Exploring casual effects and shared molecular mechanism between psoriasis and liver cancer through Mendelian randomization and comprehensive bioinformatic analyses.

Psoriasis (Ps), a chronic inflammatory disease affecting approximately 2 % of the global population, has been associated with an increased risk of liver cancer in observational studies. However, their causal relationships as well as underlying shared molecular mechanisms between Ps and liver cancer remain unclear. Using bidirectional Mendelian randomization analysis, we revealed that a genetic predisposition to liver cancer increased the risk of Ps in European and East Asian populations but not the other way around. Moreover, we analyzed three transcriptomic datasets of patients with Ps and liver cancer from open-source databases. Differentially expressed genes (DEGs) and disease-specific gene co-expression module analyses revealed that cell-cycle dysregulation was the shared mechanism of Ps and liver cancer. Moreover, we identified a rank-conservative gene signature shared between these two diseases, which demonstrated significance in diagnostic and prognostic predictions. These findings provided valuable insights into the interconnections between Ps and liver cancer, which may be helpful to guide therapeutic management.

Reusable magnetic molecular imprinted polymers based on magnetic graphene oxide for selective identification and detection of eugenol in environmental water samples.

In this study, a reliable method for determining eugenol content in environmental water samples was established by combining magnetic solid-phase extraction with high-performance liquid chromatography. Magnetic molecular imprinted polymers MGO@MIPs were prepared through surface molecular imprinting technique with eugenol as the template molecule. The material displayed good superparamagnetic properties and magnetic responsiveness in favor of rapid separation. The adsorption properties of MGO@MIPs for eugenol were evaluated through adsorption kinetics and selectivity experiments. MGO@MIPs were found to have favorable reusability and obvious selectivity for eugenol. In addition, adsorption and elution conditions were investigated. Under optimal conditions, a linear relationship was obtained between the concentration of eugenol and its peak area in the range of 0.02-5 mg/L (R2 = 0.9998) and the limit of detection was 4.0 × 10-6 mg/mL. The performance of the established method was assessed with the average recovery of 96.59-102.20% and the relative standard deviation (RSD) below 3.5%. The application of this method provides a new perspective for the separation, enrichment and detection of eugenol in water environment.

Identification of receptors and factors associated with human coronaviruses in the oral cavity using single-cell RNA sequencing.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) ravaged the world, and Coronavirus Disease 2019 (COVID-19) exhibited highly prevalent oral symptoms that had significantly impacted the lives of affected patients. However, the involvement of four human coronavirus (HCoVs), namely SARS-CoV-2, SARS-CoV, MERS-CoV, and HCoV-229E, in oral cavity infections remained poorly understood. We integrated single-cell RNA sequencing (scRNA-seq) data of seven human oral tissues through consistent normalization procedure, including minor salivary gland (MSG), parotid gland (PG), tongue, gingiva, buccal, periodontium and pulp. The Seurat, scDblFinder, Harmony, SingleR, Ucell and scCancer packages were comprehensively used for analysis. We identified specific cell clusters and generated expression profiles of SARS-CoV-2 and coronavirus-associated receptors and factors (SCARFs) in seven oral regions, providing direction for predicting the tropism of four HCoVs for oral tissues, as well as for dental clinical treatment. Based on our analysis, it appears that various SCARFs, including ACE2, ASGR1, KREMEN1, DPP4, ANPEP, CD209, CLEC4G/M, TMPRSS family proteins (including TMPRSS2, TMPRSS4, and TMPRSS11A), and FURIN, are expressed at low levels in the oral cavity. Conversely, BSG, CTSB, and CTSL exhibit enrichment in oral tissues. Our study also demonstrates widespread expression of restriction factors, particularly IFITM1-3 and LY6E, in oral cells. Additionally, some replication, assembly, and trafficking factors appear to exhibit broad oral tissues expression patterns. Overall, the oral cavity could potentially serve as a high-risk site for SARS-CoV-2 infection, while displaying a comparatively lower degree of susceptibility towards other HCoVs (including SARS-CoV, MERS-CoV and HCoV-229E). Specifically, MSG, tongue, and gingiva represent potential sites of vulnerability for four HCoVs infection, with the MSG exhibiting a particularly high susceptibility. However, the expression patterns of SCARFs in other oral sites demonstrate relatively intricate and may only be specifically associated with SARS-CoV-2 infection. Our study sheds light on the mechanisms of HCoVs infection in the oral cavity as well as gains insight into the characteristics and distribution of possible HCoVs target cells in oral tissues, providing potential therapeutic targets for HCoVs infection in the oral cavity.

A PANoptosis pattern to predict prognosis and immunotherapy response in head and neck squamous cell carcinoma.

Individuals diagnosed with head and neck squamous cell carcinoma (HNSCC) experience a significant occurrence rate and are susceptible to premature spreading, resulting in a bleak outlook. Therapeutic approaches, such as chemotherapy, targeted therapy, and immunotherapy, may exhibit primary and acquired resistance during the advanced phases of HNSCC. There is currently no viable solution to tackle this issue. PANoptosis-a type of non-apoptotic cell death-is a recently identified mechanism of cellular demise that entails communication and synchronization among thermal apoptosis, apoptosis, and necrosis mechanisms. However, the extent to which PANoptosis-associated genes (PRG) contribute to the forecast and immune reaction of HNSCC remains mostly undisclosed. The present study aimed to thoroughly analyze the potential importance of PRG in HNSCC and report our discoveries. We systematically analyzed 19 PRG from previous studies and clinical data from HNSCC patients to establish a PAN-related signature and assess its prognostic, predictive potential. Afterward, the patient information was separated into two gene patterns that corresponded to each other, and the analysis focused on the connection between patient prognosis, immune status, and cancer immunotherapy. The PAN score was found to correlate with survival rates, immune systems, and cancer-related pathways. We then validated the malignant role of CD27 among them in HNSCC. In summary, we demonstrated the effectiveness of PAN.Score-based molecular clustering and prognostic features in predicting the outcome of HNSCC. The discovery we made could enhance our comprehension of the significance of PAN.Score in HNSCC and facilitate the development of more effective treatment approaches.

The analysis of the structural parameter influences on measurement errors in a binocular 3D reconstruction system: a portable 3D system.

This study used an analytical model to investigate the factors that affect the reconstruction accuracy composed of the baseline length, lens focal length, the angle between the optical axis and baseline, and the field of the view angle. Firstly, the theoretical expressions of the above factors and measurement errors are derived based on the binocular three-dimensional reconstruction model. Then, the structural parameters' impact on the error propagation coefficient is analyzed and simulated using MATLAB software. The results show that structural parameters significantly impact the error propagation coefficient, and the reasonable range of structural parameters is pointed out. When the angle between the optical axis of the binocular camera and the baseline is between 30° and 55°, the ratio of the baseline length to the focal length can be reasonably reduced. In addition, using the field angle of the view that does not exceed 20° could reduce the error propagation coefficient. While the angle between the binocular optical axis and the baseline is between 40° and 50°, the reconstruction result has the highest accuracy, changing the angle out of this range will lead to an increase in the reconstruction error. The angle between the binocular optical axis and the baseline changes 30° through 60° leads to the error propagation coefficient being in a lower range. Finally, experimental verification and simulation results show that selecting reasonable structural parameters could significantly reduce measurement errors. This study proposes a model that constructs a binocular three-dimensional reconstruction system with high precision. A portable three-dimensional reconstruction system is built in the article.

The analysis of cathepsin L that mediates cellular SARS-CoV-2 infection leading to COVID-19 in head and neck squamous cell carcinoma.

The vulnerability of the oral cavity to SARS-CoV-2 infection is well-known, and cancer patients are at a higher risk of COVID-19, emphasizing the need to prioritize this patient population. Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignant cancers associated with early metastasis and poor prognosis. It has been established that cancerous tissues express Cathepsin L (CTSL), a proteinase that regulates cancer progression and SARS-CoV-2 entry. Therefore, it is essential to evaluate the correlation between disease outcomes and CTSL expression in cancer tissues and predict the susceptibility of cancer patients to SARS-CoV-2. In this study, we used transcriptomic and genomic data to profile CTSL expression in HNSCC and developed a CTSL signature that could reflect the response of HNSCC patients to chemotherapy and immunotherapy. Additionally, we investigated the relationship between CTSL expression and immune cell infiltration and established CTSL as a potential carcinogenic factor for HNSCC patients. These findings could aid in understanding the mechanisms underlying the increased susceptibility of HNSCC patients to SARS-CoV-2 and contribute to the development of therapy for both HNSCC and COVID-19.

Dichloroacetophenone biphenylsulfone ethers as anticancer pyruvate dehydrogenase kinase inhibitors in non-small cell lung cancer models.

Pyruvate dehydrogenase kinase 1 (PDK1) is an important metabolic enzyme which is often overexpressed in many types of cancers, including non-small-cell lung cancers (NSCLC). Targeting PDK1 appears to be an attractive anticancer strategy. Based on a previously reported moderate potent anticancer PDK1 inhibitor, 64, we developed three dichloroacetophenone biphenylsulfone ethers, 30, 31 and 32, which showed strong PDK1 inhibitions of 74%, 83% and 72% at 10 µM, respectively. Then we investigated the anticancer effects of 31 in two NSCLC cell lines, namely, NCI-H1299 and NCI-H1975. It was found that 31 exhibited sub-micromolar cancer cell IC50s, suppressed colony formation, induced mitochondrial membrane potential depolarization, triggered apoptosis, altered cellular glucose metabolism, with concomitant reductions in extracellular lactate levels and enhanced the generation of reactive oxygen species in NSCLC cells. Moreover, 31 significantly suppressed the tumor growth in an NCI-H1975 mouse xenograft model, outperforming the anticancer effects of 64. Taken together our results suggested that inhibition of PDK1 via dichloroacetophenone biphenylsulfone ethers may provide a novel direction leading to an alternative treatment option in NSCLC therapy.

Trichosanthin Promotes Anti-Tumor Immunity through Mediating Chemokines and Granzyme B Secretion in Hepatocellular Carcinoma.

Trichosanthin (TCS) is a type I ribosome-inactivating protein extracted from the tuberous root of the plant Trichosanthes. TCS shows promising potential in clinical drug abortion, anti-tumor and immunological regulation. However, the molecular mechanisms of its anti-tumor and immune regulation properties are still not well discovered. In the present study, we investigated the anti-tumor activity of TCS in hepatocellular carcinoma (HCC), both in vitro and in vivo. Both HCC cell lines and xenograft tumor tissues showed considerable growth inhibition after they were treated with TCS. TCS provoked caspase-mediated apoptosis in HCC cells and xenograft tumor tissues. The recruitment of CD8+ T cells to HCC tissues and the expression of chemokines, CCL2 and CCL22, were promoted upon TCS treatment. In addition, TCS induced an upregulation of Granzyme B (GrzB), TNF-α and IFN-γ in HCC tissues, which are the major cytotoxic mediators produced by T cells. Furthermore, TCS also resulted in an increase of mannose-6-phosphate receptor (M6PR), the major receptor of GrzB, in HCC tissues. In summary, these results suggest that TCS perhaps increases T-cell immunity via promoting the secretion of chemokines and accelerating the entry of GrzB to HCC cells, which highlights the potential role of TCS in anti-tumor immunotherapy.

Erosive effects of commercially available alcoholic beverages on enamel.

This study aimed to investigate the effects of four alcoholic beverages on enamel erosion. Fifty enamel specimens were randomly allocated into the following five groups (n=10): group 1, water as negative control; group 2, red wine; group 3, white wine; group 4, distilled spirit; and group 5, beer. The specimens were immersed in the respective solution for a 16 h demineralization, followed by an 8 h remineralization in artificial saliva. Cyclic de- and re-mineralization were performed for 8 days. Surface roughness, microhardness and morphology of the enamel specimens were studied after the cycling. The results were analyzed by One-way ANOVA and Dunnett's post-hoc test (p<0.05). All investigated beverages showed an erosive effect on enamel. White wine had the highest erosive potential whereas distilled spirit had the least.

Long-Term Protection Elicited by an Inactivated Vaccine Supplemented with a Water-Based Adjuvant against Infectious Hematopoietic Necrosis Virus in Rainbow Trout (Oncorhynchus mykiss).

Previous inactivated vaccines against infectious hematopoietic necrosis (IHN) usually had a strong early immune protective effect but failed to provide long-term protection in rainbow trout (Oncorhynchus mykiss). To find a method for stabilizing the desired protective effect of IHN vaccines, we assessed the immune enhancement effect of four adjuvants on formaldehyde inactivated vaccine for IHN at 60 days postvaccination (dpv). The efficacy of a two-dose vaccination with the candidate adjuvant-formaldehyde inactivated vaccine for IHN was evaluated in terms of early protection and long-term protection (30 to 285 dpv). Neutralizing antibody titers were also measured at each time point. The Montanide GEL 02 PR (Gel 02) adjuvant significantly enhanced the immune protection provided by the IHN inactivated vaccine, whereas the immune-boosting effect of the other tested adjuvants lacked statistical significance. Both tested Gel 02-adjuvanted IHN inactivated vaccine dosages had a strong immune protection effect within 2 months postvaccination, with a relative percent of survival (RPS) of 89.01% to 100%, and the higher dosage provided complete protection at 204 dpv and a RPS of 60.79% on 285 dpv by reducing viral titers in rainbow trout. The neutralizing antibodies were observed only in vaccinated fish on 30 and 60 dpv. Through compatibility with an appropriate adjuvant, the highly immune protective effect of an IHN inactivated vaccine was prolonged from 60 dpv to at least 284 dpv; this novel adjuvant-IHN inactivated vaccine has promise as a commercial vaccine that provides the best available and longest duration of protection against IHN to rainbow trout. IMPORTANCE Infectious hematopoietic necrosis virus (IHNV) is one of the most serious pathogens threatening the global salmon and trout industry. However, there is currently only one commercialized infectious hematopoietic necrosis (IHN) vaccine, and it is inadequate for solving the global IHN problem. In this study, a promising adjuvanted inactivated vaccine with long-term protection was developed and comprehensively studied. We confirmed the presence of a late antiviral response stage in vaccinated rainbow trout that lacked detectable neutralizing antibodies, which are commonly recognized to be responsible for long-term specific protection in mammals. These findings further our understanding of unique features of fish immune systems and could lead to improved prevention and control of fish diseases.

CCHCR1-astrin interaction promotes centriole duplication through recruitment of CEP72.

BACKGROUND: The centrosome is one of the most important non-membranous organelles regulating microtubule organization and progression of cell mitosis. The coiled-coil alpha-helical rod protein 1 (CCHCR1, also known as HCR) gene is considered to be a psoriasis susceptibility gene, and the protein is suggested to be localized to the P-bodies and centrosomes in mammalian cells. However, the exact cellular function of HCR and its potential regulatory role in the centrosomes remain unexplored. RESULTS: We found that HCR interacts directly with astrin, a key factor in centrosome maturation and mitosis. Immunoprecipitation assays showed that the coiled-coil region present in the C-terminus of HCR and astrin respectively mediated the interaction between them. Astrin not only recruits HCR to the centrosome, but also protects HCR from ubiquitin-proteasome-mediated degradation. In addition, depletion of either HCR or astrin significantly reduced centrosome localization of CEP72 and subsequent MCPH proteins, including CEP152, CDK5RAP2, and CEP63. The absence of HCR also caused centriole duplication defects and mitotic errors, resulting in multipolar spindle formation, genomic instability, and DNA damage. CONCLUSION: We conclude that HCR is localized and stabilized at the centrosome by directly binding to astrin. HCR are required for the centrosomal recruitment of MCPH proteins and centriolar duplication. Both HCR and astrin play key roles in keeping normal microtubule assembly and maintaining genomic stability.

Identification of Human Global, Tissue and Within-Tissue Cell-Specific Stably Expressed Genes at Single-Cell Resolution.

Stably Expressed Genes (SEGs) are a set of genes with invariant expression. Identification of SEGs, especially among both healthy and diseased tissues, is of clinical relevance to enable more accurate data integration, gene expression comparison and biomarker detection. However, it remains unclear how many global SEGs there are, whether there are development-, tissue- or cell-specific SEGs, and whether diseases can influence their expression. In this research, we systematically investigate human SEGs at single-cell level and observe their development-, tissue- and cell-specificity, and expression stability under various diseased states. A hierarchical strategy is proposed to identify a list of 408 spatial-temporal SEGs. Development-specific SEGs are also identified, with adult tissue-specific SEGs enriched with the function of immune processes and fetal tissue-specific SEGs enriched in RNA splicing activities. Cells of the same type within different tissues tend to show similar SEG composition profiles. Diseases or stresses do not show influence on the expression stableness of SEGs in various tissues. In addition to serving as markers and internal references for data normalization and integration, we examine another possible application of SEGs, i.e., being applied for cell decomposition. The deconvolution model could accurately predict the fractions of major immune cells in multiple independent testing datasets of peripheral blood samples. The study provides a reliable list of human SEGs at the single-cell level, facilitates the understanding on the property of SEGs, and extends their possible applications.

A Therapeutic Whole-Tumor-Cell Vaccine Covalently Conjugated with a TLR7 Agonist.

A single-protein or -peptide vaccine is not sufficient to arouse immune responses in cancer therapy. A whole-tumor-cell vaccine with complete cancer cell antigens and all conformations elicits robust immune responses and is a promising method for the treatment of advanced malignant tumors. In this study, we used 5-azacitidine to stimulate B16-F10 melanoma cells to express toll-like receptor (TLR) 3 on the cell surface and then chemically linked SZU-106, a small-molecule TLR7 agonist, to the cell surface with a pegylated linker to produce a novel whole-tumor-cell vaccine, abbreviated as Aza-BFcell-106. The vaccine stimulated mouse splenic lymphocytes and bone marrow-derived dendritic cells to secrete cytokines, promoted the maturation of dendritic cells and enhanced the capability of dendritic cells to present antigens. In a mouse model of melanoma, the vaccine effectively inhibited tumor growth, decreased tumor volume and prolonged survival. Further combination of the vaccine with a chemokine inhibitor, reparixin, significantly increased the infiltration of CD4+ and CD8+ T cells into the tumor environment, while the antitumor effect was significantly enhanced. The whole-tumor-cell vaccine Aza-BFcell-106 induced immune-activating responses in both in vitro and in vivo experiments, indicating that this vaccine has great potential to treat advanced malignant tumors.

The oral manifestations and related mechanisms of COVID-19 caused by SARS-CoV-2 infection.

Coronavirus disease 2019 (COVID-19) was reported to be associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, and patients present mostly with respiratory symptoms. There have been an increasing number of reports on oral manifestations, and some of these signs are informative in terms of identifying SARS-CoV-2 infection. The goal of present study was to review and synthesize the clinical characteristics and underlying mechanisms of COVID-19 oral manifestations, as well as to evaluate the factors influencing SARS-CoV-2 infectivity, in order to conduct further in-depth investigations and help clinicians diagnose COVID-19 patients exhibiting oral symptoms.

Transmembrane protein 97 exhibits oncogenic properties via enhancing LRP6-mediated Wnt signaling in breast cancer.

Upregulation of transmembrane protein 97 (TMEM97) has been associated with progression and poor outcome in multiple human cancers, including breast cancer. Recent studies suggest that TMEM97 may be involved in the activation of the Wnt/ß-catenin pathway. However, the molecular mechanism of TMEM97 action on Wnt/ß-catenin signaling is completely unclear. In the current study, TMEM97 was identified as an LRP6-interacting protein. TMEM97 could interact with LRP6 intracellular domain and enhance LRP6-mediated Wnt signaling in a CK1δ/ε-dependent manner. The binding of TMEM97 to LRP6 facilitated the recruitment of CK1δ/ε to LRP6 complex, resulting in LRP6 phosphorylation at Ser 1490 and the stabilization of ß-catenin. In breast cancer cells, knockout of TMEM97 attenuated the Wnt/ß-catenin signaling cascade via regulating LRP6 phosphorylation, leading to a decrease in the expression of Wnt target genes AXIN2, LEF1, and survivin. TMEM97 deficiency also suppressed cell viability, proliferation, colony formation, migration, invasion, and stemness properties in breast cancer cells. Importantly, TMEM97 knockout suppressed tumor growth through downregulating the Wnt/ß-catenin signaling pathway in a breast cancer xenograft model. Taken together, our results revealed that TMEM97 is a positive modulator of canonical Wnt signaling. TMEM97-mediated Wnt signaling is implicated in the tumorigenesis of breast cancer, and its targeted inhibition may be a promising therapeutic strategy for breast cancer.

Conversion of stem cells from apical papilla into endothelial cells by small molecules and growth factors.

OBJECTIVES: Recently, a new strategy has been developed to directly reprogram one cell type towards another targeted cell type using small molecule compounds. Human fibroblasts have been chemically reprogrammed into neuronal cells, Schwann cells and cardiomyocyte-like cells by different small molecule combinations. This study aimed to explore whether stem cells from apical papilla (SCAP) could be reprogrammed into endothelial cells (ECs) using the same strategy. MATERIALS AND METHODS: The expression level of endothelial-specific genes and proteins after chemical induction of SCAP was assessed by RT-PCR, western blotting, flow cytometry and immunofluorescence. The in vitro functions of SCAP-derived chemical-induced endothelial cells (SCAP-ECs) were evaluated by tube-like structure formation assay, acetylated low-density lipoprotein (ac-LDL) uptake and NO secretion detection. The proliferation and the migration ability of SCAP-ECs were evaluated by CCK-8 and Transwell assay. LPS stimulation was used to mimic the inflammatory environment in demonstrating the ability of SCAP-ECs to express adhesion molecules. The in vivo Matrigel plug angiogenesis assay was performed to assess the function of SCAP-ECs in generating vascular structures using the immune-deficient mouse model. RESULTS: SCAP-ECs expressed upregulated endothelial-specific genes and proteins; displayed endothelial transcriptional networks; exhibited the ability to form functional tubular-like structures, uptake ac-LDL and secrete NO in vitro; and contributed to generate blood vessels in vivo. The SCAP-ECs could also express adhesion molecules in the pro-inflammatory environment and have a similar migration and proliferation ability as HUVECs. CONCLUSIONS: Our study demonstrates that the set of small molecules and growth factors could significantly promote endothelial transdifferentiation of SCAP, which provides a promising candidate cell source for vascular engineering and treatment of ischemic diseases.

Solvent-free mechanochemical preparation of graphene oxide-Fe3 O4 and its application in magnetic dispersive solid-phase extraction of illegal dyes in food samples.

A simple, green, and efficient mechanochemical approach was developed herein to prepare tunable magnetic graphene oxide nanoparticles. The obtained nanoparticles were successfully used as adsorbents in a magnetic dispersive solid-phase extraction method to extract three cationic dyes (i.e., thioflavine T, auramine-O, and basic orange 2) found in food samples. Our proposed approach also utilized high-performance liquid chromatography with ultraviolet detection. Several key variables affecting the extraction recovery were investigated. These included the sample pH, amount of extractant, extraction time, sample volume, elution solvent type and volume, and the stability and reusability of the magnetic graphene oxide nanoparticles. Under optimized conditions, the calibration curve was linear at a concentration range of 0.005-1.0 µg/mL with a correlation coefficient of 0.9992-0.9996. Moreover, the limits of detection were determined at 0.97-1.35 µg/mL. The extraction mechanism was investigated via ultraviolet-visible spectrophotometry and zeta-potential analyses. The developed method was used to analyze the above-mentioned cationic dyes in bean products and yellow fish samples. Notably, satisfactory spiked recoveries ranging from 90.7 to 104.9% were achieved.

Trichosanthin cooperates with Granzyme B to restrain tumor formation in tongue squamous cell carcinoma.

BACKGROUND: Tongue squamous cell carcinoma (TSCC) is a common type of oral cancer, with a relatively poor prognosis and low post-treatment survival rate. Various strategies and novel drugs to treat TSCC are emerging and under investigation. Trichosanthin (TCS), extracted from the root tubers of Tian-Hua-Fen, has been found to have multiple biological and pharmacological functions, including inhibiting the growth of cancer cells. Granzyme B (GrzB) is a common toxic protein secreted by natural killer cells and cytotoxic T cells. Our group has reported that TCS combined with GrzB might be a superior approach to inhibit liver tumor progression, but data relating to the use of this combination to treat TSCC remain limited. The aim of this study was to examine the effectiveness of TCS on TSCC processes and underlying mechanisms. METHODS: First, we screened the potential antitumor activity of TCS using two types of SCC cell lines. Subsequently, a subcutaneous squamous cell carcinoma xenograft model in nude mice was established. These model mice were randomly divided into four groups and treated as follows: control group, TCS treatment group, GrzB treatment group, and TCS/GrzB combination treatment group. Various tumorigenesis parameters, such as Ki67, PCNA, caspase-3, Bcl-2 and VEGFA, et al., were performed to determine the effects of these treatments on tumor development. RESULTS: Screening confirmed that the SCC25 line exhibited greater sensitivity than the SCC15 line to TCS in vitro studies. TCS or GrzB treatment significantly inhibited tumor growth compared with the inhibition seen in the control group. The TCS/GrzB combination inhibited tumor growth more than either drug alone. TCS treatment inhibited tumor proliferation by downregulating Ki67 and Bcl2 protein expression while accelerating tumor apoptosis. In the TCS/GrzB-treated group, expression of Ki67 was further downregulated, while the level of activated caspase-3 was increased, compared with their expression in either of the single drug treatment groups. CONCLUSION: These results suggest that the TCS/GrzB combination could represent an effective immunotherapy for TSCC.

Astrin: A Key Player in Mitosis and Cancer.

Astrin, which is a spindle-associated protein, was found to be closely related to mitotic spindle formation and maintenance. It interacts with other spindle-related proteins to play a key role in maintaining the attachment of the kinetochore-microtubule and integrity of centrosomes and promoting the centriole duplication. In addition, Astrin was quite recently found to be abnormally highly expressed in a variety of cancers. Astrin promotes the development of cancer by participating in various molecular pathways and is considered as a potential prognostic and survival predictor.

Separation and Determination of Paraquat and Diquat in Human Plasma and Urine by Magnetic Dispersive Solid Phase Extraction Coupled with High-Performance Liquid Chromatography.

A magnetic dispersive solid phase extraction method coupled with high-performance liquid chromatography was proposed for the simultaneous separation and determination of paraquat (PQ) and diquat (DQ) in human plasma and urine samples. Based on the reduction of PQ and DQ to a blue radical and yellow-green radical by sodium dithionite in an alkaline medium, a fast colorimetric method was also developed for the fast detection of PQ or DQ. In this paper, CoFe2O4@SiO2 magnetic nanoparticles were used as the adsorbent for the magnetic dispersive solid phase extraction of paraquat and diquat, and these two analytes were found to be eluted directly from the adsorbent by NaOH solution. The main factors affecting the extraction efficiency including amount of extractant, extraction time, sample volume, sample solution pH, and elution volume were optimized. Under the optimized experimental conditions, the calibration curve was linear at a concentration range of 28.5-570.2 µg/L, and the correlation coefficient of paraquat and diquat was 0.9986 and 0.9980, respectively. The limits of detection of paraquat and diquat were 4.5 µg/L and 4.3 µg/L. The proposed MSPE-HPLC method was successfully applied to the detection of the paraquat and diquat in human plasma and urine with satisfied recoveries of PQ and DQ in the range of 87.5%-98.7%.