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Soil salinization is a global environmental problem. To investigate the spatiotemporal heterogeneity of soil salinity and the coupling relationship of soil salinity ions under water-saving renovation conditions, we chose Shenwu Irrigation Area, where water-saving renovation projects are being conducted comprehensively. Specifically, for our field experiments, we chose 46 soil sampling points. Specifically, we used different spatial interpolation methods and coupling coordination models were applied to study the spatial and temporal distribution of soil salinity and soil salt-based ion coupling relationship changes during different water-saving periods in the irrigation area between 2015 and 2022. The results showed that (1) the emergence of soil salinity extremes after water-saving renovation project led to an increase in the variability of soil salinity. (2) Compared with the Inverse Distance Weighted, Radial Basis Function, and Universal Kriging interpolations, the Mean Absolute Error of the Ordinary Kriging interpolation was reduced by 12.68 %, 43.96 %, and 38.77 %, the Root Mean Square Error was reduced by 14.34 %, 60.85 %, and 36.53 %, reflective of a significant improvement in accuracy, and thus confirming this method to be optimal for elucidating soil salinity. (3) Compared with pre-water-saving renovation project, the average soil desalination rates in the 0-50 cm soil layer during and after project implementation were 5.71 % and 35.67 %. The impact of the water-saving renovation project was highest in channelside areas, followed by croplands, and lowest in lakeside areas. (4) The growth rates of soil salt-based ion coupling degree and coupling coordination degree after project implementation, compared with before implementation, were 17.07 % and 10.81 %. The implementation of water-saving renovation project improved soil quality. This study provides scientific support for the prevention and control of soil salinization in irrigation areas.
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RNA polymerases (RNAPs) carry out the first step in the central dogma of molecular biology by transcribing DNA into RNA. Despite their importance, much about how RNAPs work remains unclear, in part because the small (3.4 Angstrom) and fast (~40 ms/nt) steps during transcription were difficult to resolve. Here, we used high-resolution nanopore tweezers to observe the motion of single Escherichia coli RNAP molecules as it transcribes DNA ~1,000 times improved temporal resolution, resolving single-nucleotide and fractional-nucleotide steps of individual RNAPs at saturating nucleoside triphosphate concentrations. We analyzed RNAP during processive transcription elongation and sequence-dependent pausing at the yrbL elemental pause sequence. Each time RNAP encounters the yrbL elemental pause sequence, it rapidly interconverts between five translocational states, residing predominantly in a half-translocated state. The kinetics and force-dependence of this half-translocated state indicate it is a functional intermediate between pre- and post-translocated states. Using structural and kinetics data, we show that, in the half-translocated and post-translocated states, sequence-specific protein-DNA interaction occurs between RNAP and a guanine base at the downstream end of the transcription bubble (core recognition element). Kinetic data show that this interaction stabilizes the half-translocated and post-translocated states relative to the pre-translocated state. We develop a kinetic model for RNAP at the yrbL pause and discuss this in the context of key structural features.
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RNA Polimerases Dirigidas por DNA , Escherichia coli , Nanoporos , RNA Polimerases Dirigidas por DNA/metabolismo , RNA Polimerases Dirigidas por DNA/química , RNA Polimerases Dirigidas por DNA/genética , Escherichia coli/metabolismo , Escherichia coli/genética , Transcrição Gênica , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/química , Pinças Ópticas , Cinética , Nucleotídeos/metabolismoRESUMO
D-allose, a rare sugar with anti-oxidant, anti-inflammatory, anti-cancer, immunosuppressing and other physiological functions, has become a research hotspot in recent years. This paper describes the physical and chemical properties, synthesis methods, metabolism, physiological functions, and applications of D-allose, aiming to promote the functional development of D-allose and facilitate the application of D-allose in the food field and clinical treatment.
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Glucose , Glucose/metabolismo , Humanos , Antioxidantes/metabolismo , Anti-Inflamatórios/farmacologia , AnimaisRESUMO
Medical immunology is an important link between basic experiments and clinical applications, and it is also the intersection of many cutting-edge disciplines. At present, there are still limitations in immunology teaching such as single teaching methods and insufficient scientific research training for students. Department of Immunology has implemented practice and exploration of "scientific research back-feeding teaching" in medical immunology course. By incorporating scientific research into teaching activities, the team has carried out teaching practice through scientific research platforms, enriched teaching content with scientific research progress, conducted scientific research activities to stimulate students' interest, which not only increase students' inner drive, improves teaching efficiency, and leads to a "win-win" situation of teaching and scientific research, but also contributes to training medical innovative talents who can shoulder the heavy responsibility of the country.
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Alergia e Imunologia , Ensino , Humanos , Alergia e Imunologia/educação , Educação Médica/métodos , Pesquisa Biomédica/educaçãoRESUMO
Emerging evidence underscores the importance of CD8+ T cells in the pathogenesis of multiple sclerosis (MS), but the precise mechanisms remain ambiguous. This study intends to elucidate the involvement of a novel subset of follicular CD8+ T cells (CD8+CXCR5+ T) in MS and an experimental autoimmune encephalomyelitis (EAE) murine model. The expansion of CD8+CXCR5+ T cells was observed in both MS patients and EAE mice during the acute phase. In relapsing MS patients, higher frequencies of circulating CD8+CXCR5+ T cells were positively correlated with new gadolinium-enhancement lesions in the central nervous system (CNS). In EAE mice, frequencies of CD8+CXCR5+ T cells were also positively correlated with clinical scores. These cells were found to infiltrate into ectopic lymphoid-like structures in the spinal cords during the peak of the disease. Furthermore, CD8+CXCR5+ T cells, exhibiting high expression levels of ICOS, CD40L, IL-21, and IL-6, were shown to facilitate B cell activation and differentiation through a synergistic interaction between CD40L and IL-21. Transferring CD8+CXCR5+ T cells into naïve mice confirmed their ability to enhance the production of anti-MOG35-55 antibodies and contribute to the disease progression. Consequently, CD8+CXCR5+ T cells may play a role in CNS demyelination through heightening humoral immune responses.
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Linfócitos T CD8-Positivos , Encefalomielite Autoimune Experimental , Esclerose Múltipla , Animais , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Camundongos , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/patologia , Humanos , Feminino , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologia , Receptores CXCR5/metabolismo , Masculino , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Adulto , Pessoa de Meia-Idade , Linfócitos B/imunologia , Linfócitos B/metabolismo , Imunoglobulinas/metabolismo , Imunoglobulinas/imunologia , Doenças Desmielinizantes/imunologia , Doenças Desmielinizantes/patologiaRESUMO
Chemoresistance is one of the major hindrances to many cancer therapies, including esophageal squamous cell carcinoma (ESCC). Ferroptosis, a new programmed cell death, plays an essential role in chemoresistance. IQ-domain GTPase activating protein 1 (IQGAP1) is a scaffold protein and functions as an oncogene in various human malignancies. However, the underlying effect and molecular mechanisms of IQGAP1 on paclitaxel (PTX) resistance and ferroptosis in ESCC remain to be elucidated. In this study, we found that IQGAP1 was highly expressed in ESCC tissues and could as a potential biomarker for diagnosis and predicting the prognosis of ESCC. Functional studies revealed that IQGAP1 overexpression reduced the sensitivity of ESCC cells to PTX by enhancing ESCC cell viability and proliferation and inhibiting cell death, and protected ESCC cells from ferroptosis, whereas IQGAP1 knockdown exhibited contrary effects. Importantly, reductions of chemosensitivity and ferroptosis caused by IQGAP1 overexpression were reversed with ferroptosis inducer RSL3, while the increases of chemosensitivity and ferroptosis caused by IQGAP1 knockdown were reversed with ferroptosis inhibitor ferrostatin-1 (Fer-1) in ESCC cells, indicating that IQGAP1 played a key role in resistance to PTX through regulating ferroptosis. Mechanistically, we demonstrated that IQGAP1 overexpression upregulated the expression of Yes-associated protein (YAP), the central mediator of the Hippo pathway. YAP inhibitor Verteporfin (VP) could reverse the effects of IQGAP1 overexpression on ESCC chemoresistance and ferroptosis. Taken together, our findings suggest that IQGAP1 promotes chemoresistance by blocking ferroptosis through targeting YAP. IQGAP1 may be a novel therapeutic target for overcoming chemoresistance in ESCC.
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Resistencia a Medicamentos Antineoplásicos , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Ferroptose , Paclitaxel , Proteínas Ativadoras de ras GTPase , Humanos , Ferroptose/efeitos dos fármacos , Proteínas Ativadoras de ras GTPase/metabolismo , Proteínas Ativadoras de ras GTPase/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Paclitaxel/farmacologia , Proteínas de Sinalização YAP/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacosRESUMO
Prebiotic oligosaccharides have attracted immense interest in the infant formula (IF) industry due to their unique health benefits for infants. There is a need for the reasonable supplementation of prebiotics in premium IF products. Herein, we characterized the profile of galacto-oligosaccharides (GOS) in human milk (HM) and IF using ultrahigh-performance liquid chromatography-cyclic ion mobility-mass spectrometry (UPLC-cIM-MS) technique. Additionally, we further performed a targeted quantitative analysis of five essential HM oligosaccharides (HMOs) in HM (n = 196), IF (n = 50), and raw milk of IF (n = 10) by the high-sensitivity UPLC-MS/MS method. HM exhibited a more abundant and variable HMO composition (1183.19 to 2892.91 mg/L) than IF (32.91 to 56.31 mg/L), whereas IF contained extra GOS species and non-negligible endogenous 3'-sialyllactose. This also facilitated the discovery of secretor features within the Chinese population. Our study illustrated the real disparity in the prebiotic glycome between HM and IF and provided crucial reference for formula improvement.
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Fórmulas Infantis , Leite Humano , Lactente , Humanos , Leite Humano/química , Fórmulas Infantis/química , Prebióticos/análise , Espectrometria de Massa com Cromatografia Líquida , Cromatografia Líquida , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas em Tandem , Oligossacarídeos/químicaRESUMO
Little is known about below-ground competition in mixed-species plantations under increasing nitrogen (N) deposition. This study aims to determine the effects of N addition on root competition in coniferous and broad-leaved species mixed plantations. A pot experiment was conducted using the coniferous species Cunninghamia lanceolata and the broad-leaved species Phoebe chekiangensis planted in mixed plantations with different competition intensities under N addition (0 or 45 kg N ha-1 yr-1). Biomass allocation, root morphology, root growth level, and competitive ability were determined after five months of treatment. Our findings indicated that root interactions in mixed plantations did not influence biomass allocation in either C. lanceolata or P. chekiangensis but promoted growth in C. lanceolata when no N was added. However, N addition decreased biomass accumulation in both species in the mixed plantation and had a negative effect on the root growth of C. lanceolata due to intensified competition. Addition of N increased the relative importance of root predatory competition in P. chekiangensis, and increased the allelopathic competitive advantage in C. lanceolata. This suggests that N addition causes a shift in the root competitive strategy from tolerance to competition. Overall, these findings highlight the significant impact that the addition of N can have on plant interactions in mixed plantations. Our results provide implications for the mechanisms of root competition in response to increasing atmospheric N deposition in mixed plantations.
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Cunninghamia , Nitrogênio , Solo , Biomassa , Cycadopsida , China , CarbonoRESUMO
Cervical cancer (CC) is the most common gynecologic malignancy, which seriously threatens the health of women. Lipid metabolism is necessary for tumor proliferation and metastasis. However, the molecular mechanism of the relationship between CC and lipid metabolism remains poorly defined. We revealed the expression of IGF2BP3 in CC exceeded adjacent tissues, and was positively associated with tumor stage using human CC tissue microarrays. The Cell Counting Kit-8, colony formation assay, 5-ethynyl-2'-deoxyuridine assay, transwell assays, wound-healing assays, and flow cytometry assessed the role of IGF2BP3 in proliferation and metastasis of CC cells. Besides, exploring the molecular mechanism participating in IGF2BP3-driven lipid metabolism used RNA-seq, which determined SCD as the target of IGF2BP3. Further, lipid droplets, cellular triglyceride (TG) contents, and fatty acids were accessed to discover that IGF2BP3 can enhance lipid metabolism in CC. Moreover, RIP assay and methylated RNA immunoprecipitation experiments seeked the aimed-gene-binding specificity. Lastly, the IGF2BP3 knockdown restrained CC growth and lipid metabolism, after which SCD overexpression rescued the influence in vitro and in vivo using nude mouse tumor-bearing model. Mechanistically, IGF2BP3 regulated SCD mRNA m6A modifications via IGF2BP3-METTL14 complex, thereby enhanced CC proliferation, metastasis, and lipid metabolism. Our study highlights IGF2BP3 plays a crucial role in CC progression and represents a therapeutic latent strategy. It is a potential tactic that blocks the metabolic pathway relevant to IGF2BP3 with the purpose of treating CC.
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Neoplasias do Colo do Útero , Animais , Feminino , Humanos , Camundongos , Linhagem Celular Tumoral , Proliferação de Células/genética , Metabolismo dos Lipídeos/genética , Neoplasias do Colo do Útero/patologiaRESUMO
A non-targeted metabolomics approach and sensory evaluation, coupled with multivariate statistical analysis, systematically uncover the impact of the rolling time on the quality parameters of black tea. GC-MS analysis reveals that a moderate extension of rolling time favorably contributes to the accumulation of characteristic aroma components in black tea. The volatile components reach their highest concentration in black tea samples processed during an 80-min rolling period. UHPLC-Q-TOF/MS analysis demonstrates a substantial decrease in the contents of catechins and flavonoids with an increase in rolling time. Simultaneously, the production of theaflavins, coupled with the degradation of green bitterness volatiles (GBVs), significantly contributes to the formation of endogenous aroma components in black tea. These findings underscore the close relationship between rolling time control and black tea quality, emphasizing that a moderate extension of the rolling time fosters the development of improved black tea flavor quality. The comprehensive quality evaluation indicates that the optimal duration is 80 min. However, the initial 0 to 20 min of rolling is a crucial phase for the genesis and transformation of black tea quality. This study offers valuable insights into the influence of rolling time on black tea quality, potentially enhancing future studies of rolling technology. It provides theoretical guidelines for optimizing the processing of Gongfu black tea.
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We performed a bidirectional 2-sample Mendelian randomization (MR) design to explore the causal relation between telomere length (TL) and colorectal polyps. Genome-wide association study summary data of TL and colorectal polyps were extracted from the IEU open genome-wide association study database. Single nucleotide polymorphisms were served as instrumental variables at the significance threshold of Pâ <â 5â ×â 10-8. The inverse variance weighted method, MR-Egger method, and weight median method were performed for causal estimation in MR. Cochran Q test, MR-Egger intercept test, and leave-one-out analyses were performed to evaluate the pleiotropy of the MR results. One hundred and twenty-four single nucleotide polymorphisms were selected as instrumental variables. We found significant casual association between TL and colorectal polyps. Long TL increased the risk of colorectal polyps using the inverse variance weighted method [ukb-a-521: odds ratio (OR): 1.004, 95% confidence interval (CI): 1.001-1.007, Pâ =â .004; ukb-d-D12: OR: 1.008, CI: 1.004-1.012, Pâ <â .001; finn-b-CD2_BENIGN_COLORECANI_EXALLC2: OR: 1.170, CI: 1.027-1.332, Pâ =â .018]. Sensitivity analyses validated that the causality between TL and colorectal polyps was robust. The study provided a causal association between TL and colorectal polyps which indicated that TL might be served as a potential biomarker of colorectal polyps for screening and prevention. Nonetheless, the conclusions need further validation.
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Pólipos do Colo , Humanos , Pólipos do Colo/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Causalidade , TelômeroRESUMO
(1) Background and Purpose: Ebola virus (EBOV) is the causative agent of Ebola virus disease (EVD), which causes extremely high mortality and widespread epidemics. The only glycoprotein (GP) on the surface of EBOV particles is the key to mediating viral invasion into host cells. DNA vaccines for EBOV are in development, but their effectiveness is unclear. The lack of immune characteristics resides in antigenic MHC class II reactivity. (2) Methods: We selected MHC-II molecules from four human leukocyte antigen II (HLA-II) superfamilies with 98% population coverage and eight mouse H2-I alleles. IEDB, NetMHCIIpan, SYFPEITHI, and Rankpep were used to screen MHC-II-restricted epitopes with high affinity for EBOV GP. Further immunogenicity and conservation analyses were performed using VaxiJen and BLASTp, respectively. EpiDock was used to simulate molecular docking. Cluster analysis and binding affinity analysis of EBOV GP epitopes and selected MHC-II molecules were performed using data from NetMHCIIpan. The selective GP epitopes were verified by the enzyme-linked immunospot (ELISpot) assay using splenocytes of BALB/c (H2d), C3H, and C57 mice after DNA vaccine pVAX-GPEBO immunization. Subsequently, BALB/c mice were immunized with Protein-GPEBO, plasmid pVAX-GPEBO, and pVAX-LAMP/GPEBO, which encoded EBOV GP. The dominant epitopes of BALB/c (H-2-I-AdEd genotype) mice were verified by the enzyme-linked immunospot (ELISpot) assay. It is also used to evaluate and explore the advantages of pVAX-LAMP/GPEBO and the reasons behind them. (3) Results: Thirty-one HLA-II-restricted and 68 H2-I-restricted selective epitopes were confirmed to have high affinity, immunogenicity, and conservation. Nineteen selective epitopes have cross-species reactivity with good performance in MHC-II molecular docking. The ELISpot results showed that pVAX-GPEBO could induce a cellular immune response to the synthesized selective peptides. The better immunoprotection of the DNA vaccines pVAX-LAMP/GPEBO coincides with the enhancement of the MHC class II response. (4) Conclusions: Promising MHC-II-restricted candidate epitopes of EBOV GP were identified in humans and mice, which is of great significance for the development and evaluation of Ebola vaccines.
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Background: Meckel Syndrome (MKS, OMIM #249000) is a rare and fatal autosomal recessive ciliopathy with high clinical and genetic heterogeneity. MKS shows complex allelism with other related ciliopathies such as Joubert Syndrome (JBTS, OMIM #213300). In MKS, the formation and function of the primary cilium is defective, resulting in a multisystem disorder including occipital encephalocele, polycystic kidneys, postaxial polydactyly, liver fibrosis, central nervous system malformations and genital anomalies. This study aimed to analyze the genotype of MKS patients and investigate the correlation between genotype and phenotype. Methods: A nonconsanguineous couple who conceived four times with a fetus affected by multiorgan dysfunction and intrauterine fetal death was studied. Whole exome sequencing (WES) was performed in the proband to identify the potentially pathogenic variant. Sanger sequencing was performed in family members. In silico tools were used to analyse the pathogenicity of the identified variants. cDNA TA-cloning sequencing was performed to validate the effects of intronic variants on mRNA splicing. Quantitative real-time PCR was performed to investigate the effect of the variants on gene expression. Immunofluorescence was performed to observe pathological changes of the primary cilium in kidney tissue from the proband. Results: Two splice site variants of TMEM231 (NM_001077418.2, c.583-1G>C and c.583-2_588delinsTCCTCCC) were identified in the proband, and the two variants have not been previously reported. The parents were confirmed as carriers. The two variants were predicted to be pathogenic by in silico tools and were classified as pathogenic/likely pathogenic variants according to the American College of Medical Genetics and Genomics guideline. cDNA TA cloning analysis showed that both splice site variants caused a deletion of exon 5. RT-PCR revealed that the expression of TMEM231 was significantly decreased and immunofluorescence showed that the primary cilium was almost absent in the proband's kidney tissue. Conclusion: We reported the clinical, genetic, molecular and histochemical characterisation of a family affected by MKS. Our findings not only extended the mutation spectrum of the TMEM231 gene, but also revealed for the first time the pathological aetiology of primary cilia in humans and provide a basis for genetic counselling of the parents to their offspring.
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BACKGROUND: This study aimed to utilize an innovative method of integrating the 20 subvolume dose of left ventricle and the Tl-201 single photon emission computed tomography (SPECT) with myocardial perfusion imaging (MPI) parameters in patients with left- and right-sided breast cancer after radiation therapy. METHODS: Female patients with breast cancer underwent SPECT MPI before commencing radiotherapy and 12 months later were enrolled from January 2014 to December 2018. The images of CT simulation and SPECT MPI were integrated into the treatment planning system. The differences of doses and parameters of MPI in all cardiac subvolumes between left- and right-sided breast cancer patients were analyzed. RESULTS: Patients with left-sided breast cancer (n = 61) received a higher radiation dose to the heart, left ventricular, and its territories and subvolumes, compared to patients with right-sided breast cancer (n = 19). The 20-segment analysis also showed statistically significant disparities in the average radiation doses received by the two groups. In different coronary artery territories, the end-diastolic perfusion and end-systolic perfusion showed a decrease in both sides, with no significant differences. However, the wall motion and wall thickening showed a significant decline in subregions within the left- and right-sided coronary artery territories. CONCLUSION: This study demonstrates an innovative integrated method combining the left ventricular 20 regional doses with SPECT MPI which shows that left-sided breast cancer patients receive a higher subvolume dose than right-sided breast cancer patients. Further research is needed to confirm the potential impact on heart function after radiotherapy on both sides.
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Neoplasias da Mama , Imagem de Perfusão do Miocárdio , Neoplasias Unilaterais da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/radioterapia , Radioisótopos de Tálio , Imagem de Perfusão do Miocárdio/métodosRESUMO
This study fristly investigated the taste quality formation and leaf conducting tissue changes in six types of Chinese tea (green, black, oolong, yellow, white, and dark) made from Mingke No.1 variety. Non-targeted metabolomics showed the vital manufacturing processes (green tea-de-enzyming, black tea-fermenting, oolong tea-turning-over, yellow tea-yellowing, white tea-withering, and dark tea-pile-fermenting) were highly related to their unique taste formation, due to different fermentation degree in these processes. After drying, the retained phenolics, theanine, caffeine, and other substances significantly impacted each tea taste quality formation. Meanwhile, the tea leaf conducting tissue structure was significantly influenced by high processing temperature, and the change of its inner diameter was related to moisture loss during tea processing, as indicated by its significant different Raman characteristic peaks (mainly cellulose and lignin) in each key process. This study provides a reference for process optimization to improve tea quality.
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Adjuvant breast radiotherapy could reduce the risk of local recurrence. However, the radiation dose received by the heart also increases the risk of cardiotoxicity and causes consequential heart diseases. This prospective study aimed to evaluate more precisely cardiac subvolume doses and corresponding myocardial perfusion defects according to the American Heart Association (AHA)'s 20-segment model for single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) interpretation for breast cancer after radiotherapy. The 61 female patients who underwent adjuvant radiotherapy following breast cancer surgery for left breast cancer were enrolled. SPECT MPI were performed before radiotherapy for baseline study, and 12 months after for follow-up. Enrolled patients were divided into two groups, new perfusion defect (NPD) and non new perfusion defect found (non-NPD) according to myocardial perfusion scale score. CT simulation data, radiation treatment planning, and SPECT MPI images were fused and registered. The left ventricle was divided into four rings, three territories, and 20 segments according to the AHA's 20-segment model of the LV. The doses between NPD and non-NPD groups were compared by the Mann-Whitney test. The patients were divided into two groups: NPD group (n = 28) and non-NPD group (n = 33). The mean heart dose was 3.14 Gy in the NPD group and 3.08 Gy in the non-NPD group. Mean LV doses were 4.84 Gy and 4.71 Gy, respectively. The radiation dose of the NPD group was higher than the non-NPD group in the 20 segments of LV. There was significant difference in segment 3 (p = 0.03). The study indicated that the radiation doses to 20 segments of LV in NPD were higher than those in non-NPD significantly at segment 3, and higher in other segments in general. In the bull's eye plot combining radiation dose and NPD area, we found that the new cardiac perfusion decline may exist even in the low radiation dose region.Trial registration: FEMH-IRB-101085-F. Registered 01/01/2013, https://clinicaltrials.gov/ct2/show/NCT01758419?cond=NCT01758419&draw=2&rank=1 .
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Neoplasias da Mama , Feminino , Humanos , Mama , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Coração/diagnóstico por imagem , Perfusão , Estudos ProspectivosRESUMO
Objective To investigate the effect of insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) on the proliferation, migration and tumor immune microenvironment of colorectal cancer cells and its possible molecular mechanism. Methods The Cancer Genome Atlas (TCGA) database was used to analyze the expression levels of IGF2BP2 and MYC in colorectal cancer and adjacent tissues. The expression of IGF2BP2 in HCT-116 and SW480 human colorectal cancer cells was silenced by RNA interference (RNAi), and the silencing effect was detected by quantitative real-time PCR. After knocking down IGF2BP2, colony formation assay, CCK-8 assay and 5-ethynyl-2'-deoxyuridine (EdU) assay were employed to detect cell colony formation and proliferation ability. TranswellTM assay was used to detect cell migration ability. Quantitative real-time PCR was used to detect the mRNA expression of IGF2BP2, MYC, tumor necrosis factor-α (TNF-α), transforming growth factor-ß (TGF-ß) and interleukin-10 (IL-10). The protein expression of IGF2BP2 and MYC was detected by western blot. The binding ability of IGF2BP2 and MYC in HCT-116 cells was detected by quantitative real-time PCR after RNA immunoprecipitation. Results The results of TCGA database showed that the expression of IGF2BP2 and MYC in colorectal cancer tissues was significantly higher than that in adjacent tissues, and the survival time of colorectal cancer patients with high expression of IGF2BP2 was shorter. After silencing IGF2BP2, the viability, proliferation and migration of HCT-116 and SW480 cells were decreased. The mRNA expression of MYC, TGF-ß and IL-10 in IGF2BP2 knockdown group was significantly decreased, while the expression of TNF-α mRNA was increased. The expression of MYC protein and the stability of MYC mRNA were significantly decreased. RIP-qPCR results showed that IGF2BP2 could bind to MYC mRNA. Conclusion Knockdown of IGF2BP2 inhibits colorectal cancer cell proliferation, migration and promotes tumor immunity by down-regulating MYC expression.
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Neoplasias Colorretais , Proteínas Proto-Oncogênicas c-myc , Proteínas de Ligação a RNA , Humanos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica , Interleucina-10/metabolismo , RNA Mensageiro , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Fator de Crescimento Transformador beta/genética , Microambiente Tumoral/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismoRESUMO
BACKGROUND: Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive system, ranking third for morbidity and mortality worldwide. At present, no effective control method is available for this cancer type. In tumor cells, especially iron metabolization, is necessary for its growth and proliferation. High levels of iron are an important feature to maintain tumor growth; however, the overall mechanism remains unclear. METHODS: We used western blotting, immunohistochemistry (IHC) and real-time quantitative PCR to analyze the expression of IGF2BP2 in cell lines and tissues. Further, RNA-sequencing, RNA immunoprecipitation and methylated RNA immunoprecipitation experiments explored the specific binding of target genes. Moreover, the RNA stability assay was performed to determine the half-life of genes downstream of IGF2BP2. In addition, the Cell Counting Kit-8, colony formation assay, 5-ethynyl-2'-deoxyuridine assay and flow cytometry were used to evaluate the effects of IGF2BP2 on proliferation and iron metabolism. Lastly, the role of IGF2BP2 in promoting CRC growth was demonstrated in animal models. RESULTS: We observed that IGF2BP2 is associated with iron homeostasis and that TFRC is a downstream target of IGF2BP2. Further, overexpression of TFRC can rescue the growth of IGF2BP2-knockdown CRC cells. Mechanistically, we determined that IGF2BP2 regulates TFRC methylation via METTL4, thereby regulating iron metabolism and promoting CRC growth. Furthermore, using animal models, we observed that IGF2BP2 promotes CRC growth. CONCLUSION: IGF2BP2 regulates TFRC mRNA methylation via METTL4, thereby regulating iron metabolism and promoting CRC growth. Our study highlights the key roles of IGF2BP2 in CRC carcinogenesis and the iron transport pathways.
Assuntos
Neoplasias Colorretais , Animais , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Proliferação de Células/genética , Carcinogênese/genética , RNA , Regulação Neoplásica da Expressão GênicaRESUMO
Nearly half a million women are diagnosed with cervical cancer (CC) each year, with the incidence of CC stabilizing or rising in low-income and middle-income countries. Cancer cells use metabolic reprogramming to meet the needs of rapid proliferation, known as the Warburg effect, but the mechanism of the Warburg effect in CC remains unclear. microRNAs (miRNAs) have a wide range of effects on gene expression and diverse modes of action, and they regulate genes for metabolic reprogramming. Dysregulation of miRNA expression leads to metabolic abnormalities in tumor cells and promotes tumorigenesis and tumor progression. In this study, we found that miR-145 was negatively correlated with metabolic reprogramming-related genes and prevented the proliferation and metastasis of CC cell lines by impeding aerobic glycolysis. A dual-luciferase reporter assay showed that miR-145 can bind to the 3'-untranslated region (3'-UTR) of MYC. Chromatin Immunoprecipitation-quantitative real-time PCR indicated that MYC was involved in the regulation of glycolysis-related genes. In addition, miR-145 mimics significantly suppressed the growth of CC cell xenograft tumor, prolonged the survival time of mice, and dramatically silenced the expression of tumor proliferation marker Ki-67. Therefore, the results suggested that miR-145 affects aerobic glycolysis through MYC, which may be a potential target for the treatment of CC.
Assuntos
MicroRNAs , Neoplasias do Colo do Útero , Humanos , Feminino , Animais , Camundongos , Linhagem Celular Tumoral , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Biomarcadores Tumorais/metabolismo , Proliferação de Células/genética , Glicólise/genética , Regulação Neoplásica da Expressão GênicaRESUMO
OBJECTIVE: In this research, the influence of breviscapine on anxiety, fear elimination, and aggression and the potential mechanism was investigated. METHODS: Anxiety and locomotion were analyzed by elevated plus maze and open field test in mice. Bussey-Saksida Mouse Touch Screen Chambers were used to perform fear conditioning. Territorial aggression was assessed by resident intruder test. Protein levels were evaluated by Western blot. Breviscapine improved fear-extinction learning in BALB/cJ mice. RESULTS: Breviscapine at 20-100 mg/kg increased center cross number, total distance traveled, and velocity in a dose-dependent manner. On the other hand, breviscapine at 20-100 mg/kg decreased the immobility time in open field test. In addition, breviscapine at 20-100 mg/kg increased the ratio of time on the open arm, time on the distal parts of the open arm, and total distance traveled in elevated plus maze. Breviscapine at 100 mg/kg increased the average attack latency and decreased the number of attacks over the last 3 days of resident intruder test. In hippocampus, protein levels of postsynaptic density protein-95 and synaptophysin were elevated by breviscapine at these three doses. CONCLUSION: The administration of breviscapine alleviates fear extinction, anxiety, and aggression, while increases locomotor in a dose-dependent manner, which might be associated with its influence on synaptic function.