OBJECTIVES: To investigate the protective effects of graphene heating film far-infrared (FIR) hyperthermia therapy against frostbite in mice and its impacts on microcirculation and coagulation function. METHODS: Seventy-six C57BL/6J mice were randomized into control, model, graphene-FIR, and carbon fiber-FIR groups. After 7-day FIR intervention (4 h/day), the mice were subjected to acute (4 ℃, 4 h) and intermittent (4 ℃, 4 h/day for 3 days) cold exposure and the changes in rectal temperature were monitored. In liquid nitrogen frostbite experiment, 24 ICR mice were divided into model, graphene-FIR, and carbon fiber-FIR groups, and after a 7-day FIR pretreatment (4 h/day), the liquid nitrogen frostbite models were established and apparent scores of the wounds were assessed on days 3 and 6 after modeling. In carrageenan-induced thrombosis experiment, 40 ICR mice were allocated to control, model, graphene-FIR, carbon fiber-FIR, and prazosin groups to test the effect of a 7-day FIR intervention on thrombosis induced by intraperitoneal carrageenan injection (2.5 mg/kg) by measuring thrombus length, blood perfusion, and serum biomarkers (6-keto-PGF1α, TXB2, t-PA, IL-6, IL-1β, TNF‑α) 24 h after the injection. RESULTS: The mice in graphene-FIR group showed significantly elevated rectal temperature in cold exposure tests. In mice with liquid nitrogen-induced frostbite, graphene-FIR treatment significantly reduced the wound scores and reduced frostbite area, producing better effects than carbon fiber. In mice with carrageenan-induced thrombosis, graphene-FIR treatment significantly decreased tail thrombosis length and thrombosis area, increased blood perfusion, lowered serum levels of TXB2, TNF-α and IL-6, and increased the levels of 6-keto-PGF1α and t-PA. CONCLUSIONS Graphene heating film FIR therapy can alleviate frostbite injury in mice by improving microcirculation, suppressing thrombosis and inflammatory responses, and reducing coagulation dysfunction.
Animals ; Frostbite/therapy* ; Graphite ; Mice, Inbred C57BL ; Mice ; Infrared Rays ; Mice, Inbred ICR ; Hyperthermia, Induced/methods* ; Male ; Microcirculation

Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications (ASMs), a condition known as pharmacoresistant epilepsy. The management of pharmacoresistant epilepsy remains an intractable issue in the clinic. Its early prediction is important for prevention and diagnosis. However, it still lacks effective predictors and approaches. Here, a classical model of pharmacoresistant temporal lobe epilepsy (TLE) was established to screen pharmacoresistant and pharmaco-responsive individuals by applying phenytoin to amygdaloid-kindled rats. Ictal electroencephalograms (EEGs) recorded before phenytoin treatment were analyzed. Based on ictal EEGs from pharmacoresistant and pharmaco-responsive rats, a convolutional neural network predictive model was constructed to predict pharmacoresistance, and achieved 78% prediction accuracy. We further found the ictal EEGs from pharmacoresistant rats have a lower gamma-band power, which was verified in seizure EEGs from pharmacoresistant TLE patients. Prospectively, therapies targeting the subiculum in those predicted as "pharmacoresistant" individual rats significantly reduced the subsequent occurrence of pharmacoresistance. These results demonstrate a new methodology to predict whether TLE individuals become resistant to ASMs in a classic pharmacoresistant TLE model. This may be of translational importance for the precise management of pharmacoresistant TLE.
Epilepsy, Temporal Lobe/diagnosis* ; Animals ; Drug Resistant Epilepsy/drug therapy* ; Electroencephalography/methods* ; Rats ; Anticonvulsants/pharmacology* ; Neural Networks, Computer ; Male ; Humans ; Phenytoin/pharmacology* ; Adult ; Disease Models, Animal ; Female ; Rats, Sprague-Dawley ; Young Adult ; Convolutional Neural Networks

Radiation-induced thrombocytopenia (RIT) faces a perplexing challenge in the clinical treatment of cancer patients, and current therapeutic approaches are inadequate in the clinical settings. In this research, oxymatrine, a new molecule capable of healing RIT was screened out, and the underlying regulatory mechanism associated with magakaryocyte (MK) differentiation and thrombopoiesis was demonstrated. The capacity of oxymatrine to induce MK differentiation was verified in K-562 and Meg-01 cells in vitro. The ability to induce thrombopoiesis was subsequently demonstrated in Tg (cd41:enhanced green fluorescent protein (eGFP)) zebrafish and RIT model mice. In addition, we carried out network pharmacological prediction, drug affinity responsive target stability assay (DARTS) and cellular thermal shift assay (CETSA) analyses to explore the potential targets of oxymatrine. Moreover, the pathway underlying the effects of oxymatrine was determined by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, Western blot (WB), and immunofluorescence. Oxymatrine markedly promoted MK differentiation and maturation in vitro. Moreover, oxymatrine induced thrombopoiesis in Tg (cd41:eGFP) zebrafish and accelerated thrombopoiesis and platelet function recovery in RIT model mice. Mechanistically, oxymatrine directly binds to toll-like receptor 2 (TLR2) and further regulates the downstream pathway stimulator of interferon genes (STING)/nuclear factor-kappaB (NF-κB), which can be blocked by C29 and C-176, which are specific inhibitors of TLR2 and STING, respectively. Taken together, we demonstrated that oxymatrine, a novel TLR2 agonist, plays a critical role in accelerating MK differentiation and thrombopoiesis via the STING/NF-κB axis, suggesting that oxymatrine is a promising candidate for RIT therapy.

OBJECTIVE: Emerging evidence suggests that exposure to ultrafine particulate matter (UPM, aerodynamic diameter < 0.1 µm) is associated with adverse cardiovascular events. Previous studies have found that Shenlian (SL) extract possesses anti-inflammatory and antiapoptotic properties and has a promising protective effect at all stages of the atherosclerotic disease process. In this study, we aimed to investigated whether SL improves UPM-aggravated myocardial ischemic injury by inhibiting inflammation and cell apoptosis. METHODS: We established a mouse model of MI+UPM. Echocardiographic measurement, measurement of myocardialinfarct size, biochemical analysis, enzyme-linked immunosorbent assay (ELISA), histopathological analysis, Transferase dUTP Nick End Labeling (TUNEL), Western blotting (WB), Polymerase Chain Reaction (PCR) and so on were used to explore the anti-inflammatory and anti-apoptotic effects of SL in vivo and in vitro. RESULTS: SL treatment can attenuate UPM-induced cardiac dysfunction by improving left ventricular ejection fraction, fractional shortening, and decreasing cardiac infarction area. SL significantly reduced the levels of myocardial enzymes and attenuated UPM-induced morphological alterations. Moreover, SL significantly reduced expression levels of the inflammatory cytokines IL-6, TNF-α, and MCP-1. UPM further increased the infiltration of macrophages in myocardial tissue, whereas SL intervention reversed this phenomenon. UPM also triggered myocardial apoptosis, which was markedly attenuated by SL treatment. The results of in vitro experiments revealed that SL prevented cell damage caused by exposure to UPM combined with hypoxia by reducing the expression of the inflammatory factor NF-κB and inhibiting apoptosis in H9c2 cells. CONCLUSION Overall, both in vivo and in vitro experiments demonstrated that SL attenuated UPM-aggravated myocardial ischemic injury by inhibiting inflammation and cell apoptosis. The mechanisms were related to the downregulation of macrophages infiltrating heart tissues.
Animals ; Apoptosis/drug effects* ; Particulate Matter/adverse effects* ; Mice ; Male ; Inflammation/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Inbred C57BL ; Myocardial Ischemia/drug therapy* ; Cell Line

The S100 calcium-binding protein family member A16(S100A16)exhibits differential expression in various malignant tumors and plays a critical role in tumor progression,including effects on tumor cell proliferation,apoptosis,adhesion,epithelial-mesenchymal transition,migration,and invasion.Its aberrant expression is associated with adverse clinical outcomes,making it a potential prognostic biomarker.Fur-thermore,S100A16 is closely linked to the infiltration of immune cells within the tumor microenvironment,contributing to the establish-ment of an immunosuppressive state.The expression level of S100A16 in tumor-associated endothelial cells may also correlate with the formation of an inhibitory immune microenvironment.Additionally,S100A16 has been implicated in tumor chemotherapy resistance.This review summarizes recent advances in our understanding of the mechanisms by which S100A16 contributes to different types of tumors,its regulatory effects on the tumor immune microenvironment,and its role in drug treatment resistance.The aim of this review is to elucidate the underlying mechanisms of tumor prevention and treatment and provide a theoretical foundation for overcoming drug resistance in can-cer therapy.

6-Shogaol is an active component of gingerol in zingiber,which can be converted from 6-Gingerol under acidic and heating conditions.Modern research shows that 6-Shogaol has rich pharmacological activities,and it is found that 6-Shogaol has stronger anti-inflammatory,anti-tumor and antioxidant activities than 6-Gingerol.In this article,the preparation technology and pharmacological effects of 6-Shogaol were reviewed,and the extraction and separation methods of 6-Shogaol,as well as the targets and pathways involved in the process of exerting its pharmacological effects,were summarized,which could lay the foundation for the comprehensive development and clinical application of 6-Shogaol.

The plants of the genus Caragana Fabr. are desert plants of the Leguminosae family, which are widely used in traditional ethnomedicine, with the effects of nourishing Yin and nourishing blood, dispelling wind and removing dampness, clearing heat and detoxifying toxins. The anti-inflammatory effect of Caragana Fabr. has attracted much attention, the research on the related mechanism has made some progress, but it lacks systematic collation. By summarising the anti-inflammatory effects of the active ingredients of Caragana Fabr., the authors found that they have good anti-inflammatory activities on different inflammatory cell models in vitro, and have good improvement effects on rheumatoid arthritis, colitis, complex nephritis, and acute lung injury and other disease models. The anti-inflammatory effects of the active components of this genus mainly include the reduction of the levels of a variety of pro-inflammatory factors, and the signalling pathways involved mainly include TLR4/NF-κB, TLR4/MAPK, TLR4/NF-κB/IRF3, JAK/STAT-1, ERK/STAT-1 and so on. Therefore, the paper mainly reviews the research progress on the anti-inflammatory effects and mechanisms of the Caragana Fabr. plants and their active components according to disease types, with a view to providing reference for the in-depth study of their anti-inflammatory activities and the development of new products with related functions.

BACKGROUND:Arthroscopic single-row fixation with knotless suture bridge fixation techniques have been commonly used in the treatment of rotator cuff injuries,but the clinical efficacy in rotator cuff injuries combined with osteoporosis is unclear.OBJECTIVE:To investigate the clinical efficacy of arthroscopic single-row fixation versus knotless suture bridge fixation in the treatment of rotator cuff injuries combined with osteoporosis.METHODS:One hundred and twenty-two patients with rotator cuff injuries combined with osteoporosis who underwent arthroscopic treatment admitted to Affiliated Hospital of Xuzhou Medical University between January 2018 and August 2022 were retrospectively analyzed.They were divided into two groups according to the treatment plan.There were 63 patients with single-row fixation(single-row group)and 59 patients with knotless suture-bridge fixation(suture-bridge group).The visual analog scale scores for pain,University of California Los Angeles Shoulder Score,American Shoulder and Elbow Surgeons Score,Constant-Murley score,and shoulder range of motion were compared between the two groups at the preoperative and 1 year postoperative periods.Rotator cuff re-tears were evaluated at 1 year postoperatively using the Sugaya staging criteria.The occurrence of complications was recorded in both groups.RESULTS AND CONCLUSION:(1)All patients received more than 1-year follow-up.No complications such as incision infection and nerve injury occurred in both groups after surgery.(2)Postoperative visual analog scale scores,University of California Los Angeles Shoulder Score,American Shoulder and Elbow Surgeons Score,Constant-Murley scores,and shoulder range of motion were significantly improved 1 year postoperatively in both groups compared with the preoperative period(P＜0.05).Visual analog scale scores,University of California Los Angeles Shoulder Score,American Shoulder and Elbow Surgeons Score,Constant-Murley scores,and shoulder range of motion were better in the suture-bridge group than in the single-row group 1 year postoperatively(P＜0.05).(3)At 1 year postoperatively,the re-tear rate in the single-row group[22％(14/63)]was significantly higher than that in the suture-bridge group[7％(4/59)],and the difference between the two groups was statistically significant(x2=5.777,P=0.016).(4)It is indicated that arthroscopic single-row fixation and knotless suture bridge fixation for rotator cuff injuries combined with osteoporosis both yielded satisfactory clinical outcomes,but knotless suture bridge fixation was more clinically effective,with a lower rate of postoperative retear.

ObjectiveTo investigate the mechanism by which Huanglian Jiedutang （HLJDT） inhibits pyroptosis and neuroinflammation in Alzheimer's disease （AD） mice via the NOD-like receptor protein 3 （NLRP3）/cysteinyl aspartate-specific protease-1 （Caspase）-1/gasdermin D （GSDMD） pathway. MethodsThirty APP/PS1 double transgenic mice were randomly and evenly divided into the model group （model group）， the positive control group （Donepezil group， 0.65 mg·kg^-1）， and the HLJDT treatment group （HLJDT group， 5.2 g·kg^-1）. Ten C57BL/6 mice were assigned to the blank control group （control group）. The Morris water maze and novel object recognition tests were used to evaluate learning and memory abilities. Nissl staining was employed to observe the morphology， quantity， and distribution of neurons in the hippocampal region. Golgi staining was used to examine the morphology and density of neuronal dendritic spines in the hippocampus. Real-time quantitative polymerase chain reaction （Real-time PCR） was performed to detect the mRNA expression of neuroinflammation-related factors and genes in the NLRP3/Caspase-1/GSDMD pyroptosis pathway in the hippocampus. Western blot was used to detect the expression of postsynaptic density protein 95 （PSD95）， amyloid precursor protein （APP）， inflammatory factors including nuclear factor-κB （NF-κB）， phosphorylated NF-κB （p-NF-κB）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， as well as pyroptosis pathway-related proteins including NLRP3， Caspase-1， GSDMD， and GSDMD-N. ResultsCompared with the control group， the model group exhibited significantly decreased learning and memory abilities （P<0.01）， reduced numbers of neurons in the hippocampal CA3 region and dendritic spines in the hippocampal CA1 region （P<0.01）， and significantly increased hippocampal mRNA expression levels of NLRP3， Caspase-1， GSDMD， NF-κB， TNF-α， IL-1β， and IL-18 （P<0.01）. Protein levels of PSD95 were markedly decreased， while the expression levels of NLRP3， Caspase-1， GSDMD， p-NF-κB/NF-κB， TNF-α， IL-1β， and APP were significantly elevated （P<0.01）. Compared with the model group， both the Donepezil and HLJDT groups showed significantly improved learning and memory abilities （P<0.05， P<0.01）， increased numbers of hippocampal neurons in the hippocampal CA3 region and dendritic spines in the hippocampal CA1 region （P<0.01）， and significantly decreased hippocampal mRNA expression levels of NLRP3， Caspase-1， GSDMD， NF-κB， TNF-α， IL-1β， and IL-18 （P<0.05， P<0.01）. Protein levels of NLRP3， Caspase-1， GSDMD， p-NF-κB/NF-κB， TNF-α， IL-1β， and APP were significantly downregulated， while PSD95 expression was significantly upregulated （P<0.05， P<0.01）. There was no statistically significant difference in GSDMD-N levels in the Donepezil group， while GSDMD-N expression was significantly decreased in the HLJDT group （P<0.05）. ConclusionThis study confirms that HLJDT can improve learning and memory abilities in APP/PS1 double transgenic mice， and attenuate neuronal loss and synaptic damage， possibly through inhibition of pyroptosis via the NLRP3/Caspase-1/GSDMD pathway.

ObjectiveTo investigate the mechanism by which Huanglian Jiedutang （HLJDT） inhibits pyroptosis and neuroinflammation in Alzheimer's disease （AD） mice via the NOD-like receptor protein 3 （NLRP3）/cysteinyl aspartate-specific protease-1 （Caspase）-1/gasdermin D （GSDMD） pathway. MethodsThirty APP/PS1 double transgenic mice were randomly and evenly divided into the model group （model group）， the positive control group （Donepezil group， 0.65 mg·kg^-1）， and the HLJDT treatment group （HLJDT group， 5.2 g·kg^-1）. Ten C57BL/6 mice were assigned to the blank control group （control group）. The Morris water maze and novel object recognition tests were used to evaluate learning and memory abilities. Nissl staining was employed to observe the morphology， quantity， and distribution of neurons in the hippocampal region. Golgi staining was used to examine the morphology and density of neuronal dendritic spines in the hippocampus. Real-time quantitative polymerase chain reaction （Real-time PCR） was performed to detect the mRNA expression of neuroinflammation-related factors and genes in the NLRP3/Caspase-1/GSDMD pyroptosis pathway in the hippocampus. Western blot was used to detect the expression of postsynaptic density protein 95 （PSD95）， amyloid precursor protein （APP）， inflammatory factors including nuclear factor-κB （NF-κB）， phosphorylated NF-κB （p-NF-κB）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， as well as pyroptosis pathway-related proteins including NLRP3， Caspase-1， GSDMD， and GSDMD-N. ResultsCompared with the control group， the model group exhibited significantly decreased learning and memory abilities （P<0.01）， reduced numbers of neurons in the hippocampal CA3 region and dendritic spines in the hippocampal CA1 region （P<0.01）， and significantly increased hippocampal mRNA expression levels of NLRP3， Caspase-1， GSDMD， NF-κB， TNF-α， IL-1β， and IL-18 （P<0.01）. Protein levels of PSD95 were markedly decreased， while the expression levels of NLRP3， Caspase-1， GSDMD， p-NF-κB/NF-κB， TNF-α， IL-1β， and APP were significantly elevated （P<0.01）. Compared with the model group， both the Donepezil and HLJDT groups showed significantly improved learning and memory abilities （P<0.05， P<0.01）， increased numbers of hippocampal neurons in the hippocampal CA3 region and dendritic spines in the hippocampal CA1 region （P<0.01）， and significantly decreased hippocampal mRNA expression levels of NLRP3， Caspase-1， GSDMD， NF-κB， TNF-α， IL-1β， and IL-18 （P<0.05， P<0.01）. Protein levels of NLRP3， Caspase-1， GSDMD， p-NF-κB/NF-κB， TNF-α， IL-1β， and APP were significantly downregulated， while PSD95 expression was significantly upregulated （P<0.05， P<0.01）. There was no statistically significant difference in GSDMD-N levels in the Donepezil group， while GSDMD-N expression was significantly decreased in the HLJDT group （P<0.05）. ConclusionThis study confirms that HLJDT can improve learning and memory abilities in APP/PS1 double transgenic mice， and attenuate neuronal loss and synaptic damage， possibly through inhibition of pyroptosis via the NLRP3/Caspase-1/GSDMD pathway.