Gut Epithelial Barrier Function is Impacted by Hyperglycemia and Secondary Bile Acids in Vitro: Possible Rescuing Effects of Specific Pectins.

Gut epithelial barrier disruption is commonly observed in Western diseases like diabetes and inflammatory bowel disease (IBD). Enhanced epithelial permeability triggers inflammatory responses and gut microbiota dysbiosis. Reduced bacterial diversity in IBD affects gut microbiota metabolism, altering microbial products such as secondary bile acids (BAs), which potentially play a role in gut barrier regulation and immunity. Dietary fibers such as pectin may substitute effects of these BAs. The study examines transepithelial electrical resistance of gut epithelial T84 cells and the gene expression of tight junctions after exposure to (un)sulfated secondary BAs. This is compared to the impact of the dietary fiber pectin with different degrees of methylation (DM) and blockiness (DB), with disruption induced by calcium ionophore A23187 under both normal and hyperglycemic conditions. Unsulfated lithocholic acid (LCA) and deoxycholic acid (DCA) show a stronger rescuing effect, particularly evident under 20 mM glucose levels. DM19 with high DB (HB) and DM43HB pectin exhibit rescuing effects under both glucose conditions. Notably, DM19HB and DM43HB display higher rescue effects under 20 mM glucose compared to 5 mM glucose. The study demonstrates that specific pectins such as DM19HB and DM43HB may serve as alternatives for preventing barrier disruption in the case of disturbed DCA metabolism.

Immobilisation remediation of arsenic-contaminated soils with promising CaAl-layered double hydroxide and bioavailability, bioaccessibility, and speciation-based health risk assessment.

Arsenic (As)-contaminated soil poses great health risk to human mostly through inadvertent oral exposure. We investigated CaAl-layered double hydroxide (CaAl-LDH), a promising immobilising agent, for the remediation of As-contaminated Chinese soils. The effects on specific soil properties and As fractionation were analyzed, and changes in the health risk of soil As were accurately assessed by means of advanced in vivo mice model and in vitro PBET-SHIME model. Results showed that the application of CaAl-LDH significantly increased soil pH and concentration of Fe and Al oxides, and effectively converted active As fractions into the most stable residual fraction, guaranteeing long-term remediation stability. Based on in vivo test, As relative bioavailability was significantly reduced by 37.75%. Based on in vitro test, As bioaccessibility in small intestinal and colon phases was significantly reduced by 25.65% and 28.57%, respectively. Furthermore, As metabolism (reduction and methylation) by the gut microbiota inhabiting colon was clearly observed. After immobilisation with CaAl-LDH, the concentration of bioaccessible As(Ⅴ) in the colon fluid was significantly reduced by 61.91%, and organic As (least toxic MMA(V) and DMA(V)) became the main species, which further reduced the health risk of soil As. In summary, CaAl-LDH proved to be a feasible option for immobilisation remediation of As-contaminated soils, and considerable progress was made in relevant health risk assessment.

Influences of coexisting aged polystyrene microplastics on the ecological and health risks of cadmium in soils: A leachability and oral bioaccessibility based study.

Whether coexisting microplastics (MPs) affect the ecological and health risks of cadmium (Cd) in soils is a cutting-edge scientific issue. In this study, four typical Chinese soils were prepared as artificially Cd-contaminated soils with/without aged polystyrene (PS). TCLP and in vitro PBET model were used to determine the leachability (ecological risk) and oral bioaccessibility (human health risk) of soil Cd. The mechanisms by which MPs influence soil Cd were discussed from direct and indirect perspectives. Results showed that there was no significant difference in the leachability of soil Cd with/without aged PS. Additionally, aged PS led to a significant decrease in the bioaccessibility of soil Cd in gastric phase, but not in small intestinal phase. The increase in surface roughness and the new characteristic peaks (e.g., Si-O-Si) of aged PS directly accounted for the change in Cd bioaccessibility. The change in organic matter content indirectly accounted for the exceptional increase in Cd bioaccessibility of black soil with aged PS in small intestinal phase. Furthermore, the changes in cation exchange capacity and Cd mobility factor caused by aged PS explained the change in Cd leachability. These results contribute to a deeper understanding about environmental and public health in complicated emerging scenarios.

Application of sintilimab combined with anlotinib hydrochloride in the clinical treatment of microsatellite stable colorectal cancer.

BACKGROUND: Microsatellite stable (MSS) colorectal cancer (CRC) is a common type of tumor with limited treatment options. Sintilimab and anlotinib hydrochloride are two extensively studied anticancer drugs. AIM: To probe the clinical value of combining sintilimab with anlotinib hydrochloride in MSS CRC treatment. METHODS: During the period spanning from April 2019 to April 2022, Zhejiang Provincial People's Hospital accommodated a cohort of 92 patients diagnosed with MSS CRC who were classified into two distinct groups in our study, the observation group and the control group. The control group was administered anlotinib hydrochloride as their designated therapy, whereas the observation group received the additional treatment of sintilimab in conjunction with the therapy assigned to the control group. The administration of treatment occurred in cycles consisting of a duration of 3 wk, and the evaluation of effectiveness took place subsequent to the completion of two consecutive cycles of treatment within both groups. A comparative analysis between the two groups was conducted to assess the short-term efficacy and ascertain the incidence of adverse events transpiring throughout the duration of the treatment period. Changes in the levels of carcinoembryonic antigen, carbohydrate antigen 199 (CA199), CA125, and T cell subsets (CD4+, CD8+, CD4+/CD8+) as well as the assessment of the quality of life using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 were compared between the two groups prior to and subsequent to therapy. Finally, a 1-year follow-up was conducted for both groups of patients, and the survival status was recorded and analyzed. RESULTS: The short-term effectiveness displayed by the observation group surpassed that exhibited by the control group, with a statistically significant discrepancy (76.09% vs 50.00%), reaching a significance level denoted as P < 0.05. Following the administration of treatment, the observation group manifested a considerable reduction in numerous serum indicators, which were found to be lower than the corresponding pretreatment levels within the same group as well as the post-treatment levels observed in the control group (P < 0.05). Post-treatment, the T lymphocyte subset levels within the observation group demonstrated a remarkable amelioration, surpassing the corresponding pre-treatment levels observed within the same group as well as the post-treatment levels observed in the control group (P < 0.05). Subsequent to the therapeutic intervention, the observation group showcased a notable amelioration in the scores associated with multiple dimensions of life quality. These scores outperformed the pretreatment scores within the same group as well as the post-treatment scores observed in the control group (P < 0.05). The safety levels of drug use in the two group were comparable (19.57% vs 13.04%), and no distinct difference was observed upon comparison (P > 0.05). After the completion of treatment, both groups of patients underwent a 1-year follow-up outside the hospital. Throughout this period, 1 patient within the observation group and 2 patients within the control group became untraceable and were lost to follow-up. During the follow-up period of the observation group, 12 patients died, resulting in a survival rate of 73.33% (33/45), while in the control group, 21 patients died, resulting in a survival rate of 52.27% (23/44). The implementation of Kaplan-Meier survival analysis revealed a conspicuous contrast in survival rates exhibited by the two groups (log-rank = 4.710, P = 0.030). CONCLUSION: The combination of sintilimab and anlotinib hydrochloride demonstrated favorable efficacy in the treatment of MSS CRC patients, leading to improvements in patient immunity and prognosis. Additionally, it exerted inhibitory effects on the expression of carcinoembryonic antigen, CA199, and CA125.

Risks of applying mobilising agents for remediation of arsenic-contaminated soils: Effects of dithionite-EDTA and citric acid on arsenic fractionation, leachability, oral bioavailability/bioaccessibility and speciation.

Arsenic (As) mobilisation assists in remediating As-contaminated soils but might increase ecological and health risks. In this study, risks of applying two mobilising agents were assessed, i.e. an emerging reducing-chelating composite agent [dithionite (Na2S2O4)-EDTA] and a classical low-molecular-weight organic acid (LMWOA) [citric acid (C6H8O7)]. Results showed that both agents induced sharp increase in leachability-based ecological risk of As. Interestingly, the two agents had opposite performances regarding health risks. Na2S2O4-EDTA significantly increased As relative bioavailability (RBA) to 1.83 times that in controls based on in vivo mouse model, and As bioaccessibility to 1.96, 1.65 and 1.20 times in gastric, small intestinal and colon phases based on in vitro PBET-SHIME model. Besides, it caused significant increase of highly toxic As(Ⅲ) in colon fluid. In contrast, C6H8O7 significantly reduced RBA and bioaccessibility of soil As in colon by 44.44% and 14.65%, respectively. Importantly, C6H8O7 restrained bioaccessible As(V) reduction and promoted bioaccessible As(Ⅲ) methylation, further reducing health risk. The phenomena could mainly be attributed to excessive metal components release from soil by C6H8O7 and gut microbiota metabolism of C6H8O7. In summary, C6H8O7 and similar LMWOAs are recommended. The study contributes to mobilising agent selection and development and provides a reference for managing remediation sites.

[Effects of Aging on the Cd Adsorption by Microplastics and the Relevant Mechanisms].

It has been verified that, as an emerging contaminant, microplastics are capable of adsorbing certain traditional contaminants like the heavy metal Cd. However, the majority of previous studies only focused on certain types of virgin microplastics, especially for PE and PS. In addition, this adsorption process might be affected by microplastics inevitably undergoing aging and consequent changes in the natural environment. Unfortunately, the relevant reports on aging effects were mainly about organic pollutants, rather than heavy metals. By far, there have been few comprehensive and mechanistic studies on the key aging effects on the Cd adsorption by various types of microplastics. In this study, five representative types of microplastics (i.e., PS, ABS, PP, PVC, and PET) were selected for aging by ultraviolet radiation, and the physicochemical properties of virgin and aged microplastics were thoroughly compared, including specific surface area, crystallinity, surface functional groups, and surface elements. Accordingly, the changes in adsorption isotherms of Cd by microplastics were discussed. The results showed that:① aging induced non-significant changes in specific surface area but a significant decrease in crystallinity. Surface functional groups also changed, including the emergence of a C=O functional group on PS and ABS, the decrease in C=C absorption peak intensity on ABS, and the increase in absorption peak intensities of C=O, C-O, and polar ester groups on PET. Regarding surface C content, C=C/C-C decreased, whereas C-O and O-C=O increased. The total O content and O/C significantly increased as well. ② The Langmuir model well-fitted the adsorption isotherms of Cd by virgin and aged microplastics. Aging significantly expanded the adsorption capacity of Cd by microplastics, as the order of saturated adsorption capacity before aging was ABS (0.2284 mg·g-1)>PVC (0.1360 mg·g-1)>PS (0.1286 mg·g-1)>PP (0.1005 mg·g-1)>PET (0.0462 mg·g-1) and then became PS (0.2768 mg·g-1)>ABS (0.2586 mg·g-1)>PVC (0.1776 mg·g-1)>PP (0.1721 mg·g-1)>PET (0.0951 mg·g-1) after aging. ③ Both crystallinity and surface functional groups played key roles in the adsorption of Cd by microplastics. As for virgin microplastics, crystallinity was negatively correlated with the saturated adsorption capacity of Cd, because the amorphous regions contributed most to Cd adsorption. Aging brought about the decrease in crystallinity and the increase in amorphous regions, which further promoted the oxidation reaction on microplastics. Consequently, oxygen-containing functional groups increased on the surface and eventually expanded the adsorption capacity of Cd by microplastics. Note that certain specific functional groups of various microplastics also had impacts on the adsorption process. These results provide valuable information about the environmental behaviors and interactions of microplastics and heavy metals in nature.

Development of a nanobody-based immunoassay for the sensitive detection of fibrinogen-like protein 1.

Immune checkpoint inhibition is an important strategy in cancer therapy. Blockade of CTLA-4 and PD-1/PD-L1 is well developed in clinical practice. In the last few years, LAG-3 has received much interest as an emerging novel target in immunotherapy. It was recently reported that FGL1 is a major ligand of LAG-3, which is normally secreted by the liver but is upregulated in several human cancers. FGL1 is a crucial biomarker and target for cancer immunotherapy. As the efficacy of immunotherapy is limited to specific types of patients, the subset of patients needs to be selected appropriately to receive precise treatment according to different biomarkers. To date, there is no test to accurately assess FGL1 expression levels. Nanobodies have some outstanding features, such as high stability, solubility and affinity for diagnostic and therapeutic applications. Here, we report the development and validation of a rapid, sensitive, and cost-effective nanobody-based immunoassay for the detection of FGL1 in human serum. In this study, human FGL1 recombinant protein was expressed and purified for the first time as an immunized antigen. Then, we constructed a nanobody phage display library and screened several nanobodies that bind FGL1 with high affinity. We selected two nanobodies targeting different epitopes of FGL1, one as a capture and the other conjugated with HRP as a probe. The double nanobody-based sandwich ELISA to detect the concentration of FGL1 showed a good response relationship in the range of 15.625-2000 ng/mL, and the recoveries from the spiked sample were in the range of 78% and 100%. This assay could be used as a potential approach for evaluating FGL1 expression for patient stratification and for predicting the therapeutic efficacy of targeting the LAG3/FGL1 axis.

Clinical Characteristics and Outcomes of Breakthrough Candidemia in 71 Hematologic Malignancy Patients and/or Allogeneic Hematopoietic Stem Cell Transplant Recipients: A Single-center Retrospective Study From China, 2011-2018.

BACKGROUND: Antifungal prophylaxis may result in breakthrough infections in hematology patients with severe agranulocytosis, with few studies assessing risk factors and clinical outcomes of breakthrough candidemia. We described the distribution of Candida species, assessed risk factors for mortality in such patients, and determined differences in the incidence and mortality of breakthrough candidemia between patients who did or did not receive an allogeneic hematopoietic stem cell transplant. METHODS: We collected clinical and microbiological data of patients with hematologic malignancies and breakthrough candidemia from a single center. Seven-day and 30-day follow-up outcomes were recorded; the incidence and mortality of breakthrough candidemia between patients who did or did not undergo an allogeneic transplant were compared. Kaplan-Meier survival estimates were used to generate survival curves, and predictors were identified using Cox regression analyses. RESULTS: Of 71 enrolled patients, 17 received allogeneic transplants. Incidences of breakthrough candidemia were 17 of 2924 (0.58%) and 54 of 12 015 (0.45%) in the transplant and nontransplant groups, respectively (P = .35). The most common isolate was Candida tropicalis, and antifungal agent combinations were the most common first-line treatment. Cumulative mortality rates of patients were 21.1% and 31.0% at days 7 and 30, respectively, and they significantly differed between both groups. Septic shock, central venous catheter removal, and granulocyte recovery were significantly associated with 7-day mortality; the latter 2 remained independent predictors of 30-day mortality. CONCLUSIONS: Breakthrough candidemia-related mortality was higher in the allogeneic transplant group, although the incidence was not significantly different between the groups. Prompt and adequate antifungal treatment with catheter removal may reduce mortality.

Clinical characteristics and implications of mixed candida/bacterial bloodstream infections in patients with hematological diseases.

The incidence of mixed candida/bacterial blood infections (BSIs) has been reported to account for 20% of all cases of candidaemia. However, its clinical characteristics and implications in patients with hematological diseases are not clear. We conducted a retrospective case-control study of hematological patients complicated with candidaemia over the past 5-year period to identify the risk factors and clinical implications of mixed candidia/bacterial BSIs (case group) vs. monobacterial candidiasis (control group). Of all 65 enrolled patients with candidaemia, 20 cases (30.8%) met the diagnostic criteria for mixed candida/bacterial BSIs. Candida tropicalis was the most common candida species in all patients. Klebsiella pneumoniae was the most detected bacteria (35%) in case group. Previous hospital stay ≥ 28 days, organic damage during candidaemia, and positive procalcitonin (PCT) test were the risk factors of mixed candida/bacterial BSIs. Cumulative mortality of all patients enrolled was 26.2% at day 30, with significant differences between case and control group. In multivariate analysis, organic damage and granulocyte recovery were the two predictive factors for 30-day mortality. Mixed candida/bacterial BSIs are fatal complications of infection which account for a considerable part of candidaemia; multicenter and large-scale clinical studies are required in the future.

A Novel Method to Detect Early Colorectal Cancer Based on Chromosome Copy Number Variation in Plasma.

BACKGROUND/AIMS: Colonoscopy screening has been accepted broadly to evaluate the risk and incidence of colorectal cancer (CRC) during health examination in outpatients. However, the intrusiveness, complexity and discomfort of colonoscopy may limit its application and the compliance of patients. Thus, more reliable and convenient diagnostic methods are necessary for CRC screening. Genome instability, especially copy-number variation (CNV), is a hallmark of cancer and has been proved to have potential in clinical application. METHODS: We determined the diagnostic potential of chromosomal CNV at the arm level by whole-genome sequencing of CRC plasma samples (n = 32) and healthy controls (n = 38). Arm level CNV was determined and the consistence of arm-level CNV between plasma and tissue was further analyzed. Two methods including regular z score and trained Support Vector Machine (SVM) classifier were applied for detection of colorectal cancer. RESULTS: In plasma samples of CRC patients, the most frequent deletions were detected on chromosomes 6, 8p, 14q and 1p, and the most frequent amplifications occurred on chromosome 19, 5, 2, 9p and 20p. These arm-level alterations detected in plasma were also observed in tumor tissues. We showed that the specificity of regular z score analysis for the detection of colorectal cancer was 86.8% (33/38), whereas its sensitivity was only 56.3% (18/32). Applying a trained SVM classifier (n = 40 in trained group) as the standard to detect colorectal cancer relevance ratio in the test samples (n = 30), a sensitivity of 91.7% (11/12) and a specificity 88.9% (16/18) were finally reached. Furthermore, all five early CRC patients in stages I and II were successfully detected. CONCLUSION: Trained SVM classifier based on arm-level CNVs can be used as a promising method to screen early-stage CRC.

[Correlation of Serum Concentration of Nilotinib with Clinical Efficacy in Patients with Chronic Myeloid Leukemia].

OBJECTIVE: To investigate the correlation of the serum minimal concentrations (Cmins) of nilotinib(NIL) with the clinical efficacy and adverse events (AEs) in CML patients. METHODS: A total of 54 patients were divided into two groups according to the dosage of nilotinib. 44 cases received dose of 600-800 mg/d were classified as group A; while 10 cases received dose of 400 mg/d as group B. The Cmins of nilotinib were determmined by liquid chromatography-tandem mass spectrometry. RESULTS: Median Cmins of nilotinib in 54 patients was 1.71 (0.52-5.93) µg/ml. Cmins of nilotinib in group A and group B were 2.09± 1.21 µg/ml and 0.94± 0.27 µg/ml respectively, Cmins of group A was significantly higher than that of group B (P=0.001). In group A, 24 out of 44 cases obtained major molecular response (MMR) in 12 months, while 20 cases did not reach MMR in 12 months; the serum drug concentrations were 1.70± 0.75 µg/ml and 2.03± 0.82 µg/ml respectively, without statistically significant differences between these 2 subgroups(P=0.154). However, Cmins of nilotinib in patients with III-IV grade of adverse events were significantly higher than those in patients with 0-II grade of adverse events (3.09± 1.76 µg/ml vs 1.76± 0.68 µg/ml)(P=0.018). There was no statistic diffence in Cmins of nilotinib with MMR in 12 months of group A MMR 1.15± 0.27 µg/ml vs no MMR 0.83± 0.24 µg/ml(P=0.051). The MMR rate at 12 months in group A was 54.5%(24/44) and that in group B was 40%(4/10) (P=0.494). But the incidence of grade III-IV adverse events in group A was 29.5%(13/44), which was significantly higher than that of group B[0/10(0%)]. CONCLUSION: Cmins of nilotinib shows significant individual differences. The Cmins of nilotinib relate with the dosage and grade III-IV of adverse events. The lower dose of nilotinib may maintain a good therapeutic effect and significantly reduce the adverse events.

Expression and clinical significance of glucose transporter-1 in pancreatic cancer.

Increasing evidence has demonstrated that malignant cells exhibit increased glucose uptake, which facilitates survival and growth in a hypoxic environment. The glucose transporter-1 (GLUT-1) is overexpressed in a variety of malignant tumors. However, the association between GLUT-1 expression and clinicopathological factors, 18F-fluorodeoxyglucose uptake and tumor proliferation in pancreatic cancer has not been investigated to date. In the present study, the expression of GLUT-1 in 53 pancreatic cancer tissues was analyzed, which revealed that GLUT-1 was overexpressed in pancreatic tissue and correlated with poor prognosis and clinicopathological characteristics, including increased tumor size, clinical stage and lymph node metastasis, maximum standardized uptake value (SUVmax) and Ki-67 expression. The receiver operating characteristic curve analysis indicated that a cut-off SUVmax value of 4.830 was associated with optimal sensitivity (88%) and specificity (71.4%) for the detection of strong positive GLUT-1 expression. In addition, as the expression of GLUT-1 was found to correlate with Ki-67 expression, GLUT-1 may exhibit a significant effect on cell proliferation in pancreatic cancer. Overall, these findings indicate that GLUT-1 may represent a prognostic indicator, and a potential therapeutic target for pancreatic cancer.

Anti-cancer effects of curcumin on lung cancer through the inhibition of EZH2 and NOTCH1.

Curcumin is potentially therapeutic for malignant diseases. The mechanisms of this effect might involve a combination of antioxidant, immunomodulatory, proapoptotic, and antiangiogenic activities. However, the exact mechanisms are not fully understood. In the present study, we provided evidences that curcumin suppressed the expression of enhancer of zeste homolog 2 (EZH2) in lung cancer cells both transcriptionally and post-transcriptionally. Curcumin inhibited the expression of EZH2 through microRNA (miR)-let 7c and miR-101. Curcumin decreased the expression of NOTCH1 through the inhibition of EZH2. There was a reciprocal regulation between EZH2 and NOTCH1 in lung cancer cells. These observations suggest that curcumin inhibits lung cancer growth and metastasis at least partly through the inhibition of EZH2 and NOTCH1.

Upregulation of the Non-Coding RNA OTUB1-isoform 2 Contributes to Gastric Cancer Cell Proliferation and Invasion and Predicts Poor Gastric Cancer Prognosis.

BACKGROUND: The deubiquitinase OTUB1 plays critical oncogenic roles and facilitates tumor progression in cancer. However, less is known regarding the aberrant expression, clinical significance and biological functions of the non-coding RNA OTUB1-isoform 2. We aimed to evaluate the OTUB1-isoform 2 levels in gastric cancer and their possible correlation with clinicopathologic features and patient survival to reveal its biological effects in gastric cancer progression. METHODS: Total RNA extraction was performed on 156 gastric cancer case samples, and RT-qPCR was conducted. Chi-square test analysis was used to calculate the correlation between pathological parameters and the OTUB1-isoform 2 mRNA levels. Kaplan-Meier and Cox proportional hazards analyses were used to analyze the overall survival (OS) and disease-free survival (DFS) rates. Nuclear and cytoplasmic RNAs were isolated to detect the subcellular localization of OTUB1-isoform 2. We also assessed whether overexpression of OTUB1-isoform 2 influenced in vitro cell proliferation, cell cycle progression, tumor cell invasion and migration, as well as in vivo nude mouse xenograft and metastasis models. RESULTS: The OTUB1-isoform 2 expression levels were higher in the gastric cancer samples than in the paratumorous gland samples. OTUB1-isoform 2 expression levels tightly correlated with tumor size, lymph node metastasis and TNM staging. Higher OTUB1-isoform 2 expression levels led to significantly poorer OS and DFS rates, and a multivariate analysis revealed that OTUB1-isoform 2 was an independent risk factor for DFS. OTUB1-isoform 2 was predominantly localized in the cell nucleus. Ectopic overexpression of OTUB1-isoform 2 in gastric cancer cells stimulated proliferation by inducing G1-S transition, suppression of cell apoptosis and promotion of tumor cell invasion and migration. Finally, OTUB1-isoform 2 overexpression promoted tumor growth and tumor metastasis in nude mice models. CONCLUSIONS: Our study suggests that OTUB1-isoform 2 independently predicts poor prognosis and promotes tumor progression in gastric cancer. The non-coding RNA OTUB1-isoform 2 should be targeted in future molecular therapies.

Improved sensitization effect of sunitinib in cancer cells of the esophagus under hypoxic microenviroment.

Radiotherapy is widely used in esophageal squamous cell carcinoma (ESCC) treatment. Promoting the radiation sensitivity of cancer cells is required. Recent studies have shown that sunitinib can inhibit the growth of several cancer lines. However, few studies on the radiosensitive effect of sunitinib on ESCC cells under hypoxic conditions have been conducted. In the present study, the radiosensitive effects of sunitinib on human ESCC cells were assessed, and the underlying mechanisms were explored. ESCC cells were exposed to hypoxia and treated with sunitinib at different concentrations prior to irradiation. Sunitinib potently inhibited ESCC cell proliferation in an MTT assay. In a clonogenic survival assay, sunitinib sensitized hypoxic ESCC cells to radiation, with sensitizing enhancement ratios of 1.31-1.59. In addition, sunitinib promoted the apoptosis of ESCC cells, but did not alter their cell cycle distribution. Radiosensitization was accompanied by inhibition of the radiation-induced upregulation of hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) expression. Thus, sunitinib confers radiosensitivity to esophageal cancer cells, which is associated with the downregulation of HIF-1α and VEGF expression. Sunitinib can be a promising radiosensitizer for esophageal cancer radiotherapy.

[Molecular identification of aucklandiae radix, vladimiriae radix, inulae radix, aristolochiae radix and kadsurae radix using ITS2 barcode].

In order to identify Aucklandiae Radix, Vladimiriae Radix, Inulae Radix, Aristolochiae Radix and Kadsurae Radix using ITS2 barcodes, genomic DNA from sixty samples was extracted and the ITS2 (internal transcribed spacer) regions were amplified and sequenced. The genetic distances were computed using MEGA 5.0 in accordance with the kimura 2-parameter (K2P) model and the neighbor-joining (NJ) phylogenetic tree was constructed. The results indicated that for Aucklandiae Radix (Aucklandia lappa), Vladimiriae Radix (Vladimiria souliei and V. souliei var. cinerea), Inulae Radix (Inula helenium), Aristolochiae Radix (Aristolochia debilis) and Kadsurae Radix (Kadsura longipedunculata), the intra-specific variation was smaller than inter-specific one. There are 162 variable sites among 272 bp after alignment of all ITS2 sequence haplotypes. For each species, the intra-specific genetic distances were also smaller than inter-specific one. Furthermore, the NJ tree strongly supported that Aucklandiae Radix, Vladimiriae Radix, Inulae Radix, Aristolochiae Radix and Kadsurae Radix can be differentiated. At the same time, V. souliei (Dolomiaea souliei) and V. souliei var. cinerea( D. souliei var. cinerea) belonging to Vladimiriae Radix were clearly identified. In conclusion, ITS2 barcode could be used to identify Aucklandiae Radix, Vladimiriae Radix, Inulae Radix, Aristolochiae Radix and Kadsurae Radix. Our study may provide a scientific foundation for clinical safe use of the traditional Chinese medicines.

Computed tomography manifestations of histologic subtypes of retroperitoneal liposarcoma.

OBJECTIVE: Liposarcoma (LPS) is the most common soft tissue sarcoma and accounts for approximately 20% of all mesenchymal malignancies, often occurring in deep soft tissue of retroperitoneal space. Accurate preoperative diagnosis is therefore necessary. We explored whether computed tomography (CT) could be used to differentiate between the various types of retroperitoneal liposarcoma (RPLS). METHOD: Forty-seven cases of RPLS, diagnosed surgically and histologically, were analyzed retrospectively. CT features were correlated with postoperative pathological appearance. RESULTS: The study radiologist identified 29, 11, 2, 2 and 3 RPLS as atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL), dedifferentiated liposarcoma (DDL), myxoid/round cell liposarcoma (ML/RCL), pleomorphic liposarcoma (PL) and mixed-type liposarcoma. Analysis of CT scans revealed the following typical findings of the different subtypes of RPLS: ALT/WDL was mainly visible as a well-delineated fatty hypodense tumor with uniform density and integrity margin; DDL was marked by the combination of focal nodular density and hypervascularity. ML/RCL, PL and mixed liposarcoma showed malignant biological behaviour and CT findings need further studies. CONCLUSIONS: CT scanning can reveal important details including internal components, margins and surrounding tissues. Based on CT findings, tumor type can be roughly evaluated and biopsy location and therapeutic scheme guided.

Fenofibrate increases radiosensitivity in head and neck squamous cell carcinoma via inducing G2/M arrest and apoptosis.

Radiation therapy is an important treatment for head and neck squamous cell carcinoma (HNSCC). However, how to promote radiation sensitivity in HNSCC remains a challenge. This study aimed to investigate the radiosensitizing effects of fenofibrate on HNSCC and explore the underlying mechanisms. HNSCC cell lines CNE-2 and KB were subjected to ionizing radiation (IR), in the presence or absence of fenofibrate treatment. Cell growth and survival, apoptosis and cell cycle were evaluated. In addition, CNE-2 cells were xenografted into nude mice and subjected to IR and/ or fenofibrate treatment. The expression of cyclinB and CDK1 was detected by Western blotting. Our results showed that fenofibrate efficiently radiosensitized HNSCC cells and xenografts in mice, and induced apoptosis and G2/M arrest via reducing the activity of the CDK1/cyclinB1 kinase complex. These data suggest that fenofibrate could be a promising radiosensitizer for HNSCC radiotherapy.

[Identification of Salvia shandongensis new species based on sequences of the plastid psbA-trnH intergenic region].

To identify Salvia shandongensis and its relatives at molecular level, the psbA-trnH intergenic region of three species including Salvia shandongensis, Salvia miltiorrhiza and S. miltiorrhiza f. alba were amplified and sequenced. Sequences were assembled with CodonCode Aligner. The K2P genetic distances between Salvia shandongensis and its relatives were calculated and UPGMA tree was performed by MEGA5.0. The results indicated that the lengths of psbA-trnH regions of Salvia shandongensis were about 391 bp, while the lengths of psbA-trnH regions of Salvia miltiorrhiza and S. miltiorrhiza f. alba were about 386 bp. The psbA-trnH sequences showed considerable variations between species and thus were revealed as a promising candidate for barcoding of Salvia shandongensis and its relatives. The intra-specific genetic distances of Salvia shandongensis were 0, while the intra-specific genetic distances of Salvia miltiorrhiza and S. miltiorrhiza f. alba were 0.002 and 0.001 respectively. Additionally, the genetic distance of Salvia shandongensis and Salvia miltiorrhiza ranged from 0.034 to 0.04, and the genetic distance of Salvia shandongensis and S. miltiorrhiza f. alba ranged from 0.005 to 0.008, the intra-specific genetic distances of Salvia shandongensis were much smaller than that of Salvia miltiorrhiza and S. miltiorrhiza f. alba; clustering results showed that there were obvious differences between Salvia shandongensis, Salvia miltiorrhiza and S. miltiorrhiza f. alba, which was consistent with morphological characteristics. This study not only firstly provides the scientific basis for establishing the taxonomy position in molecular level and revealing their genetic relationships of S. shandongensis, S. miltiorrhiza and S. miltiorrhiza f. alba; but also provides DNA molecular identification scientific basis for the development of new medicinal plant resources of Salvia shandongensis. Our results suggest that the psbA-trnH intergenic spacer region can be used as a barcoding to identify Salvia shandongensis, Salvia miltiorrhiza and S. miltiorrhiza f. alba.