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OBJECTIVE: Bibliometrics was employed in this study to determine the research trends in the worldwide application of 3D printing technology to treat bone tumors over the previous 10 years. METHODS: Published from 2013 to 2022, the papers related to bone tumors treated with 3D printing were located in Web of Science Core Collection (WoSCC), PubMed, and Scopus. The screened articles were included in this bibliometric study. From these papers in WoSCC, information on annual publications, journals, keywords, countries, authors, institutions, and cited references were extracted and visualized with CiteSpace (version 6.1.R6) software to investigate the state of bone tumor treatment using 3D printing as well as research hotspots. The Carrot2 online visualization tool and Vosviewer software (version 1.6.20) were employed to visualize the publications from PubMed and Scopus, respectively, in order to ascertain the most popular research topics from both databases. RESULTS: A total of 606, 233, and 364 publications were obtained from WoSCC, PubMed, and Scopus, respectively, between the years 2013 and 2022. In WoSCC, the peak number of publications was found in 2021, with 145 publications published. Acta Biomaterialia (11 publications) and World Neurosurgery (10 publications) were the most prolific journals, and Biomaterials was the journal cited the most (244 times). Yong Zhou was the most productive author with 14 publications, while Kwok-Chuen Wong (69 citations) and William F Enneking, (69 citations) possessed the most citations. The country with the largest quantity of publications was China (207). Among all institutions, Shanghai Jiao Tong University produced the most publications (29). Rapid prototyping was the keyword with the strongest citation burst (4.73). 'Reconstruction', 'surgery', 'resection', and 'design' caught the significant attention of researchers. 3D-printed materials, pelvic reconstruction, mandibular reconstruction, computer-assisted surgical techniques, photothermal therapy, and in vitro experiments were recognized as hot subjects and trends in current research. The most frequently occurring topics in Scopus are not significantly different from those found in WoSCC. The most prevalent research areas in PubMed encompass implant, patient-specific, bioceramic, models, and pelvic.
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Environmental stressors such as salinity fluctuations can significantly impact the ecological dynamics of mussel beds. The present study evaluated the influence of hyposalinity stress on the detachment and survival of attached mussels by simulating a mussel farming model in a laboratory setting. Byssus production and mechanical properties of thread in response to varying salinity levels were assessed, and histological sections of the mussel foot were analyzed to identify the changes in the byssus secretory gland area. The results showed that hyposalinity stress (20 and 15 psu) led to a significant decrease in mussel byssus secretion, delayed initiation of new byssus production, and reduced plaque adhesion strength and breaking force of byssal threads compared to the control (30 psu) (p < 0.05). The complete suppression of byssal thread secretion in mussels under salinity conditions of 10 and 5 psu, leading to lethality, indicates the presence of a blockade in byssus secretion when mussels are subjected to significant physiological stressors. Histological analysis further demonstrated a decrease in the percentage of foot secretory gland areas in mussels exposed to low salinities. However, contrary to expectations, the study found that mussels did not exhibit marked detachment from ropes in response to the reduced salinity levels during one week of exposure. Hyposalinity stress exposure reduced the byssal secretion capacity and the mechanical properties of threads, which could be a cause for the detachment of suspension-cultured mussels. These results highlight the vulnerability of mussels to hyposalinity stress, which significantly affects their byssus mechanical performance.
Subject(s)
Salinity , Animals , Stress, Physiological , Bivalvia/physiology , Salt StressABSTRACT
Microglia have both protective and pathogenic properties, while polarization plays a decisive role in their functional diversity. Apart from being an energetic organelle, mitochondria possess biological capabilities of signaling and immunity involving mitochondrial dynamics. The N-methyl-D-aspartate (NMDA)-type glutamate receptor displays excitatory neurotransmission, excitatory neurotoxicity and pro-inflammatory properties in a membrane location- and cell context-dependent manner. In this study, we have provided experimental evidence showing that by acting on mitochondrial dynamics, NMDA receptors displayed pro-inflammatory properties, while its non-competitive inhibitor MK801 exhibited anti-inflammatory potential in Lipopolysaccharide (LPS)-challenged BV-2 microglia cells. LPS stimulation increased the protein phosphorylation of cells regarding their NMDA receptor component subunits and Calcium/Calmodulin-dependent Protein Kinase II (CaMKII), along with mobilizing intracellular calcium. Additionally, parallel changes occurred in the activation of Transforming Growth Factor-ß (TGF-ß)-Activated Kinase 1 (TAK1), NF-κB p65 and NF-κB DNA binding activity, acquisition of pro-inflammatory M1 polarization and expression of pro-inflammatory cytokines. LPS-treated cells further displayed signs of mitochondrial dysfunction with higher expressions of the active form of Dynamin-Related Protein 1 (Drp1), NADPH Oxidase-2 (NOX2) expression and the generation of DCFDA-/MitoSOX-sensitive Reactive Oxygen Species (ROS). NMDA receptor blockade by MK801, along with CaMKII inhibitor KN93, Drp1 inhibitor Mdivi-1 and antioxidant apocynin alleviated LPS-induced pro-inflammatory changes. Other than the reported CaMKII/TAK1/NF-κB axis, our in vitro study revealed the CaMKII/Drp1/ROS/NF-κB axis being an alternative cascade for shaping pro-inflammatory phenotypes of microglia upon LPS stimulation, and MK801 having the potential for inhibiting microglia activation and any associated inflammatory damages.
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This study aimed to investigate whether interbout foot cooling (FC) may enhance repeated lower limb power performance and the corresponding physiological responses based on interset FC, which has been demonstrated to enhance leg-press performance. In a repeated-measures crossover design, ten active men (aged 21.5 ± 1.5 years, exercising >3 times per week) performed four bouts of 10-s cycle ergometer sprints with interbout FC at 10°C water for 2.5 min or non-cooling (NC) with a 5-day interval. The results indicated that FC elicited higher total work (27.57 ± 5.66 kJ vs. 26.55 ± 5.76 kJ) and arousal scores than NC (p < 0.05). Furthermore, under the NC condition, participants decreased mean power (p < 0.05) with no alteration of vastus lateralis (VL) electromyography (EMG) activities after the second bout; whereas under the FC condition, participants maintained steady mean power accompanied by increased VL EMG activities in the last two bouts (p < 0.05). Jointly, participants had higher mean power ([3rd = 10.14 ± 1.15 vs. 9.37 ± 1.30; 4th = 9.79 ± 1.22 vs. 9.23 ± 1.27] W/kg) and VL EMG activities in the last two bouts under the FC than NC condition (p < 0.05). However, perceived exertion and the heart rate were comparable between the two conditions (p > 0.05). In conclusion, interbout FC elicited a higher arousal level and repeated lower limb power performance, which could be explained by delaying peripheral fatigue via increasing excitatory drive and recruiting additional motor units to compensate for fatigue-related responses and power decrements.
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OBJECTIVE: To observe the effect of moxibustion on the indicators of autophagy and apoptosis in the synovium of toes of rats with adjuvant-induced arthritis (AA), so as to explore the underlying mechanism of moxibustion in the treatment of rheumatoid arthritis. METHODS: Forty-five SD rats were randomly divided into the blank control group, model group, moxibustion group, methotrexate group and rapamycin group, with 9 rats in each group. The rat model of AA was established by injecting Freund's complete adjuvant. Rats in the moxibustion group received moxibustion treatment at "Zusanli" (ST36) and "Guanyuan" (CV4) for 20 min, once a day. The methotrexate group was given methotrexate intragastrically (0.35 mg/kg) twice a week. The rapamycin group was given rapamycin by intraperitoneal injection (1 mg/kg), once every other day. The toe volume of the left hind limb was measured by the toe volume measuring instrument after 3-day modeling and 3-week intervention respectively. The contents of interlukin(IL)-1 and tumor necrosis factor(TNF)-α in serum were detected by ELISA. The autophagosomes of synovial cells of the toe joint were observed under transmission electron microscope. The expressions of mammalian target of rapamycin(mTOR)C1, p-mTORC1, Caspase-3, Fas and FasL in synovial tissue were detected by Western blot. RESULTS: Under transmission electron microscope, the model group showed decreased autophagosomes in synovial tissues, but the moxibustion, methotrexate, and rapamycin groups showed increased autophagosomes. Compared with the blank control group, the toe volume, the contents of IL-1 and TNF-α in serum and the expression of p-mTORC1 protein in synovial tissue were significantly increased (P<0.01, P<0.001), while the expressions of Caspase-3, Fas and FasL proteins in synovial tissue were significantly decreased (P<0.05, P<0.01) in the model group. Compared with the model group, the toe volume, the contents of IL-1 and TNF-α in the serum, and expression of p-mTORC1 protein were significantly decreased (P<0.05, P<0.01, P<0.001) in the moxibustion group and the methotrexate group, while the expression of Caspase-3, Fas and FasL proteins in synovial tissue in the moxibustion group and the methotrexate group, the expression of Caspase-3 in the rapamycin group were significantly increased (P<0.05). CONCLUSION: Moxibustion can improve joint swelling in AA rats and decrease the contents of serum IL-1 and TNF-α. The mechanism may be related to regulating the expressions of p-mTORC1, Caspase-3, Fas and FasL proteins, and promoting autophagy and apoptosis of synovial cells.
Subject(s)
Arthritis, Experimental , Moxibustion , Rats , Animals , Caspase 3/genetics , Caspase 3/metabolism , Rats, Sprague-Dawley , Arthritis, Experimental/genetics , Arthritis, Experimental/therapy , Methotrexate/metabolism , Methotrexate/pharmacology , Tumor Necrosis Factor-alpha/metabolism , Synovial Membrane/metabolism , Apoptosis , Autophagy , Interleukin-1/metabolism , Interleukin-1/pharmacology , MammalsABSTRACT
Vagus nerve stimulation through the action of acetylcholine can modulate inflammatory responses and metabolism. α7 Nicotinic Acetylcholine Receptor (α7nAChR) is a key component in the biological functions of acetylcholine. To further explore the health benefits of vagus nerve stimulation, this study aimed to investigate whether α7nAChR agonists offer beneficial effects against poststroke inflammatory and metabolic changes and to identify the underlying mechanisms in a rat model of stroke established by permanent cerebral ischemia. We found evidence showing that pretreatment with α7nAChR agonist, GTS-21, improved poststroke brain infarction size, impaired motor coordination, brain apoptotic caspase 3 activation, dysregulated glucose metabolism, and glutathione reduction. In ischemic cortical tissues and gastrocnemius muscles with GTS-21 pretreatment, macrophages/microglia M1 polarization-associated Tumor Necrosis Factor-α (TNF-α) mRNA, Cluster of Differentiation 68 (CD68) protein, and Inducible Nitric Oxide Synthase (iNOS) protein expression were reduced, while expression of anti-inflammatory cytokine IL-4 mRNA, and levels of M2 polarization-associated CD163 mRNA and protein were increased. In the gastrocnemius muscles, stroke rats showed a reduction in both glutathione content and Akt Serine 473 phosphorylation, as well as an elevation in Insulin Receptor Substrate-1 Serine 307 phosphorylation and Dynamin-Related Protein 1 Serine 616 phosphorylation. GTS-21 reversed poststroke changes in the gastrocnemius muscles. Overall, our findings, provide further evidence supporting the neuroprotective benefits of α7nAChR agonists, and indicate that they may potentially exert anti-inflammatory and metabolic effects peripherally in the skeletal muscle in an acute ischemic stroke animal model.
Subject(s)
Brain Injuries , Ischemic Stroke , Stroke , Rats , Animals , alpha7 Nicotinic Acetylcholine Receptor/agonists , alpha7 Nicotinic Acetylcholine Receptor/genetics , alpha7 Nicotinic Acetylcholine Receptor/metabolism , Acetylcholine , GlucoseABSTRACT
OBJECTIVE: To observe the effect of moxibustion on AMP-activated protein kinase (AMPK)/UNC-51-like kinase 1 (ULK1) signaling pathway in the synovial tissue of toes in rheumatoid arthritis rats, so as to explore the mechanism of mo-xibustion in the treatment of rheumatoid arthritis (RA). METHODS: A total of 45 SD rats were randomly divided into blank, modelï¼ moxibustion, methotrexate and rapamycin groups, with 9 rats in each group. RA rat model was established by injection of Freund's complete adjuvant. Moxibustion was applied to "Zusanli" (ST36) and "Guanyuan" (CV4) for 20 min, once a day for 3 weeks. Methotrexate group was given methotrexate (0.35 mg/kg) by gavage, twice a week for 3 weeks. Rapamycin group was intraperitoneally injected with rapamycin (1 mg/kg)ï¼once every other day for 3 weeks. The toe volume of the left hind limb of rats was measured by the toe volume measuring instrument. The content of AMP in toe synovium was detected by ELISA. The expression of AMPK and VPS34 protein in toe synovium was detected by Western blot.The expression of ULK1 and Atg13 mRNA in toe synovium was detected by RT-PCR. RESULTS: Compared with the blank group, the volume of toe in the model group was increased (P<0.01)ï¼while the content of AMP, the expression of AMPK and VPS34 proteins, the expression of ULK1 and Atg13 mRNAs were significantly decreased(P<0.01).Compared with the model group, the volume of toe in the moxibustionï¼methotre-xate and rapamycin groups was decreased (P<0.05); the content of AMP, the expression of AMPK and VPS34 proteins, the expression of ULK1 and Atg13 mRNAs were significantly increased(P<0.05) in the moxibustion group; the content of AMP, the expression of VPS34 protein, the expression of Atg13 mRNA were significantly increased(P<0.05) in the methotrexate group; the expression of AMPK and VPS34 proteins, the expression of ULK1 and Atg13 mRNAs were significantly increased (P<0.05, P<0.01) in the rapamycin group. Compared with the moxibustion group, the expression of AMPK protein in the methotrexate group and the content of AMP in the rapamycin group were significantly decreased (P<0.05). CONCLUSION: Moxibustion can improve joint swelling in RA rats, and the mechanism may be related to promoting the activity of AMPK/ULK1 signaling pathway.
Subject(s)
Arthritis, Rheumatoid , Moxibustion , Rats , Animals , Rats, Sprague-Dawley , AMP-Activated Protein Kinases/genetics , Methotrexate , Synovial Membrane , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/therapy , Toes , Signal Transduction , Sirolimus , RNA, Messenger , Adenosine Monophosphate , Autophagy-Related Protein-1 Homolog/geneticsABSTRACT
The surfactant modification of catalyst morphology is considered as an effective method to improve photocatalytic performance. In this work, the visible-light-driven composite photocatalyst was obtained by growing CdS nanoparticles in the cubic crystal structure of CdCO3, which, after surfactant modification, led to the formation of CdCO3 elliptical spheres. This reasonable composite-structure-modification design effectively increased the specific surface area, fully exposing the catalytic-activity check point. Cd2+ from CdCO3 can enter the CdS crystal structure to generate lattice distortion and form hole traps, which productively promoted the separation and transfer of CdS photogenerated electron-hole pairs. The prepared 5-CdS/CdCO3@SDS exhibited excellent Cr(VI) photocatalytic activity with a reduction efficiency of 86.9% within 30 min, and the reduction rate was 0.0675 min-1, which was 15.57 and 14.46 times that of CdS and CdCO3, respectively. Finally, the main active substances during the reduction process, the photogenerated charge transfer pathways related to heterojunctions and the catalytic mechanism were proposed and analyzed.
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A 29-year-old female with treated acute lymphoblastic leukemia in remission presented with blurred vision and pain on movement of the right eye. On examination, visual acuity was 20/25 in the right eye and 20/20 in the left eye. Direct ophthalmoscopy revealed that the optic disc was swollen with peripapillary hemorrhage in the right eye. The rest of the clinical examination was within normal limits. Magnetic resonance imaging demonstrated enhancement of her right optic nerve. Lumbar puncture and bone marrow examination revealed no malignant cells. Only vitreous fluid cytology showed blast cells. Intravitreal injection of methotrexate was given, and repeated vitreous tapping was normal. The vision of her right eye remained 20/20 until 1 year later when optic disc and retinal vascular occlusion was noted. Her vision deteriorated to no light perception within 2 weeks, and optociliary shunt vessels occurred. Isolated disc swelling with positive vitreous cytology can be the first and only presentation of relapsed hematologic disorders. Infiltrative optic neuropathy should be considered in the differential diagnosis of optic disc edema. Vitreous tapping could be considered as the diagnostic procedure even if the results of lumbar puncture were negative.
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Two previously undescribed steroidal alkaloids, compounds 1-2, along with two known ones(3-4), were isolated from the 80% ethanol extract of ripe berries of Solanum nigrum by chromatographic methods, including silica gel, ODS, and HPLC. Based on spectroscopic and chemical evidence, including IR, NMR, and HR-ESI-MS data, the structures of the isolated compounds were identified as 12ß,27-dihydroxy solasodine-3-O-ß-D-glucopyranoside(1), 27-hydroxy solasodine-3-O-ß-D-glucopyranosyl-(1â4)-α-L-rhamnopyranosyl-(1â2)-[α-L-rhamnopyranosyl-(1â4)]-ß-D-glucopyranoside(2), solalyraine A(3), and 12ß,27-dihydroxy solasodine(4). Compounds 1-2 were tested for their potential effects against the proliferation of A549 cells, which revealed that compounds 1-2 had weak cytotoxic activity.
Subject(s)
Alkaloids , Saponins , Solanum nigrum , Solanum , Alkaloids/analysis , Ethanol , Fruit/chemistry , Molecular Structure , Plant Extracts/chemistry , Saponins/analysis , Silica Gel/analysis , Solanum/chemistry , Solanum nigrum/chemistry , Steroids/pharmacologyABSTRACT
OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Zusanli"(ST36) and "Guanyuan"(CV4) on the apoptosis rate of synoviocytes and protein expression of Fas, FasL and Caspase-3 in synovial tissue of adjuvant-induced arthritis (AIA) rats, so as to explore its mechanisms underlying improvement of rheumatoid arthritis ï¼RAï¼. METHODS: A total of 24 rats were randomly divided into normal, model, medication and EA groups, with 6 rats in each group. The AIA model was established by injection of complete Freund's adjuvant (CFA, 0.1 mL) into the left hindlimb paw. The rats in the medication group received intraperitoneal injection of 0.35 mg/kg of methotrexate, twice a week for 4 weeks. The rats in the EA group received EA stimulation of ST36 and CV4 (20 Hz/50 Hz, 1 mA) for 20 min, 6 times a week for 4 weeks. The left hind paw volume was measured using a paw volume meter, and histopathological changes of synovial tissue were observed by light microscope after H.E. staining. The serum contents of tumor necrosis factor-αï¼TNF-αï¼ and interleukin-1 ï¼IL-1ï¼ were measured by ELISA. The apoptosis of synoviocytes was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL), and the expression of apoptosis-associated proteins Fas, FasL and Caspase-3 in synovium were detected by Western blot. RESULTS: Compared with the normal group, the left hind paw volume from day 3 to 24 after administration of CFA, serum IL-1 and TNF-α contents were significantly increased (P<0.01), while the expressions of Fas, FasL and Caspase-3 proteins and apoptotic rate of synoviocytes were significantly decreased in the model group (P<0.01). In comparison with the model group, the paw volume from day 17 to 24 after modeling, the serum IL-1 and TNF-α contents were significantly reduced (P<0.01), while the apoptotic rate of synoviocytes, expressions of Fas protein in both medication and EA groups, Caspase-3 protein in the acupuncture group and FasL protein in the medication group were increased (P<0.01, P<0.05). Compared with the medication group, the expression of FasL protein was decreased in EA group (P<0.05). H.E. stain showed obvious hyperplasia of the synovial lining layer, and disordered arrangement of synovial cells, with edema and enlargement in some cells in the model group, which was relatively milder in both medication and EA groups. CONCLUSION: EA of ST36 and CV4 can promote the apoptosis of synoviocytes and the expressions of Fas and FasL proteins in AIA rats, which may contribute to its role in relieving synovitis through activating Fas/FasL signaling.
Subject(s)
Arthritis, Experimental , Electroacupuncture , Synoviocytes , Acupuncture Points , Animals , Apoptosis , Caspase 3 , Fas Ligand Protein , Interleukin-1 , Rats , Tumor Necrosis Factor-alphaABSTRACT
BACKGROUND: We investigated the survival impact and toxicity of maintenance metronomic chemotherapy in patients with metastatic/recurrent nasopharyngeal carcinoma (met/rec NPC). METHODS: Ninety-eight patients with met/rec NPC were first salvaged by IV cisplatin-based chemotherapy and showed nonprogression disease; then maintenance metronomic chemotherapy for at least 12 months was recommended. We analyzed the treatment outcome between patients who received (n = 51) and did not receive (n = 47) maintenance chemotherapy. RESULTS: Baseline patient characteristics showed no significant differences between both arms. Median overall survival for patients with and without maintenance chemotherapy was 36.0 and 12.3 months, respectively (p < 0.0001). Similarly, median progression-free survival was 24.7 and 7.3 months, respectively (p < 0.0001). Furthermore, toxicities during maintenance oral chemotherapy period were usually mild. Transient grade 3 leucopenia (9.8%), anemia (3.9%), thrombocytopenia (7.8%), and no grade 4 toxicity were observed. CONCLUSION: After IV salvage chemotherapy, maintenance oral metronomic chemotherapy significantly improved overall and progression-free survivals while demonstrating low toxicity in patients with met/rec NPC.
Subject(s)
Nasopharyngeal Neoplasms , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cisplatin , Disease-Free Survival , Humans , Nasopharyngeal Carcinoma/drug therapy , Nasopharyngeal Neoplasms/pathology , Neoplasm Recurrence, Local/pathology , Salvage TherapyABSTRACT
PURPOSE: To study serial changes in branching neovascular networks (BNN) by using optical coherence tomography angiography (OCTA) in patients with polypoidal choroidal vasculopathy (PCV) who underwent combined photodynamic therapy (PDT) and anti-vascular endothelial growth factor (anti-VEGF) therapy. METHODS: In this retrospective study of 30 PCV patients who underwent combined therapy, OCTA images obtained at baseline and 1, 3, and 6 months after treatment were collected. The vessel area, vessel percentage area, average vessel length, and presence of polypoidal lesions on OCTA images as well as best-corrected visual acuity (BCVA), central retinal thickness (CRT), and central choroidal thickness (CCT) were recorded at each time point. RESULTS: The BNN- and polypoidal lesion-detection rates on baseline OCTA images were 100% and 71%, respectively. The vessel area decreased during the first 3 months, and increased 6 months post-treatment, showing significant differences from baseline (p = 0.031). The vessel percentage area also reduced 1 and 3 months post-treatment (p = 0.025) and increased 6 months post-treatment. Continuous polypoidal lesion regression was observed from 1 to 3 and 6 months post-treatment (p = 0.031, p = 0.004, p = 0.002, respectively, in comparison with baseline). Patients with a decreasing vessel area over 6 months showed greater choroidal thickness than those with increasing vessel area (p = 0.004). CONCLUSIONS: The BNN showed initial regression but were enlarged at 6 months after therapy. Patients showing continuous BNN regression showed a thicker choroid at baseline. This difference should be considered during treatment for PCV, and OCTA could be used for follow-up evaluations of PCV patients.
Subject(s)
Choroid Diseases , Eye Diseases , Photochemotherapy , Polyps , Choroid/pathology , Choroid Diseases/diagnosis , Fluorescein Angiography/methods , Humans , Intravitreal Injections , Photochemotherapy/methods , Polyps/diagnosis , Polyps/drug therapy , Retrospective Studies , Tomography, Optical Coherence/methods , Vascular Endothelial Growth FactorsABSTRACT
Elevation of intracellular cAMP levels has been implicated in glioma cell proliferation inhibition, differentiation, and apoptosis. Inhibition of phosphodiesterase is a way to elevate intracellular cAMP levels. The present study aimed to investigate the anti-glioma potential of dipyridamole, an inhibitor of phosphodiesterase. Upon treatment with dipyridamole, human U87 glioma cells decreased cell viability, clonogenic colonization, migration, and invasion, along with Noxa upregulation, Endoplasmic Reticulum (ER) stress, impaired autophagic flux, Yes-associated Protein 1 (YAP1) phosphorylation, and YAP1 reduction. Pharmacological and genetic studies revealed the ability of dipyridamole to initiate Noxa-guided apoptosis through ER stress. Additionally, the current study further identified the biochemical role of YAP1 in communicating with ER stress and autophagy under situations of dipyridamole treatment. YAP1 promoted autophagy and protected glioma cells from dipyridamole-induced apoptotic cell death. Dipyridamole impaired autophagic flux and rendered glioma cells more vulnerable to apoptotic cell death through ER stress-inhibitable YAP1/autophagy axis. The overall cellular changes caused by dipyridamole appeared to ensure a successful completion of apoptosis. Dipyridamole also duplicated the biochemical changes and apoptosis in glioma T98G cells. Since dipyridamole has additional biochemical and pharmacological properties, further research centered on the anti-glioma mechanisms of dipyridamole is still needed.
Subject(s)
Apoptosis , Autophagy , Dipyridamole/pharmacology , Endoplasmic Reticulum Stress , Glioblastoma/drug therapy , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Glioblastoma/genetics , Glioblastoma/metabolism , Glioblastoma/physiopathology , Humans , Phosphodiesterase Inhibitors/pharmacology , Phosphorylation , Protein Processing, Post-Translational , Proto-Oncogene Proteins c-bcl-2/genetics , YAP-Signaling Proteins/genetics , YAP-Signaling Proteins/metabolismABSTRACT
Poststroke hyperglycemia and inflammation have been implicated in the pathogenesis of stroke. Janus Kinase 2 (Jak2), a catalytic signaling component for cytokine receptors such as Interleukin-6 (IL-6), has inflammatory and metabolic properties. This study aimed to investigate the roles of Jak2 in poststroke inflammation and metabolic abnormality in a rat model of permanent cerebral ischemia. Pretreatment with Jak2 inhibitor AG490 ameliorated neurological deficit, brain infarction, edema, oxidative stress, inflammation, caspase-3 activation, and Zonula Occludens-1 (ZO-1) reduction. Moreover, in injured cortical tissues, Tumor Necrosis Factor-α, IL-1ß, and IL-6 levels were reduced with concurrent decreased NF-κB p65 phosphorylation, Signal Transducers and Activators of Transcription 3 phosphorylation, Ubiquitin Protein Ligase E3 Component N-Recognin 1 expression, and Matrix Metalloproteinase activity. In the in vitro study on bEnd.3 endothelial cells, AG490 diminished IL-6-induced endothelial barrier disruption by decreasing ZO-1 decline. Metabolically, administration of AG490 lowered fasting glucose, with improvements in glucose intolerance, plasma-free fatty acids, and plasma C Reactive Proteins. In conclusion, AG490 improved the inflammation and oxidative stress of neuronal, hepatic, and muscle tissues of stroke rats as well as impairing insulin signaling in the liver and skeletal muscles. Therefore, Jak2 blockades may have benefits for combating poststroke central and peripheral inflammation, and metabolic abnormalities.
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OBJECTIVE: To observe the effects of electroacupuncture (EA) on autophagosomes, unc-51-like autophage activating kinase 1 (ULK1), Beclin1, and microtubule-associated protein light chain 3 (LC3) expression, and synoviocyte ultrastructure in the synovial tissues of rheumatoid arthritis (RA) rats, and to explore the mechanism of EA in regulating the proliferation of synoviocytes via the autophagy pathway. METHODS: The SD rats were randomly divided into a normal group, a model group, a methotrexate (MTX) group, and an EA group, with 6 rats in each group. Following RA modeling with Freund's complete adjuvant, rats in the MTX group were treated with intragastric administration of 0.35 mg/kg MTX, twice a week, for 4 weeks, while those in the EA group received 20-min EA stimulation at "Zusanli" (ST36) and "Guanyuan" (CV4), once per day, for 4 weeks, with an interval of one day between weeks. The rat left hind toe volume was measured using the toe volume measuring instrument. HE staining was conducted for detecting the morphology of rat synovial tissues, followed by the observation of autophagosomes under the transmission electron microscope. The levels of serum interleukin (IL)-1 and tumor necrosis factor (TNF)-α were assayed by ELISA, and the protein expression levels of ULK1, Beclin1, and LC3 were detected by Western blot. RESULTS: Compared with the normal group, the left hind toe volume of the model group increased significantly (P<0.01), while serum IL-1 and TNF-α (P<0.01), synovial ULK1, Beclin1, and LC3 protein expression (P<0.01, P<0.05) up-regulated. HE stain and electron microscope showed obvious synovial hyperplasia, and doublemembrane autophagosomes scattering in the synoviocytes. The comparison with the model group showed that MTX and EA remarkably decreased the left hind toe volume (P<0.01), serum IL-1 and TNF-α (P<0.01), down-regulated the protein expression levels of ULK1 and LC3 in synovial tissues (P<0.05, P<0.01), and inhibited the synovial hyperplasia, with no obvious autophagosomes observed in the synoviocytes. The protein expression of ULK1 in the EA group was significantly lower than that in the MTX group (P<0.01). CONCLUSION: EA alleviates the joint swelling and synoviocyte injury of RA rats possibly by regulating the expression of ULK1, LC3, and Beclin1 and inhibiting the synoviocyte autophagy and proliferation.
Subject(s)
Arthritis, Rheumatoid , Electroacupuncture , Animals , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/therapy , Autophagy , Rats , Rats, Sprague-Dawley , Synovial MembraneABSTRACT
Inter-set peripheral cooling can improve high-intensity resistance exercise performance. However, whether foot cooling (FC) would increase 1 repetition maximum (RM) lower-limb strength is unclear. This study investigated the effect of intermittent FC on 1 RM leg press strength. Ten recreational male lifters performed three attempts of 1 RM leg press with FC or non-cooling (NC) in a repeated-measures crossover design separated by 5 days. FC was applied by foot immersion in 10 °C water for 2.5 min before each attempt. During the 1 RM test, various physiological measures were recorded. The results showed that FC elicited higher 1 RM leg press strength (Δ [95% CI]; Cohen's d effect size [ES]; 13.6 [7.6-19.5] kg; ES = 1.631) and electromyography values in vastus lateralis (57.7 [8.1-107.4] µV; ES = 0.831) and gastrocnemius (15.1 [-3.1-33.2] µV; ES = 0.593) than in NC. Higher arousal levels (felt arousal scale) were found in FC (0.6 [0.1-1.2]; ES = 0.457) than in NC. In conclusion, the preliminary findings, although limited, suggest intermittent FC has a potential ergogenic role for recreational athletes to enhance maximal lower-limb strength and may partly benefit strength-based competition events.
Subject(s)
Leg , Resistance Training , Humans , Male , Muscle Strength , Muscle, Skeletal , Pilot Projects , Quadriceps Muscle , Weight LiftingABSTRACT
The present study examined the sustained effects of acute resistance exercise on inhibitory function in healthy middle-aged adults. Seventy healthy middle-aged adults (mean age = 46.98 ± 5.70 years) were randomly assigned to exercise or control groups, and the Stroop test was administered before, immediately after, and 40 min after exercise. The resistance exercise protocol involved two sets of seven exercises performed for a maximum of 10 repetitions, with 60 s between sets and exercises. Acute resistance exercise resulted in higher Stroop test performance under the incongruent (inhibition) and interference conditions immediately post-exercise and 40 min post-exercise. Furthermore, the difference in scores after 40 min was significant. The findings indicate that a moderately intensive acute resistance exercise could facilitate Stroop performance and has a more beneficial effect on sustaining of cognition that involves executive control at least 40 min.
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The outbreak of COVID-19 has already generated a huge societal, economic and political losses worldwide. The present study aims to investigate the antiviral activity of Poly(hexamethylene biguanide) hydrochloride (PHMB) treated fabric against COVID-19 by using the surrogate Feline coronavirus. The antiviral analysis indicated that up to 94% of coronavirus was killed after contacting the CVC fabric treated with PHMB for 2 h, which suggests that PHMB treated fabric could be used for developing protective clothing and beddings with antiviral activity against coronavirus and can play a role in fighting the transmission of COVID-19 in the high-risk places.
ABSTRACT
ABSTRACT: EFNA1 is a key gene that is associated with the pathogenesis of several human cancers. However, the prognostic role of EFNA1 in many cancers and the relationship between EFNA1 and tumor-infiltrating lymphocytes in different cancers remain unclear.The expression levels of EFNA1 in 33 types of cancer in the TCGA (The Cancer Genome Atlas) database were collected via the UCSC Xena browser. The clinical data of LGG (low grade glioma) patients were downloaded from the TCGA database. The glioma data from the CGGA (Chinese Glioma Genome Atlas) database were also downloaded to verify the results. Kaplan-Meier and Cox regression analyses were used to investigate the prognostic value of EFNA1 in different cancers using R software. We verified the differential expression of EFNA1 in glioma and normal brain tissue via gene expression profiling interactive analysis. We evaluated the relationship between the expression level of EFNA1 and the clinicopathological features of LGG patients via the Wilcoxon signed-rank test. The immune infiltration levels were evaluated via tumor immune estimation resource (TIMER) and CIBERSORT, and the correlations between EFNA1 and immune cell levels were investigated via TIMER. Finally, we conducted gene set enrichment analysis (GSEA) to explore the potential mechanisms.Data from the TCGA database showed that EFNA1 was differentially expressed in many kinds of cancers when compared with normal tissues. Upregulated EFNA1 expression in esophageal carcinoma (ESCA), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), and LGG correlated with shorter patient overall survival (OS) times. The Cox regression analysis revealed that the expression of EFNA1 was also a risk factor for the disease-specific survival (DSS) and progression-free interval (PFI) of LGG patients. The multiple Cox regression analysis revealed that EFNA1 was an independent prognostic factor for LGG patients. In addition, EFNA1 expression was increased in the WHO grade III group and the 1p19q non-codeletion group. Moreover, EFNA1 expression was positively correlated with the levels of infiltrating CD4+ T cells, myeloid dendritic cells and neutrophils in LGG. GSEA suggested that several GO and kyoto encyclopedia of genes and genomes (KEGG) items associated with nervous system function and apoptotic pathway were significantly enriched in the EFNA1-low and EFNA1-high expression phenotypes.EFNA1 may play a pivotal role in the development of LGG and may serve as a potential marker for LGG prognosis and therapy.