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1.
Radiat Oncol ; 19(1): 46, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594678

RESUMO

OBJECTIVE: To evaluate effects of bone marrow sparing (BMS) radiotherapy on decreasing the incidence of acute hematologic toxicity (HT) for locoregionally advanced cervical cancer (LACC) patients treated by pelvic irradiation. MATERIALS AND METHODS: LACC patients were recruited prospectively from May 2021 to May 2022 at a single center and were evenly randomized into the BMS group and the control group. All patients received pelvic irradiation with concurrent cisplatin (40 mg/m2 weekly), followed by brachytherapy and BM V40 < 25% in the BMS group was additionally prescribed. Acute HT was assessed weekly. Binary logistic regression model and receiver operating characteristic (ROC) curve were used for predictive value analysis. The trial was registered with Chinese clinical trial registry (ChiCTR2200066485). RESULTS: A total of 242 patients were included in the analysis. Baseline demographic, disease and treatment characteristics were balanced between the two groups. In the intention-to-treat population, BMS was associated with a lower incidence of grade ≥ 2 and grade ≥ 3 acute HT, leukopenia and neutropenia s(72.70% v 90.90%, P < 0.001*; 16.50% vs. 65.30%, P < 0.001*; 66.10% vs. 85.10%, P = 0.001*; 13.20% vs. 54.50%, P < 0.001*; 37.20% vs. 66.10%, P < 0.001*; 10.70% vs. 43.80%, P < 0.001*). BMS also resulted in decreased dose delivered to the organs at risk (OARs) including rectum, bladder and left and right femoral head. Univariate and multivariate analyses showed that BM V40 was an independent risk factor for grade ≥ 3 acute HT (odds ratio [OR] = 2.734, 95% confidence interval [CI] = 1.959-3.815, P < 0.001*). Cutoff value was 25.036% and area under the curve (AUC) was 0.786. The nomogram was constructed, which was rigorously evaluated and internally cross-validated, showing good predictive performance. CONCLUSIONS: Receiving BMS pelvic irradiation could reduce the incidence of acute HT in LACC patients, and BM V40 < 25% may be a significant factor in reducing the risks of acute HT.


Assuntos
Leucopenia , Lesões por Radiação , Radioterapia de Intensidade Modulada , Neoplasias do Colo do Útero , Feminino , Humanos , Medula Óssea/efeitos da radiação , Neoplasias do Colo do Útero/radioterapia , Estudos Prospectivos , Radioterapia de Intensidade Modulada/métodos , Dosagem Radioterapêutica , Cisplatino , Leucopenia/etiologia , Quimiorradioterapia/efeitos adversos , Lesões por Radiação/etiologia
2.
Cancer ; 130(S8): 1424-1434, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38217532

RESUMO

BACKGROUND: Immunohistochemistry (IHC) is an essential technique in surgical and clinical pathology for detecting diagnostic, prognostic, and predictive biomarkers for personalized cancer therapy. However, the lack of standardization and reference controls results in poor reproducibility, and a reliable tool for IHC quantification is urgently required. The objective of this study was to describe a novel approach in which H3F3B (histone H3, family 3B) can be used as an internal reference standard to quantify protein expression levels using IHC. METHODS: The authors enrolled 89 patients who had human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). They used a novel IHC-based assay to measure protein expression using H3F3B as the internal reference standard. H3F3B was uniformly expressed at the protein level in all tumor regions in cancer tissues. HER2 expression levels were measured with the H-score using HALO software. RESULTS: Kaplan-Meier analysis indicated that, among patients who had HER2-positive BC in The Cancer Genome Atlas data set and the authors' data set, the subgroup with low HER2 expression had a significantly better prognosis than the subgroup with high HER2 expression. Furthermore, the authors observed that HER2 expression levels were precisely evaluated using the proposed method, which can classify patients who are at higher risk of HER2-positive BC to receive trastuzumab-based adjuvant therapy. Dual-color IHC with H3F3B is an excellent tool for internal and external quality control of HER2 expression assays. CONCLUSIONS: The proposed IHC-based quantification method accurately assesses HER2 expression levels and provides insights for predicting clinical prognosis in patients with HER2-positive BC who receive trastuzumab-based adjuvant therapy.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Histonas , Imuno-Histoquímica , Reprodutibilidade dos Testes , Receptor ErbB-2/genética , Trastuzumab/uso terapêutico , Padrões de Referência , Biomarcadores Tumorais/metabolismo
3.
Int J Biochem Cell Biol ; 169: 106530, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38246263

RESUMO

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) has a high mortality rate and incidence of complications. The pathophysiology of ALI/ARDS is still not fully understood. The lipopolysaccharide (LPS)-induced mouse model of ALI has been widely used to study human ALI/ARDS. Sulfasalazine (SASP) has antibacterial and anti-inflammatory effects and is used for treating inflammatory bowel and rheumatic diseases. However, the effect of SASP on LPS-induced ALI in mice has not yet been reported. Therefore, we aimed to investigate the effect of SASP on LPS-induced ALI in mice. Mice were intraperitoneally injected with SASP 2 h before or 4 h after LPS modeling. Pulmonary pathological damage was measured based on inflammatory factor expression (malondialdehyde and superoxide dismutase levels) in the lung tissue homogenate and alveolar lavage fluid. The production of inflammatory cytokines and occurrence of oxidative stress in the lungs induced by LPS were significantly mitigated after the prophylactic and long-term therapeutic administration of SASP, which ameliorated ALI caused by LPS. SASP reduced both the production of inflammatory cytokines and occurrence of oxidative stress in RAW264.7 cells, which respond to LPS. Moreover, its mechanism contributed to the suppression of NF-κB and nuclear translocation. In summary, SASP treatment ameliorates LPS-induced ALI by mediating anti-inflammatory and antioxidant effects, which may be attributed to the inhibition of NF-κB activation and promotion of antioxidant defenses. Thus, SASP may be a promising pharmacologic agent for ALI therapy.


Assuntos
Lesão Pulmonar Aguda , Síndrome do Desconforto Respiratório , Camundongos , Humanos , Animais , NF-kappa B/metabolismo , Lipopolissacarídeos/farmacologia , Sulfassalazina/efeitos adversos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Pulmão/patologia , Estresse Oxidativo , Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Síndrome do Desconforto Respiratório/tratamento farmacológico , Síndrome do Desconforto Respiratório/metabolismo , Síndrome do Desconforto Respiratório/patologia
4.
Mol Pharm ; 21(2): 781-790, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38153044

RESUMO

There is an urgent need to develop efficient treatments for highly invasive triple-negative breast cancer (TNBC) with a high rate of postoperative. Baicalin (BA) has shown inhibitory effects on several tumor cells and could activate ferroptosis in some tumor cells by producing reactive oxygen species (ROS). For overcoming the shortcomings of BA in clinical applications and enhancing the effect of ferroptosis in TNBC, herein, a multifunctional liposome (BA-Fe(III) coordination-polymer-loaded liposome, BA-Fe(III) Lipo) was developed for synergistic chemotherapy of TNBC with ferroptosis activation. Fe(III) released from BA-Fe(III) Lipo could be efficiently reduced to Fe(II) in the presence of high glutathione in tumor microenvironment, which in turn catalyzed the oxidation of unsaturated fats through lipid peroxidation for more ROS production. In addition, BA-Fe(III) Lipo activated tumor cell ferroptosis by down-regulating the enzymatic activity of ferritin heavy chain 1 protein and glutathione peroxidase. This study provided a novel therapeutic strategy for the treatment of TNBC by ingeniously combining chemotherapy with the activation of ferroptosis, which presented potential clinical applications.


Assuntos
Ferroptose , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Lipossomos , Compostos Férricos , Espécies Reativas de Oxigênio , Glutationa , Linhagem Celular Tumoral , Microambiente Tumoral
5.
J Agric Food Chem ; 71(51): 20690-20700, 2023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-38100375

RESUMO

Aspongamide F (1), a novel N-acetyldopamine (NADA) dimer possessing a 6/6/6 ring system, and (±)-aspongamides G (2) and H (3), rare NADA derivatives with fragmented benzene rings, were isolated from Aspongopus chinensis. (±)-Cicadamides C (4) and D (5), the first 1,4-Benzodioxane NADA dimers featuring a seco-benzene system, and (±)-cicadamides E (6) and F (7), the NADA dimers derivatives, were isolated from Periostracum cicadae. The structures of all compounds were elucidated by spectroscopic analyses and computational methods. A plausible biosynthetic pathway for compounds 1-5 was proposed. The biological assay revealed that (+)-4 and (-)-4 exhibit renal protection in a dose-dependent manner.


Assuntos
Benzeno , Heterópteros , Animais , Insetos
6.
Front Med (Lausanne) ; 10: 1163371, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38034526

RESUMO

Purpose: This study aimed to evaluate the efficacy and safety of same-session flexible ureteroscopy (fURS) for the treatment of bilateral upper urinary tract stones and to examine the influence of stone load on the outcome of same-session fURS, stratifying by total diameter of stones (TDS) ≤30 mm vs. >30 mm. Patients and methods: We retrospectively reviewed all cases of same-session fURS performed for bilateral upper urinary tract stones at four institutions between January 2017 and September 2020. All patients were divided into two groups based on TDS, ≤30 mm and >30 mm. Data on patient demographics, stone characteristics, surgical results, and complications were collected and analyzed for differences between the two groups. Stone-free rate (SFR) was defined as patients endoscopically stone-free or with radiological fragments <2 mm of each renal unit. Results: A total of 121 patients with bilateral upper urinary tract stones underwent same-session fURS, consisting of 73 patients in the TDS ≤ 30 mm group and 48 patients in the TDS > 30 mm group. The mean bilateral stone size was 28.2 ± 12.2 mm (range: 9.1-38.4 mm), with a mean operating time of 97.1 ± 39.6 min (range: 19-220 min). The SFR was 54.5% after the first fURS, and SFR increased to 97.5% after re-fURS for residual stones. The operation time for the TDS > 30 mm group was longer than that of the TDS ≤ 30 mm group (85.1 ± 36.5 vs. 115.4 ± 37.4 min, p < 0.001). The SFR after the first fURS was significantly lower in the TDS > 30 mm group than in the TDS ≤ 30 mm group (25.0% vs. 73.9%, p < 0.001). Although there was no statistically significant difference in overall SFR between the two groups (93.7% vs. 100%, p = 0.060), the rate of re-fURS for residual stones was higher in the TDS > 30 mm group than in the TDS ≤ 30 mm group (75% vs. 26%, p < 0.001). There were no significant differences in length of hospital stay (LOS) (2.2 ± 0.7 vs. 2.3 ± 1.0, p = 0.329) or complication rate (10.9% vs. 14.6%, p = 0.582) between the two groups. Conclusion: The results suggested that same-session fURS can be effectively performed with a low complication rate. A higher SFR after the first fURS can be achieved in the case of bilateral upper urinary tract stones with TDS ≤ 30 mm, and priority should be given to same-session fURS.

7.
GM Crops Food ; 14(1): 1-16, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37387261

RESUMO

Unintended effects of gene edit crops may pose safety issues. Omics is a useful tool for researchers to evaluate these unexpected effects. Transcriptome and proteomics analyses were performed for two gene editors, CRISPR-Cas9 and adenine base editor (ABE) gene edit rice, as well as corresponding wild-type plants (Nipponbare). Transcriptome revealed 520 and 566 rice differentially expressed genes (DEGs) in the Cas9/Nip and ABE/Nip comparisons, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that most DEGs participated in metabolism of terpenoids and polyketones, plant-pathogen interactions, and plant signal transduction. It mainly belongs to environmental adaptation. Proteomics revealed 298 and 54 rice differentially expressed proteins (DEPs) in the Cas9/Nip and ABE/Nip comparisons, respectively. KEGG pathway enrichment analysis showed that most DEPs participated in the biosynthesis of secondary metabolite and metabolic pathways.According to integrated transcriptomes and proteomics analysis, the results showed that no newly generated genes were identified as new transcripts of these differentially expressed genes, and gene edit tools had little effect on rice transcription levels and no new proteins were generated in the gene-edited rice.


Assuntos
Terapia Ocupacional , Oryza , Humanos , Proteômica , Adenina , Produtos Agrícolas , Interações Ervas-Drogas , Oryza/genética
8.
Aging (Albany NY) ; 15(3): 810-829, 2023 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-36787437

RESUMO

Lung adenocarcinoma (LUAD) is one of the most commonly malignant tumors, and major challenges remain in the treatment of LUAD. Budding uninhibited by benzimidazole 1/3 (BUB1/3) play significant roles in the process of spindle-assembly checkpoint (SAC) during mitosis. However, their roles in LUAD have not been established. Here, we performed an immunological analysis of BUB1/3 in LUAD using a comprehensive bioinformatics approach, quantitative real-time-PCR and Western blotting technique. Our results indicated that the expression levels of BUB1 and BUB3 in LUAD samples were higher than the expression levels in the control groups and were associated with some clinicopathologic parameters in patients with LUAD. BUB1/3 and their related genes were enriched in cell immune, and the immune infiltration analysis revealed that the BUB1/3 expression profile was significantly correlated with characteristics of immune cell infiltration. Survival analysis showed that the disease-free survival and overall survival of patients with LUAD decreased with an increase in the BUB1/3 expression levels. The mRNA and protein expression levels of BUB1 and BUB3 in each of the LUAD cell lines were upregulated to varying degrees. BUB1 and BUB3 are the potential immunological therapeutic intervention targets for patients with LUAD.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Adenocarcinoma de Pulmão/genética , Pontos de Checagem da Fase M do Ciclo Celular , Neoplasias Pulmonares/genética
9.
Fitoterapia ; 164: 105341, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36309142

RESUMO

Five new norneolignans sinkianlignans G-K (1-5), one phenolic compound ferulagenol A (6) and seven known compounds (7-13) were isolated from Ferula sinkiangensis. All the norneolignans were racemic mixtures, and chiral HPLC was used to further separate them. Their structures were assigned, including absolute configurations, using spectroscopic and computational methods. Biological evaluation showed that compounds 1-9 had significant COX-2 inhibitory activity with IC50 values ranging from 3.00 µM to 23.19 µM.


Assuntos
Inibidores de Ciclo-Oxigenase 2 , Ferula , Estrutura Molecular , Inibidores de Ciclo-Oxigenase 2/farmacologia , Ferula/química , Ciclo-Oxigenase 2
10.
Comput Methods Programs Biomed ; 228: 107252, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36434959

RESUMO

BACKGROUND AND OBJECTIVE: The cystic cavity and its surrounding dense glial scar formed in chronic spinal cord injury (SCI) hinder the regeneration of nerve axons. Accurate location of the necrotic regions formed by the scar and the cavity is conducive to eliminate the re-growth obstacles and promote SCI treatment. This work aims to realize the accurate and automatic location of necrotic regions in the chronic SCI magnetic resonance imaging (MRI). METHODS: In this study, a method based on superpixel is proposed to identify the necrotic regions of spinal cord in chronic SCI MRI. Superpixels were obtained by a simple linear iterative clustering algorithm, and feature sets were constructed from intensity statistical features, gray level co-occurrence matrix features, Gabor texture features, local binary pattern features and superpixel areas. Subsequently, the recognition effects of support vector machine (SVM) and random forest (RF) classification model on necrotic regions were compared from accuracy (ACC), positive predictive value (PPV), sensitivity (SE), specificity (SP), Dice coefficient and algorithm running time. RESULTS: The method is evaluated on T1- and T2-weighted MRI spinal cord images of 24 adult female Wistar rats. And an automatic recognition method for spinal cord necrosis regions was established based on the SVM classification model finally. The recognition results were 1.00±0.00 (ACC), 0.89±0.09 (PPV), 0.88±0.12 (SE), 1.00±0.00 (SP) and 0.88±0.07 (Dice), respectively. CONCLUSIONS: The proposed method can accurately and noninvasively identify the necrotic regions in MRI, which is helpful for the pre-intervention assessment and post-intervention evaluation of chronic SCI research and treatments, and promoting the clinical transformation of chronic SCI research.


Assuntos
Imageamento por Ressonância Magnética , Traumatismos da Medula Espinal , Feminino , Ratos , Animais , Ratos Wistar , Traumatismos da Medula Espinal/diagnóstico por imagem , Necrose
11.
Zhonghua Nan Ke Xue ; 29(3): 227-232, 2023 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-38597703

RESUMO

OBJECTIVE: To observe the changes in semen parameters after COVID-19 infection and clarify its impact on male fertility. METHODS: We collected semen samples from 82 male patients infected with COVID-19 in the past 2 months (the infection group) and 14 normal healthy men (the control group), obtained their semen parameters and compared them between the two groups before and after COVID-19 infection. RESULTS: There were no statistically significant differences in the baseline semen parameters between the infection and control groups (P > 0.05), nor in the semen volume within the infection group before and after infection (P > 0.05). Compared with the normal controls, the patients showed significantly decreased sperm concentration, total sperm count, percentage of progressively motile sperm, sperm motility and percentage of morphologically normal sperm after COVID-19 infection (P < 0.05), which were reduced even more significantly in those with than in those without fever during infection (P < 0.05). No statistically significant difference was observed in the semen quality of the patients with normal body temperature before and after COVID-19 infection (P > 0.05). Spearman correlation analysis showed no significant correlation between semen parameters and the severity of fever during infection (P > 0.05). CONCLUSION: COVID-19 infection decreases the semen quality of the patient, and fever during infection is a significant influencing factor. The severity of fever, however, is not related to the reduction of semen quality.


Assuntos
COVID-19 , Sêmen , Masculino , Humanos , Análise do Sêmen , Estudos Retrospectivos , Motilidade dos Espermatozoides , Contagem de Espermatozoides , Espermatozoides
12.
Zhonghua Nan Ke Xue ; 29(9): 856-858, 2023 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-38639602

RESUMO

Male infertility is a common condition in urology with complex etiology. This article explores the understanding of male infertility through the theories of traditional Classic prescriptions based on the text "Jin Gui Yao Lue". The aim is to provide references for clinical diagnosis and treatment of male infertility.


Assuntos
Infertilidade Masculina , Urologia , Masculino , Humanos , Prescrições , Infertilidade Masculina/etiologia , Infertilidade Masculina/terapia , Medicina Tradicional Chinesa
13.
Zhonghua Nan Ke Xue ; 29(12): 1028-1031, 2023 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-38639957

RESUMO

The occurrence of varicocele infertility can be attributed to the small and flexural spermatic plexus which constitutes the main structure of spermatic cord.Obstruction of blood circulation, stagnation of qi and blood, ultimately leading to infertility. The spermatic plexus ' physiological and pathological symptoms are consistent with the theory of visceral collateral. Based on the theory of visceral collaterals, the varicocele infertility caused by stagnation of liver collateral and deficiency of kidney collateral. And the acupuncture is used to directly act on the relevant points on the meridians, so as to dredge the meridians, strengthen the healthy and expel the evil, and harmonize the yin and yang of visceral, which is more in line with the therapeutic principle of " unblocking the meridians " for collateral diseases. For varicocele infertility caused by liver meridian stasis, it can regulate the liver meridian Chong Ren, eliminate blood stasis and promote stagnation, and be combined with LR3, LI4, GB34, SP6, CV3. For varicocele infertility caused by kidney deficiency and meridian syndrome, it can tonify the kidney meridian Du Yang, warm and disperse the essence, and mainly focus on GV4, CV4, KI3, BL23 and BL43.


Assuntos
Terapia por Acupuntura , Infertilidade , Meridianos , Varicocele , Masculino , Humanos , Varicocele/complicações , Varicocele/terapia , Síndrome , Pontos de Acupuntura
14.
Front Genet ; 13: 873869, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36118875

RESUMO

The gene SYF2-an RNA splicing factor-can interact with Cyclin D-type binding protein 1 (GICP) in many biological processes, including splicing regulation, cell cycle regulation, and DNA damage repair. In our previous study we performed genome-wide identification and functional analysis of SYF2 in plant species. The phylogenetic relationships and expression profiles of SYF2 have not been systematically studied in animals, however. To this end, the gene structure, genes, and protein conserved motifs of 102 SYF2 homologous genes from 91 different animal species were systematically analyzed, along with conserved splicing sites in 45 representative vertebrate species. A differential comparative analysis of expression patterns in humans and mice was made. Molecular bioinformatics analysis of SYF2 showed the gene was conserved and functional in different animal species. In addition, expression pattern analysis found that SYF2 was highly expressed in hematopoietic stem cells, T cells, and lymphoid progenitor cells; in ovary, lung, and spleen; and in other cells and organs. This suggests that changes in SYF2 expression may be associated with disease development in these cells, tissues, or organs. In conclusion, our study analyzes the SYF2 disease resistance genes of different animal species through bioinformatics, reveals the relationship between the SYF2 genotype and the occurrence of certain diseases, and provides a theoretical basis for follow-up study of the relationship between the SYF2 gene and animal diseases.

15.
Bioorg Chem ; 127: 105986, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35777232

RESUMO

Sinkianlignans A - D (1-4), four new sesquilignans with an unusual architectures was characterized with a rarely α-γ', ß-γ', and γ-γ' linkage pattern, and sinkianlignans E - F (5 and 6), two lignans, were isolated from the Ferula sinkiangensis. Hypothetic biosynthetic pathway of compound 3 contain a newly formed six-membered C-ring by Diels-Alder cycloaddition. The structures of isolates were established by spectroscopic techniques and computational methods. Biological evaluation of all the isolated compounds revealed that compounds 2a and 2b could inhibit IL-6 and TNF-α production in lipopolysaccharide (LPS) induced RAW264.7 cells in a dose-dependent manner.


Assuntos
Ferula , Sesquiterpenos , Anti-Inflamatórios/farmacologia , Ferula/química , Estrutura Molecular , Resinas Vegetais , Sesquiterpenos/química
16.
J Biomed Nanotechnol ; 18(3): 747-753, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35715921

RESUMO

This study investigated the impact of magnetic mesoporous silica nanoparticles (MMSN)-encapsulated X-linked inhibitor of apoptosis protein (XIAP) and miR-233 on tumor microenvironment in cervical cancer, to provide targeted treatment and strategy, to improve radio sensitization of cancer cells. Cervical cancer cells were treated with normal saline (control group), XIAP-loaded metallic mesoporous silica nanoparticles (MMSNs), and miR-233-targeted material (XIAP group, XIAP+miR-233 group). Proliferation, apoptosis and colony forming ability of cancer cells were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method, flow cytometry and colony formation experiments. In vivo experiments were established to observe the impact of XIAP-loaded MMSNs and miR-233 on tumor growth. Administration of XIAP-loaded MMSNs suppressed tumor growth of cervical cancer, and presence of miR-233 targeted material further decreased tumor volume, increasing radio sensitization of cancer cells. In vitro experiments confirmed that, combined treatment of XIAP and miR-233 suppressed cancer cell proliferation and invasion when inducing apoptosis. XIAP MMSNs characterized by large unit surface area, high dispersion and adhesion, and prolonged circulation time, improving drug delivery and treatment selectivity of chemotherapeutic drugs. This study suggests that XIAP MMSNs with miR-233 material suppress cervical cancer cell progression and tumor growth when augmenting radiosensitization of cancer cells, providing evidence for targeted therapy for the disease.


Assuntos
MicroRNAs , Nanopartículas , Neoplasias do Colo do Útero , Apoptose , Linhagem Celular Tumoral , Feminino , Humanos , Fenômenos Magnéticos , MicroRNAs/genética , Dióxido de Silício , Microambiente Tumoral , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/genética , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo
17.
EBioMedicine ; 80: 104019, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35490460

RESUMO

BACKGROUND: N6-methyladenosine (m6A) is the most common and abundant mRNA modification and it plays crucial roles in many biological processes. However, as a key RNA demethylase, alkylation repair homolog protein 5 (ALKBH5) has not been well studied in human osteosarcoma. The present study sought to explore ALKBH5-mediated m6A modification and the underlying mechanisms in human osteosarcoma. METHODS: The expression of ALKBH5 and its correlation with clinicopathological features were examined by bioinformatics analysis and tissue microarrays. Cellular proliferation was detected by CCK8 assays. Cell cycle and apoptosis were analyzed by TUNEL and Flow cytometry assay. Finally, investigation of the regulatory mechanism of ALKBH5 in human osteosarcoma was performed by MeRIP assay, RNA-sequencing, dual luciferase reporter assay, RNA pull-down and RNA stability assay. Tumor xenograft models were established for in vivo experiments. FINDINGS: Our data showed that low expression of ALKBH5 was associated with worse overall survival for osteosarcoma patients. Reducing m6A mRNA levels in human osteosarcoma cells through ALKBH5 up-regulation lead to cell proliferation inhibition, cell apoptosis and cycle arrest. We identified SOCS3, a negative regulator of STAT3, as a downstream target of ALKBH5-mediated m6A modification. And the m6A modified SOCS3 mRNA was recognized by YTHDF2, which promotes the decay of SOCS3. Mechanistically, our data revealed that ALKBH5 inactivated STAT3 pathway by increasing SOCS3 expression via an m6A-YTHDF2-dependent manner. INTERPRETATION: M6A methylation is rising as a pathway affecting tumorigenicity and tumor progression. Our findings illuminate the clinical significance of ALKBH5-mediated m6A modification in human osteosarcoma and the regulatory mechanisms underlying tumor proliferation and growth, suggesting that ALKBH5 is a potential biomarker for treatment in human osteosarcoma. FUNDING: This work was supported by and Science and Technology foundation of Hubei, China (Grant No.2017CFB762); the Tongji hospital foundation (Grant No.2201103013); and the National Natural Science Foudation of China (No.82002849).


Assuntos
Adenosina/análogos & derivados , Homólogo AlkB 5 da RNA Desmetilase , Neoplasias Ósseas , Osteossarcoma , Proteínas de Ligação a RNA , Fator de Transcrição STAT3 , Adenosina/genética , Homólogo AlkB 5 da RNA Desmetilase/genética , Neoplasias Ósseas/genética , Proliferação de Células/genética , Humanos , Osteossarcoma/genética , RNA/genética , RNA Mensageiro/genética , Proteínas de Ligação a RNA/genética , Fator de Transcrição STAT3/metabolismo
18.
J Gastroenterol Hepatol ; 37(1): 144-153, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34370878

RESUMO

BACKGROUND AND AIM: Colorectal cancer, as a common malignant carcinoma in the gastrointestinal tract, has a high mortality globally. However, the specific molecular mechanisms of long non-coding RNA (lncRNA) thymopoietin antisense transcript 1 (TMPO-AS1) in colorectal cancer were unclear. METHODS: We tested the expression level of TMPO-AS1 via qRT-PCR in colorectal cancer cells, while the protein levels of branched chain amino acid transaminase 1 (BCAT1) and the stemness-related proteins were evaluated by western blot analysis. Colony formation, EdU staining, TUNEL, flow cytometry, and sphere formation assays were to assess the biological behaviors of colorectal cancer cells. Then, luciferase reporter, RIP, and RNA pull down assay were applied for confirming the combination between microRNA-98-5p (miR-98-5p) and TMPO-AS1/BCAT1. RESULTS: TMPO-AS1 was aberrantly expressed at high levels in colorectal cancer cells. Silenced TMPO-AS1 restrained cell proliferation and stemness and promoted apoptosis oppositely, while overexpressing TMPO-AS1 exerted the adverse effects. Furthermore, miR-98-5p was proven to a target of TMPO-AS1 inhibit cell progression in colorectal cancer. Additionally, BCAT1 was proved to enhance cell progression as the target of miR-98-5p, and it offset the effect of silenced TMPO-AS1 on colorectal cancer cells. CONCLUSION: TMPO-AS1 promotes the progression of colorectal cancer cells via sponging miR-98-5p to upregulate BCAT1 expression.


Assuntos
Neoplasias Colorretais , Proteínas Nucleares , RNA Longo não Codificante , Timopoietinas , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Timopoietinas/genética , Timopoietinas/metabolismo , Transaminases/metabolismo
19.
Ying Yong Sheng Tai Xue Bao ; 32(12): 4411-4418, 2021 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-34951282

RESUMO

Northwest China is burdened by declining soil fertility and poor capacity of water and nutrient retention. A pot experiment was conducted to examine the effects of organic acid conditio-ners (OASC) with four application rates (0, 20, 40, and 60 g·kg-1) on soil nutrients and crop growth. Maize and common vetch were the focus crops and loessial soil and irrigated desert soil were the soil types. The results showed that OASC application reduced water evaporation loss and significantly improved soil available nutrient content, with the most obvious effects on soil phosphorus. Available phosphorus content and proportion were increased by 256.5% and 227.4%, respectively, compared with no OASC treatment. The shoot dry weights of maize and common vetch on loessial soil were initially increased with the increasing OASC application rate and were highest at the application rate of 20 g·kg-1. The values progressively decreased with increasing OASC addition rates. Total salt content was significantly increased and the rate of emergence of common vetch decreased at OASC rate exceeding 20 g·kg-1. For irrigated desert soil, the OASC application rate did not affect total salt content when maize was planted. There was significant increase in soil total salt contents when common vetch was planted and at the OASC rate of 60 g·kg-1. The shoot dry weight of common vetch and maize was highest with the OASC application rates at 40 g·kg-1 and 60 g·kg-1, respectively. The optimal OASC rate for planting common vetch and maize on loess soil was 20 g·kg-1. The application rates of 40 g·kg-1 and 60 g·kg-1 were optimal for planting common vetch and maize on irrigated desert, respectively.


Assuntos
Fertilizantes , Solo , Agricultura , China , Fertilizantes/análise , Nitrogênio/análise , Nutrientes , Zea mays
20.
Ying Yong Sheng Tai Xue Bao ; 32(9): 3249-3256, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34658211

RESUMO

We examined the effects of long-term no-tillage sowing with crop stubbles on seedling emergence quality and yield of spring wheat under the three typical spring wheat planting modes of single wheat, wheat-corn intercropping and wheat-soybean intercropping in a long-term field experiment in Hexi oasis irrigated area, aiming to provide theoretical support for the efficient and sustai-nable production of spring wheat. The results showed that, compared with traditional tillage, no-tillage sowing with crop stubbles significantly decreased seedling emergence rate and emergence evenness of spring wheat in wheat-corn intercropping and wheat-soybean intercropping by 3.3%-8.6%, 9.6%-20.5%, 2.9%-8.8%, and 10.7%-61.7%, respectively. Emergence evenness was significantly increased by 14.9% in 2019, while seedling emergence rate was significantly decreased by 4.2% in 2020 under the mode of single wheat compared with traditional tillage. Seedling uniformity of spring wheat seedling stage were reduced under the three typical planting modes, including single wheat, wheat-corn intercropping and wheat-soybean intercropping. Spike number of spring wheat were equal to that of traditional tillage at harvest under the three planting modes of no-tillage sowing with crop stubbles, and the differences were not significant. Effects of seedling emergence rate of spring wheat on yield was weakened by increasing grain number per spike and 1000-grain weight of spring wheat under the three planting modes. Grain yield was significantly increased by 10.3%-12.9% (single wheat), 10.5%-11.9% (wheat-corn intercropping), and 10.3%-22.5% (wheat-soybean intercropping) at harvest, respectively. Our results indicated that no-tillage sowing with crop stubbles was the feasible tillage mode in the production process of spring wheat in Hexi oasis irrigation area with extremely serious farmland wind erosion degradation.


Assuntos
Agricultura , Triticum , Agricultura/métodos , China , Grão Comestível , Zea mays
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