DDX5 inhibits inflammation by modulating m6A levels of TLR2/4 transcripts during bacterial infection.

DExD/H-box helicases are crucial regulators of RNA metabolism and antiviral innate immune responses; however, their role in bacteria-induced inflammation remains unclear. Here, we report that DDX5 interacts with METTL3 and METTL14 to form an m6A writing complex, which adds N6-methyladenosine to transcripts of toll-like receptor (TLR) 2 and TLR4, promoting their decay via YTHDF2-mediated RNA degradation, resulting in reduced expression of TLR2/4. Upon bacterial infection, DDX5 is recruited to Hrd1 at the endoplasmic reticulum in an MyD88-dependent manner and is degraded by the ubiquitin-proteasome pathway. This process disrupts the DDX5 m6A writing complex and halts m6A modification as well as degradation of TLR2/4 mRNAs, thereby promoting the expression of TLR2 and TLR4 and downstream NF-κB activation. The role of DDX5 in regulating inflammation is also validated in vivo, as DDX5- and METTL3-KO mice exhibit enhanced expression of inflammatory cytokines. Our findings show that DDX5 acts as a molecular switch to regulate inflammation during bacterial infection and shed light on mechanisms of quiescent inflammation during homeostasis.

Biorthogonal Dynamical Quantum Phase Transitions in Non-Hermitian Systems.

By utilizing biorthogonal bases, we develop a comprehensive framework for studying biorthogonal dynamical quantum phase transitions in non-Hermitian systems. With the help of the previously overlooked associated state, we define the automatically normalized biorthogonal Loschmidt echo. This approach is capable of handling arbitrary non-Hermitian systems with complex eigenvalues and naturally eliminates the negative value of Loschmidt rate obtained without the biorthogonal bases. Taking the non-Hermitian Su-Schrieffer-Heeger model as a concrete example, a 1/2 change of dynamical topological order parameter in biorthogonal bases is observed which is not shown in self-normal bases. Furthermore, we discover that the periodicity of biorthogonal dynamical quantum phase transitions depends on whether the two-level subsystem at the critical momentum oscillates or reaches a steady state.

Cost-Effectiveness of New Quadruple Therapy Compared With Standard Treatment for Patients With Heart Failure in China.

ABSTRACT: This study aimed to compare the cost-effectiveness of the new quadruple therapy regimen of adding sodium-glucose-linked transporter 2 (SGLT2) inhibitors, with standard treatment for patients with heart failure (HF) in China. From the payer's perspective, the dates of cardiovascular event recurrences were extracted from a meta-analysis including 6 trials, combined with the treatment cost for patients with HF in China to construct a Markov model. The outcomes included per capita medical costs and incremental cost-effectiveness ratio, using quality-adjusted life years (QALYs) data. Single-factor, probability sensitivity analysis, and scenario analysis were used to explore the potential uncertainties of the model. The per capita costs of the new quadruple therapy regimen and standard treatment were $87441.26 and $87087.54, respectively. The new regimen was associated with a mean of 21.44 QALYs gained, compared with 18.60 QALYs gained with the standard treatment. The incremental cost-effectiveness ratio was $124.03 per QALY gained. The sensitivity analysis revealed that changes in the parameters within the set range did not affect the model results. In China, compared with standard treatment, the new quadruple therapy regimen with SGLT2 inhibitors reduce the frequency of cardiovascular events among patients with HF, and it has economic advantages.

Management and Clinical Outcomes of Membranous Nephropathy, IgA Nephropathy, and Minimal Change Disease Two Years Post-Kidney Biopsy.

INTRODUCTION: This study evaluated the phenotypic and pathology characteristics of patients undergoing kidney biopsy at a single center, while also determining the frequency and factors associated with clinical outcomes. METHODS: The incidence and distribution of biopsy-proven kidney diseases in 2000-2019 were surveyed. Consecutive individuals diagnosed with membranous nephropathy (MN), immunoglobulin A nephropathy (IgAN), and minimal change disease (MCD) between August 2015 and December 2019 were enrolled in the prospective 2-year follow-up study. Outcomes included remission of proteinuria and kidney disease progression events. Multivariable-adjusted Cox proportional hazards model was applied. RESULTS: 4,550 kidney biopsies were performed in 2000-2019, showing a noticeable increase in the proportion of MN. 426 patients were enrolled in the follow-up cohort. 346 (81.2%) achieved remission of proteinuria, 39 (9.2%) suffered kidney disease progression and 51.3% of them were diagnosed with IgAN. Kidney pathological diagnosis (MN vs. MCD: hazard ratio [HR], 0.42; 95% confidence interval [95% CI], 0.31-0.57; IgAN vs. MCD: 0.58; 0.39-0.85), levels of 24-h urine protein at biopsy (1.04; 1.00-1.08) and presence of nodular mesangial sclerosis (0.70; 0.49-0.99) were significantly correlated with remission of proteinuria after adjusting for baseline variables. 24-h urine protein levels at biopsy (1.14; 1.04-1.25) and the presence of crescents (2.30; 1.06-4.95) were the independent risk factors for kidney disease progression events after adjusting for baseline variables. CONCLUSION: The increasing frequency of MN has been affirmed over the past 2 decades. The therapeutic status, clinical outcomes, and factors influencing these outcomes were presented in this single-center study for the three primary glomerular diseases.

Recent development of VEGFR small molecule inhibitors as anticancer agents: A patent review (2021-2023).

VEGFR, a receptor tyrosine kinase inhibitor (TKI), is an important regulatory factor that promotes angiogenesis and vascular permeability. It plays a significant role in processes such as tumor angiogenesis, tumor cell invasion, and metastasis. VEGFR is mainly composed of three subtypes: VEGFR-1, VEGFR-2, and VEGFR-3. Among them, VEGFR-2 is the crucial signaling receptor for VEGF, which is involved in various pathological and physiological functions. At present, VEGFR-2 is closely related to a variety of cancers, such as non-small cell lung cancer (NSCLC), Hepatocellular carcinoma, Renal cell carcinoma, breast cancer, gastric cancer, glioma, etc. Consequently, VEGFR-2 serves as a crucial target for various cancer treatments. An increasing number of VEGFR inhibitors have been discovered to treat cancer, and they have achieved tremendous success in the clinic. Nevertheless, VEGFR inhibitors often exhibit severe cytotoxicity, resistance, and limitations in indications, which weaken the clinical therapeutic effect. In recent years, many small molecule inhibitors targeting VEGFR have been identified with anti-drug resistance, lower cytotoxicity, and better affinity. Here, we provide an overview of the structure and physiological functions of VEGFR, as well as some VEGFR inhibitors currently in clinical use. Also, we summarize the in vivo and in vitro activities, selectivity, structure-activity relationship, and therapeutic or preventive use of VEGFR small molecule inhibitors reported in patents in the past three years (2021-2023), thereby presenting the prospects and insights for the future development of targeted VEGFR inhibitors.

Suture Net Technique for Mid-face Superficial Fat Compartments Restoration.

BACKGROUND: Facial fold and groove formation is influenced by the ptosis of the superficial fat compartments in the mid-face region. OBJECTIVE: This study aimed to design a facial rejuvenation technique that targets sagging of the mid-face fat compartments and achieves a youthful facial configuration. MATERIALS AND METHODS: A total of 102 patients underwent suture net restoration. Each specific ptosis fat compartment was carefully lifted and held at the regional facial ligaments to effectively restore volume distribution. Patient outcomes were evaluated through preoperative and postoperative photography comparison, 3-D photographic analysis, and postoperative evaluations. RESULTS: Significant mid-cheek rejuvenation was observed. The procedure resulted in a remarkable, 10.89% increase in malar projection. The nasolabial fold improved by at least 1 grade in 61.43% of the patients and by at least 2 grades in 37.14%. A total of 87.65% of the patients expressed high satisfaction or satisfaction with the outcomes of the procedure. CONCLUSION: By specifically targeting the mid-face ptosis fat compartments, the technique demonstrated significant enhancements of both the nasolabial fold and the malar projection. The results indicate that this novel technique holds promise as an efficient approach for satisfactorily addressing facial aging concerns.

26SCS-Loaded SilMA/Col Composite Sponge with Well-Arranged Layers Promotes Angiogenesis-Based Diabetic Wound Repair by Mediating Macrophage Inflammatory Response.

Diabetic wound healing is a significant clinical challenge because abnormal immune cells in the wound cause chronic inflammation and impair tissue regeneration. Therefore, regulating the behavior and function of macrophages may be conducive to improving treatment outcomes in diabetic wounds. Herein, sulfated chitosan (26SCS)-containing composite sponges (26SCS-SilMA/Col-330) with well-arranged layers and high porosity were constructed based on collagen and silk fibroin, aiming to induce an appropriate inflammatory response and promote angiogenesis. The results indicated that the ordered topological structure of composite sponges could trigger the pro-inflammatory response of Mφs in the early stage, and rapid release of 26SCS in the early and middle stages (within the concentration range of 1-3 mg/mL) induced a positive inflammatory response; initiated the pro-inflammatory reaction of Mφs within 3 days; shifted M1 Mφs to the M2 phenotype within 3-7 days; and significantly up-regulated the expression of two typical angiogenic growth factors, namely VEGF and PDGF-BB, on day 7, leading to rapid HUVEC migration and angiogenesis. In vivo data also demonstrated that on the 14th day after surgery, the 26SCS-SilMA/Col-330-implanted areas exhibited less inflammation, faster re-epithelialization, more abundant collagen deposition and a greater number of blood vessels in the skin tissue. The composite sponges with higher 26SCS contents (the (5.0) 26SCS-SilMA/Col-330 and the (7.5) 26SCS-SilMA/Col-330) could better orchestrate the phenotype and function of Mφs and facilitate wound healing. These findings highlight that the 26SCS-SilMA/Col-330 sponges developed in this work might have great potential as a novel dressing for the treatment of diabetic wounds.

Single Amino Acid Modifications for Controlling the Helicity of Peptide-Based Chiral Gold Nanoparticle Superstructures.

Assembling nanoparticles (NPs) into well-defined superstructures can lead to emergent collective properties that depend on their 3-D structural arrangement. Peptide conjugate molecules designed to both bind to NP surfaces and direct NP assembly have proven useful for constructing NP superstructures, and atomic- and molecular-level alterations to these conjugates have been shown to manifest in observable changes to nanoscale structure and properties. The divalent peptide conjugate, C16-(PEPAu)2 (PEPAu = AYSSGAPPMPPF), directs the formation of one-dimensional helical Au NP superstructures. This study examines how variation of the ninth amino acid residue (M), which is known to be a key Au anchoring residue, affects the structure of the helical assemblies. A series of conjugates of differential Au binding affinities based on variation of the ninth residue were designed, and Replica Exchange with Solute Tempering (REST) Molecular Dynamics simulations of the peptides on an Au(111) surface were performed to determine the approximate surface contact and to assign a binding score for each new peptide. A helical structure transition from double helices to single helices is observed as the peptide binding affinity to the Au(111) surface decreases. Accompanying this distinct structural transition is the emergence of a plasmonic chiroptical signal. REST-MD simulations were also used to predict new peptide conjugate molecules that would preferentially direct the formation of single-helical AuNP superstructures. Significantly, these findings demonstrate how small modifications to peptide precursors can be leveraged to precisely direct inorganic NP structure and assembly at the nano- and microscale, further expanding and enriching the peptide-based molecular toolkit for controlling NP superstructure assembly and properties.

Hemolytic disease of the newborn due to anti-Jra from a Chinese mother with one novel and one classic heterozygous mutation.

OBJECTIVE: Investigation of a Jr(a-) family samples, identification of the mutant and assessment of the differences of Jr antigen density of the Jr(a-) family members, random adult and newborn individuals' RBCs. BACKGROUND: The anti-Jra antibody is generated when a Jr(a-) individual pregnant or transfused with Jr(a+) blood unit, which can lead to mild-to-moderate hemolytic disease of the foetus and newborn (HDFN) or hemolytic transfusion reaction (HTR). Several mutations had been identified. The anti-Jra caused HDFN is not rare in East Asia, but due to the lack of antibody and molecular background, it is likely to lead missed detection. METHODS AND MATERIALS: One G4P1 woman had been detected as IAT positive during prenatal examination. Suspected as anti-Jra after the laboratory serological testing, the maternal sample was further assessed by molecular analysis. The antigen density was detected by flow cytometry after reacting with anti-Jra serum in family members and the normal individuals. RESULTS: One novel frameshift mutation c.717delC and one previously identified mutation c.706C > T in ABCG2 was identified on proband. The infant haemoglobin(Hb) and bilirubin increased significantly after exchange transfusion and the severe HDFN was relieved. Flow cytometry results showed that the Jra antigens on adult RBCs were significantly less than those on the infant. CONCLUSION: The c.717delC mutation can lead to the shortening of protein ABCG2 in the site of p.Leu307Stop, result in the loss of Jra antigen. The difference in antigen density between adult and infant RBCs may be a possible reason that leads to severe HDFN but not transfusion reaction. Breastfeeding may lead to slower recovery from HDFN.

Coordination of mRNA and tRNA methylations by TRMT10A.

The posttranscriptional modification of messenger RNA (mRNA) and transfer RNA (tRNA) provides an additional layer of regulatory complexity during gene expression. Here, we show that a tRNA methyltransferase, TRMT10A, interacts with an mRNA demethylase FTO (ALKBH9), both in vitro and inside cells. TRMT10A installs N1-methylguanosine (m1G) in tRNA, and FTO performs demethylation on N6-methyladenosine (m6A) and N6,2'-O-dimethyladenosine (m6Am) in mRNA. We show that TRMT10A ablation not only leads to decreased m1G in tRNA but also significantly increases m6A levels in mRNA. Cross-linking and immunoprecipitation, followed by high-throughput sequencing results show that TRMT10A shares a significant overlap of associated mRNAs with FTO, and these mRNAs have accelerated decay rates potentially through the regulation by a specific m6A reader, YTHDF2. Furthermore, transcripts with increased m6A upon TRMT10A ablation contain an overrepresentation of m1G9-containing tRNAs codons read by tRNAGln(TTG), tRNAArg(CCG), and tRNAThr(CGT) These findings collectively reveal the presence of coordinated mRNA and tRNA methylations and demonstrate a mechanism for regulating gene expression through the interactions between mRNA and tRNA modifying enzymes.

The Impact of Food Additives on the Abundance and Composition of Gut Microbiota.

The gut microbiota has been confirmed as an important part in human health, and is even take as an 'organ'. The interaction between the gut microbiota and host intestinal environment plays a key role in digestion, metabolism, immunity, inflammation, and diseases. The dietary component is a major factor that affects the composition and function of gut microbiota. Food additives have been widely used to improve the color, taste, aroma, texture, and nutritional quality of processed food. The increasing variety and quantity of processed food in diets lead to increased frequency and dose of food additives exposure, especially artificial food additives, which has become a concern of consumers. There are studies focusing on the impact of food additives on the gut microbiota, as long-term exposure to food additives could induce changes in the microbes, and the gut microbiota is related to human health and disease. Therefore, the aim of this review is to summarize the interaction between the gut microbiota and food additives.

Understanding the Quantum Rabi Ring Using Analogies to Quantum Magnetism.

We map a quantum Rabi ring, consisting of N cavities arranged in a ring geometry, into an effective magnetic model containing the XY exchange and the Dzyaloshinskii-Moriya (DM) interactions. The analog of the latter is induced by an artificial magnetic field, which modulates photon hopping between nearest-neighbor cavities with a phase. This mapping facilitates the description and understanding of the different phases in the quantum optical model through simple arguments of competing magnetic interactions. For the square geometry (N=4) the rich phase diagram exhibits three superradiant phases denoted as ferro-superradiant, antiferro-superradiant, and chiral superradiant. In particular, the DM interaction is responsible for the chiral phase in which the energetically degenerate configurations of the order parameters are similar to the in-plane magnetizations of skyrmions with different helicities. The antiferro-superradiant phase is suppressed in the triangle geometry (N=3) as geometric frustration contributes to stabilize the chiral phase even for small values of the DM interaction. The chiral phases for odd and even N show a different scaling behavior close to the phase transition. The equivalent behavior on both systems opens the possibility of simulating chiral magnetism in a few-body quantum optical platform, as well as understanding one system using the insights gained from the other.

Recent trends in aroma release and perception during food oral processing: A review.

The dynamic and complex peculiarities of the oral environment present several challenges for controlling the aroma release during food consumption. They also pose higher requirements for designing food with better sensory quality. This requires a comprehensive understanding of the basic rules of aroma transmission and aroma perception during food oral processing and its behind mechanism. This review summarized the latest developments in aroma release from food to retronasal cavity, aroma release and delivery influencing factors, aroma perception mechanisms. The individual variance is the most important factor affecting aroma release and perception. Therefore, the intelligent chewing simulator is the key to establish a standard analytical method. The key odorants perceived from the retronasal cavity should be given more attention during food oral processing. Identification of the olfactory receptor activated by specific odorants and its binding mechanisms are still the bottleneck. Electrophysiology and image technology are the new noninvasive technologies in elucidating the brain signals among multisensory, which can fill the gap between aroma perception and other senses. Moreover, it is necessary to develop a new approach to integrate the relationship among aroma binding parameters, aroma concentration, aroma attributes and cross-modal reactions to make the aroma prediction model more accurate.

The flavors of edible mushrooms: A comprehensive review of volatile organic compounds and their analytical methods.

Due to their distinctive flavors, edible mushrooms have gained attention in flavor-related research, and the quality of their flavors determines their consumption. The odor is a vital element of food flavor that significantly impacts consumers' perceptions and purchase decisions. The volatile organic compounds (VOCs) of the odorant ingredient is the primary factors affecting scent characteristics. VOCs analysis and identification require technical assistance. The production and use of edible mushrooms can be aided by a broader examination of their volatile constituents. This review discusses the composition of VOCs in edible mushrooms and how they affect flavors. The principles, advantages, and disadvantages of various methods for extraction, isolation, and characterization of the VOCs of edible mushrooms are also highlighted. The numerous VOCs found in edible mushrooms such as primarily C-8 compounds, organic sulfur compounds, aldehydes, ketones, alcohols, and esters are summarized along with their effects on the various characteristics of scent. Combining multiple extraction, isolation, identification, and quantification technologies will facilitate rapid and accurate analysis of VOCs in edible mushrooms as proof of sensory attributes and quality.

Research progress on mechanism and imaging of temporal lobe injury induced by radiotherapy for head and neck cancer.

Radiotherapy (RT) is an effective treatment for head and neck cancer (HNC). Radiation-induced temporal lobe injury (TLI) is a serious complication of RT. Late symptoms of radiation-induced TLI are irreversible and manifest as memory loss, cognitive impairment, and even temporal lobe necrosis (TLN). It is currently believed that the mechanism of radiation-induced TLI involves microvascular injury, neuron and neural stem cell injury, glial cell damage, inflammation, and the production of free radicals. Significant RT-related structural changes and dose-dependent changes in gray matter (GM) and white matter (WM) volume and morphology were observed through computed tomography (CT) and magnetic resonance imaging (MRI) which were common imaging assessment tools. Diffusion tensor imaging (DTI), dispersion kurtosis imaging (DKI), susceptibility-weighted imaging (SWI), resting-state functional magnetic resonance (rs-fMRI), magnetic resonance spectroscopy (MRS), and positron emission tomography (PET) can be used for early diagnosis and prognosis evaluation according to functional, molecular, and cellular processes of TLI. Early diagnosis of TLI is helpful to reduce the incidence of TLN and its related complications. This review summarizes the clinical features, mechanisms, and imaging of radiation-induced TLI in HNC patients. KEY POINTS: • Radiation-induced temporal lobe injury (TLI) is a clinical complication and its symptoms mainly include memory impairment, headache, and cognitive impairment. • The mechanisms of TLI include microvascular injury, cell injury, and inflammatory and free radical injury. Significant RT-related structural changes and dose-dependent changes in TL volume and morphology were observed through CT and MRI. • SWI, MRS, DTI, and DKI and other imaging examinations can detect anatomical and functional, molecular, and cellular changes of TLI.

Physiological and metabolomics responses of Hydrangea macrophylla (Thunb.) Ser. and Hydrangea strigosa Rehd. to lead exposure.

Hydrangea is a potential remediation plant for lead (Pb) pollution. Plant roots communicate with soil through the release of root exudates. It is crucial to study rhizoremediation mechanisms to understand the response of root exudates to contamination stress. Here, we investigated the physiological responses and metabolomic profiling of two Hydrangea species, a horticultural cultivar (Hydrangea macrophylla (Thunb.) Ser.) and a wild type (Hydrangea strigosa Rehd.), under Pb-free and Pb-stressed conditions for 50 days. The results showed that Pb treatment adversely affected the biomass and root growth of the two species. H. strigosa was a Pb-tolerant species with higher superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) activities and more ascorbic acid (AsA) content in roots. Metabolomic profiling showed that 181 and 169 compounds were identified in H. macrophylla and H. strigosa root exudates, respectively, among which 18 showed significant differences between H. macrophylla and H. strigosa under Pb exposure. H. strigosa showed significantly (P < 0.05) higher secretion of sucrose, glycolic acid, and nonanoic acid than H. macrophylla after Pb treatment. Pb stress promoted fatty acid metabolism in H. strigosa, suppressed amino acid metabolism in H. macrophylla, and promoted a higher carbohydrate metabolism in H. strigosa compared with H. macrophylla. This study provides a possible mechanism for the high Pb absorption potential of Hydrangea.

Exploring the Extraction Methods of Phenolic Compounds in Daylily (Hemerocallis citrina Baroni) and Its Antioxidant Activity.

Daylily is a valuable plant resource with various health benefits. Its main bioactive components are phenolic compounds. In this work, four extraction methods, ultrasonic-assisted water extraction (UW), ultrasonic-assisted ethanol extraction (UE), enzymatic-assisted water extraction (EW), and enzymatic-assisted ethanol extraction (EE), were applied to extract phenolic compounds from daylily. Among the four extracts, the UE extract exhibited the highest total phenolic content (130.05 mg/100 g DW) and the best antioxidant activity. For the UE extract, the DPPH value was 7.75 mg Trolox/g DW, the FRAP value was 14.54 mg Trolox/g DW, and the ABTS value was 15.37 mg Trolox/g DW. A total of 26 phenolic compounds were identified from the four extracts, and the UE extract exhibited a higher abundance range of phenolic compounds than the other three extracts. After multivariate statistical analysis, six differential compounds were selected and quantified, and the UE extract exhibited the highest contents of all six differential compounds. The results provided theoretical support for the extraction of phenolic compounds from daylily and the application of daylily as a functional food.

Genome-wide identification of B-box proteins and VvBBX44 involved in light-induced anthocyanin biosynthesis in grape (Vitis vinifera L.).

MAIN CONCLUSION: Genome-wide identification, analysis and functional characterization of an unreported VvBBX gene showed a response to light and positive correlation with anthocyanin content, but also inhibition of light-induced anthocyanin synthesis. B-box (BBX) proteins are a class of zinc (Zn) finger transcription factors or regulators characterized by the presence of one or two BBX domains and play important roles in plant growth and development. However, the BBX genes' potential functions are insufficiently characterized in grape, a globally popular berry with high economic value. Here, 25 BBX family genes including a novel member (assigned VvBBX44) were identified genome widely in grape. The expression level of these VvBBXs were analyzed in 'Cabernet Sauvignon' (V. vinifera) stem, flower, leaf, tendril, petiole, and developing berries. The expression of VvBBX44 increased in developing 'Cabernet Sauvignon' berries. Its expression was inhibited in 'Jingxiu' and 'Muscat Hamburg' berry skin without sunlight. Furthermore, overexpression of VvBBX44 decreased the expression of LONG HYPOCOTYL 5 (VvHY5) and UDP-glucose flavonoid 3-O-glucosyltransferase (VvUFGT), and reduced the anthocyanin content in grape calli. Our results suggest that VvBBX44 may play an important role in grape berry coloring by directly repressing VvHY5 expression. This study provides new insights into the potential role of VvBBXs in berry development and light response and contributes to the understanding on the regulation mechanism of VvBBX44 in anthocyanin biosynthesis.

Mesenchymal stromal cells can repair radiation-induced pulmonary fibrosis via a DKK-1-mediated Wnt/ß-catenin pathway.

Pulmonary injury occurring after thoracic radiotherapy is a main factor limiting the curative effect of radiotherapy. Robust activation of the Wnt signalling pathway induced by ionizing radiation stress plays a critical role in epithelial-mesenchymal transition (EMT) in irradiated type II alveolar epithelial cells and in the proliferation of pulmonary fibroblasts, which contributes to the formation of fibrotic lesions in irradiated lungs. The pathogenesis of radiation-induced pulmonary fibrosis could be restricted by systemic delivery of human adipose-derived mesenchymal stromal cells (Ad-MSCs), as evidenced by the inhibitory effects of Ad-MSCs on EMT in irradiated type II alveolar epithelial cells. The purpose of this study is to observe the effects of mesenchymal stromal cells (MSCs) on repairing fibrosis caused by radiation. We used western blotting and real-time PCR to observe the expression of DKK-1 in MSCs of different origins and passages. After the successful establishment of a radiation-induced lung injury model, we investigated the potency of the supernatant from stromal cells to reduce pro-fibrotic events, including EMT and fibroblast activation. To study the mechanism, we evaluated the levels of active ß-catenin, TCF4 and the target genes Snail, Twist and c-Myc. After the injection of Ad-MSCs into mice via the tail vein, proteins related to EMT, fibroblasts and Wnt/ß-catenin signalling were investigated. The TGF-ß and IL-10 protein concentrations in peripheral blood were measured by ELISA. Ad-MSC-derived supernatant effectively reversed the decrease in E-cadherin expression and inhibited the increase in vimentin expression induced by ionizing radiation in epithelial cells and suppressed the expression of α-SMA, a mediator of fibroblast proliferation. The canonical Wnt pathway may be activated by irradiation but the nuclear localization of active ß-catenin was reduced in the presence of the supernatant from Ad-MSCs. In addition, the expression of target genes involved in EMT was downregulated. Additionally, when DKK-1 in the supernatant was neutralized, all these effects were reversed. Changes in the levels of proteins related to EMT and fibroblast activation, as well as those of active ß-catenin and TCF4, were similar in vivo and in vitro. The serum level of the immunosuppressive factor IL-10 was increased after radiation and was further enhanced after Ad-MSC interference for one month. In conclusion, Ad-MSCs medium can contain DKK-1 and inhibit the induction of EMT via Wnt/ß-catenin signalling in vitro and in vivo.

Potential of fecal microbiota for detection and postoperative surveillance of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers. In recent studies, the gut microbiota has been reported to be potentially involved in aggravating or favoring CRC development. However, little is known about the microbiota composition in CRC patients after treatment. In this study, we explored the fecal microbiota composition to obtain a periscopic view of gut microbial communities. We analyzed microbial 16S rRNA genes from 107 fecal samples of Chinese individuals from three groups, including 33 normal controls (NC), 38 CRC patients (Fa), and 36 CRC post-surgery patients (Fb). RESULTS: Species richness and diversity were decreased in the Fa and Fb groups compared with that of the NC group. Partial least squares discrimination analysis showed clustering of samples according to disease with an obvious separation between the Fa and NC, and Fb and NC groups, as well as a partial separation between the Fa and Fb groups. Based on linear discriminant analysis effect size analysis and a receiver operating characteristic model, Fusobacterium was suggested as a potential biomarker for CRC screening. Additionally, we found that surgery greatly reduced the bacterial diversity of microbiota in CRC patients. Some commensal beneficial bacteria of the intestinal canal, such as Faecalibacterium and Prevotella, were decreased, whereas the drug-resistant Enterococcus was visibly increased in CRC post-surgery group. Meanwhile, we observed a declining tendency of Fusobacterium in the majority of follow-up CRC patients who were still alive approximately 3 y after surgery. We also observed that beneficial bacteria dramatically decreased in CRC patients that recidivated or died after surgery. This revealed that important bacteria might be associated with prognosis. CONCLUSIONS: The fecal bacterial diversity was diminished in CRC patients compared with that in NC. Enrichment and depletion of several bacterial strains associated with carcinomas and inflammation were detected in CRC samples. Fusobacterium might be a potential biomarker for early screening of CRC in Chinese or Asian populations. In summary, this study indicated that fecal microbiome-based approaches could be a feasible method for detecting CRC and monitoring prognosis post-surgery.