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Mesenchymal stem cell - originated exosomes (MSC-exo) are promising non-cellular treatment agents for various diseases. The present study aimed to explore whether human umbilical cord MSC - originated exosomes (HUC-MSC-exo) have the function of protecting human cells (16HBE) against the damage caused by HQ and the related mechanism. HUC-MSC-exo was isolated with differential gradient ultracentrifugation method and characterized by using transmission electron microscope (TEM). 16HBE cells were used as the tool cells and co-cultured with HUC-MSC-exo. Confocal laser scanning microscope was employed to confirm the ingestion of HUC-MSC-exo by 16HBE. Cell proliferation, migration, oxidative stress, DNA and chromosome damages of 16HBE were analyzed under HQ stress, and the role of miR-221/PTEN axis was investigated. Our data showed that under HQ stress, different groups of cells exhibited significantly decreased proliferation and migration abilities, and significant oxidative stress, DNA and chromosome damage effects. HUC-MSC-exo could alleviate the cytotoxic, oxidative stress and genotoxic damage effects of HQ on 16HBE cells. Mechanistically, HQ exposure up-regulated the level of miR-221 and down-regulated PTEN, while HUC-MSC-exo could significantly reduce the level of miR-221 and promote PTEN expression, which was involved in alleviating the toxic effects of HQ on 16HBE cells. Our data indicates that HUC-MSC-exo can alleviate the oxidative stress, cytotoxic and genotoxic effects of HQ on 16HBE cells via miR-221/PTEN pathway, and it may be a promising agent for protecting against the toxicity of HQ.
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Proliferação de Células , Dano ao DNA , Exossomos , Hidroquinonas , Células-Tronco Mesenquimais , MicroRNAs , Estresse Oxidativo , PTEN Fosfo-Hidrolase , Humanos , PTEN Fosfo-Hidrolase/metabolismo , MicroRNAs/metabolismo , MicroRNAs/genética , Estresse Oxidativo/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Hidroquinonas/toxicidade , Linhagem Celular , Cordão Umbilical/citologia , Movimento Celular/efeitos dos fármacosRESUMO
This study examines the effects of comprehensive nursing care on hand-foot syndrome (HFS) in breast cancer patients treated with capecitabine. A retrospective analysis was conducted on 71 patients, divided into a study group receiving comprehensive care and a control group receiving conventional care. Results showed that the study group experienced significant improvements in skin symptoms, self-efficacy, quality of life, and lower anxiety and depression levels compared to the control group. Additionally, patients who were compliant with medications were notably better in the study group. Comprehensive care effectively alleviates the symptoms of hand-foot syndrome in breast cancer patients treated with capecitabine and enhances patient well-being.
Cette étude examine les effets des soins infirmiers complets sur le syndrome main-pied (SMP) chez les patientes atteintes de cancer du sein traitées par capécitabine. Une analyse rétrospective a été réalisée sur 71 patientes, divisées en un groupe d'étude recevant des soins complets et un groupe témoin recevant des soins conventionnels. Les résultats ont montré que le groupe d'étude a connu des améliorations significatives des symptômes cutanés, de l'auto-efficacité, de la qualité de vie, ainsi qu'une réduction des niveaux d'anxiété et de dépression par rapport au groupe témoin. De plus, les patientes adhérant au traitement médicamenteux étaient notablement meilleures dans le groupe d'étude. Les soins complets atténuent efficacement les symptômes du syndrome main-pied chez les patientes atteintes de cancer du sein traitées par capécitabine et améliorent leur bien-être.
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Antimetabólitos Antineoplásicos , Neoplasias da Mama , Capecitabina , Síndrome Mão-Pé , Qualidade de Vida , Humanos , Capecitabina/efeitos adversos , Capecitabina/uso terapêutico , Síndrome Mão-Pé/etiologia , Neoplasias da Mama/tratamento farmacológico , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/uso terapêutico , Adulto , Resultado do TratamentoRESUMO
Background: This study aimed to assess the knowledge, attitudes and practices (KAP) among patients with diabetes mellitus and hyperuricemia toward disease self-management. Methods: This web-based cross-sectional study was conducted between June 2023 and January 2024 at Heilongjiang Provincial Hospital. A self-designed questionnaire was developed to collect demographic information of patients with diabetes mellitus and hyperuricemia, and assess their knowledge, attitudes and practices toward disease self-management. Results: A total of 482 participants were enrolled in this study, among them, 364 (75.52%) were male, 235 (48.76%) were aged between 40 and 59 years, 226 (46.89%) had a body mass index (BMI) ranging from 24 to 28 kg/m2, 337 (69.92%) had received a diagnosis of diabetes for a duration of 2 years or more, while 245 (50.83%) had been diagnosed with hyperuricemia for a similar duration. Their median (range) knowledge, attitude and practice scores were 10.00 (9.00, 11.00) (possible range: 0-12), 38.00 (36.00, 40.00) (possible range: 9-45), and 30.00 (26.00, 34.75) (possible range: 10-50), respectively. The path analysis demonstrated that knowledge had direct effects on attitude (ß = 0.508, p < 0.001), and attitude had direct effects on practice (ß = 0.448, p < 0.001). Additionally, there was an indirect effect of knowledge on practice mediated through attitude, with a path coefficient of 0.228 (p < 0.001). Conclusion: This study demonstrates that patients with diabetes mellitus and hyperuricemia exhibit relatively proficient responses to certain items within the KAP dimensions. However, it also exposes a certain degree of inadequacy in the KAP level toward disease management. Interventions should focus on improving patients' understanding of their conditions while fostering positive attitudes, ultimately translating into better self-management practices.
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Diabetes Mellitus , Conhecimentos, Atitudes e Prática em Saúde , Hiperuricemia , Autogestão , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Transversais , Feminino , Adulto , Inquéritos e Questionários , Diabetes Mellitus/terapia , Diabetes Mellitus/psicologia , China , IdosoRESUMO
When chloroaluminate (AlCl4-) serves as the electrolyte, aluminum nitride (AlN) has shown promise as a cathode material in aluminum ion batteries. However, there is currently a lack of research on the mechanisms of charge transfer and cluster intercalation between AlCl4 and AlN cathode materials. Herein, first-principles calculations are employed to investigate the intercalation mechanism of AlCl4 within the AlN cathode. By calculating the formation energies of stage-1-5 AlN-AlCl4 intercalation compounds with the insertion of individual AlCl4 cluster, we found that the structure of the stage-4 intercalation compounds exhibits the highest stability, suggesting that when the clusters begin to intercalate, it is important to start with the formation of the stage-4 intercalation compounds. In the subsequent phases of the charging process (stages 1 and 2), the stabilized structure with four inserted clusters demonstrates two characteristics: the coexistence of standing and lying clusters and the insertion of two standing clusters in an upside-down doubly stacked configuration, which further improve the spatial utilization while maintaining the structural stability. In addition, we infer that a phenomenon of coexisting intercalation compounds with mixed stages will occur in the course of the charging and discharging processes. More importantly, the diffusion barrier of AlCl4 in AlN-AlCl4 intercalation compounds decreases with the reduction of stage number, ensuring the rate performance of batteries. Therefore, we expect that our work will contribute to comprehend the intercalation mechanism of AlCl4 into the AlN cathode materials of aluminum ion batteries, providing guidance for related experimental work.
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Most plant phylogeographic studies in China have focused on the importance of genetic divergence and where should the shelter be located. Little attention has been paid to range expansion and recolonization routes in this region. In this study, two cpDNA fragments (psbK-psbI and trnL-F), two pairs of nuclear gene sequences (ITS and ETS), and nine pairs of SSR molecular markers were used, combined with Bayesian Skyline Plot method, gene barrier analysis, and species distribution models to explore the phylogeographical pattern, potential expansion routes and population dynamic history of Pinellia ternata from 22 population. The results showed that phylogeograhical pattern and genetic structure for P. ternata are effected by environmental heterogeneity and climate fluctuation, and it can be divided into two groups (Southwest group, Central and Eastern group) and thus there are at least two glacial refugia in China. Three expanding routes within groups were explored to contribute to the phylogeogrephic pattern of P. ternata based on the geographical distribution and network analysis of haplotypes. In a word, our study reveals repeated range expansions and inter/postglacial recolonization routes on the fragmented distribution pattern in China and resolves the refugia distributing in China and has also certain reference value for the protection of the medicinal plant P. ternata.
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Objective: This study aimed to explore the potential causal relationship between the gut microbiota and/or its metabolites and the progression of chronic hepatitis B (CHB). Method: The gut microbiota was used as the exposure factor. The training set exposure data were obtained from the China Nucleotide Sequence Archive (CNSA). Genome-wide association study (GWAS) data from Asia were used as the outcome variables. Outcome data for both the training and validation sets were sourced from the GWAS Catalog database. A dual-sample Mendelian randomization approach was used to analyze the causal relationships, with the inverse variance-weighted method serving as the main analytical strategy. Sensitivity analysis was conducted to assess the robustness of Mendelian randomization analysis results. Result: In the training set database, analysis using the inverse variance-weighted method revealed a positive correlation between Fusobacterium varium and chronic hepatitis B [OR = 1.122, 95% CI (1.016, 1.240), p = 0.022]. Conversely, Veillonella parvula exhibited a negative correlation with chronic hepatitis B [OR = 0.917, 95% CI (0.852, 0.987), p = 0.021]. Sensitivity analysis revealed no evidence of pleiotropy and heterogeneity. No gut microbiota metabolites with a causal effect on chronic hepatitis B were identified. Additionally, no associations between the gut microbiota and the progression of chronic hepatitis B were found in the validation data from the European cohort. Conclusion: This study suggests that F. varium may facilitate the progression of chronic hepatitis B, whereas V. parvula may impede it. No causal relationships between gut microbiota metabolites and chronic hepatitis B were established.
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Microbioma Gastrointestinal , Estudo de Associação Genômica Ampla , Hepatite B Crônica , Análise da Randomização Mendeliana , Humanos , Microbioma Gastrointestinal/genética , Hepatite B Crônica/microbiologia , China , MasculinoRESUMO
Infection with Schistosoma japonicum (S. japonicum) is an important zoonotic parasitic disease that causes liver fibrosis in both human and domestic animals. The activation of hepatic stellate cells (HSCs) is a crucial phase in the development of liver fibrosis, and inhibiting their activation can alleviate this progression. Total flavonoids of litchi seed (TFL) is a naturally extracted drug, and modern pharmacological studies have shown its anti-fibrotic and liver-protective effects. However, the role of TFL in schistosomiasis liver fibrosis is still unclear. This study investigated the therapeutic effects of TFL on liver fibrosis in S. japonicum infected mice and explored its potential mechanisms. Animal study results showed that TFL significantly reduced the levels of Interleukin-1ß (IL-1ß), Tumor Necrosis Factor-α (TNF-α), Interleukin-4 (IL-4), and Interleukin-6 (IL-6) in the serum of S. japonicum infected mice. TFL reduced the spleen index of mice and markedly improved the pathological changes in liver tissues induced by S. japonicum infection, decreasing the expression of alpha-smooth muscle actin (α-SMA), Collagen I and Collagen III protein in liver tissues. In vitro studies indicated that TFL also inhibited the activation of HCSs induced by Transforming Growth Factor-ß1 (TGF-ß1) and reduced the levels of α-SMA. Gut microbes metagenomics study revealed that the composition, abundance, and functions of the mice gut microbiomes changed significantly after S. japonicum infection, and TLF treatment reversed these changes. Therefore, our study indicated that TFL alleviated granulomatous lesions and improved S. japonicum induced liver fibrosis in mice by inhibiting the activation of HSCs and by improving the gut microbiomes.
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Flavonoides , Microbioma Gastrointestinal , Células Estreladas do Fígado , Litchi , Cirrose Hepática , Sementes , Animais , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/parasitologia , Cirrose Hepática/patologia , Microbioma Gastrointestinal/efeitos dos fármacos , Flavonoides/farmacologia , Camundongos , Litchi/química , Sementes/química , Esquistossomose Japônica/tratamento farmacológico , Esquistossomose Japônica/complicações , Citocinas/metabolismo , Schistosoma japonicum/efeitos dos fármacos , Schistosoma japonicum/patogenicidade , Masculino , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/parasitologiaRESUMO
Overexposure of sewage workers to bioaerosol released from wastewater treatment plants (WWTPs) can cause serious infections, but practical method for controlling their health risk is lacking. In this study, reverse quantitative microbial risk assessment was used to estimate the daily critical exposure time (CET) of sewage workers exposing to Staphylococcus aureus bioaerosol emitted by three emission sources facilities in a WWTP based on either U.S. EPA or WHO benchmark, and sensitivity analysis was conducted to analyze the influence of various parameters on the outcomes of CET. The results showed that the CET of females was always 1.12-1.29 times that of males. In addition, the CET after wearing face masks was 28.28-52.37 times as long as before. The working time can be determined based on the CET results of male workers wearing face masks exposed to the inverted-umbrella aeration tank (14.73-550.98 min for U.S. EPA benchmark and 55.07-1972.24 min for WHO benchmark). In each scenario, the variable parameter exposure concentration (ec) always showed the most influence on the CET results. After wearing the face masks, the removal fraction by employing face masks also had a significant effect on the results, only second to ec. Therefore, the wearing of face mask is the most convenient and effective measure to prolong the CET. Furthermore, practical methods to reducing bioaerosol concentration in WWTPs exposure are also necessary to extend CET and safeguard worker health. This study enriches the application range of reverse quantitative microbial risk assessment framework and provides theoretical support for stakeholders to establish reasonable working time threshold guidelines, and practical method and novel perspective to protect the on-site health risks of sewage workers exposing to various facilities.
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Aerossóis , Exposição Ocupacional , Águas Residuárias , Aerossóis/análise , Águas Residuárias/química , Exposição Ocupacional/análise , Humanos , Medição de Risco , Staphylococcus aureus , Eliminação de Resíduos Líquidos/métodos , Monitoramento Ambiental , Microbiologia do Ar , Feminino , Masculino , Poluentes Ocupacionais do Ar/análiseRESUMO
Vivipary is a prominent feature of mangroves, allowing seeds to complete germination while attached to the mother plant, and equips propagules to endure and flourish in challenging coastal intertidal wetlands. However, vivipary-associated genetic mechanisms remain largely elusive. Genomes of two viviparous mangrove species and a non-viviparous inland relative were sequenced and assembled at the chromosome level. Comparative genomic analyses between viviparous and non-viviparous genomes revealed that DELAY OF GERMINATION 1 (DOG1) family genes (DFGs), the proteins from which are crucial for seed dormancy, germination, and reserve accumulation, are either lost or dysfunctional in the entire lineage of true viviparous mangroves but are present and functional in their inland, non-viviparous relatives. Transcriptome dynamics at key stages of vivipary further highlighted the roles of phytohormonal homeostasis, proteins stored in mature seeds, and proanthocyanidins in vivipary under conditions lacking DFGs. Population genomic analyses elucidate dynamics of syntenic regions surrounding the missing DFGs. Our findings demonstrated the genetic foundation of constitutive vivipary in Rhizophoraceae mangroves.
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Genoma de Planta , Rhizophoraceae/genética , Rhizophoraceae/fisiologia , Germinação/genética , Transcriptoma , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , SapindaceaeRESUMO
In response to the energy crisis caused by the exhaustion of fossil energy sources, as well as to combat global warming and achieve carbon neutrality, a sandwiched-structure fabric-based moisture-enabled electricity generator (SMEG) has been developed. Cotton fabric coated with MWCNT and PEDOT: PSS solution is used as the upper and bottom electrodes, while the acid-treated cotton fabric with coating PVA and HCl hydrogel electrolyte serves as the middle layer. A single SMEG can generate a maximum open-circuit voltage (Voc) of 0.44 V and a maximum short-circuit current (Isc) of 30 µA. When a drop of LiCl is dripped on one side of SMEGs, the maximum Voc and Isc increases to 0.57 V and 66 µA, respectively. The decline in output performance slows down when LiCl is applied. The Voc increases almost linearly in series and reaches 3.55 V when six SMEGs are connected, while the Isc increases linearly in parallel and reaches 204 µA when six SMEGs are connected. The maximum power density of a single SMEG yields 0.29 µW/cm2 with an external resistance of 1 kΩ. The series connection of six SMEGs successfully lit an LED and a calculator under ambient humidity conditions, demonstrating their potential application in small electronics.
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Several coprinoid fungi have been identified as promotors of Cremastra appendiculata seed germination, while others appear ineffective. This study aimed to discern which genera within the Psathyrellaceae family exhibit this capability and to identify the most effective coprinoid fungi for the cultivation of C. appendiculata. We collected 21 coprinoid fungi from diverse sources and symbiotically cultured them with C. appendiculata seeds. 9 fungi were found to induce seed germination and support seed development, specifically within the genera Coprinellus, Tulosesus, and Candolleomyces. In contrast, fungi that failed to promote germination predominantly belonged to the genera Coprinopsis and Parasola. Notably, four fungi-Coprinellus xanthothrix, Coprinellus pseudodisseminatus, Psathyrella singeri, and Psathyrella candolleana-were documented for the first time as capable of enhancing C. appendiculata seed germination. Strain 218LXJ-10, identified as Coprinellus radians, demonstrated the most significant effect and has been implemented in large-scale production, underscoring its considerable practical value. These findings contribute vital scientific insights for the conservation and sustainable use of C. appendiculata resources.
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Germinação , Sementes , Simbiose , Sementes/microbiologia , Sementes/crescimento & desenvolvimento , Filogenia , Fungos/classificação , Fungos/isolamento & purificação , Fungos/genética , Fungos/fisiologiaRESUMO
Background: Breast-conserving surgery (BCS) stands as the favored modality for treating early-stage breast cancer. Accurately forecasting the feasibility of BCS preoperatively can aid in surgical planning and reduce the rate of switching of surgical methods and reoperation. The objective of this study is to identify the radiomics features and preoperative breast magnetic resonance imaging (MRI) characteristics that are linked with positive margins following BCS in patients with breast cancer, with the ultimate aim of creating a predictive model for the feasibility of BCS. Methods: This study included a cohort of 221 pretreatment MRI images obtained from patients with breast cancer. A total of seven MRI semantic features and 1,561 radiomics features of lesions were extracted. The feature subset was determined by eliminating redundancy and correlation based on the features of the training set. The least absolute shrinkage and selection operator (LASSO) logistic regression was then trained with this subset to classify the final BCS positive and negative margins and subsequently validated using the test set. Results: Seven features were significant in the discrimination of cases achieving positive and negative margins. The radiomics signature achieved area under the curve (AUC), accuracy, sensitivity, and specificity of 0.760 [95% confidence interval (CI): 0.630, 0.891], 0.712 (95% CI: 0.569, 0.829), 0.882 (95% CI: 0.623, 0.979) and 0.629 (95% CI: 0.449, 0.780) in the test set, respectively. The combined model of radiomics signature and background parenchymal enhancement (BPE) demonstrated an AUC, accuracy, sensitivity, and specificity of 0.759 (95% CI: 0.628, 0.890), 0.654 (95% CI: 0.509, 0.780), 0.679 (95% CI: 0.476, 0.834) and 0.625 (95% CI: 0.408, 0.804). Conclusions: The combination of preoperative MRI radiomics features can well predict the success of breast conserving surgery.
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BACKGROUND: Triatomines (kissing bugs) are natural vectors of trypanosomes, which are single-celled parasitic protozoans, such as Trypanosoma cruzi, T. conorhini and T. rangeli. The understanding of the transmission cycle of T. conorhini and Triatoma rubrofasciata in China is not fully known. METHODS: The parasites in the faeces and intestinal contents of the Tr. rubrofasciata were collected, and morphology indices were measured under a microscope to determine the species. DNA was extracted from the samples, and fragments of 18S rRNA, heat shock protein 70 (HSP70) and glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) were amplified and sequenced. The obtained sequences were then identified using the BLAST search engine, followed by several phylogenetic analyses. Finally, laboratory infections were conducted to test whether Tr. rubrofasciata transmit the parasite to rats (or mice) through bites. Moreover, 135 Tr. rubrofasciata samples were collected from the Guangxi region and were used in assays to investigate the prevalence of trypanosome infection. RESULTS: Trypanosoma sp. were found in the faeces and intestinal contents of Tr. rubrofasciata, which were collected in the Guangxi region of southern China and mostly exhibited characteristics typical of epimastigotes, such as the presence of a nucleus, a free flagellum and a kinetoplast. The body length ranged from 6.3 to 33.9 µm, the flagellum length ranged from 8.7 to 29.8 µm, the nucleus index was 0.6 and the kinetoplast length was -4.6. BLAST analysis revealed that the 18S rRNA, HSP70 and gGAPDH sequences of Trypanosoma sp. exhibited the highest degree of similarity with those of T. conorhini (99.7%, 99.0% and 99.0%, respectively) and formed a well-supported clade close to T. conorhini and T. vespertilionis but were distinct from those of T. rangeli and T. cruzi. Laboratory experiments revealed that both rats and mice developed low parasitaemia after inoculation with Trypanosoma sp. and laboratory-fed Tr. rubrofasciata became infected after feeding on trypanosome-positive rats and mice. However, the infected Tr. rubrofasciata did not transmit Trypanosoma sp. to their offspring. Moreover, our investigation revealed a high prevalence of Trypanosoma sp. infection in Tr. rubrofasciata, with up to 36.3% of specimens tested in the field being infected. CONCLUSIONS: Our study is the first to provide a solid record of T. conorhini from Tr. rubrofasciata in China with morphological and molecular evidence. This Chinese T. conorhini is unlikely to have spread through transovarial transmission in Tr. rubrofasciata, but instead, it is more likely that the parasite is transmitted between Tr. rubrofasciata and mice (or rats). However, there was a high prevalence of T. conorhini in the Tr. rubrofasciata from our collection sites and numerous human cases of Tr. rubrofasciata bites were recorded. Moreover, whether these T. conorhini strains are pathogenic to humans has not been investigated.
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Insetos Vetores , Filogenia , RNA Ribossômico 18S , Triatoma , Trypanosoma , Animais , China/epidemiologia , Ratos , Camundongos , Trypanosoma/genética , Trypanosoma/isolamento & purificação , Trypanosoma/classificação , Triatoma/parasitologia , RNA Ribossômico 18S/genética , Insetos Vetores/parasitologia , Tripanossomíase/parasitologia , Tripanossomíase/transmissão , Tripanossomíase/veterinária , Tripanossomíase/epidemiologia , Fezes/parasitologia , Proteínas de Choque Térmico HSP70/genética , DNA de Protozoário/genética , Feminino , MasculinoRESUMO
Chemotherapeutics can induce immunogenic cell death (ICD) in tumor cells, offering new possibilities for cancer therapy. However, the efficiency of the immune response generated is insufficient due to the inhibitory nature of the tumor microenvironment (TME). Here, we developed a pH/reactive oxygen species (ROS) dual-response system to enhance chemoimmunotherapy for melanoma. The system productively accumulated in tumors by specific binding of phenylboronic acid (PBA) to sialic acids (SA). The nanoparticles (NPs) rapidly swelled and released quercetin (QUE) and doxorubicin (DOX) upon the stimulation of tumor microenvironment (TME). The in vitro and in vivo results consistently demonstrated that the NPs improved anti-tumor efficacy and prolonged survival of mice, significantly enhancing the effects of the combination. Our study revealed DOX was an ICD inducer, stimulating immune responses and promoting maturation of dendritic cells (DCs). Additionally, QUE served as a TME regulator by inhibiting the cyclooxygenase-2 (COX2)-prostaglandin E2 (PGE2) axis, which influenced various immune cells, including increasing cytotoxic T cells (CLTs) infiltration, promoting M1 macrophage polarization, and reducing regulatory T cells (Tregs) infiltration. The combination synergistically facilitated chemoimmunotherapy efficacy by remodeling the immunosuppressive microenvironment. This work presents a promising strategy to increase anti-tumor efficiency of chemotherapeutic agents.
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Introduction: Zinc (Zn) is an essential trace element in animals, but excessive intake can lead to renal toxicity damage. Thus, the exploration of effective natural antagonists to reduce the toxicity caused by Zn has become a major scientific problem. Methods: Here, we found that hesperidin could effectively alleviate the renal toxicity induced by Zn in pigs by using hematoxylin-eosin staining, transmission electron microscope, immunohistochemistry, fluorescence quantitative PCR, and microfloral DNA sequencing. Results: The results showed that hesperidin could effectively attenuate the pathological injury in kidney, and reduce autophagy and apoptosis induced by Zn, which evidenced by the downregulation of LC3, ATG5, Bak1, Bax, Caspase-3 and upregulation of p62 and Bcl2. Additionally, hesperidin could reverse colon injury and the decrease of ZO-1 protein expression. Interestingly, hesperidin restored the intestinal flora structure disturbed by Zn, and significantly reduced the abundance of Tenericutes (phylum level) and Christensenella (genus level). Discussion: Thus, altered intestinal flora and intestinal barrier function constitute the gut-kidney axis, which is involved in hesperidin alleviating Zn-induced nephrotoxicity. Our study provides theoretical basis and practical significance of hesperidin for the prevention and treatment of Zn-induced nephrotoxicity through gut-kidney axis.
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Apoptose , Microbioma Gastrointestinal , Hesperidina , Rim , Zinco , Animais , Hesperidina/farmacologia , Suínos , Zinco/metabolismo , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo , Apoptose/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Nefropatias/induzido quimicamente , Nefropatias/prevenção & controleRESUMO
Tributyltin chloride (TBTC) is a ubiquitous environmental pollutant with various adverse effects on human health. Exosomes are cell - derived signaling and substance transport vesicles. This investigation aimed to explore whether exosomes could impact the toxic effects caused by TBTC via their transport function. Cytotoxicity, DNA and chromosome damage caused by TBTC on MCF-7 cells were analyzed with CCK-8, flow cytometry, comet assay and micronucleus tests, respectively. Exosomal characterization and quantitative analysis were performed with ultracentrifugation, transmission electron microscope (TEM) and bicinchoninic acid (BCA) methods. TBTC content in exosomes was detected with Liquid Chromatography-Mass Spectrometry (LC-MS). The impacts of exosomal secretion on the toxic effects of TBTC were analyzed. Our data indicated that TBTC caused significant cytotoxicity, DNA and chromosome damage effects on MCF-7 cells, and a significantly increased exosomal secretion. Importantly, TBTC could be transported out of MCF-7 cells by exosomes. Further, when exosomal secretion was blocked with GW4869, the toxic effects of TBTC were significantly exacerbated. We concluded that TBTC promoted exosomal secretion, which in turn transported TBTC out of the source cells to alleviate its toxic effects. This investigation provided a novel insight into the role and mechanism of exosomal release under TBTC stress.
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Dano ao DNA , Exossomos , Compostos de Trialquitina , Humanos , Exossomos/efeitos dos fármacos , Exossomos/metabolismo , Compostos de Trialquitina/toxicidade , Células MCF-7 , Dano ao DNA/efeitos dos fármacos , Transporte Biológico/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Sobrevivência Celular/efeitos dos fármacosRESUMO
An interfacial solar steam generation evaporator for seawater desalination has attracted extensive interest in recent years. Nevertheless, challenges still remain in relatively low evaporation rate, unsatisfactory energy conversion efficiency, and salt accumulation. Herein, we have demonstrated a biomimetic bilayer composite aerogel consisting of bottom hydrophilic and vertically aligned EVOH channels and an upper hydrophobic conical Fe3O4 array. Thanks to the design merits, the 3D Fe3O4/V-EVOH evaporator exhibits a high evaporation rate of â¼2.446 kg m-2 h-1 and an impressive solar energy conversion efficiency of â¼165.5% under 1 sun illumination, which is superior to those of state-of-the-art evaporators reported so far. Moreover, the asymmetrical wettability not only allows the evaporator to self-float on the water but also facilitates the salt ion diffusion in the channels; thus, the evaporator shows no salt crystals on its surface and only a 6% decrease in evaporation performance even after the salt concentration increases from 0 to 10.0 wt %.
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The mechanistic target of rapamycin (RAPA) complex 1 (mTORC1) - transcription factor EB (TFEB) pathway plays a crucial role in response to nutritional status, energy and environmental stress for maintaining cellular homeostasis. But there is few reports on its role in the toxic effects of arsenic exposure and the related mechanisms. Here, we show that the exposure of bronchial epithelial cells (BEAS-2B) to sodium arsenite promoted the activation of mTORC1 (p-mTORC1) and the inactivation of TFEB (p-TFEB), the number and activity of lysosomes decreased, the content of reduced glutathione (GSH) and superoxide dismutase (SOD) decreased, the content of malondialdehyde (MDA) increased, the DNA and chromosome damage elevated. Further, when mTORC1 was inhibited with RAPA, p-mTORC1 and p-TFEB down-regulated, GSH and SOD increased, MDA decreased, the DNA and chromosome damage reduced significantly, as compared with the control group. Our data revealed for the first time that mTORC1 - TFEB pathway was involved in sodium arsenite induced lysosomal alteration, oxidative stress and genetic damage in BEAS-2B cells, and it may be a potential intervention target for the toxic effects of arsenic.
Assuntos
Arsenitos , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Dano ao DNA , Lisossomos , Alvo Mecanístico do Complexo 1 de Rapamicina , Estresse Oxidativo , Compostos de Sódio , Arsenitos/toxicidade , Compostos de Sódio/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Linhagem Celular , Dano ao DNA/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Transdução de Sinais/efeitos dos fármacos , Brônquios/efeitos dos fármacos , Brônquios/metabolismo , Brônquios/citologia , Brônquios/patologia , Glutationa/metabolismo , Superóxido Dismutase/metabolismo , Complexos Multiproteicos/metabolismo , Malondialdeído/metabolismoRESUMO
Background: The prognostic effects of different treatment modalities on patients with hypopharyngeal squamous cell carcinoma (HPSCC) remain unclear. Methods: HPSCC patients diagnosed and treated at either West China Hospital or Sichuan Cancer Hospital between January 1, 2009, and December 31, 2019, were enrolled in this retrospective, real-world study. Survival rates were presented using Kaplan-Meier curves and compared using log-rank tests. Univariable and multivariable Cox proportional hazards regression models were used to identify the predictors of overall survival (OS). Subgroup analyses were conducted for patients with advanced-stage HPSCC (stages III and IV and category T4). Results: A total of 527 patients with HPSCC were included. Patients receiving SRC (surgery, radiotherapy [RT], and chemotherapy) showed the best OS (p < 0.0001). In comparison with RT alone, both surgery alone (all cases: hazard ratio [HR] = 0.39, p = 0.0018; stage IV cases: HR = 0.38, p = 0.0085) and surgery-based multimodality treatment (SBMT; all cases: HR = 0.27, p < 0.0001; stage IV cases: HR = 0.30, p = 0.00025) showed prognostic benefits, while SBMT also showed survival priority over chemoradiotherapy (CRT; all cases: HR = 0.52, p < 0.0001; stage IV cases: HR = 0.59, p = 0.0033). Moreover, patients who underwent surgery alone had comparable OS to those who underwent SBMT (all patients: p = 0.13; stage IV cases: p = 0.34), while CRT yielded similar prognostic outcomes as RT alone (all patients: p = 0.054; stage IV cases: p = 0.11). Conclusions: Surgery alone was comparable to SBMT and superior to RT/CRT in terms of OS in patients with HPSCC. We suggest that surgery should be encouraged for the treatment of HPSCC, even in patients with advanced-stage disease.