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PURPOSE: To investigate the implications of Lobectomy (LT) or total thyroidectomy (TT) on psychological distress and sleep quality in PTC patients with a low to intermediate risk of recurrence and tumors measuring 1 to 4 cm. METHODS: Patients who were admitted to our hospital between July 2021 and July 2022 were prospectively enrolled in this survey. Psychological distress and sleep quality were assessed at hospitalization, discharge, and 1, 3, and 6 months post-treatment using validated scales. Participants were divided into LT and TT groups, with propensity score matching (PSM) applied for analyses. RESULTS: Among 525 eligible PTC patients, 440 patients completed all the questionnaires throughout the follow-up. After PSM, 166 patients underwent LT, and 166 patients underwent TT were enrolled. The psychological distress and sleep quality of patients in the LT group remained relatively stable during the 6-month follow-up, but patients in the TT group may have faced greater sleep quality concerns in the longitudinal assessment. Additionally, the sleep quality of the TT group was also worse than that of the LT group postoperatively. CONCLUSIONS: The sleep quality rather than other psychological distress of patients with PTC with a low to intermediate risk of recurrence is associated with the extent of surgery.
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Osteoarthritis (OA), a joint disease that is associated with inflammatory processes is involved in joint destruction. Scutellarein (Scu), a component of the medicinal herbs Scutellaria barbata D. Don and Erigeron breviscapus (vant) Hand Mass, has anti-inflammatory effects. We explored the role of Scu in the development of OA and the underlying mechanisms. CCK-8 assays, Calcein-AM/PI and EdU staining were used to determine chondrocyte viability after Scu exposure. Western blot, qPCR, as well as ELISA were utilized to measure extracellular matrix (ECM) degradation and inflammation. Immunofluorescence (IF), western blot and luciferase assays were used to examine the NF-kappaB (NF-κB) pathway. Scu interacting proteins were predicted using network pharmacology analysis and molecular docking. X-ray, H&E, Safranin O-Fast Green(S-O), toluidine blue, and immunohistochemistry analysis were used to examine the therapeutic effects of Scu in OA using destabilization of medial meniscus (DMM) models. Scu demonstrated inhibitory effects on ECM degradation and pro-inflammatory factor levels in chondrocytes treated with IL-1ß. Mechanistically, Scu inhibited the IL-1ß-induced activation of the PI3K/Akt/ NF-κB signaling pathway cascades. Furthermore, Scu has been shown to have significant binding capacities to PI3K. Additionally, Scu ameliorated the OA progression in DMM models. Our findings suggest that Scu may contribute to the amelioration of OA progression by targeting the PI3K/Akt/NF-κB signaling pathway, implying Scu possesses promising therapeutic potential for the treatment of OA.
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Apigenina , Condrócitos , NF-kappa B , Osteoartrite , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Osteoartrite/tratamento farmacológico , NF-kappa B/metabolismo , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Apigenina/farmacologia , Masculino , Simulação de Acoplamento Molecular , Ratos Sprague-Dawley , Anti-Inflamatórios/farmacologia , Ratos , Humanos , Matriz Extracelular/metabolismo , Matriz Extracelular/efeitos dos fármacosRESUMO
Immunoglobulin nephropathy (IgAN) stands as the most prevalent primary glomerular nephropathy globally, typically diagnosed through an invasive renal biopsy. Emerging research suggests the significant involvement of chiral amino acids in kidney disease progression. This study introduces a nonderivative LC-tandem mass spectrometry approach, offering efficient separation outcomes within 15 min for identifying chiral amino acids in human urine samples. Subsequently, using this method, the analysis of l- and d-amino acids in the urine of both patients with IgAN and healthy individuals was conducted. Fourteen d-amino acids and 20 l-amino acids were identified in the urine samples obtained from 17 patients with IgAN and 21 healthy individuals. The results indicated notable variances in the concentrations of both l- and d-amino acids between the IgAN and healthy control groups. In contrast to the healthy group, the IgAN group exhibited higher mean urine concentrations of most l-amino acids and lower concentrations of d-amino acids. Furthermore, correlations between amino acids and clinical markers were investigated. These results propose a novel method for monitoring trace amino acids in urine samples and introduce a new concept for potential markers of IgAN.
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Aminoácidos , Glomerulonefrite por IGA , Espectrometria de Massas em Tandem , Humanos , Espectrometria de Massas em Tandem/métodos , Aminoácidos/urina , Glomerulonefrite por IGA/urina , Cromatografia Líquida/métodos , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Biomarcadores/urina , Estereoisomerismo , Modelos Lineares , Estudos de Casos e Controles , Adulto JovemRESUMO
BACKGROUND: The clinical outcomes and implications of radioactive iodine therapy (RAIT) on cancer-specific survival (CSS) in World Health Organization classification of follicular thyroid carcinoma (FTC) are not well established. MATERIAL AND METHODS: The data of eligible patients with minimally invasive FTC (mi-FTC), encapsulated angioinvasive FTC (ea-FTC), or widely invasive FTC (wi-FTC) between 2000 and 2020 were extracted from the Surveillance, Epidemiology, and End Results database. CSS, the primary outcome, was compared among the 3 subtypes of patients with FTC before and after adjusting for differences using propensity score matching (PSM). The patients with FTC in different subtypes were then divided into 2 groups: the RAIT group and the no-RAIT group. Cox proportional hazards regression analyses were applied to discover the relationships of factors associated with CSS in the each PSM cohort. RESULTS: A total of 2433 patients with mi-FTC, 216 patients with ea-FTC, and 554 patients with wi-FTC were enrolled in the original cohorts, respectively. Patients with mi-FTC or ea-FTC had similar CSS (P = .805), which was better than that of patients with wi-FTC (P < .001; P = .021). Cox proportional hazards regression analysis revealed that RAIT was not associated with improved CSS in either the mi-FTC PSM cohort (hazard ratio [HR], 1.21; 95% CI, .46-3.18; P = .705) or the wi-FTC PSM cohort (HR, 0.56; 95% CI, .35-1.08; P = .086). However, subgroup analysis demonstrated that patients with wi-FTC and N1 stage (HR, 0.44; 95% CI, .20-.99; P = .018) or M1 stage (HR, 0.25; 95% CI, .11-.53; P < .001) could gain CSS advantage from RAIT. CONCLUSION: The RAIT can provide a CSS advantage for patients with wi-FTC who with N1-stage or M1-stage disease.
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Adenocarcinoma Folicular , Radioisótopos do Iodo , Neoplasias da Glândula Tireoide , Humanos , Radioisótopos do Iodo/uso terapêutico , Feminino , Masculino , Pessoa de Meia-Idade , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia , Adenocarcinoma Folicular/radioterapia , Adenocarcinoma Folicular/mortalidade , Adenocarcinoma Folicular/patologia , Adulto , Organização Mundial da Saúde , Programa de SEER , Idoso , Resultado do Tratamento , Prognóstico , Taxa de Sobrevida , Estudos RetrospectivosRESUMO
Extracellular vesicles (EVs) are small lipid bilayer-enclosed vesicles that mediate vital cellular communication by transferring cargo between cells. Among these, tissue-derived extracellular vesicles (Ti-EVs) stand out due to their origin from the tissue microenvironment, providing a more accurate reflection of changes in this setting. This unique advantage makes Ti-EVs valuable in investigating the intricate relationship between extracellular vesicles and cancer progression. Despite considerable research efforts exploring the association between Ti-EVs and cancers, a comprehensive clustering or grouping of these studies remains lacking. In this review, we aim to fill this gap by presenting a comprehensive synthesis of the mechanisms underlying Ti-EV generation, release, and transport within cancer tissues. Moreover, we delve into the pivotal roles that Ti-EVs play in cancer progression, shedding light on their potential as diagnostic and therapeutic tools. The review culminates in the construction of a comprehensive functional spectrum of Ti-EVs, providing a valuable reference for future research endeavors. By summarizing the current state of knowledge on Ti-EVs and their significance in tumor biology, this work contributes to a deeper understanding of cancer microenvironment dynamics and opens up avenues for harnessing Ti-EVs in diagnostic and therapeutic applications.
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In the ever evolving field of functional genomics, CRISPR-based screening technologies have become pivotal tools for elucidating gene function across various cell types. A recent study by Gilan and colleagues advances this technological frontier by introducing CRISPR-ChIP, a platform designed to investigate the complex dynamics of epigenetic regulation of chromatin. In proof-of-concept experiments, the authors demonstrate the potential of this tool to identify key molecular regulators of two major histone modifications associated with active transcription, H3 lysine 4 trimethylation (H3K4me3) and H3 lysine 79 dimethylation (H3K79me2). They further unveiled a previously unknown functional partitioning of the H3K79-specific methyltransferase DOT1L into an oncogenic complex with MLL-AF9 and a native complex with MLLT10, which cooperatively regulate mixed lineage leukemia fusion protein (MLL-FP) target gene expression. This novel epigenomic approach integrates high-throughput CRISPR screening with chromatin immunoprecipitation-based direct readout of chromatin modifications in situ, offering a powerful tool to investigate the epigenetic regulatory layers across a diverse spectrum of biological processes and disease states.
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Cromatina , Epigênese Genética , Humanos , Cromatina/genética , Epigenômica , Lisina/metabolismo , Fatores de Transcrição/metabolismo , Proteína de Leucina Linfoide-Mieloide/genética , Proteína de Leucina Linfoide-Mieloide/metabolismoRESUMO
PURPOSE: To screen for the differentially expressed genes in experimental retinal detachment rats, and to explore the expression of S100 calcium-binding protein A9 and Toll-like receptor 4 in the vitreous of rhegmatogenous retinal detachment patients. METHODS: Three rats of experimental retinal detachment and three normal rats were enrolled in the study. Transcriptomics (RNAseq) sequencing technology was used to screen differentially expressed genes in the retinas of the experimental retinal detachment group and the normal group. The selected differentially expressed genes for gene ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis were performed. In addition, the vitreous of 15 patients with rhegmatogenous retinal detachment and six patients with the control group were collected. The expressions of S100 calcium-binding protein A9 and Toll-like receptor 4 were detected by Elisa, and the differences in expression levels were analyzed statistically. RESULTS: A total of 198 differentially expressed genes were screened by RNAseq sequencing, including 118 upregulated genes and 80 downregulated genes. Kyoto Encyclopedia of Genes and Genomes analysis confirmed that the most enriched pathway was the mitogen-activated protein kinase signaling pathway. Compared to the normal group, the expressions of suppressor of cytokine signaling-3, Storkhead box-2, S100 calcium-binding protein A9, Spi-1 proto-oncogene, phosphodiesterase 1B, and kinesin-light chain 1 mRNA in the retinas of the experimental retinal detachment rats were up-regulated, and the expressions of Max interacting protein 1 and the voltage-gated sodium 1 were down-regulated. Compared to the control group, the expressions of S100 calcium-binding protein A9 and Toll-like receptor 4 were upregulated by Elisa in the vitreous humor of rhegmatogenous retinal detachment patients with a statistically significant difference (p all <.05). CONCLUSION: The differentially expressed genes of experimental retinal detachment rats were suppressor of cytokine signaling-3, Storkhead box-2, S100 calcium-binding protein A9, Spi-1 proto-oncogene, phosphodiesterase 1B, kinesin-light chain 1, Max interacting protein 1, voltage-gated sodium 1, etc. The differences of S100 calcium-binding protein A9 and Toll-like receptor 4 expressions between the rhegmatogenous retinal detachment patients and the control group were statistically significant, indicating that they may play a potential role in the inflammatory process of rhegmatogenous retinal detachment.
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Calgranulina B , Descolamento Retiniano , Receptor 4 Toll-Like , Animais , Humanos , Ratos , Proteínas de Ligação ao Cálcio , Citocinas/metabolismo , Perfilação da Expressão Gênica , Cinesinas/genética , Diester Fosfórico Hidrolases/metabolismo , Descolamento Retiniano/genética , Descolamento Retiniano/metabolismo , Sódio/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Calgranulina B/genética , Calgranulina B/metabolismoRESUMO
BACKGROUND CONTEXT: Standard partial facetectomies, (Smith-Petersen Osteotomy, (SPO), (Schwab-grade-I) and complete facet resection also known as Ponte osteotomy, (PO), (Schwab-grade-II) are narrowly akin and collectively appreciated as posterior column shortening osteotomies (PCOs). The former is considered a gentler osteotomy grade than the latter. The spine literature provides very little information on their comparison regarding perioperative complications and major curve correction rate outcomes. PURPOSE: To determine whether Schwab-grade-I PCO (SPO) and Schwab-grade-II PCO (PO) are comparably safe in the surgical management of severe rigid scoliosis or kyphoscoliosis patients. STUDY DESIGN/SETTING: Retrospective single-center comparative clinical study. PATIENT SAMPLE: A total of 38 patients with severe rigid scoliosis or kyphoscoliosis were propensity score matched in this study, (SPO-treated); n=21 (55.30%) and (PO-treated); n=17 (44.70%), who underwent primary spinal deformity corrective surgery, respectively. OUTCOME MEASURES: Outcomes included demographics, baseline pulmonary functional outcomes, perioperative complications incidence, hospital costs, Oswestry disability index (ODI), and the Scoliosis Research Society-22 (SRS-22) questionnaire scores. METHODS: Following approval by the Institutional Review Board (IRB) of Beijing Chaoyang Hospital-Affiliated Capital Medical University in Beijing, out of a total of 82 consecutive surgical patients with complete data demonstrating severe and/or rigid spinal deformity, a pool of 38 of the 82 (46.3%) propensity-matched adult (≥18 years) patients with severe rigid scoliosis or kyphoscoliosis defined with a preoperative major curve magnitude of ≥80° on anteroposterior plain radiographs, and flexibility of <25% on bending plain radiographs who underwent primary spinal deformity corrective surgery were retrospectively evaluated. The patients were dichotomized into two osteotomy groups: standard (partial) facetectomy (SPO-treated), n=21 with an average age of 24.67 years, (Schwab-grade-I PCO) and complete facet excision, (PO-treated), (ie, Schwab-grade-II PCO), n=17 with an average age of 23.12 years. The minimum follow-up period was 2 years. Primary outcomes included baseline demographics and clinical features. Secondary outcomes included perioperative [intraoperative, immediate, and 2-year postoperative] complication rates. Tertiary outcomes included perioperative ODI and SRS-22 scores. Statistical analyses were carried out by Student t-test and Pearson's Chi-square test (Fisher's Exact Test), through Python statistical software package. Statistical significance was set at (p<.05). RESULTS: Of the 38 matched severe rigid scoliosis or kyphoscoliosis patients, 55.30% (n=21) were SPO-treated and 44.70% (n=17) were PO-treated patients, respectively. The overall average age of patients was 23.97 years, with a female incidence of 76.32%. Major curve correction rates were 49.19% and 57.40% in SPO-treated and PO-treated patients, respectively, (p>.05). Immediately following surgery, comparable overall complication rates of 28.57% (n=6/21) versus 29.41% (n=5/17) were observed in the SPO-treated and PO-treated patients, respectively, (p=.726). We observed incidences of 9.52%, (n=2/21) versus 5.88%, (n=1/17) for surgical intensive care unit (SICU) admission, and incidences of 4.76%, (n=1/21) versus 5.88%, (n=1/17) for cardiopulmonary events in SPO-treated versus PO-treated patients following corrective surgery, respectively, (p>.05). The incidences of neurological deficits in the SPO-treated and PO-treated patients were respectively, 14.29%, (n=3/21) versus 17.65%, (n=3/17) immediately following surgery, (p>.05), and 0.00%, (n=0/21) in SPO-treated versus 14.28%, (n=3/21) in PO-treated patients at ≥2 years postoperative, (p<.05). Among the three patients that reported neurological deficits in the PO-treated group at ≥2 years postoperative, two patients had pre-existing baseline neurological deficits. The ODI score in the PO-treated group was significantly inferior at a minimum 2-year follow-up, (p<.05). CONCLUSIONS: In the current study, both SPO-treated and PO-treated patients demonstrated statistically comparable surgical complications immediately following corrective surgery. Severe rigid kyphoscoliosis patients with preexisting baseline neurological deficits were more inclined to sustain neurological morbidity following corrective surgery. PCO corrective techniques are warranted as safe options for treating patients with severe rigid spine deformity phenotypes.
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Cifose , Escoliose , Adulto , Humanos , Feminino , Adulto Jovem , Escoliose/cirurgia , Escoliose/complicações , Estudos Retrospectivos , Seguimentos , Resultado do Tratamento , Cifose/diagnóstico por imagem , Cifose/cirurgia , Cifose/complicações , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologiaRESUMO
INTRODUCTION: A unique surgical approach - the minimally invasive direct interbody fusion (MIS-DTIF) - was previously introduced in our proof-of-concept study, which included four patients who underwent thoracic interbody fusion below the scapula at the T6/7 vertebral level. However, due to the novelty of this method, a report of associated operative parameters such as pain, function, and clinical outcomes from an expanded patient cohort was needed to assess the validity of our results. MATERIALS AND METHODS: Following IRB approval, data were analyzed retrospectively from electronic health records between 2014 and 2021. Inclusion criteria were patients ≥18 years old who underwent minimally invasive thoracic interbody fusion using the MIS-DTIF technique for at least one vertebral level. The primary outcomes included demographic/radiographic features (e.g., age). Secondary outcomes included perioperative clinical features (e.g., preoperative and ≥1-year final follow-up (FFU)). Tertiary outcomes included perioperative complications. Both preoperative and FFU patient-reported pain and functional outcomes (ODI scores) were analyzed using t-tests to establish significance. Results: A total of 13 patients who underwent MIS-DTIF surgery were observed, with eight male patients and five female patients. The average age was 49.2 years, with an average BMI of 30.5 kg/m2. Of the surgeries included, the majority (69.23%) were 1-level thoracic vertebrae fusions - with 2-level fusions and ≥ 3-level fusions accounting for 15.38% and 15.38% of cases, respectively. The mean operative time was 58.9 ± 19.9 minutes, with an average fluoroscopy time of 285.7 ± 126.8 seconds and an average actual blood loss volume of 109.0 ± 79.0 mL. The average hospital length of stay was 1.1 (±1.7) days, and no clinically significant perioperative complications were observed in this patient cohort. The average follow-up period was 12.1 ± 9.6 months, with preoperative and FFU back pain visual analog scale (VAS) scores showing highly significant improvement (p<0.001). In addition to pain reduction, quality of life improvements was noted, with significant differences in some of the ODI domains between preoperative and FFU scores (p<0.05), as well as the overall total score between preoperative and FFU ODI assessment (p<0.001) - both of which reflect increased patient function and decreased disability. CONCLUSION: This study provides further evidence for the safety and efficacy of the MIS-DTIF approach for surgical management of symptomatically refractory patients with thoracic disc herniation or stenosis owing to degenerative disc disease or compression fractures. Additionally, the data gathered suggests that this minimally invasive procedure offers many clinical benefits, including less tissue damage, decreased intraoperative blood loss, shortened surgery time, and shortened hospital length of stay. Finally, in addition to significant pain intensity improvement, this study showed that treated patients highly benefited from 'sleeping' and 'return-to-work' domains and other ODI functional domains in activities of daily living (ADLs). More clinical studies are recommended in larger patient cohorts to ascertain the findings reported in this study.
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STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: Compilation of complication outcomes data from the surgical management of severe rigid kyphoscoliosis patients using VCR-based vs non-VCR-based corrective maneuvers is lacking. This meta-analysis aimed to compare complication outcomes between those classified osteotomy approaches. METHODS: Thorough literature review and meta-analysis were conducted between January 2000 and September 2021. The selection criteria were studies: i) reporting major curve Cobb angle of ≥80° and flexibility of <25% or 30%; ii) comparing VCR or ≥ Type V Schwab osteotomy defined as VCR-based vs [non-VCR-based] techniques, (any osteotomy or technique other than VCR); iii) published in English with ≥10 patients; iv) reporting complication rates; and v) having minimum of 2-year follow-up. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Significance level was set at (P < .05). RESULTS: Of the 174 patients included, 52.30% (n = 91) and 47.70% (n = 83) were VCR-based and non-VCR-based, respectively. The incidence of dural tears/nerve injuries/significant intraoperative-neuromonitoring changes was significantly higher; [OR = 6.78, CI= (1.75 to 26.17), I2 = 0%, (P = .006)] in the VCR-based group than the non-VCR-based group. The 'overall surgical and medical' complication rate was significantly higher in the VCR-based group, [OR = 1.94, CI= (1.02 to 3.67), I2 = 31%, (P = .04)]. CONCLUSION: Both VCR-based and non-VCR-based surgical techniques for management of severe rigid scoliosis and kyphoscoliosis patients pose comparable overall surgical complication rates, while a significantly higher perioperative neurological complication incidence was associated with VCR-based technique compared to the non-VCR-based techniques. The VCR-based technique was associated with 6.78 times higher incidence of neurological complications compared to non-VCR-based techniques.
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It is still uncertain whether the consumption of Lachnum sp. polysaccharides (LEP) alleviates colorectal cancer (CRC) through the gut microbiota. In this study, our efforts are focused on the influence of LEP on CRC, intestinal barrier and inflammation, and fecal microbiota and the metabolites, in azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced CRC mice. Results showed that LEP inhibited CRC mouse colon shortening and weight loss, decreased tumor incidence, restored intestinal barrier integrity, and reduced excessive inflammation. LEP consumption significantly altered microbiota overall structure and community, with reduced pernicious bacteria (such as Parabacteroides, Escherichia_Shigella, Desulfovibrio and Helicobacter), and increased beneficial bacterium (such as Alistipes, Alloprevotella and Ruminiclostridium). Fecal-metabolome profile indicated that a total of 43 metabolites were clearly changed, with 10 down-regulated and 33 up-regulated metabolites. In addition, short-chain fatty acids (SCFAs), including acetic acid, propionic acid and n-butyric acid, were significantly increased after LEP administration. Moreover, a strong correlation between the fluctuant gut microbiota and metabolites was found. These findings provided not only deeper insights into the responsibility of LEP for CRC alleviation, and but also the potential of LEP as a promising candidate for CRC prevention and treatment.
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Colite , Microbioma Gastrointestinal , Animais , Bactérias , Carcinogênese , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colo , Sulfato de Dextrana/farmacologia , Modelos Animais de Doenças , Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêuticoRESUMO
Therapeutic strategies that targeting tumor-associated macrophages (TAMs) reprogramming play a crucial role in ameliorating the immunosuppressive tumor microenvironment and boosting anti-tumor immune responses. In this study, we demonstrated that Lachnum polysaccharide (LEP) could work as an immunomodulator to reset TAMs from pro-tumor M2 to anti-tumor M1 phenotype. Mechanistically, LEP promoted Th1 polarization and the secretion of IFN-γ, which played a key role in M1 phenotype polarization. In parallel, LEP might directly activate M1 macrophages via TLR4 mediated NF-κB signaling pathway. Moreover, LEP also resulted in the accumulation of anti-tumor immune cells and decreased the infiltration of immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs) and Treg cells, thereby potentiating anti-tumor immunity. In summary, these results revealed a novel mechanism of the anti-tumor effect of LEP and provided a potential new avenue targeting TAMs and cancer immunotherapy.
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Ascomicetos/química , Polissacarídeos Fúngicos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Fenótipo , Sarcoma/imunologia , Animais , Linhagem Celular Tumoral , Humanos , Macrófagos/citologia , Masculino , Camundongos , Células RAW 264.7 , Sarcoma/patologia , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Receptor 4 Toll-Like/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologiaRESUMO
The antimetabolite 5-fluorouracil (5-FU) is a widely used antitumor agent, however the overall response rate to 5-FU as a single agent is usually limited. Herein, how Lachnum expolysaccharide (LEP-2a), a type of active polysaccharide isolated from Lachnum sp., acted synergistically with 5-FU on HepG2 cells was investigated. It was found that LEP-2a notably enhanced 5-FU sensitivity in HepG2 cells in a synergistic manner. After combination treatment of 5-FU and LEP-2a, Ras/Raf/MEK/ERK and PI3K/AKT/mTOR pathway were inactivated. In addition, combination treatment induced generation of reactive oxygen species, decreased the levels of intracellular antioxidant enzymes and triggered mitochondrial apoptosis pathway. Furthermore, 5-FU combined with LEP-2a also resulted in p53 activation and NF-κB inhibition, and cell cycle arrest in the S phase as well as cell metastasis stagnation. Interestingly, LEP-2a treatment also blocked the DNA damage repair procedure. These findings demonstrate that LEP-2a enhanced 5-FU sensitivity and combination of 5-FU and LEP-2a exerts synergistic antitumor efficiency through multiple approaches.
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The physicochemical properties and the immunoregulatory actions in vitro of an exopolysaccharide from Lachnum (LEP) and its conjugation with a dipeptide (LEP-RH) were investigated aiming to improve their functional characteristics. The structure characteristic of the LEP and LEP-RH were determined via FT-IR and NMR. The physicochemical properties were evaluated by scanning electron microscopy (SEM), rheometer, and differential scanning calorimeter (DSC). SEM results showed that LEP-RH had a rough surface and relatively loose distribution that different from LEP. Rheological studies of LEP and LEP-RH at the same concentration indicated that LEP and LEP-RH have similar shear-thinning behaviors and gel-like structures, while LEP-RH has a better thermal stability than LEP. Bioassay results showed that treatment with the higher dosage (200 µg/mL) of LEP and LEP-RH stimulated the proliferation, cytokine secretion (IL-2, IL-6 and TNF-α) of RAW264.7 macrophages.
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Adjuvantes Imunológicos/farmacologia , Ascomicetos/química , Dipeptídeos/farmacologia , Polissacarídeos/farmacologia , Adjuvantes Imunológicos/química , Animais , Proliferação de Células/efeitos dos fármacos , Dipeptídeos/química , Elasticidade , Interleucina-2/metabolismo , Interleucina-6/metabolismo , Macrófagos/efeitos dos fármacos , Camundongos , Polissacarídeos/química , Células RAW 264.7 , Fator de Necrose Tumoral alfa/metabolismo , Substâncias Viscoelásticas/química , Substâncias Viscoelásticas/farmacologia , ViscosidadeRESUMO
This study was designed to investigate the liver and kidney protective efficacy of a Lachnum polysaccharide (LEP) against Pb-induced toxicity in mice. The results showed that LEP decreased the Pb-induced bodyweight loss and organ index. Moreover, biochemical analysis showed that treatment of LEP could improve antioxidant status (CAT, GSH-Px and MDA) and the injury of tissues (liver and kidney). In addition, the histopathological observations indicated that LEP could attenuate liver and kidney cell injury induced by Pb. For further studies, key proteins involved in hepatic and kidney apoptosis, including cleaved caspase-3, Bax, Bcl-2, TGF-ß1 and α-SMA, were quantified. The present findings demonstrated that LEP is strongly effective in protecting against the liver and kidney injury induced by Pb. We hope this research can offer a theoretical base for development of polysaccharide based on nutraceutical food in future.
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Ascomicetos/química , Rim/efeitos dos fármacos , Rim/patologia , Intoxicação por Chumbo/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Polissacarídeos/farmacologia , Substâncias Protetoras/farmacologia , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Biomarcadores , Biópsia , Modelos Animais de Doenças , Rim/metabolismo , Testes de Função Renal , Intoxicação por Chumbo/tratamento farmacológico , Intoxicação por Chumbo/metabolismo , Intoxicação por Chumbo/prevenção & controle , Fígado/metabolismo , Testes de Função Hepática , Masculino , Camundongos , Estresse Oxidativo , Polissacarídeos/química , Substâncias Protetoras/químicaRESUMO
In the present study, we investigated the anti-tumor activities of the intracellular homogeneous melanin (LM) of Lachnum YM226 and its derivative (ALM) on liver cancer using murine H22 hepatocarcinoma model. The results showed that LM and ALM (50 and 200 mg kg-1) could effectively inhibit tumor growth of H22 tumour-bearing mice. The body weight, liver, spleen and thymus indices also improved in the LM and ALM treated groups. Moreover, the levels of alanine aminotransferase (ALT), aspartate aminotransaminase (AST), alkaline phosphatase (ALP), creatinine (CRE), blood urea nitrogen (BUN) and uric acid (UA) were lowered. Serum cytokines of interleukin-2 (IL-2), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were increased on LM and ALM administration, while LM and ALM significantly decreased the vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) levels. The H&E staining indicated that LM and ALM exhibited antitumor activity in vivo by promoting apoptosis and inhibiting angiogenesis. The anti-tumor effect of ALM was more significant than that of LM for the same dose. In summary, the findings demonstrated that LM and ALM might be promising candidates for the prevention and treatment of HCC.
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Combination therapy with chemotherapeutics is attracting increasing attention as an important treatment option for hepatocellular carcinoma (HCC) due to its complex pathological characteristics. In this study, as a new therapy strategy, combination treatment of LEP-2a (a non-toxic polysaccharide from Lachnum sp.) with cyclophosphamide (CTX) was investigated. Results showed that combination treatment with LEP-2a and CTX processed a significantly synergistic anti-tumor effect in H22 tumor-bearing mice through Fas/FasL mediated caspase-dependent death pathway and mitochondria apoptosis pathway. Moreover, our study indicated that LEP-2a played a crucial role in enhancement of immune response, inhibition of tumor angiogenesis and down-regulation of survival associated proteins. Notably, side effects induced by CTX were relieved after LEP-2a treatment. These results support the conception that LEP-2a has the potential as an ideal adjuvant agent for a more effective combination therapy with CTX against HCC.