Circular RNAs are a class of noncoding RNAs with covalently linked 5 ' and 3 ' ends that arise from backsplicing events. The absence of a 5 ' cap and a 3 ' poly(A) tail makes circular RNAs relatively more stable than their linear counterparts. They are evolutionary conserved and tissue-specific, and some show disease-specific expression patterns. Although their biological functions remain largely unknown, circular RNAs have been shown to play regulatory roles by acting as microRNA sponges, regulators of RNA-binding proteins, alternative splicing, and parental gene expression, and they could even encode proteins. Over the past few decades, circular RNAs have attracted wide attention in oncology owing to their implications in various tumors. Many circular RNAs have been characterized as key players in gastrointestinal cancers and influence cancer growth, progression, metastasis, and therapeutic resistance. Accumulating evidence reveals that their unique characteristics, coupled with their critical roles in tumorigenesis, make circular RNAs promising non-invasive clinical biomarkers for gastrointestinal cancers. In the present review, we summarized the biological roles of the emerging circular RNAs and their potential as biomarkers and therapeutic targets, which may help better understand their clinical significance in the management of gastrointestinal cancers. 1 image

Histone deacetylase-8 (HDAC8) is a unique member of class I Zn2+-dependent metalloenzyme of the classical histone deacetylases owing to its highly structural and kinetic characterization. Of interest, the diminution in the expression level of HDAC8 and or the impaired activity of the enzyme has been correlated with various pathophysiological events, such as neuroblastoma cancer, chronic obstructive pulmonary disease (COPD), Cornelia de Lange syndrome (CdLs) and other metabolic dysfunction. Notwithstanding, HDAC8 has been considered a high priority drug target, and because of the therapeutic benefits associated with HDAC8 inhibitors, the majority of the current research is geared toward searching for inhibitors of this enzyme. In addition, the potential for treating metabolic and age-related diseases by activation is gradually gaining attention. However, currently only a few researchers have reported on the biochemical significance of activators of HDAC8 and the information gathered further indicates that the combination of both activators and inhibitors could be a promising therapeutic strategy toward dissecting the role of HDAC8 in associated diseases. Therefore, the primary aim of this review is to elaborate on the prospects of combining HDAC8 activators and inhibitors for disease treatments due to HDAC8 diminution or impaired activity.

Ectomesenchymal stem cells (EMSCs) are typical adult stem cells obtained from the cranial neural crest. They have the potential to differentiate into various cell types, such as osseous cells, neurons and glial cells. Three-dimensional (3 D) printing is a novel method to construct biological structures by rapid prototyping. Previously, our group reported on the stemness and multi-lineage differentiation potential of EMSCs on gels. However, the exploration of EMSCs in 3 D printing and then evaluation of the growth and neuronal differentiation of EMSCs on extruded 3 D printable hybrid hydrogels has not been reported. Therefore, the current study explored the novel hybrid Sodium alginate-Matrigel (SA-MA) hydrogel extruded 3 D printing to design an in vitro scaffold to promote the differentiation and growth of EMSCs. In addition, the physical properties of the hydrogel were characterized and its drug-releasing property determined. Notably, the results showed that the construct exhibited a sustain-released effect of growth factor BDNF in accordance with the Higuchi equation. Moreover, the cell survival rate on the 3 D printed scaffold was 88.22 ± 1.13% with higher neuronal differentiation efficiency compared with 2 D culture. Thus, SA-MA's ability to enhanced EMSCs neuronal differentiation offers a new biomaterial for neurons regeneration in the treatment of spinal cord injury.

Herein, a nano-micelle drug delivery system was developed to orally improved zingerone's bioavailability and its antitumor effect. Indeed, zingerone-loaded d-α-tocopheryl polyethylene glycol succinate micelles (ZTMs) were effectively prepared, characterised and assessed. The ZTMs had diameter, polydispersity index, and zeta potential of 50.62 ± 0.25 nm, 0.168 ± 0.006, and -28.07 ± 0.33 mV, respectively, coupled with a high entrapment efficiency (m/m, %) were 94.71 ± 2.02. The release rate of ZTMs in three media was significantly greater than that of free zingerone. Intriguingly, results obtained from pharmacokinetic studies showed that the oral bioavailability of the ZTMs was enhanced by 5.10 times in comparison with the free zingerone. Further, the half inhibitory concentration (IC50) of ZTMs and free zingerone was 7.56 μg/ml and 14.30 μg/ml, respectively, on HepG2 cells. Hence, ZTMs may be used as a potential approach to enrich the solubility, bioavailability, and concomitant anti-proliferative effect of zingerone in vitro.

Objectives Cuminaldehyde self-emulsified nanoemulsion (CuA-SEN) was prepared and optimised to improve its oral bioavailability and antihepatotoxicity. Methods Cuminaldehyde self-emulsified nanoemulsion was developed through the self-nanoemulsification method using Box-Behnken Design (BBD) tool while appropriate physicochemical indices were evaluated. The optimised CuA-SEN was characterised via droplet size (DS), morphology, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency, in-vitro release, and pharmacokinetic studies while its antihepatotoxicity was evaluated. Key findings Cuminaldehyde self-emulsified nanoemulsion with acceptable characteristics (mean DS-48.83 +/- 1.06 nm; PDI-0.232 +/- 0.140; ZP-29.92 +/- 1.66 mV; EE-91.51 +/- 0.44%; and drug-loading capacity (DL)-9.77 +/- 0.75%) was formulated. In-vitro drug release of CuA-SEN significantly increased with an oral relative bioavailability of 171.02%. Oral administration of CuA-SEN to CCl4-induced hepatotoxicity mice markedly increased the levels of superoxide dismutase, glutathione and catalase in serum. Also, CuA-SEN reduced the levels of tumour necrosis factor-alpha and interleukin-6 in both serum and liver tissues while aspartate aminotransferase, alanine aminotransferase and malonaldehyde levels were significantly decreased. Conclusions These findings showed that the improved bioavailability of cuminaldehyde via SEN provided an effective approach for enhancing antioxidation, anti-inflammation and antihepatotoxicity of the drug.

Punicic acid of pomegranate oil (PAP) has gained heightened interest due to several health benefits, such as anticarcinogenic, antidiabetic, and antiatherosclerotic properties. However, these bioactivities have been hampered by chemical instability, poor water solubility, rapid metabolism, and low bioavailability of PAP. Therefore, this study was aimed at optimizing the liposomal formulation of Triacylglycerol-bound punicic acid with its regioisomers (TPAR) for improved oral bioavailability and increased hepatoprotection through antioxidation and anti-inflammation. Herein, the optimized TPAR nanoliposome (TPAR-NL) was developed using thin-film dispersion method and subsequently characterized with appropriate indices. The optimized TPAR-NL produced fairly stable spherical nanoparticles (< 200 nm) with encapsulation efficiency (%EE) of 85.77%, as well as enhanced in vitro release and improved oral bioavailability. The TPAR-NL exhibited profound antihepatotoxic effect in mice pretreated with carbon tetrachloride (CCl4) via reduction of serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels compared with free TPAR. The TPAR-loaded liposome also significantly reduced oxidative stress by increasing superoxide dismutase and glutathione levels while lowering malonaldehyde concentration compared with the free TPAR. The TPAR-LNF further exhibited remarkable anti-inflammatory activity compared with the free drug via inhibition of interleukin-6 and tumor necrosis factor-alpha generation. Thus, the developed nanoliposomes potentiated the antihepatotoxic activity of TPAR via antioxidation and anti-inflammation.

Hepatocellular carcinoma (HC) and glioblastoma (GBA) are the most commonly aggressive malignant liver and brain tumors. Based on an established method for the synthesis of amide, two novel analogues (4 and 5) of (S)-perillic acid were synthesized and their structures were affirmed using nuclear magnetic resonance spectroscopic analysis. An MTT cytotoxic assay showed that our derivatives (4 and 5) demonstrated a substantial anti-proliferative effect against HC (HepG2) and GBA (U251) cell lines. Particularly, compound 5 showed growth inhibitory (IC50) effects on U251 (IC50 = 3.10 ± 0.12 μg mL-1) and HepG2 cells (IC50 = 1.49 ± 0.43 μg mL-1), which fall within the acceptable standard recommended by the National institute of cancer (Bethesda, MD, USA) for the selection of anticancer drug candidates. Consequently, we assessed the in vivo antitumor and organ/tissue toxicity of 4, 5 and 5-fluorouracil (5-FU) in hepatoma H22-inoculated mice. The results obtained indicated remarkable tumor growth inhibition with no substantial toxicological effects on the mice and the organs/tissues in the treated groups compared well with the control.

Background Surgery alone or surgery after neoadjuvant chemoradiotherapy or chemotherapy, often cause complications of varying degrees of severity. There seems to be an association between these complications and patient age, gender, as well as the treatment modalities and surgical techniques employed. This study investigated these probable relationships with regards to the current management of esophageal squamous cell carcinoma (ESCC). Methods A total of 245 ESCC patients who had received either neoadjuvant chemoradiotherapy or chemotherapy plus surgery or surgery alone, were recruited for this study. The relationships among patients’ demographic factors, treatment modalities, surgical techniques, as well as postoperative complications were analyzed. Results Two hundred and forty patients (98%) received surgery alone, 3 (1.2%) received neoadjuvant chemotherapy plus surgery, and 2 (0.8%) received neoadjuvant chemoradiotherapy plus surgery. Ivor-Lewis approach was the main surgical technique used. Pneumonia and pleural effusion were among the most frequent postoperative complications. There was a significant association between age and postoperative complications (=10.194, P=0.017). Gender and postoperative complications also had a significant association (=9.274, P=0.026). Neither age nor gender had a significant correlation with treatment modalities (=1.297, P=0.523 and =1.348, P=0.510, respectively). Surgical techniques and postoperative complications had no significant relationship (=9.308, P=0.409). Interpretations Age and gender are risk factors that determine the occurrence of postoperative complications. Patients can be offered any potentially good treatment irrespective of their age and gender. The surgical approach used may not be a risk factor to postoperative complications.

Emerging evidence has suggested that nutraceutical ingredients like pomegranate seed oil (PSO) possesses health‐promoting effects in cell and animal models. However, these health benefits (anticancer, antioxidant, anti‐inflammatory, anti‐diabetic, and so on) are limited by low physicochemical stability, slow intestinal absorption, and rapid metabolism of PSO. In order to overcome these drawbacks, some carriers viz., nanoemulsion, encapsulation, and nanoparticles are developed recently. This paper assesses the chemical compositions and physicochemical properties of PSO, as well as biological activities and possible mechanisms. It also discusses the formulation of PSO for improved stability and health‐promoting activities.Practical Applications: This review highlights the prospects of PSO formulation. The relevance of this study is that the stability and biological properties of PSO could be enhanced through nanocarriers. A formulated PSO has a potential use in nutraceutical, functional foods, pharmaceutical and cosmetic industries.PSO, a source of various nutrients and antioxidants with immense benefits to human health is incorporated into nanocarriers such as microencapsulation, nanoemulsion and nanoparticle. This improved the health‐promoting benefits of the oil.

Monocyclic monoterpenes have been recognized as useful pharmacological ingredients due to their ability to treat numerous diseases. Limonene and perillyl alcohol as well as their metabolites (especially perillic acid and its methyl ester) possess bioactivities such as antitumor, antiviral, anti-inflammatory, and antibacterial agents. These therapeutic properties have been well documented. Based on the aforementioned biological properties of limonene and its metabolites, their structural modification and development into effective drugs could be rewarding. However, utilization of these monocyclic monoterpenes as scaffolds for the design and developments of more effective chemoprotective agents has not received the needed attention by medicinal scientists. Recently, some derivatives of limonene metabolites have been synthesized. Nonetheless, there have been no thorough studies on their pharmacokinetic and pharmacodynamic properties as well as their inhibition against isoprenylation enzymes. In this review, recent research progress in the biochemical significance of limonene and its metabolites was summarized with emphasis on their antitumor effects. Future prospects of these bioactive monoterpenes for drug design and development are also highlighted.

In the current study, seven compounds (i.e. 1-7) were found to be novel activators for the N-epsilon-acetyl lysine deacetylation reaction catalyzed by human histone deacetylase 8 (HDAC8). When assessed with the commercially available HDAC8 peptide substrate Fluor-de-Lys (R)-HDAC8 that harbors the unnatural 7-amino-4-methylcoumarin (AMC) residue immediately C-terminal to the N-epsilon-acetyl-lysine residue to be deacetylated, our compounds exhibited comparable activation potency to that of TM-2-51, the strongest HDAC8 activator reported in the current literature. However, when assessed with an AMC-less peptide substrate derived from the native HDAC8 non-histone substrate protein Zinc finger protein ZNF318, while our compounds were all found to be able to activate HDAC8 deacetylation reaction, TM-2-51 was found not to be able to. Our compounds also seemed to be largely selective for HDAC8 over other classical HDACs. Moreover, treatment with the strongest activator among our compounds (i.e. 7) was found to decrease the KM of the above AMC-less HDAC8 substrate, while nearly maintaining the k(cat) of the HDAC8-catalyzed deacetylation on this substrate. (C) 2017 Elsevier Ltd. All rights reserved.