Tumor microenvironment characteristics association with clinical outcome in patients with resected intestinal-type gastric cancer.

BACKGROUND: Tumor microenvironment (TME) characteristics including tumor stroma ratio (TSR), tumor budding (TB), and tumor-infiltrating lymphocytes (TILs) were examined in resected gastric cancer. These TME features have been shown to indicate metastatic potential in colon cancer, and intestinal-type gastric cancer (IGC) has pathological similarities with that malignancy. METHODS: TSR, TB, and TILs were quantified in routine histological sections from 493 patients with IGC who underwent radical resection at 2 university hospitals in China from 2010 to 2016. TME variables were dichotomized as follows: TSR (50%), TILs (median), TB per international guidelines (4 buds/0.785mm2), and platelet-lymphocyte ratio (PLR) per survival ROC. Association of TME features with patient clinicopathological characteristics, time-to-recurrence (TTR), and cancer-specific-survival (CSS) were examined using univariate and multivariate analysis, including a relative contribution analysis by Cox regression. RESULTS: Patients whose tumors showed high TSR or high TB or low TILs were each significantly associated with increased T and N stage, higher histological grade, and poorer TTR and CSS at 5 years. Only TSR and N stage were independently associated with TTR and CSS after adjustment for covariates. PLR was only independently associated with TTR after adjustment for covariates. Among the variables examined, only TSR was significantly associated with both TTR (HR 1.72, 95% CI, 1.14-2.60, P = .01) and CSS (HR 1.62, 95% CI, 1.05-2.51, P = .03) multivariately. Relative contribution to TTR revealed that the top 3 contributors were N stage (45.1%), TSR (22.5%), and PLR (12.9%), while the top 3 contributors to CSS were N stage (59.9%), TSR (14.7%), and PLR (10.9%). CONCLUSIONS: Among the examined TME features, TSR was the most robust for prognostication and was significantly associated with both TTR and CSS. Furthermore, the relative contribution of TSR to patient TTR and CSS was second only to nodal status.

Increasing Sufu gene dosage reveals its unorthodox role in promoting polydactyly and medulloblastoma tumorigenesis.

Suppressor of fused (SUFU) is widely regarded as a key negative regulator of the sonic hedgehog (SHH) morphogenic pathway and a known tumor suppressor of medulloblastoma (MB). However, we report here that SUFU expression was markedly increased in 75% of specimens compiled in a tissue array comprising 49 unstratified MBs. The SUFU and GLI1 expression levels in this MB array showed strong positive correlation, which was also identified in a large public data set containing 736 MBs. We further report that increasing Sufu gene dosage in mice caused preaxial polydactyly, which was associated with the expansion of the Gli3 domain in the anterior limb bud and heightened Shh signaling responses during embryonic development. Increasing Sufu gene dosage also led to accelerated cerebellar development and, when combined with ablation of the Shh receptor encoded by Patched1 (Ptch1), promoted MB tumorigenesis. These data reveal multifaceted roles of SUFU in promoting MB tumorigenesis by enhancing SHH signaling. This revelation clarifies potentially counterintuitive clinical observation of high SUFU expression in MBs and may pave way for novel strategies to reduce or reverse MB progression.

Solid pseudopapillary neoplasm: Report of a case of primary ovarian origin and review of the literature.

Background: Solid pseudopapillary neoplasms (SPNs) are uncommon tumors of low malignancy with a generally favorable prognosis, mostly originating from the pancreas. To date, 12 cases of SPNs with a primary ovarian origin (SPN-Os) have been reported globally, and their detailed characteristics have not been fully elucidated. Case description: We reported the 13th SPN-O case, which occurred in a 52-year-old woman with an 18.5 cm left ovarian mass. Four imaging methods, including ultrasound, computed tomography, magnetic resonance imaging and positron emission tomography, were utilized before surgery. An elevated level of serum cancer antigen 125 was detected and a total hysterectomy plus bilateral salpingo-oophorectomy was performed. Microscopic examination revealed a typical solid pseudopapillary structure. The tumor cells were stained focally for pan-cytokeratin, synaptophysin, CD99 and CD10, while ß-catenin, vimentin and CD56 were diffusely expressed. The Ki-67 proliferation index was 3%, and immunohistochemical (IHC) staining for chromogranin-A, inhibin-a, and E-cadherin was negative. No evidence of recurrence or metastasis was observed by clinical and imaging data during a 5-month postoperative follow-up. Conclusion: This is a report of an unusual case of a primary ovarian SPN with an up-to-date review of SPN-Os. A minimum combination of imaging methods and IHC stains was proposed for SPN-Os, which may prove beneficial in clinical practice.

Individual prefrontal neurons contribute to sensory-to-motor information transformation by rotating reference frames during spatial working memory performance.

Performing working memory tasks correctly requires not only the temporary maintenance of information but also the visual-to-motor transformation of information. Although sustained delay-period activity is known to be a mechanism for temporarily maintaining information, the mechanism for information transformation is not well known. An analysis using a population of delay-period activities recorded from prefrontal neurons visualized a gradual change of maintained information from sensory to motor as the delay period progressed. However, the contributions of individual prefrontal neurons to this process are not known. In the present study, we used a version of the delayed-response task, in which monkeys needed to make a saccade 90o clockwise from a visual cue after a 3-s delay, and examined the temporal change in the preferred directions of delay-period activity during the delay period for individual neurons. One group of prefrontal neurons encoded the cue direction by a retinotopic reference frame and either maintained it throughout the delay period or rotated it 90o counterclockwise to adjust visual information to saccade information, whereas other groups of neurons encoded the cue direction by a saccade-based reference frame and rotated it 90o clockwise. The results indicate that visual-to-motor information transformation is achieved by manipulating the reference frame to adjust visual coordinates to motor coordinates.

Preparation of photothermal responsive, antibacterial hydrogel by using PVA-Alg and silver nanofibers as building blocks.

Introduction: Photothermal responsive, antimicrobial hydrogels are very attractive and have great potential in the field of tissue engineering. The defective wound environment and metabolic abnormalities in diabetic skin would lead to bacterial infections. Therefore, multifunctional composites with antimicrobial properties are urgently needed to improve the current therapeutic outcomes of diabetic wounds. We prepared an injectable hydrogel loaded with silver nanofibers for efficient and sustained bactericidal activity. Methods: To construct this hydrogel with good antimicrobial activity, homogeneous silver nanofibers were first prepared by solvothermal method and then dispersed in PVA-lg solution. After homogeneous mixing and gelation, injectable hydrogels (Ag@H) wrapped with silver nanofibers were obtained. Results: By virtue of Ag nanofibers, Ag@H exhibited good photothermal conversion efficiency and good antibacterial activity against drug-resistant bacteria, while the in vivo antibacterial also showed excellent performance. The results of antibacterial experiments showed that Ag@H had significant bactericidal effects on MRSA and E. coli with 88.4% and 90.3% inhibition rates, respectively. Discussion: The above results indicate that Ag@H with photothermal reactivity and antibacterial activity is very promising for biomedical applications, such as wound healing and tissue engineering.

Natriuretic peptides as predictors for atrial fibrillation recurrence after catheter ablation: A meta-analysis.

BACKGROUND: Catheter ablation (CA) has become the first-line treatment strategy for atrial fibrillation (AF) but remains with a substantial recurrence rate. The aim of this meta-analysis was to determine the association between baseline natriuretic peptide levels and AF recurrence after CA. METHODS: We systematically searched PubMed, EMBASE, Web of Science, and Wiley-Cochrane Library for relevant studies published up until May 2022. Overall effect analysis and subgroup analysis were performed with Review Manager software. RESULTS: Finally, 61 studies that met the inclusion criteria were included in our meta-analysis. Compared with the nonrecurrence group, the recurrence group had increased baseline level of atrial natriuretic peptide (ANP) (standardized mean difference [SMD] = 0.39, 95% confidence interval [CI]: 0.21-0.56), brain natriuretic peptide (BNP) (SMD = 0.51, 95% CI: 0.31-0.71), N-terminal pro-BNP (SMD = 0.71, 95% CI: 0.49-0.92), and midregional N-terminal pro-ANP (SMD = 0.91, 95% CI: 0.27-1.56). CONCLUSIONS: Increased baseline natriuretic peptide levels, including ANP, BNP, N-terminal pro-BNP, and midregional N-terminal pro-ANP, are associated with a higher risk of AF recurrence after CA. Nonetheless, further studies are needed to elucidate the predictive value of baseline natriuretic peptides in AF patients undergoing CA.

Rizatriptan-Loaded Oral Fast Dissolving Films: Design and Characterizations.

Rizatriptan (RZT) is an efficient anti-migraine drug which belongs to the class of selective 5 HT (1B/1D) serotonin receptor agonists. Nevertheless, RZT elicits several adverse effects and RZT nasal sprays have a limited half-life, requiring repeated doses that could cause patient noncompliance or harm to the nasopharynx and cilia. The current research aimed to develop orally disintegrating films (ODFs) of RZT employing maltodextrin (MTX) and pullulan (PUL) as film-forming polymers, as well as propylene glycol (PG) as a plasticizer. The ODFs were prepared by solvent casting method (SCM). The technique was optimized using Box-Behnken design (BBD), contemplating the ratios of PUL: MTX and different levels of PG (%) as factor variables. The influence of these factors was systematically analyzed on the selected dependent variables, including film thickness, disintegration time (D-time), folding endurance (FE), tensile strength (TS), percent elongation (%E), moisture content (%), and water uptake (%). In addition, the surface morphology, solid state analysis, drug content uniformity (%), drug release (%), and pH of the RZT-ODFs were also studied. The results demonstrated a satisfactory stable RZT-ODFs formulation that exhibited surface homogeneity and amorphous RZT in films with no discernible interactions between the model drug and polymeric materials. The optimized film showed a rapid D-time of 16 s and remarkable mechanical features. The in vitro dissolution kinetics showed that 100% RZT was released from optimized film compared to 61% RZT released from conventional RZT formulation in the initial 5 min. An animal pharmacokinetic (PK) investigation revealed that RZT-ODFs had a shorter time to achieve peak plasma concentration (Tmax), a higher maximum plasma concentration (Cmax), and area under the curve (AUC0-t) than traditional oral mini capsules. These findings proposed a progressive approach for developing anti-migraine drugs that could be useful in reducing the complications of dysphagia in geriatric and pediatric sufferers.

Development and Characterizations of Pullulan and Maltodextrin-Based Oral Fast-Dissolving Films Employing a Box-Behnken Experimental Design.

Migraine is a neurological disorder characterized by severe headaches, visual aversions, auditory, and olfactory disorders, accompanied by nausea and vomiting. Zolmitriptan (ZMT®) is a potent 5HT1B/1D serotonin receptor agonist frequently used for the treatment of migraine. It has erratic absorption from the gastrointestinal tract (GIT), but its oral bioavailability is low (40-45%) due to the hepatic metabolism. This makes it an ideal candidate for oral fast dissolving formulations. Hence, the current study was undertaken to design and develop oral fast-dissolving films (OFDFs) containing ZMT for migraine treatment. The OFDFs were formulated by the solvent casting method (SCM) using Pullulan (PU) and maltodextrin (MDX) as film-forming agents and propylene glycol (PG) as a plasticizer. The strategy was designed using Box-Behnken experimental design considering the proportion of PU:MDX and percentage of PG as independent variables. The effectiveness of the OFDF's was measured based on the following responses: drug release at five min, disintegration time (D-time), and tensile strength (TS). The influence of formulation factors, including percent elongation (%E), thickness, water content, moisture absorption, and folding endurance on ZMT-OFDFs, were also studied. The results showed a successful fabrication of stable ZMT-OFDFs, with surface uniformity and amorphous shape of ZMT in fabricated films. The optimized formulation showed a remarkable rapid dissolution, over 90% within the first 5 min, a fast D-time of 18 s, and excellent mechanical characteristics. Improved maximum plasma concentration (C max) and area under the curve (AUC 0-t) in animals (rats) treated with ZMT-OFDFs compared to those treated with an intra-gastric (i-g) suspension of ZMT were also observed. Copolymer OFDFs with ZMT is an exciting proposition with great potential for the treatment of migraine headache. This study offers a promising strategy for developing ZMT-OFDFs using SCM. ZMT-OFDFs showed remarkable rapid dissolution and fast D-time, which might endeavor ZMT-OFDFs as an auspicious alternative approach to improve patient compliance and shorten the onset time of ZMT in migraine treatment.

EF-Hand Domain-Containing Protein D2 (EFHD2) Correlates with Immune Infiltration and Predicts the Prognosis of Patients: A Pan-Cancer Analysis.

Background: EF-hand domain-containing protein D2 (EFHD2) has recently been reported to participate in initiation of cancer. More evidence indicates that EFHD2 plays an important role in tumors, but the pan-cancer analysis of EFHD2 is still very limited. Methods: In this study, we downloaded the original mRNA expression data and SNP data of 33 kinds of tumor data. The gene expression data of different tissues were downloaded from the GTEX database, combined with TCGA data and corrected to calculate the difference of gene expression. The data of total survival time (OS) and progression-free survival (PFS) of TCGA patients were downloaded from the Xena database to further survey the relationship between the EFHD2 expression and prognosis. The CIBERSORT algorithm was used to analyze the RNA-seq data of 33 kinds of cancer patients in different subgroups. In this study, NCI-60 drug sensitivity data and RNA-seq data were downloaded to explore the relationship between genes and common antineoplastic drug sensitivity through correlation analysis. In this study, GSEA analysis was carried out from the Molecular Signature database through the packages of "clusterprofiler" and "enrichplot." By comparing the differences of signal pathways between high and low gene expression groups, the possible molecular mechanism of prognostic differences among 33 kinds of tumors was determined. Results: Our results indicated that EFHD2 was highly expressed in 23 kinds of tumors. In addition, EFHD2 was associated with stage in many kinds of tumors. The expression of EFHD2 was closely related to the OS of 12 kinds of cancer patients. In addition, Kaplan-Meier- (KM-) plot survival analysis indicated that the high expression of EFHD2 was related to the poor OS of 5 kinds of cancer, and the expression of EFHD2 was closely related to the PFI of 5 kinds of cancer patients. The expression of EFHD2 was closely related to immune infiltration, among which 18 cancers were significantly correlated with CD8T cells, 14 cancers were significantly correlated with T regulatory (Tregs) cells, 15 cancers were significantly correlated with CD4 memory activated Tcells, and EFHD2 was significantly correlated with common tumor-related regulatory genes such as TGF beta signaling, TNFA signaling, hypoxia, scorch death, DNA repair, autophagy, and iron death-related genes. The expression level of EFHD2 was significantly correlated with each tumor of TMB, including STAD, SARC, ACC, THYM, KICH, THCA, and TGCT. In MSI, there were significant differences in THYM, STAD, THCA, and TGCT. We used the CellMiner database to explore the sensitivity between EFHD2 gene and common antineoplastic drugs and found that the prediction of high expression of EFHD2 was related to the resistance of many antineoplastic drugs. In renal cell carcinoma, the high expression of EFHD2 is mainly concentrated in ALLOGRAFT_REJECTION, REACTIVE_OXYGEN_SPECIES_PATHWAY, INTERFERON_GAMMA_RESPONSE, IL6_JAK_STAT3_SIGNALING, INTERFERON_ALPHA_RESPONSE, and other signal pathways. GO results showed that the genes were mainly enriched in response to interferon-gamma, antigen processing and presentation, cellular response to interferon-gamma, and other pathways. KEGG results demonstrated that EFHD2 was mainly rich in phagosome, Epstein-Barr virus infection, Staphylococcus aureus infection, and other pathways. The results of Kaplan-Meier survival analysis demonstrated that the high expression of EFHD2 was significantly related to the poor prognosis. Conclusion: Our findings highlight the predictive value of EFHD2 in cancer and provide a potential research direction for elucidating the role of EFHD2 in tumorigenesis and drug resistance.

Development of a new rapid, economical and eco-friendly HPLC method for in vitro and in vivo determination of zolmitriptan.

Multiple high-performance liquid chromatographic (HPLC) approaches have been briefly defined for the assessment of zolmitriptan (ZMT). These methods are either cumbersome or require a plentiful volume of organic solvents, thus offering extortionate procedures. The objective of this study was to establish and validate a new rapid, eco- friendly and cost-effective HPLC method for the analysis of ZMT. The calibration curve for ZMT was established using simulated salivary fluid (SSF) and rat plasma for in-vitro and in-vivo analysis, respectively. Chromatogram separation was performed using a CST column (250mm × 4.6mm, 5µm) as a stationary phase and maintained at a temperature of 40°C. The methods were authenticated for linearity, system suitability, accuracy, precision, reproducibility, limit of detection (LOD) and limit of quantification (LOQ). The results of the validation variables and stability studies indicated that the methods were established in accordance with the guidelines of ICH and the USFDA. The established technique was time-saving, precise, eco- friendly and economical compared with the reported technique. In addition, the developed method was sufficiently repeatable for in vitro and in vivo analysis of ZMT.

An NIR-Triggered Au Nanocage Used for Photo-Thermo Therapy of Chronic Wound in Diabetic Rats Through Bacterial Membrane Destruction and Skin Cell Mitochondrial Protection.

Bacterial infection and its severe oxidative stress reaction will cause damage to skin cell mitochondria, resulting in long-lasting wound healing and great pain to patients. Thus, delayed wound healing in diabetic patients with Staphylococcus aureus infection is a principal challenge worldwide. Therefore, novel biomaterials with multifunction of bacterial membrane destruction and skin cell mitochondrial protection are urgently needed to be developed to address this challenge. In this work, novel gold cage (AuNCs) modified with epigallocatechin gallate (EGCG) were prepared to treat delayed diabetic wounds. The results showed that Au-EGCG had a high and stable photothermal conversion efficiency under near-infrared irradiation, and the scavenging rate of Au-EGCG for S. aureus could reach 95%. The production of large amounts of reactive oxygen species (ROS) leads to the disruption of bacterial membranes, inducing bacterial lysis and apoptosis. Meanwhile, Au-EGCG fused into hydrogel (Au-EGCG@H) promoted the migration and proliferation of human umbilical cord endothelial cells, reduced cellular mitochondrial damage and oxidative stress in the presence of infection, and significantly increased the basic fibroblast growth factor expression and vascular endothelial growth factor. In addition, animal studies showed that wound closure was 97.2% after 12 days of treatment, and the healing of chronic diabetic wounds was significantly accelerated. Au-EGCG nanoplatforms were successfully prepared to promote cell migration and angiogenesis in diabetic rats while removing S. aureus, reducing oxidative stress in cells, and restoring impaired mitochondrial function. Au-EGCG provides an effective, biocompatible, and multifunctional therapeutic strategy for chronic diabetic wounds.

Learning to Discover Multi-Class Attentional Regions for Multi-Label Image Recognition.

Multi-label image recognition is a practical and challenging task compared to single-label image classification. However, previous works may be suboptimal because of a great number of object proposals or complex attentional region generation modules. In this paper, we propose a simple but efficient two-stream framework to recognize multi-category objects from global image to local regions, similar to how human beings perceive objects. To bridge the gap between global and local streams, we propose a multi-class attentional region module which aims to make the number of attentional regions as small as possible and keep the diversity of these regions as high as possible. Our method can efficiently and effectively recognize multi-class objects with an affordable computation cost and a parameter-free region localization module. Over three benchmarks on multi-label image classification, our method achieves new state-of-the-art results with a single model only using image semantics without label dependency. In addition, the effectiveness of the proposed method is extensively demonstrated under different factors such as global pooling strategy, input size and network architecture. Code has been made available at https://github.com/gaobb/MCAR.

SPOP-PTEN-SUFU axis promotes progression of clear cell renal cell carcinoma via activating SHH and WNT pathway.

Although E3 ligase Speckle type BTB/POZ protein (SPOP) promotes tumorigenesis by acting as a key regulatory hub in clear cell renal cell carcinoma (ccRCC), the detailed molecular mechanism remains unclear. Here, we demonstrate that a well-known tumor suppressor, Suppressor of Fused (SUFU), is downregulated by SPOP. Interestingly, this downregulation depends on cullin-3(Cul3)-SPOP E3 ligase, but SUFU is not a direct substrate of SPOP. Phosphatase and tensin homolog (PTEN), a ubiquitinated substrate of SPOP, is involved in SPOP-mediated SUFU reduction. Importantly, inhibition of SUFU leads to elevated SHH and WNT signaling, consequently rescuing the reduced proliferation, migration, and invasion abilities of ccRCC cells caused by SPOP-knockdown. Moreover, combinatorial treatment with SHH and WNT inhibitors shows more effective for suppressing ccRCC cell proliferation and aggressiveness. These findings demonstrate that a novel SPOP-PTEN-SUFU axis promotes ccRCC carcinogenesis by activating SHH and WNT pathway, providing a new treatment strategy for ccRCC.

YTHDF2 is a potential target of AML1/ETO-HIF1α loop-mediated cell proliferation in t(8;21) AML.

The t(8;21) fusion product, AML1/ETO, and hypoxia-inducible factor 1α (HIF1α) form a feed-forward transcription loop that cooperatively transactivates the DNA methyltransferase 3a gene promoter that leads to DNA hypermethylation and drives leukemia cell growth. Suppression of the RNA N6-methyladenosine (m6A)-reader enzyme YTH N6-methyladenosine RNA binding protein 2 (YTHDF2) specifically compromises cancer stem cells in acute myeloid leukemia (AML) but promotes hematopoietic stem cell expansion without derailing normal hematopoiesis. However, the relevance of expression between AML1/ETO-HIF1α loop and YTHDF2, and its functional relationship with t(8;21) AML have not been documented. Here, we show that YTHDF2 is highly expressed in t(8;21) AML patients and associated with a higher risk of relapse and inferior relapse-free survival. Knockdown of YTHDF2 in leukemia cells causes an impaired cell proliferation rate in vitro and in mice. Mechanistically, HIF1α is able to bind to the hypoxia-response elements of the 5'-untranslated region of the YTHDF2 gene and promotes the transactivity of the YTHDF2 promoter. Knockdown and overexpression of either AML1/ETO or HIF1α resulted in decreased and increased YTHDF2 protein and mRNA expression in t(8;21) AML cells. In particular, knockdown of YTHDF2 resulted in increased global mRNA m6A levels in t(8;21) AML cells, accompanied by increased TNF receptor superfamily member 1b (TNFRSF1b) mRNA and protein expression levels. Last, we demonstrated that the m6A methylation and expression levels of the TNFRSF1b gene were both negatively correlated with HIF1α expression levels. In conclusion, YTHDF2 is a downstream target of the AML1/ETO-HIF1α loop and promotes cell proliferation probably by modulating the global m6A methylation in t(8;21) AML.

The Anti-Inflammatory Effect and Mucosal Barrier Protection of Clostridium butyricum RH2 in Ceftriaxone-Induced Intestinal Dysbacteriosis.

This study aimed at determining the beneficial effect of Clostridium butyricum (CB) RH2 on ceftriaxone-induced dysbacteriosis. To this purpose, BALB/c mice were exposed to ceftriaxone (400 mg/ml) or not (control) for 7 days, and administered a daily oral gavage of low-, and high-dose CB RH2 (108 and 1010 CFU/ml, respectively) for 2 weeks. CB RH2 altered the diversity of gut microbiota, changed the composition of gut microbiota in phylum and genus level, decreased the F/B ratio, and decreased the pro-inflammatory bacteria (Deferribacteres, Oscillibacter, Desulfovibrio, Mucispirillum and Parabacteroides) in ceftriaxone-treated mice. Additionally, CB RH2 improved colonic architecture and intestinal integrity by improving the mucous layer and the tight junction barrier. Furthermore, CB RH2 also mitigated intestinal inflammation through decreasing proinflammatory factors (TNF-α and COX-2) and increasing anti-inflammatory factors (IL-10). CB RH2 had direct effects on the expansion of CD4+ T cells in Peyer's patches (PPs) in vitro, which in turn affected their immune response upon challenge with ceftriaxone. All these data suggested that CB RH2 possessed the ability to modulate the intestinal mucosal and systemic immune system in limiting intestinal alterations to relieve ceftriaxone-induced dysbacteriosis.

RNAi-mediated IARS2 knockdown inhibits proliferation and promotes apoptosis in human melanoma A375 cells.

IARS2, which encodes the mitochondrial form of isoleucyl-tRNA synthetase, has been found to play an important role in a range of diseases, including cancer. However, the relationship between IARS2 and melanoma is still unclear. To evaluate the role of IARS2 in melanoma, we constructed a stable A375 cell line with IARS2 knockdown via lentivirus-mediated small interfering RNAs. The expression of IARS2 was measured by real time-quantitative Polymerase Chain Reaction and western blot analysis. Cell counting, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and colony formation assay were conducted to assess the effect of IARS2 on melanoma cell proliferation. Flow cytometry assay was used to determine cell apoptosis and cell cycle distribution in melanoma A375 cells. Finally, immunohistochemistry was employed to validate the expression of IARS2 protein in melanoma tissues. In this study it was found that IARS2 was highly expressed in melanoma cell lines. Furthermore, IARS2 protein also exhibited elevated expression in the tumour tissues obtained from melanoma patients. After suppression of the mRNA expression of IARS2, the proliferation and colony formation ability of the A375 cells were significantly inhibited, while the proportion of apoptotic A375 cells increased significantly, as indicated by an enhanced phosphatidylserine externalization and caspase 3/7 activity after IARS2 knockdown. Further investigations found that knockdown of IARS2 arrested cells in the G1 phase. The results suggested that IARS2 is critical for proliferation and apoptosis of melanoma cells.

Chemotherapy Resistance Molecular Mechanism in Small Cell Lung Cancer.

The malignancy of small cell lung cancer (SCLC) is the highest amongst all lung cancer types. It is characterized by rapid growth, early occurrence of distant sites metastasis, poor survival rates and is initially sensitive to chemotherapy and radiotherapy. However, most patients eventually relapse or disease progresses because of chemotherapy resistance. Because of lack of effective second-line therapies, the prognosis of SCLC patients is usually poor. For the development of novel therapies, it is necessary to understand the mechanisms of chemotherapy resistance in SCLC. The mechanism is complex, because multiple factors could lead to chemotherapy resistance. An overview of multiple events triggering the formation of chemotherapy resistance phenotypes of SCLC cells is discussed.

Mixomics analysis of breast cancer: Long non-coding RNA linc01561 acts as ceRNA involved in the progression of breast cancer.

OBJECTIVE: This study aimed at finding the long non-coding RNA (lncRNA), miRNA and mRNA which played critical roles in breast cancer (BrCa) by using mixOmics R package. METHOD: The BrCa dataset were obtained from TCGA and then analyzed using "DESeq2" R package. Multivariate analyses were performed with the "mixOmics" R package and the first component of the stacked partial least-Squares discriminant analysis results were used for searching the interested lncRNA, miRNA and mRNA. qRT-PCR was applied to identify the bioinformatics results in four BrCa cell lines (MCF7, BT-20, ZR-75-1, and MX-1) and the breast epithelial cell line MCF-10 A. Then cells (MCF-1 and MX-1) were transfected with si-linc01561, miR-145-5p mimics and si-MMP11 to further investigate the effects of linc01561, miR-145-5p and MMP11 on the BrCa cells proliferation and apoptosis. RESULTS: MixOmics results showed that linc01561, miR-145-5p and MMP11 might play important roles in BrCa. qRT-PCR results identified that in BrCa cell lines, linc01561 and MMP11 were higher expressed while miR-145-5p was lower expressed compared with those in epithelial cell line. The linc01561 inhibition elevated miR-145-5p expression and then suppressed MMP11 expression. Moreover, linc01561 inhibition suppressed the BrCa cells proliferation and promoted the apoptosis, which was realized by up-regulating expression of miR-145-5p and down-regulating expression of MMP11. CONCLUSION: In summary, the findings of this study, based on ceRNA theory, combining the research foundation of miR-145-5p and MMP11, and taking linc01561 as a new study point, provide new insight into molecular-level reversing proliferation and apoptosis of BrCa.

Preparation of carbon-based AuAg alloy nanoparticles by using the heterometallic [Au4Ag4] cluster for efficient oxidative coupling of anilines.

We herein report the preparation of unique heteroatom-doped and carbon-based AuAg alloy nanoparticles (NPs) via the pyrolysis of a structurally defined octanuclear heterometallic Au(i)-Ag(i) cluster [Au4Ag4(Dppy)4(Tab)4(MeCN)4](PF6)8 (2, Dppy = diphenylphosphine-2-pyridine and Tab = 4-(trimethylammonio)benzenethiolate). This cluster-precursor approach exerts a fine control over the spatial arrangement, size and uniformity of the AuAg alloy NPs as well as the doped heteroatoms (P, N, F and S). The optimized material prepared at 450 °C efficiently catalyzes the oxidative coupling of anilines to yield azobenzenes under mild conditions.

[Cd(H2O)6]@{Cd6Cl4(nico)12[Hg(Tab)2(µ-Cl)]2}: a heterometallic host-guest icosidodecahedron cage via hierarchical assembly.

Complexation of a preformed complex [Hg(Tab)2](PF6)2 (1) with nicotinic acid in the presence of Et3N afforded a mononuclear complex [Hg(Tab)2(nico)]2(PF6)2 (2) (nico = nicotinate, Tab = 4-(trimethylammonio)benzenethiolate) which, upon subsequent treatment with one or three equiv. of CdCl2·2.5H2O, gave rise to an unprecedented heterometallic cage complex [Cd(H2O)6]@{Cd6Cl4(nico)12[Hg(Tab)2(µ-Cl)]2} (3) or a simple salt of [Hg(Tab)2][CdCl4] (4).