Application of nano-radiosensitizers in non-small cell lung cancer.

Radiotherapy stands as a cornerstone in the treatment of numerous malignant tumors, including non-small cell lung cancer. However, the critical challenge of amplifying the tumoricidal effectiveness of radiotherapy while minimizing collateral damage to healthy tissues remains an area of significant research interest. Radiosensitizers, by methods such as amplifying DNA damage and fostering the creation of free radicals, play a pivotal role in enhancing the destructive impact of radiotherapy on tumors. Over recent decades, nano-dimensional radiosensitizers have emerged as a notable advancement. Their mechanisms include cell cycle arrest in the G2/M phase, combating tumor hypoxia, and others, thereby enhancing the efficacy of radiotherapy. This review delves into the evolving landscape of nanomaterials used for radiosensitization in non-small cell lung cancer. It provides insights into the current research progress and critically examines the challenges and future prospects within this burgeoning field.

Relationship Between Microstructural Alterations and Cognitive Decline After Whole-Brain Radiation Therapy for Brain Metastases: An Exploratory Whole-Brain MR Analysis Based on Neurite Orientation Dispersion and Density Imaging.

BACKGROUND: Cognitive impairment frequently occurs in patients with brain metastases (BM) after whole-brain radiotherapy (WBRT). It is crucial to explore the underlying mechanisms of cognitive impairment in BM patients receiving WBRT. PURPOSE: To detect brain microstructural alterations in patients after WBRT by neurite orientation dispersion and density imaging (NODDI), and evaluate the performance of microstructural alterations in predicting cognitive impairment. STUDY TYPE: Prospective. POPULATION: Twenty-six patients (seven female; mean age, 60.9 years). FIELD STRENGTH/SEQUENCE: 3-T, multi-shell diffusion-weighted single-shot echo-planar sequence. Three-dimensional magnetization-prepared rapid acquisition with gradient echo sequence. ASSESSMENT: Mini-mental state examination (MMSE) evaluations were conducted prior to, following, 1 and 3 months after WBRT. The diffusion data were collected twice, 1 week before and 1 week after WBRT. NODDI analysis was conducted to assess microstructural alterations in whole brain (orientation dispersion index, neurite density index, volume fraction of isotropic water molecules). Reliable change indices (RCI) of MMSE were used to measure cognitive decline. The performance of support vector machine models based on NODDI parameters and clinical features (prednisone usage, tumor volume, etc.) in predicting MMSE-RCI was evaluated. STATISTICAL TESTS: Paired t-test to assess alterations of NODDI measures and MMSE during follow-up. Statistical significance level of P-value <0.05. RESULTS: Significantly decreased MMSE score was found at 3 months after WBRT. After WBRT, corpus callosum, medial prefrontal cortex, limbic lobe, occipital lobe, parietal lobe, putamen, globus pallidus lentiform, and thalamus demonstrated damage in NODDI parameters. The predicted MMSE-RCI based on NODDI features was significantly associated with the measured MMSE-RCI at 1 month (R = 0.573; P = 0.003) and 3 months (R = 0.687; P < 0.0001) after WBRT. DATA CONCLUSION: Microstructural alterations in several brain regions including the middle prefrontal and limbic cortexes were observed in patients with BM following WBRT, which may contribute to subsequent cognitive decline. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Molecular cloning of the hepcidin gene from crescent sweetlips (Plectorhinchus cinctus) and characterization of its encoded antimicrobial peptide.

Hepcidin has been identified as an important antimicrobial peptide exerting important innate immunomodulatory activities in many fish species. In the present study, reverse transcription PCR coupled with the rapid amplification of cDNA ends was used to obtain the full-length cDNA of the crescent sweetlips hepcidin gene, which is 829 bp in length and includes an 273 bp ORF encoding a peptide with 90 amino acid residues. Sequence alignment showed a typical RXKR motif and eight conserved cysteine residues in the deduced amino acid sequences. Four disulfide bonds were predicted to form between these eight cysteines, which may stabilize the hairpin structure in hepcidin molecule. Furthermore, phylogenetic analysis showed that the deduced amino acid sequences of crescent sweetlips hepcidin had high sequence homology to hepcidins from fish species of Eupercaria. In addition, the crescent sweetlips hepcidin peptide demonstrated a strong antimicrobial activity in vitro against several types of pathogenic bacteria in fish. In conclusion, the obtained results suggested that crescent sweetlips hepcidin possessed the typical structure similar to other fish hepcidins and had strong antibacterial activity, which showed great potential in the prevention of fish diseases in aquaculture.

Prokaryotic Expression, Purification, and Antibacterial Activity of the Hepcidin Peptide of Crescent Sweetlips (Plectorhinchus cinctus).

The hepcidin peptide of crescent sweetlips (Plectorhinchus cinctus) is a cysteine-rich, cationic antimicrobial peptide that plays a crucial role in the innate immune system's defense against invading microbes. The aim of this study was to identify the optimal parameters for prokaryotic expression and purification of this hepcidin peptide and characterize its antibacterial activity. The recombinant hepcidin peptides were expressed in Escherichia coli strain Arctic Express (DE3), with culture and induction conditions optimized using response surface methodology (RSM). The obtained hepcidin peptides were then purified before tag cleavage, and their antibacterial activity was determined. The obtained results revealed that induction temperature had the most significant impact on the production of soluble recombinant peptides. The optimum induction conditions were determined to be an isopropylthio-ß-galactoside (IPTG) concentration of 0.21 mmol/L, induction temperature of 18.81 °C, and an induction time of 16.01 h. Subsequently, the recombinant hepcidin peptide was successfully purified using Ni-IDA affinity chromatography followed by SUMO protease cleavage. The obtained hepcidin peptide (without His-SUMO tag) demonstrated strong antimicrobial activity in vitro against V. parahaemolyticus, E. coli, and S. aureus. The results showed prokaryotic (E. coli) expression is a feasible way to produce the hepcidin peptide of crescent sweetlips in a cost-effective way, which has great potential to be used as an antimicrobial agent in aquaculture.

Whole brain atlas-based diffusion kurtosis imaging parameters for the evaluation of multiple cognitive-related brain microstructure injuries after radiotherapy in lung cancer patients with brain metastasis.

Background: Whole brain radiation therapy (WBRT) can cause cognitive dysfunctions in lung cancer patients with brain metastasis (BM). Diffusion kurtosis imaging (DKI) can detect brain microstructural alterations sensitivly. We aimed to identify the potential of DKI parameters for early radiation-induced brain injury and investigate the association between microstructure changes and neurocognitive function (NCF) decline. Methods: Lung cancer patients with BM (n=35) who underwent WBRT in a single center in Zhejiang, China, were consecutively and prospectively enrolled between June 24th, 2020 and December 22nd, 2021, and the median follow-up time was 6.0 months (3.6-6.6 months). DKI and T1-weighted (T1W) MRI scans were acquired prior to and following WBRT. Diffusivity-based (mean diffusivity, MD; fractional anisotropy, FA) and kurtosis-based (mean kurtosis, MK; axial kurtosis, AK) parameters were calculated within the automated anatomical labeling (AAL) atlas-based regions. Reliable change indices practice effects (RCI-PE) scores of the Mini-Mental State Examination (MMSE) were calculated to determine significant neurocognitive decline by a one-sample t-test from baseline to 2-6 months post-WBRT. To assess the subacute induced effects within the whole brain, percentage changes of DKI parameters were evaluated at 170 atlas-based regions by a one-sample t-test. Linear regression analyses were used to evaluate the association between DKI parameter changes and RCI-PE scores. Results: Finally, the study included 19 patients in the longitudinal follow-up. RCI-PE scores declined at 2-6 months post-WBRT (mean RCI-PE =-0.842, 95% CI, -0.376 to -1.310; P=0.002). With the atlas-based analysis of subacute effects after post-WBRT, a total of 28 regions changed in at least one diffusion parameter, revealing region-wise microstructural alterations in the brain. Significant correlations of at least one diffusion parameters with RCI-PEs were observed in 9 regions, such as the right orbital part of the inferior frontal gyrus [right IFGorb, r(AK) =0.47, P=0.03] and left middle temporal gyrus [left MTG, r(MK) =-0.49, P=0.03]. Conclusions: DKI parameters can be used to detect early microstructure changes and represent important imaging predictors for cognitive decline. The reported 9 regions are more particularly vulnerable to neurocognitive radiation-induced impairment for lung cancer patients with BM, representing potential dose-avoidance targets for cognitive function preservation.

Radiomics for the Prediction of Pathological Complete Response to Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer: A Prospective Observational Trial.

(1) Background: An increasing amount of research has supported the role of radiomics for predicting pathological complete response (pCR) to neoadjuvant chemoradiation treatment (nCRT) in order to provide better management of locally advanced rectal cancer (LARC) patients. However, the lack of validation from prospective trials has hindered the clinical adoption of such studies. The purpose of this study is to validate a radiomics model for pCR assessment in a prospective trial to provide informative insight into radiomics validation. (2) Methods: This study involved a retrospective cohort of 147 consecutive patients for the development/validation of a radiomics model, and a prospective cohort of 77 patients from two institutions to test its generalization. The model was constructed using T2-weighted, diffusion-weighted, and dynamic contrast-enhanced MRI to understand the associations with pCR. The consistency of physicians' evaluations and agreement on pathological complete response prediction were also evaluated, with and without the aid of the radiomics model. (3) Results: The radiomics model outperformed both physicians' visual assessments in the prospective test cohort, with an area under the curve (AUC) of 0.84 (95% confidence interval of 0.70-0.94). With the aid of the radiomics model, a junior physician could achieve comparable performance as a senior oncologist. (4) Conclusion: We have built and validated a radiomics model with pretreatment MRI for pCR prediction of LARC patients undergoing nCRT.

Marine glycoproteins: a mine of their structures, functions and potential applications.

Many bioactive compounds are reported from marine organisms, which are significantly different from those found in terrestrial organisms regarding their chemical structures and pharmacological activities. Marine glycoproteins (MGs) have aroused increasing attention as a good nutrient source owing to their potential applications in medicine, cosmetics and food. However, there is a lack of a comprehensive study on MGs to help readers understand the current state of research on marine-derived glycoproteins. The current review compiles the recent progress made on the structures and functions of MGs with future perspectives to maximize their value and applications via bibliometric analysis methods for the first time. The current research on MGs appears mostly limited to the laboratory, with no large-scale production of marine glycoproteins developed. The sugar chains are bound to proteins through covalent bonds that can readily be cleaved leading to difficultly in their separation and purification. Health effects attributed to MGs include treatment of inflammatory diseases, as well as anti-oxidant, immune modulation, anti-tumor, hypolipidemic, hypoglycemic, anti-bacterial and anti-freeze activities. This review can not only deepen the understanding of the functions of MGs, but also lay an important foundation for the further development and utilization of marine resources.

Overview on isolation, structural and functional properties of marine glycoproteins (MGs) via bibliometric analysis methods for the first time.Marine glycoproteins (MGs) have various biological activities and potential health applications.glycoproteins from marine organisms (MGs) significantly enhanced anti-oxidant and anti-inflammatory activities.

The emerging potential of quantitative MRI biomarkers for the early prediction of brain metastasis response after stereotactic radiosurgery: a scoping review.

Background: At present, the simple prognostic models based on clinical information for predicting the treatment outcomes of brain metastases (BMs) are subjective and delayed. Thus, we performed this systematic review of multiple studies to assess the potential of quantitative magnetic resonance imaging (MRI) biomarkers for the early prediction of treatment outcomes of brain metastases with stereotactic radiosurgery (SRS). Methods: We systematically searched the PubMed, Embase, Cochrane, Web of Science, and Clinical Trials.gov databases for articles published between February 1, 1991, and April 11, 2022, with no language restrictions. We included studies involving patients with BMs receiving SRS; the included patients were required to have definite pathology of a primary tumor and complete imaging data (pre- and post-SRS). We excluded the articles that included patients who had undergone previous surgery and those that did not include regular follow-up or corresponding MRI scans. Results: We identified 2,162 studies, of which 26 were included in our analysis, involving a total of 1,362 participants. All 26 studies explored the relevant MRI parameters to predict the prognosis of patients with BMs who received SRS. The outcomes were generalized according to the relationships between the anatomical/morphological, microstructural, vascular, and metabolic changes and SRS. Generally, with traditional MRI, there are several quantitative prognostic models based on preradiosurgical radiomics that predict the outcome of SRS treatment in local BM control. With the implementation of advanced MRI, the relative apparent diffusion coefficient (ADC), perfusion fraction (f), relative cerebral blood volume (rCBV), relative regional cerebral blood flow (rrCBF), interstitial fluid pressure (IFP), quadratic of time-dependent leakage (Ktrans 2), extracellular extravascular volume (ve), choline/creatine (Cho/Cr), nuclear Overhauser effect (NOE) peak, and intraextracellular water exchange rate constant (kIE ) were confirmed to be indicative of the therapeutic effect of SRS for BMs. Conclusions: Quantitative MRI biomarkers extracted from traditional or advanced MRI at different time points, which can represent the anatomical/morphological, microstructural, vascular, and metabolic changes, respectively, have been proposed as promising markers for the early prediction of SRS response in those with BMs. There are some limitations in this review, including the risk of selection bias, the limited number of study objects, the incomparability of the total data, and the subjectivity of the review process.

Roles of activator protein-2 gamma in breast cancer: A narrative review (SANRA).

Activator protein-2 gamma (AP-2γ) is a crucial transcription factor involved in breast cancer development. Abnormal expression and activity of AP-2γ have also been identified as important markers of malignancy. In the last decade, the importance of AP-2γ in breast cancer progression has been widely studied. In this review, we summarize the current knowledge on the regulatory roles of AP-2γ in breast cancer oncogenesis and progression and its potential as a diagnostic biomarker and drug target in breast cancer treatment.

Purification and characterization of antioxidant peptides from hairtail surimi hydrolysates and their effects on beef color stability.

The antioxidant peptides extracted from plants or animals have shown great potential in preventing food quality deterioration caused by oxidization. Here, peptide fractions obtained from hairtail surimi hydrolysates (HSH) were investigated for structure and color-protective effect. The results showed the <3 kDa fraction obtained from HSH by ultrafiltration could be separated into five major fractions (A-E) by gel chromatography, among which fraction A possessed the highest antioxidant activities. This fraction A could be further separated into two fractions (A1 and A2 ) by the reversed-phase high-performance liquid chromatography, and fraction A2 with lower α-helix content exhibited the higher antioxidant activities. The amino acids sequence of fraction A2 was identified as DLYANTVLSGGTTMYPGIADR (2214.0627 Da). The synthetic peptide with this sequence was also found to exhibit obvious antioxidant activity. Moreover, both HSH, fractions A1 and A2 , and synthetic peptide demonstrated color-protective effects during the beef preservation. Taken together, the results obtained showed that the natural antioxidant peptides could be isolated from HSH, which can be used in meat preservation for inhibiting color deterioration. PRACTICAL APPLICATION: This study demonstrated the potential of hairtail surimi hydrolysates (HSH) as a source of antioxidant peptides. Furthermore, these antioxidant peptides purified from HSH exhibited the potential for prevention of beef color deterioration of beef, providing a potential application for meat preservation. Particularly, using the antioxidant peptides sourced from fish surimi for meat preservation may not only ease the safety concerns about artificial preservatives but also create a unique selling proposition, especially in far eastern Asian countries, since consumers in these countries believe "umami" is the combination of "fish" and "meat."

Developing a Peptide That Inhibits DNA Repair by Blocking the Binding of Artemis and DNA Ligase IV to Enhance Tumor Radiosensitivity.

PURPOSE: Artemis and DNA Ligase IV are 2 critical elements in the nonhomologous end joining pathway of DNA repair, acting as the nuclease and DNA ligase, respectively. Enhanced cellular radiosensitivity by inhibition of either protein contributes to a promising approach to develop molecular targeted radiosensitizers. The interaction between Artemis and DNA Ligase IV is required for the activation of Artemis as nuclease at 3'overhang DNA; thus, we aim to generate an inhibitory peptide targeting the interaction between Artemis and DNA Ligase IV for novel radiosensitizer development. METHODS AND MATERIALS: We synthesized the peptide BAL, which consists of the interaction residues of Artemis to DNA Ligase IV. The radiosensitization effect of BAL was evaluated by colony formation assay. The effects of BAL on radiation-induced DNA repair were evaluated with Western blotting and immunofluorescence. The effects of BAL on cell proliferation, cell cycle arrest, and cell apoptosis were assessed via CCK-8 and flow cytometry assays. The potential synergistic effects of BAL and irradiation in vivo were investigated in a xenograft mouse model. RESULTS: The generated peptide BAL blocking the interaction between Artemis and DNA Ligase IV significantly enhanced the radiosensitivity of GBC-SD and HeLa cell lines. BAL prolonged DNA repair after irradiation; BAL and irradiation showed synergistic effects on cell proliferation, cell cycle, and cell apoptosis, and these functions are all DNA Ligase IV-related. Finally, we confirmed the endogenous radiosensitization effect of BAL in a xenograft mouse model. CONCLUSIONS: The inhibitory peptide BAL targeting the binding of Artemis and DNA Ligase IV successfully functions as a novel radiosensitizer that delays DNA repair and synergizes with irradiation to inhibit cell proliferation, induce cell cycle arrest, and promote cell apoptosis.

Ferulic acid ameliorates intrahepatic triglyceride accumulation in vitro but not in high fat diet-fed C57BL/6 mice.

Phenolic acids can improve obesity-related and metabolic syndrome-related conditions including non-alcoholic fatty liver disease (NAFLD). In this study, the effects of ferulic acid (FA) on the metabolic changes related to NAFLD were investigated in oleic acid (OA)-treated HepG2 cells and C57BL/6 mice fed a high fat diet (HFD). In vitro, FA (25 and 50 µg/mL) treatment significantly reduced cellular lipid accumulation with no obvious cytotoxicity, in-part mediated by the suppression of ERK1/2, JNK1/2/3, and HGMB1 expression. However, in vivo administration of FA (20 mg/kg bw·day) for 17 weeks led to no obvious effects on body weight and liver weight gain, blood lipid profiles, or histological abnormalities in obese C57BL/6 mice induced by HFD. Taken together, the positive effects of FA on the reduction of hepatic triglyceride accumulation were therefore demonstrated in cellular model, while its hepatic protective effects might need to be further explored in rodent models and clinical trials.

Research on a Specialty Mushroom (Pleurotus tuber-regium) as a Functional Food: Chemical Composition and Biological Activities.

Pleurotus tuber-regium (PTR) is an edible specialty mushroom that has attracted growing interest recently because of its sensory attributes, high nutritional values, and important medicinal properties. PTR is rich in bioactive polysaccharides, proteins with essential amino acids, essential fatty acids, dietary fiber, minerals, and vitamins. Current studies have shown that the nutrients and bioactive ingredients of PTR contribute to their antitumor, antihypercholesterolemic, antihypertensive, antiobesity, hepatic-protective, antimicrobial, antioxidant, and prebiotic activities, indicating that PTR is a promising functional food and nutraceutical. In this review, the chemical constituents and physiological functions of PTR are summarized, which provide the scientific basis to support the further research and development of its application in the food and pharmaceutical industries.

Antihypertensive effects of Trichiurus lepturus myosin hydrolysate in spontaneously hypertensive rats.

In this study, the blood pressure-lowering effects of Trichiurus lepturus myosin hydrolysate (TMH) and its possible mechanism were investigated in spontaneously hypertensive rats (SHRs). After gavage administration of TMH for 4 h, systolic blood pressure (SBP) was significantly decreased in SHRs. Furthermore, the SBP of SHRs remained low at 1 month after daily TMH treatment at 400 mg kg-1. Meanwhile, plasma levels of angiotensin II, bradykinin and nitric oxide in SHRs were ameliorated by TMH. Western blotting also suggested that TMH down-regulated the expression of ICAM-1 and VCAM-1, indicating a strong anti-inflammatory effect. Additionally, nitrotyrosine and collagen I were down-regulated, revealing a significant anti-oxidant effect of TMH. No obvious side effects or toxicity were observed in normal Wistar rats given TMH. Various pathogenic factors related to hypertension were improved by TMH, which may explain the underlying mechanism by which TMH synergistically reduces blood pressure.

Role of intestinal microecology in the regulation of energy metabolism by dietary polyphenols and their metabolites.

BACKGROUND: Polyphenols are a class of plant secondary metabolites with a variety of physiological functions. Polyphenols and their intestinal metabolites could greatly affect host energy metabolism via multiple mechanisms. OBJECTIVE: The objective of this review was to elaborate the role of intestinal microecology in the regulatory effects of dietary polyphenols and their metabolites on energy metabolism. METHODS: In this review, we illustrated the potential mechanisms of energy metabolism regulated by the crosstalk between polyphenols and intestinal microecology including intestinal microbiota, intestinal epithelial cells, and mucosal immune system. RESULTS: Polyphenols can selectively regulate the growth of susceptible microorganisms (eg. reducing the ratio of Firmicutes to Bacteroides, promoting the growth of beneficial bacteria and inhibiting pathogenic bacteria) as well as alter bacterial enzyme activity. Moreover, polyphenols can influence the absorption and secretion of intestinal epithelial cells, and alter the intestinal mucosal immune system. CONCLUSION: The intestinal microecology play a crucial role for the regulation of energy metabolism by dietary polyphenols.

n-Butanol Extract of Lotus Seeds Exerts Antiobesity Effects in 3T3-L1 Preadipocytes and High-Fat Diet-Fed Mice via Activating Adenosine Monophosphate-Activated Protein Kinase.

In this study, the antiobesity effects of n-butanol extract of lotus seeds (LBE) were evaluated in cultured 3T3-L1 preadipocytes and in high-fat diet (HFD)-fed mice. LBE decreased lipid contents in mature 3T3-L1 cells without obvious cytotoxicity. Meanwhile, LBE supplementation also led to weight loss and improved plasma lipid profiles in HFD-fed mice. Furthermore, LBE could activate AMP-activated protein kinase (AMPK) accompanied by down-regulation of lipogenesis related genes (PPARγ, aP2, LPL, C/EBPα, FAS, SREBP-1c) and up-regulation of lipolysis genes (adiponectin and PPARα) in vitro and in vivo. Collectively, our data demonstrated LBE possesses antiadipogenic and antilipogenic activities which are, at least partially, mediated by the activation of AMPK signaling pathways.

Mechanistic Study of the In Vitro and In Vivo Inhibitory Effects of Protocatechuic Acid and Syringic Acid on VEGF-Induced Angiogenesis.

The antiangiogenic activities of two structurally similar phenolics, protocatechuic acid (PA) and syringic acid (SA), were investigated. In vitro study using HUVECs demonstrated that both PA and SA (at 25 µM) significantly ( p < 0.05) inhibited VEGF-induced cell proliferation by 22.68 ± 5.6% and 21.93 ± 2.0%, respectively; cell migration by 50.04 ± 3.3% and 39.72 ± 4.7%, respectively; cell invasion by 44.16 ± 4.23% and 51.90 ± 2.73%, respectively; and cellular ROS generation by 11.48 ± 6.32% and 21.17 ± 9.10%, respectively. Our mechanistic study revealed that PA and SA blocked the VEGFR2-dependent Akt/ MMP2 and ERK pathways in HUVECs. These inhibitory effects were further confirmed by a decrease of endogenous alkaline phosphatase activity for PA and SA (21.47 ± 1.77% and 10.37 ± 1.27%, respectively) and the suppression of subintestinal vessel plexus formation in Tg (fli1a:EGFP) y1-type transgenic zebrafish embryos. PA and SA down-regulated the angiogenesis-related signal transduction pathway of VEGFα-VEGFR2 or Ang2- Tie2 in zebrafish. Moreover, it was also found that PA demonstrated a better inhibition on VEGF-induced migration of HUVEC and zebrafish vasculature. This might be due to the different number of hydroxyl and methoxy substituents possessed by PA and SA. Taken together, these findings indicate that phenolics PA and SA have potent antiangiogenic activities and are potential targets for the design and development of anticancer agents.

Identification of a Wells-Dawson polyoxometalate-based AP-2γ inhibitor with pro-apoptotic activity.

AP-2 gamma (AP-2γ) is a transcription factor that plays pivotal roles in breast cancer biology. To search for small molecule inhibitors of AP-2γ, we performed a high-throughput fluorescence anisotropy screen and identified a polyoxometalate compound with Wells-Dawson structure K6[P2Mo18O62] (Dawson-POM) that blocks the DNA-binding activity of AP-2γ. We showed that this blocking activity is due to the direct binding of Dawson-POM to AP-2γ. We also provided evidence to show that Dawson-POM decreases AP-2γ-dependent transcription similar to silencing the gene. Finally, we demonstrated that Dawson-POM contains anti-proliferative and pro-apoptotic effects in breast cancer cells. In summary, we identified the first small molecule inhibitor of AP-2γ and showed Dawson-POM-mediated inhibition of AP-2γ as a potential avenue for cancer therapy.

Nesfatin-1 inhibits proliferation and enhances apoptosis of human adrenocortical H295R cells.

NUCB2/nesfatin and its proteolytically cleaved product nesfatin-1 are recently discovered anorexigenic hypothalamic neuroproteins involved in energy homeostasis. It is expressed both centrally and in peripheral tissues, and appears to have potent metabolic actions. NUCB2/nesfatin neurons are activated in response to stress. Central nesfatin-1 administration elevates circulating ACTH and corticosterone levels. Bilateral adrenalectomy increased NUCB2/nesfatin mRNA levels in rat paraventricular nuclei. To date, studies have not assessed the effects of nesfatin-1 stimulation on human adrenocortical cells. Therefore, we investigated the expression and effects of nesfatin-1 in a human adrenocortical cell model (H295R). Our findings demonstrate that NUCB2 and nesfatin-1 are expressed in human adrenal gland and human adrenocortical cells (H295R). Stimulation with nesfatin-1 inhibits the growth of H295R cells and promotes apoptosis, potentially via the involvement of Bax, BCL-XL and BCL-2 genes as well as ERK1/2, p38 and JNK1/2 signalling cascades. This has implications for understanding the role of NUCB2/nesfatin in adrenal zonal development. NUCB2/nesfatin may also be a therapeutic target for adrenal cancer. However, further studies using in vivo models are needed to clarify these concepts.

Low serum cartonectin/CTRP3 concentrations in newly diagnosed type 2 diabetes mellitus: in vivo regulation of cartonectin by glucose.

OBJECTIVES: Cartonectin is a novel adipokine of the C1q complement/TNF-related protein (CTRP) superfamily, with glucose lowering effects, anti-inflammatory and cardio-protective properties. We sought to investigate circulating cartonectin concentrations in subjects with type 2 diabetes mellitus (T2DM) as well as age and BMI matched control subjects. We also examined the effects of a 2 hour 75 g oral glucose tolerance test (OGTT) on serum cartonectin concentrations in T2DM subjects. DESIGN: Cross-sectional study [newly diagnosed (first discovery, not on any treatments) T2DM (n = 47) and control (n = 63) subjects]. Serum cartonectin was measured by ELISA. RESULTS: Serum cartonectin concentrations were significantly lower in patients with T2DM compared to controls (P<0.05). Furthermore, serum cartonectin was significantly negatively correlated with glucose and CRP, and significantly positively correlated with leptin, in all subjects (n = 110). When subjected to multiple regression analysis, none of these variables were predictive of serum cartonectin (P>0.05). There were no significant correlations in T2DM subjects (n = 47). In control subjects (n = 63), serum cartonectin was significantly negatively correlated with CRP, and significantly positively correlated with insulin, HOMA-IR and leptin. However, when subjected to multiple regression analysis, none of these variables were predictive of serum cartonectin (P>0.05). Finally, serum cartonectin concentrations were significantly lower in T2DM subjects after a 2 hour 75 g OGTT (P<0.01). CONCLUSIONS: Cartonectin may serve as a novel biomarker for the prediction and early diagnosis of T2DM patients. Furthermore, cartonectin and/or pharmacological agents that increase circulating cartonectin levels can represent a new therapeutic field in the treatment of T2DM patients. Further research is needed to clarify these points.