Microbiota refers to a colony of microorganisms, and they are found in all multicellular organisms. This colony plays a major role in both the physiology and disease of the organism it inhabits. Much ...attention has been paid to host–microbiota interactions, but there has been little investigation on its role in carcinogenesis. In this study, we characterized a fecal mycobiota, also known as fungal signature, for the first time with 131 subjects, comprising polyp and colorectal cancer (CRC) patients, as well as a healthy control population. The data obtained were analyzed to assess the biodiversity and composition of the fungi. The impacts of anatomic position and tumor stage on the mycobiota were also evaluated. Correlations between fungi were investigated using the Spearman test. We observed fungal dysbiosis in colon polyps and CRC, including decreased diversity in polyp patients, an increased Ascomycota/Basidiomycota ratio, and an increased proportion of opportunistic fungi
Trichosporon
and
Malassezia
, which might favor the progression of CRC. Subsequent analysis with regard to tumor stage demonstrated a lower diversity and significant mycobiota alteration in early-stage tumors. Finally, the fungal correlation showed a close relationship within the community and concomitantly revealed a dramatically structured discrepancy in each clinical phenotype. In conclusion, our study has uncovered a distinct fungal dysbiosis and an alteration in the fungal network, which could play important roles in polyp and CRC pathogenesis.
Understanding the structure‐activity relationship of catalytic reactions at a molecular level still remains a great challenge. Herein, shell‐isolated nanoparticle‐enhanced Raman spectroscopy ...(SHINERS) is employed to in‐situ study the catalytic hydrogenation of para‐nitrothiophenol (pNTP) on Pt‐based nanocatalysts with different size and composition. The nanocatalysts are assembled on pinhole‐free shell‐isolate nanoparticles (SHINs), which work as Raman amplifiers to enhance the Raman signals of species on the catalysts, allowing the in‐situ monitoring of catalytic reactions carried out on the catalysts. Using this strategy, we find that the catalytic activity of the Pt nanocatalysts shows a volcanic trend with the Pt size, and that PtM (M=Ni or Cu) bimetallic nanocatalysts display much higher performance compared with Pt due to better activation of the nitro group. This work demonstrates that SHINERS is a promising technique for in‐situ study of nanocatalysis thus can deepen the understanding of the behaviors of different catalysts.
Shine like a diamond! Shell‐isolated nanoparticles enhanced Raman spectroscopy (SHINERS) has been employed to reveal the size and composition effect of Pt‐based nanocatalysts towards the hydrogenation of pNTP.
We report on the measurement of the γp→J/ψp cross section from E_{γ}=11.8 GeV down to the threshold at 8.2 GeV using a tagged photon beam with the GlueX experiment. We find that the total cross ...section falls toward the threshold less steeply than expected from two-gluon exchange models. The differential cross section dσ/dt has an exponential slope of 1.67±0.39 GeV^{-2} at 10.7 GeV average energy. The LHCb pentaquark candidates P_{c}^{+} can be produced in the s channel of this reaction. We see no evidence for them and set model-dependent upper limits on their branching fractions B(P_{c}^{+}→J/ψp) and cross sections σ(γp→P_{c}^{+})×B(P_{c}^{+}→J/ψp).
Transient receptor potential V2 (TRPV2) has been proposed to be a high-threshold thermosensor. However, further elucidation of the channel properties and physiological role of TRPV2 have been ...hindered by the lack of selective pharmacological tools as well as by the species-dependent differences in the activation of this channel. In the present study, we have used cell-based calcium mobilization and electrophysiological assays to identify and characterize several novel cannabinoid TRPV2 agonists. Among these, cannabidiol was found to be the most robust and potent (EC(50) = 3.7 microM), followed by Delta(9)-tetrahydrocannabinol (EC(50) = 14 microM) and cannabinol (EC(50) = 77.7 microM). We also demonstrated that cannabidiol evoked a concentration-dependent release of calcitonin gene-related peptide (CGRP) from cultured rat dorsal root ganglion neurons in a cannabinoid receptor- and TRPV1-independent manner. Moreover, the cannabidiol-evoked CGRP release depended on extracellular calcium and was blocked by the nonselective TRP channel blocker, ruthenium red. We further provide evidence through the use of small interfering RNA knockdown and repetitive stimulation studies, to show that cannabidiol-evoked CGRP release is mediated, at least in part, by TRPV2. Together, these data suggest not only that TRPV2 may comprise a mechanism whereby cannabidiol exerts its clinically beneficial effects in vivo, but also that TRPV2 may constitute a viable, new drug target.
1. The proliferation of granulosa cells is vital for the development and recruitment of hen ovarian prehierarchical follicles (PF). The RAB23 protein is a member of the Rab family, belonging to the ...GTPase family. This study studied the regulatory roles of the RAB23 gene in PF.2. The expression of RAB23 was significantly increased in granulosa cells (GC) during PF growth and was highest in GC at 6-8 mm diameter (p < 0.05). The RAB23 protein was mainly expressed in the GC, oocytes (OC) as well as somatic cells (SC) of the PF.3. The mRNA expression of FSHR, CCND1,CYP11A1, StAR and HSD3B1 was significantly increased in the siRNA RAB23 group (p < 0.05). Additionally, protein expression of FSHR, CCND1, CYP11A1, HSD3B1 was significantly increased (p < 0.05) after GC were transfected with RAB23-specific siRNA. Protein expression of StAR in the siRNA RAB23 group was numerically higher than that in the positive control (PC) and negative control (NC) groups. The GC proliferation rate and progesterone synthesis of the prehierarchical follicles in hen ovaries were markedly increased in vitro (p < 0.05).4.This study revealed that RAB23 might play an inhibitory role in GC proliferation and progesterone synthesis during the prehierarchical follicles development in vitro.1. The proliferation of granulosa cells is vital for the development and recruitment of hen ovarian prehierarchical follicles (PF). The RAB23 protein is a member of the Rab family, belonging to the GTPase family. This study studied the regulatory roles of the RAB23 gene in PF.2. The expression of RAB23 was significantly increased in granulosa cells (GC) during PF growth and was highest in GC at 6-8 mm diameter (p < 0.05). The RAB23 protein was mainly expressed in the GC, oocytes (OC) as well as somatic cells (SC) of the PF.3. The mRNA expression of FSHR, CCND1,CYP11A1, StAR and HSD3B1 was significantly increased in the siRNA RAB23 group (p < 0.05). Additionally, protein expression of FSHR, CCND1, CYP11A1, HSD3B1 was significantly increased (p < 0.05) after GC were transfected with RAB23-specific siRNA. Protein expression of StAR in the siRNA RAB23 group was numerically higher than that in the positive control (PC) and negative control (NC) groups. The GC proliferation rate and progesterone synthesis of the prehierarchical follicles in hen ovaries were markedly increased in vitro (p < 0.05).4.This study revealed that RAB23 might play an inhibitory role in GC proliferation and progesterone synthesis during the prehierarchical follicles development in vitro.
Chemotherapy is a significant and effective therapeutic strategy that is frequently utilized in the treatment of cancer. Small molecular prodrug-based nanoassemblies (SMPDNAs) combine the benefits of ...both prodrugs and nanomedicine into a single nanoassembly with high drug loading, increased stability, and improved biocompatibility.
In this study, a disulfide bond inserted 7-ethyl-10-hydroxycamptothecin (SN38) prodrug was rationally designed and then used to prepare nanoassemblies (SNSS NAs) that were selectively activated by rich glutathione (GSH) in the tumor site. The characterization of SNSS NAs and the in vitro and in vivo evaluation of their antitumor effect on a pancreatic cancer model were performed.
In vitro findings demonstrated that SNSS NAs exhibited GSH-induced SN38 release and cytotoxicity. SNSS NAs have demonstrated a passive targeting effect on tumor tissues, a superior antitumor effect compared to irinotecan (CPT-11), and satisfactory biocompatibility with double dosage treatment.
The SNSS NAs developed in this study provide a new method for the preparation of SN38-based nano-delivery systems with improved antitumor effect and biosafety.
The utility of patient-derived tumor cell lines as experimental models for glioblastoma has been challenged by limited representation of the in vivo tumor biology and low clinical translatability. ...Here, we report on longitudinal epigenetic and transcriptional profiling of seven glioblastoma spheroid cell line models cultured over an extended period. Molecular profiles were associated with drug response data obtained for 231 clinically used drugs. We show that the glioblastoma spheroid models remained molecularly stable and displayed reproducible drug responses over prolonged culture times of 30 in vitro passages. Integration of gene expression and drug response data identified predictive gene signatures linked to sensitivity to specific drugs, indicating the potential of gene expression-based prediction of glioblastoma therapy response. Our data thus empowers glioblastoma spheroid disease modeling as a useful preclinical assay that may uncover novel therapeutic vulnerabilities and associated molecular alterations.
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•Glioma spheroid cell lines are molecularly stable in vitro models over time.•Tumor spheroid cell lines allow for reproducible drug testing.•Gene expression profiles may predict in vitro drug response of glioma cells.
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