ABSTRACT
Currently, the treatment of bone defects in arthroplasty is a challenge in clinical practice. Nonetheless, commercially available orthopaedic scaffolds have shown limited therapeutic effects for large bone defects, especially for massiveand irregular defects. Additively manufactured porous tantalum, in particular, has emerged as a promising material for such scaffolds and is widely used in orthopaedics for its exceptional biocompatibility, osteoinduction, and mechanical properties. Porous tantalum has also exhibited unique advantages in personalised rapid manufacturing, which allows for the creation of customised scaffolds with complex geometric shapes for clinical applications at a low cost and high efficiency. However, studies on the effect of the pore structure of additively manufactured porous tantalum on bone regeneration have been rare. In this study, our group designed and fabricated a batch of precision porous tantalum scaffolds via laser powder bed fusion (LPBF) with pore sizes of 250 µm (Ta 250), 450 µm (Ta 450), 650 µm (Ta 650), and 850 µm (Ta 850). We then performed a series of in vitro experiments and observed that all four groups showed good biocompatibility. In particular, Ta 450 demonstrated the best osteogenic performance. Afterwards, our team used a rat bone defect model to determine the in vivo osteogenic effects. Based on micro-computed tomography and histology, we identified that Ta 450 exhibited the best bone ingrowth performance. Subsequently, sheep femur and hip defect models were used to further confirm the osteogenic effects of Ta 450 scaffolds. Finally, we verified the aforementioned in vitro and in vivo results via clinical application (seven patients waiting for revision total hip arthroplasty) of the Ta 450 scaffold. The clinical results confirmed that Ta 450 had satisfactory clinical outcomes up to the 12-month follow-up. In summary, our findings indicate that 450 µm is the suitable pore size for porous tantalum scaffolds. This study may provide a new therapeutic strategy for the treatment of massive, irreparable, and protracted bone defects in arthroplasty.
ABSTRACT
Diabetic infected bone defects (DIBD) with abnormal immune metabolism are prone to the hard-to-treat bacterial infections and delayed bone regeneration, which present significant challenges in clinic. Control of immune metabolism is believed to be important in regulating fundamental immunological processes. Here, we developed a macrophage metabolic reprogramming hydrogel composed of modified silk fibroin (Silk-6) and poly-l-lysine (ε-PL) and further integrated with M2 Macrophage-derived Exo (M2-Exo), named Silk-6/ε-PL@Exo. This degradable hydrogel showed a broad-spectrum antibacterial performance against both Gram-positive and -negative bacteria. More importantly, the release of M2-Exo from Silk-6/ε-PL@Exo could target M1 macrophages, modulating the activity of the key enzyme hexokinase II (HK2) to control the inflammation-related NF-κB pathway, alleviate lactate accumulation, and inhibit glycolysis to normalize the cycle, thereby promoting M1-to-M2 balance. Using a rat model of DIBD, Silk-6/ε-PL@Exo hydrogel promoted infection control, balanced immune responses and accelerated the bone defect healing. Overall, this study demonstrates that this Silk-6/ε-PL @Exo is a promising filler biomaterial with multi-function to treat DIBD and emphasizes the importance of metabolic reprogramming in bone regeneration.
ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Zhenzhu Tiaozhi (FTZ) capsule is a hospital preparation of a patented traditional Chinese medicine compound. FTZ has been clinically used for nearly 13 years in the treatment of diabetes and glycolipid metabolic diseases. With the significant benefits of SGLT2 inhibitor in patients with diabetic kidney disease (DKD), it provides a research avenue to explore the mechanism of FTZ in treating this disease based on glycolysis pathway. AIM OF THE STUDY: To explore the pharmacological characteristics of FTZ in DKD mice and its impact on the glycolysis pathway. MATERIALS AND METHODS: We induced a DKD model in C57BL/6 mice by injection of streptozotocin (STZ) combined with long-term high-fat diet. We administered three doses of FTZ for 12 weeks of treatment. Kidney function, blood lipid levels, glucose tolerance, and key glycolytic enzymes were evaluated. Renal pathological changes were observed using HE, MASSON, and PAS staining. The potential targets of the active ingredients of FTZ in the glycolysis pathway were predicted using network pharmacology and molecular docking. Validation was performed using immunohistochemistry and Western blotting. RESULTS: FTZ effectively reduces blood glucose, total cholesterol, triglyceride, low density lipoprotein cholesterol, 24 h proteinuria, serum creatinine, blood urea nitrogen, and increases urinary glucose levels. Glucose tolerance and renal pathological changes were significantly improved by FTZ treatment. Pinusolidic acid, a component of FTZ, shows good binding affinity with three active pockets of SGLT2. WB and immunohistochemistry revealed that FTZ significantly inhibits the expression of SGLT2 and its glycolytic related proteins (GLUT2/PKM2/HK2). Hexokinase, pyruvate kinase, and lactate dehydrogenase in the kidney were also significantly inhibited by FTZ in a dose-dependent manner. CONCLUSION: FTZ may alleviate the progression of DKD by inhibiting the activation of the SGLT2/glycolytic pathway. Our study provides new insights into the clinical application of FTZ in DKD.
Subject(s)
Diabetes Mellitus, Experimental , Diabetic Nephropathies , Drugs, Chinese Herbal , Glycolysis , Mice, Inbred C57BL , Sodium-Glucose Transporter 2 Inhibitors , Sodium-Glucose Transporter 2 , Animals , Diabetic Nephropathies/drug therapy , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/therapeutic use , Male , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Diabetes Mellitus, Experimental/drug therapy , Glycolysis/drug effects , Sodium-Glucose Transporter 2/metabolism , Mice , Blood Glucose/drug effects , Kidney/drug effects , Kidney/metabolism , Kidney/pathology , Molecular Docking Simulation , Streptozocin , Capsules , Diet, High-Fat/adverse effectsABSTRACT
The specific mechanisms underlying bacteria-triggered cell death and osteogenic dysfunction in host bone marrow mesenchymal stem cells (BMSCs) remain unclear, posing a significant challenge to the repair of infected bone defects. This study identifies ferroptosis as the predominant cause of BMSCs death in the infected bone microenvironment. Mechanistically, the bacteria-induced activation of the innate immune response in BMSCs leads to upregulation and phosphorylation of interferon regulatory factor 7 (IRF7), thus facilitating IRF7-dependent ferroptosis of BMSCs through the transcriptional upregulation of acyl-coenzyme A synthetase long-chain family member 4 (ACSL4). Moreover, it is found that intervening in ferroptosis can partially rescue cell injuries and osteogenic dysfunction. Based on these findings, a hydrogel composite 3D-printed scaffold is designed with reactive oxygen species (ROS)-responsive release of antibacterial quaternized chitosan and sustained delivery of the ferroptosis inhibitor Ferrostatin-1 (Fer-1), capable of eradicating pathogens and promoting bone regeneration in a rat model of infected bone defects. Together, this study suggests that ferroptosis of BMSCs is a promising therapeutic target for infected bone defect repair.
ABSTRACT
Macrophage metabolism dysregulation, which is exacerbated by persistent stimulation in infectious and inflammatory diseases, such as diabetic infectious bone defects (DIBD), eventually leads to the failure of bone repair. Here, we have developed an injectable, macrophage-modulated GAPDH-Silence drug delivery system. This microsphere comprises chondroitin sulfate methacrylate (CM) and methacrylated gelatin (GM), while the dimethyl fumarate (DMF)-loaded liposome (D-lip) is encapsulated within the microsphere (CM@GM), named D-lip/CM@GM. Triggered by the over-expressed collagenase in DIBD, the microspheres degrade and release the encapsulated D-lip. D-lip could modulate metabolism by inhibiting GAPDH, which suppresses the over-activation of glycolysis, thus preventing the inflammatory response of macrophages in vitro. While beneficial for macrophages, D-lip/CM@GM is harmful to bacteria. GAPDH, while crucial for glycolysis of staphylococcal species (S. aureus), can be effectively countered by D-lip/CM@GM. We are utilizing existing drugs in innovative ways to target central metabolism for effective eradication of bacteria. In the DIBD model, our results confirmed that the D-lip/CM@GM enhanced bacteria clearance and reprogrammed dysregulated metabolism, thereby significantly improving bone regeneration. In conclusion, this GAPDH-Silence microsphere system may provide a viable strategy to promote diabetic infection bone regeneration.
Subject(s)
Bone Regeneration , Macrophages , Microspheres , Staphylococcus aureus , Animals , Macrophages/metabolism , Macrophages/drug effects , Mice , Bone Regeneration/drug effects , RAW 264.7 Cells , Staphylococcus aureus/drug effects , Glyceraldehyde-3-Phosphate Dehydrogenases/metabolism , Male , Glycolysis/drug effects , Drug Delivery Systems/methods , Diabetes Complications/drug therapy , Liposomes/chemistry , Anti-Bacterial Agents/pharmacologyABSTRACT
BACKGROUND: Interferon-gamma release assay (IGRA) for tuberculosis (TB) remains limited in its ability to discriminate between active TB (ATB) and latent TB infection (LTBI). Activation markers on host T and NK cells are currently considered to be promising markers in the diagnosis of ATB. METHODS: This prospective observational study enrolled 213 participants and the participants were divided into ATB, LTBI, other lung-related diseases (ORD), and health control (HC) groups. CD69 and HLA-DR on T and NK cells were detected in QFT-TB assay, and a composite scoring system (TB-Flow) was created for the diagnosis of ATB. RESULTS: The expression of activation markers (CD69 and HLA-DR) were significantly increased in ATB. HLA-DR on NK cells, CD69 on T cells, and QFT-TB in the differential diagnosis of ATB and HC were all of good diagnostic value (AUC>0.90). In addition, the TB-Flow greatly improved the efficiency of differential diagnosis between ATB and LTBI (AUC=0.90, 95%CI: 0.84-0.96), with sensitivity and specificity of 79.17 % (95%CI: 64.60%-89.04 %) and 88.68 % (95%CI: 76.28%-95.31 %). CONCLUSIONS: CD69 and HLA-DR on host T and NK cells are promising markers in distinguishing different TB infection status. Our blood-based TB-Flow scoring system can distinguish ATB from LTBI with good diagnostic efficacy.
ABSTRACT
Tioxazafen (TXF) is the first 1,2,4-oxadiazole nematicide. In the present study, the aqueous degradation of TXF was investigated in terms of hydrolysis and photolysis. Under the irradiation of simulated sunlight, TXF degraded very fast in ultrapure water and buffers with half-lives (t1/2s) <8.3 min. A sole photoproduct (PP) PP228a was isolated, and identified by spectroscopic means (UV, IR, HRMS, and 1H NMR) to be the thiophen-3-yl isomer converted from its thiophen-2-yl parent. Comparing with TXF, PP228a had quite extended t1/2s ranging from 6.9 to 7.9 d. The photolysis kinetics of TXF and PP228a showed no pH-dependence, and varied for each individual compound as affected by nitrate, fulvic acid, and humic acid. Besides, both compounds were hydrolytically stable. 6 PPs of PP228a were identified, with two of them being its isomers. The mechanisms involved in the process included the biradical photosensitization, photoinduced electron transfer, and ring contraction-ring expansion reactions. The 48 h-EC50 to Daphnia magna was 0.808 mg/L for PP228a comparing to >1.12 mg/L for TXF, while the results of Vibrio fischeri assays indicated that one or more PPs of PP228a might have higher toxicity.
Subject(s)
Photolysis , Water Pollutants, Chemical , Kinetics , Water Pollutants, Chemical/toxicity , Water Pollutants, Chemical/chemistry , Oxadiazoles/chemistry , Oxadiazoles/toxicity , Daphnia/drug effects , AnimalsABSTRACT
This study aims to evaluate the role of trefoil factor 3 (TFF3) peptides in type 2 diabetes mellitus (T2DM) from an inflammatory perspective. The focus was on exploring how TFF3 affects the function of T cells. TFF3 overexpression model was constructed using lentivirus in Jurkat cell lines. We evaluated the impact of TFF3 on the proliferation, apoptosis, and IL-17A levels of Jurkat cells cultured in high glucose. The T2DM model was induced in TFF3 knockout (KO) mice through streptozotocin combined with high-fat diet. The measurements included glucose tolerance, insulin tolerance, inflammation markers, Th17 cell proportion, and pancreatic pathological changes. The T2DM modeling led to splenomegaly in mice, and increased expression of TFF3 in their spleens. Overexpression of TFF3 increased the proportion of IL-17+ T cells and the levels of Th17-related cytokines in Jurkat cells. There was no difference in body weight and blood glucose levels between wild-type and TFF3 KO mice. However, T2DM mice lacking the TFF3 gene showed improved glucose utilization, ameliorated pancreatic pathology, decreased inflammation levels, and reduced Th17 cell ratio. TFF3 may be involved in the chronic inflammatory immune response in T2DM. Its mechanism may be related to the regulation of the RORγt/IL-17 signaling pathway and its impact on T cell proliferation and apoptosis.
Subject(s)
Diabetes Mellitus, Type 2 , Mice, Knockout , Th17 Cells , Trefoil Factor-3 , Th17 Cells/immunology , Th17 Cells/metabolism , Animals , Humans , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/immunology , Mice , Trefoil Factor-3/metabolism , Trefoil Factor-3/genetics , Jurkat Cells , Interleukin-17/metabolism , Diabetes Mellitus, Experimental/immunology , Diabetes Mellitus, Experimental/metabolism , Male , Cell Proliferation , Apoptosis , Diet, High-Fat/adverse effectsABSTRACT
BACKGROUND: Intervertebral disc degeneration (IVDD) is a multifaceted condition characterized by heterogeneity, wherein the balance between catabolism and anabolism in the extracellular matrix of nucleus pulposus (NP) cells plays a central role. Presently, the available treatments primarily focus on relieving symptoms associated with IVDD without offering an effective cure targeting its underlying pathophysiological processes. D-mannose (referred to as mannose) has demonstrated anti-catabolic properties in various diseases. Nevertheless, its therapeutic potential in IVDD has yet to be explored. METHODS: The study began with optimizing the mannose concentration for restoring NP cells. Transcriptomic analyses were employed to identify the mediators influenced by mannose, with the thioredoxin-interacting protein (Txnip) gene showing the most significant differences. Subsequently, small interfering RNA (siRNA) technology was used to demonstrate that Txnip is the key gene through which mannose exerts its effects. Techniques such as colocalization analysis, molecular docking, and overexpression assays further confirmed the direct regulatory relationship between mannose and TXNIP. To elucidate the mechanism of action of mannose, metabolomics techniques were employed to pinpoint glutamine as a core metabolite affected by mannose. Next, various methods, including integrated omics data and the Gene Expression Omnibus (GEO) database, were used to validate the one-way pathway through which TXNIP regulates glutamine. Finally, the therapeutic effect of mannose on IVDD was validated, elucidating the mechanistic role of TXNIP in glutamine metabolism in both intradiscal and orally treated rats. RESULTS: In both in vivo and in vitro experiments, it was discovered that mannose has potent efficacy in alleviating IVDD by inhibiting catabolism. From a mechanistic standpoint, it was shown that mannose exerts its anti-catabolic effects by directly targeting the transcription factor max-like protein X-interacting protein (MondoA), resulting in the upregulation of TXNIP. This upregulation, in turn, inhibits glutamine metabolism, ultimately accomplishing its anti-catabolic effects by suppressing the mitogen-activated protein kinase (MAPK) pathway. More importantly, in vivo experiments have further demonstrated that compared with intradiscal injections, oral administration of mannose at safe concentrations can achieve effective therapeutic outcomes. CONCLUSIONS: In summary, through integrated multiomics analysis, including both in vivo and in vitro experiments, this study demonstrated that mannose primarily exerts its anti-catabolic effects on IVDD through the TXNIP-glutamine axis. These findings provide strong evidence supporting the potential of the use of mannose in clinical applications for alleviating IVDD. Compared to existing clinically invasive or pain-relieving therapies for IVDD, the oral administration of mannose has characteristics that are more advantageous for clinical IVDD treatment.
Subject(s)
Cell Cycle Proteins , Glutamine , Intervertebral Disc Degeneration , Mannose , Intervertebral Disc Degeneration/drug therapy , Mannose/pharmacology , Mannose/therapeutic use , Animals , Rats , Glutamine/pharmacology , Glutamine/metabolism , Male , Rats, Sprague-Dawley , Humans , Nucleus Pulposus/drug effects , Nucleus Pulposus/metabolismABSTRACT
Most patients with myopia have dry eye, which has been shown to adversely affect ocular symptoms, myopia progression, and quality of life in patients with myopia. Needle prickling has been shown to be effective in providing symptom relief in patients with myopia and dry eye. Press needle is a long-lasting, easy-to-operate, and inexpensive traditional Chinese medicine treatment. The standard practice of needle insertion is very important for the treatment of myopia and dry eye. The specific steps include selecting the appropriate acupoints, piercing them with appropriate needles, and fixing them in the skin or subcutaneously at the acupoints, burying them for 2 days, resting for 1 day; the course of treatment lasts for 2 weeks. Specifically, the following indicators were assessed: uncorrected visual acuity and the ocular surface disease index. This article will explain how to standardize the operation of a press needle in the treatment of myopia and dry eye.
Subject(s)
Acupuncture Therapy , Dry Eye Syndromes , Medicine, Chinese Traditional , Myopia , Humans , Dry Eye Syndromes/therapy , Myopia/therapy , Medicine, Chinese Traditional/methods , Acupuncture Therapy/methods , Acupuncture Therapy/instrumentation , NeedlesABSTRACT
The objective of this work is to develop a closed-loop recycling method specifically tailored for acrylic fibers. Recycling waste acrylic is essential, given the vast volumes of acrylic-containing textiles produced yearly and the strong capability of acrylics to generate toxic microplastics. However, none of the available closed-loop recycling, mechanical recycling, chemical recycling, and direct extrusion technologies work for acrylics. Acrylic fibers are always blended with other textile fibers, making fiber separation via mechanical recycling almost impossible. Polyacrylonitrile, an addition-polymerized thermoplastic material, cannot be depolymerized into its original monomer. Direct extrusion of waste acrylics faces issues of uncontrollable colors on fibers and pollution of spinning lines due to the influence of existing colorants. In our method, acrylic fibers were extracted from waste textiles using a novel approach involving maximized acrylic swelling and dissolution with dimethyl sulfoxide and butanediol. Cationic dyes were effectively removed through cost-effective recycling technology. This work demonstrates that cationic dyes seriously affect the acrylic dissolution, color consistency, and dyeability of regenerated fibers via direct wet extrusion. Such negative impacts of dyes have been eliminated by our cost-effective and closed-loop acrylic recycling technology, which enables the efficient separation of non-acrylic fibers and dyes from acrylic fibers. Our recycling system achieved zero discharges through recycling solvents, dyes, and acrylics. The regenerated acrylic fibers exhibited mechanical properties and dyeability comparable to virgin acrylic fibers. The material and energy costs to produce pure acrylic from waste textiles were only 40 % of those from fossils. This study successfully introduces a closed-loop recycling method for acrylic fibers from waste textiles, addressing key challenges in acrylic fiber recycling. Further research and implementation of this technology are recommended to advance its commercial viability and widespread adoption.
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BACKGROUND: Human T cells play an important role in immunity against tuberculosis (TB) infection. Activating receptor HLA-DR and inhibitory receptor KLRG1 are critical regulators of T cell function during viral infection and tumorigenesis, but they have been less studied in TB infection. METHODS: In this study, we explored the relationship between CD3+ T cell expression of HLA-DR and KLRG1 receptors and function against TB infection. Flow cytometry was conducted to assess the immunomodulatory effects of HLA-DR and KLRG1 receptors on CD3+ T cells in patients with different TB infection status. RESULTS: We found activating receptors HLA-DR, NKG2C, CD57 and NKP46, and inhibitory receptors KLRG1 and KIR on CD3+ T cells in different TB infection status showed different distribution patterns; the cytotoxic potential and cytokine secretion capacity of CD3+ T cells after Mtb-specific antigen stimulation were significantly enhanced in TB infection groups. Further studies revealed HLA-DR+ T and KLRG1+ T cells expressed higher activating and inhibitory receptors than the negative population. In addition, the expression of cytotoxic potential and cytokine secretion capacity of HLA-DR+ T and KLRG1+ T cells was significantly higher than that of HLA-DR- T and KLRG1- T cells. CONCLUSIONS: Expression of HLA-DR and KLRG1 enhances the cytotoxic potential and cytokine secretion capacity of CD3+ T cells in TB patients, suggesting CD3+ T cells expressing HLA-DR and KLRG1 are important effector cell phenotypes involved in the host anti-TB infection. HLA-DR and KLRG1 expressed by CD3+ T cells may be potential predictive markers of TB disease progression and clinical immune assessment.
Subject(s)
Cytokines , HLA-DR Antigens , Lectins, C-Type , Receptors, Immunologic , Tuberculosis , Adult , Female , Humans , Male , Middle Aged , Young Adult , CD3 Complex/metabolism , CD3 Complex/immunology , Cells, Cultured , Cytokines/metabolism , Cytotoxicity, Immunologic , HLA-DR Antigens/metabolism , HLA-DR Antigens/immunology , Lectins, C-Type/metabolism , Mycobacterium tuberculosis/immunology , Receptors, Immunologic/metabolism , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Tuberculosis/immunologyABSTRACT
Type 17 T helper (Th17) cells, which are a subtype of CD4+ T helper cells, secrete pro-inflammatory cytokines such as IL-17A, IL-17F, IL-21, IL-22, and GM-CSF, which play crucial roles in immune defence and protection against fungal and extracellular pathogen invasion. However, dysfunction of Th17 cell immunity mediates inflammatory responses and exacerbates tissue damage. This pathological process initiated by Th17 cells is common in kidney diseases associated with renal injury, such as glomerulonephritis, lupus nephritis, IgA nephropathy, hypertensive nephropathy, diabetic kidney disease and acute kidney injury. Therefore, targeting Th17 cells to treat kidney diseases has been a hot topic in recent years. This article reviews the mechanisms of Th17 cell-mediated inflammation and autoimmune responses in kidney diseases and discusses the related clinical drugs that modulate Th17 cell fate in kidney disease treatment.
IL-17 and IL-17-producing cells (mainly Th17 cells) are crucial for kidney diseases. Multiple factors and mechanisms are involved in Th17 cell polarization, including oxidative stress, abnormal glucolipid metabolism, miRNA dysfunction, and microbial metabolism. This pathological process initiated by Th17 cells is common in kidney diseases associated with renal injury, such as glomerulonephritis, lupus nephritis, IgA nephropathy, hypertensive nephropathy, diabetic kidney disease and acute kidney injury. Modulating the direction of Th17 cell differentiation is a highly attractive therapeutic approach. This article reviews the mechanisms of Th17 cell-mediated inflammation and autoimmune responses in kidney diseases and discusses the related clinical drugs that modulate Th17 cell fate in kidney disease treatment.
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Breast cancer stem cells (BCSCs) is a subpopulation of cancer cells with self-renewal and differentiation capacity, have been suggested to give rise to tumor heterogeneity and biologically aggressive behavior. Accumulating evidence has shown that BCSCs play a fundamental role in tumorigenesis, progression, and recurrence. The development of immunotherapy, primarily represented by programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors, has greatly changed the treatment landscape of multiple malignancies. Recent studies have identified pervasive negative associations between cancer stemness and anticancer immunity. Stemness seems to play a causative role in the formation of cold tumor immune microenvironment (TIME). The multiple functions of long non-coding RNAs (lncRNAs) in regulating stemness and immune responses has been recently highlighted in breast cancer. The review focus on lncRNAs and keys pathways involved in the regulation of BCSCs and TIME. Potential clinical applications using lncRNAs as biomarkers or therapies will be discussed.
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Conventional nondegradable packaging and mulch films, after reaching the end of their use, become a major source of waste and are primarily disposed of in landfills. Accumulation of non-degradable film residues in the soil leads to diminished soil fertility, reduced crop yield, and can potentially affect humans. Application of degradable films is still limited due to the high cost, poor mechanical, and gas barrier properties of current biobased synthetic polymers. In this respect, natural polysaccharides and proteins can offer potential solutions. Having versatile functional groups, three-dimensional network structures, biodegradability, ease of processing, and the potential for surface modifications make polysaccharides and proteins excellent candidates for quality films. Besides, their low-cost availability as industrial waste/byproducts makes them cost-effective alternatives. This review paper covers the performance properties, cost assessment, and in-depth analysis of macromolecular structures of some natural polysaccharides and proteins-based films that have great potential for packaging and mulch applications. Proper dissolution of biopolymers to improve molecular interactions and entanglement, and establishment of crosslinkages to form an ordered and cohesive polymeric structure can help to obtain films with good properties. Simple aqueous-based film formulation techniques and utilization of waste/byproducts can stimulate the adoption of affordable biobased films on a large-scale.
Subject(s)
Food Packaging , Polymers , Humans , Food Packaging/methods , Biopolymers/chemistry , Polysaccharides , SoilABSTRACT
Synthetic cannabinoids (SCs) represent a diverse class of new psychoactive substances characterized by extensive substance variety and severe abuse implications. The current situation of synthetic cannabinoid abuse in China is getting worse, with an increasing number of SC variants emerging. Therefore, it is imperative to improve synthetic cannabinoid detecting methods to align with the prevalent abuse situation in the region. In this study, a reliable and validated liquid chromatography-tandem mass spectrometry method was developed for the qualitative and quantitative analysis of 65 SC analogues in human hair samples. The validation results demonstrated satisfactory linearity (r ≥ 0.99) within the range of 25-2500 pg/mg for each SC analogue. The method exhibited limits of detection ranging from 10 to 15 pg/mg and limits of quantification ranging from 25 to 40 pg/mg. The relative standard deviations of intra-day precision and inter-day precision were below 15 %. Furthermore, negligible matrix effects were observed, with recovery rates ranging from 85.70 % to 119.43 %. Analysis of abuser demographics revealed that the primary group engaged in SC analogue abuse consisted of adolescents, predominantly males, accounting for 79.5 % of cases. Among the suspected individuals, ADB-BUTINACA and MDMB-4en-PINACA were the most frequently detected substances. The present study develops a highly sensitive analytical method and provides a comprehensive overview of the prevalence of SC abuse in the eastern region of China.
Subject(s)
Cannabinoids , Illicit Drugs , Male , Humans , Adolescent , Female , Chromatography, Liquid/methods , Tandem Mass Spectrometry/methods , Liquid Chromatography-Mass Spectrometry , Illicit Drugs/analysis , Substance Abuse Detection/methods , Cannabinoids/analysis , Hair/chemistryABSTRACT
PURPOSE: To investigate the effect of TFF3 in the pathogenesis of Diabetic Kidney Disease (DKD), and explore the dynamic changes of TFF3 expression pattern in renal injury process. METHODS: DKD animal model was established by streptozotocin (STZ) (40 mg/kg/d, ip, for 5 days, consecutively) combined with the high fat diet (HFD) for 12 weeks. While animals were sacrificed at different time stages in DKD process (4 weeks, 8 weeks and 12 weeks, respectively). RESULTS: STZ combined with high-fat diet induced weight gain, increased blood glucose and decreased glucose tolerance in DKD mice. Compared to the control group, the DKD group exhibits extracellular matrix (ECM) accumulation and the renal injury was aggravated in a time-dependent manner. The TFF3 expression level was decreased in kidney, and increased in colon tissue. CONCLUSION: TFF3 is not only expressed in colon, but also expressed in renal medulla and cortex. TFF3 might be play a pivotal role in renal mucosal repair by gut-kidney crosstalk, and protect renal from high glucose microenvironment damage.
Subject(s)
Diabetes Mellitus , Diabetic Nephropathies , Mice , Animals , Diabetic Nephropathies/metabolism , Trefoil Factor-3/metabolism , Biological Factors/metabolism , Kidney/pathology , Glucose/metabolism , Diabetes Mellitus/metabolismABSTRACT
Low-dimensional materials exhibit unique quantum confinement effects and morphologies as a result of their nanoscale size in one or more dimensions, making them exhibit distinctive physical properties compared to bulk counterparts. Among all low-dimensional materials, due to their atomic level thickness, two-dimensional materials possess extremely large shape anisotropy and consequently are speculated to have large optically anisotropic absorption. In this work, we demonstrate an optoelectronic device based on the combination of two-dimensional material and carbon dot with wide bandgap. High-efficient luminescence of carbon dot and extremely large shape anisotropy (>1500) of two-dimensional material with the wide bandgap of >4 eV cooperatively endow the optoelectronic device with multi-functions of optically anisotropic blue-light emission, visible light modulation, wavelength-dependent ultraviolet-light detection as well as blue fluorescent film assemble. This research opens new avenues for constructing multi-function-integrated optoelectronic devices via the combination of nanomaterials with different dimensions.
ABSTRACT
Existing clinical treatments for tendinopathy mainly focus on reducing pain, whereas inhibiting or reversing disease progression remains challenging. Local therapeutic drugs, such as glucocorticoids, cause adverse effects on the metabolism of tendon tissues and injection-related complications. Therefore, new administration modalities for tendinopathy need to be developed. In this study, we designed a hydrogel-based microneedle (MN) system for the long-term transdermal delivery of our novel biological cell-free fat extract (CEFFE) to treat tendinopathies. We found that CEFFE-loaded MNs (CEFFE-MNs) had good biosafety and inhibited lipopolysaccharide (LPS)-induced apoptosis and matrix degradation in Achilles tendon cells of rats. The Achilles tendons of rats returned to their maximum mechanical strength after applying CEFFE-MNs. The administration of CEFFE-MNs had better anti-apoptosis and tendon repair-promoting effects than CEFEF injections in vivo. Transcriptome sequencing indicated that the anti-apoptosis effect of CEFFE-MNs was highly related to tumor necrosis factor (TNF) signaling. CEFFE-MNs inhibited the expression of TNF, TNF receptor 1, and downstream nuclear factor-kappa B signaling. Additionally, CEFFE-MNs rescued LPS-induced mitochondrial dynamics in tendon cells via the TNF-Drp1 axis. Our study reports a novel CEFFE-MN system that exhibits long-term anti-inflammatory and anti-apoptotic effects, suggesting it as a new treatment route for tendinopathy with broad clinical translation prospects.
ABSTRACT
Recent studies on osteosarcoma and matrix stiffness are still mostly performed in a 2D setting, which is distinct from in vivo conditions. Therefore, the results from the 2D models may not reflect the real effect of matrix stiffness on cell phenotype. Here, we employed a 3D bioprinted osteosarcoma model, to study the effect of matrix stiffness on osteosarcoma cells. Through density adjustment of GelMA, we constructed three osteosarcoma models with distinct matrix stiffnesses of 50, 80, and 130 kPa. In this study, we found that osteosarcoma cells proliferated faster, migrated more actively, had a more stretched morphology, and a lower drug sensitivity in a softer 3D matrix. When placed in a stiffer matrix, osteosarcoma cells secrete more MMP and VEGF, potentially to fight for survival and attract vascular invasion. Transcriptomic analysis showed that matrix stiffness could impact the signaling pathway of integrin α5-MAPK. The transplantation of 3D printed models in nude mice showed that cells encapsulated in the softer hydrogel were more likely to form subcutaneous tumors. These results suggest that matrix stiffness plays an important role in the development of osteosarcoma in a 3D environment and that inhibition of integrin α5 could block the signal transduction of matrix stiffness.