Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 55
Filter
1.
Bioresour Technol ; 406: 131015, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38906196

ABSTRACT

Combining iron-carbon micro-electrolysis and autotrophic denitrification is promising for nitrate removal from wastewater. In this study, four continuous reactors were constructed using CO2 and weak magnetic field (WMF) to address challenges like iron passivation and pH stability. In the reactors with CO2 + WMF (10 and 35 mT), the increase in total nitrogen removal efficiency was significantly higher (96.2 ± 1.6 % and 94.1 ± 2.7 %, respectively) than that of the control (51.6 ± 2.7 %), and Fe3O4 converted to low-density FeO(OH) and FeCO3, preventing passivation film formation. The WMF application decreased the N2O emissions flux by 8.7 % and 20.5 %, respectively. With CO2 + WMF, the relative enzyme activity and abundance of denitrifying bacteria, especially unclassified_Rhodocyclaceae and Denitratisoma, increased. Thus, this study demonstrates that CO2 and WMF optimize the nitrate removal process, significantly enhancing removal efficiency, reducing greenhouse gas emissions, and improving process stability.

2.
Front Immunol ; 15: 1371527, 2024.
Article in English | MEDLINE | ID: mdl-38915406

ABSTRACT

With advancements in medical oncology, immune checkpoint inhibitors (ICIs) have become the first-line treatment for many malignancies. ICIs play a significant role in improving cancer prognosis, but a series of immune-related adverse events (irAEs), including immune-related endocrine events (irEEs), caused by ICIs have also aroused concerns. Rapid clinical identification of irAEs caused by ICIs is particularly important. We describe a case of secondary adrenocortical insufficiency (AI) after PD-1 treatment in a postoperative patient with endometrial cancer. A 73-year-old female patient developed anorexia, nausea, vomiting, malaise, electrolyte disturbances, ineffective symptomatic treatment, and decreased serum adrenocorticotropin and cortisol levels six months after retifanlimab treatment. The vomiting resolved, and the electrolyte levels were corrected after 3 days of treatment with glucocorticoids (hydrocortisone, intravenous, 200 mg/day). When patients present with gastrointestinal symptoms, such as poor appetite and nausea, not only symptomatic treatment but also a search for the etiology behind the symptoms is needed, especially in immunotherapy patients who should undergo a thorough evaluation of the endocrine system and be alert for adrenocortical insufficiency.


Subject(s)
Adrenal Insufficiency , Humans , Female , Aged , Adrenal Insufficiency/chemically induced , Adrenal Insufficiency/etiology , Adrenal Insufficiency/diagnosis , Immune Checkpoint Inhibitors/adverse effects , Immune Checkpoint Inhibitors/therapeutic use , Addison Disease/drug therapy , Addison Disease/diagnosis , Addison Disease/chemically induced , Addison Disease/etiology , Hydrocortisone/therapeutic use
3.
Nat Sci Sleep ; 16: 125-141, 2024.
Article in English | MEDLINE | ID: mdl-38348055

ABSTRACT

Objective: To evaluate the clinical performance of the OPPO Watch (OW) Sleep Analyzer (OWSA) on OSA screening with polysomnography reference. Methods: We recruited 350 participants using OWSA and PSG simultaneously in a sleep laboratory. The respiratory event index (REI) derived from OWSA and the apnea-hypopnea index (AHI) provided by PSG were compared. SHapley Additive exPlanation (SHAP) values were calculated to explain the model of OWSA. Results: The OWSA-REI (26.5±18.5 events/h) correlated well with PSG-AHI (33.2±25.7 events/h; r = 0.91, p < 0.001), with an intraclass correlation coefficient (ICC) of 0.83. Using a threshold of AHI ≥15 events/h, the sensitivity, specificity, accuracy, and area under the curve (AUC) were 86.1%, 86.7%, 86.3%, and 0.94, respectively. Bland-Altman analysis showed that OWSA-REI and PSG-AHI were in good agreement (Mean Difference: -6.7, 95% CI:16.0 to -29.3 events/h). In addition, the effectiveness of the models in OWSA were also explained by visualizing SHAP values. Conclusion: The OWSA demonstrated a reasonable performance for OSA screening in the clinical setting. In light of this, it is possible for smartwatches to become a complementary tool to PSG, which is particularly useful for larger-scale preliminary screenings.

4.
Hum Vaccin Immunother ; 20(1): 2297455, 2024 Dec 31.
Article in English | MEDLINE | ID: mdl-38174857

ABSTRACT

With the widespread vaccination of COVID-19 vaccine, a few cases have been reported that COVID-19 vaccine may cause endocrine disorders. A 59-y-old man presented with a loss of appetite after the first COVID-19 vaccination, which resolved spontaneously after 3 d. After the second COVID-19 vaccination, the symptoms including the loss of appetite, nausea, and vomiting reappeared and worsened along with loss of vision. He was found to have severe hyponatremia, and further investigations revealed secondary adrenal insufficiency, secondary hypothyroidism and Rathke's cleft cyst. The patient responded well to glucocorticoid and levothyroxine supplementation, and at 1-y follow-up the patient developed hypogonadism. We hypothesize that hypophysitis is probably induced by COVID-19 vaccine and report the rare but serious adverse reactions for early recognition and intervention.


Subject(s)
COVID-19 Vaccines , COVID-19 , Central Nervous System Cysts , Hypophysitis , Humans , Male , Central Nervous System Cysts/complications , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Hypophysitis/chemically induced , Middle Aged
5.
Cell Signal ; 114: 110977, 2024 02.
Article in English | MEDLINE | ID: mdl-37984605

ABSTRACT

Circular RNAs (circRNAs) are a class of non-coding RNAs which take part in the regulation of the initiation and development of different types of cancer. Numerous studies have demonstrated that circRNAs are involved in the progression of osteosarcoma (OS) as well. Thus, we put our emphasis on the exploration of crucial circRNAs in the process of OS initiation and progression. Using RNA sequencing, we found that circSATB2 was highly expressed in OS tissues compared with adjacent normal tissues. Then, we confirmed the high expression of circSATB2 in OS cell lines and OS tissues and its high expression was related to poor prognosis of OS patients. Functional experiments exhibited that circSATB2 promoted OS proliferation and migration in vitro, primary OS model and OS lung metastasis model showed that circSATB2 aggravated OS progression in vivo. Mechanistically, circSATB2 was found to promote OS progression through sponging miR-661 and FUS regulating the mRNA of ZNFX1. Therefore, circSATB2 could act as a prognostic marker and a therapeutic target for osteosarcoma in the future.


Subject(s)
Bone Neoplasms , MicroRNAs , Osteosarcoma , RNA, Circular , Humans , Antigens, Neoplasm , Bone Neoplasms/genetics , Bone Neoplasms/metabolism , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , MicroRNAs/metabolism , Osteosarcoma/genetics , Osteosarcoma/metabolism , RNA, Circular/genetics , RNA, Messenger/genetics , RNA-Binding Protein FUS/genetics , RNA-Binding Protein FUS/metabolism
6.
Gene ; 898: 148118, 2024 Mar 10.
Article in English | MEDLINE | ID: mdl-38159618

ABSTRACT

FRS2 has demonstrated oncogenic roles in various malignancies, including liposarcoma and giant cell tumor of bone. However, its role in osteosarcoma remains less understood, and the upstream regulatory molecules influencing FRS2 remain unclear. This study aims to explore the clinical implications and biological function of FRS2 in osteosarcoma, and the potential regulatory microRNAs (miRNAs) governing its expression. Our study indicated significant upregulation of FRS2 in osteosarcoma cells and tissues by Western blotting and immunohistochemical staining. Elevated FRS2 expression correlated positively with increased angiogenesis and poor prognosis, possibly serving as an independent prognostic indicator for osteosarcoma patients. Functional assays revealed that attenuating FRS2 in osteosarcoma cells could mitigate proliferation, migration, and angiogenesis of vascular endothelial cells. Further investigations revealed that miR-429 and miR-206 directly targeted FRS2, exerting a negative regulation on its expression. Furthermore, FRS2 played a role in repressing osteosarcoma advancement influenced by miR-429 or miR-206. In summary, FRS2, influenced by miR-429 and miR-206, emerges as a promising therapeutic candidate for antiangiogenic osteosarcoma treatments.


Subject(s)
Bone Neoplasms , MicroRNAs , Osteosarcoma , Humans , Endothelial Cells/metabolism , Angiogenesis , Cell Line, Tumor , MicroRNAs/genetics , MicroRNAs/metabolism , Osteosarcoma/metabolism , Bone Neoplasms/metabolism , Cell Proliferation/genetics , Cell Movement/genetics , Gene Expression Regulation, Neoplastic , Membrane Proteins/genetics , Membrane Proteins/metabolism , Adaptor Proteins, Signal Transducing/genetics
7.
Article in English | MEDLINE | ID: mdl-38083356

ABSTRACT

Obstructive Sleep Apnea (OSA) is the most common sleep-related breathing disorder, with an overall population prevalence ranging from 9% to 38%, and it is associated with many cardiovascular diseases. The diagnosis of OSA requires polysomnography (PSG) testing, which is unsuitable for large-scale preliminary screening due to its high cost and discomfort to wear. Therefore, a simple and inexpensive screening method would be of great value. This study presents a novel at-home OSA screening method using a smartwatch and a smartphone to obtain several physiological signals, snoring segments, and questionnaire information during a whole night's sleep. The proposed method can distinguish four OSA risk levels based on machine learning (ML) classifications; the system was validated by conducting an in-hospital study on 350 subjects with sleep disorders. The estimated OSA risk levels are in good agreement with the OSA severity diagnosed by PSG (correlation with apnea-hypopnea index (AHI) = 0.92), and an encouraging classification performance is achieved (accuracy = 88.1%, 84.5%, 85.1%, sensitivity = 89.1%, 84.2%, 85.6% for mild, moderate and severe OSA). These findings reveal that wearable devices have the potential for large-scale OSA screening.


Subject(s)
Sleep Apnea, Obstructive , Humans , Sleep Apnea, Obstructive/diagnosis , Sleep/physiology , Polysomnography , Mass Screening , Smartphone
9.
Chem Biodivers ; 20(10): e202301270, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37697440

ABSTRACT

In the investigation of Meehania fargesii, eighteen triterpenoids were isolated and identified, including a previously unknown compound with an 13,27-cycloursane skeleton, using techniques like 1D and 2D NMR, and HR-MS. Furthermore, the cytotoxicity of these compounds were evaluated against HCT116, MCF-7, and AGS cell lines using the CCK-8 method to examine their structure-activity relationship. Remarkably, compounds 13 and 16 exhibited higher cytotoxicity across all three cell lines compared to the positive drug. Western blot analysis revealed that these compounds activated apoptosis in HCT116 cells by promoting the Bax protein and inhibiting the Bcl-2 protein. This suggests that compounds 13 and 16 have potential as apoptosis-inducing agents in HCT116 cells.

10.
Cell Death Dis ; 14(9): 626, 2023 09 22.
Article in English | MEDLINE | ID: mdl-37739958

ABSTRACT

The prognosis of lung metastatic osteosarcoma (OS) remains disappointing. siRNA-based gene silencing of VEGFR2 is a promising treatment strategy for lung metastatic OS, but there is a lack of safe and efficient delivery systems to encapsulate siRNAs for in vivo administration. This study presented a synthetic biological strategy that remolds the host liver with synthesized genetic circuits for efficient in vivo VEGFR2 siRNA delivery. After being taken-up by hepatocytes, the genetic circuit (in the form of a DNA plasmid) reprogrammed the liver to drive the autonomous intrahepatic assembly and encapsulation of VEGFR2 siRNAs into secretory small extracellular vesicles (sEVs), thus allowing for the transport of self-assembled VEGFR2 siRNAs towards the lung. The results showed that our strategy was superior to the positive medicine (Apatinib) for OS lung metastasis in terms of therapeutic efficacy and toxic adverse effects and may provide a feasible and viable therapeutic solution for lung metastatic OS.


Subject(s)
Bone Neoplasms , Extracellular Vesicles , Osteosarcoma , Humans , RNA, Small Interfering/genetics , Osteosarcoma/genetics , Osteosarcoma/therapy , Bone Neoplasms/genetics , Bone Neoplasms/therapy , Lung
11.
J Ethnopharmacol ; 309: 116330, 2023 Jun 12.
Article in English | MEDLINE | ID: mdl-36868438

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Clinopodium chinense Kuntze (CC), traditional Chinese medicine with anti-inflammatory, anti-diarrheal, and hemostatic activities, has been used to treat dysentery and bleeding diseases for thousands of years, which are similar to the symptoms of ulcerative colitis (UC). AIM OF THE STUDY: To obtain a novel treatment for UC, an integrated strategy was developed in this study to investigate the effect and mechanism of CC against UC. MATERIALS AND METHODS: The chemical characterization of CC was scanned by UPLC-MS/MS. Network pharmacology analysis was performed to predict the active ingredients and pharmacological mechanisms of CC against UC. Further, the results of network pharmacology were validated using LPS-induced RAW 264.7 cells and DSS-induced UC mice. The production of pro-inflammatory mediators and biochemical parameters was tested using the ELISA kits. The expression of NF-κB, COX-2, and iNOS proteins was evaluated using Western blot analysis. Body weight, disease activity index, colon length, histopathological examination, and metabolomics analysis in colon tissues were carried out to confirm the effect and mechanism of CC. RESULTS: Based on the chemical characterization and literature collection, a rich database of ingredients in CC was constructed. Network pharmacology analysis provided five core components as well as revealed that the mechanism of CC against UC was highly related to inflammation, especially the NF-κB signaling pathway. In vitro experiments showed CC could inhibit inflammation by LPS-TLR4-NF-κB-iNOS/COX-2 signaling pathway in RAW264.7 cells. Meanwhile, in vivo experimental results proved that CC significantly alleviated pathological features with increased body weight and colonic length, decreased DAI and oxidative damage, as well as mediated inflammatory factors like NO, PGE2, IL-6, IL-10, and TNF-ɑ. In addition, colon metabolomics analysis revealed CC could restore the abnormal endogenous metabolite levels in UC. 18 screened biomarkers were further enriched in four pathways including Arachidonic acid metabolism, Histidine metabolism, Alanine, aspartate and glutamate metabolism as well as the Pentose phosphate pathway. CONCLUSION: This study demonstrates that CC could alleviate UC by reducing systematic inflammation and regulating metabolism, which is beneficial for providing scientific data for the development of UC treatment.


Subject(s)
Colitis, Ulcerative , Colitis , Mice , Animals , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/pathology , NF-kappa B/metabolism , Dextran Sulfate/toxicity , Cyclooxygenase 2/metabolism , Chromatography, Liquid , Lipopolysaccharides/pharmacology , Tandem Mass Spectrometry , Inflammation/pathology , Colon , Disease Models, Animal , Mice, Inbred C57BL , Colitis/metabolism
12.
Biomed Res Int ; 2023: 1150768, 2023.
Article in English | MEDLINE | ID: mdl-36817861

ABSTRACT

Background: Osteosarcoma (OS) is the most common primary aggressive sarcoma of bone, with massive aberrant expression of oncogenes related to the development of OS. RALA, a kind of small Ras-like guanosine triphosphatases, has been identified as a potential therapeutic target in several types of tumor, but its role in OS remains largely unknown. Methods: Abnormal expression of RALA was proven in the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Therapeutically Applicable Research to Generate Effective Treatments (TARGET), and RNA-sequence of samples and cell lines. The role of RALA in OS was analyzed in terms of DNA methylation, immune cell infiltration, and patient survival. The cancer-promoting effect of RALA was demonstrated in cell lines and xenograft osteosarcoma models. A prognostic scoring model incorporating RALA as an indicator was established with the clinical samples that we collected. Results: The results showed that RALA was highly expressed in human OS tissues and cell lines. Survival analysis demonstrated that RALA was the sole independent risk factor for poor overall survival and disease-free survival in OS patients and impacted the proportion of infiltrating immune cells and DNA methylation in the OS tumor microenvironment. By gene-gene interaction analysis, we found that the expression of RALA was highly correlated to the expression of ABCE1. Similar to RALA, upregulated ABCE1 is correlated with poor survival outcome of OS patients. In addition, the functional experiment demonstrated that higher expression of RALA promoted the proliferation, migration, and invasion of OS cells. In vivo results were similar with the in vitro results. We examined m6a methylation-related genes and found that m6A methylation is responsible for the abnormal expression of RALA. Finally, the prognostic prediction model of RALA could be used to predict the long-term outcome of OS patients. Conclusions: We identified RALA as an oncogene in OS, and RALA upregulation in a concerted manner with ABCE1 was significantly associated with worse outcomes of OS patients. Targeting RALA may prove to be a novel target for OS immunotherapy in future clinical practice.


Subject(s)
Bone Neoplasms , Osteosarcoma , Humans , Prognosis , Bone Neoplasms/pathology , Cell Movement/genetics , Bone and Bones/metabolism , Osteosarcoma/pathology , Tumor Microenvironment , ral GTP-Binding Proteins/metabolism
13.
Nat Prod Res ; 37(2): 348-353, 2023 Jan.
Article in English | MEDLINE | ID: mdl-34396839

ABSTRACT

The phytochemical investigation on the leaves of Psidium guajava Linn. led to the isolation and identification of 18 compounds, including six guavinoside (1-6), four flavonoids (7-10), eight triterpenoids (11-17) and one lignans (18). All chemical structures were elucidated via NMR spectroscopic methods, and further supported by comparison with literature data. Compounds 12, 14, 16 and 18 was isolated from the Myrtaceae family for the first time. The chemotaxonomic significance of these compounds was also discussed based on their structure types, as well as compounds-genus/family network analysis. The results showed that there were close chemotaxonomic relationships among the Myrtaceae, Asteraceae, and Lamiaceae families. Guavinosides A-F could be considered as valuable chemotaxonomic markers of Myrtaceae family, while guavinosides C-F might serve as chemotaxonomic markers for distinguishing the P. guajava.


Subject(s)
Myrtaceae , Psidium , Humans , Psidium/chemistry , Plant Leaves/chemistry , Plant Extracts/chemistry , Flavonoids/chemistry
14.
Front Neurol ; 14: 1336382, 2023.
Article in English | MEDLINE | ID: mdl-38344111

ABSTRACT

We present the case of a 54-year-old woman with reasonable blood sugar control who presented with a diabetic foot combined with severe peripheral neuropathy and vascular disease. Lower limb muscle weakness, muscle atrophy, skin pigmentation, and emaciation were also observed. Although her muscle strength improved after glucocorticoid treatment, it remained challenging to account for the other symptoms in this particular patient with chronic inflammatory demyelinating polyneuropathy. Plump liver and spleen, hidden bone lesions combined with seemingly unexplained cerebral infarction, and serous effusion led us to suspect polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. The abnormal proliferation of monoclonal plasma cells and a significant increase in vascular endothelial growth factor (VEGF) levels confirmed the diagnosis of POEMS syndrome. After 1 month of treatment with lenalidomide and dexamethasone, the diabetic foot ulcers healed, and the symptoms of myasthenia and fatigue improved. Diabetic feet may represent only the tip of the iceberg of an underlying POEMS syndrome. Our report aimed to increase awareness of this rare yet significant situation, advocating for the prompt identification and treatment of POEMS syndrome.

15.
Front Oncol ; 12: 980390, 2022.
Article in English | MEDLINE | ID: mdl-36276118

ABSTRACT

Background: Osteosarcoma (OS) is the most common primary malignant bone tumors in children and adolescents. Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) is a key gene in mediating the formation of the stabilized collagen cross-link, playing an important role in the progression of cancer. However, the interaction between OS and PLOD2 has not been clarified so far. Methods: The target gene PLOD2 was screened through our own RNA-seq results and other two RNA-seq results from GEO database. The expression of PLOD2 in OS was detected by RT-qPCR, Western blot and immunohistochemistry. Functional experiments were performed to investigate the role of PLOD2 in OS cell invasion, migration and angiogenesis in vitro. An OS lung metastasis model was established to investigate the function of PLOD2 in OS metastasis and angiogenesis in vivo. The role of PLOD2 in immune infiltration in OS was explored by KEGG/GO analysis and immune infiltration analysis with TARGET, TCGA and TIMER. Results: PLOD2 was high-expressed in OS, which was related to poor prognosis of OS patients. PLOD2 promoted OS cell migration, invasion and angiogenesis in vitro and aggravated OS metastasis and angiogenesis in vivo. Bioinformatic analysis showed that PLOD2 played an important role in immune cell infiltration in OS, including CD8 positive T cells, macrophages M0 cells, DC cells, endothelial cells, iDC cells, ly endothelial cells, MEP cells, mv endothelial cells, native B cells, smooth muscle cells and Th1 cells. Immunohistochemical results showed that the expression of CD4 and CD8A was negatively correlated with the expression of PLOD2 in OS. Conclusion: PLOD2 was high-expressed in OS and promoted OS migration, invasion and angiogenesis in vitro and facilitated OS metastasis and angiogenesis in vivo. PLOD2 was associated with immune cell infiltration in OS, which could be a promising target to treat OS patients with metastasis and utilized to guide clinical immunotherapy in the future.

16.
Front Bioeng Biotechnol ; 10: 1003677, 2022.
Article in English | MEDLINE | ID: mdl-36312529

ABSTRACT

Objective: Promoting bone regeneration and repairing in bone defects is of great significance in clinical work. Using a simple and effective surface treatment method to enhance the osteogenic ability of existing bone scaffold is a promising method. In this article, we study the application of catecholic amino acid 3,4-dihydroxyphenylalanine (DOPA) surface coating chelated with vascular endothelial growth factor (VEGF) on allogeneic bone. Method: Allogeneic bone is immersed in DOPA solution and DOPA form polydopamine (PDA) with good adhesion. Electron microscopy is used to characterize the surface characteristics of allogeneic bone. MC3T3-E1 cells were tested for biocompatibility and osteogenic signal expression. Finally, a 12-week rabbit bone defect model was established to evaluate bone regeneration capability. Results: We found that the surface microenvironment of DOPA bonded allogeneic bone was similar to the natural allogeneic bone. VEGF loaded allografts exhibited satisfying biocompatibility and promoted the expression of osteogenic related signals in vitro. The VEGF loaded allografts healed the bone defect after 12 weeks of implantation that continuous and intact bone cortex was observed. Conclusion: The PDA coating is a simple surface modification method and has mild properties and high adhesion. Meanwhile, the PDA coating can act on the surface modification of different materials. This study provides an efficient surface modification method for enhancing bone regeneration by PDA coating, which has a high potential for translational clinical applications.

17.
Mol Cancer ; 21(1): 167, 2022 08 19.
Article in English | MEDLINE | ID: mdl-35986280

ABSTRACT

BACKGROUND: Disappointing clinical efficacy of standard treatment has been proven in refractory metastatic osteosarcoma, and the emerging anti-angiogenic regimens are still in the infantile stage. Thus, there is an urgent need to develop novel therapeutic approach for osteosarcoma lung metastasis. METHODS: circFIRRE was selected from RNA-sequencing of 4 matched osteosarcoma and adjacent samples. The expression of circFIRRE was verified in clinical osteosarcoma samples and cell lines via quantitative real-time polymerase chain reaction (RT-qPCR). The effect of circFIRRE was investigated in cell lines in vitro models, ex vivo models and in vivo xenograft tumor models, including proliferation, invasion, migration, metastasis and angiogenesis. Signaling regulatory mechanism was evaluated by RT-qPCR, Western blot, RNA pull-down and dual-luciferase reporter assays. RESULTS: In this article, a novel circular RNA, circFIRRE (hsa_circ_0001944) was screened out and identified from RNA-sequencing, and was upregulated in both osteosarcoma cell lines and tissues. Clinically, aberrantly upregulated circFIRRE portended higher metastatic risk and worse prognosis in osteosarcoma patients. Functionally, in vitro, ex vivo and in vivo experiments demonstrated that circFIRRE could drive primary osteosarcoma progression and lung metastasis by inducing both tumor cells and blood vessels, we call as "tumorigenic-angiogenic coupling". Mechanistically, upregulated circFIRRE was induced by transcription factor YY1, and partially boosted the mRNA and protein level of LUZP1 by sponging miR-486-3p and miR-1225-5p. CONCLUSIONS: We identified circFIRRE as a master regulator in the tumorigenesis and angiogenesis of osteosarcoma, which could be purposed as a novel prognostic biomarker and therapeutic target for refractory osteosarcoma.


Subject(s)
Bone Neoplasms , Lung Neoplasms , MicroRNAs , Osteosarcoma , Bone Neoplasms/pathology , Carcinogenesis/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , MicroRNAs/genetics , MicroRNAs/metabolism , Osteosarcoma/pathology , RNA, Circular/genetics
18.
Comput Math Methods Med ; 2022: 3287961, 2022.
Article in English | MEDLINE | ID: mdl-35991143

ABSTRACT

Methods: The medical data of 47 patients with refractory bone and soft tissue sarcoma, who received anlotinib from January 2019 to December 2020, were retrospectively collected. The overall response rate (ORR) and disease control rate (DCR) were evaluated according to the solid tumor response evaluation version 1.1 standard. The progression-free survival (PFS), overall survival (OS), and adverse reactions were recorded. Results: A total of 44 patients, including 13 with osteosarcoma and 31 with soft tissue sarcoma, were enrolled in this study. Among patients with osteosarcoma, no patients achieved complete response (CR) or partial response (PR), while seven patients (54%) had stable disease (SD). Besides, the median PFS (m-PFS) was 4.4 months, and the median OS (m-OS) was 15.7 months. Among patients with soft tissue sarcoma, the ORR and DCR were 19% and 71%, respectively. The median m-PFS was 5.4 months, and m-OS was 17.9 months. Anlotinib plus chemotherapy had a higher ORR compared with anlotinib monotherapy (6% vs. 38%, P = 0.047). The most common grade 3/4 adverse reactions were pneumothorax (5%) and pleural effusion (5%), and no treatment-related deaths occurred. Conclusions: Anlotinib alone showed encouraging efficacy and favorable tolerability in refractory bone and soft tissue sarcoma. Anlotinib plus chemotherapy did not show a significant clinical benefit compared with anlotinib alone. Anlotinib showed better tumor control when used as first-line drug treatment in refractory bone and soft tissue sarcoma.


Subject(s)
Bone Neoplasms , Osteosarcoma , Sarcoma , Soft Tissue Neoplasms , Bone Neoplasms/drug therapy , Humans , Indoles , Quinolines , Retrospective Studies , Sarcoma/drug therapy , Soft Tissue Neoplasms/drug therapy , Soft Tissue Neoplasms/pathology , Treatment Outcome
19.
Chem Biodivers ; 19(7): e202200463, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35785443

ABSTRACT

A new amide (1), two new phenylpropanoid derivatives (2, 3), along with three new natural products, including three nitrogen chirality compounds, N-(3-methoxy-1,3-dioxopropyl)-D-phenylalanine methyl ester (4), N-(3-methoxy-1,3-dioxopropyl)-L-phenylalanine methyl ester (5), and N-acetyl-L-phenylalanine methyl ester (6), as well as dimethyl (2R,3R)-2-hydroxy-3-(((E)-3-(4-hydroxyphenyl)acryloyl)oxy)succinate (7) and dimethyl (S,E)-2-((3-(4-hydroxy-3-methoxyphenyl)acryloyl)oxy)succinate (8) were isolated from Delphinium kamaonense Hunth. Their structures were elucidated by extensive analysis of 1D and 2D NMR, and HR-ESI-MS experiments, and the absolute configurations were determined by comparative analysis of specific optical rotation. Compound 1 exhibited a moderate cytotoxicity effect against Hep-3B cancer cell lines (IC50 41.39±0.13 µM) and an excellent antioxidant activity (IC50 0.527±0.06 µM in ABTS assay, and 1.235±0.09 µM in DPPH assay, respectively), which was superior to vitamin C in ABTS (IC50 1.670±0.07 µM) and DPPH (IC50 19.10±0.40 µM) methods.


Subject(s)
Antineoplastic Agents , Delphinium , Antineoplastic Agents/pharmacology , Antioxidants/pharmacology , Delphinium/chemistry , Magnetic Resonance Spectroscopy , Molecular Structure , Succinates
20.
BMC Cancer ; 22(1): 728, 2022 Jul 04.
Article in English | MEDLINE | ID: mdl-35787258

ABSTRACT

BACKGROUND: Osteosarcoma (OS) is the most common primary malignant bone tumors in children and adolescents. Large numbers of studies have focused on the long non-coding RNA (lncRNA) that plays essential roles in the progression of osteosarcoma. Nevertheless, the functions and underlying mechanisms of LncRNA NDRG1 in osteosarcoma remain unknown. METHODS: Differentially expressed lncRNAs between osteosarcoma and adjacent normal tissues were identified through RNA sequencing. The role of LncRNA NDRG1 in osteosarcoma proliferation and metastasis were investigated through in vitro and in vivo functional experiments. The interaction between LncRNA NDRG1 and miR-96-5p was verified through bioinformatic analysis and luciferase reporter assay. Regulation relationship between LncRNA NDRG1 and miR-96-5p was further evaluated by the rescue experiments. Additionally, the changes in the expression of epithelial-mesenchymal transition (EMT) and the PI3K/AKT pathway were verified by Western blot. RESULTS: LncRNA NDRG1 was up-regulated in osteosarcoma cell lines and tissues and the expression of LncRNA NDRG1 was correlated with the overall survival of osteosarcoma patients. Functional experiments exhibited that LncRNA NDRG1 aggravated osteosarcoma proliferation and migration in vitro; meanwhile, animals experiments showed that LncRNA NDRG1 promoted osteosarcoma growth and metastasis in vivo. Mechanistically, LncRNA NDRG1 was found to aggravate osteosarcoma progression and regulate the PI3K/AKT pathway by sponging miR-96-5p. CONCLUSIONS: LncRNA NDRG1 aggravates osteosarcoma progression and regulates the PI3K/AKT pathway by sponging miR-96-5p. Therefore, LncRNA NDRG1 could act as a prognostic marker and a therapeutic target for osteosarcoma in the future.


Subject(s)
Bone Neoplasms , MicroRNAs , Osteosarcoma , RNA, Long Noncoding , Animals , Bone Neoplasms/genetics , MicroRNAs/genetics , Osteosarcoma/genetics , Phosphatidylinositol 3-Kinases/genetics , Proto-Oncogene Proteins c-akt , RNA, Long Noncoding/genetics
SELECTION OF CITATIONS
SEARCH DETAIL
...