The role of tumor-associated macrophages in the radioresistance of esophageal cancer cells via regulation of the VEGF-mediated angiogenic pathway.

Tumor-associated macrophages (TAMs) are known to promote tumor growth, invasion, metastasis, and protumor angiogenesis, but the role of TAMs in evading radiotherapy in esophagus cancer remains unclear. In this study, we first induced TAMs from human monocytes (THP-1) and identified using immunofluorescence and Western blotting assays. We then co-cultured them with human esophageal cancer cell lines. CCK-8, colony formation, Transwell, scratch test, and TUNEL assays showed that TAMs could promote proliferation, survival rate, invasion, migration, and radioresistance and could inhibit apoptosis of the esophageal squamous carcinoma cell lines KYSE-150 and TE-1 before and after radiotherapy both in vivo and in vitro. Using LV-VEGFA-RNAi lentiviral vectors, we also found that TAMs could increase the expression of VEGFA and that inhibition of VEGFA could inhibit the biological function caused by TAMs. Finally, a Western blotting assay was used to evaluate the expression of various factors underlying the mechanism of TAMs. VEGFA, MAPK, P-MAPK, BCL-2, and Snail proteins were found to be overexpressed in co-cultured groups, whereas after VEGFA inhibition, MAPK, P-MAPK, BCL-2, and Snail proteins were found to be significantly downregulated in the radiotherapy group. These study results offer important information regarding the mechanism of radioresistance in esophageal cancer.

p-d Orbital Hybridization-Engineered PdSn Nanozymes for a Sensitive Immunoassay.

Nanozymes with peroxidase-like activity have been extensively studied for colorimetric biosensing. However, their catalytic activity and specificity still lag far behind those of natural enzymes, which significantly affects the accuracy and sensitivity of colorimetric biosensing. To address this issue, we design PdSn nanozymes with selectively enhanced peroxidase-like activity, which improves the sensitivity and accuracy of a colorimetric immunoassay. The peroxidase-like activity of PdSn nanozymes is significantly higher than that of Pd nanozymes. Theoretical calculations reveal that the p-d orbital hybridization of Pd and Sn not only results in an upward shift of the d-band center to enhance hydrogen peroxide (H2O2) adsorption but also regulates the O-O bonding strength of H2O2 to achieve selective H2O2 activation. Ultimately, the nanozyme-linked immunosorbent assay has been successfully developed to sensitively and accurately detect the prostate-specific antigen (PSA), achieving a low detection limit of 1.696 pg mL-1. This work demonstrates a promising approach for detecting PSA in a clinical diagnosis.

Research status and prospects of organic photocatalysts in algal inhibition and sterilization: a review.

An increasing amount of sewage has been discharged into water bodies in the progression of industrialization and urbanization, causing serious water pollution. Meanwhile, the increase of nutrients in the water induces water eutrophication and rapid growth of algae. Photocatalysis is a common technique for algal inhibition and sterilization. To improve the utilization of visible light and the conversion efficiency of solar energy, more organic photocatalytic materials have been gradually developed. In addition to ultraviolet light, partial infrared light and visible light could also be used by organic photocatalysts compared with inorganic photocatalysts. Simultaneously, organic photocatalysts also exhibit favorable stability. Most organic photocatalysts can maintain a high degradation rate for algae and bacteria after several cycles. There are various organic semiconductors, mainly including small organic molecules, such as perylene diimide (PDI), porphyrin (TCPP), and new carbon materials (fullerene (C60), graphene (GO), and carbon nanotubes (CNT)), and large organic polymers, such as graphite phase carbon nitride (g-C3N4), polypyrrole (PPy), polythiophene (PTH), polyaniline (PANI), and polyimide (PI). In this review, the classification and synthesis methods of organic photocatalytic materials were elucidated. It was demonstrated that the full visible spectral response (400-750 nm) could be stimulated by modifying organic photocatalysts. Moreover, some problems were summarized based on the research status related to algae and bacteria, and corresponding suggestions were also provided for the development of organic photocatalytic materials.

Optimal treatment strategy and prognostic analysis for patients with non-metastatic pT4 colon adenocarcinoma.

Objective: This study endeavored to explore the optimal treatment strategy and conduct a prognostic analysis for patients diagnosed with pT4M0 (pathologic stage T4) colon adenocarcinoma (COAD). Methods and materials: A total of 8,843 patients diagnosed with pT4M0 COAD between January 2010 and December 2015 were included in this study from the Surveillance, Epidemiology, and End Results (SEER) database. These patients were randomly divided into a training set and an internal validation set using a 7:3 ratio. Variables that demonstrated statistical significance (P<0.05) in univariate COX regression analysis or held clinical significance were incorporated into the multivariate COX regression model. Subsequently, this model was utilized to formulate a nomogram. The predictive accuracy and discriminability of the nomogram were assessed using the C-index, area under the curve (AUC), and calibration curves. Decision curve analysis (DCA) was conducted to confirm the clinical validity of the model. Results: In the entire SEER cohort, the 3-year overall survival (OS) rate (74.22% vs. 63.20%, P<0.001) and the 3-year cancer-specific survival (CSS) rate (76.25% vs. 66.98%, P<0.001) in the surgery combined with postoperative adjuvant therapy (S+ADT) group surpassed those in the surgery (S) group. Multivariate COX regression analysis of the training set unveiled correlations between age, race, N stage, serum CEA (carcinoembryonic antigen), differentiation, number of resected lymph nodes, and treatment modalities with OS and CSS. Nomograms for OS and CSS were meticulously crafted based on these variables, achieving C-indexes of 0.692 and 0.690 in the training set, respectively. The robust predictive ability of the nomogram was further affirmed through receiver operating characteristic (ROC) and calibration curves in both the training and validation sets. Conclusion: In individuals diagnosed with pT4M0 COAD, the integration of surgery with adjuvant chemoradiotherapy demonstrated a substantial extension of long-term survival. The nomogram, which incorporated key factors such as age, race, differentiation, N stage, serum CEA level, tumor size, and the number of resected lymph nodes, stood as a dependable tool for predicting OS and CSS rates. This predictive model held promise in aiding clinicians by identifying high-risk patients and facilitating the development of personalized treatment plans.

Investigating the predictive value of vascular endothelial growth factor in the evaluation of treatment efficacy and prognosis for patients with non-surgical esophageal squamous cell carcinoma.

In this study, we aim to investigate the predictive value of serum vascular endothelial growth factor (VEGF) in evaluating treatment efficacy and long-term prognosis for patients with non-surgical esophageal squamous cell carcinoma (ESCC). The patients diagnosed with ESCC by histopathology who didn't receive surgical treatment were retrospectively analyzed. Through follow-up and prognostic analysis, we explored the value of serum VEGF changes before, during, and after radiotherapy for predicting treatment efficacy, and identified important indicators to construct the predictive model. Eighty-four patients were enrolled in this study, and the objective response rate (ORR) after treatment was 75.0%. The serum VEGF before, during and after radiotherapy were 108.2 ± 38.4, 98.6 ± 20.3 and 96.9 ± 20.0pg/ml, respectively. Staging and serum VEGF during radiotherapy were the independent factors affecting the treatment efficacy of non-surgical ESCC patients (OR=0.182 and 0.959, P<0.05). The median overall survival (OS) and progression-free survival (PFS) were 24.4 and 15.8 months. The 3-year, 5-year, 10-year OS rates and PFS rates were 35.7%, 26.2%, 14.4%, and 26.2%, 22.6%, 12.3%, respectively. By performing COX regression analysis, we found that the TNM stage, changes of VEGF after radiotherapy (∆VEGF2), and endoscopic histopathological response were the independent prognostic factors for OS and PFS (P<0.05). The R2 of the constructed prediction model was 0.328 and 0.362, and the C-index was 0.697 and 0.708, respectively. The follow-up time-dependent AUC showed that the predicted AUC was stable and greater than 0.7 as the follow-up time increased. For patients with non-surgical ESCC, those with low VEGF levels during radiotherapy had better treatment efficacy, and those with significant VEGF reduction after radiotherapy had a better prognosis. In summary, our results demonstrate that it is feasible to construct a model to evaluate and predict the efficacy and prognosis of patients with non-surgical ESCC based on serum VEGF measurement.

Incidence and risk factor analysis for swelling after apical microsurgery.

BACKGROUND: Swelling after apical microsurgery is a postoperative reaction and may reduce quality of life during healing. AIM: To evaluate periapical swelling after apical microsurgery and determine potential risk factors. METHODS: Ninety-eight apical microsurgery patients were selected for this study. Before surgery, bone shadow volume and density of pathological tissue were measured by cone beam computed tomography. The other variables (age, gender, operative teeth number, fistula, preoperative swelling, drug use and preoperative root canal treatments) were assessed during examination. Swelling degree was confirmed by questionnaires for patients on postoperative days 1, 7, 14 and 21. Statistical analyses were performed to identify predictors for swelling. RESULTS: Majority of patients reported moderate (45.9%) or severe (34.7%) swelling on day 1, and moderate (44.9%) or mild (45.9%) on postoperative day 7. Ninety-nine percent of patients had no or mild swelling on postoperative day 14. The average swelling level peaked on day 1 postoperatively and gradually decreased. Of statistical significance, age, bone shadow volume and density of pathological tissue acted as predictors of swelling (P < 0.05). However, there was no significant difference in gender, tooth number, fistula, preoperative swelling, drug use, or preoperative root canal treatments (P > 0.05). CONCLUSION: Younger patients with larger shadow volume and density were significantly more likely to develop swelling after apical microsurgery.

Nanodrugs Incorporating LDHA siRNA Inhibit M2-like Polarization of TAMs and Amplify Autophagy to Assist Oxaliplatin Chemotherapy against Colorectal Cancer.

Oxaliplatin (OXA) is a first-line chemotherapeutic agent for treating colorectal cancer (CC). However, the chemotherapeutic effect of OXA on CC is limited by the M2-like polarization of tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) and protective autophagy of tumor cells. Here, a cationic polymer APEG-PAsp(PEI) (PAPEI) was prepared to deliver small-interfering RNA (siRNA) to silence the lactate dehydrogenase A (LDHA) gene (LDHA-siRNA) to enhance the chemotherapeutic effect of OXA on CC. The PAPEI/LDHA-siRNA nanocomplex effectively silenced the LDHA gene to inhibit the secretion of lactic acid from tumor cells, resulting in inhibition of the M2-like polarization of TAMs. In addition, the nanocomplex also amplified OXA-induced autophagy and transformed protective autophagy into autophagic death. Consequently, the combination treatment of OXA and PAPEI/LDHA-siRNA showed a dramatically increased chemotherapeutic effect on CC compared with the OXA-alone treatment, which also suggested its attractive potential for treating CC-like immune "cold" tumors.

KIF26B in the Prognosis and Immune Biomarking of Various Cancers: A Pan-Cancer Study.

KIF26B has been identified as an oncogene in several tumors; however, its utility as a prognostic indicator for various cancers has not yet been comprehensively evaluated. Here, we first examined how KIF26B intervenes in thirty-three cancers within the TCGA database, including potential immunological functions, and how it affects the prognosis. Based on the open databases TCGA, TIMER2, GEPIA2, GTEx, CPTAC, and HPA, we found that, when compared with normal tissues, KIF26B is overexpressed in 22 tumor tissues. Following a survival analysis, a relationship between the expression of KIF26B and the prognosis of various cancers was observed. Among the genetic alterations assessed, mutations were the most frequent. On the contrary, high phosphorylation levels of S977 were detected in breast cancer, KIRC, LUAD, and UCEC. We also found positive or negative correlations between KIF26B and the immune infiltration of endothelial cells and cancer-associated fibroblast infiltration. This could imply that patients may benefit from immunotherapy. Finally, KEGG pathways and GO enrichment analyses were implemented to identify the molecular mechanisms of KIF26B. This study illustrates the function of KIF26B from a pan-cancer perspective and offers a new horizon for cancer prognostic and immunotherapeutic investigations.

Biological function, mediate cell death pathway and their potential regulated mechanisms for post-mortem muscle tenderization of PARP1: A review.

Tenderness is a key attribute of meat quality that affects consumers' willingness to purchase meat. Changes in the physiological environment of skeletal muscles following slaughter can disrupt the balance of redox homeostasis and may lead to cell death. Excessive accumulation of reactive oxygen species (ROS) in the myocytes causes DNA damage and activates poly ADP-ribose polymerase 1 (PARP1), which is involved in different intracellular metabolic pathways and is known to affect muscle tenderness during post-slaughter maturation. There is an urgent requirement to summarize the related research findings. Thus, this paper reviews the current research on the protein structure of PARP1 and its metabolism and activation, outlines the mechanisms underlying the function of PARP1 in regulating muscle tenderness through cysteine protease 3 (Caspase-3), oxidative stress, heat shock proteins (HSPs), and energy metabolism. In addition, we describe the mechanisms of PARP1 in apoptosis and necrosis pathways to provide a theoretical reference for enhancing the mature technology of post-mortem muscle tenderization.

Fusobacterium nucleatum Facilitates M2 Macrophage Polarization and Colorectal Carcinoma Progression by Activating TLR4/NF-κB/S100A9 Cascade.

Fusobacterium nucleatum (Fn) has been considered as a significant contributor in promoting colorectal carcinoma (CRC) development by suppressing host anti-tumor immunity. Recent studies demonstrated that the aggregation of M2 macrophage (Mφ) was involved in CRC progress driven by Fn infection. However, the underlying molecular mechanisms are poorly characterized. Here, we investigated the role of Fn in Mφ polarization as well as its effect on CRC malignancy. Fn infection facilitated differentiation of Mφ into the M2-like Mφ phenotype by in vitro study. Histological observation from Fn-positive CRC tissues confirmed the abundance of tumor-infiltrating M2-like Mφ. Fn-induced M2-like Mφ polarization was weakened once inhibiting a highly expressed damage-associated molecular pattern (DAMP) molecule S100A9 mainly derived from Fn-challenged Mφ and CRC cells. In addition, Fn-challenged M2-like Mφ conferred CRC cells a more malignant phenotype, showing stronger proliferation and migration characteristics in vitro and significantly enhanced tumor growth in vivo, all of which were partially inhibited when S100A9 was lost. Mechanistic studies further demonstrated that activation of TLR4/NF-κB signaling pathway mediated Fn-induced S100A9 expression and subsequent M2-like Mφ activation. Collectively, these findings indicate that elevated S100A9 in Fn-infected CRC microenvironment participates in M2-like Mφ polarization, thereby facilitating CRC malignancy. Furthermore, targeting TLR4/NF-κB/S100A9 cascade may serve as promising immunotherapeutic strategy for Fn-associated CRC.

Effectiveness of photobiomodulation in the treatment of primary burning mouth syndrome-a systematic review and meta-analysis.

To evaluate the effectiveness of photobiomodulation (PBM) on primary burning mouth syndrome (pBMS). We searched Chinese and English studies published before February 10, 2020. The databases used include PubMed, EMBASE, the Cochrane Library, Web of Science, Wanfang Database, and China National Knowledge Infrastructure (CNKI). Randomized controlled clinical trials (RCTs) that used the PBM to treat pBMS and reported specific treatment outcomes were considered for inclusion. We eventually included 12 RCTs, and 574 samples were included in these studies. The primary outcomes investigated were pain reduction and life quality improvement. A meta-analysis performed on 9 groups in 5 trials showed that PBM was effective in reducing pain compared with placebo (MD - 1.86, 95% CI - 2.59 to - 1.13, Z = 4.99, P < 0.00001). Meta-analysis was also performed on 7 groups in 4 trials and showed that PBM was effective in improving life quality compared with placebo (MD - 3.43, 95% CI - 5.11 to - 1.75, Z = 4.00, P < 0.0001). Qualitative analysis of the included RCTs found that PBM might also play a role in the decrease of TNF-α and IL-6 in saliva. Three studies that compared PBM with medications were evaluated by descriptive analysis. None of the treatment-related adverse event was reported. Up to date, PBM appears to have an effect on pain reduction and life quality improvement in pBMS patients. However, more evidence is still required to warrant its efficacy and safety in treating pBMS.

The Safety and Efficacy of Apatinib Treatment in Addition to Concurrent Chemoradiotherapy in Patients with Nonoperative Locally Advanced Esophageal Squamous Cell Carcinoma.

BACKGROUND Esophageal cancer is a common gastrointestinal malignancy in China. We evaluated the efficacy and safety of adding Apatinib to concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma. MATERIAL AND METHODS In this single-center retrospective study, we compared short-term efficacy, long-term efficacy, and adverse events between patients who received Apatinib and concurrent chemoradiotherapy (Apatinib group), and those who received only concurrent chemoradiotherapy (CCRT group). RESULTS Sixty-five patients with stage II and III esophageal squamous cell carcinoma were enrolled (31 in the Apatinib group, 34 in the CCRT group). After treatment, the therapy response rate (the sum of the complete and partial remission rates) was significantly higher in the Apatinib group than in the CCRT group (P=0.045); the complete remission rate was particularly higher in the Apatinib group. Median progression-free survival in the Apatinib group (12 months) was higher than that of the CCRT group (7 months), and the 1- and 2-year progression-free survival rates were significantly higher in the Apatinib group than in the CCRT group (47.0% vs. 30.3% and 20.2% vs. 12.1%, respectively; P=0.040). The main adverse effects of Apatinib treatment were elevated blood pressure, proteinuria, hand-foot syndrome, fatigue, and oral mucositis, all of which were level 1-2. Cox multivariate regression analysis indicated T stage and short-term efficacy were independent prognostic factors for overall and progression-free survival. CONCLUSIONS For patients with locally advanced esophageal squamous cell carcinoma, combining Apatinib with concurrent chemoradiotherapy can improve patient survival and significantly prolong progression-free survival, with tolerable adverse reactions.

Molecular mechanisms of bufadienolides and their novel strategies for cancer treatment.

Bufadienolides are cardioactive C24 steroids with an α-pyrone ring at position C17. In the last ten years, accumulating studies have revealed the anticancer activities of bufadienolides and their underlying mechanisms, such as induction of autophagy and apoptosis, cell cycle disruption, inhibition of angiogenesis, epithelial-mesenchymal transition (EMT) and stemness, and multidrug resistance reversal. As Na+/K+-ATPase inhibitors, bufadienolides have inevitable cardiotoxicity. Short half-lives, poor stability, low plasma concentration and oral bioavailability in vivo are obstacles for their applications as drugs. To improve the drug potency of bufadienolides and reduce their side effects, prodrug strategies and drug delivery systems such as liposomes and nanoparticles have been applied. Therefore, systematic and recapitulated information about the antitumor activity of bufadienolides, with special emphasis on the molecular or cellular mechanisms, prodrug strategies and drug delivery systems, is of high interest. Here, we systematically review the anticancer effects of bufadienolides and the molecular or cellular mechanisms of action. Research advancements regarding bufadienolide prodrugs and their tumor-targeting delivery strategies are critically summarized. This work highlights recent scientific advances regarding bufadienolides as effective anticancer agents from 2011 to 2019, which will help researchers to understand the molecular pathways involving bufadienolides, resulting in a selective and safe new lead compound or therapeutic strategy with improved therapeutic applications of bufadienolides for cancer therapy.

Potential of coronavirus 3C-like protease inhibitors for the development of new anti-SARS-CoV-2 drugs: Insights from structures of protease and inhibitors.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), similar to SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), which belong to the same Betacoronavirus genus, induces severe acute respiratory disease that is a threat to human health. Since the outbreak of infection by SARS-CoV-2 began, which causes coronavirus disease 2019 (COVID-19), the disease has rapidly spread worldwide. Thus, a search for effective drugs able to inhibit SARS-CoV-2 has become a global pursuit. The 3C-like protease (3CLpro), which hydrolyses viral polyproteins to produce functional proteins, is essential for coronavirus replication and is considered an important therapeutic target for diseases caused by coronaviruses, including COVID-19. Many 3CLpro inhibitors have been proposed and some new drug candidates have achieved success in preclinical studies. In this review, we briefly describe recent developments in determining the structure of 3CLpro and its function in coronavirus replication and summarise new insights into 3CLpro inhibitors and their mechanisms of action. The clinical application prospects and limitations of 3CLpro inhibitors for COVID-19 treatment are also discussed.

Hepatoprotective effects of ZLY16, a dual peroxisome proliferator-activated receptor α/δ agonist, in rodent model of nonalcoholic steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD), a chronic progressive liver disease, covers a series of liver damage encompassing steatosis, nonalcoholic steatohepatitis (NASH), fibrosis and cirrhosis. However, there are no approved therapies for NAFLD. Herein, we characterize the pharmacological profile of ZLY16 ((E)-2-(4-(3-(2,3-dihydrobenzo[b]thiophen -5-yl)-3-oxoprop-1-en-1-yl)-2,6-dimethylphenoxy)-2-methylpropanoic acid), a novel highly potent PPARα/δ agonist with relative higher potency on PPARγ. The chronic effects of ZLY16 on NASH development were evaluated in MCD-induced db/db mice. ZLY16 revealed decreased liver injury biomarkers, hepatic steatosis, inflammation, ballooning, and oxidative stress. Further mechanism researches suggested that ZLY16 inhibited liver inflammation and fibrosis by regulating gene expression including COLIA1, TIMP, TGFß, TNFα, and IL6. Moreover, ZLY16 offers more favorable effects in decreasing liver TC and TG accumulation, blocking liver fibrosis and inflammation than GFT505, the most advanced candidate of PPARα/δ agonist for the treatment of NASH. These results indicate that ZLY16 is a highly potent PPARα/δ agonist that provides great protection against NASH development, and may be useful for the treatment of NAFLD/NASH.

Hepatic steatosis is associated with abnormal hepatic enzymes, visceral adiposity, altered myocardial glucose uptake measured by 18F-FDG PET/CT.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a multisystem disease that affects the liver and a variety of extra-hepatic organ systems. This study aimed to investigate the relationship between hepatic steatosis and glucose metabolism in liver and extra-hepatic tissues and organs. METHODS: The whole body 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) images of 191 asymptomatic tumor screening patients were retrospectively analyzed. Patients with the ratio of spleen/liver CT densities > 1.1 were defined to have NAFLD, and their clinical symptoms, laboratory markers, FDG uptake in a variety of tissues and organs including heart, mediastinal blood pool, liver, spleen, pancreas, and skeletal muscle, as well as abdominal adipose tissue volumes including visceral adipose tissue (VAT) volume and subcutaneous adipose tissue (SAT) volume were compared with those of the non-NAFLD patients and used to analyze the independent correlation factors of NAFLD. RESULTS: Among the 191 patients, 33 (17.3%) were NAFLD, and 158 (82.7%) were non-NAFLD. There was no significant correlation between the mean standardized uptake value (SUVmean) and CT density of liver as well as the ratio of spleen/liver CT densities. Hepatic steatosis, but not FDG intake, was more significant in NAFLD patients with abnormal liver function than those with normal liver function. Compared with the non-NAFLD patients, NAFLD patients had significantly reduced myocardial glucose metabolism, but significantly increased mediastinal blood pool, spleen SUVmean and abdominal adipose tissue volumes (including VAT and SAT volumes) (P < 0.05). Multivariate regression analysis showed that elevated serum ALT, increased abdominal VAT volume, and decreased myocardial FDG uptake were independent correlation factors for NAFLD. Further studies showed that hepatic steatosis and myocardial FDG uptake were mildly linearly correlated (r = 0.366 with hepatic CT density and - 0.236 with the ratio of spleen/liver CT densities, P < 0.05). CONCLUSIONS: NAFLD is a systemic disease that can lead to the change of glucose metabolism in some extra-hepatic tissues and organs, especially the myocardium.

Septin6 regulates cell growth and casein synthesis in dairy cow mammary epithelial cells via mTORC1 pathway.

This research paper addresses the hypothesis that Septin6 is a key regulatory factor influencing amino acid (AA)-mediated cell growth and casein synthesis in dairy cow mammary epithelial cells (DCMECs). DCMECs were treated with absence of AA (AA-), restricted concentrations of AA (AAr) or normal concentrations of AA (AA+) for 24 h. Cell growth, expression of CSN2 and Septin6 were increased in response to AA supply. Overexpressing or inhibiting Septin6 demonstrated that cell growth, expression of CSN2, mTOR, p-mTOR, S6K1 and p-S6K1 were up-regulated by Septin6. Furthermore, overexpressing or inhibiting mTOR demonstrated that the increase in cell growth and expression of CSN2 in response to Septin6 overexpression were inhibited by mTOR inhibition, and vice versa. Our hypothesis was supported; we were able to show that Septin6 is an important positive factor for cell growth and casein synthesis, it up-regulates AA-mediated cell growth and casein synthesis through activating mTORC1 pathway in DCMECs.

Apatinib enhances the radiosensitivity of the esophageal cancer cell line KYSE-150 by inducing apoptosis and cell cycle redistribution.

To determine the radiosensitizing effect of apatinib on esophageal cancer cells, and to preliminarily investigate the underlying mechanism, KYSE-150 cells were treated with apatinib, x-ray or apatinib combined with x-ray, and compared with a blank control. It was observed that apatinib significantly inhibited vascular endothelial growth factor (VEGF) secretion and the proliferation of KYSE-150 cells in a dose-dependent manner. As the concentration of apatinib increased, the radiobiological parameters inactivation dose (D0), quasi domain does (Dq) and survival fraction (SF2) of KYSE-150 cells decreased, while the sensitization enhancement ratio SERD0 increased. The rate of apoptosis in cells treated with apatinib and x-ray was markedly higher compared with those of the blank control, x-ray and apatinib alone groups (P<0.05). The proportion of cells in the G2/M phase was significantly increased in the apatinib, x-ray and combination groups compared with the blank control group (P<0.05). Compared with the control and x-ray groups, combination treatment did not significantly alter the expression level of polyADP-ribose polymerase (PARP), although it significantly increased the expression of cleaved-PARP (P<0.05). Moreover, the expression of cell serine/threonine-protein kinase-2 (CHK2) was downregulated (P<0.05), whilst expression of the phosphorylated form, pCHK2, was significantly increased (P<0.05) in the combination group when compared with the control and x-ray groups. In conclusion, the present study suggested that apatinib increases the radiosensitivity of KYSE-150 esophageal cancer cells by inhibiting VEGF secretion and cell proliferation, and promoting apoptosis and cell cycle redistribution.

Self-assembly of biotinylated poly(ethylene glycol)-poly(curcumin) for paclitaxel delivery.

Paclitaxel (PTX), one of the most potent anticancer agents, has showed a remarkable activity against varieties of tumors. However, the bioavailability of PTX is quite low due to its poor aqueous solubility. Moreover, the emerging multidrug resistance (MDR) in cancer to PTX remains a major obstacle for successful chemotherapy. In order to address these problems, we developed self-assembly of biotinylated poly(ethylene glycol)-poly(curcumin) (Biotin-PEG-PCDA) for PTX delivery (termed as PTX-BPC NPs) with the application of mPEG2K-P(CL-co-LLA) as an emulsifier. The loading content and encapsulation efficiency of PTX were 13.2% and 92.0%, respectively. In vitro drug release study showed that PTX-BPC NPs could degrade rapidly and then release the PTX payload in a 10 mM glutathione (GSH) environment. Compared with free PTX, PTX-BPC NPs exhibited enhanced anticancer efficacy (IC50(MCF-7/ADR cells), 17.28 µg/mL vs. 1.15 µg/mL). In addition, these biotin-modified nanoparticles could also significantly reverse PTX resistance by suppressing the over-expression of P-gp, thus resulting in increased intracellular drug accumulation and reduced drug efflux in MCF-7/ADR cells, which showed a great anticancer effect.

Angiopep-2 modified PEGylated 2-methoxyestradiol micelles to treat the PC12 cells with oxygen-glucose deprivation/reoxygenation.

2-Methoxyestradiol (2ME2), as a microtubule and hypoxia-inducible factor-1 (HIF-1) inhibitor, can be used to treat cerebral ischemia-reperfusion (I/R) injury. However, its poor water solubility compromises its efficacy as a neuroprotectant. Herein, we synthesized PEGylated 2ME2 and angiopep-2 capped PEGylated 2ME2 and fabricated angiopep-2 modified PEGylated 2ME2 micelles containing free 2ME2 (ANG-PEG-2ME2/2ME2) via emulsion-solvent evaporation method. The effect of the micelles on ischemia-reoxygenation injury was evaluated by oxygen-glucose deprivation/reoxygenation (OGD/R) models with different degrees of PC12 cell damage. In comparison with free 2ME2, the micelles significantly increased the cell viability, inhibited reactive oxygen species (ROS) generation and apoptosis for PC12 cells with 0.5 and 4 h OGD followed by 24 h reoxygenation. Taken together, the angiopep-2 modified 2ME2-loaded micelles could effectively reduce the injury of PC12 cells induced by OGD/R.