ABSTRACT
Contrary to the initial belief that myofibroblasts are terminally differentiated cells, myofibroblasts have now been widely recognized as an activation state that is reversible. Therefore, strategies targeting myofibroblast to be a quiescent state may be an effective way for antihypertrophic scar therapy. Graphene quantum dots (GQDs), a novel zero-dimensional and carbon-based nanomaterial, have recently garnered significant interest in nanobiomedicine, owing to their excellent biocompatibility, tunable photoluminescence, and superior physiological stability. Although multiple nanoparticles have been used to alleviate hypertrophic scars, a GQD-based therapy has not been reported. Our in vivo studies showed that GQDs exhibited significant antiscar efficacy, with scar appearance improvement, collagen reduction and rearrangement, and inhibition of myofibroblast overproliferation. Further in vitro experiments revealed that GQDs inhibited α-SMA expression, collagen synthesis, and cell proliferation and migration, inducing myofibroblasts to become quiescent fibroblasts. Mechanistic studies have demonstrated that the effect of GQDs on myofibroblast proliferation blocked cell cycle progression by disrupting the cyclin-CDK-E2F axis. This study suggests that GQDs, which promote myofibroblast-to-fibroblast transition, could be a novel antiscar nanomedicine for the treatment of hypertrophic scars and other types of pathological fibrosis.
Subject(s)
Cell Proliferation , Cicatrix, Hypertrophic , Graphite , Myofibroblasts , Quantum Dots , Quantum Dots/chemistry , Myofibroblasts/drug effects , Myofibroblasts/pathology , Myofibroblasts/metabolism , Graphite/chemistry , Graphite/pharmacology , Cicatrix, Hypertrophic/drug therapy , Cicatrix, Hypertrophic/pathology , Cell Proliferation/drug effects , Animals , Humans , Mice , Collagen/chemistry , Cell Movement/drug effectsABSTRACT
Diabetic wounds, characterized by prolonged inflammation and impaired vascularization, are a serious complication of diabetes. This study aimed to design a gelatin methacrylate (GelMA) hydrogel for the sustained release of netrin-1 and evaluate its potential as a scaffold to promote diabetic wound healing. The results showed that netrin-1 was highly expressed during the inflammation and proliferation phases of normal wounds, whereas it synchronously exhibited aberrantly low expression in diabetic wounds. Neutralization of netrin-1 inhibited normal wound healing, and the topical application of netrin-1 accelerated diabetic wound healing. Mechanistic studies demonstrated that netrin-1 regulated macrophage heterogeneity via the A2bR/STAT/PPARγ signaling pathway and promoted the function of endothelial cells, thus accelerating diabetic wound healing. These data suggest that netrin-1 is a potential therapeutic target for diabetic wounds.
ABSTRACT
Silver (Ag) nanowires, as an important one-dimensional (1D) nanomaterial, have garnered wide attention, owing to their applications in electronics, optoelectronics, sensors, and other fields. In this study, an alternative hydrothermal route was developed to synthesize Ag nanowires via modified reduction of Ag+. Silver sulfamate plays an important role in the formation of Ag nanowires via controlled release of free Ag+. Results of controlled experiments and characterizations such as UV-vis spectroscopy, FTIR, XPS, and 1H NMR revealed that sulfamic acid does not function as a reductant, supporting by the generation of free Ag+ instead of Ag nanostructures in hydrothermally treated silver sulfamate solution. The initial reduction of Ag+ was induced by the combination of poly (vinylpyrrolidone) (PVP) end group and degradation products. This phenomenon was supported by abundant free Ag+ in the mixed preheated silver sulfamatic and preheated PVP aqueous solutions, indicating a second and distinct Ag+ autocatalytic reduction. Thus, the roles of different reagents and Ag+ reduction must be studied for nanomaterial syntheses.
ABSTRACT
The abuse of olaquindox (OLA) as both an antimicrobial agent and a growth promoter poses significant threats to the environment and human health. While nanoreactors have proven effective in hazard detection, their widespread adoption has been hindered by tedious chemical processes and limited functionality. In this study, we introduce a novel green self-assembly strategy utilizing invertase, horseradish peroxidase, antibodies, and gold nanoclusters to form an aggregation-induced emission-type zeolitic imidazolate framework-8 nanoreactor. The results demonstrate that the lateral flow immunoassay not only allows for qualitative naked eye detection but also enables optical analysis through the fluorescence generated by aggregated gold nanoclusters and enzyme-catalyzed enhancement of visible colorimetric signals. To accommodate more detection scenarios, the photothermal effects and redox reactions of the nanoreactor can fulfill the requirements of thermal sensing and electrochemical analysis for smartphone applications. Remarkably, the proposed approach achieves a detection limit 17 times lower than conventional methods. Besides, the maximum linear range spans from 0.25 to 5 µg/L with high specificity, and the recovery is 85.2-112.9% in environmental water and swine urine. The application of this high-performance nanoreactor opens up avenues for the construction of multifunctional biosensors with great potential in monitoring hazardous materials.
Subject(s)
Quinoxalines , Smartphone , Zeolites , Animals , Bionics , Gold , Nanotechnology , SwineABSTRACT
BACKGROUND: Plantar fasciitis (PF) is the most common cause of heel pain. Among conservative treatments, extracorporeal shock wave therapy (ESWT) is considered effective for refractory PF. Studies have shown that applying ESWT to the trigger points (TrPs) in the triceps surae may play an important role in pain treatment in patients with PF. Therefore, the purpose of this study was to combine the concept of trigger points and ESWT to explore the effect of this combination on plantar temperature and pressure in patients with PF. METHODS: After applying inclusion and exclusion criteria, 86 patients with PF were recruited from the pain clinic of Huadong Hospital, Fudan University and randomly divided into experimental (n = 43) and control groups (n = 43). The experimental group was treated with extracorporeal shock waves to treat the medial heel pain point and the gastrocnemius and soleus TrPs. The control group was only treated with extracorporeal shock waves at the medial heel pain point. The two groups were treated twice with an interval of 1 week. Primary measurements included a numerical rating scale (NRS) score (overall, first step, heel pain during daily activities), and secondary measurements included heel temperature, Roles-Maudsley score (RMS), and plantar pressure. All assessments were performed before treatment (i.e., baseline) and 6 and 12 weeks after treatment. RESULTS: During the trial, 3 patients in the experimental group withdrew from the study, 2 due to interruption of the course of treatment by the COVID-19 epidemic and 1 due to personal reasons. In the control group, 3 patients fell and were removed due to swelling of the heel. Therefore, only 80 patients with PF were finally included. After treatment, the two groups showed good results in NRS score (overall, first step, heel pain during daily activities), RMS, and plantar temperature, especially in the experimental group, who showed a significantly better effect than the control group. CONCLUSION: ESWT of the heel combined with the triceps trigger point of the calf can more effectively improve the pain, function and quality of life of refractory PF than ESWT of the heel alone. In addition, ESWT of the heel combined with the triceps trigger point of the calf can effectively reduce the skin temperature of the heel on the symptomatic side, indicating that the heel temperature as measured by infrared thermal imaging may be used as an independent tool to evaluate the therapeutic effect for patients with chronic PF. Although extracorporeal shock waves combined with TrPs treatment can cause changes in the patients' gait structure, plantar pressure is still difficult to use as an independent tool to evaluate the therapeutic effect for PF. TRIAL REGISTRATION: Registered in the Chinese Clinical Trial Registry ( www.chictr.org.cn ) on 12/17/2021 with the following code: ChiCTR-INR-2,100,054,439.
Subject(s)
Fasciitis, Plantar , Humans , Fasciitis, Plantar/complications , Heel , Trigger Points , Quality of Life , Temperature , Treatment Outcome , Pain/etiologyABSTRACT
Chronic diabetic wounds are a serious complication of diabetes and often result in limb amputations and confer high mortality rates. The proinflammatory secretome in the wound perpetuates defective neovascularization and contributes to dysregulated tissue repair. This study aims to design a gelatin methacrylamide (GelMA) hydrogel to sustained the release of grancalcin-neutralizing antibody (GCA-NAb) and evaluate it as a potential scaffold to promote diabetic wound healing. Results show that the expression of grancalcin(GCA), a protein secreted by bone marrow-derived immune cells, is elevated in the wound sites of individuals and animals with diabetic ulcers. Genetic inhibition of grancalcin expression accelerates vascularization and healing in an animal model. Mechanistic studies show that grancalcin binds to transient receptor potential melastatin 8(TRPM8) and partially inactivates its downstream signaling pathways, thereby impairing angiogenesis in vitro and ex vivo. Systemic or topical administration of a GCA-NAb accelerate wound repair in mice with diabetes. The data suggest that GCA is a potential therapeutic target for the treatment of diabetic ulcers.
Subject(s)
Calcium-Binding Proteins , Diabetes Mellitus , Animals , Mice , Angiogenesis , Diabetes Complications , Diabetes Mellitus/drug therapy , Neovascularization, Pathologic/drug therapy , Ulcer , Wound Healing/physiology , Calcium-Binding Proteins/antagonists & inhibitorsABSTRACT
PURPOSE: This study is aimed to delve into the crucial proteins associated with hormonal osteonecrosis of the femoral head (ONFH) and its intra-articular lesions through data-independent acquisition (DIA) proteomics and bioinformatics analysis. METHODS: We randomly selected samples from eligible ONFH patients and collected samples from the necrotic area of the femoral head and load-bearing cartilage. The control group comprised specimens from the same location in patients with femoral neck fractures. With DIA proteomics, we quantitatively and qualitatively tested both groups and analyzed the differentially expressed proteins (DEPs) between groups. Additionally, we enriched the analysis of DEP functions using gene ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways and verified the key proteins in ONFH through Western blot. RESULTS: Proteomics experiment uncovered 937 common DEPs (422 upregulated and 515 downregulated) between the two groups. These DEPs mainly participate in biological processes such as hidden attributes, catalytic activity, molecular function regulators, and structural molecule activity, and in pathways such as starch and sucrose metabolism, ECM-receptor interaction, PI3K-Akt signaling, complement and coagulation cascades, IL-17 signaling, phagosome, transcriptional misregulation in cancers, and focal adhesion. Through protein-protein interaction network target gene analysis and Western blot validation, we identified C3, MMP9, APOE, MPO, LCN2, ELANE, HPX, LTF, and THBS1 as key proteins in ONFH. CONCLUSIONS: With DIA proteomics and bioinformatics analysis, this study reveals the molecular mechanisms of intra-articular lesions in ONFH. A correlation in the necrotic area and load-bearing cartilage of ONFH at ARCO stages IIIB-IV as well as potential key regulatory proteins was identified. These findings will help more deeply understand the pathogenesis of ONFH and may provide important clues for seeking more effective treatment strategies.
Subject(s)
Femur Head Necrosis , Osteonecrosis , Humans , Femur Head Necrosis/metabolism , Femur Head/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proteomics , Osteonecrosis/genetics , Cartilage/pathologyABSTRACT
OBJECTIVE: Osteonecrosis of the femoral head (ONFH) is a disease that occurs frequently in young and middle-aged people. Because of its high disability rate, it affects the ability to work, so the early treatment of this disease is particularly important. This retrospective study aimed to evaluate the clinical efficacy of hip arthroscopy combined with multiple small-diameter fan-shaped low-speed drilling decompression (MSFLD) in treating early-mid stage ONFH (ARCO II-IIIA) compared to MSFLD, with at least 10-year follow-up. METHODS: A total of 234 patients who underwent hip arthroscopy and MSFLD for ONFH from 1998 to 2012 were analyzed retrospectively. This study enrolled patients between 18 and 60 years old with ARCO stage II-III A, diagnosed clinically and through imaging, in accordance with the 2021 guidelines for the treatment of ONFH. Clinical data, including demographics, operation mode, BMI, pre- and postoperative Harris score, and femoral head survival rate, were collected. Patients were divided into hip arthroscopy + MSFLD and MSFLD groups based on the operation mode. The t-test was used to compare the postoperative efficacy, Harris scores, and survival rates of the femoral head between the two groups. RESULTS: Among the 234 patients, 160 cases were followed up, including 92 cases in the hip arthroscopy + MSFLD group and 68 cases in MSFLD group, the follow-up rate was 68.38%, and the follow-up time was (10-22)14.11 ± 3.06 years. The Harris score (80.65 ± 6.29) in the hip arthroscopy + MSFLD group was significantly higher than that in the MSFLD group (p = 0.00), and the survival rate of femoral head (5-year survival rate was 84.78%, 10-year survival rate was 23.91%) was also higher than that in the MSFLD group (5-year survival rate was 63.24%, 10-year survival rate was 8.82%). The 5-year and 10-year survival rates of patients with ARCO II were 82.11% and 28.42%, which were better than 54% and 33% for ARCO III A. The femur head survival rate of alcoholic ONFH (5-year survival rate 61.54%, 10-year survival rate 9.23%) was significantly higher than that of other types of ONFH. CONCLUSION: Clinical follow-up of at least 10 years suggests that hip arthroscopy combined with MSFLD is an effective treatment for early-mid stage ONFH, with good clinical effect and high survival rate of femoral head.
Subject(s)
Femur Head Necrosis , Femur Head , Middle Aged , Humans , Adolescent , Young Adult , Adult , Follow-Up Studies , Femur Head/surgery , Retrospective Studies , Femur Head Necrosis/surgery , Arthroscopy/methods , Debridement , Treatment Outcome , Bone Transplantation , DecompressionABSTRACT
BACKGROUND: During unmanned aerial vehicles (UAVs) spraying, downwash and crosswind generate back pressure in comprehensive, which changes in spatial atomization characteristics of spraying droplets. However, the process of such atomization characteristics needs to be clarified. This study focuses on the effect of rotor speed and crosswind speed on spatial atomization characteristics. The computational fluid dynamics (CFD) models of the distributions of airflow, back pressure and atomization characteristics were established, and verification was conducted by developing a validation platform. RESULTS: The CFD results indicated that small droplets of 65-130 µm atomized by negative pressure would be coalesced near the nozzle, while large droplets of 390-520 µm atomized by positive pressure would be aggregated further away. Crosswind caused atomization stratification with droplet sizes of approximately 90 µm, 320 µm and 390 µm. When crosswind speed increased from 3 m/s to 6 m/s, the spraying drifted from 0.5 m to 1 m. When rotor speed increased from 2000 RPM to 3000 RPM, droplet distribution was expanded and droplet particle size was more uniform. Verification results demonstrated that the spraying distribution and the droplet size variation were consistent with the CFD. CONCLUSIONS: Spatial atomization characteristics were highly correlated with airflow and back pressure. Moreover, as crosswind generated droplet drift and atomization stratification and downwash could improve the uniformity of droplet distribution, spraying performance was superior by enhancing downwash to restrain the adverse effect of crosswind in real applications. © 2023 Society of Chemical Industry.
Subject(s)
Hydrodynamics , Particle SizeABSTRACT
The effect of ultrasonic pre-treatment on moisture removal characteristics of ginger in a convective dryer was investigated. The slabs were dried by practicing sonication durations of 0, 15 and 30 min at different levels of the air temperature and velocity. Following increasing the sonication duration and air temperature, required time and energy to dehydrate the samples were decreased. The pre-treatment played important role in improving rehydration capability and surface color retention in the dried gingers. Content of the main volatile component (α-Zingiberene) was not influenced by the sonication. Mean values for the phenolic contents and antioxidant activity at sonication duration of 0, 15 and 30 min were determined to be 18.93, 18.15 and 17.49 GAE/g dry matter and 83.57, 78.33 and 74.58 %, respectively. The desired values for the temperature, velocity and sonication duration were revealed to be about 66 °C, 3 m/s and 20 min, respectively.
ABSTRACT
Hydrogel materials show promise for diverse applications, particular as biocompatible materials due to their high water content. Despite advances in hydrogel technology in recent years, their application is often severely limited by inadequate mechanical properties and time-consuming fabrication processes. Here we report a rapid hydrogel preparation strategy that achieves the simultaneous photo-crosslinking and establishment of biomimetic soft-hard material interface microstructures. These biomimetic interfacial-bonding nanocomposite hydrogels are prepared within seconds and feature clearly separated phases but have a strongly bonded interface. Due to effective interphase load transfer, biomimetic interfacial-bonding nanocomposite gels achieve an ultrahigh toughness (138 MJ m-3) and exceptional tensile strength (15.31 MPa) while maintaining a structural stability that rivals or surpasses that of commonly used elastomer (non-hydrated) materials. Biomimetic interfacial-bonding nanocomposite gels can be fabricated into arbitrarily complex structures via three-dimensional printing with micrometre-level precision. Overall, this work presents a generalizable preparation strategy for hydrogel materials and acrylic elastomers that will foster potential advances in soft materials.
ABSTRACT
Umbilical cord-derived mesenchymal stem cells (UC-MSC) are promising candidates for wound healing. However, the low amplification efficiency of MSC in vitro and their low survival rates after transplantation have limited their medical application. In this study, we fabricated a micronized amniotic membrane (mAM) as a microcarrier to amplify MSC in vitro and used mAM and MSC (mAM-MSC) complexes to repair burn wounds. Results showed that MSC could live and proliferate on mAM in a 3D culture system, exhibiting higher cell activity than in 2D culture. Transcriptome sequencing of MSC showed that the expression of growth factor-related, angiogenesis-related, and wound healing-related genes was significantly upregulated in mAM-MSC compared to traditional 2D-cultured MSC, which was verified via RT-qPCR. Gene ontology (GO) analysis of differentially expressed genes (DEGs) showed significant enrichment of terms related to cell proliferation, angiogenesis, cytokine activity, and wound healing in mAM-MSC. In a burn wound model of C57BL/6J mice, topical application of mAM-MSC significantly accelerated wound healing compared to MSC injection alone and was accompanied by longer survival of MSC and greater neovascularization in the wound.
ABSTRACT
Altered Krüppel-like factor 9 (KLF9) expression can regulate the progression of several cancers, including renal cell carcinoma (RCC). This study was conducted to investigate the role of KLF9 in the proliferation, invasion, and migration of RCC cells via regulation of stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4). The expression patterns of KLF9, SDF-1, and CXCR4 in the experimental cell lines were determined by real-time quantitative polymerase chain reaction and Western blotting. After transfection of the KLF9 siRNA and KLF9 pcDNA, cell proliferation, invasion, and migration were evaluated by experiments including cell counting kit-8, colony formation, and Transwell assays. The binding of KLF9 to the SDF-1 promoter was analyzed by chromatin immunoprecipitation and dual-luciferase assay. The rescue experiment was performed using the recombinant SDF-1 protein and KLF9 pcDNA. KLF9 was downregulated in the RCC cells. KLF9 knockdown induced the proliferation, invasion, and migration of RCC cells, whereas KLF9 overexpression elicited the opposite roles. Mechanically, KLF9 bound to the SDF-1 promoter, repressed SDF-1 transcription, and reduced the SDF-1/CXCR4 expression levels. Activation of the SDF-1/CXCR4 axis attenuated the inhibitory role of KLF9 overexpression in RCC cell growth. Ordinarily, KLF9 suppressed the proliferation, invasion, and migration of RCC cells by repressing the SDF-1/CXCR4 signaling.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Receptors, CXCR4/genetics , Carcinoma, Renal Cell/genetics , Chemokine CXCL12/genetics , Chemokine CXCL12/metabolism , Signal Transduction/genetics , Cell Proliferation/genetics , Kidney Neoplasms/genetics , Cell Movement/genetics , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Kruppel-Like Transcription Factors/geneticsABSTRACT
Hydrogen peroxide (H2O2) steaming, a green and highly efficient delignification method, has been demonstrated to provide a wood skeleton with a very low content of residual lignin in the manufacturing of transparent wood. It usually requires a long reaction time and a large amount of H2O2 because the piece of wood is treated using steaming equipment. Herein, a H2O2 solution steaming method was developed for the highly efficient removal of lignin from wood. Specifically, several wood samples were simultaneously immersed in a hot H2O2 solution to obtain delignified wood with a relatively high content of residual lignin, which provided a high strength and preserved the cellulose skeleton. Subsequently, the delignified wood with a relatively high content of residual lignin was further treated with H2O2 steam to obtain a very low lignin delignified wood. Compared with the previous H2O2 steaming method, the reaction time and used H2O2 volume of the H2O2 solution steaming method was reduced by 37.3% and 52.7%, respectively. All-biomass transparent wood could be obtained by infiltrating the delignified wood with cellulose acetate, which showed both a high transmittance of 83.0% and a low thermal conductivity of 0.30 Wm-1K-1.
ABSTRACT
Mesenchymal stem cells (MSCs) is promising in promoting wound healing mainly due to their paracrine function. Nonetheless, the transplanted MSCs presented poor survival with cell dysfunction and paracrine problem in diabetic environment, thus limiting their therapeutic efficacy and clinical application. JAM-A, an adhesion molecule, has been reported to play multi-functional roles in diverse cells. We therefore investigated the potential effect of JAM-A on MSCs under diabetic environment and explored the underlying mechanism. Indeed, high-glucose condition inhibited MSCs viability and JAM-A expression. However, JAM-A abnormality was rescued by lentivirus transfection and JAM-A overexpression promoted MSCs proliferation, migration and adhesion under hyperglycemia. Moreover, JAM-A overexpression attenuated high-glucose-induced ROS production and MSCs apoptosis. The bio-effects of JAM-A on MSCs under hyperglycemia were confirmed by RNA-seq with enrichment analyses. Moreover, Luminex chip results showed JAM-A overexpression dramatically upregulated PDGF-BB and VEGF in the supernatant of MSCs, which was verified by RT-qPCR and western blotting. The supernatant was further found to facilitate HUVECs proliferation, migration and angiogenesis under hyperglycemia. In vivo experiments revealed JAM-A overexpression significantly enhanced MSCs survival, promoted wound angiogenesis, and thus accelerated diabetic wound closure, partially by enhancing PDGF-BB and VEGF expression. This study firstly demonstrated that JAM-A expression of MSCs was inhibited upon high-glucose stimulation. JAM-A overexpression alleviated high-glucose-induced MSCs dysfunction, enhanced their anti-oxidative capability, protected MSCs from hyperglycemia-induced apoptosis and improved their survival, thus strengthening MSCs paracrine function to promote angiogenesis and significantly accelerating diabetic wound healing, which offers a promising strategy to maximize MSCs-based therapy in diabetic wound.
Subject(s)
Diabetes Mellitus , Hyperglycemia , Mesenchymal Stem Cells , Neovascularization, Physiologic , Wound Healing , Wounds and Injuries , Humans , Becaplermin/genetics , Becaplermin/metabolism , Cell Survival/genetics , Diabetes Mellitus/genetics , Diabetes Mellitus/metabolism , Glucose/pharmacology , Hyperglycemia/genetics , Hyperglycemia/metabolism , Mesenchymal Stem Cells/metabolism , Neovascularization, Physiologic/genetics , Paracrine Communication/genetics , Umbilical Cord/cytology , Vascular Endothelial Growth Factor A/metabolism , Wound Healing/genetics , Wounds and Injuries/genetics , Wounds and Injuries/metabolismABSTRACT
Senescence and altered differentiation potential of bone marrow stromal cells (BMSCs) lead to age-related bone loss. As an important posttranscriptional regulatory pathway, alternative splicing (AS) regulates the diversity of gene expression and has been linked to induction of cellular senescence. However, the role of splicing factors in BMSCs during aging remains poorly defined. Herein, we found that the expression of the splicing factor Y-box binding protein 1 (YBX1) in BMSCs decreased with aging in mice and humans. YBX1 deficiency resulted in mis-splicing in genes linked to BMSC osteogenic differentiation and senescence, such as Fn1, Nrp2, Sirt2, Sp7, and Spp1, thus contributing to BMSC senescence and differentiation shift during aging. Deletion of Ybx1 in BMSCs accelerated bone loss in mice, while its overexpression stimulated bone formation. Finally, we identified a small compound, sciadopitysin, which attenuated the degradation of YBX1 and bone loss in old mice. Our study demonstrated that YBX1 governs cell fate of BMSCs via fine control of RNA splicing and provides a potential therapeutic target for age-related osteoporosis.
Subject(s)
Mesenchymal Stem Cells , Osteoporosis , Humans , Mice , Animals , Osteogenesis/genetics , Aging/metabolism , Cellular Senescence , Cell Differentiation/genetics , Osteoporosis/metabolism , Bone Marrow Cells , Y-Box-Binding Protein 1/metabolismABSTRACT
Sepsis is a systemic inflammatory disease caused by an infection that can lead to multiple organ failure. Sepsis alters energy metabolism, leading to metabolic reprogramming of immune cells, which consequently disrupts innate and adaptive immune responses, triggering hyperinflammation and immunosuppression. This review summarizes metabolic reprogramming and its regulatory mechanism in sepsis-induced hyperinflammation and immunosuppression, highlights the significance and intricacies of immune cell metabolic reprogramming, and emphasizes the pivotal role of mitochondria in metabolic regulation and treatment of sepsis. This review provides an up-to-date overview of the relevant literature to inform future research directions in understanding the regulation of sepsis immunometabolism. Metabolic reprogramming has great promise as a new target for sepsis treatment in the future.
ABSTRACT
Continuous monitoring of glucose allows diabetic patients to better maintain blood glucose level by altering insulin dosage or diet according to prevailing glucose values and thus to prevent potential hyperglycemia and hypoglycemia. However, current continuous glucose monitoring (CGM) relies mostly on enzyme electrodes or micro-dialysis probes, which suffer from insufficient stability, susceptibility to corrosion of electrodes, weak or inconsistent correlation, and inevitable interference. A fluorescence-based glucose sensor in the skin will likely be more stable, have improved sensitivity, and can resolve the issues of electrochemical interference from the tissue. This study develops a fluorescent nanodiamond boronic hydrogel system in porous microneedles for CGM. Fluorescent nanodiamond is one of the most photostable fluorophores with superior biocompatibility. When surface functionalized, the fluorescent nanodiamond can integrate with boronic polymer and form a hydrogel, which can produce fluorescent signals in response to environmental glucose concentration. In this proof-of-concept study, the strategy for building a miniatured device with fluorescent nanodiamond hydrogel is developed. The device demonstrates remarkable long-term photo and signal stability in vivo with both small and large animal models. This study presents a new strategy of fluorescence based CGM toward treatment and control of diabetes.
Subject(s)
Blood Glucose , Nanodiamonds , Animals , Blood Glucose Self-Monitoring , Hydrogels , GlucoseABSTRACT
BACKGROUND: Latent and active myofascial trigger points (MTrPs) in knee-associated muscles may play a key role in pain management among patients with knee osteoarthritis (KOA). The aim of this study was to investigate the effect of dry needling treatment on pain intensity, disability, and range of motion (ROM) in patients with KOA. METHODS: This randomized, single-blinded, clinical trial was carried out for 6 weeks of treatment and 6-month follow-up. A total of 98 patients met the entry criteria and were randomly assigned to the dry needling latent and active myofascial trigger point (MTrPs) with the stretching group or the oral diclofenacwith the stretching group. Numeric Pain Rating Scale (NPRS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and ROM were statistically analyzed before and after treatment and at the 6-month follow-up. RESULTS: A total of 42 patients in the dry needling group (DNG) and 35 patients in the diclofenac group (DG), respectively, completed the study, and there was no significant difference in the general data between the two groups. After treatments, both the groups showed a good effect in knee pain, function, and ROM, However, the DNG showed a significantly better result than the DG. Especially in the results of the 6-month follow-up, the DNG showed much better results than the DG. CONCLUSIONS: Dry needling on latent and active MTrPs combined with stretching and oral diclofenac combined with stretching can effectively relieve pain, improve function, and restore knee ROM affected by KOA. However, the effects of dry needling and stretching are better and longer lasting than those of oral diclofenac and stretching for at least 6 months. TRIAL REGISTRATION: Registered in the Chinese Clinical Trial Registry ( www.chictr.org.cn ) in 17/11/2017 with the following code: ChiCTR-INR-17013432.