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1.
Biomed Environ Sci ; 37(7): 739-753, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39198238

RESUMO

Objective: A high sodium (HS) diet is believed to affect bone metabolism processes. Clarifying its impact on osseointegration of titanium (Ti) implants holds significant implications for postoperative dietary management of implanted patients. Methods: This investigation probed the impact of sodium ions (Na +) on neovascularization and osteogenesis around Ti implants in vivo, utilizing micro-computed tomography, hematoxylin and eosin staining, and immunohistochemical analyses. Concurrently, in vitro experiments assessed the effects of varied Na + concentrations and exposure durations on human umbilical vein endothelial cells (HUVECs) and MC3T3-E1 cells. Results: In vivo, increased dietary sodium (0.8%-6.0%) led to a substantial decline in CD34 positive HUVECs and new bone formation around Ti implants, alongside an increase in inflammatory cells. In vitro, an increase in Na + concentration (140-150 mmol/L) adversely affected the proliferation, angiogenesis, and migration of HUVECs, especially with prolonged exposure. While MC3T3-E1 cells initially exhibited less susceptibility to high Na + concentrations compared to HUVECs during short-term exposure, prolonged exposure to a HS environment progressively diminished their proliferation, differentiation, and osteogenic capabilities. Conclusion: These findings suggest that HS diet had a negative effect on the early osseointegration of Ti implants by interfering with the process of postoperative vascularized bone regeneration.


Assuntos
Células Endoteliais da Veia Umbilical Humana , Osseointegração , Titânio , Animais , Osseointegração/efeitos dos fármacos , Humanos , Camundongos , Neovascularização Fisiológica/efeitos dos fármacos , Masculino , Sódio/metabolismo , Osteogênese/efeitos dos fármacos , Dieta
2.
Artigo em Inglês | MEDLINE | ID: mdl-39033356

RESUMO

OBJECTIVE: Obstructive sleep apnea (OSA) is a prevalent disorder, with oral breathing influencing its severity. Expiratory velopharyngeal obstruction (EVO), observed during drug-induced sleep endoscopy (DISE), may contribute to oral breathing in OSA patients. EVO results in obstruction between the pharynx and nasal cavity during expiration. This study aims to identify factors associated with positive EVO during DISE. STUDY DESIGN: Case series. SETTING: Tertiary Medical Center. METHODS: Seventy-two OSA patients underwent clinical evaluation, polysomnography, and DISE, utilizing interventions like intraoral negative airway pressure (iNAP), mouth closure, and oral appliances (OAs) in supine positions with head rotation. The findings, classified under velopharynx, oropharynx, tongue base, epiglottis, included the presence of EVO. RESULTS: The results demonstrated that interventions including mouth closure and iNAP were associated with increased observation of EVO (43.1% and 34.7%) compared to OA (20.1%). However, head rotation was associated with decreased presence of EVO during DISE compare to supine (26% vs 35.8%). Noticeably, per 1 year increase of age was associated with an increased odds of EVO (odds ratio: 1.03, 95% confidence interval: 1.01-1.06). However, no other baseline characteristics were significantly associated the odds of EVO. CONCLUSION: Our study reveals the effectiveness of head rotation and OA in reducing EVO and improving mouth breathing in OSA patients, offering valuable insights for future treatment strategies.

3.
IEEE Internet Things J ; 11(5): 7935-7947, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38859814

RESUMO

This paper presents the design and evaluation of an engagement-free and contactless vital signs and occupancy monitoring system called BedDot. While many existing works demonstrated contactless vital signs estimation, they do not address the practical challenge of environment noises, online bed occupancy detection and data quality assessment in the realworld environment. This work presents a robust signal quality assessment algorithm consisting of three parts: bed occupancy detection, movement detection, and heartbeat detection, to identify high-quality data. It also presents a series of innovative vital signs estimation algorithms that leverage the advanced signal processing and Bayesian theorem for contactless heart rate (HR), respiration rate (RR), and inter-beat interval (IBI) estimation. The experimental results demonstrate that BedDot achieves over 99% accuracy for bed occupancy detection, and MAE of 1.38 BPM, 1.54 BPM, and 24.84 ms for HR, RR, and IBI estimation, respectively, compared with an FDA-approved device. The BedDot system has been extensively tested with data collected from 75 subjects for more than 80 hours under different conditions, demonstrating its generalizability across different people and environments.

4.
J Virol ; 98(4): e0177323, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38530012

RESUMO

Dengue vaccine candidates have been shown to improve vaccine safety and efficacy by altering the residues or accessibility of the fusion loop on the virus envelope protein domain II (DIIFL) in an ex vivo animal study. The current study aimed to comprehensively investigate the impact of DIIFL mutations on the antigenicity, immunogenicity, and protective efficacy of Japanese encephalitis virus (JEV) virus-like particles (VLPs) in mice. We found the DIIFL G106K/L107D (KD) and W101G/G106K/L107D (GKD) mutations altered the binding activity of JEV VLP to cross-reactive monoclonal antibodies but had no effect on their ability to elicit total IgG antibodies in mice. However, JEV VLPs with KD or GKD mutations induced significantly less neutralizing antibodies against JEV. Only 46% and 31% of the KD and GKD VLPs-immunized mice survived compared to 100% of the wild-type (WT) VLP-immunized mice after a lethal JEV challenge. In passive protection experiments, naïve mice that received sera from WT VLP-immunized mice exhibited a significantly higher survival rate of 46.7% compared to those receiving sera from KD VLP- and GKD VLP-immunized mice (6.7% and 0%, respectively). This study demonstrated that JEV DIIFL is crucial for eliciting potently neutralizing antibodies and protective immunity against JEV. IMPORTANCE: Introduction of mutations into the fusion loop is one potential strategy for generating safe dengue and Zika vaccines by reducing the risk of severe dengue following subsequent infections, and for constructing live-attenuated vaccine candidates against newly emerging Japanese encephalitis virus (JEV) or Japanese encephalitis (JE) serocomplex virus. The monoclonal antibody studies indicated the fusion loop of JE serocomplex viruses primarily comprised non-neutralizing epitopes. However, the present study demonstrates that the JEV fusion loop plays a critical role in eliciting protective immunity in mice. Modifications to the fusion loop of JE serocomplex viruses might negatively affect vaccine efficacy compared to dengue and zika serocomplex viruses. Further studies are required to assess the impact of mutant fusion loop encoded by commonly used JEV vaccine strains on vaccine efficacy or safety after subsequent dengue virus infection.


Assuntos
Vírus da Encefalite Japonesa (Espécie) , Encefalite Japonesa , Vacinas contra Encefalite Japonesa , Animais , Camundongos , Aminoácidos , Anticorpos Neutralizantes , Anticorpos Antivirais , Dengue , Vírus da Encefalite Japonesa (Espécie)/fisiologia , Encefalite Japonesa/imunologia , Encefalite Japonesa/prevenção & controle , Epitopos , Vacinas contra Encefalite Japonesa/genética , Proteínas do Envelope Viral/genética , Zika virus , Infecção por Zika virus
5.
Plants (Basel) ; 12(24)2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38140404

RESUMO

As a photophilous plant, rice is susceptible to low-light stress during its growth. The Sichuan Basin is a typical low-light rice-producing area. In this study, eight rice varieties with different shade tolerances were studied from 2021 to 2022. The physiological adaptability and yield formation characteristics of rice were studied with respect to photosynthetic physiological characteristics and dry matter accumulation characteristics, and the response mechanism of rice to low light stress was revealed. The results showed that the shading treatment significantly increased the chlorophyll a, chlorophyll b, and total chlorophyll contents in the leaves of direct-seeded rice after heading, and the total chlorophyll content increased by 1.68-29.70%. Nitrate reductase (NR) activity first increased and then decreased under each treatment, and the shading treatment reduced the NR activity of direct-seeded rice. Compared to the control treatment, the peroxidase (POD) activity of each variety increased from 7 to 24 d after the shading treatment. The transketolase (TK) activity in direct-seeded hybrid rice increased under low light stress. Compared with the control, shading treatment significantly reduced the aboveground dry matter, grain number per panicle, and seed setting rate of direct-seeded rice at the full heading stage and maturity stage, thus reducing the yield of direct-seeded rice by 26.10-34.11%. However, under the shading treatment, Zhenliangyou 2018 and Jingliangyou 534 maintained higher chlorophyll content and related enzyme activities, accumulated more photosynthetic products, and reduced yield. In general, Zhenliangyou 2018 and Jingliangyou 534 still had a yield of 7.06-8.33 t·hm-2 under low light. It indicated that Zhenliangyou 2018 and Jingliangyou 534 had better stability and stronger tolerance to weak light stress and had a higher yield potential in weak light areas such as Sichuan.

6.
Opt Lett ; 48(21): 5563-5566, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37910703

RESUMO

The applications of two-dimensional transition metal carbide/nitride (MXene) in the fields of optoelectronics, sustainable energy, and sensors, among others, have been broadly investigated due to their special electrical, optical, and structural properties. In this Letter, MXene (Ti3C2Tx) has been firstly, to the best of our knowledge, adopted for the application of a photoacoustic transducer by taking advantage of the photothermal property. The efficiency of the photoacoustic transducer based on a sandwich structure of glass/MXene/polydimethylsiloxane (PDMS) has been experimentally demonstrated to be 1.25 × 10-2 by converting laser pulses into ultrasonic waves, generating a high acoustic pressure of 15.7 MPa without additional acoustic focusing. That can be explained by the great light absorption and photothermal conversion of the Ti3C2Tx layer.

7.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 45(5): 730-736, 2023 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-37927013

RESUMO

Objective To investigate the food preferences and explore the potential association between dietary knowledge and food preferences in residents aged 18 and over in China,so as to provide a basis for promoting healthy diets.Methods The latent class analysis was carried out with the 2015 cross-sectional data of China health and nutrition survey to categorize the food preferences among 8 783 residents aged 18 and over.Multinomial Logistic regression was adopted to assess the association between and dietary knowledge and food preferences.Results The food preferences of the residents aged 18 and over in China were classified into preference for less vegetable(3.28%),lack of preference(11.20%),diverse preferences(4.19%),and preference for healthy diets(81.33%).The proportion of the adults with dietary knowledge was 36.87%(3 238/8 783).The dietary knowledge varied in the adults with different food preferences(all P<0.001).After adjusting for gender,age,urban and rural distribution,education background,and annual household income,for each point increase in the dietary knowledge score,there was an estimated reduction of 22% in the probability of preferring less vegetables(OR=0.78,95%CI=0.76-0.80, P<0.001),13% in the probability of lacking preference(OR=0.87,95%CI=0.86-0.89, P<0.001),and 3% in the probability of having diverse preferences(OR=0.97,95%CI=0.94-1.00, P=0.030).Compared with those lacking dietary knowledge,the individuals with dietary knowledge had a 77% less probability of preferring less vegetables(OR=0.23,95%CI=0.16-0.32, P<0.001),a 55% less probability of lacking preference(OR=0.45,95%CI=0.39-0.53, P<0.001),and a 23% less probability of having diverse preferences(OR=0.77,95%CI=0.61-0.96, P=0.023).Conclusions The residents aged 18 and over in China presented four food preferences,including preference for less vegetables,lack of preference,diverse preferences,and preference for healthy diets,the last of which had the highest proportion.The individuals with lower levels of dietary knowledge have higher probability of preferring unhealthy food.


Assuntos
Dieta , Preferências Alimentares , Adulto , Humanos , Adolescente , Análise de Classes Latentes , Estudos Transversais , Inquéritos Nutricionais , China
8.
Org Lett ; 25(45): 8067-8071, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37939226

RESUMO

A visible-light-induced ß-acyl difunctionalization of alkenes with acyl oxime esters and various nucleophiles was developed to achieve molecular complexity from readily available raw materials via oxidative radical-polar crossover. A variety of nucleophiles, including NH-sulfoximines, indoles, indazole, and trimethoxybenzene, were all effectively applicable to the sustainable reaction system. The novel synthetic strategy features mild reaction conditions, a broad substrate scope (39 examples), easy scale-up, and excellent regioselectivity.

9.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(9): 971-975, 2023.
Artigo em Chinês | MEDLINE | ID: mdl-37718405

RESUMO

OBJECTIVES: To study the efficacy of different drug treatment regimens in children with streptococcal toxic shock syndrome (STSS). METHODS: Clinical data of children diagnosed with STSS confirmed by bacterial culture and treated in Hunan Children's Hospital and Chenzhou First People's Hospital from January 2009 to April 2023 were retrospectively collected. The efficacy of different drug treatment regimens was analyzed. The children were divided into four groups based on the treatment regimens: standard group (regimens containing penicillin), Group A (carbapenem + glycopeptides/linezolid), Group B (carbapenems, broad-spectrum antibiotics, glycopeptides/linezolid used alone or in combination, excluding the regimens in Group A), and Group C (macrolides/not receiving antimicrobial drugs). RESULTS: A total of 32 cases of STSS were included. Antimicrobial susceptibility testing showed that all strains were sensitive to beta-lactam antibiotics such as ampicillin and vancomycin, while resistant to clindamycin, erythromycin, and tetracycline. There was a statistically significant difference in the efficacy rate among the four groups (P<0.05). The standard group exhibited the highest efficacy rate (100%), while the efficacy rates for Group A, Group B, and Group C were 40%, 40%, and 0%, respectively. CONCLUSIONS: The use of antimicrobial regimens containing penicillin can improve the therapeutic efficacy of STSS in children.

10.
Plants (Basel) ; 12(9)2023 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-37176958

RESUMO

To investigate changes in the yield and physiological characteristics of indica hybrid rice varieties sown on different dates, we evaluated appropriate hybrid rice varieties and their optimal sowing dates in the hilly areas of Sichuan. Three popular indica rice varieties were used as experimental materials, and five sowing dates were set uniformly locally [16 May (SD1), 23 May (SD2), 30 May (SD3), 6 June (SD4), and 13 June (SD5)] to investigate differences in the yield characteristics, growth period, and dry matter accumulation. The results showed that, over the two years, the sowing-to-heading period and overall growth period of the three varieties shortened as the sowing date was delayed, and the difference in yield between the SD1 and SD2 treatments was not significant, owing to higher material accumulation after flowering and higher assimilative material transport capacity. These varieties are both photosensitive and tolerant to low temperatures. Among the three varieties tested, the Huangyouyuehesimiao (V3) cultivar had the highest yield, with 10.75 t ha-1 under the SD2 treatment. The impact of shifting the sowing date on yield components varied. Delaying the sowing date increased and then decreased the number of effective panicles, and the number of grains per panicle and the seed setting rate decreased by differing degrees. In summary, a high yield of indica hybrid rice can be maintained by sowing between 16 and 23 May each year in the study area. It indicated that indica hybrid rice in the hilly rice-producing region of Sichuan is highly adaptable to different sowing dates.

11.
Microbiol Spectr ; : e0422522, 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36939351

RESUMO

The endoplasmic reticulum (ER) stress response is a highly conserved stress-defense mechanism and activates the adaptive unfolded protein response (UPR) to mitigate imbalance. The ER stress-activated signaling pathways can also trigger autophagy to facilitate cellular repair. Bovine viral diarrhea virus (BVDV) utilizes the host cellular ER as the primary site of the life cycle. However, the interplay between cellular ER stress and BVDV replication remains unclear. This report reveals that cytopathic (cp) and noncytopathic (ncp) BVDV have distinct strategies to regulate UPR mechanisms and ER stress-mediated autophagy for their own benefit. Immunoblot analysis revealed that cp and ncp BVDV differentially regulated the abundance of ER chaperone GRP78 for viral replication, while the protein kinase RNA-like ER kinase (PERK)-eukaryotic translation initiation factor 2 subunit α (eIF2α)-activating transcription factor 4 (ATF4) pathway of the UPR was switched on at different stages of infection. Pretreatment with ER stress inducer promoted virion replication, but RNA interference (RNAi) knockdown of ATF4 in BVDV-infected cells significantly attenuated BVDV infectivity titers. More importantly, the effector ATF4 activated by cp BVDV infection translocated into the nucleus to mediate autophagy, but ATF4 was retained in the cytoplasm during ncp BVDV infection. In addition, we found that cp BVDV core protein was localized in the ER to induce ER stress-mediated autophagy. Overall, the potential therapeutic target ATF4 may contribute to the global eradication campaign of BVDV. IMPORTANCE The ER-tropic viruses hijack the host cellular ER as the replication platform of the life cycle, which can lead to strong ER stress. The UPR and related transcriptional cascades triggered by ER stress play a crucial role in viral replication and pathogenesis, but little is known about these underlying mechanisms. Here, we report that cytopathic and noncytopathic BVDV use different strategies to reprogram the cellular UPR and ER stress-mediated autophagy for their own advantage. The cytopathic BVDV unconventionally downregulated the expression level of GRP78, creating perfect conditions for self-replication via the UPR, and the noncytopathic BVDV retained ATF4 in the cytoplasm to provide an advantage for its persistent infection. Our findings provide new insights into exploring how BVDV and other ER-tropic viruses reprogram the UPR signaling pathway in the host cells for replication and reveal the attractive host target ATF4 for new antiviral agents.

12.
Chem Commun (Camb) ; 59(28): 4189-4192, 2023 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-36939750

RESUMO

Dimensionality plays a vital role at the nanoscale in tuning the electronical and photophysical properties and surface features of perovskite nanocrystals. Here, 3D and 1D all-inorganic CsPbBr3 nanocrystals were chosen as model materials to systemically reveal the dimensionality-dependent effect in photocatalytic H2 evolution. In terms of facilitating photoinduced electron-hole pair separation and charge transfer, as well as inducing proton reduction potential with the presence of fewer Br vacancies, 1D CsPbBr3 nanorods gave about a 5-fold improvement for solar H2 evolution.

14.
Front Plant Sci ; 13: 924482, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35812928

RESUMO

Plant argonautes (AGOs) play important roles in the defense responses against viruses. The expression of Nicotiana benthamiana AGO5 gene (NbAGO5) is highly induced by Bamboo mosaic virus (BaMV) infection; however, the underlying mechanisms remain elusive. In this study, we have analyzed the potential promoter activities of NbAGO5 and its interactions with viral proteins by using a 2,000 bp fragment, designated as PN1, upstream to the translation initiation of NbAGO5. PN1 and seven serial 5'-deletion mutants (PN2-PN8) were fused with a ß-glucuronidase (GUS) reporter and introduced into the N. benthamiana genome by Agrobacterium-mediated transformation for further characterization. It was found that PN4-GUS transgenic plants were able to drive strong GUS expression in the whole plant. In the virus infection tests, the GUS activity was strongly induced in PN4-GUS transgenic plants after being challenged with potexviruses. Infiltration of the transgenic plants individually with BaMV coat protein (CP) or triple gene block protein 1 (TGBp1) revealed that only TGBp1 was crucial for inducing the NbAGO5 promoter. To identify the factors responsible for controlling the activity of the NbAGO5 promoter, we employed yeast one-hybrid screening on a transcription factor cDNA library. The result showed that NbNAC42 and NbZFP3 could directly bind the 704 bp promoter regions of NbAGO5. By using overexpressing and virus-induced gene silencing techniques, we found that NbNAC42 and NbZFP3 regulated and downregulated, respectively, the expression of the NbAGO5 gene. Upon virus infection, NbNAC42 played an important role in regulating the expression of NbAGO5. Together, these results provide new insights into the modulation of the defense mechanism of N. benthamiana against viruses. This virus inducible promoter could be an ideal candidate to drive the target gene expression that could improve the anti-virus abilities of crops in the future.

15.
Artigo em Inglês | MEDLINE | ID: mdl-35646141

RESUMO

Objective: This study attempted to verify the applicability of the microbial limit test (plate culture and membrane filtration) for 10 proprietary Chinese medicines for children. Methods: In this study, we collected 10 proprietary Chinese medicines for children as study objects and performed plate culture and membrane filtration to calculate the colony-forming unit (cfu) of microorganisms in these medicines and verify its applicability in objectionable microorganisms. Results: It was found that the recovery rate of microorganisms including Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Candida albicans, and Aspergillus niger ranged from 70% to 150%. This verification was performed by plate culture or membrane filtration. Inspection for objectionable microorganisms (Escherichia coli, Salmonella paratyphi B, and bile salt-tolerant Gram-negative bacteria) was applicable for most medicines. Conclusion: Microbial limit test is feasible for the determination of microorganisms in 10 proprietary Chinese medicines for children.

16.
Front Oncol ; 12: 880153, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35686110

RESUMO

Background: Recent clinical trials of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in human lung adenocarcinoma (LUAD) have not achieved satisfactory results. The disappointing results of single-drug treatments have prompted studies about synergistic therapies of CDK4/6i with other drugs. We aimed to test the anti-tumor effect of ribociclib (a CDK4/6i) combined with pemetrexed on LUAD and the potential mechanisms. Methods: Cell lines were exposed to ribociclib and pemetrexed at different doses. Antitumor effects were measured using growth inhibition. Cell cycle distribution and apoptosis were evaluated using flow cytometry. Cell migration and invasion were measured using wound healing and transwell invasion assays, respectively. The expression levels of proteins were analyzed using western blotting. Mice xenograft models were used for validation in vivo. Results: Synergism was associated with a combination of cell cycle effects from both agents. Cell cycle analysis revealed that pemetrexed blocked cells in the S phase, whereas ribociclib arrested cells in the G1 phase. Concomitant treatment with pemetrexed and ribociclib resulted in a significantly stronger antitumor ability than treatment alone. We also found that ribociclib strongly enhanced the pro-apoptotic activity of pemetrexed via the caspase/bcl-2 signaling pathway. In addition, we report for the first time that combination treatment with ribociclib and pemetrexed significantly inhibits the migration and invasion of LUAD cells. Conclusions: Combining ribociclib and pemetrexed showed a powerful ability to inhibit cancer proliferation, invasion, and metastasis, and it holds potential as a novel effective combinative therapy for patients with LUAD.

17.
Phytomedicine ; 104: 154140, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35752081

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) is a long-term, progressive, and disabling autoimmune disease. It causes inflammation, swelling and pain in and around the joints and other body organs. Currently, no cure is available for RA. Clinical interventions can only relieve the condition, and at least 30% of RA patients do not respond to first­line therapy. This means that the development of more effective therapies against RA is urgently needed. OBJECTIVE: This study aimed to assess the anti-rheumatoid arthritis effect of chelerythrine (CLT) and explore its mechanism of action. METHODS: The cytotoxic effect of CLT on human rheumatoid arthritis fibroblast-like synoviocyte (HFLS-RA) cells and HFLS-normal cells were measured by MTT assay. The growth and migration of HFLS-RA cells were determined by colony-formation and wound-healing assay. The level of intracellular reactive oxygen species (ROS) was detected using the DCFH-DA reagent. Cell apoptosis was measured by flow cytometry, TUNEL staining, caspase 3 activity, as well as the activation of apoptosis related proteins. In addition, the levels of autophagy related markers such as LC3B and P62 were determined by immunocytochemistry and western blotting. Lastly, the anti-RA effect of CLT was evaluated in an Adjuvant-Induced Arthritis(AIA) rat model and the severity of arthritis was detected and quantified using macroscopic inspection and X­ray imaging. RESULTS: We discovered that treatment with CLT effectively inhibited the migration and colony-formation of the HFLS-RA cells and resulted in cell death. Moreover, CLT increased the intracellular level of ROS and the apoptotic rate of HFLS-RA by activating the AMPK/mTOR/ULK-1 signaling pathways. In vivo study showed CLT effectively ameliorated AIA in rats, protecting them from inflammation and bone damage. CONCLUSION: Our study shows CLT is an effective agent for ameliorating RA in vitro and in vivo by modulation of the AMPK/mTOR/ULK-1 signaling pathway. These findings indicate that CLT is a great potential candidate for development as a therapeutic agent for the prevention and treatment of RA.


Assuntos
Proteínas Quinases Ativadas por AMP , Artrite Reumatoide , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Apoptose , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Benzofenantridinas , Proliferação de Células , Humanos , Inflamação/complicações , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Ratos , Espécies Reativas de Oxigênio , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo
19.
Oncogene ; 41(12): 1780-1794, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35132181

RESUMO

Non-small cell lung cancer (NSCLC) is a fatal disease, and its metastatic process is poorly understood. Although aberrant methylation is involved in tumor progression, the mechanisms underlying dynamic DNA methylation remain to be elucidated. It is significant to study the molecular mechanism of NSCLC metastasis and identify new biomarkers for NSCLC early diagnosis. Here, we performed MeDIP-seq and hMeDIP-seq analyses to detect the genes regulated by dynamic DNA methylation. Comparison of the 5mC and 5hmC sites revealed that the CD147 gene underwent active demethylation in NSCLC tissues compared with normal tissues, and this demethylation upregulated CD147 expression. Significantly high levels of CD147 expression and low levels of promoter methylation were observed in NSCLC tissues. Then, we identified the CD147 promoter as a target of KLF6, MeCP2, and DNMT3A. Treatment of cells with TGF-ß triggered active demethylation involving loss of KLF6/MeCP2/DNMT3A and recruitment of Sp1, Tet1, TDG, and SMAD2/3 transcription complexes. A dCas9-SunTag-DNMAT3A-sgCD147-targeted methylation system was constructed to reverse CD147 expression. The targeted methylation system downregulated CD147 expression and inhibited NSCLC proliferation and metastasis in vitro and in vivo. Accordingly, we used cfDNA to detect the levels of CD147 methylation in NSCLC tissues and found that the CD147 methylation levels exhibited an inverse relationship with tumor size, lymphatic metastasis, and TNM stage. In conclusion, this study clarified the mechanism of active demethylation of CD147 and suggested that the targeted methylation of CD147 could inhibit NSCLC invasion and metastasis, providing a highly promising therapeutic target for NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Metilação de DNA/genética , Desmetilação , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Oxigenases de Função Mista/genética , Oxigenases de Função Mista/metabolismo , Proteínas Proto-Oncogênicas/metabolismo
20.
Carbohydr Polym ; 275: 118673, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34742409

RESUMO

Chitosan oligosaccharides (COS) are a derivative of low molecular weight chitosan and are potent natural antimicrobial agents. The antimicrobial activity of COS against Aspergillus flavus and Aspergillus fumigatus was evaluated by minimum inhibitory concentration (MIC) and inhibition of mycelial growth. The MICs of COS against these two fungi were 31.2 and 15.6 mg/mL, respectively. COS treatment rendered fungal mycelia wrinkled and deformed with a fractured appearance. COS also increased cellular permeability leading to a significant leakage of cellular components indicating membrane damage. This compound also dose-dependently reduced chitin production and enhanced chitinase activity while enhancing the accumulation of reactive oxygen species (ROS). These characteristics suggested that COS has inhibitory effects against food spoilage fungi and acts on the cell wall and membrane and alters cellular metabolism. COS shows promise for food industry applications since it is non-toxic to higher organisms.


Assuntos
Antifúngicos/farmacologia , Aspergillus flavus/efeitos dos fármacos , Aspergillus fumigatus/efeitos dos fármacos , Quitosana/farmacologia , Oligossacarídeos/farmacologia , Animais , Anti-Infecciosos/farmacologia , Membrana Celular/efeitos dos fármacos , Parede Celular/efeitos dos fármacos , Indústria Alimentícia/métodos , Humanos , Testes de Sensibilidade Microbiana/métodos , Microscopia Eletrônica de Varredura/métodos , Espécies Reativas de Oxigênio/metabolismo
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