMO

In this paper, a method for predicting residual film content in the cotton field plough layer based on UAV imaging and deep learning was proposed to solve the issues of high labour intensity, low efficiency, and high cost of traditional methods for residual film content monitoring. Images of residual film on soil surface in the cotton field were collected by UAV, and residual film content in the plough layer was obtained by manual sampling. Based on the three deep learning frameworks of LinkNet, FCN, and DeepLabv3, a model for segmenting residual film from the cotton field image was built. After comparing the segmentation results, DeepLabv3 was determined to be the best model for segmenting residual film, and then the area of residual film was obtained. In addition, a linear regression prediction model between the residual film coverage area on the cotton field surface and the residual film content in the plough layer was built. The results showed that the correlation coefficient (R2), root mean square error, and average relative error of the prediction of residual film content in the plough layer were 0.83, 0.48, and 11.06%, respectively. It indicates that a quick and accurate prediction of residual film content in the cotton field plough layer can be realized based on UAV imaging and deep learning. This study provides certain technical support for monitoring and evaluating residual film pollution in the cotton field plough layer.

11.
Food Chem X ; 15: 100411, 2022 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-36211781

RESUMO

Yellowing is the main reason for deterioration of edible quality of fresh cut water chestnuts (FCWCs). The mechanism of aurone inhibiting the yellowing of FCWCs was studied. FCWCs were treated with aurone (0.2, 0.6 and 1.0 %). The controls yellowed completely on day 9. The treatment sample with 1.0 % aurone did not yellow on day 9. Compared to the controls, aurone (1.0 %) completely inhibited the production of eriodictyol during 9 d of storage. Aurone (1.0 %) reduced peroxidase activity of FCWCs by 23 % on day 9. The effects of aurone on naringenin concentration, polyphenol oxidase activity, phenylalanine lyase activity, number of thermophilic bacteria colonies, and number of yeasts and molds colonies of FCWCS were not significant. Aurone reduced the yellowing by decreasing the yield of eriodictyol and inhibiting POD activity. Aurone (1.0 %) can be used to inhibit the yellowing of FCWCs in practice.

12.
Drug Deliv ; 29(1): 3186-3196, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36226475

RESUMO

Nanoparticles can promote the accumulation of drugs in tumors. However, they find limited clinical applications because they cannot easily penetrate the stroma of cancer tissues, and it is difficult to control drug release. We developed a multiresponse multistage drug-delivery nanogel with improved tumor permeability and responsiveness to the tumor microenvironment for the controlled delivery of anticancer agents. For this purpose, ∼100 nm multistage drug delivery nanogels with pH, redox, near-infrared stimulation, and enzyme responsiveness were grown in situ using 20 nm gold nanoparticles (AuNPs) via an emulsion-aiding crosslinking technique with cysteine crosslinker. An alginate cysteine AuNP (ACA) nanocarrier can efficiently load the cationic drug doxorubicin (DOX) to produce a multistage drug delivery nanocarrier (DOX@ACA). DOX@ACA can maintain the slow release of DOX and reduce its toxicity. In cancer tissues, the high pH and reductase microenvironment combined with the in vitro delivery of alginate and near-infrared light drove drug release. The developed nanoparticles effectively inhibited cancer cells, and in vivo evaluations showed that they effectively enhanced antitumor activity while having negligible in vivo toxicity to major organs.


Assuntos
Antineoplásicos , Nanopartículas Metálicas , Nanopartículas , Alginatos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Cisteína , Doxorrubicina , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Emulsões , Ouro , Concentração de Íons de Hidrogênio , Nanogéis , Sistemas de Liberação de Fármacos por Nanopartículas , Oxirredutases
13.
Molecules ; 27(20)2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36296667

RESUMO

A unique porous material, namely, MXene/SiO2 hybrid aerogel, with a high surface area, was prepared via sol-gel and freeze-drying methods. The hierarchical porous hybrid aerogel possesses a three-dimensional integrated network structure of SiO2 cross-link with two-dimensional MXene; it is used not only as a scaffold to prepare sulfur-based cathode material, but also as an efficient functional separator to block the polysulfides shuttle. MXene/SiO2 hybrid aerogel as sulfur carrier exhibits good electrochemical performance, such as high discharge capacities (1007 mAh g-1 at 0.1 C) and stable cycling performance (823 mA h g-1 over 200 cycles at 0.5 C). Furthermore, the battery assembled with hybrid aerogel-modified separator remains at 623 mA h g-1 over 200 cycles at 0.5 C based on the conductive porous framework and abundant functional groups in hybrid aerogel. This work might provide further impetus to explore other applications of MXene-based composite aerogel.

14.
Artigo em Inglês | MEDLINE | ID: mdl-36284387

RESUMO

BACKGROUND: At present, the treatment of hepatocellular carcinoma (HCC) is disturbed by the treatment failure and recurrence caused by the residual liver cancer stem cells (CSCs). Therefore, drugs targeting HCC CSCs should be able to effectively eliminate HCC and prevent its recurrence. In this study, we demonstrated the effect of Polyphyllin VII (PP7) to HCC CSCs, and explored their potential mechanism. METHODS: HepG2 and Huh7 cells, were used to analyze the antitumor activity of PP7 by quantifying cell growth and metastasis as well as to study the effect on stemness. RESULTS: Our results demonstrated that PP7 promoted apoptosis and significantly inhibited proliferation and migration of both HepG2 and Huh7 cells. PP7 also inhibited tumor spheroid formation and induced significant changes in the expression of stemness markers (CD133 and OCT-4). These effects of PP7 were mediated by the STAT3 signaling. CONCLUSION: PP7 can effectively suppress tumor initiation, growth, metastasis, and inhibit stemness through regulation of STAT3 signaling pathway in liver cancer cells. Our data would add more evidence to further clarify the therapeutic effect of PP7 against HCC.

15.
Ann Transl Med ; 10(18): 976, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36267713

RESUMO

Background: Osteoarthritis (OA) is one of the most common joint diseases and a major global public health concern. Mesenchymal stem cells (MSCs) have been widely used for the treatment of OA owing to their paracrine secretion of trophic factors, a phenomenon in which exosomes may play a major role. Here, we investigate the potential of exosomes from human umbilical cord-derived MSCs (hUC-MSCs-Exos) in alleviating OA. Methods: The hUC-MSCs-Exos were harvested from hUC-MSC-conditioned medium using ultracentrifugation. Rats with surgically-induced OA were intra-articularly injected with hUC-MSCs-Exos. The effect of hUC-MSCs-Exos in repairing osteoarticular cartilage was assessed using hematoxylin and eosin (HE) staining, safranin-O and fast green staining and immunohistochemistry. The in vitro experiments were further carried out to verify the therapeutic effect. The effects of hUC-MSCs-Exos on the proliferation and migration of human chondrocytes were evaluated using the cell counting kit-8, EdU-555 cell proliferation kit, and transwell assays. Annexin V-FITC/PI staining were used to evaluate the effect of exosomes on chondrocyte apoptosis. An in vitro model of human articular chondrocytes treated with interleukin 1 beta (IL-1ß) was used to evaluate the effects of exosomes, analyses involved using quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence, and western blotting. The role of hUC-MSCs-Exos in macrophage polarization was examined in the monocyte cell line, Tohoku Hospital Pediatrics-1 (THP-1) by qRT-PCR and immunofluorescence. Results: The results showed that hUC-MSCs-Exos prevented severe damage to the knee articular cartilage in the rat OA model. We confirmed the high efficacy of hUC-MSCs-Exos in promoting chondrocyte proliferation and migration and inhibiting chondrocyte apoptosis. Additionally, hUC-MSCs-Exos could reverse IL-1ß-induced injury of chondrocytes and regulate the polarization of macrophages in vitro. Conclusions: There is potential for hUC-MSCs-Exos to be used as a treatment strategy for OA.

16.
Jpn J Radiol ; 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36097236

RESUMO

Benign tumors or tumor-like lesions of the tongue are uncommon lesions that comprise a heterogeneous group of neoplasms. Although there are a variety of benign tumors or tumor-like lesions, the imaging appearance of these diseases is not well defined because of a paucity of scientific literature on this topic. Most benign tongue tumors usually appear as submucosal bulges located in the deep portion of the tongue. Their true features and extent may only be identified on cross-sectional images such as CT and MRI. Thus, CT and MRI play an important role in the diagnosis of these unusual lesions. It is important that radiologists be able to identify the characteristic CT and MR imaging features that can be used to narrow the differential diagnosis with increased diagnostic confidence, suggest specific histologic tumor types. In this pictorial essay, we provide insights into the MRI presentations of benign tongue tumors and tumor-like diseases and their radiologic-pathologic correlation. Benign tumors or tumor-like lesions of the tongue described herein include papilloma, lipoma, hemangioma, venous malformations, schwannoma, neurofibroma, epidermoid cyst, and dermoid cyst.

17.
Sheng Wu Gong Cheng Xue Bao ; 38(9): 3353-3362, 2022 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-36151805

RESUMO

A fusion protein containing a tetanus toxin peptide, a tuftsin peptide and a SARS-CoV-2S protein receptor-binding domain (RBD) was prepared to investigate the effect of intramolecular adjuvant on humoral and cellular immunity of RBD protein. The tetanus toxin peptide, tuftsin peptide and S protein RBD region were connected by a flexible polypeptide, and a recombinant vector was constructed after codon optimization. The recombinant S-TT-tuftsin protein was prepared by prokaryotic expression and purification. BALB/c mice were immunized after mixed with aluminum adjuvant, and the humoral and cellular immune effects were evaluated. The recombinant S-TT-tuftsin protein was expressed as an inclusion body, and was purified by ion exchange chromatography and renaturated by gradient dialysis. The renaturated protein was identified by Dot blotting and reacted with serum of descendants immunized with SARS-CoV-2 subunit vaccine. The results showed that the antibody level reached a plateau after 35 days of immunization, and the serum antibody ELISA titer of mice immunized with recombinant protein containing intramolecular adjuvant was up to 1:66 240, which was significantly higher than that of mice immunized with S-RBD protein (P < 0.05). At the same time, the recombinant protein containing intramolecular adjuvant stimulated mice to produce a stronger lymphocyte proliferation ability. The stimulation index was 4.71±0.15, which was significantly different from that of the S-RBD protein (1.83±0.09) (P < 0.000 1). Intramolecular adjuvant tetanus toxin peptide and tuftsin peptide significantly enhanced the humoral and cellular immune effect of the SARS-CoV-2 S protein RBD domain, which provideda theoretical basis for the development of subunit vaccines for SARS-CoV-2 and other viruses.


Assuntos
COVID-19 , Tuftsina , Vacinas Virais , Adjuvantes Imunológicos , Alumínio , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19/genética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Recombinantes/genética , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , Toxina Tetânica , Vacinas de Subunidades
18.
Oxid Med Cell Longev ; 2022: 6881322, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36124087

RESUMO

Advancements in technology have resulted in increasing concerns over the safety of eye exposure to light illumination, since prolonged exposure to intensive visible light, especially to short-wavelength light in the visible spectrum, can cause photochemical damage to the retina through a photooxidation-triggered cascade reaction. Poly(ADP-ribose) polymerase-1 (PARP-1) is the ribozyme responsible for repairing DNA damage. When damage to DNA occurs, including nicks and breaks, PARP-1 is rapidly activated, synthesizing a large amount of PAR and recruiting other nuclear factors to repair the damaged DNA. However, retinal photochemical damage may lead to the overactivation of PARP-1, triggering PARP-dependent cell death, including parthanatos, necroptosis, and autophagy. In this review, we retrieved targeted articles with the keywords such as "PARP-1," "photoreceptor," "retinal light damage," and "photooxidation" from databases and summarized the molecular mechanisms involved in retinal photooxidation, PARP activation, and DNA repair to clarify the key regulatory role of PARP-1 in retinal light injury and to determine whether PARP-1 may be a potential marker in response to retinal photooxidation. The highly sensitive detection of PARP-1 activity may facilitate early evaluation of the effects of light on the retina, which will provide an evidentiary basis for the future assessment of the safety of light illumination from optoelectronic products and medical devices.


Assuntos
Inibidores de Poli(ADP-Ribose) Polimerases , RNA Catalítico , Biomarcadores , DNA/metabolismo , Dano ao DNA , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Retina/metabolismo
19.
Aging (Albany NY) ; 14(17): 6957-6974, 2022 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-36057261

RESUMO

Fibroblasts (FBs) are the most important functional cells in the process of wound repair, and their functions can be activated by different signals at the pathological site. Although wound repair is associated with microenvironmental stiffness, the effect of matrix stiffness on FBs remains elusive. In this study, TGF-ß1 was used to mimic the fibrotic environment under pathological conditions. We found that the soft substrates made FBs slender compared with tissue culture plastic, and the main altered biological function was the inhibition of proliferation and differentiation ability. Through PPI and WGCNA analysis, 63 hub genes were found, including GADD45A, CDKN3, HIST2H3PS2, ACTB, etc., which may be the main targets of soft substrates affecting the proliferation and differentiation of FBs. Our findings not only provide a more detailed report on the effect of matrix stiffness on the function of human skin FBs, but also may provide new intervention ideas for improving scars and other diseases caused by excessive cell proliferation, with potential clinical application prospects.


Assuntos
Fibroblastos , Fator de Crescimento Transformador beta1 , Proliferação de Células/genética , Células Cultivadas , Humanos , Plásticos/farmacologia , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/farmacologia
20.
Front Cardiovasc Med ; 9: 911358, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36017095

RESUMO

Background: Coronary heart disease (CHD) patients with standard low-density lipoprotein cholesterol (LDL-C) remain at risk of cardiovascular events, making it critical to explore new targets to reduce the residual risk. The relationship between ß-sheet conformation and CHD is gaining attention. This study was designed to compare the coronary lesions in CHD patients with varying LDL-C and evaluate whether serum ß-sheets are associated with coronary damage. Methods: Two hundred and one patients diagnosed with stable CHD were recruited and divided into four groups according to LDL-C. Baseline information, coronary lesion-related indicators, and peripheral blood samples were collected. Serum ß-sheet content was determined by thioflavin T fluorescence. Results: The baseline information was comparable in CHD patients with different LDL-C. No difference was found in indicators relevant to coronary lesions among groups. The content of ß-sheet was negatively correlated with LDL-C. Multiple linear regression revealed that serum ß-sheet was positively correlated with coronary lesion when risk factors such as age, smoking, and LDL-C were controlled. Conclusions: This is the first study that reports the serum ß-sheet levels of CHD patients being gradually increased with decreasing LDL-C when coronary lesions were comparable. Serum ß-sheet might exacerbate the coronary lesions in CHD patients independent of known risk factors such as LDL-C.

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