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Recurrent spontaneous abortion (RSA) is a complex pathological process involving diverse factors, in which the dysregulated functions of trophoblasts cannot be ignored. Long noncoding RNA (lncRNA) has been reported to play a significant role in regulating the functions of trophoblasts in RSA. However, the impact and potential mechanism of lncRNA small nucleolar RNA host gene 12 (lncSNHG12) remain unclear. The role of lncSNHG12 in RSA was investigated through in vivo experiments and clinical samples. Co-IP and RNA pull down were conducted to explore the molecular mechanisms in trophoblasts. Our results showed that lncSNHG12 promoted the migration and invasion of trophoblasts by interacting with Iodothyronine deiodinase 2 (Dio2), which regulating the EMT process of trophoblasts by interacting with Snail. Moreover, in vivo experiments confirmed that lncSNHG12 could improve the fetal absorption rate of the abortion mice. The clinical samples revealed that lncSNHG12, Dio2 and Snail were down-regulated in the villous tissues of RSA patients, and positive correlations were confirmed between lncSNHG12 and Dio2, as well as Dio2 and Snail. In summary, the lncSNHG12/Dio2/Snail axis might be involved in the development of RSA by regulating the invasion and migration of trophoblasts. Abbreviations: RSA, recurrent spontaneous abortion; EVTs, extravillous trophoblasts; EMT, epithelial-to-mesenchymal transition; lncRNA, long non-coding RNA; Dio2, iodothyronine deiodinase 2; SNHGs, small nuclear RNA host genes; snoRNAs, small nuclear cell RNAs; LPS, lipopolysaccharide; De, derived decidua; Jz, junctional zone; Lz, labyrinth zones; RIP, RNA Binding Protein Immunoprecipitation; Co-IP, Co-Immunoprecipitation; RPISeq, RNA-Protein Interaction Prediction.
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The Ag cluster-POM assemblies have been shown to possess interesting and potentially useful properties. However, there is no precedent example of atomically precise Ag cluster-POM assemblies showing heterojunction effects in photocatalysis. Herein, the synthesis and total structure determination of the periodically distributed molecular heterojunction [Ag12(SCy)6(CH3CN)12(PW12O40)]n (Ag12-PW12) are reported. The assembly of Ag/W clusters into 3D network can endow the resulting binary structure with an aesthetic topology and unique physicochemical properties. More remarkably, the incorporation of Ag12 cluster with PW12 can efficiently facilitate the separation of photogenerated electrons and holes, thus significantly promoting the catalytic efficiency in selective oxidation of sulfides. The Ag12-PW12 heterojunction can be recovered and reused five times with no drastic change in the catalytic performance. This research is expected to assist in the rational design of cluster-based heterojunction catalysts. The increase of catalytic activity of the Ag12-PW12 assembly in comparison with the unassembled Ag12 and PW12 clusters is attributed to the synergistic effect of Ag12 and PW12 clusters, offering the splendid opportunity for deciphering structure-reactivity relationship of heterostructure-coupled photosystem.
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Renal fibrosis is the final pathological change of kidney disease, it has also been recognized to be critical for the final progression of diabetic nephropathy (DN) to kidney failure. Acteoside (ACT) is a phenylethanoid glycoside widely distributed in dicotyledonous plants. It has many pharmacological activities, such as anti-oxidation, anti-inflammation, anti-cancer, neuroprotection, cardiovascular protection, anti-diabetes, bone and cartilage protection, liver and kidney protection, and antibacterial activity. This study aims to investigate the protective effects of ACT on renal interstitial fibrosis in rats with DN induced by intraperitoneal injection of streptozocin (STZ) combined with unilateral nephrectomy and its mechanism. In vivo and in vitro, the effects of ACT on reactive oxygen species (ROS) level, oxidative tubular injury, as well as damage of autophagic flux and lysosome in the DN model were detected. Results indicate that administration of ACT delayed the progression of renal interstitial fibrosis in DN by anti-oxidation and regulating the autophagy-lysosome pathway, which may potentially be attributed to the regulatory influence of ACT on transcription factor EB (TFEB).
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Antioxidantes , Autofagia , Nefropatías Diabéticas , Fibrosis , Glucósidos , Lisosomas , Fenoles , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno , Animales , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/patología , Nefropatías Diabéticas/metabolismo , Autofagia/efectos de los fármacos , Ratas , Masculino , Lisosomas/efectos de los fármacos , Lisosomas/metabolismo , Glucósidos/farmacología , Glucósidos/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , Fenoles/farmacología , Fenoles/uso terapéutico , Antioxidantes/farmacología , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Riñón/efectos de los fármacos , Riñón/patología , Riñón/metabolismo , Estrés Oxidativo/efectos de los fármacos , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Experimental/metabolismo , Transducción de Señal/efectos de los fármacos , PolifenolesRESUMEN
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation and the production of autoantibodies. Previous studies have indicated an association between high-salt diets (HSD) and an increased risk of RA, yet the underlying mechanisms remain unclear. Macrophage pyroptosis, a pro-inflammatory form of cell death, plays a pivotal role in RA. In this study, we demonstrate that HSD exacerbates the severity of arthritis in collagen-induced arthritis (CIA) mice, correlating with macrophage infiltration and inflammatory lesions. Given the significant alterations observed in macrophages from CIA mice subjected to HSD, we specifically investigate the impact of HSD on macrophage responses in the inflammatory milieu of RA. In our in vitro experiments, pretreatment with NaCl enhances LPS-induced pyroptosis in RAW.264.7 and THP-1 cells through the p38 MAPK/NF-κB signaling pathway. Subsequent experiments reveal that Slc6a12 inhibitors and SGK1 silencing inhibit sodium-induced activation of macrophage pyroptosis and the p38 MAPK/NF-κB signaling pathway, whereas overexpression of the SGK1 gene counteracts the effect of sodium on macrophages. In conclusion, our findings verified that high salt intake promotes the progression of RA and provided a detailed elucidation of the activation of macrophage pyroptosis induced by sodium transportation through the Slc6a12 channel.
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Artritis Reumatoide , Macrófagos , Proteínas Serina-Treonina Quinasas , Piroptosis , Animales , Ratones , Artritis Reumatoide/metabolismo , Artritis Reumatoide/patología , Macrófagos/metabolismo , Piroptosis/efectos de los fármacos , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Cloruro de Sodio/farmacología , Células RAW 264.7 , Humanos , Masculino , Proteínas Inmediatas-Precoces/metabolismo , Proteínas Inmediatas-Precoces/genética , Artritis Experimental/metabolismo , Transducción de Señal , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Ratones Endogámicos DBARESUMEN
RATIONALE AND OBJECTIVES: To evaluate the diagnostic performance of contrast-enhanced ultrasound (CEUS) combined with immune-inflammatory markers in predicting axillary lymph node metastasis (ALNM) in breast cancer patients. METHODS: From January 2020 to June 2023, the clinicopathological data and ultrasound features of 401 breast cancer patients who underwent biopsy or surgery were recorded. Patients were randomly divided into a training set (321 patients) and a validation set (80 patients). The risk factors for ALNM were determined using univariate, least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression analysis, and prediction models were constructed. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to assess their diagnostic performance. RESULTS: Logistic regression analysis demonstrated that systemic immunoinflammatory index (SII), CA125, Ki67, pathological type, lesion size, enhancement pattern and Breast Imaging Reporting and Data System (BI-RADS) category were significant risk factors for ALNM. Three different models were constructed, and the combined model yielded an AUC of 0.903, which was superior to the clinical model (AUC=0.790) and ultrasound model (AUC=0.781). A nomogram was constructed based on the combined model, calibration curves and DCA demonstrated its satisfactory performance in predicting ALNM. CONCLUSION: The nomogram combining ultrasound features and immune-inflammatory markers could serve as a valuable instrument for predicting ALNM in breast cancer patients. DATA AVAILABILITY STATEMENT: The original contributions presented in the study are included in the article. Further inquiries can be directed to the corresponding authors.
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Despite significant advances in assisted reproductive technology (ART), recurrent implantation failure (RIF) still occurs in some patients. Poor endometrial receptivity and abnormal human endometrial stromal cell (HESC) proliferation and decidualization have been identified as the major causes. Ubiquitin-specific protease 22 (USP22) has been reported to participate in the decidualization of endometrial stromal cells in mice. However, the role of USP22 in HESC function and RIF development remains unknown. In this study, clinical endometrial tissue samples were gathered to investigate the involvement of USP22 in RIF, and HESCs were utilized to examine the molecular mechanisms of USP22 and Forkhead box M1 (FoxM1). The findings indicated a high expression of USP22 in the secretory phase of the endometrium. Knockdown of USP22 led to a notable reduction in the proliferation and decidualization of HESCs, along with a decrease in FoxM1 expression, while overexpression of USP22 yielded opposite results. Furthermore, USP22 was found to deubiquitinate FoxM1 in HESCs. Moreover, both USP22 and FoxM1 were downregulated in the endometria of patients with RIF. In conclusion, these results suggest that USP22 may have a significant impact on HESCs proliferation and decidualization through its interaction with FoxM1, potentially contributing to the underlying mechanisms of RIF pathogenesis.
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Proliferación Celular , Endometrio , Proteína Forkhead Box M1 , Células del Estroma , Ubiquitina Tiolesterasa , Ubiquitinación , Humanos , Proteína Forkhead Box M1/metabolismo , Femenino , Ubiquitina Tiolesterasa/metabolismo , Ubiquitina Tiolesterasa/genética , Células del Estroma/metabolismo , Endometrio/metabolismo , Endometrio/citología , Adulto , Decidua/metabolismo , Decidua/citología , Implantación del EmbriónRESUMEN
Objective: Molidustat is a novel agent investigated for the treatment of anemia in both dialysisdependent (DD) and non-dialysis-dependent (NDD) patients. Its efficacy and safety are still unclear. Methods: We searched five databases to identify randomized controlled trials comparing molidustat to erythropoiesis-stimulating agents (ESAs) or placebo in patients with anemia. Results: Six studies containing 2025 eligible participants were identified. For NDD patients, the change in Hb levels from baseline (ΔHb) was significantly higher for molidustat than for placebo [mean difference (MD) = 1.47 (95 % CI: 1.18 to 1.75), P < 0.00001] and ΔHb was also significantly higher for molidustat than for ESAs [MD = 0.25 (95 % CI 0.09 to 0.40), P = 0.002]. For NDD patients, Δhepcidin was significantly lower for molidustat than for placebo [MD = -20.66 (95 % CI: -31.67 to -9.66), P = 0.0002] and Δhepcidin was also significantly lower for molidustat than for ESAs [MD = -24.51 (95 % CI: -29.12 to -19.90), P < 0.00001]. For NDD patients, Δiron was significantly lower for molidustat than for ESAs [MD = -11.85 (95 % CI: -15.52 to -8.18), P < 0.00001], and ΔTSAT was also significantly lower for molidustat than for ESAs [MD = -5.29 (95 % CI: -6.81 to -3.78), P < 0.00001]. For NDD patients, Δferritin was significantly lower for molidustat than for placebo [MD = -90.01 (95 % CI: -134.77 to -45.25), P < 0.00001]. However, for DD-CKD patients, molidustat showed an effect similar to that of ESAs on increasing the Hb level [MD = -0.18 (95 % CI: -0.47 to 0.11), P = 0.23], Δiron level [MD = 3.78 (95 % CI: -7.21 to 14.76), P = 0.5], Δferritin level [MD = 25.03 (95 % CI: -34.69 to 84.75), P = 0.41], and Δhepcidin level [MD = 1.20 (95 % CI: -4.36 to 6.76), P = 0.67]. For DD-CKD patients, compared with the placebo or ESA group, molidustat showed a significantly higher level on ΔTSAT[MD = 3.88 (95 % CI: 2.10 to 5.65), P < 0.0001] and a slightly increased level on ΔTIBC level [MD = 1.08 (95 % CI: -0.07 to 2.23), P = 0.07]. There was no significant difference in the incidence of severe adverse events (SAEs), death, and cardio-related adverse events between molidustat and the ESAs groups. Conclusions: Moricizine can effectively improves Hb levels in NDD patients and corrects anemia in DD patients without increasing adverse event incidence.
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OBJECTIVES: Orthodontic tooth movement is a mechanobiological reaction induced by appropriate forces, including bone remodeling. The mechanosensitive Piezo channels have been shown to contribute to bone remodeling. However, information about the pathways through which Piezo channels affects osteoblasts remains limited. Thus, we aimed to investigate the influence of Piezo1 on the osteogenic and osteoclast factors in osteoblasts under mechanical load. MATERIALS AND METHODS: Cyclic stretch (CS) experiments on MC3T3-E1 were conducted using a BioDynamic mechanical stretching device. The Piezo1 channel blocker GsMTx4 and the Piezo1 channel agonist Yoda1 were used 12 h before the application of CS. MC3T3-E1 cells were then subjected to 15% CS, and the expression of Piezo1, Piezo2, BMP-2, OCN, Runx2, RANKL, p-p65/p65, and ALP was measured using quantitative real-time polymerase chain reaction, western blot, alkaline phosphatase staining, and immunofluorescence staining. RESULTS: CS of 15% induced the highest expression of Piezo channel and osteoblast factors. Yoda1 significantly increased the CS-upregulated expression of Piezo1 and ALP activity but not Piezo2 and RANKL. GsMTx4 downregulated the CS-upregulated expression of Piezo1, Piezo2, Runx2, OCN, p-65/65, and ALP activity but could not completely reduce CS-upregulated BMP-2. CONCLUSIONS: The appropriate force is more suitable for promoting osteogenic differentiation in MC3T3-E1. The Piezo1 channel participates in osteogenic differentiation of osteoblasts through its influence on the expression of osteogenic factors like BMP-2, Runx2, and OCN and is involved in regulating osteoclasts by influencing phosphorylated p65. These results provide a foundation for further exploration of osteoblast function in orthodontic tooth movement.
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Proteína Morfogenética Ósea 2 , Subunidad alfa 1 del Factor de Unión al Sitio Principal , Canales Iónicos , Osteoblastos , Osteogénesis , Osteoblastos/metabolismo , Canales Iónicos/metabolismo , Animales , Ratones , Proteína Morfogenética Ósea 2/metabolismo , Osteogénesis/fisiología , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Osteoclastos/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Ligando RANK/metabolismo , Western Blotting , Estrés Mecánico , Diferenciación Celular , Osteocalcina/metabolismo , Fosfatasa Alcalina/metabolismo , Oligopéptidos/farmacología , Técnicas de Movimiento Dental , Mecanotransducción Celular/fisiología , Línea Celular , Remodelación Ósea/fisiología , Pirazinas , Venenos de Araña , Tiadiazoles , Péptidos y Proteínas de Señalización IntercelularRESUMEN
INTRODUCTION: This study aimed to evaluate the effects of varying auxiliaries on tooth movement and stress distribution when maxillary central incisors were torqued 1° with a clear aligner through finite element analysis. METHODS: Three-dimensional finite element models, including maxillary alveolar bone, periodontal ligament, dentition, and clear aligner, were constructed. According to the auxiliaries designed on the maxillary central incisor, 5 models were created: (1) without auxiliaries (control model), (2) with the power ridge, (3) with the semi-ellipsoid attachment, (4) with the horizontal rectangular attachment, and (5) with the horizontal cylinder attachment. The tooth movement and periodontal ligament stress distribution after a palatal root torque of 1° were analyzed for each of the 5 models. RESULTS: With 1° torque predicted, the maxillary central incisor without auxiliaries showed a tendency of labial tipping, mesial tipping, and intrusion. The rotation center moved occlusally in the power ridge model. The labiolingual inclination variation increased in the semi-ellipsoid attachment model but decreased in the power ridge model. The maxillary central incisor is twisted in the distal direction in the power ridge model. The maxillary central incisor of the horizontal rectangular attachment and the horizontal cylinder attachment model behaved similarly to the control model. Periodontal stresses were concentrated in the cervical and apical areas. The maximum von Mises stresses were 11.6, 12.4, 3.81, 1.14, and 11.0 kPa in the 5 models. The semi-ellipsoid attachment model exhibited a more uniform stress distribution than the other models. CONCLUSIONS: Semi-ellipsoid attachment performed better efficacy on labiolingual inclination, and power ridge performed better efficacy on root control. However, a distal twist of maxillary incisors could be generated by the power ridge.
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Análisis de Elementos Finitos , Incisivo , Maxilar , Técnicas de Movimiento Dental , Torque , Humanos , Técnicas de Movimiento Dental/métodos , Técnicas de Movimiento Dental/instrumentación , Ligamento Periodontal/fisiología , Análisis del Estrés Dental/métodos , Diseño de Aparato Ortodóncico , Aparatos Ortodóncicos RemoviblesRESUMEN
Dental pulp regeneration is a promising strategy for addressing tooth disorders. Incorporating this strategy involves the fundamental challenge of establishing functional vascular networks using dental pulp stem cells (DPSCs) to support tissue regeneration. Current therapeutic approaches lack efficient and stable methods for activating DPSCs. In the study, we used a chemically modified microRNA (miRNA)-loaded tetrahedral-framework nucleic acid nanostructure to promote DPSC-mediated angiogenesis and dental pulp regeneration. Incorporating chemically modified miR-126-3p into tetrahedral DNA nanostructures (miR@TDNs) represents a notable advancement in the stability and efficacy of miRNA delivery into DPSCs. These nanostructures enhanced DPSC proliferation, migration, and upregulated angiogenesis-related genes, enhancing their paracrine signaling effects on endothelial cells. This enhanced effect was substantiated by improvements in endothelial cell tube formation, migration, and gene expression. Moreover, in vivo investigations employing matrigel plug assays and ectopic dental pulp transplantation confirmed the potential of miR@TDNs in promoting angiogenesis and facilitating dental pulp regeneration. Our findings demonstrated the potential of chemically modified miRNA-loaded nucleic acid nanostructures in enhancing DPSC-mediated angiogenesis and supporting dental pulp regeneration. These results highlighted the promising role of chemically modified nucleic acid-based delivery systems as therapeutic agents in regenerative dentistry and tissue engineering.
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MicroARNs , MicroARNs/genética , MicroARNs/metabolismo , Células Endoteliales , Pulpa Dental , Células Madre , Diferenciación Celular , Regeneración , ADN/metabolismo , Proliferación Celular/fisiologíaRESUMEN
Cone beam computed tomography (CBCT) is widely employed in modern dentistry, and tooth segmentation constitutes an integral part of the digital workflow based on these imaging data. Previous methodologies rely heavily on manual segmentation and are time-consuming and labor-intensive in clinical practice. Recently, with advancements in computer vision technology, scholars have conducted in-depth research, proposing various fast and accurate tooth segmentation methods. In this review, we review 55 articles in this field and discuss the effectiveness, advantages, and disadvantages of each approach. In addition to simple classification and discussion, this review aims to reveal how tooth segmentation methods can be improved by the application and refinement of existing image segmentation algorithms to solve problems such as irregular morphology and fuzzy boundaries of teeth. It is assumed that with the optimization of these methods, manual operation will be reduced, and greater accuracy and robustness in tooth segmentation will be achieved. Finally, we highlight the challenges that still exist in this field and provide prospects for future directions.
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OBJECTIVES: Coffin-Siris Syndrome (CSS) is a congenital disorder characterized by delayed growth, dysmorphic facial features, hypoplastic nails and phalanges of the fifth digit, and dental abnormalities. Tooth agenesis has been reported in CSS patients, but the mechanisms regulating this syndromic tooth agenesis remain largely unknown. This study aims to identify the pathogenic mutation of CSS presenting tooth genesis and explore potential regulatory mechanisms. MATERIALS AND METHODS: We utilized whole-exome sequencing to identify variants in a CSS patient, followed by Sanger validation. In silico analysis including conservation analysis, pathogenicity predictions, and 3D structural assessments were carried out. Additionally, single-cell RNA sequencing and fluorescence in situ hybridization (FISH) were applied to explore the spatio-temporal expression of Sox4 expression during murine tooth development. Weighted Gene Co-expression Network Analysis (WGCNA) was employed to examine the functional role of SOX4. RESULTS: A novel de novo SOX4 missense mutation (c.1255C > G, p.Leu419Val) was identified in a Chinese CSS patient exhibiting tooth agenesis. Single-cell RNA sequencing and FISH further verified high expression of Sox4 during murine tooth development, and WGCNA confirmed its central role in tooth development pathways. Enriched functions included cell-substrate junctions, focal adhesion, and RNA splicing. CONCLUSIONS: Our findings link a novel SOX4 mutation to syndromic tooth agenesis in CSS. This is the first report of SOX4 missense mutation causing syndromic tooth agenesis. CLINICAL RELEVANCE: This study not only enhances our understanding of the pathogenic mutation for syndromic tooth agenesis but also provides genetic diagnosis and potential therapeutic insights for syndromic tooth agenesis.
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Anodoncia , Secuenciación del Exoma , Cara , Discapacidad Intelectual , Micrognatismo , Mutación Missense , Cuello , Factores de Transcripción SOXC , Animales , Femenino , Humanos , Masculino , Ratones , Anomalías Múltiples/genética , Anodoncia/genética , Cara/anomalías , Deformidades Congénitas de la Mano/genética , Hibridación Fluorescente in Situ , Micrognatismo/genética , Cuello/anomalías , Factores de Transcripción SOXC/genéticaRESUMEN
Unexplained recurrent spontaneous abortion (URSA) is a serious reproductive issue that affects women of childbearing age. Studies have shown a close association between disrupted circadian rhythm and impaired epithelial-mesenchymal transition (EMT) in trophoblasts during URSA, although the underlying mechanism is not known. The current study investigated the regulatory relationship between circadian rhythm gene cryptochrome 2 (CRY2) and ferroptosis on the migratory ability of trophoblast cells. Cell proliferation experiments, wound-healing assays, and expression of related markers were conducted to study EMT. Trophoblastic ferroptosis was confirmed by the expressions of malondialdehyde, glutathione, mitochondrial membrane potential, divalent iron ions, and related genes. The results showed significant increased expression of CRY2 and decreased expression of brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 (BMAL1) in the URSA villous tissues, accompanied by iron-dependent oxidative changes and abnormal expression of ferroptosis-related proteins. CRY2 and BMAL1 were co-localized and functioned as a feedback loop, which regulated the dynamic changes of EMT-related markers in trophoblast cells. CRY2 promoted trophoblastic ferroptosis, whereas BMAL1 had the opposite effect. Particularly, the ferroptosis inhibitor (ferrostatin-1) effectively reversed the trophoblastic ferroptosis and EMT inhibition caused by CRY2 overexpression. Collectively, these results suggest that CRY2 regulates trophoblastic ferroptosis and hinders cellular EMT and migratory ability by suppressing BMAL1 expression.
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Criptocromos , Transición Epitelial-Mesenquimal , Ferroptosis , Trofoblastos , Ferroptosis/fisiología , Humanos , Femenino , Criptocromos/metabolismo , Criptocromos/genética , Trofoblastos/metabolismo , Trofoblastos/patología , Embarazo , Adulto , Aborto Habitual/metabolismo , Aborto Habitual/patología , Proliferación Celular , Movimiento Celular , Factores de Transcripción ARNTL/metabolismo , Factores de Transcripción ARNTL/genéticaRESUMEN
The primary challenges posed by oral mucosal diseases are their high incidence and the difficulty in managing symptoms. Inspired by the ability of bioelectricity to activate cells, accelerate metabolism, and enhance immunity, a conductive polyacrylamide/sodium alginate crosslinked hydrogel composite containing reduced graphene oxide (PAA-SA@rGO) is developed. This composite possesses antibacterial, anti-inflammatory, and antioxidant properties, serving as a bridge to turn the "short circuit" of the injured site into a "completed circuit," thereby prompting fibroblasts in proximity to the wound site to secrete growth factors and expedite tissue regeneration. Simultaneously, the PAA-SA@rGO hydrogel effectively seals wounds to form a barrier, exhibits antibacterial and anti-inflammatory properties, and prevents foreign bacterial invasion. As the electric field of the wound is rebuilt and repaired by the PAA-SA@rGO hydrogel, a 5 × 5 mm2 wound in the full-thickness buccal mucosa of rats can be expeditiously mended within mere 7 days. The theoretical calculations indicate that the PAA-SA@rGO hydrogel can aggregate and express SOX2, PITX1, and PITX2 at the wound site, which has a promoting effect on rapid wound healing. Importantly, this PAA-SA@rGO hydrogel has a fast curative effect and only needs to be applied for the first three days, which significantly improves patient satisfaction during treatment.
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Grafito , Hidrogeles , Cicatrización de Heridas , Hidrogeles/química , Hidrogeles/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Grafito/química , Grafito/farmacología , Ratas , Resinas Acrílicas/química , Mucosa Bucal/metabolismo , Mucosa Bucal/efectos de los fármacos , Ratas Sprague-Dawley , Alginatos/química , Alginatos/farmacología , Conductividad Eléctrica , Antibacterianos/farmacología , Antibacterianos/química , Masculino , HumanosRESUMEN
As a means of communication between immune cells and non-immune cells, Interleukins (ILs) has the main functions of stimulating the proliferation and activation of inflammatory immune cells such as dendritic cells and lymphocytes, promote the development of blood cells and so on. However, dysregulation of ILs expression is a major feature of autoinflammatory diseases. The drugs targeting ILs or IL-like biologics have played an important role in the clinical treatment of autoinflammatory diseases. Nevertheless, the widespread use of IL products may result in significant off-target adverse reactions. Thus, there is a clear need to develop next-generation ILs products in the biomedical field. Fusion proteins are proteins created through the joining of two or more genes that originally coded for separate proteins. Over the last 30 years, there has been increasing interest in the use of fusion protein technology for developing anti-inflammatory drugs. In comparison to single-target drugs, fusion proteins, as multiple targets drugs, have the ability to enhance the cytokine therapeutic index, resulting in improved efficacy over classical drugs. The strategy of preparing ILs or their receptors as fusion proteins is increasingly used in the treatment of autoimmune and chronic inflammation. This review focuses on the efficacy of several fusion protein drugs developed with ILs or their receptors in the treatment of autoinflammatory diseases, in order to illustrate the prospects of this new technology as an anti-inflammatory drug development protocol in the future.
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Enfermedades Autoinflamatorias Hereditarias , Interleucinas , Humanos , Interleucinas/genética , Interleucinas/metabolismo , Citocinas/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Antiinflamatorios/uso terapéuticoRESUMEN
Objective: To review the research progress of the principle and clinical application of keloid core excision technique. Methods: The literature on keloid core excision technique at home and abroad in recent years was extensively reviewed, and the principle, development history, indications, advantages and disadvantages of this technique were summarized, and the existing controversies were analyzed. Results: Keloid core excision is a technique to remove the inner fibrous core from the keloid and cover the defect with the keloidal flap. It reduces the wound tension, yields good aesthetic results in the treatment of ear keloids, and reduces the recurrence rate of keloids combining with adjuvant therapies. Conclusion: The keloid core excision technique has specific advantages, yet its overall efficacy remains controversial. Further studies are imperative to explore the mechanisms regarding keloid recurrence and the vascular supply principles of the keloidal flap. It is also necessary to define appropriate surgical indications and safety protocols of this technique.
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Queloide , Procedimientos de Cirugía Plástica , Humanos , Queloide/cirugía , Queloide/patología , Recurrencia , Colgajos Quirúrgicos/patología , Resultado del Tratamiento , Investigación Biomédica/tendenciasRESUMEN
During embryo implantation, trophoblast cells rely on large amounts of energy produced by glycolysis for their rapid growth and invasion. The disorder of trophoblast metabolism may lead to recurrent spontaneous abortion (RSA). Lactate, which is produced by the glycolysis of trophoblast cells during early pregnancy, can promote the polarization of M2 macrophages and maintain an anti-inflammatory environment at the maternal-fetal interface. Our study found that amine oxidase copper-containing 4 pseudogene (AOC4P) was abnormally increased in villi from RSA patients. It inhibited the glycolysis of trophoblast cells and thus hindered the polarization of M2 macrophages. Further studies showed that AOC4P combines with tumor necrosis factor receptor-associated factor 6 (TRAF6) to upregulate TRAF6 expression. TRAF6 acted as an E3 ubiquitin ligase to promote ubiquitination and degradation of zeste homolog 2 (EZH2). These results provided new insights into the important role played by AOC4P at the maternal-fetal interface.
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Aborto Habitual , Aborto Espontáneo , Amina Oxidasa (conteniendo Cobre) , ARN Largo no Codificante , Femenino , Humanos , Embarazo , Aborto Habitual/metabolismo , Aborto Espontáneo/metabolismo , Amina Oxidasa (conteniendo Cobre)/genética , Amina Oxidasa (conteniendo Cobre)/metabolismo , Proteína Potenciadora del Homólogo Zeste 2/genética , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Macrófagos/metabolismo , Seudogenes , ARN Largo no Codificante/genética , Factor 6 Asociado a Receptor de TNF/metabolismo , Trofoblastos/metabolismo , UbiquitinaciónRESUMEN
Objective: To explore the feasibility of using indocyanine green angiography in mapping the superficial temporal vessels and assisting design and harvesting of the superficial temporal artery based forehead flap. Methods: A clinical data of 14 patients with facial soft tissue defects repaired with superficial temporal artery based forehead flaps between October 2015 and November 2022 was retrospectively analyzed. There were 9 males and 5 females with a median age of 9.5 years (range, 3-38 years). The forehead flaps were used to reconstruct facial soft tissue defects following excision of facial scar (8 cases) or congenital melanocyte nevus (6 cases). The size of defects ranged from 3 cm×2 cm to 24 cm×9 cm. Before operation, the indocyanine green angiography was used to map the superficial temporal artery and vein, and to analyze the relationship of the arteries and veins. The forehead flaps with unilateral superficial temporal fascia as the pedicle was transferred to repair the small facial defect in 2 cases. The facial pedicle contained the frontal branch of the superficial temporal artery and 2 cm of the superficial temporal fascia around the vessel, and the tiny accompanying vein of the frontal branch of the superficial temporal artery was used as the outflow of the flap. The forehead flaps with the skin pedicle including bilateral or unilateral superficial temporal fascia and the overlying skin was pre-expanded and transferred to repair the large facial defect in 12 cases. The skin pedicle contained the frontal branch of superficial temporal artery and one of main branches of superficial temporal vein. Among the 12 cases, the frontal branch of superficial temporal vein was used as the outflow in 4 cases, and the parietal branch was used as the outflow in 8 cases. The size of the flaps ranged from 3 cm×2 cm to 30 cm×13 cm. The skin pedicles were divided at 3 weeks after the flap transfer. Results: Indocyanine green angiography could clearly showed the course and branching of the superficial temporal artery and vein. Individual differences existed in the location where the frontal branch of the superficial temporal artery entered the forehead. The superficial temporal vein had great variability and did not follow the artery. One patient had expander-related complication, which resulted in 3-cm flap necrosis. The necrotic tissue was debrided and repaired with skin grafting. The other flaps totally survived and the incisions healed by first intention. All patients were followed up 2-24 months, with a median of 11.5 months. The color, texture, and thickness of the flaps matched well with those of recipient sites. Hypertrophic scar was not observed in recipient or donor site. All patients were satisfied with the reconstructive outcomes. Conclusion: Indocyanine green angiography can clearly visualize the course and the branches of the superficial temporal arteries and veins, which can help surgeons understand the position, distribution, and concomitant relationship of the superficial temporal vessels, and make a rational surgical plan of the forehead flap.
Asunto(s)
Colgajo Perforante , Traumatismos de los Tejidos Blandos , Masculino , Femenino , Humanos , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Arterias Temporales/cirugía , Verde de Indocianina , Frente/cirugía , Estudios Retrospectivos , Trasplante de Piel , Angiografía , Traumatismos de los Tejidos Blandos/cirugía , Colgajo Perforante/irrigación sanguínea , Resultado del TratamientoRESUMEN
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Ethanol consumption has been reported to reduce morbidity in RA patients, but the mechanism behind it remains unclear. Our results showed that Muribaculaceae was predominant in the gut microbiota of mice after ethanol treatment, and the levels of microbiota metabolite acetate were increased. Acetate reduced arthritis severity in collagen-induced arthritis (CIA) mice, which was associated with a decrease in the articular neutrophils and the myeloperoxidase-deoxyribonucleic acid complex in serum. Meanwhile, in vitro experiments confirmed that acetate affected neutrophil activity by acting on G-protein-coupled receptor 43, which reduced endoplasmic reticulum stress in neutrophils and inhibited neutrophil extracellular traps formation. Furthermore, exogenous acetate reversed CIA mice with exacerbated gut microbial disruption, further confirming that the effect of gut microbial metabolite acetate on neutrophils in vivo is crucial for the immune regulation. Our findings illuminate the metabolic and cellular mechanisms of the gut-joint axis in the regulation of autoimmune arthritis, and may offer alternative avenues to replicate or induce the joint-protective benefits of ethanol without associated detrimental effects.