Silencing CK19 regulates ferroptosis by affecting the expression of GPX4 and ACSL4 in oral squamous cell carcinoma in vivo and in vitro.

To analyze the mechanism of how interfering with the cytokeratin 19 (CK19) pathway via the ferroptosis pathway affects tumor biological behaviors in the process of oral squamous cell carcinoma (OSCC) development. TCGA was used to analyze the expression of CK19 in pan-cancer and head and neck squamous cell carcinoma (HNSC) and to explore the ferroptosis-related genes related to HNSC. The effect of silencing CK19 on the migration ability of HSC-4 cells was verified by wound healing and migration assay. HSC-4 cells with silencing of CK19 and tumor-bearing nude mouse model were constructed. RT-qPCR, immunofluorescence and western blot were used to analyze the expression of ferroptosis-related genes. CK19 is highly expressed in human OSCC and nude mice. The migration ability of cells in the CK19-silenced group was lower than that of the control group. In vivo and in vitro, CK19 was negatively correlated with the expression of ACSL4 and positively correlated with the expression of GPX4. Compared with the control group, GPX4 expression was down-regulated and ACSL4 expression was up-regulated in the CK19-silenced group. Silencing CK19 also increased intracellular Fe2+ content and MDA content. Silencing CK19 can affect the expression of GPX4 and ACSL4 to regulate ferroptosis and at the same time increase the content of MDA, Fe2+ and ROS levels, thereby activating the regulation of ferroptosis pathway in the development of OSCC.

Ultrathin and Self-Supporting MOF/COF-Based Composite Membranes for Hydrogen Separation and Purification from Coke Oven Gas.

Coke oven gas (COG) is considered to be one of the most likely raw materials for large-scale H2 production in the near or medium term, with membrane separation technologies standing out from traditional technologies due to their less energy-intensive structures as well as simple operation and occupation. Based on the "MOF-in/on-COF" pore modification strategy, the COF membrane (named the PBD membrane) and ZIF-67 were used as assembly elements to design advanced molecular sieving membranes for hydrogen separation. The composition and microstructure of membranes before and after ZIF-67 loading as well as ZIF-67-in-PBD membranes under different preparation conditions (metal ion concentration, metal-ligand ratio, and reaction time) were investigated by various characterizations to reveal the synthesis regularity and microstructure regulation. Furthermore, H2/CH4 separation performances and separation mechanisms were also analyzed and compared. Finally, a dense, continuous, ultrathin, and self-supporting ZIF-67-in-PBD membrane with a Co2+ concentration of 0.02 mol/L, a metal-ligand ratio of 1:4, and a reaction time of 6 h exhibited the largest specific surface area, micropore proportion, and the best H2/CH4 separation selectivity (α = 33.48), which was significantly higher than the Robeson upper limit and was in a leading position among reported MOF membranes. The separation mechanism was mainly size screening, and adsorption selectivity also contributed a little.

Verification of the expression trend and interaction prediction of innate immune cells and immune-checkpoint molecules in the process of oral mucosal carcinogenesis.

OBJECTIVES: This study aimed to explore the expression trends of innate immune cells and immune-checkpoint molecules validated by data calculation in the process of oral mucosal carcinogenesis, as well as to explore methods of suppressing oral mucosal carcinogenesis based on immunotherapy by predicting their interactions. Me-thods 1) The cancer genome atlas (TCGA) database comprehensively scores immune cells and immune-checkpoint molecules in the process of oral mucosal carcinogenesis and screens out intrinsic immune cells and immune-checkpoint molecules that interfere with tumor immune escape. 2) Clinical patient blood routine data were collected for the statistical analysis of peripheral blood immune cells during the progression of oral mucosal carcinogenesis. Immune cells in peripheral blood that may affect the progression of oral mucosal carcinogenesis were screened. 3) Immunohistochemical staining was performed on intrinsic immune cells and immune-checkpoint molecules validated based on data calculation in various stages of oral mucosal carcinogenesis. 4) Special staining was used to identify innate immune cells in various stages of oral mucosal carcinogenesis based on data-calculation verification. 5) Survival analysis was conducted on intrinsic immune cells and immune-checkpoint molecules validated based on data calculation during the process of oral mucosal carcinogenesis. The association of intrinsic immune cells and immune-checkpoint molecules with the prognosis of oral squamous cell carcinoma was verified. RESULTS: The expression of monocytes and neutrophils increased during the process of oral mucosal carcinogenesis. The expression of eosinophils showed a single peak trend of up and down. The expression of mast cells decreased. In the process of oral mucosal carcinogenesis, the expression of the immune-checkpoint molecules cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and programmed cell death-ligand (PD-L1) increased. The expression trends of monocytes, neutrophils, and eosinophils were positively correlated with those of CTLA4 and PD-L1 immune-checkpoint molecules. The expression trend of mast cells was negatively correlated with the expression of CTLA4 and PD-L1. Monocytes, neutrophils, and eosinophils may promote tumor immune escape mediated by CTLA4 and/or PD-L1, thereby accelerating the progression of oral mucosal carcinogenesis. Mast cells may inhibit tumor immune escape mediated by CTLA4 and/or PD-L1, delaying the progression of oral mucosal carcinogenesis. CONCLUSIONS: Therefore, interference with specific immune cells in innate immunity can regulate the expression of CTLA4 and/or PD-L1 to a certain extent, inhibit tumor immune escape, and delay the progression of oral mucosal carcinogenesis.

Purification and characterization of a chicory polysaccharide and its application in stabilizing genistein for cancer therapy.

Genistein is an isoflavone with chemopreventive and therapeutic effects on various types of cancers. Apparently, in contrast to the advantages of multi-target therapy, the poor water solubility of this molecule is a major obstacle to its clinical application. In this work, zein/chicory polysaccharide nanoparticles (G-zein-P NPs) were prepared by pH-induced antisolvent precipitation method for the encapsulation of genistein. Firstly, an acidic polysaccharide (CIP70-2) with a molecular weight of 66.7 kDa was identified from the roots of chicory (Cichorium intybus). This natural macromolecule was identified as a plant pectin, for which the structure included RG-I (rhamnogalacturonan I) and HG (homogalacturonan) regions. Using this polysaccharide, G-zein-P NPs were prepared, in which the water solubility of genistein was improved by encapsulation. The encapsulation efficiency and loading efficiency of genistein by composite nanoparticles reached 99.0 % and 6.96 %, respectively. In vitro tumor inhibition experiments showed that the inhibitory effect of G-zein-P NPs on HepG2 cells was twice that of unencapsulated genistein. Moreover, the significant inhibition of tumor development and metastasis by G-zein-P NPs was observed in zebrafish xenograft models. The results suggested that zein/chicory polysaccharide nanoparticles may be a promising delivery carrier for genistein application in cancer prevention and therapy.

Baicalin prevents fibrosis of human trabecular meshwork cells via inhibiting the MyD88/NF-κB pathway.

Trabecular meshwork fibrosis contributes to increased aqueous humor outflow resistance, leading to elevated intraocular pressure in primary open-angle glaucoma. Baicalin, an extract from Scutellaria baicalensis Georgi, has shown anti-fibrotic effects in liver, lung, and kidney diseases. However, its anti-fibrotic effect on human trabecular meshwork (HTM) cells has not yet been clarified. In this study, we investigated its effects on TGF-ß2-induced HTM fibrosis as well as the underlying regulatory mechanisms. HTM cells were pretreated with baicalin, TAK-242, and baicalin + TAK-242 for 2 h followed by treatment with or without 5 ng/mL TGF-ß2 for 48 h. Cell viability was assayed using cell counting Kit-8 and fibronectin (FN), laminin (LN), and α-smooth muscle actin (α-SMA) were assessed by western blotting, reverse transcription-polymerase chain reaction (RT-PCR), and immunocytochemistry. Further, the protein and gene expression levels of the TLR4/MyD88/NF-κB pathway (TLR4, MyD88, and NF-κB p65) were also examined by western blotting and RT-PCR, respectively. Thus, we observed that high doses of baicalin (40 µM) decreased (p < 0.1) HTM cell viability and 20 µM baicalin pretreatment was identified as the optimum pretreatment concentration. TGF-ß2 upregulated (p < 0.5) the expression of FN, LN, α-SMA, MyD88, NF-κB p65 proteins and mRNA in HTM cells, and these effects were inhibited by baicalin and TAK-242 (p < 0.5). However, western blot analysis showed that baicalin did not repress TLR4 expression in HTM cells. Therefore, our findings suggested that baicalin could prevent TGF-ß2-induced extracellular matrix (FN, LN) deposition and α-SMA expression in HTM cells by inhibiting the MyD88/NF-κB pathway.

ResnetAge: A Resnet-Based DNA Methylation Age Prediction Method.

Aging is a significant contributing factor to degenerative diseases such as cancer. The extent of DNA methylation in human cells indicates the aging process and screening for age-related methylation sites can be used to construct epigenetic clocks. Thereby, it can be a new aging-detecting marker for clinical diagnosis and treatments. Predicting the biological age of human individuals is conducive to the study of physical aging problems. Although many researchers have developed epigenetic clock prediction methods based on traditional machine learning and even deep learning, higher prediction accuracy is still required to match the clinical applications. Here, we proposed an epigenetic clock prediction method based on a Resnet neuro networks model named ResnetAge. The model accepts 22,278 CpG sites as a sample input, supporting both the Illumina 27K and 450K identification frameworks. It was trained using 32 public datasets containing multiple tissues such as whole blood, saliva, and mouth. The Mean Absolute Error (MAE) of the training set is 1.29 years, and the Median Absolute Deviation (MAD) is 0.98 years. The Mean Absolute Error (MAE) of the validation set is 3.24 years, and the Median Absolute Deviation (MAD) is 2.3 years. Our method has higher accuracy in age prediction in comparison with other methylation-based age prediction methods.

Controllable Construction of Amino-Functionalized Dynamic Covalent Porous Polymers for High-Efficiency CO2 Capture from Flue Gas.

The design of high-efficiency CO2 adsorbents with low cost, high capacity, and easy desorption is of high significance for reducing carbon emissions, which yet remains a great challenge. This work proposes a facile construction strategy of amino-functional dynamic covalent materials for effective CO2 capture from flue gas. Upon the dynamic imine assembly of N-site rich motif and aldehyde-based spacers, nanospheres and hollow nanotubes with spongy pores were constructed spontaneously at room temperature. A commercial amino-functional molecule tetraethylenepentamine could be facilely introduced into the dynamic covalent materials by virtue of the dynamic nature of imine assembly, thus inducing a high CO2 capacity (1.27 mmol·g-1) from simulated flue gas at 75 °C. This dynamic imine assembly strategy endowed the dynamic covalent materials with facile preparation, low cost, excellent CO2 capacity, and outstanding cyclic stability, providing a mild and controllable approach for the development of competitive CO2 adsorbents.

Respiratory Prediction Based on Multi-Scale Temporal Convolutional Network for Tracking Thoracic Tumor Movement.

Radiotherapy is one of the important treatments for malignant tumors. The precision of radiotherapy is affected by the respiratory motion of human body, so real-time motion tracking for thoracoabdominal tumors is of great significance to improve the efficacy of radiotherapy. This paper aims to establish a highly precise and efficient prediction model, thus proposing to apply a depth prediction model composed of multi-scale enhanced convolution neural network and temporal convolutional network based on empirical mode decomposition (EMD) in respiratory prediction with different delay times. First, to enhance the precision, the unstable original sequence is decomposed into several intrinsic mode functions (IMFs) by EMD, and then, a depth prediction model of parallel enhanced convolution structure and temporal convolutional network with the characteristics specific to IMFs is built, and finally training on the respiratory motion dataset of 103 patients with malignant tumors is conducted. The prediction precision and time efficiency of the model are compared at different levels with those of the other three depth prediction models so as to evaluate the performance of the model. The result shows that the respiratory motion prediction model determined in this paper has superior prediction performance under different lengths of input data and delay time, and, furthermore, the network update time is shortened by about 60%. The method proposed in this paper will greatly improve the precision of radiotherapy and shorten the radiotherapy time, which is of great application value.

LncRNA MALAT1 promotes decidualization of endometrial stromal cells via sponging miR-498-3p and targeting histone deacetylase 4.

Decidualization of human endometrial stromal cells (hESCs) is important for the maintenance of a successful pregnancy. Histone deacetylase 4 (HDAC4) was reported to be involved in the dysfunction of decidua-derived mesenchymal stem cells. However, the role of HDAC4 underlying decidualization of hESCs remains unclear. We intended to explore the function and molecular mechanism of HDAC4 in hESCs. In vitro expansion of hESCs using a serum-free medium was used to confirm the characteristics of hESCs. Gene expression in hESCs was evaluated by reverse transcription-quantitative polymerase chain reaction. CCK-8 assay, TUNEL staining, flow cytometry analysis, and Western blot analysis were performed to test the effects of HDAC4 and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on hESCs. RNA pull-down and luciferase reporter assays were performed to validate the relationship between genes. In this study, the characteristics of hESCs were sustained in serum-free medium during a process of propagation. HDAC4 knockdown suppressed hESCs viability and promoted hESCs apoptosis. HDAC4 was targeted by miR-498-3p in hESCs. MALAT1 bound with miR-498-3p in hESCs. HDAC4 expression was positively regulated by MALAT1 and negatively regulated by miR-498-3p in hESCs. HDAC4 upregulation countervailed the effects of MALAT1 silencing on hESCs proliferation, apoptosis, and decidualization of hESCs. Overall, MALAT1 facilitated the decidualization of hESCs via binding with miR-498-3p and upregulating HDAC4, which might provide a new direction for the maintenance of a successful pregnancy.

CircMCTP2 (has-circ-0000658) facilitates the proliferation and metastasis of bladder carcinoma through modulating the miR-498/murine double minute-2 axis.

CircMCTP2 is a novel circRNA, which is associated with various kinds of malignant tumors progression, such as gastric cancer. However, the function of circMCTP2 in bladder carcinoma (BC) has no idea. The purpose of this study was tantamount to functionally dissect circMCTP2 in the progression of BC. In our study, circMCTP2 expression was strongly increased in BC tissues and cell lines. High expression of circMCTP2 predicted a poor prognosis of BC patients. CircMCTP2 deficiency impaired the cell growth, migration as well as invasive ability of BC cell lines (J82 and T24). In vivo, circMCTP2 deficiency cut the tumor growth rates and the tumor weight. In BC cells, circMCTP2 deficiency enhanced the translation of E-cadherin, while diminishing the translation of N-cadherin, Vimentin, and Snail. Moreover, circMCTP2 acted as a sponge of miR-498 to regulate murine double minute-2 (MDM2) expression. In BC tissues, a negative correlation was observed between the expression levels of circMCTP2 and miR-498. Additionally, either miR-498 silencing or MDM2 over-expression augmented the carcinogenic action of circMCTP2 on BC. In conclusion, our study showed that circMCTP2 regulates the expression of MDM2 by sponging miR-498 to promote the development of BC. These findings offer a new strategy for early diagnosis of BC and its therapeutics.

Construction of inulin-based selenium nanoparticles to improve the antitumor activity of an inulin-type fructan from chicory.

Cancer has become one of the leading causes of death worldwide. It is urgent to develop new antitumor drugs with high efficiency and low toxicity. In this study, an inulin-type fructan CIP70-1 was purified and characterized from chicory and showed weak antitumor activity. To improve its antitumor effects, inulin-based selenium nanoparticles (CIP-SeNPs) were constructed and characterized. CIP-SeNPs were spherical nanoparticles (60 nm), which remained stable in water for more than 3 months. A cellular antitumor assay revealed that CIP-SeNPs had stronger inhibitory effects on cancer cells (MCF-7, A549, and HepG2) than CIP70-1 alone. Furthermore, the in vivo antitumor effects of CIP-SeNPs were confirmed using zebrafish models. The results showed that CIP-SeNPs significantly inhibited the proliferation and migration of tumors as well as the angiogenesis of transgenic zebrafish in the concentration range of 1-4 µg/mL.

Prediction of occult tumor progression via platelet RNAs in a mouse melanoma model: a potential new platform for early detection of cancer.

BACKGROUND: Cancer screening provides the opportunity to detect cancer early, ideally before symptom onset and metastasis, and offers an increased opportunity for a better prognosis. The ideal biomarkers for cancer screening should discriminate individuals who have not developed invasive cancer yet but are destined to do so from healthy subjects. However, most cancers lack effective screening recommendations. Therefore, further studies on novel screening strategies are urgently required. METHODS: We used a simple suboptimal inoculation melanoma mouse model to obtain 'pre-diagnostic samples' of mice with macroscopic melanomas. High-throughput sequencing and bioinformatic analysis were employed to identify differentially expressed RNAs in platelet signatures of mice injected with a suboptimal number of melanoma cells (eDEGs) compared with mice with macroscopic melanomas and negative controls. Moreover, 36 genes selected from the eDEGs via bioinformatics analysis were verified in a mouse validation cohort via quantitative real-time PCR. LASSO regression was utilized to generate the prediction models with gene expression signatures as the best predictors for occult tumor progression in mice. RESULTS: These RNAs identified from eDEGs of mice injected with a suboptimal number of cancer cells were strongly enriched in pathways related to immune response and regulation. The prediction models generated by 36 gene qPCR verification data showed great diagnostic efficacy and predictive value in our murine validation cohort, and could discriminate mice with occult tumors from control group (area under curve (AUC) of 0.935 (training data) and 0.912 (testing data)) (gene signature including Cd19, Cdkn1a, S100a9, Tap1, and Tnfrsf1b) and also from macroscopic tumor group (AUC of 0.920 (training data) and 0.936 (testing data)) (gene signature including Ccr7, Cd4, Kmt2d, and Ly6e). CONCLUSIONS: Our proof-of-concept study provides evidence for potential clinical relevance of blood platelets as a platform for liquid biopsy-based early detection of cancer.

Effect of crosstalk among conspirators in tumor microenvironment on niche metastasis of gastric cancer.

In Traditional Chinese medicine, the metaphoric views of the human body are based on observations of nature guided by the theory of "Yin-Yang". The direct meanings of yin and yang are the bright and dark sides of an object, which often represent a wider range of opposite properties. When we shifted our view to gastric cancer (GC), we found that there are more distinctive Yin and Yang features in the mechanism of GC development and metastasis, which is observed in many mechanisms such as GC metastasis, immune escape, and stem cell homing. When illustrating this process from the yin-yang perspective, categorizing different cells in the tumor microenvironment enables new and different perspectives to be put forward on the mechanism and treatment of GC metastasis.

Structure features, selenylation modification, and improved anti-tumor activity of a polysaccharide from Eriobotrya japonica.

A homogeneous polysaccharide, EJP90-1, was isolated from the leaves of E. japonica by hot water extraction in this study. EJP90-1 (7702 Da) was a heteropolysaccharide mainly consisting of →5)-linked-α-L-Araf-(1→, →4)-linked-ß-D-Manp-(1→, →2,4)-linked-α-L-Rhap-(1→, →4)-linked-α-D-Xylp-(1→, →4)-linked-ß-D-Galp-(1→, →2)-linked-ß-D-Galp-(1→, →6)-linked-ß-D-Glcp-(1→, α-D-Glcp-(4→, and t-linked-α-L-Araf. EJP90-1 was found to show moderate anti-tumor activity at the cellular level. In order to improve the anti-tumor activity and the potential applications of EJP90-1, a typical sodium selenite-nitric acid (Na2SeO3-HNO3) modification on EJP90-1 was carried out. X-ray photoelectron spectroscopy (XPS) and energy dispersive spectrometer (EDS) analysis confirmed that Se was successfully introduced into the polymer chain of EJP90-1. The subsequent in vitro cytotoxicity evaluation showed the selenylation modification derivative (EJP90-1-Se) possessed significant antiproliferative activity against cancer cells (HepG2 and A549 cells) through inducing cell apoptosis. The anti-tumor activity of EJP90-1-Se was further confirmed by zebrafish models, which inhibited the proliferation and migration of HepG2 cells and the angiogenesis.

A dandelion polysaccharide and its selenium nanoparticles: Structure features and evaluation of anti-tumor activity in zebrafish models.

In this study, an inulin fructan (TMP50-2) with moderate anti-tumor activity was obtained from dandelion. To further improve the anti-tumor activity of TMP50-2, a monodisperse and stable spherical nanoparticle (Tw-TMP-SeNP, 50 nm) was fabricated. Physico-chemical analysis revealed that TMP50-2 and Tween 80 were tightly wrapped on the surface of SeNPs by forming CO⋯Se bonds or through hydrogen bonding interaction (OH⋯Se). In vitro anti-tumor assay showed that Tw-TMP-SeNP treatment could significantly inhibit the proliferation of cancer cells (HepG2, A549, and HeLa) in a dose-dependent manner, while HepG2 cells were more susceptible to Tw-TMP-SeNP with an IC50 value of 46.8 µg/mL. The apoptosis induction of HepG2 cells by Tw-TMP-SeNP was evidenced by increasing the proportion of apoptotic cells ranging from 12.5% to 27.4%. Furthermore, in vivo zebrafish model confirmed the anti-tumor activity of Tw-TMP-SeNP by inhibiting the proliferation and migration of tumor cells as well as the angiogenesis of zebrafish embryos.

Predictive factors of surgical site infection after hysterectomy for endometrial carcinoma: a retrospective analysis.

BACKGROUND: Surgical site infection (SSI) is a common postoperative complication. We aimed to analyze the potential risk factors of SSI in patients with endometrial carcinoma. METHODS: Patients with endometrial carcinoma who underwent surgery treatment in our hospital from Sept 1, 2018 to August 31, 2020 were included. We retrospectively compared the characteristics of SSI and no SSI patients, and logistic regression analyses were performed to identify the risk factors of SSI in patients with endometrial carcinoma. RESULTS: A total of 318 postoperative patients with endometrial carcinoma were included. The incidence of SSI in patients with endometrial carcinoma was 14.47 %. There were significant differences on the FIGO stage, type of surgery, durations of drainage, postoperative serum albumin and postoperative blood sugar (all p < 0.05), and no significant differences on the age, BMI, hypertension, diabetes, hyperlipidemia, estimated blood loss, length of hospital stay were found (all p > 0.05). FIGO stage IV (HR3.405, 95 %CI 2.132-5.625), open surgery (HR2.692, 95 %CI 1.178-3.454), durations of drainage ≥ 7 d (HR2.414,95 %CI 1.125-2.392), postoperative serum albumin < 30 g/L (HR1.912,95 %CI 1.263-2.903), postoperative blood sugar ≥ 10 mmol/L (HR1.774,95 %CI 1.102-2.534) were the independent risk factors of SSI in patients with endometrial carcinoma (all p < 0.05). CONCLUSIONS: Measures including reasonable control of serum albumin and blood glucose levels, minimally invasive surgery as much as possible, timely assessment of drainage and early removal of the tube may be beneficial to reduce the postoperative SSI in in patients with endometrial carcinoma.

Circular RNA ZNF609 functions as a competing endogenous RNA in regulating E2F transcription factor 6 through competitively binding to microRNA-197-3p to promote the progression of cervical cancer progression.

Countless studies have demonstrated that Circular RNAs (circRNAs) exert vital effects in regulating tumorigenesis of various cancers. CircRNA ZNF609 (circ-ZNF609) has been reported as an oncogene in various human cancers. Nevertheless, its regulating effect in cervical cancer (CC) remains to be further explored. RT-qPCR was adopted to measure circ-ZNF609, miR-197-3p and E2F6 levels. CC cell proliferation, migration and invasion were analyzed via CCK-8 and transwell assays. Dual-luciferase reporter assay was adopted to confirm the interaction between miR-197-3p and circ-ZNF609 or E2F6. In the present study, it was found that circ-ZNF609 was elevated in CC tissues and cell lines, and circ-ZNF609 deletion repressed cell viability, migration and invasion in CC. Moreover, circ-ZNF609 was identified to negatively regulate miR-197-3p expression in CC cells. The inhibition of miR-197-3p abrogated the inhibitory effect on CC cell proliferation, migration and invasion induced by circ-ZNF609 knockdown. Additionally, we further demonstrated that circ-ZNF609 upregulated E2F6 by interacting with miR-197-3p. Finally, rescue assays indicated that E2F6 overexpression upended the suppression of CC progression induced by circ-ZNF609 deletion. In conclusion, circ-ZNF609 promoted CC progression through modulating the miR-197-3p/E2F6 axis as an oncogene. This finding offers a unique insight into CC molecular mechanism and suggests a potential target for CC therapy.

Structural elucidation of an immunological arabinan from the rhizomes of Ligusticum chuanxiong, a traditional Chinese medicine.

In the present study, an immunological arabinan, LCP70-2A, was isolated from Ligusticum chuanxiong for the first time. The absolute molecular weight of LCP70-2A was determined to be 6.46 × 104 g/mol using the HPSEC-MALLS-RID method. The absolute configuration of arabinose in LCP70-2A was determined to be L-configuration. Physicochemical characterization revealed that LCP70-2A was a homogeneous polysaccharide and had a backbone of (1 â†’ 5)-linked α-L-Araf with terminal α-L-arabinose residues at position O-2 and O-3. Molecular conformation analysis showed that LCP70-2A was a branching polysaccharide with a compact coil chain conformation in 0.1 M NaCl solution. In addition, in vitro cell assays showed that LCP70-2A can activate macrophages by enhancing the phagocytosis and potentiating the secretion of immunoregulatory factors including NO, TNF-α, IL-6, and IL-1ß. Furthermore, LCP70-2A was proved to promote the production of ROS and NO using the zebrafish model, suggesting that LCP70-2A can be further developed as a candidate supplement for immunological enhancement.

Treatment of HPV Infection-Associated Low Grade Cervical Intraepithelial Neoplasia with 5-Aminolevulinic Acid-Mediated Photodynamic Therapy.

OBJECTIVE: To investigate the efficacy of 5-aminoketovalic acid (5-ALA) photodynamic therapy (PDT) in the treatment of patients with low cervical intraepithelial neoplasia (CINI) combined with high-risk human papillomavirus ((HR-HPV), and the factors affecting the efficacy. METHODS: 80 patients with CINI and HR-HPV infection were selected for the study. They received once weekly 5-ALA-PDT for either three or six treatments. To evaluate the clinical efficacy of 5-ALA-PDT treatment, follow-up evaluations were conducted at 3, 6 and 12 months, utilizing thinPrep cytology test(TCT)and colposcopic histopathological biopsy for the detection of HPVDNA. RESULTS: Following PDT, HR-HPV remission rates at 3, 6 and 12 months were 75.32%, 80.52%, and 81.82%, respectively. Complete remission rate of CINI was 94.81% (73/77 patients). There was no statistically significant difference in the remission rate of HR-HPV between 3 and 6 treatments with PDT (P > 0.05). Likewise, there was no difference in the remission rate comparing patients ≤40 years old and those >40 years old (P > 0.05). However, the remission rate was statistically greater in patients with normal vaginal microecology compared to patients with vaginal microecologic imbalance (P = 0.004). CONCLUSIONS: Not only can 5-ALA-PDT effectively clear CINI, but it also can clear HR-HPV. Vaginal microecological imbalance can reduce the effect of PDT on HR-HPV, whereas differences in age or frequency of PDT do not affect the remission rate of PDT on HR-HPV.

NUP210 and MicroRNA-22 Modulate Fas to Elicit HeLa Cell Cycle Arrest.

PURPOSE: Cervical cancer is one of the most fatal diseases among women in under-developed countries. To improve cervical cancer treatment, discovery of new targets is needed. In this study, we investigated the expression of NUP210, miR-22, and Fas in cervical cancer tissues and their functions in cell cycle regulation. MATERIALS AND METHODS: We detected and compared the expression levels of NUP210, miR-22, and Fas in cervical cancer tissues with paired normal tissues using immunohistochemistry, Western blot, and real-time quantitative polymerase chain reaction. NUP210 was knocked down in HeLa cells via lentivirus, followed by cell cycle and proliferation analysis. Using a luciferase reporter assay, we explored the link between miR-22 and NUP210. We overexpressed miR-22 in HeLa cells and analyzed cell cycle and proliferation function. We then overexpressed miR-22 in NUP210 knockdown cells to explore the connection between Fas and miR-22-NUP210 signaling. RESULTS: We found that NUP210 was overexpressed in cervical cancer patients. Knocking down NUP210 restored cell apoptosis and proliferation. We confirmed miR-22 as a regulator of NUP210 and verified that miR-22 was inhibited in cervical cancer development. We also found that restoring miR-22 expression could induce cell apoptosis. Finally, we found that miR-22-regulated expression of NUP210 could alter Fas expression and, in turn, elicit cell cycle arrest and proliferation. CONCLUSION: miR-22 in cervical cancer is downregulated, resulting in NUP210 overexpression and inhibition of Fas-induced cell apoptosis.