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Ozone (O3) pollution is a severe environmental problem in China. The incomplete understanding of atmospheric photochemical reaction mechanisms prevents us from accurately understanding the chemistry of O3 production. Here, we used an improved dual-channel reaction chamber technique to measure net photochemical O3 production rate (P(O3)net) directly in Dongguan, a typical industrial city in China. The maximum P(O3)net was 46.3 ppbv h-1 during the observation period, which is at a relatively high level compared to previous observations under different environment worldwide. We employed an observation-based box model coupled with the state-of-the-art atmospheric chemical mechanism (MCM v3.3.1) to investigate the chemistry of O3 production. Under the base scenario, the modelling underestimates P(O3)net by ~30â¯%. Additionally considering HO2 uptake by ambient aerosols, inorganic deposition, and Cl chemistry only caused a small change (< 13â¯%) in the simulation of P(O3)net. Further analysis indicates that unmeasured reactive volatile organic compounds (VOCs), such as oxygenated VOCs and branched alkenes are potential contributors to the underestimation of P(O3)net. This study underscores the underestimation of P(O3)net in conventional atmospheric modelling setups, providing a crucial scientific foundation for further investigation aimed at promoting our understanding of photochemical O3 formation.
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In near-road neighborhoods, residents are more frequently exposed to traffic-related air pollution (TRAP), and they are increasingly aware of pollution levels. Given this consideration, this study adopted portable air pollutant sensors to conduct a mobile monitoring campaign in two near-road neighborhoods, one in an urban area and one in a suburban area of Shanghai, China. The campaign characterized spatiotemporal distributions of fine particulate matter (PM2.5) and black carbon (BC) to help identify appropriate mitigation measures in these near-road micro-environments. The study identified higher mean TRAP concentrations (up to 4.7-fold and 1.7-fold higher for PM2.5 and BC, respectively), lower spatial variability, and a stronger inter-pollutant correlation in winter compared to summer. The temporal variations of TRAP between peak hour and off-peak hour were also investigated. It was identified that district-level PM2.5 increments occurred from off-peak to peak hours, with BC concentrations attributed more to traffic emissions. In addition, the spatiotemporal distribution of TRAP inside neighborhoods revealed that PM2.5 concentrations presented great temporal variability but almost remained invariant in space, while the BC concentrations showed notable spatiotemporal variability. These findings provide valuable insights into the unique spatiotemporal distributions of TRAP in different near-road neighborhoods, highlighting the important role of hyperlocal monitoring in urban micro-environments to support tailored designing and implementing appropriate mitigation measures.
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Poluentes Atmosféricos , Monitoramento Ambiental , Material Particulado , Emissões de Veículos , Poluentes Atmosféricos/análise , Material Particulado/análise , Emissões de Veículos/análise , China , Poluição do Ar/estatística & dados numéricos , Poluição Relacionada com o Tráfego/análise , Fuligem/análiseRESUMO
Background: The botulinum toxin is an extremely potent substance that impacts the nervous system. There has been a rise in cases of medical poisoning associated with it, particularly in the field of plastic and aesthetic procedures, in recent years. Case description: A 51-year-old woman underwent a facial wrinkle reduction procedure with an unauthorized injection of 100 U of botulinum toxin at an unlicensed medical facility six days prior to hospitalization. Over time, her toxicity symptoms intensified, impacting her respiratory muscles, and she did not receive antitoxin treatment. She was concurrently diagnosed with a COVID-19 infection during this period. Nonetheless, she experienced a full recovery 86 days after the injection. Conclusion: Currently, there is no effective antidote for botulism. Nevertheless, the timely administration of antitoxin can contribute to reducing the duration of the illness, alleviating symptoms, and preventing its recurrence. It is essential to recognize that individual responses may vary, and in this instance, the absence of antitoxin treatment did not significantly prolong the course of the disease. Accurate diagnosis of medical poisoning can be based on injection history and clinical symptoms. Early indications like fatigue and dry mouth warrant particular attention, emphasizing the importance of immediate medical intervention. To address emergencies, the Center for Disease Control (CDC) should maintain an accessible supply of antitoxin. Patients with severe poisoning should be hospitalized until their respiratory muscle strength is fully restored.
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PURPOSE: This study investigated the effects of different temperatures and capsaicin solution on changes of morphology and inflammatory factor expressions in the oral mucosa. METHODS: The oral mucosa of rats was stimulated with normal saline (NS) and capsaicin solution at 25, 45, and 55 â respectively for 4 weeks, and then the rats were sacrificed with chloral hydrate. H-E staining and immunohistochemical staining of the oral mucosa were prepared. The morphological changes of oral mucosa epithelium were observed and the expressions of TNF-α, IL-6 and IL-8 were detected. SPSS 22.0 software package was used for statistical analysis, and Graphpad Prism 8.0 software was used for statistical graphing. RESULTS: When stimulated with NS and capsaicin solution at different temperatures, the results of H-E staining showed that there was no distinct injury in the mucosal epithelium at 25 â and 45 â. Histopathological changes were observed in the oral mucosa at 55 â. The expressions of IL-6 and IL-8 in the epithelium were significantly increased (Pï¼0.05). CONCLUSIONS: 55 â NS solution and 55 â capsaicin solution stimulated oral mucosa of the rats and caused infiltration of inflammatory cells in the lamina propria of the oral mucosa. They also stimulated the oral mucosa of rats, resulting in a significant increase in the expression of IL-6 and IL-8 in the oral mucosal epithelium. The effect of capsaicin on IL-8 expression was enhanced with increasing temperature.
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Capsaicina , Mucosa Bucal , Ratos , Animais , Capsaicina/farmacologia , Temperatura , Interleucina-8 , Interleucina-6RESUMO
Trace amine-associated receptor 1 (TAAR1) senses a spectrum of endogenous amine-containing metabolites (EAMs) to mediate diverse psychological functions and is useful for schizophrenia treatment without the side effects of catalepsy. Here, we systematically profiled the signaling properties of TAAR1 activation and present nine structures of TAAR1-Gs/Gq in complex with EAMs, clinical drugs, and synthetic compounds. These structures not only revealed the primary amine recognition pocket (PARP) harboring the conserved acidic D3.32 for conserved amine recognition and "twin" toggle switch for receptor activation but also elucidated that targeting specific residues in the second binding pocket (SBP) allowed modulation of signaling preference. In addition to traditional drug-induced Gs signaling, Gq activation by EAM or synthetic compounds is beneficial to schizophrenia treatment. Our results provided a structural and signaling framework for molecular recognition by TAAR1, which afforded structural templates and signal clues for TAAR1-targeted candidate compounds design.
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Receptores Acoplados a Proteínas G , Transdução de Sinais , Humanos , Aminas/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Esquizofrenia/metabolismoRESUMO
Background: In Weber syndrome, one side of the cerebral peduncle of the midbrain is infarcted due to the occlusion of the interpeduncular branch of the posterior cerebral artery and the posterior choroidal artery, resulting in ipsilateral oculomotor nerve palsy and contralateral hemiparesis. However, Weber syndrome induced by simple anterior choroidal artery lesions has rarely been reported. Case Description: Computed tomographic angiography revealed occlusion of the left internal carotid artery in a 57-year-old male patient who was admitted to the Beijing Haidian Hospital with cerebral infarction. Thrombectomy to clear the occlusion of the left internal carotid artery and the middle cerebral artery was successfully performed in the emergency department. However, postoperative digital subtraction angiography indicated occlusion of the middle and distal segments of the left anterior choroidal artery. After recovery from anesthesia, the patient had left blepharoptosis, inability to abduct the left eye, limitation of the upward and downward gaze, left mydriasis, absence of response to light, and right hemiplegia. Complete head magnetic resonance imaging suggested left cerebral peduncle and basal ganglia infarction. Therefore, the diagnosis was that the patient had left Weber syndrome caused by a left anterior choroidal arterial embolism. Conclusion: When the anterior choroidal artery is the dominant supplier of blood to the medial region of the ipsilateral cerebral peduncle, the occlusion of this artery may lead to ipsilateral Weber syndrome.
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Background: Paclitaxel-based chemotherapy represented by nanoparticle albumin-bound paclitaxel (nab-ptx) combined with programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors has become the standard model for the 1st treatment of advanced non-small cell lung cancer (NSCLC) with negative driver genes (such as EGFR, ALK, etc.), indicating that nab-ptx and PD-1/PD-L1 inhibitors are synergistic. Considering PD-1/PD-L1 inhibitors alone or chemotherapy single has limited efficiency in the 2nd line or above of NSCLC, so it is of great significance to explore the combination of PD-1/PD-L1 inhibitors and nab-ptx to further improve the therapeutic efficiency in such field. Methods: We retrospectively collected the date of these advanced NSCLC patients who accept the combination treatment of PD-1/PD-L1 inhibitor and nab-ptx in the 2nd or above line. We further analysed baseline clinical characteristics, therapeutic efficacy, treatment-related adverse events (AEs) and followed up survival. The main parameters of the study were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and AEs. Results: A total of 53 patients were enrolled in this study. The preliminary results indicated that the ORR of the combination of camrelizumab and nab-ptx was about 36% in the 2nd or above line of NSCLC, with 19 cases of partial response (PR), 16 of stable disease (SD), and 18 cases of progressive disease (PD); the mean PFS and OS were 5 months and 10 months, respectively. Further subgroup analysis demonstrated that the expression of PD-L1 level and the decrease of regulatory T cell (Treg) correlated with the efficiency. the main adverse reactions were neuropathy, bone marrow suppression, fatigue, and hypothyroidism, most of which were mild and tolerable, indicating such regimen was higher efficiency and lower cytotoxicity for NSCLC. Conclusions: The combination of nab-ptx and camrelizumab shows promising efficiency and lower toxicities for advanced NSCLC in the 2nd or above line treatment. The mechanism of action may be related to depleting Treg ratio; such a regimen may have the potential to become an effective treatment approach for NSCLC. However, due to the limitation of sample size, the real value of this regimen needs to be further confirmed in the future.
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Hemp seed-derived inhibitors of dipeptidyl peptidase IV (DPP-IV) demonstrate potential as novel therapeutics for diabetes; however, their proteome and genome remain uncharacterized. We used multi-omics technology to mine peptides capable of inhibiting DPP-IV. First, 1261 and 1184 proteins were identified in fresh and dry hemp seeds, respectively. Simulated protease cleavage of dry seed proteins yielded 185,446 peptides for virtual screening to select the potential DPP-IV-inhibiting peptides. Sixteen novel peptides were selected according to their DPP-IV-binding affinity determined via molecular docking. In vitro DPP-IV inhibition assays identified the peptides LPQNIPPL, YPYY, YPW, LPYPY, WWW, YPY, YPF, and WS with half-maximal inhibitory concentration (IC50) values lower than 0.5 mM, which were 0.08 ± 0.01, 0.18 ± 0.03, 0.18 ± 0.01, 0.20 ± 0.03, 0.22 ± 0.03, 0.29 ± 0.02, 0.42 ± 0.03, and 0.44 ± 0.09 mM, respectively. The dissociation constants (KD) of the 16 peptides ranged from 1.50 × 10-4 to 1.82 × 10-7 M. Furthermore, Caco2 and INS-1 cell assays showed that all 16 peptides could efficiently inhibit DPP-IV activity and increase insulin and glucagon-like peptide-1 concentrations. These results demonstrate a well-established and efficient method to isolate food-derived therapeutic DPP-IV-inhibiting peptides.
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Cannabis , Inibidores da Dipeptidil Peptidase IV , Humanos , Simulação de Acoplamento Molecular , Cannabis/metabolismo , Dipeptidil Peptidase 4/química , Multiômica , Células CACO-2 , Inibidores da Dipeptidil Peptidase IV/química , Peptídeos/química , Sementes/metabolismoRESUMO
Volatile organic compounds (VOCs) are key components of tropospheric chemistry, of which industrial emissions are an important source of atmospheric VOCs. In this study, online measurements of 74 VOCs were made in a typical industrial area of the Pearl River Delta in southern China during the early summer of 2021. The mean volume mixing ratio of total volatile organic compounds (TVOC) was (81.9±45.4)×10-9 during the campaign. Among them, oxygenated volatile organic compounds (OVOCs) accounted for the largest fraction of TVOC, with an average of 51.5%, followed by aromatics, accounting for 19.4% of TVOC. The proportion of OVOCs in TVOC gradually increased with the increase in TVOC concentration. Industry-related emissions were the main contributors to aromatics and OVOCs in this region. Aromatics and OVOCs were the two major contributors to the ozone formation potential (OFP), accounting for 56.4% and 26.7%, respectively. Furthermore, OVOCs also contributed 40.0% of the total ·OH reactivity from VOCs. Xylenes, toluene, acrolein, and ethyl acetate had a greater contribution to the formation of secondary pollution; thus, these species should be given priority for controlling secondary pollution. Our results underscore the severity of OVOCs pollution in industrial areas and the important roles of OVOCs in secondary pollution.
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INTRODUCTION: Luteolin is a flavonoid polyphenolic compound exerting broad pharmacological and medicinal properties. Diabetes-related obesity increases the total blood volume and cardiac output and may increase the myocardial hypertrophy progression. However, the mechanism of luteolin in diabetic myocardial hypertrophy remains uncertain. Therefore, this study aimed to evaluate whether luteolin improved diabetic cardiomyopathy (DCM) by inhibiting the proteasome activity. METHODS: Cardiomyopathy was induced in streptozotocin-treated diabetes mellitus (DM) and db/db mice. Luteolin (20 mg kg-1·day-1) was administrated via gavage for 12 weeks. In vitro, high glucose and high insulin (HGI, glucose at 25.5 mM and insulin at 0.1 µM) inducing primary neonatal rat cardiomyocytes (NRCMs) were treated with or without luteolin for 48 h. Echocardiography, reverse transcription quantitative polymerase chain reaction, histology, immunofluorescence, and Western blotting were conducted. Proteasome activities were also detected using a fluorescent peptide substrate. RESULTS: Luteolin administration significantly prevented the onset of cardiac hypertrophy, fibrosis, and dysfunction in type 1 DM (T1DM) and type 2 DM (T2DM). Compared with DCM mice, luteolin groups showed lower serum triglyceride and total cholesterol levels. Furthermore, luteolin attenuated HGI-induced myocardial hypertrophy and reduced atrial natriuretic factor mRNA level in NRCMs. Proteasome activities were inhibited by luteolin in vitro. Luteolin also reduces the proteasome subunit levels (PSMB) 1, PSMB2, and PSMB5 of the 20S proteasome, as well as proteasome-regulated particles (Rpt) 1 and Rpt4 levels of 19S proteasome. Furthermore, luteolin treatment increased protein kinase B (AKT) and GSK-3α/ß (inactivation of GSK-3) phosphorylation. The phosphorylation level of AMPK activity was also reversed after the treatment with luteolin in comparison with the HGI-treated group. CONCLUSION: This study indicates that luteolin protected against DCM in mice, including T1DM and T2DM, by upregulating phosphorylated protein AMPK and AKT/GSK-3 pathways while decreasing the proteasome activity. These findings suggest that luteolin may be a potential therapeutic agent for DCM.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Cardiomiopatias Diabéticas , Insulinas , Ratos , Camundongos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Quinase 3 da Glicogênio Sintase/efeitos adversos , Quinase 3 da Glicogênio Sintase/metabolismo , Luteolina/farmacologia , Luteolina/uso terapêutico , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Proteínas Quinases Ativadas por AMP/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Complexo de Endopeptidases do Proteassoma/uso terapêutico , Transdução de Sinais , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Glucose , Cardiomegalia/tratamento farmacológico , Cardiomegalia/prevenção & controle , Insulinas/efeitos adversosRESUMO
PURPOSE: To study the effect of slow maxillary expansion(SME) appliance on the development of premolar tooth germ, primary molar and alveolar crest in the central segment of maxilla in the mixed dentition. METHODS: According to the inclusion and exclusion criteria, 17 children (average age 7.41±0.80 years old ) with maxillary transverse deficiency were selected for SME. Before and after treatment, based on cone-beam CT(CBCT) and Dolphin Imaging software, the position of maxillary premolar tooth germ, the position of maxillary primary molar, the shape of maxillary alveolar crest in the central segment were analyzed. SPSS 21.0 software package was used for data analysis. RESULTS: There was no significant change in the buccal-lingual movement and inclination of the tooth germs of the maxillary first and second premolars relative to the maxillary alveolar bone cortex after expansion(Pï¼0.05).After expansion, the maxillary alveolar crest in the central segment had an obvious expansion effect(Pï¼0.05). There was an arch expansion effect in the alveolar crest bottom of the maxillary second primary molar(Pï¼0.05), but there was no significant difference in the alveolar crest bottom of the maxillary first primary molar before and after treatment. Buccal cusp width of maxillary first and second primary molars increased after arch expansion (Pï¼0.05) without inclination of alveolar crest(Pï¼0.05). CONCLUSIONS: SME in the mixed dentition did not affect the position of premolar tooth germ in alveolar bone. SME can expand and buccally tilt central alveolar crest and dental arch, and buccal inclination is greater than that of skeletal expansion and buccal inclination. The closer tooth site is to the first molar, the greater the skeletal effect of arch expansion is at this site. SME is an effective treatment for early maxillary expansion in the clinic.
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Dentição Mista , Técnica de Expansão Palatina , Criança , Humanos , Processo Alveolar/diagnóstico por imagem , Dente Molar/diagnóstico por imagem , Tomografia Computadorizada de Feixe Cônico , Dente Pré-Molar/diagnóstico por imagem , Maxila/diagnóstico por imagemRESUMO
This article reviewed two-stage orthodontic treatment of a patient with skeletal Classâ ¡malocclusion with mandibular retrusion and maxillary dental arch stenosis. The patient was also accompanied by premature loss of bilateral mandibular deciduous canines and mesialization of mandibular posterior teeth. The first-stage treatment mainly corrected the maxillary dental arch stenosis, maxillary anterior teeth protrusion, mandibular retrusion and skeletal Classâ ¡malocclusion, while the second-stage treatment mainly corrected the mesialization of mandibular posterior teeth and alignment of maxillary and mandibular dentition. The two-stage orthodontic treatment finally enabled the patient to achieve good dental arch shape, tooth alignment, skeletal face pattern and soft tissue profile.
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Retrognatismo , Humanos , Arco Dental/diagnóstico por imagem , Constrição Patológica , Mandíbula/diagnóstico por imagem , Maxila/diagnóstico por imagemRESUMO
Online food delivery (OFD) is one of the top industries in the Online-to-offline (O2O) commerce sector. Deliverymen need to complete a large number of delivery orders in limited default time every day, which cause high working stress to them. Therefore, a high level of traffic violations and crashes by deliverymen and corresponding negative impact on public safety are observed. To reduce traffic violations by deliverymen and resulting crashes, a hierarchical online food delivery framework is proposed, which is based on data from questionnaire surveys conducted in Xi'an City, China. The study includes the analysis of the root cause correlated with traffic violations during online food delivery as part of an empirical study on the priority delivery fee by applying a conditional price sensitivity measurement (PSM) model. The feasibility and rationality of the framework are further investigated by using cross analysis of urban dwellers' occupation, income, and commuting cost. The results identify that, through rationally shunting the demand of online food delivery, prolonging the default delivery duration, and providing diversified delivery services, the proposed hierarchical online food delivery mechanism is able to relieve the stress of deliverymen during peak hours of food requests. This reduces the willingness of deliverymen to engage in traffic violations, and other risky behaviors during food delivery trips. All of which facilitate high-quality and timely online food delivery service while enabling improved safety of deliverymen and others as part of enhanced public safety and health.
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Comércio , Renda , China , Cidades , Inquéritos e QuestionáriosRESUMO
In this study, the vocal intonation therapy (VIT) was compared with the standard respiratory therapy for people suffering from respiratory dysfunction as a result of cervical spinal cord injury (CSCI) to observe its effect on vocal quality. Thirty patients with vocal dysfunction after CSCI with the injury time of more than 3 months were screened for inclusion in the trial, and 18 patients completed the 12-weeks, each participant had 60 sessions in total in the clinical trial. All patients were allocated to the intervention group or the control group. The intervention group received VIT training and the control group received respiratory phonation therapy. Both groups were trained by professional therapists, and the training time was 30 min/day, 5 days/week, for 60 sessions for each group in a total of 12 weeks. In the Baseline (T0), mid-intervention period (after 6 weeks, T1), and after intervention (after 12 weeks, T2), the vocal quality of the two groups of patients was tested with a computer-aided real-time audio analyzer 2.1.6 (Adobe Systems, United States) for Sing-SPL (p < 0.0001), Speech-SPL (p < 0.0001), SNL (p < 0.0001), and F0 (p < 0.0001) of the intervention group were significantly improved compared with the control group. In comparing the spectrometry analysis of vocal quality for the 2 groups of participants, there was a significant difference in the results of Sing-SPL and Speech-SPL acoustic analysis in the intervention group of patients at T2 (after 12 weeks) compared to the control group. Vocal intonation therapy-music therapy can improve the speech sound quality of cervical CSCI patients and provide CSCI patients with a practical, highly operable treatment that has both functional training effects and can bring a pleasant experience that can be promoted in the medical field. This study was approved by the Ethics Committee of China Rehabilitation Research Center (CRRC) (approval No. 2019-83-1) on May 20th, 2019. It was registered with the National Health Security Information Platform, medical research registration, and filing information system (Registration No. MR-11-21-011802) on January 28th, 2021.
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In spring, ozone (O3) pollution frequently occurrs in eastern China, but key drivers remain uncertain. In this study, interannual variations in springtime ozone in Shanghai, China, from 2013 to 2021, were investigated to assess the health impacts and the effectiveness of recent air pollution control measures. A combination of ground-level measurements of regulated air pollutants, lidar observations, and backward trajectories of air masses was used to identify the key drivers for enhancing springtime O3. The results show that external imports of O3 driven by atmospheric circulation are notable sources of springtime surface O3. For example, the downward transport from the free troposphere could contribute to over 50% of surface O3 in the morning. The surface O3 mixing ratios in spring exhibited an upward trend of 0.93 ppb yr-1 (p < 0.05) from 2013 to 2021. The change in meteorological variables, particularly the increase in air temperature, could explain nearly 87% of the springtime O3 upward trend. The change in anthropogenic emissions of precursors only contributed to a small fraction (<13%) of the increase in springtime O3. The cumulative exposure of urban residents to O3 in spring also exhibited a significant upward trend (111 ppb yr-1, p < 0.05). With the rapid increase in surface O3, premature respiratory mortality attributable to O3 exposure has fluctuated at approximately 2933 deaths per year since 2016, even though the total deaths from respiratory diseases have significantly declined. Long-term exposure to high O3 concentrations is a significant contributor to premature respiratory mortality.
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Poluentes Atmosféricos , Poluição do Ar , Ozônio , Doenças Respiratórias , Poluentes Atmosféricos/análise , Poluição do Ar/análise , China , Monitoramento Ambiental , Humanos , Ozônio/análiseRESUMO
Kudoa (Myxosporea: Multivalvulida) parasites are critical pathogens in marine and freshwater fish associated with significant economic losses and reduced market prices caused by post-mortem myoliquefaction or numerous cysts on muscles. In the present study, large yellow croakers infected by Kudoa were found during fish disease surveillance in China in November 2020 and used for morphological observation and characterization using light DIC microscopy and electron microscopy. Numerous creamy-white oval plasmodia were observed in muscles and on the surface of brain cartilage, gill arches, and serosal surfaces. The spores were considerably longer and thicker than previously reported Kudoa, with protruding polar filaments (PFs) in the mature spores, fingertip-shaped apical projections (APs), and polar capsules. Phylogenetic analyses with SSU rDNA, LSU rDNA, and mitochondrial DNA showed that the Kudoa-infected sample (LcK-2020) had the highest similarity to Kudoa iwatai reported in Japan. Based on the morphological characterization and phylogenetic analysis, it could be concluded that the sample LcK-2020 was infected by Kudoa iwatai, which would be the first report of Kudoa iwatai infection in large yellow croaker in China.
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The main objective of this study was to evaluate the in vitro antiproliferative effects of isoalantolactone against liver cancer cells (Hep-G2) and also monitor its mechanism of action. The MTT assay was involved in proliferation assessments and phase contrast microscopy was used to check cellular morphology. Acridine orange/ethidium bromide staining along with western blotting was used to evaluate proapoptotic effects of isoalantolactone. DCFH-DA staining was used in ROS measurements. Transwell migration and invasion assay were executed to check the effects of isoalantolactone on migration and invasion of Hep-G2 cells. Western blotting was used to check the expressions of Ras/Raf/MEK signalling pathway in Hep-G2 cells. Results demonstrated that isoalantolactone significantly (*p<0.05 and **p<0.01) inhibited the proliferation of Hep-G2 cells in a concentration and time-reliant fashion. The IC50 value of the tested isoalantolactone molecule was found to be 71.2 µM and 53.4 µM at 12 h and 24 h time intervals respectively. Moreover, the antiproliferative effects of isoalantolactone were mediated through induction of caspase-dependent apoptosis and oxidative stress (ROS mediated). The proapoptotic effects of isoalantolactone were evident from morphological assessments and improved expressions of caspase-3, -8, and -9 and Bax while antiapoptotic Bcl-2 was reduced significantly. Additionally, antiproliferative and proapoptotic effects of isoalantolactone were found to be a consequence of blocking of Ras/Raf/MEK signalling in Hep-G2 cells. Furthermore, isoalantolactone significantly (*p<0.05) targeted the migration and invasion of Hep-G2 cells. In conclusion, these results validated that isoalantolactone shows strong antiproliferative activity against Hep-G2 liver cancer cells. Therefore, it could prove as a leading candidate in liver cancer research, drug discovery and design.
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Apoptose , Neoplasias Hepáticas , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Quinases de Proteína Quinase Ativadas por Mitógeno/farmacologia , Espécies Reativas de Oxigênio/metabolismo , SesquiterpenosRESUMO
In previous studies, researchers have used singing to treat respiratory function in patients with spinal cord injury. However, few studies have examined the way in which vocal training affects respiratory neural plasticity in patients with spinal cord injury. Vocal respiratory training (VRT) is a type of vocal muscle-related treatment that is often a component of music therapy (MT) and focuses on strengthening respiratory muscles and improving lung function. In this randomized controlled study, we analyzed the therapeutic effects of VRT on respiratory dysfunction at 3 months after cervical spinal cord injury. Of an initial group of 37 patients, 26 completed the music therapy intervention, which comprised five 30-minute sessions per week for 12 weeks. The intervention group (n = 13) received VRT training delivered by professional certified music therapists. The control group (n = 13) received respiratory physical therapy delivered by professional physical therapists. Compared with the control group, we observed a substantial increase in respiratory function in the intervention group after the 12-week intervention. Further, the nerve fiber bundles in the respiratory center in the medulla exhibited a trend towards increased diversification, with an increased number, path length, thickness, and density of nerve fiber bundles. These findings provide strong evidence for the effect of music therapeutic VRT on neural plasticity. This study was approved by the Ethics Committee of China Rehabilitation Research Center (approval No. 2020-013-1) on April 1, 2020, and was registered with the Chinese Clinical Trial Registry (registration No. ChiCTR2000037871) on September 2, 2020.
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The neuron derived synaptic adhesion molecular neuroligin-3 (NLGN3) plays an important role in glioma growth. While the role of autocrine NLGN3 in glioma has not been well-studied. The expression of NLGN3 in glioma was detected using immunohistochemistry. We further explored its function and regulatory mechanism in U251 and U87 cells with high expression of NLGN3. Knockdown of endogenous NLGN3 significantly reduced the proliferation, migration, and invasion of glioma cells and down-regulated the activity of the PI3K-AKT, ERK1/2, and LYN signaling pathways. In comparison, overexpression of NLGN3 yielded opposite results. Our results further demonstrate that LYN functions as a feedback mechanism to promote NLGN3 cleavage. This feedback regulation was achieved by upregulating the ADAM10 sheddase responsible for NLGN3 cleavage. Inhibition of ADAM10 suppressed the proliferation, migration, and invasion of glioma cells; oppositely, the expression of ADAM10 was correlated with a higher likelihood of lower grade glioma (LGG) in the brain. Our study demonstrates that glioma-derived NLGN3 promotes glioma progression by upregulating activity of LYN and ADAM10, which in turn promote NLGN3 cleavage to form a positive feedback loop. This pathway may open a potential therapeutic window for the treatment of human glioma.