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Chronic wound healing is a common clinical challenge, characterized by bacterial infection, protracted inflammatory response, oxidative stress, and insufficient neovascularization. Nanozymes have emerged as a promising solution for treating skin wounds due to their antioxidant, antibacterial, and angiogenic properties. In recent years, combining nanozymes with hydrogels to jointly promote wound healing has attracted increasing research interest. However, most of the current nanocomposite hydrogels are still not effective in simultaneously controlling inflammatory, oxidative stress and bacterial invasion in wound healing. Improving the therapeutic functional diversity and efficacy of nanocomposite hydrogels remains a problem that needs to be addressed. In this study, we prepared nanocomposite hydrogels (GelMD-Cur@ZHMCe) by combining methylacrylated gelatin modified with dopamine (GelMD) with Zinc-doped hollow mesoporous cerium oxide nanoparticles loaded with curcumin (Cur@ZHMCe). The resulting hydrogels exhibited excellent water absorption, adhesion, and biocompatibility. In vitro and in vivo studies have demonstrated that GelMD-Cur@ZHMCe has excellent antioxidant, antibacterial, anti-inflammatory and vasculature-promoting properties, which enable it to rapidly promote wound repair. The wound healing rate of the rat total skin defect infection model treated with GelMD-Cur@ZHMCe reached 98.5±4.9â¯% after 14â¯days of treatment. It was demonstrated that this multifunctional nanocomposite hydrogel provides a promising therapeutic strategy for skin repair.
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BACKGROUND: Cartilage metabolism dysregulation is a crucial driver in knee osteoarthritis (KOA). Modulating the homeostasis can mitigate the cartilage degeneration in KOA. Curcumenol, derived from traditional Chinese medicine Curcuma Longa L., has demonstrated potential in enhancing chondrocyte proliferation and reducing apoptosis. However, the specific mechanism of Curcumenol in treating KOA remains unclear. This study aimed to demonstrate the molecular mechanism of Curcumenol in treating KOA based on the transcriptomics and metabolomics, and both in vivo and in vitro experimental validations. MATERIALS AND METHODS: In this study, a destabilization medial meniscus (DMM)-induced KOA mouse model was established. And the mice were intraperitoneally injected with Curcumenol at 4 and 8 mg/kg concentrations. The effects of Curcumenol on KOA cartilage and subchondral was evaluated using micro-CT, histopathology, and immunohistochemistry (IHC). In vitro, OA chondrocytes were induced with 10 µg/mL lipopolysaccharide (LPS) and treated with Curcumenol to evaluate the proliferation, apoptosis, and extracellular matrix (ECM) metabolism through CCK8 assay, flow cytometry, and chondrocyte staining. Furthermore, transcriptomics and metabolomics were utilized to identify differentially expressed genes (DEGs) and metabolites. Finally, integrating multi-omics analysis, virtual molecular docking (VMD), and molecular dynamics simulation (MDS), IHC, immunofluorescence (IF), PCR, and Western blot (WB) validation were conducted to elucidate the mechanism by which Curcumenol ameliorates KOA cartilage degeneration. RESULTS: Curcumenol ameliorated cartilage destruction and subchondral bone loss in KOA mice, promoted cartilage repair, upregulated the expression of COL2 while downregulated MMP3, and improved ECM synthesis metabolism. Additionally, Curcumenol also alleviated the damage of LPS on the proliferation activity and suppressed apoptosis, promoted ECM synthesis. Transcriptomic analysis combined with weighted gene co-expression network analysis (WGCNA) identified a significant downregulation of 19 key genes in KOA. Metabolomic profiling showed that Curcumenol downregulates the expression of d-Alanyl-d-alanine, 17a-Estradiol, Glutathione, and Succinic acid, while upregulating Sterculic acid and Azelaic acid. The integrated multi-omics analysis suggested that Curcumenol targeted KDM6B to regulate downstream protein H3K27me3 expression, which inhibited methylation at the histone H3K27, consequently reducing Succinic acid levels and improving KOA cartilage metabolism homeostasis. Finally, both in vivo and in vitro findings indicated that Curcumenol upregulated KDM6B, suppressed H3K27me3 expression, and stimulated collagen II expression and ECM synthesis, thus maintaining cartilage metabolism homeostasis and alleviating KOA cartilage degeneration. CONCLUSION: Curcumenol promotes cartilage repair and ameliorates cartilage degeneration in KOA by upregulating KDM6B expression, thereby reducing H3K27 methylation and downregulating Succinic Acid, restoring metabolic stability and ECM synthesis.
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Toll receptors are important regulators of insects' innate immune system which, upon binding of pathogen molecules, activate a conserved signal transduction cascade known as the Toll pathway. RNA interference (RNAi) is a powerful tool to study the function of genes via reverse genetics. However, due to the reported refractory of RNAi efficiency in lepidopteran insects, successful reports of silencing of Toll receptors in the silkworm Bombyx mori have not been reported yet. In this study, a Toll receptor of the silkworm Bombyx Toll9-2 (BmToll9-2) was cloned and its expression and function were analyzed. The results showed that BmToll9-2 contains an ectodomain (ECD) with a signal peptide and nine leucine-rich repeats, a transmembrane helix, and a cytoplasmic region with a Toll/interleukin-1 domain. Phylogenetic analysis indicates that BmToll9-2 clusters with other insect Toll9 receptors and mammalian Toll-like receptor 4. Oral infection of exogenous pathogens showed that the Gram-negative bacterium Escherichia coli and its main cell wall component lipopolysaccharide (LPS), as well as the Gram-positive bacterium Staphylococcus aureus and its main cell wall component peptidoglycan, significantly induce BmToll9-2 expression in vivo. LPS also induced the expression of BmToll9-2 in BmN4 cells in vitro. These observations indicate its role as a sensor in the innate immunity to exogenous pathogens and as a pathogen-associated receptor that is responsive to LPS. RNAi of BmToll9-2 was effective in the midgut and epidermis. RNAi-mediated knock-down of BmToll9-2 reduced the weight and growth of the silkworm. Bacterial challenge following RNAi upregulated the expression of BmToll9-2 and rescued the weight differences of the silkworm, which may be related to its participation in the immune response and the regulation of the microbiota in the midgut lumen of the silkworm larvae.
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Bombyx , Escherichia coli , Proteínas de Insectos , Larva , Lipopolisacáridos , Filogenia , Animales , Bombyx/inmunología , Bombyx/genética , Bombyx/crecimiento & desarrollo , Bombyx/microbiología , Bombyx/metabolismo , Larva/inmunología , Larva/crecimiento & desarrollo , Larva/microbiología , Larva/genética , Larva/metabolismo , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Lipopolisacáridos/farmacología , Receptores Toll-Like/metabolismo , Receptores Toll-Like/genética , Inmunidad Innata , Staphylococcus aureus , Tracto Gastrointestinal/inmunología , Tracto Gastrointestinal/microbiología , Tracto Gastrointestinal/metabolismo , Secuencia de Aminoácidos , Interferencia de ARNRESUMEN
Background: Some research have indicated that Bariatric and metabolic surgery (BMS) can reduce the risk of cardiovascular disease (CVD) among individuals with obesity. However, there are few reports available that focuses on assessing effect of BMS on the risk of CVD in Chinese population using multiple models. Objective: This research aims to assess the function of BMS on the risk of CVD in Chinese patients with obesity using multiple CVD risk models. Methods: We performed a retrospective analysis of the basic data and glycolipid metabolism data preoperatively and postoperatively from patients with obesity at our hospital. Subgroup analysis was carried out according to different surgical procedures. Then, the function of BMS on the risk of CVD in the Chinese population was assessed using four models, including: China-PAR risk model, Framingham risk score (FRS), World Health Organization (WHO) risk model, and Globorisk model. Results: We enrolled 64 patients, 24 (37.5%) of whom underwent laparoscopic sleeve gastrectomy (LSG) while 40 (62.5%) underwent Roux-en-Y gastric bypass (RYGB). The 10-year CVD risk for patients calculated using the China-PAR risk model decreased from 6.3% preoperatively to 2.0% at 1 year postoperatively and was statistically significantly different. Similarly, the 10-year CVD risk of patients calculated using the FRS, WHO, Global risk model decreased significantly at 1 year postoperatively compared to preoperatively. When the FRS risk model was used to calculate the patients' 30-year postoperative CVD risk, there was a significant decrease at 1 year after surgery compared to the preoperative period. When employing various models to evaluate the 10-year CVD risk for LSG and RYGB, no statistically significant difference was found in the 1-year postoperative RRR between the procedures. Conclusion: The CVD risk after BMS was significantly reduced compared to preoperatively. In terms of improving cardiovascular risk, SG and RYGB appear to be equally effective.
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In recent years, thanks to the development of integrated circuits, clinical medicine has witnessed significant advancements, enabling more efficient and intelligent treatment approaches. Particularly in the field of neuromedical, the utilization of brain-machine interfaces (BMI) has revolutionized the treatment of neurological diseases such as amyotrophic lateral sclerosis, cerebral palsy, stroke, or spinal cord injury. The BMI acquires neural signals via recording circuits and analyze them to regulate neural stimulator circuits for effective neurological treatment. However, traditional BMI designs, which are often isolated, have given way to closed-loop brain-machine interfaces (CL-BMI) as a contemporary development trend. CL-BMI offers increased integration and accelerated response speed, marking a significant leap forward in neuromedicine. Nonetheless, this advancement comes with its challenges, notably the stimulation artifacts (SA) problem inherent to the structural characteristics of CL-BMI, which poses significant challenges on the neural recording front-ends (NRFE) site. This paper aims to provide a comprehensive overview of technologies addressing artifacts in the NRFE site within CL-BMI. Topics covered will include: (1) understanding and assessing artifacts; (2) exploring the impact of artifacts on traditional neural recording front-ends; (3) reviewing recent technological advancements aimed at addressing artifact-related issues; (4) summarizing and classifying the aforementioned technologies, along with an analysis of future trends.
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BACKGROUND: Malignant cerebral edema (MCE) is associated with both net water uptake (NWU) and infarct volume. We hypothesized that NWU weighted by the affected Alberta Stroke Program Early Computed Tomography Score (ASPECTS) regions could serve as a quantitative imaging biomarker of aggravated edema development in acute ischemic stroke with large vessel occlusion (LVO). The aim of this study was to evaluate the performance of weighted NWU (wNWU) to predict MCE in patients with mechanical thrombectomy (MT). METHODS: We retrospectively analyzed consecutive patients who underwent MT due to LVO. NWU was computed from nonenhanced computed tomography scans upon admission using automated ASPECTS software. wNWU was derived by multiplying NWU with the number of affected ASPECTS regions in the ischemic hemisphere. Predictors of MCE were assessed through multivariate logistic regression analysis and receiver operating characteristic curves. RESULTS: NWU and wNWU were significantly higher in MCE patients than in non-MCE patients. Vessel recanalization status influenced the performance of wNWU in predicting MCE. In patients with successful recanalization, wNWU was an independent predictor of MCE (adjusted odds ratio 1.61; 95% confidence interval [CI] 1.24-2.09; P < 0.001). The model integrating wNWU, National Institutes of Health Stroke Scale, and collateral score exhibited an excellent performance in predicting MCE (area under the curve 0.80; 95% CI 0.75-0.84). Among patients with unsuccessful recanalization, wNWU did not influence the development of MCE (adjusted odds ratio 0.99; 95% CI 0.60-1.62; P = 0.953). CONCLUSIONS: This study revealed that wNWU at admission can serve as a quantitative predictor of MCE in LVO with successful recanalization after MT and may contribute to the decision for early intervention.
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Edema Encefálico , Humanos , Edema Encefálico/diagnóstico por imagen , Edema Encefálico/etiología , Masculino , Femenino , Anciano , Estudios Retrospectivos , Persona de Mediana Edad , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/cirugía , Anciano de 80 o más Años , Trombectomía/métodos , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Background: Skin wounds are a prevalent issue that can have severe health consequences if not treated correctly. Nanozymes offer a promising therapeutic approach for the treatment of skin wounds, owing to their advantages in regulating redox homeostasis to reduce oxidative damage and kill bacteria. These properties make them an effective treatment option for skin wounds. However, most of current nanozymes lack the capability to simultaneously address inflammation, oxidative stress, and bacterial infection during the wound healing process. There is still great potential for nanozymes to increase their therapeutic functional diversity and efficacy. Methods: Herein, copper-doped hollow mesopores cerium oxide (Cu-HMCe) nanozymes with multifunctional of antioxidant, antimicrobial and pro-vascularity is successfully prepared. Cu-HMCe can be efficiently prepared through a simple and rapid solution method and displays sound physiological stability. The biocompatibility, pro-angiogenic, antimicrobial, and antioxidant properties of Cu-HMCe were assessed. Moreover, a full-thickness skin defect infection model was utilized to investigate the wound healing capacity, as well as anti-inflammatory and pro-angiogenic properties of nanozymes in vivo. Results: Both in vitro and in vivo experiments have substantiated Cu-HMCe's remarkable biocompatibility. Moreover, Cu-HMCe possesses potent antioxidant enzyme-like catalytic activity, effectively clearing DPPH radicals (with a scavenging rate of 80%), hydroxyl radicals, and reactive oxygen species. Additionally, Cu-HMCe exhibits excellent antimicrobial and pro-angiogenic properties, with over 70% inhibition of both E. coli and S. aureus. These properties collectively promote wound healing, and the wound treated with Cu-HMCe achieved a closure rate of over 90% on the 14th day. Conclusion: The results indicate that multifunctional Cu-HMCe with antioxidant, antimicrobial, and pro-angiogenic properties was successfully prepared and exhibited remarkable efficacy in promoting wound healing. This nanozymes providing a promising strategy for skin repair.
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Antiinfecciosos , Antioxidantes , Antioxidantes/farmacología , Cobre/farmacología , Escherichia coli , Staphylococcus aureus , Antiinfecciosos/farmacología , Antibacterianos/farmacología , HidrogelesRESUMEN
Alzheimer's disease (AD) and osteoarthritis (OA) are both senile degenerative diseases. Clinical studies have found that OA patients have a significantly increased risk of AD in their later life. This study hypothesized that chronic aseptic inflammation might lead to AD in KOA patients. However, current research has not yet clarified the potential mechanism between AD and KOA. Therefore, this study intends to use KOA transcriptional profiling and single-cell sequencing analysis technology to explore the molecular mechanism of KOA affecting AD development, and screen potential molecular biomarkers and drugs for the prediction, diagnosis, and prognosis of AD in KOA patients. It was found that the higher the expression of TXNIP, MMP3, and MMP13, the higher the risk coefficient of AD was. In addition, the AUC of TXNIP, MMP3, and MMP13 were all greater than 0.70, which had good diagnostic significance for AD. Finally, through the virtual screening of core proteins in FDA drugs and molecular dynamics simulation, it was found that compound Cobicistat could be targeted to TXNIP, Itc could be targeted to MMP3, and Isavuconazonium could be targeted to MMP13. To sum up, TXNIP, MMP3, and MMP13 are prospective molecular markers in KOA with AD, which could be used to predict, diagnose, and prognosis.
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Introduction: As an effective alternative choice to traditional mono-therapy, multifunctional nanoplatforms hold great promise for cancer therapy. Based on the strategies of Fenton-like reactions and reactive oxygen species (ROS)-mediated therapy, black phosphorus (BP) nanoplatform BP@Cu2O@L-Arg (BCL) co-assembly of cuprous oxide (Cu2O) and L-Arginine (L-Arg) nanoparticles was developed and evaluated for synergistic cascade breast cancer therapy. Methods: Cu2O particles were generated in situ on the surface of the BP nanosheets, followed by L-Arg incorporation through electrostatic interactions. In vitro ROS/nitric oxide (NO) generation and glutathione (GSH) depletion were evaluated. In vitro and in vivo anti-cancer activity were also assessed. Finally, immune response of BCL under ultrasound was investigated. Results: Cu2O was incorporated into BP to exhaust the overexpressed intracellular GSH in cancer cells via the Fenton reaction, thereby decreasing ROS consumption. Apart from being used as biocompatible carriers, BP nanoparticles served as sonosensitizers to produce excessive ROS under ultrasound irradiation. The enhanced ROS accumulation accelerated the oxidation of L-Arg, which further promoted NO generation for gas therapy. In vitro experiments revealed the outstanding therapeutic killing effects of BCL under ultrasound via mechanisms involving GSH deletion and excessive ROS and NO generation. In vivo studies have illustrated that the nanocomplex modified the immune response by promoting macrophage and CD8+ cell infiltration and inhibiting MDSC infiltration. Discussion: BCL nanoparticles exhibited multifunctional characteristics for GSH depletion-induced ROS/NO generation, making a new multitherapy strategy for cascade breast cancer therapy.
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Nanopartículas , Neoplasias , Humanos , Especies Reactivas de Oxígeno , Óxido Nítrico , Arginina , Glutatión , Línea Celular Tumoral , Peróxido de Hidrógeno , Microambiente TumoralRESUMEN
BACKGROUND: The existence of anxiety and depression is not conducive to the rehabilitation of patients, so it is particularly important to apply reasonable and effective nursing methods in operating room to calm the negative emotions of patients. This study aimed to investigate the impact of operating room care utilizing the Wutong mode on the anxiety and depression levels of patients undergoing abdominal surgery. Methods: The study included 167 patients who underwent abdominal surgery at our hospital from April 2021 to April 2023. These individuals were selected as the research subjects. Based on distinct perioperative management programs, the patients were categorized into the control group (comprising 85 patients receiving conventional perioperative management) and the study group (consisting of 82 patients undergoing operating room care based on the Wutong mode). Comprehensive baseline data, as well as scores from the Pittsburgh Sleep Quality Index (PSQI), Beck Depression Inventory (BDI), Self-Rating Anxiety Scale (SAS), General Self-Efficacy Scale-6 (GSE-6), and Short-Form-36 Health Survey (SF-36), were collected from all participants. A comparative analysis was performed on sleep status, depression levels, anxiety levels, self-efficacy, and quality of life between the two groups. Results: Following the intervention, the PSQI scores, as well as BDI and SAS scores of patients in both groups, were significantly reduced compared to pre-intervention levels (p < 0.001). Notably, the study group exhibited markedly lower PSQI scores, BDI scores, and SAS scores compared to the control group post-intervention (p < 0.001). Additionally, the GSE-6 scores of patients in both groups showed a substantial increase after the intervention compared to pre-intervention levels (p < 0.001). The study group demonstrated significantly higher GSE-6 scores and SF-36 scores than the control group after the intervention (p < 0.001). Conclusion: The Wutong mode-based operating room care has a pronounced impact on patients undergoing abdominal surgery, demonstrating clear clinical application value. This finding offers valuable insights for the development and selection of perioperative nursing plans for patients, providing a significant reference point for healthcare practitioners.
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Quirófanos , Calidad de Vida , Humanos , Estudios Retrospectivos , Ansiedad/epidemiología , Ansiedad/etiología , Ansiedad/psicología , SueñoRESUMEN
BACKGROUND: Bariatric surgery is an effective treatment for morbid obesity. However, a subset of individuals seeking bariatric surgery may exhibit a metabolically healthy obesity (MHO) phenotype, suggesting that they may not experience metabolic complications despite being overweight. OBJECTIVE: This study aimed to determine the prevalence and metabolic features of MHO in a population undergoing bariatric surgery. METHODS: A representative sample of 665 participants aged 14 or older who underwent bariatric surgery at our center from January 1, 2010 to January 1, 2020 was included in this cohort study. MHO was defined based on specific criteria, including blood pressure, waist-to-hip ratio, and absence of diabetes. RESULTS: Among the 665 participants, 80 individuals (12.0%) met the criteria for MHO. Female gender (P = .021) and younger age (P < .001) were associated with a higher likelihood of MHO. Smaller weight and BMI were observed in individuals with MHO. However, a considerable proportion of those with MHO exhibited other metabolic abnormalities, such as fatty liver (68.6%), hyperuricemia (55.3%), elevated lipid levels (58.7%), and abnormal lipoprotein levels (88%). CONCLUSION: Approximately 1 in 8 individuals referred for bariatric surgery displayed the phenotype of MHO. Despite being metabolically healthy based on certain criteria, a significant proportion of individuals with MHO still exhibited metabolic abnormalities, such as fatty liver, hyperuricemia, elevated lipid levels, and abnormal lipoprotein levels, highlighting the importance of thorough metabolic evaluation in this population.
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Cirugía Bariátrica , Obesidad Metabólica Benigna , Obesidad Mórbida , Humanos , Femenino , Masculino , Adulto , Prevalencia , Factores de Riesgo , Persona de Mediana Edad , Obesidad Metabólica Benigna/epidemiología , Obesidad Mórbida/cirugía , Obesidad Mórbida/metabolismo , Estudios de Cohortes , Adulto Joven , AdolescenteRESUMEN
BACKGROUND: Assessing the 3-dimensional (3D) relationship between critical anatomical structures and the surgical channel can help select percutaneous endoscopic lumbar discectomy (PELD) approaches, especially at the L5/S1 level. However, previous evaluation methods for PELD were mainly assessed using 2-dimensional (2D) medical images, making the understanding of the 3D relationship of lumbosacral structures difficult. Artificial intelligence based on automated magnetic resonance (MR) image segmentation has the benefit of 3D reconstruction of medical images. OBJECTIVES: We developed and validated an artificial intelligence-based MR image segmentation method for constructing a 3D model of lumbosacral structures for selecting the appropriate approach of percutaneous endoscopic lumbar discectomy at the L5/S1 level. STUDY DESIGN: Three-dimensional reconstruction study using artificial intelligence based on MR image segmentation. SETTING: Spine and radiology center of a university hospital. METHODS: Fifty MR data samples were used to develop an artificial intelligence algorithm for automatic segmentation. Manual segmentation and labeling of vertebrae bone (L5 and S1 vertebrae bone), disc, lumbosacral nerve, iliac bone, and skin at the L5/S1 level by 3 experts were used as ground truth. Five-fold cross-validation was performed, and quantitative segmentation metrics were used to evaluate the performance of artificial intelligence based on the MR image segmentation method. The comparison analysis of quantitative measurements between the artificial intelligence-derived 3D (AI-3D) models and the ground truth-derived 3D (GT-3D) models was used to validate the feasibility of 3D lumbosacral structures reconstruction and preoperative assessment of PELD approaches. RESULTS: Artificial intelligence-based automated MR image segmentation achieved high mean Dice Scores of 0.921, 0.924, 0.885, 0.808, 0.886, and 0.816 for L5 vertebrae bone, S1 vertebrae bone, disc, lumbosacral nerves, iliac bone, and skin, respectively. There were no significant differences between AI-3D and GT-3D models in quantitative measurements. Comparative analysis of quantitative measures showed a high correlation and consistency. LIMITATIONS: Our method did not involve vessel segmentation in automated MR image segmentation. Our study's sample size was small, and the findings need to be validated in a prospective study with a large sample size. CONCLUSION: We developed an artificial intelligence-based automated MR image segmentation method, which effectively segmented lumbosacral structures (e.g., L5 vertebrae bone, S1 vertebrae bone, disc, lumbosacral nerve, iliac bone, and skin) simultaneously on MR images, and could be used to construct a 3D model of lumbosacral structures for choosing an appropriate approach of PELD at the L5/S1 level.
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Discectomía Percutánea , Desplazamiento del Disco Intervertebral , Humanos , Endoscopía/métodos , Desplazamiento del Disco Intervertebral/cirugía , Inteligencia Artificial , Discectomía Percutánea/métodos , Estudios Prospectivos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Estudios RetrospectivosRESUMEN
Toll, immune deficiency and prophenoloxidase cascade represent vital immune signaling pathways in insects. Peptidoglycan recognition proteins (PGRPs) are innate immune receptors that activate and regulate the immune signaling pathways. Previously, we reported that BmPGPR-L4 was induced in the silkworm Bombyx mori larvae by bacteria and peptidoglycan challenges. Here, we focused on the function of BmPGRP-L4 in regulating the expression of antimicrobial peptides (AMPs). The hemolymph from BmPGRP-L4-silenced larvae exhibited an enhanced inhibitory effect on the growth of Escherichia coli, either by growth curve or inhibitory zone experiments. Coincidentally, most of the AMP genes were upregulated after RNAi of BmPGRP-L4. Oral administration of heat-inactivated E. coli and Staphylococcus aureus after RNAi of BmPGRP-L4 resulted in the increased expression of BmPGRP-L4 in different tissues of the silkworm larvae, revealing an auto-regulatory mechanism. By contrast, the expression of most AMP genes was downregulated by oral bacterial administration after RNAi of BmPGRP-L4. The above results demonstrate that BmPGRP-L4 recognizes bacterial pathogen-associated molecular patterns and negatively regulates AMP expression to achieve immunological homeostasis. As a negative regulator, BmPGPR-L4 is proposed to be involved in the feedback regulation of the immune signaling pathways of the silkworm to prevent excessive activation of the immune response.
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Bombyx , Animales , Bombyx/metabolismo , Inmunidad Humoral , Escherichia coli , Bacterias/metabolismo , Proteínas de Insectos/metabolismo , LarvaRESUMEN
Osteoporosis (OP) is a prevalent age-related disease that is characterized by a decrease in bone mineral density (BMD) and systemic bone microarchitectural disorders. With age, senescent cells accumulate and exhibit the senescence-associated secretory phenotype (SASP) in bone tissue, leading to the imbalance of bone homeostasis, osteopenia, changes in trabecular bone structure, and increased bone fragility. Cellular senescence in the bone microenvironment involves osteoblasts, osteoclasts, and bone marrow mesenchymal stem cells (BMSCs), whose effects on bone homeostasis are regulated by epigenetics. Therefore, the epigenetic regulatory mechanisms of cellular senescence have received considerable attention as potential targets for preventing and treating osteoporosis. In this paper, we systematically review the mechanisms of aging-associated epigenetic regulation in osteoporosis, emphasizing the impact of epigenetics on cellular senescence, and summarize three current methods of targeting cellular senescence, which is helpful better to understand the pathogenic mechanisms of cellular senescence in osteoporosis and provides strategies for the development of epigenetic drugs for the treatment of osteoporosis.
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Senescencia Celular , Epigénesis Genética , Osteoporosis , Humanos , Osteoporosis/genética , Senescencia Celular/genética , Animales , Envejecimiento/genética , Envejecimiento/fisiologíaRESUMEN
BACKGROUND: The understanding of the heterogeneous cellular microenvironment of colonic polyps in paediatric patients with solitary juvenile polyps (SJPs), polyposis syndrome (PJS) and Peutz-Jeghers syndrome (PJS) remains limited. METHODS: We conducted single-cell RNA sequencing and multiplexed immunohistochemistry (mIHC) analyses on both normal colonic tissue and different types of colonic polyps obtained from paediatric patients. RESULTS: We identified both shared and disease-specific cell subsets and expression patterns that played important roles in shaping the unique cellular microenvironments observed in each polyp subtype. As such, increased myeloid, endothelial and epithelial cells were the most prominent features of SJP, JPS and PJS polyps, respectively. Noticeably, memory B cells were increased, and a cluster of epithelial-mesenchymal transition (EMT)-like colonocytes existed across all polyp subtypes. Abundant neutrophil infiltration was observed in SJP polyps, while CX3CR1hi CD8+ T cells and regulatory T cells (Tregs) were predominant in SJP and JPS polyps, while GZMAhi natural killer T cells were predominant in PJS polyps. Compared with normal colonic tissues, myeloid cells exhibited specific induction of genes involved in chemotaxis and interferon-related pathways in SJP polyps, whereas fibroblasts in JPS polyps had upregulation of myofiber-associated genes and epithelial cells in PJS polyps exhibited induction of a series of nutrient absorption-related genes. In addition, the TNF-α response was uniformly upregulated in most cell subsets across all polyp subtypes, while endothelial cells and fibroblasts separately showed upregulated cell adhesion and EMT signalling in SJP and JPS polyps. Cell-cell interaction network analysis showed markedly enhanced intercellular communication, such as TNF, VEGF, CXCL and collagen signalling networks, among most cell subsets in polyps, especially SJP and JPS polyps. CONCLUSION: These findings strengthen our understanding of the heterogeneous cellular microenvironment of polyp subtypes and identify potential therapeutic approaches to reduce the recurrence of polyps in children.
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Pólipos del Colon , Humanos , Niño , Linfocitos T CD8-positivos , Células Endoteliales , Microambiente Celular , Comunicación CelularRESUMEN
Ginger (Zingiber officinale Roscoe) has traditionally been used as a cooking spice and herbal medicine for treating nausea and vomiting. More recently, ginger was found to effectively reduce the risk of diseases such as gastroenteritis, migraine, gonarthritis, etc., due to its various bioactive compounds. 6-Shogaol, the pungent phenolic substance in ginger, is the most pharmacologically active among such compounds. The aim of the present study was to review the pharmacological characteristic of 6-shogaol, including the properties of anti-inflammatory, antioxidant and antitumour, and its corresponding molecular mechanism. With its multiple mechanisms, 6-shogaol is considered a beneficial natural compound, and therefore, this review will shed some light on the therapeutic role of 6-shogaol and provide a theoretical basis for the development and clinical application of 6-shogaol.
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Antiinflamatorios , Antioxidantes , Catecoles , Zingiber officinale , Humanos , Catecoles/farmacología , Catecoles/química , Zingiber officinale/química , Antioxidantes/farmacología , Antioxidantes/química , Antiinflamatorios/farmacología , Antiinflamatorios/química , Animales , Extractos Vegetales/farmacología , Extractos Vegetales/química , Antineoplásicos/farmacología , Antineoplásicos/químicaRESUMEN
Lipoma is a common type of benign soft tissue tumor that can occur in the shoulders, neck and back, in addition to other body parts. The Retzius space is a small anatomical space between the pubic symphysis and the bladder located extraperitoneally and filled with loose fatty connective tissue. Giant lipomas are rare in the Retzius space. A 61-year-old Chinese male arrived at Beijing Yanhua Hospital (Beijing, China) due to frequent urination, and CT scan images of the lower abdomen observed a large pelvic mass and left inguinal hernia. Preoperative clinical manifestations and auxiliary examination suggested that the tumor originated from the urinary bladder wall. The maximum tumor diameter was ~25 cm and abdominal pressure was increased. Therefore, laparoscopic pelvic tumor resection combined with inguinal hernia repair was attempted. Intraoperatively, the tumor was found to originate from the Retzius space and the postoperative pathological diagnosis was lipoma. The present case report may serve as a reference for minimally invasive treatment of this type of rare disease in future.
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Solar-driven biosynthesis and bioconversion are essential for achieving sustainable resources and renewable energy. These processes harness solar energy to produce biomass, chemicals, and fuels. While they offer promising avenues, some challenges and limitations should be investigated and addressed for their improvement and widespread adoption. These include the low utilization of light energy, the inadequate selectivity of products, and the limited utilization of inorganic carbon/nitrogen sources. Organic semiconducting polymers offer a promising solution to these challenges by collaborating with natural microorganisms and developing artificial photosynthetic biohybrid systems. In this Perspective, we highlight the latest advancements in the use of appropriate organic semiconducting polymers to construct artificial photosynthetic biohybrid systems. We focus on how these systems can enhance the natural photosynthetic efficiency of photosynthetic organisms, create artificial photosynthesis capability of nonphotosynthetic organisms, and customize the value-added chemicals of photosynthetic synthesis. By examining the structure-activity relationships and emphasizing the mechanism of electron transfer based on organic semiconducting polymers in artificial photosynthetic biohybrid systems, we aim to shed light on the potential of this novel strategy for artificial photosynthetic biohybrid systems. Notably, these coupling strategies between organic semiconducting polymers and organisms during artificial photosynthetic biohybrid systems will pave the way for a more sustainable future with solar fuels and chemicals.
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BACKGROUND: There are accumulating type 2 diabetes patients who have osteoporosis simultaneously. More effective therapeutic strategies should be discovered. Biochanin A (BCA) has been indicated that can play a role in improving metabolic disorders of type 2 diabetes and preventing osteoporosis. But whether BCA can treat type 2 diabetic osteoporosis has not been studied. PURPOSE: To investigate if the BCA can protect against type 2 diabetic osteoporosis and clarify the mechanism. METHODS: Micro-CT and histology assays were performed to detect the trabecular bone and analyze the bone histomorphology effect of BCA. CCK-8 assay was performed to detect the toxicity of BCA. TRAcP staining, immunofluorescence and hydroxyapatite resorption assay were used to observe osteoclasts differentiation and resorptive activity. Molecular docking provided evidence about BCA regulating the MAPK axis via prediction by the algorithm. QRT-PCR and Western Blotting were utilized to detect the expression of osteoclastogenesis-related markers and MAPK signaling pathway. RESULTS: Accumulation of bone volume after BCA treatment could be found based on the 3D reconstruction. Besides, there were fewer osteoclasts in db/db mice treated with BCA than db/db mice treated with saline. In vitro, we found that BCA hadn't toxicity in osteoclasts precursor, but also inhibited differentiation of osteoclasts. Further, we found that BCA suppresses osteoclastogenesis via ROS/MAPK signaling pathway. CONCLUSION: BCA can prevent type 2 diabetic osteoporosis by restricting osteoclast differentiation via ROS/MAPK signaling pathway.
Asunto(s)
Diabetes Mellitus Tipo 2 , Osteogénesis , Animales , Ratones , Humanos , Simulación del Acoplamiento Molecular , Especies Reactivas de Oxígeno , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Transducción de SeñalRESUMEN
The accurate and effective identification of hydrogen sulfide holds great significance for environmental monitoring. Azide-binding fluorescent probes are powerful tools for hydrogen sulfide detection. We combined the 2'-Hydroxychalcone scaffold with azide moiety to construct probe Chal-N3, the electron-withdrawing azide moiety was utilized to block the ESIPT process of 2'-Hydroxychalcone and quenches the fluorescence. The fluorescent probe was triggered with the addition of hydrogen sulfide, accompanied by great fluorescence intensity enhancement with a large Stokes shift. With excellent fluorescence properties including high sensitivity, specificity selectivity, and wider pH range tolerance, the probe was successfully applied to natural water samples.