Bladder cancer (BLCA), particularly due to the high recurrence and progression rates of non-muscle-invasive bladder cancer (NMIBC), is a significant global health challenge. Current treatments, such as Bacillus Calmette-Guérin (BCG) immunotherapy and intravesical chemotherapy, often cause substantial side effects and exhibit limited efficacy, highlighting the urgent need for novel therapeutic strategies. Single-cell spatial transcriptomic advancements have identified cuproptosis as a critical pathway in BLCA, presenting a promising target for treatment. In this study, these insights were leveraged to design Cu-VT nanoparticles (NPs), an innovative composite material that combines the unique properties of copper ions and the natural flavonoid vitexin, to induce cuproptosis. Cu-VT NPs could effectively induce apoptosis and oxidative stress in BLCA cells concurrently modulating the immune response within the tumor microenvironment. Comprehensive in vitro and in vivo experiments demonstrated that Cu-VT NPs significantly inhibited tumor growth and reduced lung metastasis through cuproptosis induction. This dual-function composite material enhances therapeutic efficacy and minimizes side effects, showcasing its potential as a revolutionary treatment for BLCA. Our findings highlight the transformative potential of Cu-VT NPs in the context of BLCA treatment, establishing a new paradigm in the use of composite materials for the treatment of advanced cancer.
Bladder cancer (BC) is a common malignancy in males, and currently lacks ideal therapeutic approaches. Exploring emerging therapeutic targets from the perspective of endogenous peptides to improve the prognosis of bladder cancer patients holds promise. In this study, we have identified CTSGDP-13, a novel endogenous peptide, which demonstrates potential anti-cancer effects in BC. Our findings reveal that CTSGDP-13 can promote ferroptosis in BC cells, both in vitro and in vivo, leading to the inhibition of BC progression. Furthermore, we have identified TRIM25 as a downstream regulatory target of CTSGDP-13. The expression of TRIM25 is significantly upregulated in BC, and its inhibition of ferroptosis promotes BC progression. Mechanistic studies have shown that CTSGDP-13 promotes the ubiquitination and subsequent degradation of TRIM25 by disrupting its interaction with the deubiquitinase USP7. Further investigations indicate that CTSGDP-13 promotes ferroptosis in BC by regulating the USP7/TRIM25/KEAP1 axis. The elucidation of the functional mechanisms of natural CTSGDP-13 and TRIM25 holds promise in providing valuable therapeutic targets for BC diagnosis and treatment.
AbstractBackgroundRecurrent bladder cancer is the most common type of urinary tract malignancy; nevertheless, the mechanistic basis for its recurrence is uncertain. Innovative technologies such as single‐cell transcriptomics and spatial transcriptomics (ST) offer new avenues for studying recurrent tumour progression at the single‐cell level while preserving spatial data.MethodThis study integrated single‐cell RNA (scRNA) sequencing and ST profiling to examine the tumour microenvironment (TME) of six bladder cancer tissues (three from primary tumours and three from recurrent tumours).FindingsscRNA data‐based ST deconvolution analysis revealed a much higher tumour heterogeneity along with TME in recurrent tumours than in primary tumours. High‐resolution ST analysis further identified that while the overall natural killer/T cell and malignant cell count or the ratio of total cells was similar or even lower in the recurrent tumours, a higher interaction between epithelial and immune cells was detected. Moreover, the analysis of spatial communication reveals a marked increase in activity between cancer‐associated fibroblasts (CAFs) and malignant cells, as well as other immune cells in recurrent tumours.InterpretationWe observed an enhanced interplay between CAFs and malignant cells in bladder recurrent tumours. These findings were first observed at the spatial level.
Transurethral resection of bladder tumor (TURBT) is the first-line treatment option for non-muscle invasive bladder cancer (NMIBC), but residual tumor often remains after TURBT, thereby leading to cancer recurrence. Here, we introduce combined use of in vivo Raman spectroscopy and in vivo cryoablation as a new approach to detect and remove residual bladder tumor during TURBT. Bladder cancer (BCa) patients treated with TURBT at our urological department between Dec 2019 and Jan 2021 were collected. First, Raman signals were collected from 74 BCa patients to build reference spectra of normal bladder tissue and of bladder cancers of different pathological types. Then, another 53 BCa patients were randomly categorized into two groups, 26 patients accepted traditional TURBT, 27 patients accepted TURBT followed by Raman scanning and cryoablation if Raman detected existence of residual tumor. The recurrence rates of the two groups until Oct 2022 were compared. Raman was capable of discriminating normal bladder tissue and BCa with a sensitivity and specificity of 90.5% and 80.8 %; and discriminating invasive (T1, T2) and noninvasive (Ta) BCa with a sensitivity and specificity of 83.3 % and 87.3 %. During follow-up, 2 in 27 patients had cancer recurrence in Raman-Cryoablation group, while 8 in 26 patients had cancer recurrence in traditional TURBT group. Combined use of Raman and cryoablation significantly reduced cancer recurrence (p = 0.0394). Raman and cryoablation can serve as an adjuvant therapy to TURBT to improve therapeutic effects and reduce recurrence rate.
Background: Melatonin is a neurohormone involved in diverse physiological processes, including regulation of circadian rhythm, oncogenesis and immune function. More attention are focused on the molecular events surrounding the occurrence of abnormally expressed lncRNAs leading to breast cancer. The purpose of this study was to evaluate the role of melatonin-related lncRNAs in the clinical management of BRCA patients and their immune responses. Methods: The transcriptome data and clinical data of BRCA patients were acquired from TCGA database. A total of 1103 patients were randomly assigned to either training set or validation set. A melatoninrelated lncRNA signature was constructed in the training set and verified in the validation set. Functional analysis, immune microenvironment and drug resistance analysis associated to melatonin-related lncRNAs were performed by utilizing GO&KEGG, ESTIMATE and TIDE analysis. A nomogram based on the signature score and clinical characteristics was established, which was calibrated to increase prediction probability of 1-year, 3-year and 5-year survival for BRCA patients. Results: BRCA patients were divided into two signature groups based on a 17-melatonin-related lncRNA signature. High-signature patients had worse prognosis than low-signature patients (p < 0.001). Univariate and multivariate Cox regression analysis proved that the signature score was an independent prognostic factor for BRCA patients. Functional analysis indicated that high-signature BRCA involved in regulation of processing and maturation of mRNA and misfolded protein response. Remarkably, immune microenvironment analysis showed that the proportion of tumor-infiltrating M2 macrophage and the expression of CTLA4 were significantly higher in high-signature BRCA. The calibration curves for the probability of invasive BRCA showed optimal agreement between the probability as predicted by the nomogram and the actual probability. Conclusions: A novel melatonin-related lncRNA signature was considered as an independent prognostic indicator for BRCA patients. Melatonin-related lncRNAs were potentially associated with tumor immune microenvironment and might be therapeutic targets for BRCA patients. (c) 2023 Asian Surgical Association and Taiwan Robotic Surgery Association. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).
We have previously demonstrated abnormal gut microbial composition in castration-resistant prostate cancer (CRPC) patients, here we revealed the mechanism of gut microbiota-derived short-chain fatty acids (SCFAs) as a mediator linking CRPC microbiota dysbiosis and prostate cancer (PCa) progression. By using transgenic TRAMP mouse model, PCa patient samples, in vitro PCa cell transwell and macrophage recruitment assays, we examined the effects of CRPC fecal microbiota transplantation (FMT) and SCFAs on PCa progression. Our results showed that FMT with CRPC patients' fecal suspension increased SCFAs-producing gut microbiotas such as Ruminococcus, Alistipes, Phascolarctobaterium in TRAMP mice, and correspondingly raised their gut SCFAs (acetate and butyrate) levels. CRPC FMT or SCFAs supplementation significantly accelerated mice's PCa progression. In vitro, SCFAs enhanced PCa cells migration and invasion by inducing TLR3-triggered autophagy that further activated NF-κB and MAPK signalings. Meanwhile, autophagy of PCa cells released higher level of chemokine CCL20 that could reprogramme the tumor microenvironment by recruiting more macrophage infiltration and simultaneously polarizing them into M2 type, which in turn further strengthened PCa cells invasiveness. Finally in a cohort of 362 PCa patients, we demonstrated that CCL20 expression in prostate tissue was positively correlated with Gleason grade, pre-operative PSA, neural/seminal vesical invasion, and was negatively correlated with post-operative biochemical recurrence-free survival. Collectively, CRPC gut microbiota-derived SCFAs promoted PCa progression via inducing cancer cell autophagy and M2 macrophage polarization. CCL20 could become a biomarker for prediction of prognosis in PCa patients. Intervention of SCFAs-producing microbiotas may be a useful strategy in manipulation of CRPC.
Metabolism vulnerability of cisplatin resistance in BCa cells remains to be discovered, which we applied integrated multi-omics analysis to elucidate the metabolism related regulation mechanism in bladder cancer (BCa) microenvironment. Integrated multi-omics analysis of metabolomics and proteomics revealed that MAT2A regulated methionine metabolism contributes to cisplatin resistance in BCa cells. We further validated MAT2A and cancer stem cell markers were up-regulated and circARHGAP10 was down-regulated through the regulation of MAT2A protein stability in cisplatin resistant BCa cells. circARHGAP10 formed a complex with MAT2A and TRIM25 to accelerate the degradation of MAT2A through ubiquitin-proteasome pathway. Knockdown of MAT2A through overexpression of circARHGAP10 and restriction of methionine up-take was sufficient to overcome cisplatin resistance in vivo in immuno-deficiency model but not in immuno-competent model. Tumor-infiltrating CD8+ T cells characterized an exhausted phenotype in tumors with low methionine. High expression of SLC7A6 in BCa negatively correlated with expression of CD8. Synergistic inhibition of MAT2A and SLC7A6 could overcome cisplatin resistance in immuno-competent model in vivo. Cisplatin resistant BCa cells rely on methionine for survival and stem cell renewal. circARHGAP10/TRIM25/MAT2A regulation pathway plays an important role in cisplatin resistant BCa cells while circARHGAP10 and SLC7A6 should be evaluated as one of the therapeutic target of cisplatin resistant BCa.
To feed the growing human population, natural grasslands are being converted to agricultural use at a massive scale. This conversion may have consequences for soil biodiversity, but its impact on the community assembly of differentially microbial groups remains largely unknown. Here, we selected the three typical land-use types: grassland, arable land (formerly grassland), and forest (formerly grassland) in the Songnen Plain, Northeastern China. Illumina MiSeq high-throughput sequencing technology based on bacterial 16S rRNA and fungal ITS rRNA was used to study the community structures and diversities of soil bacteria and fungi and to explore the drivers of these changes. The results showed that bacterial community diversity did not change after grassland conversion to forest and arable land, but affected bacterial community abundance at the phylum level. Actinomycetes and Proteobacteria were significantly reduced, Acidobacteria were significantly increased, and Gemmatimonadetes and Bacteroidetes were the most abundant in arable land. Land conversion had significant effects on both fungal community diversity and abundance. After the grassland was converted into forest, the fungal community diversity decreased, but the community abundance increased significantly, the Ascomycetes decreased significantly, and Basidiomycetes became the dominant phylum, especially white rot fungi. Interestingly, the fungal community diversity and community abundance increased significantly after grassland was converted to arable land, and the abundance of Zygomycota increased significantly but the dominant phylum was still Ascomycetes. Canonical correlation analysis (CCA) showed pH, MC, NO3−-N, TP, AP, and other soil factors are important factors affecting the composition of microbial communities. In the soil of this study area, the composition of bacterial communities is mainly driven by changes in pH and soil texture, and the composition of fungal communities is most closely related to changes in soil nutrient utilization. Changes in land-use patterns have an effect on the structure and diversity of microbial communities by changing the physical and chemical properties of the soil.
Several studies have found that pathological imbalance of alterative splicing (AS) events is associated with cancer susceptibility. carcinogenicity. Nevertheless, the relationship between heritable variation in AS events and carcinogenicity has not been extensively explored. Here, we downloaded AS event signatures, transcriptome profiles, and matched clinical information from The Cancer Genome Atlas (TCGA) database, identified the prognostic AS-related events via conducting the univariate Cox regression algorism. Subsequently, the prognostic AS-related events were further reduced by the least absolute shrinkage and selection operator (LASSO) logistic regression model, and employed for constructing the risk model. Single-sample (ssGSEA), ESTIMATE, and the CIBERSORT algorithms were conducted to evaluate tumor microenvironment status. CCK8, cell culture scratch, transwell invasion assays and flow cytometry were conducted to confirm the reliability of the model. We found 2751 prognostic-related AS events, and constructed a risk model with seven prognostic-related AS events. Compared with high-risk score patients, the overall survival rate of the patients with low-risk score was remarkably longer. Besides, we further found that risk score was also closely related to alterations in immune cell infiltration and immunotherapeutic molecules, indicating its potential as an observation of immune infiltration and clinical response to immunotherapy. In addition, the downstream target gene (DYM) could be a promising prognostic factor for bladder cancer. Our investigation provided an indispensable reference for ulteriorly exploring the role of AS events in the tumor microenvironment and immunotherapy efficiency, and rendered personalized prognosis monitoring for bladder cancer.
Background: Considering the heterogeneity and complexity of epigenetic regulation in bladder cancer, the underlying mechanisms of global DNA methylation modification in the immune microenvironment must be investigated to predict the prognosis outcomes and clinical response to immunotherapy. Methods: We systematically assessed the DNA methylation modes of 985 integrated bladder cancer samples with the unsupervised clustering algorithm. Subsequently, these DNA methylation modes were analyzed for their correlations with features of the immune microenvironment. The principal analysis algorithm was performed to calculate the DMRscores of each samples for qualification analysis. Findings: Three DNA methylation modes were revealed among 985 bladder cancer samples, and these modes are related to diverse clinical outcomes and several immune microenvironment phenotypes, e.g., immune-desert, immune-inflamed, and immune-excluded ones. Then patients were classified into high- and low-DMRscore subgroups according to the DMRscore, which was calculated based on the expression of DNA methylation related genes (DMRGs). Patients with the low-DMRscore subgroup presented a prominent survival advantage that was significantly correlated to the immune-inflamed phenotype. Further analysis revealed that patients with low DMRscores exhibited less TP53 wild mutation, lower cancer stage and molecular subtypes were mainly papillary subtypes. In addition, an independent immunotherapy cohort confirmed that DMRscore could serve as a signature to predict prognosis outcomes and immune responses. Conclusion: Global DNA methylation modes can be used to predict the immunophenotypes, aggressiveness, and immune responses of bladder cancer. DNA methylation status assessments will strengthen our insights into the features of the immune microenvironment and promote the development of more effective treatment strategies.
Atrazine is still widely used in China. Atrazine residue (1.86-1 100 mg/kg) in the soil has exceeded the allowable limit (1.0 mg/kg), affecting soil structure and soil aggregate composition. To understand the long-term application of atrazine on soil aggregates and the binding agent, four treatments were established in cornfield planted since 1998, including without atrazine applied (AT0), atrazine applied (28% atrazine, 1 200-1 350 mL/ha/year) once a year from 2012 to 2018 (AT6, 167 mg/kg), from 2008 to 2018 (AT10, 127.64 mg/kg) as well as from 2002 to 2018 (AT16, 102 mg/kg) with three replications. Along with the increase of atrazine application time, the mass fraction of soil aggregates > 5 mm and 2-5 mm decreased significantly while the mass fraction of soil aggregates 0.5-2 mm and < 0.5 mm increased gradually, and the change of aggregate binding agents contents were the same as that of aggregates. The contents of soil organic carbon (SOC) and glomalin-related soil protein (GRSP) in the aggregates > 5 mm and 2-5 mm were significantly negatively correlated with the years of atrazine application. Our results show that although atrazine residue in the soil does not increase with the increased yearly application, its concentration is still markedly higher than the permitted limit value and seriously affected the content of SOC and GRSP of aggregates > 2 mm, which can lead to a decrease of soil aggregate stability and soil quality.
Gut microbiota dysbiosis is related to cancer development and progression. Our previous study showed that Ruminococcus was more abundant in CRPC (Castration-resistant prostate cancer) than HSPC (Hormone-sensitive prostate cancer) individuals. Here, we determined the potential mechanism of microbiota dysbiosis in prostate cancer (PCa) progression. Metagenomics was used to verify the gut microbial discrepancies between CRPC and HSPC individuals. Fecal microbiota transplantation (FMT) was performed by transferring the fecal suspension of CRPC or HSPC individuals to TRAMP mice. Afterwards, the mice’s prostate histopathology and gut microbiota composition were determined. Since Ruminococcus was demonstrated to correlate with phospholipid metabolism, we used lipidomics to examine the mice’s fecal lipid profiles. The expression of LPCAT1 the key enzyme for phospholipid remodeling in mice prostate was also examined. Meanwhile, both microbial functions prediction and LPCAT1 GSEA analysis (Gene Set Enrichment Analysis) indicated DNA repair pathways, we further determined the expressions of RAD51 and DNA-PKcs in mice prostate. The results showed that gut Ruminococcus was significantly more abundant in CRPC individuals. FMT using CRPC feces accelerated mice’s PCa progression and increased their gut Ruminococcus abundance. Majority of fecal lipids including lysophosphatidylcholine and phosphatidylcholine were upregulated in CRPC FMT treated mice, accompanied with enhanced expressions of LPCAT1, RAD51, and DNA-PKcs in mice prostate. We reported an abundant colonization of Ruminococcus in the gut of CRPC individuals and mice receiving their fecal suspensions, and revealed the promotive capability of Ruminococcus in PCa progression via upregulating LPCAT1 and DNA repair protein expressions. The bacterium and its downstream pathways may become the targets of therapies for PCa in the future.
Background: Forkhead box protein f1 (Foxf1) is associated with oncogenesis, and maybe play a key role in prostate cancer. However, the effect of Foxf1 on the development of prostate cancer and its clinical implications were still unknown. Method: The transcriptome data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). The differential co-expression genes which were the most closely correlated with prostate cancer were identified by weighted gene co-expression network analysis (WGCNA) and differential expression analysis method. The univariate cox regressions were performed to identify the prognostic genes. Finally, Foxf1 were verified in clinical tumor samples and matched normal tissues. Results: A total of 108 differential co-expression genes were identified. Foxf1 was identified that significantly associated with overall survival rate and biochemical recurrence of prostate. Then, protein-protein interaction (PPI) networks were constructed, including 21 nodes and 26 edges. The data revealed GAPVD1, MIR522, MIR937, CPS1, HOXB9, FUBP3, MIR936, SDF4, SATB2, HOXB13, MIR375, PUSL1, SATB1, MIR382, MIR429, HOXD13, PRSS50, FLNC, STRBP, KHSRP were significant associated with the regulation and function of differentially expressed Foxf1 in prostate. The experimental results confirmed the Foxf1 were downregulated in the prostate cancer tissues compared with the matched normal tissues. Conclusion: we obtained a gene Foxf1 which is significantly related with the prognosis of prostate cancer, Foxf1 have significant values in predicting the patients’ Overall survival and may serve as a potential prognosis biomarker and a new therapeutic target of prostate cancer.
We aimed to develop a noninvasive radiomics approach to reveal the m6A methylation status and predict survival outcomes and therapeutic responses in patients. A total of 25 m6A regulators were selected for further analysis, we confirmed that expression level and genomic mutations rate of m6A regulators were significantly different between cancer and normal tissues. Besides, we constructed methylation modification models and explored the immune infiltration and biological pathway alteration among different models. The m6A subtypes identified in this study can effectively predict the clinical outcome of bladder cancer (including m6AClusters, geneClusters, and m6Ascore models). In addition, we observed that immune response markers such as PD1 and CTLA4 were significantly corelated with the m6Ascore. Subsequently, a total of 98 obtained digital images were processed to capture the image signature and construct image prediction models based on the m6Ascore classification using a radiomics algorithm. We constructed seven signature radiogenomics models to reveal the m6A methylation status, and the model achieved an area under curve (AUC) degree of 0.887 and 0.762 for the training and test datasets, respectively. The presented radiogenomics models, a noninvasive prediction approach that combined the radiomics signatures and genomics characteristics, displayed satisfactory effective performance for predicting survival outcomes and therapeutic responses of patients. In the future, more interdisciplinary fields concerning the combination of medicine and electronics remains to be explored.
Background : To study the impact of land-use change on soil microbial community structure and diversity in Northeast China, three typical land-use types (plough, grassland, and forest), grassland change to forest land and grassland change to plough, in the Qiqihar region of Heilongjiang Province were taken as research objects. Methods : MiSeq high-throughput sequencing technology based on bacterial 16S rRNA and fungal ITS rRNA was used to study the above community structure of soil bacteria and fungi and to explore the relationship between soil bacteria and soil environmental factors. Results : The results showed that the dominant bacterial phyla changed from Actinobacteria to Acidobacteria , the dominant fungal phyla changed from Ascomycetes to Basidiomycetes , and the ECM functional group increased significantly after the grassland was completely changed to forest land. After the grassland was changed to plough, the dominant phyla changed from Actinomycetes to Proteobacteria . The functional groups of pathogens and parasites increased significantly. There was no significant difference in the diversity of soil bacterial communities, and the diversity of fungal communities increased significantly. CCA showed that pH, MC, NO 3 - -N, TP and AP of soil were important factors affecting the composition of soil microbial communities, and changes in land-use patterns changed the physical and chemical properties of soils, thereby affecting the structure and diversity of microbial communities. Conclusions : Our research results clarify the impact of changes in land use on the characteristics of soil microbial communities and provide basic data on the healthy use of land.
Atrazine has been used on Chinese farmlands for a long time and over a wide range. The concentration of atrazine (1.86-1100 mg kg(-1)) has exceeded the allowable limit in the soil (1.0 mg kg(-1)), and concern is increasing about the potential harm to farmland soil. Four treatments (AT0, AT 6, AT10, AT16) were established to reveal the effects of the long-term application of atrazine on soil health. The results showed a nonlinear regulation of the atrazine residue concentrations in the four treatments. The highest concentration of atrazine residue was in AT6, at 167 mg kg(-1), and the lowest concentration of atrazine residue was in AT16, at 102 mg kg(-1), but there was no significant difference between AT10 and AT16. The soil urease activity decreased significantly with the increase in the years of atrazine application, the saccharase and cellulase activities in the AT6 were significantly higher than those observed in the other three treatments, the catalase activity gradually decreased with the increase in atrazine application years, and the activity in AT6 was significantly higher than that in AT16. A total of 238 genera were identified by Illumina MiSeq sequencing, and 28 dominant genera were screened. Atrazine significantly increased the relative abundance of Actinobacteria and contributed to the relative abundance of Rubrobacter, Blastococcus, Promicromonospora, Jiangella, Psychroglaciecola and Acetobacteraceae_uncultured, which exhibited significantly higher abundance in AT16 than in AT0. Although there were atrazine-degrading bacteria in the soil, and the atrazine residue decreased with the increase in application years, the concentration of the atrazine residue was still nearly 100 times higher than the allowable limit in the soil, which is a great threat to the soil health. (C) 2020 Elsevier Ltd. All rights reserved.
Objective: Obesity resulting from high-fat diets has a close relationship with the morbidity and mortality associated with Prostate cancer (PCa) in males. The anti-cancer role of Icaritin (ICT, a traditional Chinese herbal medicine) has been reported in several types of cancer including PCa. Adipokines are novel adipocyte-specific secretory protein, which plays a key role in the development of various diseases including obesity, diabetes, atherosclerosis, and cancer. However, the function of ICT and the molecular mechanisms underlying its role in PCa regression through modulation of adipokines have not been studied. Here, we assessed the anti-cancer properties of ICT under the influence of human epidermal growth factor receptor type 2 (HER2) pathway modulating adipokines in obese PCa models. Materials and Methods: In this study, we used transgenic adenocarcinoma of mouse prostate (TRAMP), a well-established animal model for the study of PCa pathogenesis. All the animals were fed on a high-fat diet (HFD with 40% fat) and divided into two groups, one received ICT solution of 30 mg/kg body bwt (i.p) while the other group served as control without any ICT treatment. The mortality rate, tumor formation and fat ratio were assessed by histopathological and magnetic resonance analysis at different time points of 20th, 24th and 28th weeks. The protein expression of HER2 and serum levels of adipokines were measured using western blotting, IHC and multiplex immunoassays. The PCa grade in 12 TRAMP mice were longitudinally evaluated to visualize PCa development and progression upon post-surgery using PET/CT scanning. Results: We observed that ICT treatment significantly reduces the total mortality rate of TRAMP mice (p = 0.045) and the percentage of prostate intraepithelial neoplasia (PIN) or PCa (p = 0.029). Interestingly, significantly decreased levels of leptin (p = 0.006 @20th wk) and the elevated levels of adiponectin (p = 0.030 @20th wk) were observed in different subgroups upon ICT treatment in a time-dependent manner. In addition, a decrease level of HER2 (p = 0.032 @28th wk) and an elevated level of PEA3 (p = 0.014 @28th wk) were also detected in ICT treated group. The PET/CT-based imaging showed that ICT vs non-ICT treated mice had different standard uptake value and metastasis. Discussion and Conclusion: Our results showed potent anti-cancer properties of ICT through the modulation of adipokine secretion may alter the expression and activation of HER2 pathway as an alternative mechanism to prevent PCa progression. Altogether, our findings indicate that ICT could be a promising cancer preventive agent with the potential to target and eradicate tumor cells in obese PCa patients.
Although it was well known that arbuscular mycorrhizal fungus (AMF) inoculation significantly increased atrazine dissipation in the soil, the effect of AMF on bacterial community, especially potential atrazine-degrading bacteria mediating atrazine dissipation has been overlooked. In the present study, there were four different treatments: Funnelliformis mosseae inoculation with or without atrazine; and non-AMF inoculation with or without atrazine. F. mosseae significantly increased atrazine dissipation rate from 28.7% to 53.3%. Then 16S rRNA gene sequencing results indicated that bacteria community differed significantly by F. mosseae inoculation and atrazine addition. The Shannon index decreased significantly with AMF and atrazine at phylum and family level, and significant inhibition of atrazine on evenness was also observed. LEFSe analysis revealed that Terrimonas and Arthrobacter were significantly associated with F. mosseae, as well as unidentified_Nitrospiraceae associated with atrazine addition. There are several bacterial taxa associated with both F. mosseae inoculation and atrazine addition. Totally, twelve atrazine-degrading bacterial genera (>0.10%) were identified. When atrazine was added, the abundance of Arthrobacter, Burkholderia, Mycobacterium and Streptomyces increased in F. mosseae inoculation treatment, but Nocardioides, Pseudomonas, Bradyrhizobium, Rhizobium, Rhodobacter, Methylobacterium, Bosea and Shinella decreased. In the presence of atrazine, activities of dehydrogenase, urease, acid and alkaline phosphatase in F. mosseae inoculation treatment were significantly higher than those in non-inoculation. However, there was no significant relationship between bacterial community and any soil enzyme activity in four treatments. Our findings reveal the potential relationship between soil bacterial community and AMF inoculation during atrazine dissipation.
Background It is known that gut microbiota can regulate cancer therapies. We hypothesized that gut microbiota may interact with androgen deprivation therapy (ADT) in the process of castration-resistant prostate cancer (CRPC). Here, the differences in gut microbiota between matched hormone-sensitive prostate cancer (HSPC) and CRPC were determined before and after ADT. Methods We profiled the fecal microbiota in matched HSPC and CRPC from 21 patients who received ADT at our urological center using 16S rRNA gene amplicon sequencing. Differences in microbiota were determined with α/β-diversity and LefSe analysis. Functional inference of microbiota was performed with PICRUSt. Results The results showed that the gut microbial community in CRPC was significantly altered with increased abundance of several bacterial flora including genus Phascolarctobacterium and Ruminococcus. For functional analyses, bacterial gene pathways involved in terpenoids/polyketides metabolism and ether lipid metabolism were significantly activated in CRPC. Conclusions Measurable differences in the gut microbiota were identified between HSPC and CRPC. Functional validations are further needed to ascertain the underlying mechanism of these differential microbiota in the process of CRPC, and their potential as new targets to enhance ADT responses.
Background: To study the impact of land-use change on soil microbial community structure and diversity in Northeast China, three typical land-use types (plough, grassland, and forest), from grassland change to forest land and grassland change to plough, in the Qiqihar region of Heilongjiang Province were taken as research objects. Methods: MiSeq high-throughput sequencing technology based on bacterial 16S rRNA and fungal ITS rRNA was used to study the above community structure of soil bacteria and fungi and to explore the relationship between soil bacteria and soil environmental factors. Results: The results showed that there was no significant difference in soil bacterial community diversity and fungal community diversity after the grassland was completely changed to forest land. The dominant bacterial phylum changed from Actinobacteria to Acidobacteria, the dominant fungal phylum changed from Ascomycetes to Basidiomycetes, and the ECM functional group increased significantly. After the grassland was changed to plough, there was no significant difference in the diversity of soil bacterial communities, and the diversity of fungal communities increased significantly. The dominant phylum changed from Actinomycetes to Proteobacteria. The dominant phylum was still Ascomycetes, and the functional groups of pathogens and parasites increased significantly. CCA showed that soil pH, MC, NO 3- -N, TP and AP were important factors affecting the composition of soil microbial communities, and changes in land-use patterns changed the physical and chemical properties of soils, thereby affecting the structure and diversity of microbial communities. Conclusions: Our research results clarify the impact of changes in land use on the characteristics of soil microbial communities and provide basic data on the healthy use of land.