RESUMO
Hypoxia as a microenvironment or niche stimulates proliferation of neural stem cells (NSCs). However, the underlying mechanisms remain elusive. Autophagy is a protective mechanism by which recycled cellular components and energy are rapidly supplied to the cell under stress. Whether autophagy mediates the proliferation of NSCs under hypoxia and how hypoxia induces autophagy remain unclear. Here, we report that hypoxia facilitates embryonic NSC proliferation through HIF-1/mTORC1 signaling pathway-mediated autophagy. Initially, we found that hypoxia greatly induced autophagy in NSCs, while inhibition of autophagy severely impeded the proliferation of NSCs in hypoxia conditions. Next, we demonstrated that the hypoxia core regulator HIF-1 was necessary and sufficient for autophagy induction in NSCs. Considering that mTORC1 is a key switch that suppresses autophagy, we subsequently analyzed the effect of HIF-1 on mTORC1 activity. Our results showed that the mTORC1 activity was negatively regulated by HIF-1. Finally, we provided evidence that HIF-1 regulated mTORC1 activity via its downstream target gene BNIP3. The increased expression of BNIP3 under hypoxia enhanced autophagy activity and proliferation of NSCs, which was mediated by repressing the activity of mTORC1. We further illustrated that BNIP3 can interact with Rheb, a canonical activator of mTORC1. Thus, we suppose that the interaction of BNIP3 with Rheb reduces the regulation of Rheb toward mTORC1 activity, which relieves the suppression of mTORC1 on autophagy, thereby promoting the rapid proliferation of NSCs. Altogether, this study identified a new HIF-1/BNIP3-Rheb/mTORC1 signaling axis, which regulates the NSC proliferation under hypoxia through induction of autophagy.
Assuntos
Proteínas de Membrana , Células-Tronco Neurais , Humanos , Proteínas de Membrana/genética , Hipóxia Celular , Hipóxia/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Autofagia , Células-Tronco Neurais/metabolismo , Proliferação de Células , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismoRESUMO
BACKGROUND: Laboratory scale experiments have shown that curdlan and gellan gum gelled together as curdlan/gellan gum (CG) hybrid gels showed better gel properties than the individual curdlan and gellan gum. In this study, CG and black wolfberry anthocyanin (BWA), CG and maltitol (ML) hybrid gels were constructed using CG hybrid gel as matrix. The effects of BWA or ML on the gel properties and microstructure of CG hybrid gels were investigated and a confectionery gel was developed. RESULTS: The presence of BWA increased the storage modulus (G') value of CG at 0.1 Hz, whereas ML had little effect on the G' value of CG. The addition of BWA (5 g L-1 ) and ML (0.3 mol L-1 ) increased the melting and gelling temperatures of CG hybrid gels to 42.4 °C and 34.1 °C and 44.2 °C and 33.2 °C, respectively. Meanwhile, the relaxation time T22 in CG-ML and CG-BWA hybrid gels was reduced to 91.96 and 410.27 ms, indicating the strong binding between BWA and CG, ML and CG. The hydrogen bond interaction between BWA or ML and CG was confirmed by the shift in the hydroxyl stretching vibration peak. Moreover, the microstructures of CG-ML and CG-BWA hybrid gels were denser than that of CG. In addition, confectionery gel containing CG-BWA-ML has good chewing properties. CONCLUSION: These results indicated that the incorporation of BWA or ML could improve the structure of CG hybrid gels and assign a sustainability potential for the development of confectionery gels based on CG complex. © 2024 Society of Chemical Industry.
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Lycium , Maltose/análogos & derivados , Álcoois Açúcares , beta-Glucanas , Antocianinas , Polissacarídeos Bacterianos/química , Géis/química , ReologiaRESUMO
Laryngeal squamous cell carcinoma (LSCC) is one of the most prevalent malignant diseases worldwide. LSCC patients suffer from a severe decline in life quality, due to the essential roles of the larynx in basic functions in the human body. The overarching goal of the present study is to explore whether exosome from M2 macrophages promotes LSCC by targeting glycolysis. In the current study, the expression of PDLIM2, an E3 ubiquitin ligase, in clinical samples was monitored by quantitative PCR and immunohistochemical examination. Extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) were measured by the Seahorse machine. Cell proliferation was measured by using Cell Counting Kit-8. A luciferase assay was performed to verify the regulation of miRNA on its target gene. The results showed that PDLIM2 exhibited downregulation in LSCC clinical samples and was associated with stage and differentiation of tumors in patients. In FaDu cell line, PDLIM2 inhibited cell proliferation and glycolysis but promoted the ubiquitination of PFKL. Exosomes from M2-type macrophages delivered miR-222-3p into LSCC cells to suppress PDLIM2 expression, leading to the elevated expression of PFKL and enhanced glycolysis which accelerated the proliferation of FaDu cells. The findings from cultured cells were supported by a subcutaneous tumor growth model in nude mice. Collectively, our data provided a snapshot of the miR-222-3p/PDLIM2/PFKL axis in LSCC tumorigenesis, and in concert with the importance of TAM exosomes and glycolysis, could be potentially translated to LSCC clinics.
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Carcinoma de Células Escamosas , Exossomos , Neoplasias de Cabeça e Pescoço , Neoplasias Laríngeas , MicroRNAs , Proteínas Adaptadoras de Transdução de Sinal , Animais , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Glicólise , Neoplasias de Cabeça e Pescoço/genética , Humanos , Proteínas com Domínio LIM , Neoplasias Laríngeas/patologia , Macrófagos , Camundongos , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Ubiquitina-Proteína Ligases/genéticaRESUMO
Peimine (PM), a natural product extracted from Fritillaria, has anti-inflammatory, drug resistance reversal, and other pharmacological effects. The purpose of this study was to investigate the antitumor effects and the molecular mechanisms of PM using gastric cancer MKN-45 cells. Cell counting kit-8 assays were used to evaluate the viability of gastric cancer cells after treatment with PM. The results showed that PM significantly reduced the activity of gastric cancer cells, and the effect was most obvious in MKN-45 cells. Annexin V-FITC/propidium iodide staining and flow cytometry were used to assess apoptosis of MKN-45 cells after PM treatment. Our results showed that PM-induced apoptosis of MKN-45 cells. Flow cytometry was also used to determine the mitochondrial membrane potential and reactive oxygen species (ROS) levels, and to assess PM-induced cell-cycle arrest. Additionally, Western blot was used to analyze the expression of signaling pathway proteins and the relationship between apoptosis and ROS accumulation. Our findings showed that PM destroyed the mitochondria by diminishing the mitochondrial membrane potential. In addition, PM regulated the mitogen-activated protein kinase (MAPK), signal transducer and activator of transcription 3, and nuclear factor kappa-B signaling pathways by promoting the accumulation of ROS in MKN-45 cells. PM also caused cell-cycle arrest in the G2/M phase by increasing ROS accumulation. Furthermore, PM inhibited cell migration by regulating the Wnt/ß-catenin pathway. In conclusion, PM plays an anticancer role through endogenous apoptosis pathways and by inhibiting cell migration, and it has the potential to be a useful treatment for gastric cancers.
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Fator de Transcrição STAT3 , Neoplasias Gástricas , Humanos , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição STAT3/metabolismo , NF-kappa B/metabolismo , Neoplasias Gástricas/metabolismo , Via de Sinalização Wnt , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas Quinases Ativadas por Mitógeno/farmacologia , Linhagem Celular Tumoral , ApoptoseRESUMO
BACKGROUND: Large yellow croaker (Pseudosciaena crocea) roe is the main by-product in the processing of large yellow croaker. Previous studies have found that its protein isolates are composed of vitellogenin, as well as vitellogenin B and C, having good functional properties. (-)-Epigallocatechin-3-gallate (EGCG) is a natural antioxidant component that can be combined with protein to improve antioxidant activity and structural characteristics of protein. RESULTS: EGCG was bound with the P. crocea roe protein isolate (pcRPI) by the free radical method to prepare the conjugate. The formation of pcRPI-EGCG conjugates was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel permeation chromatography, which showed that the calculated weight-average molar masses of native-pcRPI and pcRPI-EGCG conjugates were 86.9 and 215.3 kDa, respectively. The results of fluorescence, ultraviolet, circular and infrared spectra indicated that the conjugation of EGCG with native-pcRPI changed the secondary and tertiary structure of native-pcRPI. The pcRPI-EGCG conjugates exhibited higher thermal stability than native-pcRPI. The radical scavenging and reducing power of native-pcRPI were increased by 2.0-2.5- and 1.4-fold, respectively, after the EGCG-grafting reaction. CONCLUSION: These results indicate that the binding of pcRPI and EGCG effectively improved the antioxidant properties and structural characteristics of the pcRPI. © 2021 Society of Chemical Industry.
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Antioxidantes/química , Catequina/análogos & derivados , Proteínas de Peixes/química , Conservação de Alimentos/métodos , Conservantes de Alimentos/química , Óvulo/química , Animais , Catequina/química , Feminino , Conservação de Alimentos/instrumentação , Ovário/química , Perciformes , Conformação ProteicaRESUMO
KEY MESSAGE: We found that a rice NADPH oxidase gene OsRbohB contributes drought tolerance and its functions are involved in the interaction of the OsRbohB-mediated ROS production and ABA signaling. The plasma membrane NADPH oxidases, also known as respiratory burst oxidase homologs, are the key producers of ROS under both normal and stress conditions in plants. However, their functions in rice development and stress tolerance are still under investigation. Here, we found that a rice NADPH oxidase gene OsRbohB, also named OsNOX1, is expressed in all tissues examined throughout the development stages with higher transcripts in leaves. The transcriptional expression of OsRbohB is also strongly stimulated by dehydration, salt and several phytohormonal treatments. Compared with wide-type and the OsRbohB-overexpressing transgenic plants, osrbohB, a Tos17 insertion knockout mutant of OsRbohB, shows lower ROS production, abscisic acid (ABA) content and transcripts of a series of stress-related genes. The osrbohB mutant also exhibits lower seed germination rate, organ size and thousand seed weight, but higher stomatal aperture and sensitivity to drought. Moreover, a number of genes involved in plant development, stress response, transcriptional regulation, and particularly ABA signaling are differentially expressed in osrbohB plants under both normal growth and drought conditions. All these results suggest the roles of OsRbohB in drought tolerance of rice, which probably performed through the interaction of the OsRbohB-mediated ROS production and ABA signaling.
Assuntos
Oryza/fisiologia , Proteínas de Plantas/genética , Espécies Reativas de Oxigênio/metabolismo , Estresse Fisiológico/fisiologia , Ácido Abscísico/metabolismo , Secas , Regulação da Expressão Gênica de Plantas , Técnicas de Inativação de Genes , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , Oryza/genética , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Plantas Geneticamente ModificadasRESUMO
To investigate the variation in the condition factor of the sea urchin Strongylocentrotus nudus (S. nudus), gonads were collected in May (MAY), June (JUN), and July (JUL), at the beginning (AUG-b) and end of August (AUG-e). Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) detection of the gonads revealed an obvious enhancement of the band at about 37 kDa from July, which was identified as transforming growth factor-beta-induced protein ig-h3 (TGFBI) by nanoLC-ESI-MS/MS. Gonadal proteins were identified by isobaric tagging for relative and absolute quantitation (iTRAQ), and regulation of the identified proteins in pairs of the collected groups was observed. A total of 174 differentially expressed proteins (DEPs) were identified. Seven of the DEPs showed significant correlations with both the gonad index (GI) and protein content. These correlations included 6-phosphogluconate dehydrogenase, decarboxylating isoform X2 (6PGD), CAD protein, myoferlin isoform X8, ribosomal protein L36 (RL36), isocitrate dehydrogenase [NADP], mitochondrial isoform X2 (IDH), multifunctional protein ADE2 isoform X3, sperm-activating peptides (SAPs) and aldehyde dehydrogenase, and mitochondrial (ALDH). However, TGFBI had no correlation with gonad index (GI) or protein content. 6PGD, IDH, multifunctional protein ADE2 isoform X3, and ALDH were shown to interact with each other and might play key roles in changing the condition factor of S. nudus gonads.
Assuntos
Proteoma/metabolismo , Ouriços-do-Mar/metabolismo , Strongylocentrotus/metabolismo , Animais , Proteínas da Matriz Extracelular/metabolismo , Gônadas/metabolismo , Estações do Ano , Fator de Crescimento Transformador beta/metabolismoRESUMO
Intermittent hypoxia (IH) has preventive and therapeutic effects on hypertension, myocardial infarction, cerebral ischemia and depression, but its effect on post-traumatic stress disorder (PTSD) has not been known. In this study, we used inescapable electric foot shock combined with context recapture to build PTSD mouse model. The levels of fear and anxiety were valued by the open field, the elevated plus maze (EPM) and the fear conditioning tests; the level of spatial memory was valued by Y maze test; the number of Fos positive neurons in hippocampus, amygdala and medial prefrontal cortex was valued by immunohistochemical staining; and the protein expressions of hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and brain derived neurotrophic factor (BDNF) in these brain area were valued by Western blot. The results showed that IH and model (foot shock) had an interaction on percentage of entering open arms (OE%) in EPM and freezing time and the number of fecal pellets in fear conditioning test. IH increased OE% in EPM and reduced the freezing time and the number of fecal pellets in fear conditioning test in PTSD model mice. At the same time, IH reduced the number of Fos positive neurons in the hippocampus, amygdala and medial prefrontal cortex of PTSD model mice, and increased the protein expression levels of HIF-1α, VEGF and BDNF in these brain tissues. In conclusion, IH pretreatment can relieve fear and anxiety behavior in post-traumatic stress model mice, suggesting that IH may be an effective means of preventing PTSD.
Assuntos
Ansiedade/terapia , Medo , Hipóxia , Transtornos de Estresse Pós-Traumáticos/terapia , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Camundongos , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Purpose To investigate the topologic architecture of white matter connectivity networks in preschool-aged children with a diagnosis of autism spectrum disorder (ASD) versus typical development (TD). Materials and Methods Forty-two participants were enrolled, including 21 preschool children with ASD (14 male children and seven female children; mean age, 4.56 years ± 0.97 [standard deviation]) and 21 children with TD (11 males and 10 females; mean age, 5.13 years ± 0.82). The diagnosis of ASD was determined according to the Diagnostic and Statistical Manual of Mental Disorders Global Assessment of Functioning scores (mean score, 8.00 ± 0.50). All participants underwent diffusion-tensor imaging (DTI) and T2-weighted imaging on a 3-T magnetic resonance system. A graph theoretical analysis was applied to investigate the topologic organization of the brain network including global and local topologic parameters. Statistical analysis was then performed for the comparison between the groups. Results Compared with the TD group, children with ASD demonstrated shortened characteristic path length (t1 = 0.536, t2 = 0.534, t3 = 0.523, t4 = 0.510, and t5 = 0.501; P < .05) and increased global efficiency (t1 = 0.499, t2 = 0.497, t3 = 0.486, t4 = 0.473, and t5 = 0.465; P < .05) and clustering coefficient (t1 = 0.673, t2 = 0.750, t3 = 0.757, t4 = 0.738, and t5 = 0.741; P < .05). Significant increases in nodal efficiency were mainly found in left pallidum (0.037 vs 0.032, respectively; P < .01) and right caudate nucleus (0.037 vs 0.032, respectively; P < .01) of the basal ganglia network. Conclusion Significantly altered patterns of global and local brain network topography may underlie the abnormal brain development in preschool children with ASD compared with those who have TD. The identification of altered structural connectivity in basal ganglia and paralimbic-limbic networks may point toward potential imaging biomarkers for preschool-age patients with ASD. © RSNA, 2018.
Assuntos
Transtorno do Espectro Autista/diagnóstico por imagem , Transtorno do Espectro Autista/fisiopatologia , Imagem de Tensor de Difusão/métodos , Imageamento por Ressonância Magnética/métodos , Substância Branca/diagnóstico por imagem , Substância Branca/fisiopatologia , Pré-Escolar , Feminino , Humanos , MasculinoRESUMO
AIMS: To confirm the efficacy of conservative treatment for laryngeal contact granuloma and identify factors influencing treatment outcome. METHODS: In this prospective study, patients with laryngeal contact granuloma were divided into a group receiving conservative treatment and a group undergoing surgery. Efficacy was assessed by analyzing the complete response after a 48-week follow-up. The association of treatment outcome with clinical factors was then evaluated. RESULTS: In total, 61 patients, 43 in the group receiving conservative treatment and 18 in the group undergoing surgery, were analyzed, and the complete response rate was 72.1% and 38.9%, respectively. Both univariate analysis and multivariate analysis revealed that treatment modality (p1 = 0.015, p2 = 0.043), voice abuse (p1 = 0.010, p2 = 0.010), and the size of the granuloma (p1 = 0.031, p2 = 0.020) were significantly associated with the complete response of laryngeal contact granuloma. Kaplan-Meier curves showed that alcohol consumption (p = 0.031), voice abuse (p < 0.001), and granuloma size (p = 0.025) were significantly related to the complete response of conservative treatment. CONCLUSIONS: This prospective study strengthens the argument for conservative treatment (instead of surgery) as the first choice for laryngeal contact granuloma. The results also suggest that voice abuse, alcohol consumption, and the size of the granuloma may predict treatment outcome.
Assuntos
Tratamento Conservador , Medicamentos de Ervas Chinesas/uso terapêutico , Granuloma Laríngeo/cirurgia , Granuloma Laríngeo/terapia , Adulto , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Análise de Variância , Feminino , Granuloma Laríngeo/patologia , Humanos , Estimativa de Kaplan-Meier , Laringoscopia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Voz/fisiologiaRESUMO
Purpose Primary peritoneal serous carcinoma (PPSC) is a rare condition with a poor survival rate, even after treatment with debulking surgery followed by systemic chemotherapy. This study evaluated the efficacy and safety of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of PPSC. Patients and methods This retrospective study included 22 female patients with primary advanced PPSC (group A, n = 12) or recurrent PPSC (group B, n = 10) treated with 25 CRS + HIPEC procedures. The primary end point was overall survival (OS), and the secondary end points were safety profiles. Results A total of 25 CRS + HIPEC procedures were performed in these 22 patients. The median OS was 31.0 months (95% confidence interval (CI) 22.3-39.7), and the 1-, 3-, and 5-year survival rates were 100%, 45.5%, and 27.3%, respectively. Subgroup analyses revealed that the median OS was 31.0 months (95% CI 19.8-42.2) for group A vs. 38.5 months (95% CI 9.6-67.4) for group B (P = 0.832, log rank test); 51.5 months (95% CI 34.9-68.1) for peritoneal cancer index (PCI) ≤ 15 vs. 20.3 months (95% CI 12.6-28.0) for PCI > 15 (P = 0.000, log rank test); and 38.5 months (95% CI 22.5-54.5) for completeness of cytoreduction (CC) of 0-1 vs. 23.5 months (95% CI 15.3-31.7) for CC of 2-3 (P = 0.178, log rank test). There were no perioperative deaths. Serious adverse events (SAEs) occurred in two patients (9.1%). A univariate analysis identified PCI ≤ 15 as the only prognostic predicator (hazard ratio (HR) 13.1, 95% CI 2.7-63.4, P = 0.001). Conclusions CRS + HIPEC could contribute to favourable outcomes for select PPSC patients with acceptable safety profiles.
Assuntos
Adenocarcinoma/terapia , Antineoplásicos/uso terapêutico , Quimioterapia do Câncer por Perfusão Regional , Procedimentos Cirúrgicos de Citorredução , Hipertermia Induzida , Neoplasias Peritoneais/terapia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Adulto , Idoso , China , Cisplatino/uso terapêutico , Terapia Combinada , Docetaxel , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Mitomicina/uso terapêutico , Paclitaxel/uso terapêutico , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/cirurgia , Estudos Retrospectivos , Taxoides/uso terapêuticoRESUMO
BACKGROUND: This work was to evaluate the perioperative safety and efficacy of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) with lobaplatin and docetaxel in patients with peritoneal carcinomatosis (PC) from gastrointestinal and gynecological cancers. METHODS: Patients were treated by CRS + HIPEC with lobaplatin 50 mg/m(2) and docetaxel 60 mg/m(2) in 6000 mL of normal saline at 43 ± 0.5 °C for 60 min. Vital signs were recorded for 6 days after CRS + HIPEC procedures. Perioperative serious adverse events (SAE), hematological, hepatic, renal, and electrolytes parameters, the changes in serum tumor markers (TM) before and after operation, patient recovery, and overall survival (OS) were analyzed. RESULTS: One hundred consecutive PC patients underwent 105 CRS + HIPEC procedures and postoperative chemotherapy. The median CRS + HIPEC duration was 463 (range, 245-820) min, and the highest temperature and heart rate during six postoperative days were 38.6 °C (median 37.5 °C) and 124 bpm (median 100 bpm), respectively. The 30-day perioperative SAE occurred in 16 (15.2 %) and mortality occurred in 2 (1.9 %) patients. Most routine blood laboratory tests at 1 week after surgery turned normal. Among 82 cases with increased preoperative TM CEA, CA125, and CA199, 71 cases had TM levels reduced or turned normal. Median time to nasogastric tube removal was 5 (range, 3-23) days, to liquid food intake 6 (range, 4-24) days, and to abdominal suture removal 15 (range, 10-30) days. At the median follow-up of 19.7 (range, 7.5-89.2) months, the median OS was 24.2 (95 % CI, 15.0-33.4) months, and the 1-, 3-, and 5-year OS rates were 77.5, 32.5, and 19.8 %, respectively. Univariate analysis identified five independent prognostic factors on OS: the origin of PC, peritoneal cancer index, completeness of CRS, cycles of adjuvant chemotherapy, and SAE. CONCLUSIONS: CRS + HIPEC with lobaplatin and docetaxel to treat PC is a feasible procedure with acceptable safety and can prolong the survival in selected patients with PC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00454519.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/terapia , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Neoplasias Gastrointestinais/patologia , Neoplasias dos Genitais Femininos/patologia , Hipertermia Induzida , Neoplasias Peritoneais/terapia , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma/mortalidade , Carcinoma/secundário , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia do Câncer por Perfusão Regional/instrumentação , Quimioterapia do Câncer por Perfusão Regional/métodos , Ciclobutanos/administração & dosagem , Ciclobutanos/farmacologia , Ciclobutanos/uso terapêutico , Docetaxel , Sinergismo Farmacológico , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/farmacologia , Compostos Organoplatínicos/uso terapêutico , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/secundário , Taxa de Sobrevida , Taxoides/administração & dosagem , Taxoides/farmacologia , Taxoides/uso terapêutico , Resultado do TratamentoRESUMO
The proliferation of neural stem cells (NSCs) is precisely regulated by extracellular environmental factors. In situ hypoxia, one of the key factors involved in the regulation of NSC characteristics, has attracted increasing amounts of attention. Numerous studies have demonstrated that hypoxia can significantly promote the formation of neurospheres and the proliferation of NSCs in vitro and that intermittent hypoxia can promote the proliferation of endogenous NSCs in vivo. In this article, the effects of different concentrations of oxygen on NSC proliferation and differentiation both in vivo and in vitro are reviewed, and the potential applications of hypoxia-preconditioned NSCs, as well as research progress and challenges in the treatment of central nervous system diseases, are further summarized. Here, the critical role of oxygen in the neurogenesis of NSCs is emphasized, and insights into the use of hypoxia to regulate NSC characteristics are provided.
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Hipóxia Celular , Proliferação de Células , Células-Tronco Neurais , Neurogênese , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/citologia , Humanos , Animais , Diferenciação Celular , Oxigênio/metabolismo , Oxigênio/farmacologiaRESUMO
This study focused on binary hydrogels constructed from lotus rhizome starch (LRS) and three types of carrageenan (κ-C, ι-C, and λ-C). The enthalpy of LRS gelatinization was reduced by 32.1%-88.4% with the incorporation of carrageenan. Compared with ι-C and λ-C, the conformations of κ-C more facilitated the development of the binary hydrogel network structure. The ability of the LRS/carrageenan binary hydrogel to immobilize water was mainly related to the effect of different types of carrageenan on starch molecular ordering. LRS-based hydrogels were recognized as level 4 in the International Dysphagia Diet Standardization Initiative (IDDSI) framework. Nevertheless, the incorporation of carrageenan significantly reduced the ability of the LRS hydrogel to resist stress under large deformations, which might be favorable to oral processing and swallowing. This research provides preliminary evidence for relevant industries to use carrageenan to adjust LRS hydrogel properties and improve the quality of starch-based foods for dysphagia management.
RESUMO
OBJECTIVE: To analyse the comparative clinical outcomes and clinicopathological significance of vocal fold leukoplakia lesions treated by appearance classification and traditional methods. METHOD: A total of 1442 vocal fold leukoplakia patients were enrolled. Group A patients were treated according to appearance classification and Group B patients were treated according to traditional methods. RESULTS: In Group A, 24.4, 14.9 and 60.6 per cent of patients had grade I, II and III dysplasia, respectively. Grade I dysplasia (63.4 per cent) was more than twice as frequent in Group B patients than in Group A patients, while grade II dysplasia (20.4 per cent) and grade III dysplasia (16.2 per cent) were significantly less frequent in Group B patients than in Group A patients (p = 0.000). There was a significant correlation between vocal fold leukoplakia appearance and the degree of dysplasia (p = 0.000). The recurrence and malignant transformation rates (17.6 and 31 per cent, respectively) in Group B were significantly greater than those in Group A (10.8 and 25.9 per cent, respectively) (p = 0.000). CONCLUSION: Vocal fold leukoplakia appearance classification is useful for guiding treatment decision-making and could help to improve therapeutic accuracy.
Assuntos
Doenças da Laringe , Prega Vocal , Humanos , Prega Vocal/patologia , Doenças da Laringe/patologia , Leucoplasia/cirurgia , Leucoplasia/patologiaRESUMO
Salidroside (Sal), the main bioactive substance in Rhodiola rosea, is a promising functional food component with a wide range of pharmacological effects, but its biological activity is challenging to sustain due to its short half-life, low oral bioavailability, and susceptibility to environmental factors. The aim of this study was to investigate the effect of sodium alginate (SA) concentration on the construction of W/O/W emulsion in the protection of Sal. With the escalation of SA concentrations, the range of droplet size distribution was smaller and the droplets were more uniform. When the concentration of SA was 2 %, the average droplet size reached 9.1 ± 0.1 µm, and the encapsulation efficiency of Sal was 77.8 ± 1.8 %. Moreover, the double emulsion with 2 % SA was the most stable for 28 days at 4 °C since the oil droplets were embedded in the network structure of SA.
RESUMO
Calcium ß-hydroxy-ß-methylbutyrate (CaHMB), a functional calcium salt, is used to maintain and improve muscle health. Here, a new hydrogel material prepared from alginate (ALG) with three M/G ratios (1:1, 2:1, and 1:2) and CaHMB (0-2 mg/mL) was investigated. CaHMB regulates the formation and properties of ALG hydrogels through chelation and hydrogen bonding. When the M/G ratio was 2:1, the anionic groups of CaHMB containing carboxyl and hydroxyl groups formed hydrogen bonds with the polysaccharide chains, hindering the capture of Ca2+ by the G-residue fragments of ALG, which in turn retarded the gelation process. The noncalcium cross-linked polysaccharide chain structure of ALG and the anionic group of CaHMB also affected the water distribution in the hydrogel, especially when M residue content ≥G residue content. Lower M/G ratios and higher CaHMB concentrations could increase the number of "egg box" crosslinking junctions of calcium alginate, and the microstructure was denser in the gel pores, resulting in a stronger gel strength and more free water bound in the gel matrix. This study provides a theoretical and methodological basis for the design of novel hydrogels by studying the crosslinking features of ALG/CaHMB.
Assuntos
Alginatos , Cálcio , Hidrogéis , Alginatos/química , Hidrogéis/química , Cálcio/química , Valeratos/química , Íons/química , Ligação de Hidrogênio , Água/químicaRESUMO
Dysphagia has emerged as a serious health issue facing contemporary society. Consuming thickened liquids is an effective approach for improving the swallowing safety for dysphagia patients. The thickening effect of chia seed gum (CSG), a novel thickener, in different dispersing media (water, orange juice, and skim milk) was investigated. Moreover, the potential application of CSG for dysphagia management was evaluated by comparison with xanthan gum (XG) and guar gum (GG). The thickened liquids prepared with 0.4 %-1.2 % (w/v) CSG, XG, and GG could be classified into levels 1-4, 2-4, and 1-3, respectively, according to the International Dysphagia Diet Standardization Initiative (IDDSI) framework. All the thickened liquids displayed shear-thinning characteristics that facilitated safe swallowing. The viscosities (η50) of CSG dissolved in water (0.202-1.027 Pa·s) were significantly greater than those of CSG dissolved in orange juice (0.070-0.690 Pa·s) and skim milk (0.081-0.739 Pa·s), indicating that CSG had a greater thickening effect in water than in orange juice and skim milk. Compared with those prepared with GG, the thickened liquids prepared with CSG and XG exhibited greater viscoelasticity, better water-holding capacity, and more compact networks. The findings suggested that CSG can be used as a potential thickener for thickening liquid foods to manage dysphagia.
Assuntos
Transtornos de Deglutição , Gomas Vegetais , Reologia , Sementes , Transtornos de Deglutição/tratamento farmacológico , Gomas Vegetais/química , Sementes/química , Viscosidade , Galactanos/química , Salvia/química , Polissacarídeos Bacterianos/química , Polissacarídeos Bacterianos/farmacologia , Humanos , Mananas/química , Mananas/uso terapêutico , Mananas/farmacologia , Leite/químicaRESUMO
To develop composite hydrogels based on low acyl gellan gum (GG), the effect of puerarin (PUE) on the gel properties of GG was investigated. The results showed that the maximum storage modulus (G') of the 1.2 % GG/0.8 % PUE composite hydrogel was 377.4 Pa at 0.1 Hz, which was enhanced by 4.7-fold compared with that of 1.2 % GG. The melting temperature of this composite hydrogel increased from 74.1 °C to >80.0 °C. LF-NMR results showed that a significant amount of free water was present in the hydrogel matrix. The surface structure aggregation and the shrinkage of the honeycomb meshes in the composite hydrogel proved the cross-linking of PUE and GG. XRD, FTIR and molecular simulation results illustrated that hydrogen bonds were the most important factor controlling the interaction between GG and PUE. Thus, the GG/PUE composite hydrogel has good elasticity, thermal stability and water retention, which lays a good foundation for further application in the food industry.
Assuntos
Hidrogéis , Polissacarídeos Bacterianos , Hidrogéis/química , Polissacarídeos Bacterianos/química , Água/químicaRESUMO
Kaempferol (KPR), a flavonoid compound found in various plants and foods, has garnered attention for its anti-inflammatory, antioxidant, and anticancer properties. In preliminary studies, KPR can modulate several signaling pathways involved in inflammation, making it a candidate for treating cholecystitis. This study aimed to explore the effects and mechanisms of KPR on lipopolysaccharide (LPS)-induced human gallbladder epithelial cells (HGBECs). To assess the impact of KPR on HGBECs, the HGBECs were divided into control, KPR, LPS, LPS + KPR, and LPS + UDCA groups. Cell viability and cytotoxicity were evaluated by MTT assay and lactate dehydrogenase (LDH) assay, respectively, and concentrations of KPR (10-200 µM) were tested. LPS-induced inflammatory responses in HGBECs were to create an in vitro model of cholecystitis. The key inflammatory markers (IL-1ß, IL-6, and TNF-α) levels were quantified using ELISA, The modulation of the MAPK/NF-κB signaling pathway was measured by western blot using specific antibodies against pathway components (p-IκBα, IκBα, p-p65, p65, p-JNK, JNK, p-ERK, ERK, p-p38, and p38). The cell viability and LDH levels in HGBECs were not significantly affected by 50 µM KPR, thus it was selected as the optimal KPR intervention concentration. KPR increased the viability of LPS-induced HGBECs. Additionally, KPR inhibited the inflammatory factors level (IL-1ß, IL-6, and TNF-α) and protein expression (iNOS and COX-2) in LPS-induced HGBECs. Furthermore, KPR reversed LPS-induced elevation of p-IκBα/IκBα, p-p65/p65, p-JNK/JNK, p-ERK/ERK, and p-p38/p38 ratios. KPR attenuates the LPS-induced inflammatory response in HGBECs, possibly by inhibiting MAPK/NF-κB signaling.