miR-22 negatively regulating NOD-like receptor protein 3 gene in the proliferation, invasion, and migration of malignant melanoma cells.

Introduction: Malignant melanoma (MM) is a highly aggressive skin tumour. Aim: To investigate whether miR-22 is involved in the proliferation, invasion, and migration of melanoma cells (MCs) by negatively regulating NOD-like receptor protein 3 (NLRP3) gene. Material and methods: Human MCs (WM239a) and human epidermal melanocytes (HEM) were used as study material. The expression levels of miR-22 and NLRP3 were detected by qRT-PCR. The expression of NLRP3 protein was determined by Western blot (WB) analysis. The effects of miR-22 and NLRP3 on the proliferation, invasion, and migration of MCs were evaluated by cell counting kit-8 (CCK-8), Transwell cell invasion assay, and scratch assay. Results: The expression of miR-22 was clearly lower in WM239a than in HEM. Up-regulation of miR-22 expression in WM239a clearly raised the expression of miR-22, Caspase-1, and E-cadherin and the apoptotic rate of WM239a; however, the levels of interleukin-1ß (IL-1ß) and NLRP3, cell proliferation activity, invasion and migration ability were clearly decreased. The negative regulation of NLRP3 by miR-22 may play a major role in activities of MM. Conclusions: Further studies will help to reveal the molecular details of this regulatory mechanism and provide new therapeutic strategies.

Bioactivity and Cell Imaging of Antitumor Fluorescent Agents (Curcumin Derivatives) Coated by Two-Way Embedded Cyclodextrin Strategy.

Curcumin has a wide range of pharmacological activities, which can be used to treat tumors, inflammation and other diseases. However, curcumin's poor solubility and low bioavailability limit its application. In this article, the structure of curcumin was modified with boron trifluoride ether to change fluorescent labeling. The compounds were then embedded into the hydrophobic cavity of α-cyclodextrin and hydroxypropyl ß-cyclodextrin to form inclusion complexes. The two inclusion complexes have excellent photophysical properties, and the maximum emission wavelength is in the range of 550-565 nm. In addition, the two compounds were applied to the fluorescence imaging of HCT-116 cells and HeLa cells, and the proliferation toxicity of the compounds was detected. Both compounds showed certain inhibitory effects on the proliferation of cancer cells. In short, the fluorescent drug molecule synthesized in this article has great reference value for the development of new dosage forms of curcumin.

Genistein promotes M1 macrophage apoptosis and reduces inflammatory response by disrupting miR-21/TIPE2 pathway.

Cardiovascular diseases are a major cause of mortality, and vascular injury, a common pathological basis of cardiovascular disease, is deeply correlated with macrophage apoptosis and inflammatory response. Genistein, a type of phytoestrogen, exerts cardiovascular protective activities, but the underlying mechanism has not been fully elucidated. In this study, RAW264.7 cells were treated with genistein, lipopolysaccharide (LPS), nuclear factor-kappa B (NF-κB) inhibitor, and/or protein kinase B (AKT) agonist to determine the role of genistein in apoptosis and inflammation in LPS-stimulated cells. Simultaneously, high fat diet-fed C57BL/6 mice were administered genistein to evaluate the function of genistein on LPS-induced cardiovascular injury mouse model. Here, we demonstrated that LPS obviously increased apoptosis resistance and inflammatory response of macrophages by promoting miR-21 expression, and miR-21 downregulated tumor necrosis factor-α-induced protein 8-like 2 (TIPE2) expression by targeting the coding region. Genistein reduced miR-21 expression by inhibiting NF-κB, then blocked toll-like receptor 4 (TLR4) pathway and AKT phosphorylation dependent on TIPE2, resulting in inhibition of LPS. Our research suggests that miR-21/TIPE2 pathway is involved in M1 macrophage apoptosis and inflammatory response, and genistein inhibits the progression of LPS-induced cardiovascular injury at the epigenetic level via regulating the promoter region of Vmp1 by NF-κB.

Evidence that increased cholecystokinin (CCK) in the periaqueductal gray (PAG) facilitates changes in Resident-Intruder social interactions triggered by peripheral nerve injury.

Individual differences in the effects of a chronic neuropathic injury on social behaviours characterize both the human experience and pre-clinical animal models. The impacts of these changes to the well-being of the individual are often underappreciated. Earlier work from our laboratory using GeneChip® microarrays identified increased cholecystokinin (CCK) gene expression in the periaqueductal gray (PAG) of rats that showed persistent changes in social interactions during a Resident-Intruder encounter following sciatic nerve chronic constriction injury (CCI). In this study, we confirmed these gene regulation patterns using RT-PCR and identified the anatomical location of the CCK-mRNA as well as the translated CCK peptides in the midbrains of rats with a CCI. We found that rats with persistent CCI-induced changes in social behaviours had increased CCK-mRNA in neurons of the ventrolateral PAG and dorsal raphe nuclei, as well as increased CCK-8 peptide expression in terminal boutons located in the lateral and ventrolateral PAG. The functional significance of these changes was explored by microinjecting small volumes of CCK-8 into the PAG of uninjured rats and observing their Resident-Intruder social interactions. Disturbances to social interactions identical to those observed in CCI rats were evoked when injection sites were located in the rostral lateral and ventrolateral PAG. We suggest that CCI-induced changes in CCK expression in these PAG regions contributes to the disruptions to social behaviours experienced by a subset of individuals with neuropathic injury.

Prognostic role of METTL1 in glioma.

BACKGROUND: Current treatment options for glioma are limited, and the prognosis of patients with glioma is poor as the available drugs show low therapeutic efficacy. Furthermore, the molecular mechanisms associated with glioma remain poorly understood. METTL1 mainly catalyzes the formation of N(7)-methylguanine at position 46 of the transfer RNA sequence, thereby regulating the translation process. However, the role of METTL1 in glioma has not been studied to date. The purpose of this study was to analyze the expression and prognosis of METTL1 in glioma, and to explore the potential analysis mechanism. METHODS: Data from five publicly available databases were used to analyze METTL1 expression across different tumor types and its differential expression between carcinoma and adjacent normal tissues. The expression of METTL1 in glioma was further validated using real-time polymerase chain reaction and immunohistochemistry. Meanwhile, siRNA was used to knockdown METTL1 in U87 glioma cells, and the resultant effect on glioma proliferation was verified using the Cell Counting Kit 8 (CCK8) assay. Furthermore, a nomogram was constructed to predict the association between METTL1 expression and the survival rate of patients with glioma. RESULTS: METTL1 expression increased with increasing glioma grades and was significantly higher in glioma than in adjacent noncancerous tissues. In addition, high expression of METTL1 promoted cell proliferation. Moreover, METTL1 expression was associated with common clinical risk factors and was significantly associated with the prognosis and survival of patients with glioma. Univariate and multivariate Cox regression analyses revealed that METTL1 expression may be used as an independent prognostic risk factor for glioma. Furthermore, results of functional enrichment and pathway analyses indicate that the mechanism of METTL1 in glioma is potentially related to the MAPK signaling pathway. CONCLUSIONS: High METTL1 expression is significantly associated with poor prognosis of patients with glioma and may represent a valuable independent risk factor. In addition, high expression of METTL1 promotes glioma proliferation and may regulate mitogen-activated protein kinase (MAPK) signaling pathway. Thus, METTL1 may be a potential biomarker for glioma. Further investigations are warranted to explore its clinical use.

Total Synthesis and Anti-Inflammatory Bioactivity of (-)-Majusculoic Acid and Its Derivatives.

The first total synthesis of marine natural product, (-)-majusculoic acid (1) and its seven analogs (9-15), was accomplished in three to ten steps with a yield of 3% to 28%. The strategy featured the application of the conformational controlled establishment of the trans-cyclopropane and stereochemical controlled bromo-olefination or olefination by Horner-Wadsworth-Emmons (HWE) reaction. The potential anti-inflammatory activity of the eight compounds (1 and 9-15) was evaluated by determining the nitric oxide (NO) production in the lipopolysaccharide (LPS)-induced mouse macrophages RAW264.7. (-)-Majusculoic acid (1), methyl majusculoate (9), and (1R,2R)-2-((3E,5Z)-6-bromonona-3,5-dien-1-yl)cyclopropane-1-carboxylic acid (12) showed significant effect with inhibition rates of 33.68%, 35.75%, and 43.01%, respectively. Moreover, they did not show cytotoxicity against RAW264.7 cells, indicating that they might be potential anti-inflammatory agents.

Effect of Cholecystokinin-8 (CCK-8) on Blood Pressure and Blood Content of Calcitonin-Gene-Related Peptide (CGRP) in Rats with Hypertension Caused by Fructose or Inhibition of Nitric Oxide Synthesis.

We studied the effect of CCK-8 on BP and blood content of CGRP in rats with hypertension caused by fructose or inhibition of NO synthase with L-NAME. The decrease in the CGRP content was found during the development of fructose-induced hypertension, but not L-NAME-caused hypertension. Administration of CCK-8 to fructose-fed animals reduced BP and increased the content of CGRP. In rats with hypertension caused by NO deficit, CCK-8 lowered BP, but did not affect the content of CGRP. These findings suggest that CGRP mediates the hypotensive effect of CCK-8 in fructose-induced hypertension, but not in NO-deficient hypertension.

The Vagus Nerve and the Celiaco-mesenteric Ganglia Participate in the Feeding Responses Evoked by Non-sulfated Cholecystokinin-8 in Male Sprague Dawley Rats.

We have shown that non-sulfated cholecystokinin-8 (NS CCK-8) reduces food intake in adult male Sprague Dawley rats by activating cholecystokinin-B receptor (CCK-BR). Here, we tested the hypothesis that the vagus nerve and the celiaco-mesenteric ganglia may play a role in this reduction. The hypothesis stems from the following facts. The vagus and the celiaco-mesenteric ganglia contain NS CCK-8, they express and have binding sites for CCK-BR, NS CCK-8 activates CCK-BR on afferent vagal and sympathetic fibers and the two structures link the gastrointestinal tract to central feeding nuclei in the brain, which also contain the peptide and CCK-BR. To test this hypothesis, three groups of free-feeding rats, vagotomy (VGX), celiaco-mesenteric ganglionectomy (CMGX) and sham-operated, received NS CCK-8 (0, 0.5 and 1 nmol/kg) intraperitoneally prior to the onset of the dark cycle and various feeding behaviors were recorded. We found that in sham-operated rats both doses of NS CCK-8 reduced meal size (MS), prolonged the intermeal interval (IMI, time between first and second meal), increased satiety ratio (SR = IMI/MS), reduced 24-h food intake and reduced the number of meals relative to saline control. In the VGX and the CMGX groups, all of the previous responses were attenuated. Consistent with our hypothesis, the findings of the current work suggest a role for the vagus nerve and the celiaco-mesenteric ganglia in the feeding responses evoked by NS CCK-8.

Fraxetin inhibits interleukin-1ß-induced apoptosis, inflammation, and matrix degradation in chondrocytes and protects rat cartilage in vivo.

Osteoarthritis (OA) is a disease characterized by degeneration of the joint complex due to cartilage destruction. Fraxetin, a widely used and studied coumarin compound extracted from a traditional Chinese herb (Qin Pi), has shown anti-inflammatory and antioxidant properties, but its effects on OA have not been studied. In the present study, western blotting, immunofluorescence, and terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) were used to evaluate the effects of fraxetin on IL-1ß-induced apoptotic activity, inflammatory responses, and catabolism in rat chondrocytes. The results showed that fraxetin prevented IL-1ß-induced apoptosis of chondrocytes and inhibited inflammatory mediator release by regulating the Toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88)/nuclear factor (NF)-κB pathway in chondrocytes. Additionally, fraxetin suppressed the upregulation of matrix metalloproteinase 13 (MMP13) and degradation of collagen II in the extracellular matrix (ECM). Moreover, the effects of fraxetin in vivo were assessed in a monosodium iodoacetate (MIA)-induced rat model of OA using hematoxylin and eosin (H&E) and Safranin O-fast green staining and magnetic resonance imaging (MRI). The results showed that fraxetin protected the cartilage against destruction. In conclusion, fraxetin could be a potential therapeutic for OA.

Cytotoxic effects to mouse and human gingival fibroblasts of a nanohybrid ormocer versus dimethacrylate-based composites.

OBJECTIVES: Tooth-colored composites have emerged as a standard restorative material in caries therapy and have largely replaced materials such as silver amalgam or glass ionomer cements. In addition to their superior esthetics and desirable mechanical properties, composites also comprise negative characteristics, such as wear, shrinkage, and an adverse biocompatibility. Modifications of classic resin-based dental composites have been developed to overcome these shortcomings. For example, ormocers are innovative inorganic-organic hybrid polymers that form a siloxane network modified by the incorporation of organic groups. Recently, a new ormocer, Admira Fusion (VOCO), was introduced to composite technology. The absence of cytotoxic matrix monomers leads to the hypothesis that ormocers have improved biocompatibility compared to resin-based dental restorative materials. MATERIALS AND METHODS: The aim of this study was to compare the cytotoxic effects of Admira Fusion to a nanohybrid composite (GrandioSO, VOCO) and a nanofiller composite (Filtek Supreme XTE, 3M Espe) on the standard dermal mouse fibroblasts (L929) and human gingival fibroblasts (GF-1) via a Cell Counting Kit-8 (CCK-8) assay. RESULTS: Admira Fusion was significantly less cytotoxic than GrandioSO and Filtek Supreme XTE to both the standard mouse dermal fibroblasts (L929) and human gingival fibroblasts. CONCLUSIONS: Compared to other resin-based dental restorative materials, the ormocer (Admira Fusion) possesses a superior biocompatibility in vitro. Future research studies are needed to confirm our results. CLINICAL SIGNIFICANCE: Clinically, dental practitioners and their patients might benefit from Admira Fusion in terms of reduced adverse biologic reactions compared to resin-based dental restorative materials.

Ex vivo human pancreatic slice preparations offer a valuable model for studying pancreatic exocrine biology.

A genuine understanding of human exocrine pancreas biology and pathobiology has been hampered by a lack of suitable preparations and reliance on rodent models employing dispersed acini preparations. We have developed an organotypic slice preparation of the normal portions of human pancreas obtained from cancer resections. The preparation was assessed for physiologic and pathologic responses to the cholinergic agonist carbachol (Cch) and cholecystokinin (CCK-8), including 1) amylase secretion, 2) exocytosis, 3) intracellular Ca2+ responses, 4) cytoplasmic autophagic vacuole formation, and 5) protease activation. Cch and CCK-8 both dose-dependently stimulated secretory responses from human pancreas slices similar to those previously observed in dispersed rodent acini. Confocal microscopy imaging showed that these responses were accounted for by efficient apical exocytosis at physiologic doses of both agonists and by apical blockade and redirection of exocytosis to the basolateral plasma membrane at supramaximal doses. The secretory responses and exocytotic events evoked by CCK-8 were mediated by CCK-A and not CCK-B receptors. Physiologic agonist doses evoked oscillatory Ca2+ increases across the acini. Supraphysiologic doses induced formation of cytoplasmic autophagic vacuoles and activation of proteases (trypsin, chymotrypsin). Maximal atropine pretreatment that completely blocked all the Cch-evoked responses did not affect any of the CCK-8-evoked responses, indicating that rather than acting on the nerves within the pancreas slice, CCK cellular actions directly affected human acinar cells. Human pancreas slices represent excellent preparations to examine pancreatic cell biology and pathobiology and could help screen for potential treatments for human pancreatitis.

MicroRNA-17-5p aggravates lipopolysaccharide-induced injury in nasal epithelial cells by targeting Smad7.

BACKGROUND: Globally, rhinitis is one of the most common chronic disorders. Despite availability of drugs to manage the symptomatology of rhinitis, researchers still focus on identification of novel molecular targets for better management. MicroRNAs are implicated in many biological and pathological processes. However, the role of miR-17-5p in rhinitis remains unexplored. This study aimed to explore the role of miR-17-5p in lipopolysaccharide (LPS)-induced injury of nasal epithelial RPMI2650 cells and to elucidate the possible underlying molecular mechanism. RESULTS: LPS damaged RPMI2650 cells by inhibiting cell proliferation, promoting apoptosis, and stimulating the release of inflammatory cytokines. miR-17-5p expression was significantly increased in RPMI2650 cells following treatment with LPS. Furthermore, it was found that overexpression of miR-17-5p led to aggravation of LPS-induced injury. miR-17-5p negatively regulated expression of Smad7; overexpression of Smad7 protected the RPMI2650 cells by inactivating NF-κB and Wnt/ß catenin pathways and vice versa. CONCLUSIONS: Overexpression of miR-17-5p aggravated LPS-induced damage of RPMI2650 cells. Expression of Smad7 was negatively regulated by miR-17-5p; Smad7 expression inactivated NF-κB and Wnt/ß catenin pathways.

Synthesis, biological evaluation and SAR of naftopidil-based arylpiperazine derivatives.

For the development of potential anti-prostate cancer agents, 24 kinds of novel naftopidil-based arylpiperazine derivatives have been synthesized and characterized by spectroscopic methods. Their antitumor activities were evaluated against several classical prostate cancer cell lines including PC-3, LNCaP, and DU145. Among all the compounds, 9, 13, 17, 21 and 27 showed strong cytotoxic activities against DU145 cells (IC50 < 1 µM). Further testing confirmed that compound 17 inhibited the growth of DU145 cells by inducing cell cycle arrest at G0/G1 phase. Besides, antagonistic activities of compounds (9, 13, 17, 21 and 27) towards a1-ARs (α1A, α1B, and α1D) were further evaluated using dual-luciferase reporter assays, and the compounds 13 and 17 exhibited better a1-ARs subtype selectivity. The structure-activity relationship (SAR) of these developed arylpiperazine derivatives was rationally discussed. Taken together, these results suggested that further development of such compounds may be of great interest.

[The Effect of Concentrate Growth Factors on the Survival, Proliferation and Differentiation of Human Dental Pulp Cells].

OBJECTIVE: To explore the cytotoxicity of concentrate growth factors (CGF) and the effects on the apoptosis, proliferation and differentiation of human dental pulp cells (hDPCs), which were closely correlated with future application of CGF in the treatment of dental pulpal and periapical diseases. METHODS: hDPCs were isolated from permanent teeth extracted for orthodontic purpose, and expanded in vitro. hDPCs were treated with CGF and mineral trioxide aggregate (MTA) respectively. The cell apoptosis, proliferation, cell cycle and ALP activity were analyzed after 1, 3 and 7 days. RESULTS: Compared with the MTA group, CGF significantly promoted cell proliferation, increased the proportion of S-phase cells and ALP activity on days 3 and 7 (P<0.01). Besides, hDPCs apoptotic rates decreased in CGF group. CONCLUSION: CGF has a good ability to promote the proliferation of dental pulp cells, resist apoptosis and induce osteogenic/odontogenic differentiation in vitro.

Design, synthesis and biological evaluation of Lenalidomide derivatives as tumor angiogenesis inhibitor.

Lenalidomide is a type of immunomodulatory agent with anti-tumor activity by mainly expressed in the anti-angiogenesis. In order to enhance the pharmacological activity of Lenalidomide, a series of Lenalidomide derivatives were designed as tumor angiogenesis inhibitors. The potential anti-angiogenesis targets of Lenalidomide derivatives were virtual screened on Auto-Dock 4.0 by using reverse docking method. The six target proteins, such as vascular endothelial growth factor receptor, epidermal growth factor receptor, fibroblast growth factor receptor, BCR-ABL tyrosine kinase, p38 mitogen activated protein kinase and metal protein kinase, were chosen as the targets. The Lenalidomide derivatives were synthesized by alkylated, acylated or sulfonylated Lenalidomide and verified by the 1H NMR, 13C NMR and LC-MS. Their anti-cancer activities were detected by using CCK-8 in the esophageal carcinoma cell line EC9706. The results indicate that the inhibitory activities of Lenalidomide derivatives were higher than that of Lenalidomide.

Synthesis and Antitumor Activity of Novel Arylpiperazine Derivatives Containing the Saccharin Moiety.

Prostate cancer is a major public health problem worldwide. For the development of potential anti-prostate cancer agents, a series of novel arylpiperazine derivatives containing the saccharin moiety based on previous studies was designed, synthesized, and evaluated in prostate (PC-3, LNCaP, and DU145) cancer cell lines for their anticancer activities. The majority of the compounds exhibited excellent selective activity for the tested cancer cells. Compounds 4 and 12 exhibited strong cytotoxic activities against DU145 cells (half maximal inhibitory concentration (IC50) < 2 µM). The structure-activity relationship (SAR) of these arylpiperazine derivatives was also discussed based on the obtained experimental data. This work provides a potential lead compound for anticancer agent development focusing on prostate cancer therapy.

Preliminary results on the interactive effects of deoxynivalenol, zearalenone and fumonisin B1 on porcine lymphocytes.

Fusarium mycotoxins, such as fumonisin B1 (FB1), deoxynivalenol (DON) and zearalenone (ZEN), frequently co-occur in feed raw materials and their presence is ubiquitous. The aims of this study were to determine the concentration that inhibits cell viability by 50% (IC50 values) for each mycotoxin (after 24, 48 and 72 h) and to investigate their combined effects in binary (DON + ZEN: DZ, DON + FB1: DF, FB1 + ZEN: FZ) and ternary (DFZ) mixtures using cyto- and genotoxicity on porcine lymphocytes as endpoints. The potency of cytotoxicity of the three toxins in an increasing order was FB1 < ZEN < DON. The range of IC values depending on the period of exposure was 0.31-0.42 µg/ml and 16.6- 22.9 µg/ml for DON and ZEN, respectively, and 101.15 µg/ml for FB1 (50% viability was reached only after 72 h). The main interaction observed was antagonism regarding cytotoxicity. Lower and higher sets of concentrations were used for the genotoxicity (comet assay) experiments. When lower concentrations were used, antagonism was again the main interaction observed. However, at higher concentrations an antagonism was confirmed only for DFZ, whereas for DZ and FZ a synergism was observed. Interactions of DF were inconsistent in different exposure periods in both series of experiments. Further studies with additional endpoints should be performed (e.g. DNA fragmentation, protein synthesis) in order to elucidate the mechanisms underlying the interactions observed.

The HepaRG cell line, a superior in vitro model to L-02, HepG2 and hiHeps cell lines for assessing drug-induced liver injury.

Drug-induced liver injury (DILI) is a leading cause of discontinuation of new drug approval or withdrawal of marketed medicine based on safety due to organ vulnerability. The aim of this research is to investigate the potential abilities of four different in vitro cell models (L-02, HepG2, HepaRG, and hiHeps cell lines) in assessing marketed drugs labeled with apparently different types of liver injury. A total of 17 drugs with versatile pharmacological profiles were chosen, of which, 14 drugs are recognized as DILI agents and 3 drugs are DILI irrelevant. Preliminary cellular screening assays indicated that the HepaRG cell line had an advantage over other cell lines in predicting drugs associated with DILI in vitro as it had the highest Youden's index (71.4%). A multi-parametric screening assay showed that oxidative stress, mitochondrial damage, and disorders of neutral lipid metabolism were changed notably in the HepaRG cell line after DILI-related drugs exposure, accounting for its high sensitivity in comparison with other three cell lines. In addition, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and malate dehydrogenase (MDH) all correlated with the cytotoxic effects of diclofenac sodium (p < 0.05), buspirone hydrochloride (p < 0.01), and danazol (p < 0.01) in the HepaRG cell line. We conclude that the HepaRG cell line is a superior in vitro cell model to other three cell lines for evaluating drugs with DILI potential.

CCK8 negatively regulates the TLR9-induced activation of human peripheral blood pDCs by targeting TRAF6 signaling.

Plasmacytoid dendritic cells (pDCs) are specialized in rapid and massive secretion of type I interferon in response to foreign nuclei acids. Combined with their antigen presentation capacity, this powerful functionality enables pDCs to orchestrate innate and adaptive immune responses. Cholecystokinin octapeptide (CCK8) is a potent immunomodulator, whose role in pDCs function is unknown. In this study, we found that two different cholecystokinin receptors, CCK1R and CCK2R, are expressed on human peripheral blood pDCs. Exogenous CCK8 was able to modulate the TLR-induced activation of pDCs, including phenotypic maturation, IFN-α synthesis and secretion, and could also regulate the potential of pDCs to induce adaptive immune responses in vitro. CCK8 inhibited TLR9-induced activation of tumor-necrosis factor receptor-associated factor 6, which is an important adapter protein in activation of interferon-regulatory factor (IRF)5 and IRF7, possibly through CCK2R, by evoking the activity of protein kinase (PK)A and reducing the activity of PKC. All these results indicate that CCK8 can inhibit the TLR9-induced phenotypic maturation and activation of pDCs, acting through CCK2R by modulating the tumor-necrosis factor receptor-associated factor 6 signaling pathways.

Design, synthesis and biological evaluation of novel arylpiperazine derivatives on human prostate cancer cell lines.

A series of novel arylpiperazine derivatives was synthesized. The in vitro cytotoxic activities of all synthesized compounds against three human prostate cancer cell lines (PC-3, LNCaP, and DU145) were evaluated by a CCK-8 assay. Compounds 10, 24 and 29 exhibited strong cytotoxic activities against LNCaP cells (IC50 <3µM). In addition, these compounds exhibited weak cytotoxic effects on human epithelial prostate normal cells RWPE-1. The structure-activity relationship (SAR) of these arylpiperazine derivatives was also discussed based on the obtained experimental data.