Effects and Significance of Dicliptera chinensis Polysaccharide on the Expression of Transforming Growth Factor ß1/Connective Tissue Growth Factor Pathway in the Masseter and Head and Neck Skin of Rats With Radiation-Induced Fibrosis.

PURPOSE: To investigate whether Dicliptera chinensis polysaccharide (DCP) can alleviate radiation-induced fibrosis of masseter and head and neck skin. METHODS: SD rats were divided into the control, the irradiation (IR), the IR + low dose DCP (200 mg/kg), and the IR + high dose DCP (400 mg/kg) groups. The head and neck of rats in the last 3 groups received a single dose of 18 Gy X-ray. At 1st, 2nd, 4th week (w) after radiation, haematoxylin and eosin staining were performed on masseter and skin to observe the histopathological changes; immunohistochemistry staining was performed to observe the pathological changes of the skin; Masson staining was performed on masseter and skin to observe the collagen deposition; western blot analysis was used on masseter to calculate the relative transforming growth factor ß1 (TGF-ß1), connective tissue growth factor (CTGF) expressions; ELISA was used to detect the contents of TGF-ß1 and CTGF in skin and the contents of type I and type III collagens in masseter and skin. RESULTS: In terms of skin, compared to the IR group, the IR + high-dose DCP group exhibited relatively smaller changes in skin structure, lower levels of TGF-ß1 and CTGF; thinner skin thickness was observed at the 4th w after radiation; and the positive rates of collagen fibre and the optical densities of type I and type III collagens were lower at the 2nd and 4th w. For the masseter, compared to the IR group, the morphological changes were improved and the expression levels of TGF-ß1 and CTGF proteins decreased in the 2 DCP dose groups at 2nd and 4th w. CONCLUSION: DCP can reduce the formation and accumulation of type I and type III collagens after IR and ameliorate radiation-induced fibrosis of masseter and skin by down-regulating the expressions of TGF-ß1 and CTGF.

Risk prediction model of uterine corpus endometrial carcinoma based on immune-related genes.

BACKGROUND: Given the significant role of immune-related genes in uterine corpus endometrial carcinoma (UCEC) and the long-term outcomes of patients, our objective was to develop a prognostic risk prediction model using immune-related genes to improve the accuracy of UCEC prognosis prediction. METHODS: The Limma, ESTIMATE, and CIBERSORT methods were used for cluster analysis, immune score calculation, and estimation of immune cell proportions. Univariate and multivariate analyses were utilized to develop a prognostic risk model for UCEC. Risk model scores and nomograms were used to evaluate the models. String constructs a protein-protein interaction (PPI) network of genes. The qRT-PCR, immunofluorescence, and immunohistochemistry (IHC) all confirmed the genes. RESULTS: Cluster analysis divided the immune-related genes into four subtypes. 33 immune-related genes were used to independently predict the prognosis of UCEC and construct the prognosis model and risk score. The analysis of the survival nomogram indicated that the model has excellent predictive ability and strong reliability for predicting the survival of patients with UCEC. The protein-protein interaction network analysis of key genes indicates that four genes play a pivotal role in interactions: GZMK, IL7, GIMAP, and UBD. The quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence, and immunohistochemistry (IHC) all confirmed the expression of the aforementioned genes and their correlation with immune cell levels. This further revealed that GZMK, IL7, GIMAP, and UBD could potentially serve as biomarkers associated with immune levels in endometrial cancer. CONCLUSION: The study identified genes related to immune response in UCEC, including GZMK, IL7, GIMAP, and UBD, which may serve as new biomarkers and therapeutic targets for evaluating immune levels in the future.

Disrupting redox homeostasis for tumor therapy based on PDT/chemo/ferroptosis therapeutic hybrid liposomes.

Synergistic photodynamic therapy (PDT) with other therapeutic modalities can enhance the therapeutic efficacy of tumor treatment and reduce the adverse effects associated with drug leakage and off-target accumulation. However, shaping combined strategies for synergistic therapy remains challenging. Herein, we developed versatile hybrid liposomes self-assembled from Ce6-lipid conjugates and loaded with the chemo drug doxorubicin (DOX) and ferroptosis inducer Fe3O4 nanoparticles for synergistic PDT/chemo/ferroptosis therapy. Abundant ROS are generated by PDT upon 650 nm light irradiation, Fe3O4-mediated Fenton reaction, and DOX-induced apoptosis. Furthermore, amplifying oxidative stress in cancer cells to disrupt cellular redox homeostasis could accelerate tumor cell death through oxidative damage to lipids, proteins, and DNA. Overall, this work highlights liposome-based therapeutic nanoformulations, thus offering a breakthrough redox homeostasis-based synergistic PDT/chemo/ferroptosis therapy for lung cancer.

Dicliptera chinensis-derived polysaccharide enhanced the growth activity of submandibular gland cells in vitro after radiotherapy.

Objective: Radiotherapy for head and neck can damage the salivary gland cells, which can easily result in xerostomia. No effective treatment for radiation-induced salivary gland dysfunction currently exists. Thus, we aimed to study the protective effect of Dicliptera chinensis polysaccharides (DCP) on the prevention of submandibular gland (SMG) cell damage caused by radiotherapy in Sprague-Dawley rats. Design: Mechanical enzyme digestion was used to extract primary rat SMG cells. A radiation injury model was established by treating these cells with a dose of 8 Gy, followed by intervention using different DCP concentrations. The cell counting kit 8 assay was used to determine the inhibition rate of SMG cells in each group. The rates of apoptosis and cell cycle progression were detected using flow cytometry. Expression of the Mre11/Rad50/Nbs1 complex (MRN) was detected using western blotting. Results: DCP increased the proliferation of SMG cells after irradiation, and cell growth activity positively correlated with polysaccharide concentration. Flow cytometry analysis of SMG cell apoptosis revealed that DCP markedly reduced the total apoptosis rate after irradiation, especially the early apoptosis rate. Cell cycle results suggested that DCP reduced the number of cells in the S and G2 phases after irradiation and alleviated the S and G2 blocks. Western blot results indicated that the expression of Mre11, Rad50, and Nbs1 decreased in the radiation-injured group, whereas their expression increased after DCP treatment. Conclusions: DCP can protect the rat SMG cells after radiation and be used as a protective agent against salivary gland cell damage caused by radiotherapy.

YAP/Aurora A-mediated ciliogenesis regulates ionizing radiation-induced senescence via Hedgehog pathway in tumor cells.

Primary cilia are antenna-like organelles that play critical roles in sensing and responding to various signals. Nevertheless, the function of primary cilia in cellular response to ionizing radiation (IR) in tumor cells remains unclear. Here, we show that primary cilia are frequently expressed in tumor cells and tissues. Notably, IR promotes cilia formation and elongation in time- and dose-dependent manners. Mechanistic study shows that the suppression of YAP/Aurora A pathway contributes to IR-induced ciliogenesis, which is diminished by Aurora A overexpression. The ciliated tumor cells undergo senescence but not apoptosis in response to IR and the abrogation of cilia formation is sufficient to elevate the lethal effect of IR. Furthermore, we show that IR-induced ciliogenesis leads to the activation of Hedgehog signaling pathway to drive senescence and resist apoptosis, and its blockage enhances cellular radiosensitivity by switching senescence to apoptosis. In summary, this work shows evidence of primary cilia in coordinating cellular response to IR in tumor cells, which may help to supply a novel sensitizing target to improve the outcome of radiotherapy.

Effect of silencing SSB1 gene on the expression of NBS1 in irradiated rat submandibular gland cells.

The salivary gland (SGS) is a kind of organ vulnerable to ionizing radiation. Radiotherapy is an important treatment for head and neck tumors, but in the process of radiotherapy, tumor cells will be injured by radiation to a certain extent. Infrared-induced DNA double-strand break (IR-DSBs) is one of the most serious DNA damage. DNA repair proteins such as Nymegan rupture syndrome protein 1 (NBS1) play a key role in the identification and repair of DNA damage. but the interaction between SSB1 and NBS1 has not been elucidated. In this study, we irradiated rat submandibular gland (SMG) cells, which were either infected with a rAdE5-SSB1-1p2-shRNA recombinant adenovirus to silence SSB or a control virus, to explore the effect of IR on the expression NBS1 in the absence of SSB. Our results showed that the SSB1 mRNA transcripts and protein expression of SSB1 and NBS1 initially increased and decreased later with increased doses. The relative expression reached the highest levels when the SMG cells were irradiated with 2Gy of IR. Silencing the SSB1 gene suppressed the expression of both SSB1 and NBS1 regardless of irradiation. The expression of NBS1 decreased when the SSB1 gene was silenced. We concluded that IR affected the expression of both SSB1 and NBS1 and there is a synergistic effect on IR-induced NBS1 suppression and DSBs repair in SMG cells. These observations shed light on further investigation and elucidation of IR-caused DNA repair mechanisms.

Genetically predicted alterations in thyroid function are associated with the risk of benign prostatic disease.

Background: Benign prostatic diseases (BPDs), such as benign prostate hyperplasia (BPH) and prostatitis, harm the quality of life of affected patients. However, observational studies exploring the association between thyroid function and BPDs have hitherto yielded inconsistent results. In this study, we explored whether there is a causal genetic association between them using Mendelian randomization (MR) analysis. Methods: We used publicly available summary statistics from the Thyroidomics Consortium and 23andMe on thyrotropin (TSH; 54,288 participants), thyroxine [free tetraiodothyronine (FT4); 49,269 participants], subclinical hypothyroidism (3,440 cases and 49,983 controls), overt hypothyroidism (8,000 cases and 117,000 controls), and subclinical hyperthyroidism (1,840 cases and 49,983 controls) to screen for instrumental variables of thyroid function. Results for BPD such as prostatic hyperplasia (13,118 cases and 72,799 controls) and prostatitis (1,859 cases and 72,799 controls) were obtained from the FinnGen study. The causal relationship between thyroid function and BPD was primarily assessed using MR with an inverse variance weighted approach. In addition, sensitivity analyses were performed to test the robustness of the results. Results: We found that TSH [OR (95% CI) = 0.912(0.845-0.984), p =1.8 x 10-2], subclinical hypothyroidism [OR (95% CI) = 0.864(0.810-0.922), p =1.04 x 10-5], and overt hypothyroidism [OR (95% CI) = 0.885 (0.831-0. 944), p =2 x 10-4] had a significant effect on genetic susceptibility to BPH, unlike hyperthyroidism [OR (95% CI) = 1.049(0.990-1.111), p =1.05 x 10-1] and FT4 [OR (95% CI) = 0.979(0.857-1.119), p = 7.59 x 10-1] had no effect. We also found that TSH [OR (95% CI) =0.823(0.700-0.967), p = 1.8 x 10-2] and overt hypothyroidism [OR (95% CI) = 0.853(0.730-0.997), p = 4.6 x 10-2] significantly influenced the prostatitis, whereas FT4 levels [OR (95% CI) = 1.141(0.901-1.444), p = 2.75 x 10-1], subclinical hypothyroidism [OR (95% CI) =0. 897(0.784- 1.026), p = 1.12 x 10-1], and hyperthyroidism [OR (95% CI) = 1.069(0.947-1.206), p = 2.79 x 10-1] did not have a significant effect. Conclusion: Overall, our study results suggest that hypothyroidism and TSH levels influence the risk of genetically predicted BPH and prostatitis, providing new insights into the causal relationship between thyroid function and BPD.

Honokiol@PF127 crosslinked hyaluronate-based hydrogel for promoting wound healing by regulating macrophage polarization.

Bacterial infection, oxidative stress and inflammation are the main obstacles in wound healing. Hydrogels with moist and inherent properties are beneficial to wound healing. Here, we fabricated a honokiol-laden micelle-crosslinked hyaluronate-based hydrogel by simply mixing honokiol-laden PF127-CHO micelles, 3,3'-dithiobis(propionohydrazide) grafted hyaluronic acid and silver ions. PF127 could not only effectively load hydrophobic small molecules but also be macromolecular crosslinker for preparing hydrogels. Hyaluronic acid plays an essential role in wound healing processes including regulating macrophage polarization towards M2 phenotype. The chemical dynamic acylhydrazone crosslinking and physical crosslinking among PF127-CHO micelles constructed hydrogel's networks, which endowed hydrogel with excellent self-healing properties. PF-HA-3 hydrogel also exhibited outstanding antioxidant and antibacterial capabilities. In a full-thickness skin defect model, this degradable and biocompatible hydrogel could promote wound healing by remodeling wound tissues, regulating M2 polarization and angiogenesis. In summary, this inherent multifunctional hydrogel will provide a promising strategy for designing bioactive compounds-based wound dressings.

Facile preparation of polyphenol-crosslinked chitosan-based hydrogels for cutaneous wound repair.

The design and facile preparation of the smart hydrogel wound dressings with inherent excellent antioxidant and antibacterial capacity to effectively promote wound healing processes is highly desirable in clinical applications. Herein, a series of multifunctional hydrogels were prepared by the dynamic Schiff base and boronate ester crosslinking among phenylboronic acid (PBA) grafted carboxymethyl chitosan (CMCS), polyphenols and Cu2+-crosslinked polyphenol nanoparticles (CuNPs). The dynamic crosslinking bonds endowed hydrogels with excellent self-healing and degradable properties. Three polyphenols including tannic acid (TA), oligomeric proanthocyanidins (OPC) and (-)-epigallocatechin-3-O-gallate (EGCG) contributed to the outstanding antibacterial and antioxidant abilities of these hydrogels. The tissue adhesive capacity of hydrogels gave them good hemostatic effect. Through a full-thickness skin defect model of mice, these biocompatible hydrogels could accelerate wound healing processes by promoting granulation tissue formation, collagen deposition, M2 macrophage polarization and cytokine secretion, demonstrating that these natural-derived hydrogels with inherent physiological properties and low-cost preparation approaches could be promising dressing materials.

Resection of inferior vena cava, abdominal aorta, bilateral common iliac arteries, and bilateral partial external iliac arteries with artificial vessel replacement during radical endometrial cancer surgery: a case report.

BACKGROUND: Endometrial carcinoma (EC) is a common malignant tumor of the female reproductive system, often accompanied by lymph node metastasis. Artificial vascular implantation is a common surgical treatment for mediastinal tumors and abdominal aortic aneurysms but is rarely used in gynecological surgery. CASE PRESENTATION: A 54-year-old female patient was first admitted to the hospital in January 2018 due to "irregular vaginal bleeding over 3 months". CT showed a mass in the uterine cavity, and several swollen lymph nodes in the retroperitoneum and pelvic cavity. The initial diagnosis was an endometrial malignant tumor. We performed radical endometrial cancer surgery with parallel resection of inferior vena cava, abdominal aorta, bilateral common iliac arteries, bilateral external iliac arteries, and artificial vessel replacement, which was successful, with good postoperative recovery and no lesion progression at 3 years postoperative follow-up. CONCLUSION: This is an early case of gynecological clinical use of prostheses. Through multidisciplinary cooperation, the surgical resection rate of patients with EC in radical surgery was improved without serious fatal complications and achieved a high long-term postoperative survival rate.

Antifungal Activity of Endophytic Bacillus K1 Against Botrytis cinerea.

Gray mold caused by Botrytis cinerea is detrimental to plants and fruits. Endophytes have been shown to modify plant disease severity in functional assays. We conducted this study to investigate the endophytic strain Bacillus K1 with excellently antagonistic B. cinerea from the wild grape endosphere. We identified a wild grape endophytic strain K1 with high antifungal activity against B. cinerea both in vitro and in vivo. Combining the phylogenetic results based on 16S rDNA and genome sequencing, K1 was assigned as Bacillus subtilis. The in vitro results displayed that K1 and its volatile substances could significantly inhibit the mycelia growth of B. cinerea. Grape fruit inoculated with Bacillus K1 showed lower gray mold during treatment. The higher levels of defense-related enzymes, including peroxidase, polyphenol oxidase, and phenylalanine ammonia lyase, were induced in grapes after inoculation. Scanning electron microscopy (SEM) suggested that K1 inhibited mycelial growth via bacterial colonization and antibiosis in grapes. The gas chromatography-mass spectrometry analysis identified 33 volatiles in which dibutyl phthalate was the major compound accounting for 74.28%. Dibutyl phthalate demonstrated strong activity in suppressing the mycelia growth of B. cinerea. Genome bioinformatics analysis revealed that the K1 chromosome harbored many known biosynthesis gene clusters encoding subtilosin, bacillaene, bacillibactin, bacilysin, and fengycin. This study provides a potential biological agent to control diseases of post-harvest grape fruit and improves our understanding of the possible biocontrol mechanisms of the Bacillus strain.

Carbazolic Conjugated Organic Polymers for Visible-Light-Driven CO2 Photoreduction with H2 O to CO with High Efficiency and Selectivity.

Visible-light-driven CO2 photoreduction with H2 O to value-added chemicals in high efficiency and selectivity is significant but challenging. Herein, a series of carbazolic conjugated organic polymers (CB-COPs) with electron donor-acceptor (D-A) structures were prepared, which showed high efficiency for visible-light-driven photocatalytic reduction of CO2 with H2 O in a solid-gas mode, affording CO as the exclusive carbonaceous product. Especially, CB-COP-mpd derived from 3,5-di(9H-carbazol-9-yl)pyridine exhibited the highest CO evolution rate up to 191.46 µmol g-1 h-1 with a selectivity of 100 %. Mechanism studies showed that carbazolyl is a promising electron donor candidate for constructing CB-COPs with D-A structures, capable of improving the catalytic efficiency and suppressing H2 generation. The acceptor building block with excessive electron withdrawing capability was favorable to H2 O adsorption, thus resulting in the generation of H2 . This work provides new insights for designing COPs photocatalysts for CO2 photocatalytic reduction.

Effect of Surfactants on the Microstructures of Hierarchical SnO2 Blooming Nanoflowers and their Gas-Sensing Properties.

Hierarchical SnO2 blooming nanoflowers were successfully fabricated via a simple yet facile hydrothermal method with the help of different surfactants. Here we focus on exploring the promotion effects of surfactants on the self-assembly of 2D SnO2 nanosheets into 3D SnO2 flower-like structures as well as their gas-sensing performances. The polyporous flower-like SnO2 sensor exhibits excellent gas-sensing performances to ethanol and H2S gas due to high porosity when polyvinyl pyrrolidone is added into the precursor solution as a surfactant. The response/recovery times were about 5 s/8 s for 100 ppm ethanol and 4 s/20 s for 100 ppm H2S, respectively. Especially, the maximum response value of H2S is estimated to be 368 at 180 °C, which is one or two orders of magnitude higher than that of other test gases in this study. That indicates that the sensor fabricated with the help of polyvinyl pyrrolidone has good selectivity to H2S.

Itraconazole inhibits invasion and migration of pancreatic cancer cells by suppressing TGF-ß/SMAD2/3 signaling.

Pancreatic cancer is the fourth leading cause of cancer-associated mortality worldwide, with an overall 5-year survival rate <8%. We studied the therapeutic effect of itraconazole (ITZ), a commonly used broad-spectrum anti-fungal agent, in the treatment of pancreatic cancer, and to reveal the underlying anticancer mechanisms. Effects of ITZ on cell proliferation, apoptosis, invasion and migration were observed by MTT assays and colony formation assays, flow cytometry, wound scratch assays and transwell assays, respectively. Western blotting and immunofluorescence were performed to investigate the effect of ITZ on the epithelial to mesenchymal transition (EMT) of pancreatic cancer cells. Recombinant transforming growth factor-ß (TGF-ß) and TGF-ß neutralizing antibody were used to study the effect of ITZ on the TGF-ß/SMAD2/3 signaling. Transgenic engineered mice which harboring the spontaneous pancreatic cancer was applied to investigate the therapeutic role of ITZ in vivo. We report that ITZ inhibited the viability and induced apoptosis of pancreatic cancer cells. Furthermore, ITZ suppressed the invasion and migration of pancreatic cancer cells. We found that ITZ treatment was efficient in suppressing EMT and that the effect of ITZ was partially mediated by impaired TGF-ß/SMAD2/3 signaling. The role of TGF-ß/SMAD2/3 signaling in mediating the effect of ITZ was confirmed based on the results that recombinant TGF-ß induced, but the TGF-ß neutralizing antibody inhibited EMT as well as the invasion and migration of pancreatic cancer cells. Also, the anticancer effect of ITZ could be partially reversed by recombinant TGF-ß. Furthermore, treatment with ITZ suppressed growth of tumor in vivo. Taken together, we suggest that ITZ may potentially serve as a new chemotherapeutic agent for the treatment of pancreatic cancer.

Porous Fe3O4 nanoparticles: synthesis and application in catalyzing epoxidation of styrene.

A facile route was employed to synthesize porous magnetite via reaction of FeCl(3)·6H(2)O with N(2)H(4)·H(2)O in ethylene glycol without any structure-directing agent. The resultant Fe(3)O(4) particles were characterized by transmission electron microscopy, N(2) adsorption, X-ray photoelectron spectroscopy, and thermal gravimetric analysis. It was demonstrated that the particle size varied in the range of 40-220 nm, and the pore size of particles was centered around 2 nm. The gases produced in the formation process of the particles played key role in the formation of the porous structure. The obtained porous magnetite was used as support to immobilize Au nanoparticles with size less than 2 nm with the assistance of L-cysteine. The as-prepared Fe(3)O(4) particles can effectively catalyze epoxidation of styrene, and the immobilization of Au nanoparticles on the Fe(3)O(4) support significantly improved the activity of the catalyst.

[The expression of laminin in the intermingled skin transplantation of allograft and autograft].

OBJECTIVE: To explore the healing mechanism of full-thickness wound treating by the intermingled skin transplantation of large sheet allograft with autograft through studying the expression of laminin (LN). METHODS: Thirty-six SD rats with 10% to 15% of total body surface area (TBSA) full-thickness were made. After 3 days, the devitalized tissue were excised and transplanted a large sheet of allograft from Wistar rats and islets of autografts were implanted 3 days later. On day 3, 5, 7, 14, 21 after allografting, the expression of LN in the grafts were detected by immunohistochemistry. RESULTS: On the 7th day postallografting, LN, which played positive action of epidermal cell adhesion, still retained in the allodermis after the rejection of alloepidermis occurred. On the 14th day postallografting, there appeared scattered LN underneath the epidermal cells migrating from islets of autografts. On the 21st day postallografting, LN in the basement membrane of skin grafts had completely formed. CONCLUSION: The intermingled transplantation of large sheet allograft with autograft may provide components of basement membrane for wound healing, which may help to improve the appearance and function of skin.