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1.
J Virol ; 98(5): e0019824, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38591879

ABSTRACT

The involvement of secreted phospholipase A2s in respiratory diseases, such as asthma and respiratory viral infections, is well-established. However, the specific role of secreted phospholipase A2 group IIE (PLA2G2E) during influenza virus infection remains unexplored. Here, we investigated the role of PLA2G2E during H1N1 influenza virus infection using a targeted mouse model lacking Pla2g2e gene (Pla2g2e-/-). Our findings demonstrated that Pla2g2e-/- mice had significantly lower survival rates and higher viral loads in lungs compared to wild-type mice following influenza virus infection. While Pla2g2e-/- mice displayed comparable innate and humoral immune responses to influenza virus challenge, the animals showed impaired influenza-specific cellular immunity and reduced T cell-mediated cytotoxicity. This indicates that PLA2G2E is involved in regulating specific T cell responses during influenza virus infection. Furthermore, transgenic mice expressing the human PLA2G2E gene exhibited resistance to influenza virus infection along with enhanced influenza-specific cellular immunity and T cell-mediated cytotoxicity. Pla2g2e deficiency resulted in perturbation of lipid mediators in the lung and T cells, potentially contributing to its impact on the anti-influenza immune response. Taken together, these findings suggest that targeting PLA2G2E could hold potential as a therapeutic strategy for managing influenza virus infections.IMPORTANCEThe influenza virus is a highly transmissible respiratory pathogen that continues to pose a significant public health concern. It effectively evades humoral immune protection conferred by vaccines and natural infection due to its continuous viral evolution through the genetic processes of antigenic drift and shift. Recognition of conserved non-mutable viral epitopes by T cells may provide broad immunity against influenza virus. In this study, we have demonstrated that phospholipase A2 group IIE (PLA2G2E) plays a crucial role in protecting against influenza virus infection through the regulation of T cell responses, while not affecting innate and humoral immune responses. Targeting PLA2G2E could therefore represent a potential therapeutic strategy for managing influenza virus infection.


Subject(s)
Influenza A Virus, H1N1 Subtype , Lung , Orthomyxoviridae Infections , Animals , Mice , Orthomyxoviridae Infections/immunology , Orthomyxoviridae Infections/virology , Influenza A Virus, H1N1 Subtype/immunology , Lung/virology , Lung/immunology , Lung/pathology , Humans , Group II Phospholipases A2/genetics , Group II Phospholipases A2/immunology , T-Lymphocytes/immunology , Mice, Knockout , Immunity, Cellular , Mice, Inbred C57BL , Mice, Transgenic , Viral Load , Disease Models, Animal , Immunity, Humoral , Immunity, Innate , Influenza, Human/immunology , Influenza, Human/virology , Female
2.
Carbohydr Polym ; 336: 122115, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38670750

ABSTRACT

To alleviate skull defects and enhance the biological activity of taxifolin, this study utilized the thin-film dispersion method to prepare paclitaxel liposomes (TL). Thiolated chitosan (CSSH)-modified TL (CTL) was synthesized through charge interactions. Injectable hydrogels (BLG) were then prepared as hydrogel scaffolds loaded with TAX (TG), TL (TLG), and CTL (CTLG) using a Schiff base reaction involving oxidized dextran and carboxymethyl chitosan. The study investigated the bone reparative properties of CTLG through molecular docking, western blot techniques, and transcriptome analysis. The particle sizes of CTL were measured at 248.90 ± 14.03 nm, respectively, with zeta potentials of +36.68 ± 5.43 mV, respectively. CTLG showed excellent antioxidant capacity in vitro. It also has a good inhibitory effect on Escherichia coli and Staphylococcus aureus, with inhibition rates of 93.88 ± 1.59 % and 88.56 ± 2.83 % respectively. The results of 5-ethynyl-2 '-deoxyuridine staining, alkaline phosphatase staining and alizarin red staining showed that CTLG also had the potential to promote the proliferation and differentiation of mouse embryonic osteoblasts (MC3T3-E1). The study revealed that CTLG enhances the expression of osteogenic proteins by regulating the Wnt signaling pathway, shedding light on the potential application of TAX and bone regeneration mechanisms.


Subject(s)
Cell Proliferation , Chitosan , Hydrogels , Liposomes , Osteoblasts , Quercetin , Quercetin/analogs & derivatives , Skull , Wnt Signaling Pathway , Animals , Chitosan/analogs & derivatives , Chitosan/chemistry , Chitosan/pharmacology , Quercetin/pharmacology , Quercetin/chemistry , Liposomes/chemistry , Wnt Signaling Pathway/drug effects , Osteoblasts/drug effects , Hydrogels/chemistry , Hydrogels/pharmacology , Cell Proliferation/drug effects , Mice , Skull/drug effects , Skull/pathology , Skull/metabolism , Rats , Bone Regeneration/drug effects , Rats, Sprague-Dawley , Osteogenesis/drug effects , Staphylococcus aureus/drug effects , Sulfhydryl Compounds/chemistry , Sulfhydryl Compounds/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Cell Differentiation/drug effects , Escherichia coli/drug effects , Male , Molecular Docking Simulation
3.
Int J Biol Macromol ; 268(Pt 2): 131670, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38643919

ABSTRACT

Bacterial infection, hyperinflammation and hypoxia, which can lead to amputation in severe cases, are frequently observed in diabetic wounds, and this has been a critical issue facing the repair of chronic skin injuries. In this study, a copper-based MOF (TAX@HKUST-1) highly loaded with taxifolin (TAX) with a drug loading of 41.94 ± 2.60 % was prepared. In addition, it has excellent catalase activity, and by constructing an oxygen-releasing hydrogel (PTH) system with calcium peroxide (CaO2), it can be used as a nano-enzyme to promote the generation of oxygen from hydrogen peroxide (H2O2) to provide sufficient oxygen to the wound, and at the same time, solve the problem of the oxidative stress damage caused by excess H2O2 to the cells during the oxygen-releasing process. On the other hand, TAX and HKUST-1 in PTH synergistically promoted antimicrobial and anti-oxidative stress properties, and the bacterial inhibition rate against Staphylococcus aureus and Escherichia coli reached 90 %. In vivo experiments have shown that PTH hydrogel is able to treat diabetic skin repair by inhibiting the expression of inflammation-related proteins and promoting epidermal neogenesis, angiogenesis and collagen deposition.

4.
Heliyon ; 10(6): e28283, 2024 Mar 30.
Article in English | MEDLINE | ID: mdl-38524603

ABSTRACT

Abscisic acid (ABA) is a plant hormone with various biological activities. Aging is a natural process accompanied by cognitive and physiological decline, and aging and its associated diseases pose a serious threat to public health, but its mechanisms remain insufficient. Therefore, the purpose of this study was to investigate the ameliorative effects of ABA on d-galactose (D-Gal)-induced aging in mice and to delve into its molecular mechanisms. Aging model was es-tablished by theintraperitoneal injection of D-Gal. We evaluated the oxidative stress by measuring superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT) levels in serum. Proteins content in brain were determined by Western blot. D-Gal-induced brain damage was monitored by measuring the levels of acetylcholinesterase (AChE) content and hematoxylin-eosin staining (H&E). To evaluate the effects of ABA on aging, we measured the gut microbiota. The results demonstrated that ABA increased SOD, CAT and AChE, decreased MDA level. H&E staining showed that ABA could improve D-Gal-induced damage. In addition, ABA regulated the B-cell-lymphoma-2 (BCL-2) family and Phosphatidylinositol 3-kinase/Protein kinase B (PI3K/AKT) signaling pathway, while further regulating the acetylation of p53 protein by modulating the AMPK pathway and activating SIRT1 protein, thereby inhibiting the apoptosis of brain neurons and thus regulating the aging process. Interestingly, ABA improved the ratio of intestinal bacteria involved in regulating multiple metabolic pathways in the aging process, such as Bacteroides, Firmicutes, Lactobacillus and Ak-kermansia. In conclusion, the present study suggests that ABA may be responsible for improving and delaying the aging process by enhancing antioxidant activity, anti-apoptosis and regulating intestinal flora.

5.
Nano Lett ; 2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38511842

ABSTRACT

Methane oxidation using molecular oxygen remains a grand challenge in which the obstacle is not only the activation of methane but also the reaction with oxygen, considering the mismatch of the ground spin states. Herein, we report TiO2-supported Pt nanocrystals (Pt/TiO2) with surface Pt-Ti alloyed layers that directly convert methane into oxygenates by using O2 as the oxidant with the assistance of CO. The oxygenate yield reached 749.8 mmol gPt-1 in a H2O aqueous solution over 0.1% Pt/TiO2 under 31 bar of mixed gas (20:5:6 CH4:CO:O2) at 150 °C for 3 h, while the CH3OH selectivity was 62.3%. On the basis of the control experiments and spectroscopic results, we identified the surface Pt-Ti alloy as the active sites. Moreover, CO promoted the dissociation of O2 on the surface of Pt-Ti alloyed layers and the subsequent activation of CH4 to form oxygenated products.

6.
Molecules ; 29(5)2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38474556

ABSTRACT

Chemotherapy is a well-established method for treating cancer, but it has limited effectiveness due to its high dosage and harmful side effects. To address this issue, researchers have explored the use of photothermal agent nanoparticles as carriers for precise drug release in vivo. In this study, three different sizes of polydopamine nanoparticles (PDA-1, PDA-2, and PDA-3) were synthesized and evaluated. PDA-2 was selected for its optimal size, encapsulation rate, and drug loading rate. The release of the drug from PDA-2@TAX was tested at different pH and NIR laser irradiation levels. The results showed that PDA-2@TAX released more readily in an acidic environment and exhibited a high photothermal conversion efficiency when exposed to an 808 nm laser. In vitro experiments on ovarian cancer cells demonstrated that PDA-2@TAX effectively inhibited cell proliferation, highlighting its potential for synergistic chemotherapy-photothermal treatment.


Subject(s)
Hyperthermia, Induced , Indoles , Nanoparticles , Ovarian Neoplasms , Polymers , Quercetin/analogs & derivatives , Humans , Female , Phototherapy/methods , Hyperthermia, Induced/methods , Ovarian Neoplasms/drug therapy , Doxorubicin/pharmacology
7.
Int J Biol Macromol ; 263(Pt 1): 130226, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38368971

ABSTRACT

With the improvement of modern living standards, the challenge of diabetic wound healing has significantly impacted the public health system. In this study, our objective was to enhance the bioactivity of taxifolin (TAX) by encapsulating it in liposomes using a thin film dispersion method. Additionally, polyvinyl alcohol/carboxymethyl chitosan-based hydrogels were prepared through repeated freeze-thawing. In vitro and in vivo experiments were conducted to investigate the properties of the hydrogel and its effectiveness in promoting wound healing in diabetic mice. The results of the experiments revealed that the encapsulation efficiency of taxifolin liposomes (TL) was 89.80 ± 4.10 %, with a drug loading capacity of 17.58 ± 2.04 %. Scanning electron microscopy analysis demonstrated that the prepared hydrogels possessed a porous structure, facilitating gas exchange and the absorption of wound exudates. Furthermore, the wound repair experiments in diabetic mice showed that the TL-loaded hydrogels (TL-Gels) could expedite wound healing by suppressing the inflammatory response and promoting the expression of autophagy-related proteins. Overall, this study highlights that TL-Gels effectively reduce wound healing time by modulating the inflammatory response and autophagy-related protein expression, thus offering promising prospects for the treatment of hard-to-heal wounds induced by diabetes.


Subject(s)
Chitosan , Diabetes Mellitus, Experimental , Quercetin/analogs & derivatives , Mice , Animals , Chitosan/chemistry , Liposomes/pharmacology , Diabetes Mellitus, Experimental/drug therapy , Polyvinyl Alcohol/chemistry , Wound Healing , Hydrogels/chemistry , Inflammation , Autophagy
8.
Int J Biol Macromol ; 263(Pt 1): 130256, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38368995

ABSTRACT

The current clinical treatment of diabetic wounds is still based on oxygen therapy, and the slow healing of skin wounds due to hypoxia has always been a key problem in the repair of chronic skin injuries. To overcome this problem, the oxygen-producing matrix CaO2NPS based on the temperature-sensitive dihydromyricetin-loaded hydrogel was prepared. In vitro activity showed that the dihydromyricetin (DHM) oxygen-releasing temperature-sensitive hydrogel composite (DHM-OTH) not only provided a suitable oxygen environment for cells around the wound to survive but also had good biocompatibility and various biological activities. By constructing a T2D wound model, we further investigated the repairing effect of DHM-OTH on chronic diabetic skin wounds and the mechanisms involved. DHM-OTH was able to reduce inflammatory cells and collagen deposition and promote angiogenesis and cell proliferation for diabetic wound healing. These in vitro and in vivo data suggest that DHM-OTH accelerates diabetic wound repair as a novel method to efficiently deliver oxygen to wound tissue, providing a promising strategy to improve diabetic wound healing.


Subject(s)
Chitosan , Diabetes Mellitus, Experimental , Flavonols , Animals , Humans , Hydrogels/pharmacology , Hydrogels/therapeutic use , Poloxamer/pharmacology , Chitosan/pharmacology , Wound Healing , Oxygen , Diabetes Mellitus, Experimental/drug therapy , Bandages
9.
Int J Biol Macromol ; 262(Pt 1): 130079, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38340939

ABSTRACT

Due to impaired immune function, diabetic wounds are highly susceptible to the development of excessive inflammatory responses and prolonged recurrent bacterial infections that impede diabetic wound healing. Therefore, it is necessary to design and develop a wound dressing that controls bacterial infection and inhibits excessive inflammatory response. In this study, hyaluronic acid (HA) was modified using dopamine (DA). Subsequently, cordycepin (COR) was loaded into dopamine-modified hyaluronic acid (OHDA)/gelatin (GEL) nanofiber wound dressing by electrostatic spinning technique. The constructed COR/OHDA/GEL nanofiber membrane has good thermal stability, hydrophilicity, and air permeability. In vitro experiments showed that the obtained COR/OHDA/GEL nanofiber membranes had good antimicrobial efficacy (S. aureus: 95.60 ± 0.99 %, E. coli: 71.17 ± 6.87 %), antioxidant activity (>90 %), and biocompatibility. In vivo experiments showed that COR/OHDA/GEL nanofiber membranes could promote wound tissue remodeling, collagen deposition, and granulation tissue regeneration. Western blot experiments showed that COR/OHDA/GEL nanofibrous membranes could inhibit the excessive inflammatory response of wounds through the TLR4/NF-κB signaling pathway. Therefore, COR/OHDA/GEL nanofiber membranes could promote diabetic wound healing by modulating the inflammatory response. The results showed that the designed nanofiber wound dressing is expected to provide a new strategy for treating chronic wounds.


Subject(s)
Deoxyadenosines , Diabetes Mellitus , Nanofibers , Humans , Gelatin , NF-kappa B , Hyaluronic Acid , Dopamine , Toll-Like Receptor 4 , Staphylococcus aureus , Escherichia coli , Wound Healing , Diabetes Mellitus/drug therapy , Signal Transduction , Anti-Bacterial Agents/pharmacology
10.
Interv Neuroradiol ; : 15910199231217547, 2024 Jan 03.
Article in English | MEDLINE | ID: mdl-38173241

ABSTRACT

OBJECTIVE: To report periprocedural thromboembolic complications of LEO Baby stent-assisted coiling of wide-necked intracranial aneurysms and to analyze the possible influencing factors. METHODS: We retrospectively identified 149 patients with aneurysms who underwent LEO Baby stent-assisted embolization between October 2018 and March 2022. Clinical and radiographic data of patients were reviewed to determine whether a thromboembolic event had occurred. Multivariate logistic analysis was performed to identify significant factors associated with thromboembolic events. RESULTS: Successful stent deployment of the stent was achieved in all patients in the target artery. There were 66 patients (44.3%) with acutely ruptured aneurysms and 83 patients (55.7%) with unruptured aneurysms. Fourteen (9.4%, 95% confidence interval: 4.7%-14.1%) patients were confirmed to have developed a thromboembolic event, including nine patients with acute intraoperative thrombosis and five patients with postoperative thromboembolic events. The rate of thromboembolic events was 6.0% (5/83) in patients with unruptured aneurysms and 13.6% (9/66) in patients with acutely ruptured aneurysms. There was a trend toward an increased rate of thromboembolic events in patients with acute ruptured aneurysms (p = 0.087). Thromboembolic events were significantly associated with the parent-artery diameter (p = 0.010). CONCLUSIONS: Our study demonstrates a low rate of thromboembolic complications in unruptured aneurysms treated with LEO Baby stent. Thromboembolic events appear to be more common in ruptured aneurysms. A small diameter of the parent artery is associated with an increased risk of thromboembolic complications, and more relevant studies are still needed.

11.
Int J Biol Macromol ; 259(Pt 1): 129160, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38181908

ABSTRACT

The healing of wounds in diabetics is commonly delayed by recurring infections and persistent inflammation at the wound site. For this reason, we conducted a study using the electrospinning technique to create nanofiber membranes consisting of polyvinylpyrrolidone/chitosan (PVP/CS) and incorporated dihydromyricetin (DHM) into them. Infrared Fourier transform spectroscopy and scanning electron microscopy were used to analyze the nanofiber membrane. Experimental results in vitro have shown that PVP/CS/DHM has exceptional properties such as hydrophilicity, porosity, water vapor transport rate, antioxidant capacity, and antibacterial activity. Moreover, our study has demonstrated that the application of PVP/CS/DHM can significantly improve wound healing in diabetic mice. After an 18-day treatment period, a remarkable wound closure rate of 88.63 ± 1.37 % was achieved. The in vivo experiments revealed that PVP/CS/DHM can promote diabetic wound healing by suppressing the activation of TLR4/MyD88/NF-κB signaling pathway and enhancing autophagy-related protein as well as CD31 and HIF-1α expression in skin tissues. This study showed that PVP/CS/DHM is a promising wound dressing.


Subject(s)
Chitosan , Diabetes Mellitus, Experimental , Flavonols , Nanofibers , Mice , Animals , Chitosan/chemistry , Povidone , Diabetes Mellitus, Experimental/drug therapy , Nanofibers/chemistry , Wound Healing , Anti-Bacterial Agents/chemistry , Anti-Inflammatory Agents
12.
Int J Biol Macromol ; 259(Pt 2): 129356, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38218300

ABSTRACT

Various types of skin wounds pose challenges in terms of healing and susceptibility to infection, which can have a significant impact on physical and mental well-being, and in severe cases, may result in amputation. Conventional wound dressings often fail to provide optimal support for these wounds, thereby impeding the healing process. As a result, there has been considerable interest in the development of multifunctional polymer matrix hydrogel scaffolds for wound healing. This review offers a comprehensive review of the characteristics of polysaccharide-based hydrogel scaffolds, as well as their applications in different types of wounds. Additionally, it evaluates the advantages and disadvantages associated with various types of multifunctional polymer and polysaccharide-based hydrogel scaffolds. The objective is to provide a theoretical foundation for the utilization of multifunctional hydrogel scaffolds in promoting wound healing.


Subject(s)
Amputation, Surgical , Hydrogels , Hydrogels/pharmacology , Polymers , Polysaccharides/pharmacology , Wound Healing , Anti-Bacterial Agents
13.
Int J Biol Macromol ; 258(Pt 2): 129118, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38163502

ABSTRACT

Colitis can significantly impact daily life. This study utilized DSS to induce acute colitis in mice and examined the regulatory effect of arabinogalactan (AG). The findings demonstrated that AG intake effectively alleviated the phenotype of DSS-induced colitis in mice and protected against small intestine damage. Furthermore, AG suppressed the secretion of pro-inflammatory factors TNF-α and IL-1ß, while promoting the secretion of anti-inflammatory factor IL-10. It also inhibited the secretion of LPS in serum and MPO in colon tissue. Additionally, AG regulated the NF-κB/MAPK/PPARγ signaling pathway and inhibited the NLRP3 inflammasome signaling pathway, thereby ameliorating DSS-induced colitis inflammation in mice. AG also influenced the metabolism of short-chain fatty acids, particularly butyrate, in the intestinal tract of mice. Moreover, AG modulated and enhanced the composition of intestinal flora in mice with colitis, increasing the diversity of dominant flora and promoting the growth of beneficial bacteria. These results highlight the protective effects of arabinogalactan against colitis and its potential applications in the food industry.


Subject(s)
Colitis, Ulcerative , Colitis , Galactans , Gastrointestinal Microbiome , Animals , Mice , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Colitis/chemically induced , Signal Transduction , NF-kappa B/metabolism , Dextran Sulfate/adverse effects , Mice, Inbred C57BL , Disease Models, Animal
14.
Emerg Microbes Infect ; 13(1): 2307513, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38240267

ABSTRACT

Re-emerging human adenovirus type 55 (HAdV55) has become a significant threat to public health due to its widespread circulation and the association with severe pneumonia, but an effective anti-HAdV55 agent remains unavailable. Herein, we report the generation of macaque-derived, human-like monoclonal antibodies (mAbs) protecting against HAdV55 infection with high potency. Using fluorophore-labelled HAdV55 virions as probes, we isolated specific memory B cells from rhesus macaques (Macaca mulatta) that were immunized twice with an experimental vaccine based on E1-, E3-deleted, replication-incompetent HAdV55. We cloned a total of 19 neutralizing mAbs, nine of which showed half-maximal inhibitory concentrations below 1.0 ng/ml. These mAbs recognized the hyper-variable-region (HVR) 1, 2, or 7 of viral hexon protein, or the fibre knob. In transgenic mice expressing human desmoglein-2, the major cellular receptor for HAdV55, a single intraperitoneal injection with hexon-targeting mAbs efficiently prevented HAdV55 infection, and mAb 29C12 showed protection at a dose as low as 0.004 mg/kg. Fibre-targeting mAb 28E8, however, showed protection only at a dose up to 12.5 mg/kg. In tree shrews that are permissive for HAdV55 infection and disease, mAb 29C12 effectively prevented HAdV55-caused pneumonia. Further analysis revealed that fibre-targeting mAbs blocked the attachment of HAdV55 to host cells, whereas hexon-targeting mAbs, regardless of their targeting HVRs, mainly functioned at post-attachment stage via inhibiting viral endosomal escape. Our results indicate that hexon-targeting mAbs have great anti-HAdV55 activities and warrant pre-clinical and clinical evaluation.


Subject(s)
Adenoviruses, Human , Pneumonia , Mice , Animals , Humans , Antibodies, Neutralizing , Mice, Transgenic , Antibodies, Viral , Adenoviruses, Human/genetics , Tupaia , Macaca mulatta , Antibodies, Monoclonal , Tupaiidae , Viral Proteins
15.
IEEE Trans Med Imaging ; 43(1): 175-189, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37440388

ABSTRACT

Deep neural networks typically require accurate and a large number of annotations to achieve outstanding performance in medical image segmentation. One-shot and weakly-supervised learning are promising research directions that reduce labeling effort by learning a new class from only one annotated image and using coarse labels instead, respectively. In this work, we present an innovative framework for 3D medical image segmentation with one-shot and weakly-supervised settings. Firstly a propagation-reconstruction network is proposed to propagate scribbles from one annotated volume to unlabeled 3D images based on the assumption that anatomical patterns in different human bodies are similar. Then a multi-level similarity denoising module is designed to refine the scribbles based on embeddings from anatomical- to pixel-level. After expanding the scribbles to pseudo masks, we observe the miss-classified voxels mainly occur at the border region and propose to extract self-support prototypes for the specific refinement. Based on these weakly-supervised segmentation results, we further train a segmentation model for the new class with the noisy label training strategy. Experiments on three CT and one MRI datasets show the proposed method obtains significant improvement over the state-of-the-art methods and performs robustly even under severe class imbalance and low contrast. Code is publicly available at https://github.com/LWHYC/OneShot_WeaklySeg.


Subject(s)
Image Processing, Computer-Assisted , Neural Networks, Computer , Humans , Supervised Machine Learning
16.
Am J Physiol Cell Physiol ; 326(1): C60-C73, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38009194

ABSTRACT

Radiotherapy has long been a main treatment option for nasopharyngeal carcinoma (NPC). However, during clinical treatment, NPC is prone to developing radioresistance, resulting in treatment failure. This study aims to examine the role of histone methylation in the induction of radioresistance. It was found that the radioresistance of NPC cells was related to the increase of the level of histone H3 lysine 27 trimethylation (H3K27me3). Treatment of cells with histone methyltransferase inhibitor GSK126 increased the radiosensitivity of NPC cells by triggering Bcl2 apoptosis regulator/BCL2-associated X, apoptosis regulator (Bcl2/BAX) signaling pathway. Bioinformatics analysis indicated that the expression of 2'-5'-oligoadenylate synthetase 1 (OAS1) was reduced in the radioresistant cells but increased in the GSK126-treated cells. Chromatin immunoprecipitation assay confirmed that the decrease of OAS1 expression in radioresistant cells was mainly due to the enrichment of H3K27me3 in its promoter region. Furthermore, downregulation of OAS1 reduced apoptosis due to the inhibition of Bcl2/BAX pathway after irradiation, while OAS1 overexpression increased radiosensitivity. Our findings revealed for the first time that the increase of H3K27me3 level was associated with the decrease of OAS1 expression, leading to the inhibition of apoptosis and ultimately contributing to the radioresistance of NPC cells. Moreover, the histone methyltransferase inhibitor GSK126 could overcome the radioresistance and thus might be a potential therapeutic strategy for NPC.NEW & NOTEWORTHY Our findings revealed for the first time that the increase of H3K27me3 level was associated with the decrease of OAS1 expression, leading to the inhibition of apoptosis and ultimately contributing to the radioresistance of NPC cells. Moreover, we demonstrated that the histone methyltransferase inhibitor GSK126 could be a promising therapeutic strategy for NPC by overcoming radioresistance, providing valuable insights into the clinical treatment of NPC.


Subject(s)
Carcinoma , Nasopharyngeal Neoplasms , Humans , Nasopharyngeal Carcinoma/genetics , Nasopharyngeal Carcinoma/radiotherapy , Histones/genetics , Histones/metabolism , Carcinoma/metabolism , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/genetics , Nasopharyngeal Neoplasms/radiotherapy , bcl-2-Associated X Protein/genetics , bcl-2-Associated X Protein/metabolism , Histone Methyltransferases/metabolism , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , 2',5'-Oligoadenylate Synthetase/metabolism
17.
Molecules ; 28(20)2023 Oct 12.
Article in English | MEDLINE | ID: mdl-37894518

ABSTRACT

Large bone defects due to trauma, infections, and tumors are difficult to heal spontaneously by the body's repair mechanisms and have become a major hindrance to people's daily lives and economic development. However, autologous and allogeneic bone grafts, with their lack of donors, more invasive surgery, immune rejection, and potential viral transmission, hinder the development of bone repair. Hydrogel tissue bioengineered scaffolds have gained widespread attention in the field of bone repair due to their good biocompatibility and three-dimensional network structure that facilitates cell adhesion and proliferation. In addition, loading natural products with nanoparticles and incorporating them into hydrogel tissue bioengineered scaffolds is one of the most effective strategies to promote bone repair due to the good bioactivity and limitations of natural products. Therefore, this paper presents a brief review of the application of hydrogels with different gel-forming properties, hydrogels with different matrices, and nanoparticle-loaded natural products loaded and incorporated into hydrogels for bone defect repair in recent years.


Subject(s)
Biological Products , Hydrogels , Humans , Hydrogels/therapeutic use , Hydrogels/chemistry , Tissue Engineering/methods , Tissue Scaffolds/chemistry , Biomedical Engineering
18.
Front Pharmacol ; 14: 1280864, 2023.
Article in English | MEDLINE | ID: mdl-37881184

ABSTRACT

Background: The Zhuyu pill (ZYP), composed of Coptis chinensis Franch. and Tetradium ruticarpum (A. Jussieu) T. G. Hartley, is an effective traditional Chinese medicine with potential anti-cholestatic effects. However, the underlying mechanisms of ZYP remain unknown. Objective: To investigate the mechanism underlying the interventional effect of ZYP on mRNA-seq analysis in cholestasis rat models. Materials and methods: This study tested the effects of a low-dose (0.6 g/kg) and high-dose (1.2 g/kg) of ZYP on a cholestasis rat model induced by α-naphthyl-isothiocyanate (ANIT, 50 mg/kg). Serum biochemistry and histopathology results were used to evaluate the therapeutic effect of ZYP, and mRNA-Seq analysis was performed and verified using real-time fluorescence quantitative PCR (qRT-PCR). GO, KEGG, and GSEA analyses were integrated to identify the mechanism by which ZYP impacted cholestatic rats. Results: ZYP was shown to significantly improve abnormal changes in the biochemical blood indexes and liver histopathology of cholestasis rats and regulate pathways related to bile and lipid metabolism, including fatty acid metabolism, retinol metabolism, and steroid hormone biosynthesis, to alleviate inflammation, cholestasis, and lipid metabolism disorders. Relative expression of the essential genes Cyp2a1, Ephx2, Acox2, Cyp1a2, Cyp2c11, and Sult2a1 was verified by qRT-PCR and showed the same trend as mRNA-seq analysis. Conclusion: ZYP has a significant anti-cholestatic effect by regulating bile metabolism and lipid metabolism related pathways. These findings indicate that ZYP is a novel and promising prospect for treating cholestasis.

19.
Int J Biol Macromol ; 253(Pt 4): 126799, 2023 Dec 31.
Article in English | MEDLINE | ID: mdl-37703965

ABSTRACT

Natural plant polysaccharides are macromolecular substances with a wide range of biological activities. They have a wide range of biological activities, especially play an important role in the treatment of inflammatory bowel disease. The molecular weight of polysaccharides, the composition of monosaccharides and the connection of glycosidic bonds will affect the therapeutic effect on inflammatory bowel disease. Traditional Chinese medicine plant polysaccharides and various types of plant polysaccharides reduce the levels of inflammatory cytokines IL-1ß, IL-6, IL-8 and IL-17, increase the level of anti-inflammatory factor IL-10, regulate NF-κB signaling pathway, and NLRP3 inflammasome to relieve colitis. At the same time, they can play a protective role by regulating the balance of intestinal flora in mice with colitis and increasing the abundance of probiotics to promote the metabolism of polysaccharide metabolites SCFAs. This review summarizes the research on the treatment of inflammatory bowel disease by many natural plant polysaccharides, and provides a theoretical basis for the later treatment of polysaccharides on inflammatory bowel disease.


Subject(s)
Colitis , Gastrointestinal Microbiome , Inflammatory Bowel Diseases , Mice , Animals , Inflammatory Bowel Diseases/drug therapy , Colitis/drug therapy , Colitis/metabolism , Signal Transduction , Polysaccharides/pharmacology , Polysaccharides/therapeutic use , Polysaccharides/chemistry , Dextran Sulfate , Disease Models, Animal , Mice, Inbred C57BL
20.
J Biomech ; 157: 111713, 2023 08.
Article in English | MEDLINE | ID: mdl-37413823

ABSTRACT

Infection with COVID-19 can cause severe complication in the respiratory system, which may be related to increased respiratory resistance. Computational fluid dynamics(CFD) was used in this study to calculate the airway resistance based on the airway anatomy and a common air flowrate. The correlation between airway resistance and COVID-19 prognosis was then investigated. A total of 23 COVID-19 patients with 54 CT scans were grouped into the good prognosis and bad prognosis group based on whether the CT scan shows significant decrease in the pneumonia volume after one week treatment and retrospectively analyzed. A baseline group of 8 healthy people with the same age and gender ratio is enrolled for comparison. Results show that the airway resistance at admission is significantly higher for COVID-19 patients with poor prognosis than those with good prognosis and the baseline(0.063 ± 0.055 vs 0.029 ± 0.011 vs 0.017 ± 0.006 Pa/(ml/s),p = 0.01). In the left superior lobe (r = 0.3974,p = 0.01),left inferior lobe (r = 0.4843,p < 0.01), the right inferior lobe (r = 0.5298,p < 0.0001), the airway resistance was significantly correlated with the degree of pneumonia infection. It is concluded that for COVID-19 patients', airway resistance at admission is closely associated with their prognosis, and has the clinical potential to be used as an index for patients' diagnosis.


Subject(s)
Airway Resistance , COVID-19 , Humans , Retrospective Studies , Hydrodynamics , Lung/diagnostic imaging
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