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1.
Front Genet ; 15: 1386411, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38974388

RESUMO

Background: Endometriosis, characterized by extrauterine endometrial tissue, leads to irregular bleeding and pelvic pain. Menstrual retrograde theory suggests fragments traverse fallopian tubes, causing inflammation and scar tissue. Prevalent among infertile women, risk factors include fewer pregnancies, delayed childbirth, irregular cycles, and familial predisposition. Treatments, medication, and surgery entail side effects. Studies link gut microbiota alterations to endometriosis, necessitating research to establish causation. We used Mendelian randomization to investigate the potential link between endometriosis and gut microbiota through genetic variants. Methods: Two-sample Mendelian randomization analyzed gut microbiota's potential causal effects on endometriosis. Instrumental variables, robustly associated with exposures, leveraged GWAS data from MiBioGen for gut microbiota and FinnGen R8 release for endometriosis. SNPs strongly associated with exposures were instrumental variables. Rigorous assessments ensured SNP impact scrutiny on endometriosis. Results: At the genus level, Anaerotruncus, Desulfovibrio, Haemophilus, and Holdemania showed causal association with endometriosis. Specific gut microbiota exhibited causal effects on different endometriosis stages. Holdemania and Ruminococcaceae UCG002 exerted reversible, stage-specific impacts. Conclusion: Mendelian randomization provides evidence for the causal link between specific gut microbiotas and endometriosis, emphasizing the pivotal role of gut microbiota dysbiosis. Modulating gut microbiota emerges as a promising strategy for preventing and treating endometriosis.

2.
Heliyon ; 10(12): e32864, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-39021919

RESUMO

Hydrogels exhibit exceptional suitability as wound dressing due to their remarkable three-dimensional (3D) characteristics. Here, we have reported the fabrication of hydrogels from biopolymers carboxymethyl cellulose (CMC), polyvinyl alcohol (PVA), and gelatin via a simple blending method to mimic the natural extracellular matrix. Scanning electron microscopy (SEM), water contact meters (WCM), and Fourier-transform infrared spectroscopy (FTIR) were used to evaluate the chemical structural, morphological, and wettability behavior. The wetting and degradation behavior were also found to be different for different formulations (Min. (51.60o) and Max. (113.60o)) and (Min. (38.82 mg) and Max. (3.72 mg)), respectively. Swelling was investigated in different media, including phosphate buffer saline solution (PBS) and aqueous media. It was observed that the hydrogel displayed the highest degree of swelling in an aqueous medium (Min. (597.32-1121.49 %) and Max. (1089.51-2139.73 %)) compared to PBS media (Min. (567.01-1021.85 %) and Max. (899.13-1639.17 %)). The release of Neomycin was studied in a PBS medium via the Franz diffusion method at 37 °C. The maximal release in various media demonstrated pH-responsive behavior. The viability and proliferation of fibroblast (3T3) cell lines were examined in vitro to evaluate cytocompatibility. Human Embryonic Kidney (HEK) 293 cells were used to evaluate the hydrogels' ability to promote vascularization and angiogenesis. Therefore, the data demonstrate that hydrogels that have been manufactured have qualities that make them promising for use as wound dressings in wound healing applications.

3.
Crit Rev Food Sci Nutr ; : 1-14, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39023856

RESUMO

Short-chain fatty acids (SCFAs) are the primary energy source of colonic epithelial cells, but oral SCFAs are digested, absorbed, or degraded before reaching the colon. The acylated starch with SCFAs can be fermented and release specific SCFAs under the action of colonic intestinal microbiota. This review first introduces the preparation method, reaction mechanism, and substitution factors. Second, the structure, physical and chemical properties, in vitro function, and mechanism of acylated starch were expounded. Finally, the application of acylated starch in foods is introduced, and its safety is evaluated, providing a basis for the further development of acylated starch-based foods. The acylated starch obtained by different acylation types and preparation methods is different in particle, molecular, and crystal structures, leading to changes in the function and physicochemical properties. Meanwhile, acylated starch has the functional potential of targeted delivery of SCFAs to the colon, which can increase SCFAs in feces and intestine, selectively regulate the intestinal microbiota, and produce a prebiotic effect conducive to host health. The safety of acetylated starch has been supported by relevant studies, which have been widely used in various food fields and have great potential in the food industry.

4.
J Mater Chem B ; 12(26): 6285-6304, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38895829

RESUMO

Phototherapy, including photothermal therapy (PTT) and photodynamic therapy (PDT), has the advantages of spatiotemporal selectivity, non-invasiveness, and negligible drug resistance. Phototherapy has been approved for treating superficial epidermal tumors. However, its therapeutic efficacy is limited by the hypoxic tumor microenvironment and the highly expressed heat shock protein. Moreover, poor tissue penetration and focused irradiation laser region in phototherapy make treating deep tissues and metastatic tumors challenging. Combination therapy strategies, which integrate the advantages of each treatment and overcome their disadvantages, can significantly improve the therapeutic efficacy. Recently, many combination therapy strategies have been reported. Our study summarizes the strategies used for combining phototherapy with other cancer treatments such as chemotherapy, immunotherapy, sonodynamic therapy, gas therapy, starvation therapy, and chemodynamic therapy. Some research cases were selected to analyze the combination therapy effect, delivery platform feature, and synergetic anticancer mechanisms. Moreover, additional research cases are summarized in the tables. This review provides strong evidence that phototherapy-based combination strategies can enhance the anticancer effect compared with phototherapy alone. Additionally, the challenges and future perspectives associated with these combinational therapies are discussed.


Assuntos
Neoplasias , Humanos , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Fototerapia/métodos , Terapia Combinada , Animais , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico
5.
Cell Mol Life Sci ; 81(1): 265, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38880863

RESUMO

Heterotopic ossification (HO) occurs as a common complication after injury, while its risk factor and mechanism remain unclear, which restricts the development of pharmacological treatment. Clinical research suggests that diabetes mellitus (DM) patients are prone to developing HO in the tendon, but solid evidence and mechanical research are still needed. Here, we combined the clinical samples and the DM mice model to identify that disordered glycolipid metabolism aggravates the senescence of tendon-derived stem cells (TSCs) and promotes osteogenic differentiation. Then, combining the RNA-seq results of the aging tendon, we detected the abnormally activated autocrine CXCL13-CXCR5 axis in TSCs cultured in a high fat, high glucose (HFHG) environment and also in the aged tendon. Genetic inhibition of CXCL13 successfully alleviated HO formation in DM mice, providing a potential therapeutic target for suppressing HO formation in DM patients after trauma or surgery.


Assuntos
Quimiocina CXCL13 , Glicolipídeos , Ossificação Heterotópica , Osteogênese , Receptores CXCR5 , Animais , Ossificação Heterotópica/metabolismo , Ossificação Heterotópica/patologia , Ossificação Heterotópica/genética , Camundongos , Humanos , Quimiocina CXCL13/metabolismo , Quimiocina CXCL13/genética , Glicolipídeos/metabolismo , Receptores CXCR5/metabolismo , Receptores CXCR5/genética , Células-Tronco/metabolismo , Tendões/metabolismo , Tendões/patologia , Masculino , Camundongos Endogâmicos C57BL , Diferenciação Celular , Senescência Celular , Transdução de Sinais , Células Cultivadas , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia
6.
Anal Chem ; 96(18): 7257-7264, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38664861

RESUMO

Confocal fluorescence imaging of fine structures of the cell membrane is important for understanding their biofunctions but is often neglected due to the lack of an effective method. Herein, we develop new amphiphilic rhodamine fluorescent probe RMGs in combination with basal imaging for this purpose. The probes show high signal-to-noise ratio and brightness and low internalization rate, making them suitable for imaging the fine substructures of the cell membrane. Using the representative probe RMG3, we not only observed the cell pseudopodia and intercellular nanotubes but also monitored the formation of migrasomes in real time. More importantly, in-depth imaging studies on more cell lines revealed for the first time that hepatocellular carcinoma cells secreted much more adherent extracellular vesicles than other cell lines, which might serve as a potential indicator of liver cells. We believe that RMGs may be useful for investigating the fine structures of the cell membrane.


Assuntos
Membrana Celular , Corantes Fluorescentes , Rodaminas , Corantes Fluorescentes/química , Rodaminas/química , Humanos , Membrana Celular/química , Imagem Óptica , Microscopia Confocal/métodos , Tensoativos/química
7.
Cancer Lett ; 590: 216868, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38593920

RESUMO

While previous studies have indicated the involvement of Isthmin 1 (ISM1), a secreted protein, in cancer development, the precise mechanisms have remained elusive. In this study, we unveiled that ISM1 is significantly overexpressed in both the blood and tissue samples of colorectal cancer (CRC) patients, correlating with their poor prognosis. Functional experiments demonstrated that enforced ISM1 expression significantly enhances CRC proliferation, migration, invasion and tumor growth. Notably, our investigation reveals an interaction of ISM1 with epidermal growth factor receptor (EGFR), a member of the receptor tyrosine kinase (RTK) family of CRC cells. The binding of ISM1 triggered EGFR activation and initiate downstream signaling pathways. Meanwhile, intracellular ISM1 interacted with Y-box binding protein 1 (YBX1), enhancing its transcriptional regulation on EGFR. Furthermore, our research uncovered the regulation of ISM1 expression by the hypoxia-inducible transcription factor HIF-1α in CRC cells. Mechanistically, we identified HIF-1α as a direct regulator of ISM1, binding to a hypoxia response element on its promoter. This novel mechanism illuminated potential therapeutic targets, offering insights into restraining HIF-1α/ISM1/EGFR-driven CRC progression and metastasis.


Assuntos
Proliferação de Células , Neoplasias Colorretais , Progressão da Doença , Receptores ErbB , Regulação Neoplásica da Expressão Gênica , Subunidade alfa do Fator 1 Induzível por Hipóxia , Proteína 1 de Ligação a Y-Box , Humanos , Receptores ErbB/metabolismo , Receptores ErbB/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Proteína 1 de Ligação a Y-Box/metabolismo , Proteína 1 de Ligação a Y-Box/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Animais , Movimento Celular , Linhagem Celular Tumoral , Camundongos , Masculino , Transdução de Sinais , Feminino , Camundongos Nus , Células HCT116 , Prognóstico
8.
Acta Biochim Biophys Sin (Shanghai) ; 56(5): 776-788, 2024 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-38495003

RESUMO

Intervertebral disc degeneration (IDD) is the cause of low back pain (LBP), and recent research has suggested that inflammatory cytokines play a significant role in this process. Maslinic acid (MA), a natural compound found in olive plants ( Olea europaea), has anti-inflammatory properties, but its potential for treating IDD is unclear. The current study aims to investigate the effects of MA on TNFα-induced IDD in vitro and in other in vivo models. Our findings suggest that MA ameliorates the imbalance of the extracellular matrix (ECM) and mitigates senescence by upregulating aggrecan and collagen II levels as well as downregulating MMP and ADAMTS levels in nucleus pulposus cells (NPCs). It can also impede the progression of IDD in rats. We further find that MA significantly affects the PI3K/AKT and NF-κB pathways in TNFα-induced NPCs determined by RNA-seq and experimental verification, while the AKT agonist Sc-79 eliminates these signaling cascades. Furthermore, molecular docking simulation shows that MA directly binds to PI3K. Dysfunction of the PI3K/AKT pathway and ECM metabolism has also been confirmed in clinical specimens of degenerated nucleus pulposus. This study demonstrates that MA may hold promise as a therapeutic agent for alleviating ECM metabolism disorders and senescence to treat IDD.


Assuntos
Degeneração do Disco Intervertebral , NF-kappa B , Núcleo Pulposo , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Ratos Sprague-Dawley , Transdução de Sinais , Triterpenos , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/tratamento farmacológico , Degeneração do Disco Intervertebral/patologia , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , NF-kappa B/metabolismo , Núcleo Pulposo/metabolismo , Núcleo Pulposo/efeitos dos fármacos , Núcleo Pulposo/patologia , Masculino , Triterpenos/farmacologia , Ratos , Humanos , Simulação de Acoplamento Molecular , Fator de Necrose Tumoral alfa/metabolismo , Matriz Extracelular/metabolismo , Matriz Extracelular/efeitos dos fármacos , Feminino , Células Cultivadas , Ácido Oleanólico/análogos & derivados
9.
Front Plant Sci ; 15: 1368869, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38545395

RESUMO

Background: Thymus mandschuricus is an aromatic and medicinal plant with notable antibacterial and antioxidant properties. However, traditional breeding methods rely on phenotypic selection due to a lack of molecular resources. A high-quality reference genome is crucial for marker-assisted breeding, genome editing, and molecular genetics. Results: We utilized PacBio and Hi-C technologies to generate a high-quality chromosome-level reference genome for T. mandschuricus, with a size of 587.05 Mb and an N50 contig size of 8.41 Mb. The assembled genome contained 29,343 predicted protein-coding genes, and evidence of two distinct whole-genome duplications in T. mandschuricus was discovered. Comparative genomic analysis revealed rapid evolution of genes involved in phenylpropanoid biosynthesis and the CYP450 gene family in T. mandschuricus. Additionally, we reconstructed the gene families of terpenoid biosynthesis structural genes, such as TPS, BAHD, and CYP, and identified regulatory networks controlling the expression of aroma-synthesis genes by integrating transcriptome data from various organs and developmental stages. We discovered that hormones and transcription factors may collaborate in controlling aroma-synthesis gene expression. Conclusion: This study provides the first high-quality genome sequence and gene annotation for T. mandschuricus, an indigenous thyme species unique to China. The genome assembly and the comprehension of the genetic basis of fragrance synthesis acquired from this research could potentially serve as targets for future breeding programs and functional studies.

10.
Foods ; 13(5)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38472834

RESUMO

The daylily (Hemerocallis citrina Baroni) flower is a traditional raw food material that is rich in a variety of nutrients. In particular, the content of polysaccharides in daylily is abundant and has been widely used as a functional component in food, cosmetics, medicine, and other industries. However, studies on the structure-effective relationship of daylily flower polysaccharides are still lacking. In view of this, daylily flower polysaccharides were isolated and purified, and their physical and chemical properties, structure, antioxidant activity, and adhesion-promoting effect on probiotics were evaluated. The results showed that a novel water-soluble polysaccharide (DPW) with an average molecular weight (Mw) of 2.224 kDa could be successfully isolated using column chromatography. Monosaccharide composition analysis showed that DPW only comprised glucose and fructose, with a molar ratio of 0.242:0.758. Through methylation and nuclear magnetic resonance (NMR) analysis, it was inferred that DPW belonged to the fructans group with a structure of α-D-Glcp-1→2-ß-D-Fruf-1→(2-ß-D-Fruf-1)n→. Antioxidant analysis showed that DPW showed strong 2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-Oxide (PTIO-scavenging activity with IC50 of 1.54 mg/mL. DPW of 1.25 to 5 mg/mL could significantly increase the adhesion rate of Lactobacillus acidophilu, Lactobacillus casei, Bifidobacterium adolescentis, and Lactobacillus plantarum on Caco-2 cells. Considering the above results, the present study provides a theoretical basis and practical support for the development and application of daylily polysaccharides as a functional active ingredient.

11.
Can J Anaesth ; 71(6): 849-869, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38418761

RESUMO

PURPOSE: Nearly all patients with hip fractures undergo surgical treatment. The use of different anesthesia techniques during surgery may influence the clinical outcomes. The optimal anesthetic technique for patients undergoing hip fracture surgery is still controversial. We performed this updated systematic review and meta-analysis to compare clinical outcomes of patients undergoing hip fracture surgery with different anesthesia techniques. SOURCE: Articles published from 2000 to May 2023 were included from MEDLINE, Embase, Web of Science, and the Cochrane Library. We included randomized controlled trials and observational studies comparing general anesthesia (GA) with regional anesthesia (RA) for the outcomes of 30-day mortality, 90-day mortality, in-hospital mortality, perioperative complications, length of hospital stay, and length of surgery in patients undergoing hip fracture surgery. Subgroup analyses were performed for the outcomes based on study design (randomized controlled trials or observational studies). We used a random-effects model for all analyses. PRINCIPAL FINDINGS: In this meta-analysis, we included 12 randomized controlled trials. There was no difference in postoperative 30-day mortality between the two groups (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.44 to 1.74; I2 = 0%). The incidence of intraoperative hypotension was lower in patients who received RA vs GA (OR, 0.52; 95% CI, 0.38 to 0.72; I2 = 0%). No significant differences were observed in 90-day mortality, in-hospital mortality, postoperative delirium, pneumonia, myocardial infarction, venous thromboembolism, length of surgery, and length of hospital stay. CONCLUSION: In this updated systematic review and meta-analysis, RA did not reduce postoperative 30-day mortality in hip fracture surgery patients compared to GA. Fewer patients receiving RA had intraoperative hypotension than those receiving GA did. Apart from intraoperative hypotension, the data showed no differences in complications between the two anesthetic techniques. STUDY REGISTRATION: PROSPERO (CRD42023411854); registered 7 April 2023.


RéSUMé: OBJECTIF: Presque toutes les personnes ayant subi une fracture de la hanche se font opérer. L'utilisation de différentes techniques d'anesthésie pendant la chirurgie peut influencer les issues cliniques. La technique d'anesthésie optimale pour la patientèle bénéficiant de chirurgie de fracture de la hanche est encore controversée. Nous avons réalisé cette mise à jour par revue systématique et méta-analyse pour comparer les issues cliniques des personnes bénéficiant d'une chirurgie de fracture de la hanche avec différentes techniques d'anesthésie. SOURCES: Les articles publiés de 2000 à mai 2023 ont été inclus à partir des bases de données MEDLINE, Embase, Web of Science et Cochrane Library. Nous avons inclus des études randomisées contrôlées et des études observationnelles comparant l'anesthésie générale (AG) à l'anesthésie régionale (AR) pour les issues de mortalité à 30 jours, de mortalité à 90 jours, de mortalité intrahospitalière, de complications périopératoires, de durée de séjour à l'hôpital et de durée de la chirurgie pour les personnes bénéficiant d'une chirurgie de fracture de la hanche. Des analyses de sous-groupes ont été réalisées pour les issues en fonction de la méthodologie utilisée (étude randomisée contrôlée ou étude observationnelle). Un modèle à effets aléatoires a été utilisé pour toutes les analyses. CONSTATATIONS PRINCIPALES: Dans cette méta-analyse, nous avons inclus 12 études randomisées contrôlées. Il n'y avait pas de différence dans la mortalité postopératoire à 30 jours entre les deux groupes (rapport de cotes [RC], 0,88; intervalle de confiance à 95 % [IC], 0,44 à 1,74; I2 = 0 %). L'incidence d'hypotension peropératoire était plus faible chez les patient·es ayant reçu une AR vs une AG (RC, 0,52; IC 95 %, 0,38 à 0,72; I2 = 0 %). Aucune différence significative n'a été observée dans les issues de mortalité à 90 jours, de mortalité intrahospitalière, de delirium postopératoire, de pneumonie, d'infarctus du myocarde, de thromboembolie veineuse, de durée de la chirurgie, et de durée du séjour à l'hôpital. CONCLUSION: Dans cette revue systématique avec méta-analyse, l'anesthésie régionale n'a pas réduit la mortalité postopératoire à 30 jours chez les personnes ayant bénéficié d'une chirurgie de fracture de la hanche par rapport à l'anesthésie générale. Une proportion moindre de patient·es ayant reçu une AR présentaient une hypotension peropératoire par rapport aux personnes ayant reçu une AG. En dehors de l'hypotension peropératoire, les données n'ont montré aucune différence dans les complications entre les deux techniques anesthésiques. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42023411854); enregistrée le 7 avril 2023.


Assuntos
Anestesia por Condução , Anestesia Geral , Fraturas do Quadril , Mortalidade Hospitalar , Tempo de Internação , Complicações Pós-Operatórias , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Fraturas do Quadril/cirurgia , Anestesia Geral/métodos , Anestesia por Condução/métodos , Tempo de Internação/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia
12.
Anal Methods ; 16(11): 1674-1685, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38419501

RESUMO

Heavy metal ions (Cr6+, Co2+, Ni2+, and Cu2+) in the electroplating and electrolysis industries are significantly related to process parameters and product quality, even at lower concentrations. Absorption spectroscopy is widely used for substance qualitative and quantitative analysis, which is an analytical method with the potential for real-time monitoring of heavy metal ions concentration in industrial processes. In this paper, a low-concentration heavy metal ion analysis method based on multiple reflection enhanced absorption (MREA) is proposed. Compared with traditional absorption, MREA has the advantages of low concentration detection limit and high-sensitivity. First, a reflective film (Al-SiO2) was prepared and a multiple reflection optical structure was designed to realize multiple parallel reflections of light in the solution medium. Then absorption spectra of low-concentration Cr6+, Co2+, Ni2+ and Cu2+ solutions were measured by MREA and traditional absorption methods. Finally, spectral bandwidth and incident light spots were optimized to obtain a superior absorption enhancement effect. The results showed that MREA could effectively increase the substance absorbance compared with traditional absorption. At the same time, with the optimal spectral bandwidth (0.4 nm) and incident light spot (1 mm), the detection limit of Cr6+, Co2+, Ni2+ and Cu2+ was reduced by 81.48%, 82.52%, 80.92% and 82.93%, respectively. The sensitivity was improved by 5-6 times, which was more obvious for low-concentration detection. In addition, the MREA method can achieve ion concentration analysis when Cr6+, Co2+, Ni2+, and Cu2+ coexist, and the linear correlative coefficients of the C-A curves were all greater than 0.999. Moreover, by adjusting reflectivity of the reflective film and the number of reflections in the optical structure, the results of the MREA method can be further optimized for the low-concentration heavy metal ion analysis. The MREA method has the advantages of simplicity, rapidity and versatility, which can provide the technical foundation for real-time monitoring method development of low-concentration heavy metal ions in industrial processes.

13.
Mol Cell Biochem ; 479(2): 325-335, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37074506

RESUMO

Burn injury is a serious traumatic injury that leads to severe physical and psychosocial impairment. Wound healing after burn injury is a substantial challenge in medical community. This study investigated the biological effects of the demethylase fat mass and obesity-associated protein (FTO) on burn injury. FTO protein level in burn skin tissues of patients was measured with Western blot assay. Keratinocytes (HaCaT cells) were given heat stimulation to induce an in vitro burn injury model, and then transfected with overexpression plasmids of FTO (pcDNA-FTO) or small interfering RNA against FTO (si-FTO). Cell proliferation, migration, and angiogenesis in keratinocytes were evaluated with CCK-8, Transwell, and tube formation assays, respectively. Tissue factor pathway inhibitor-2 (TFPI-2) m6A methylation level was detected with MeRIP­qPCR assay. Then rescue experiments were conducted to explore the effects of FTO/TFPI-2 axis on keratinocyte functions. Lentivirus carrying FTO overexpression plasmids was injected into a burn rat model to detect its effects on wound healing and depressive-like behaviors in burn rats. FTO was downregulated in burn skin and heat-stimulated keratinocytes. FTO prominently augmented proliferation, migration and angiogenesis in heat-stimulated keratinocytes, while FTO knockdown showed the opposite results. FTO inhibited TFPI-2 expression by FTO-mediated m6A methylation modification. TFPI-2 overexpression abrogated FTO mediated enhancement of proliferation, migration and angiogenesis in keratinocytes. Additionally, FTO overexpression accelerated wound healing and improved depressive-like behaviors in burn rat model. FTO prominently augmented proliferation, migration and angiogenesis in heat-stimulated keratinocytes though inhibiting TFPI-2, and then improved wound healing and depressive-like behaviors.


Assuntos
Angiogênese , Queimaduras , Glicoproteínas , Animais , Humanos , Ratos , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Queimaduras/genética , Proliferação de Células , Desmetilação , Depressão/genética , Queratinócitos , Cicatrização
14.
Spine J ; 24(2): 317-324, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37844628

RESUMO

BACKGROUND CONTEXT: Facet joint osteoarthritis (FJOA) is associated with lumbar disc degeneration and has a significant role in the development of lumbar spinal stenosis (LSS). The relationship between various radiographic parameters and the grade of FJOA is not well understood. PURPOSE: To explore radiographical parameters associated with FJOA in LSS without lumbar dynamic instability. STUDY DESIGN: Retrospective study analysis. PATIENT SAMPLE: A total of 122 patients diagnosed with LSS who visited our hospital between January 2015 and July 2022. OUTCOME MEASURES: We evaluated radiographic parameters of patients at L4-5 including lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), grades of FJOA, facet joint orientation (FO), facet joint tropism (FT), intervertebral height index (IHI) and the relative cross-sectional area (RCSA) of paraspinal muscles. METHODS: Patients diagnosed with LSS between January 2015 and July 2022 were enrolled. Demographic characteristics and radiographic parameters were collected. Spinopelvic parameters were measured through the preoperative lateral image of the whole spine, including LL, PI, pelvic tilt, and sacral slope. Lumbar computed tomography scan and magnetic resonance imaging were collected to measure the FO, FT, IHI, and the RCSA of paraspinal muscles respectively. Patients were divided into three groups according to the severity of FJOA graded by the Weishaupt classification: grade 0 and grade 1 were group A, grade 2 were group B, and grade 3 were group C. All variables were compared among the three groups, while the relationship between parameters and grades of FJOA were also analyzed. RESULTS: A total of 122 patients were included. PI was significantly greater in group C compared to group A (p = 0.025) and group B (p=0.022). FT was significantly greater in group C compared to group A (p<.001) and group B (p<.001). The RCSA of multifidus in group A were significantly greater than that in group B (p=0.02) and C (p=0.002). Additionally, FO in group C were significantly lower than group A (p<.001) and group B (p=0.028). The IHI in group C was significantly lower than group A (p=0.017). The correlation analysis indicated that grades of FJOA was positively related to Age, BMI (body mass index), PI, LL and FT, while negatively related to IHI, FO, RCSA of multifidus and RCSA of psoas major. Furthermore, the logistics regression showed that FT, PI, and IHI were important influence factors for FJOA. CONCLUSIONS: The current study confirmed that FT, PI and IHI were significantly associated with grades of FJOA at L4-5. Additionally, longitudinal studies are needed to understand the causal relationship between these parameters and FJOA.


Assuntos
Lordose , Osteoartrite , Estenose Espinal , Articulação Zigapofisária , Humanos , Articulação Zigapofisária/diagnóstico por imagem , Articulação Zigapofisária/patologia , Estenose Espinal/diagnóstico por imagem , Estenose Espinal/patologia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Estudos Retrospectivos , Lordose/patologia , Tropismo , Osteoartrite/epidemiologia
15.
Biochem Biophys Res Commun ; 694: 149410, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38134478

RESUMO

Klebsiella aerogenes (K. aerogenes, KA) is a gram-negative opportunistic pathogen from the Klebsiella species and the Enterobacteriaceae family. However, the impact of K. aerogenes on colorectal cancer (CRC) remains uncertain. A colitis-associated tumorigenesis animal model was established by administering azoxymethane (AOM) and dextran sulfate sodium (DSS) to C57BL/6J mice. The concentration of K. aerogenes gavage in mice was 109 cfu. The study measured the following parameters: tumor formation (number and size), intestinal permeability (MUC2, ZO-1, and Occludin), colonic inflammation (TNF-α, IL-1ß, IL-6, and IL-10), proliferation and the fluctuation of the intestinal flora. Under the AOM/DSS-treated setting, K. aerogenes colonization worsened colitis by exacerbating intestinal inflammatory reaction and destroying the mucosal barrier. The intervention markedly augmented the quantity and dimensions of neoplasm in the AOM/DSS mice, stimulated cellular growth, and impeded cellular programmed cell death. In addition, K. aerogenes exacerbated the imbalance of the intestinal microbiota by elevating the abundance of Pseudomonas, Erysipelatoclostridium, Turicibacter, Rikenella, and Muribaculum and leading to a reduction in the abundance of Odoribacter, Alloprevotella, Roseburia, and Lachnospiraceae_NK4A136_group. The presence of K. aerogenes in AOM/DSS-treated mice promoted tumorigenesis, worsened intestinal inflammation, disrupted the intestinal barrier, and caused disturbance to the gut microbiota.


Assuntos
Colite , Enterobacter aerogenes , Animais , Camundongos , Azoximetano/toxicidade , Azoximetano/metabolismo , Camundongos Endogâmicos C57BL , Colite/patologia , Colo/patologia , Inflamação/patologia , Carcinogênese/patologia , Transformação Celular Neoplásica/patologia , Bacteroidetes , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças
16.
World J Clin Cases ; 11(35): 8247-8255, 2023 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-38130627

RESUMO

Anterior cruciate ligament (ACL) injury is one of the most common types of sports injuries. People's need to participate in sports and desire for a high quality of life promotes the continuous development of ACL reconstruction technology. Arthroscopic ACL reconstruction has been recognized as an effective method for the treatment of ACL injuries. This review analyses and summarizes the advantages and limitations of each surgical procedure for arthroscopic ACL reconstruction reported in the relevant literature so as to promote the future development of more relevant techniques.

17.
Cell Death Differ ; 30(10): 2293-2308, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37608075

RESUMO

Proper development of the limb bud relies on the concordance of various signals, but its molecular mechanisms have not yet been fully illustrated. Here we report that heterogeneous nuclear ribonucleoprotein K (hnRNPK) is essential for limb bud development. Its ablation in the limb bud results in limbless forelimbs and severe deformities of the hindlimbs. In terms of mechanism, hnRNPK functions as a transcription activator for the vital genes involved in the three regulatory axes of limb bud development. Simultaneously, for the first time we elucidate that hnRNPK binds to and coordinates with the insulator protein CCCTC binding factor (CTCF) to maintain a three-dimensional chromatin architecture. Ablation of hnRNPK weakens the binding strength of CTCF to topologically associating domain (TAD) boundaries, then leading to the loose TADs, and decreased interactions between promoters and enhancers, and further decreased transcription of developmental genes. Our study establishes a fundamental and novel role of hnRNPK in regulating limb bud development.

18.
Materials (Basel) ; 16(13)2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37444996

RESUMO

This paper investigates the thermal mechanical bending response of symmetric functionally graded material (FGM) plates. This article proposes a thermodynamic analysis model of both the FGM plate and FGM sandwich plate, and the model only involves four control equations and four unknown variables. The control equation is based on the refined shear deformation theory and the principle of minimum potential energy. The Navier method is used to solve the control equation. According to the method, numerical examples are provided for the thermo-mechanical bending of the symmetric FGM plate and FGM sandwich plate under a simply supported boundary condition, and the accuracy of the model is verified. Finally, parameter analysis is conducted to investigate the effects of the volume fraction index, side-to-thickness ratio, thermal load, and changes in core thickness on the thermal mechanical bending behavior of the symmetric FGM plate and FGM sandwich plate in detail. It was found that the deflection of the FGM plate is greater than that of the FGM sandwich plate, while the normal stress of the FGM plate is smaller than that of the FGM sandwich plate. Moreover, the FGM plate and FGM sandwich plate are sensitive to nonlinear temperature changes.

19.
Behav Brain Res ; 452: 114560, 2023 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-37394125

RESUMO

The rostral anterior cingulate cortex (rACC) of rat brain is associated with pain-related emotions. However, the underlying molecular mechanism remains unclear. Here, we investigated the effects of the N-methyl-D-aspartate (NMDA) receptor and Ca2+/Calmodulin-dependent protein kinase type II (CaMKII)α signal on pain-related aversion in the rACC of a rat model of neuropathic pain (NP). Mechanical and thermal hyperalgesia were examined using von Frey and hot plate tests in a rat model of NP induced by spared nerve injury (SNI) of the unilateral sciatic nerve. Bilateral rACC pretreatment with the CaMKII inhibitor tat-CN21 (derived from the cell-penetrating tat sequence and CaM-KIIN amino acids 43-63) or tat-Ctrl (the tat sequence and the scrambled sequence of CN21) was performed on postoperative days 29-35 in Sham rats or rats with SNI. Spatial memory performance was tested using an eight-arm radial maze on postoperative days 34-35. Pain-related negative emotions (aversions) were evaluated using the place escape/avoidance paradigm on postoperative day 35 following the spatial memory performance test. The percentage of time spent in the light area was used to assess pain-related negative emotions (i.e., aversion). The expression levels of the NMDA receptor GluN2B subunit, CaMKIIα, and CaMKII-Threonine at position 286 (Thr286) phosphorylation in contralateral rACC specimens were detected by Western blot or real time PCR following the aversion test. Our data showed that pretreatment of the rACC with tat-CN21 increased determinate behavior but did not alter hyperalgesia or spatial memory performance in rats with SNI. In addition, tat-CN21 reversed the enhanced CaMKII-Thr286 phosphorylation and had no effect on the upregulated expression of GluN2B, CaMKIIα protein, and mRNA. Our data suggested that activation of the NMDA receptor-CaMKIIα signal in rACC is associated with pain-related aversion in rats with NP. These data may provide a new approach for the development of drugs that modulate cognitive and emotional pain aspects.


Assuntos
Neuralgia , Traumatismos dos Nervos Periféricos , Ratos , Animais , Giro do Cíngulo/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Cálcio/metabolismo , Ratos Sprague-Dawley , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Traumatismos dos Nervos Periféricos/complicações , Traumatismos dos Nervos Periféricos/metabolismo , Neuralgia/metabolismo , Hiperalgesia/metabolismo
20.
Langmuir ; 39(26): 9144-9153, 2023 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-37337305

RESUMO

Absorption spectra are fundamental bases for the qualitative and quantitative analysis of the target chemical, and the development of an analytical model can be improved by studying its characteristics and rules. In the present study, the electronic excitation characteristics of phosphate anions (H2PO4-, HPO42-, and PO43-) were analyzed based on the charge-transfer spectrum. In addition, the absorption spectra of phosphate anions at the energy level of PBE0/6-311+G (d,p) were recorded based on the time-dependent density functional theory (TD-DFT) method. Different (HPO42-)n·(H2O)10-n molecular clusters were theoretically constructed, and the combined TD-DFT method and independent gradient model revealed that red shift of the maximum absorption wavelength (λmax) with the increase of phosphate anion concentration (0-10 mM) may be caused by the decrease of hydrogen bond interaction. In addition, the prominent dispersion in the short-wave region mainly resulted in the red shift of λmax with the increase in optical path length (1-100 mm). Moreover, with the increase in spectral bandwidth (0.4-3.0 nm), λmax slightly blue-shifted because of the increase in energy through the slit, and repeatability of the corresponding absorbance measurement at λmax gradually improved. As the spectral bandwidth increased, light monochromaticity became poor, resulting in the decrease of the linearly fitted correlation coefficient of the concentration-absorbance curve. Finally, the multivariate analysis of variance results showed that the optical path length was the most significant factor that influenced the absorption spectral characteristics of phosphate anions. This study provides a basis for the qualitative and quantitative analysis of phosphate anions by using absorption spectra and also renders a theoretical reference for absorption spectroscopy of other chemicals.

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