Authors and Reviewers
2017 Vol. 31, No. 5
Discovering new therapeutic interventions to treat lipid and lipoprotein disorders is of great interest and the
discovery of autophagy as a regulator of lipid metabolism has opened up new avenues for targeting modulators of this
pathway. Autophagy is a degradative process that targets cellular components to the lysosome and recent studies have
indicated a role for autophagy in regulating hepatic lipid metabolism (known as lipophagy) as well as lipoprotein
assembly. Autophagy directly targets apolipoprotein B-100 (apoB100), the structural protein component of very lowdensity lipoproteins (VLDLs), and further targets lipid droplets (LDs), the cellular storage for neutral lipids.
Autophagy thus plays a complex and dual role in VLDL particle assembly by regulating apoB100 degradation as well
as aiding the maturation of VLDL particles by hydrolyzing lipid from LDs. The purpose of this article is to review our
current understanding of molecular and cellular mechanisms mediating authophagic control of hepatic lipid
biogenesis and VLDL production as well as dysregulation in insulin resistance and dyslipidemia.
The importance of extracellular vesicles (EVs) in cell-cell communication has long been recognized due to their
ability to transfer important cellular cargoes such as DNA, mRNA, miRNAs, and proteins to target cells. Compelling
evidence supports the role of EVs in the horizontal transfer of cellular material which has the potential to influence
normal cellular physiology and promote various disease states. Of the different types of EVs, exosomes have garnered
much attention in the past decade due to their abundance in various biological fluids and ability to affect multiple
organ systems. The main focus of this review will be on cancer and how cancer-derived exosomes are important
mediators of metastasis, angiogenesis, immune modulation, and the tumor macro-/microenvironment. We will also
discuss exosomes as potential biomarkers for cancers due to their abundance in biological fluids, ease of uptake, and
cellular content. Exosome use in diagnosis, prognosis, and in establishing treatment regimens has enormous potential
to revolutionize patient care.
Ursolic acid (UA) and oleanolic acid (OA) are insoluble drugs. The objective of this study was to encapsulate them
into β-cyclodextrin (β-CD) and compare the solubility and intermolecular force of β-CD with the two isomeric
triterpenic acids. The host-guest interaction was explored in liquid and solid state by ultraviolet-visible absorption, 1 H
NMR, phase solubility analysis, and differential scanning calorimetry, X-ray powder diffractometry, and molecular
modeling studies. Both experimental and theoretical studies revealed that β-CD formed 1: 1 water soluble inclusion
complexes and the complexation process was naturally favorable. In addition, the overall results suggested that ring E
with a carboxyl group of the drug was encapsulated into the hydrophobic CD nanocavity. Therefore, a clear different
inclusion behavior was observed, and UA exhibited better affinity to β-CD compared with OA in various media due
to little steric interference, which was beneficial to form stable inclusion complex with β-CD and increase its water
solubility effectively.
Consumption of kava (Piper methysticum Forst) has been linked to reduced cancer risk in the South Pacific Islands.
Kavalactones are major bioactive components in kava root extracts, which have recently demonstrated anti-cancer
activities. However, molecular mechanisms of kavalactones' anti-cancer action remain largely unknown. We have
identified two kavalactones, yangonin and 5′ 6'-dehydrokawain, as potent inducers of autophagic cell death in bladder
cancer cells. The effect of yangonin inducing autophagy is associated with increased expression of beclin and ATG5.
In addition, yangonin increases the expression of LKB1 and decreases the phosphorylation of Akt, PRAS40, rpS6,
p70S6K and 4E-BP1, leading to increased binding of 4E-BP1 to m7 GTP. The growth inhibitory effects of yangonin
were attenuated in TSC1 or LKB1 knockout mouse embryonic fibroblasts, suggesting that TSC1 and LKB1
expression may contribute to optimal growth inhibition by yangonin. Furthermore, yangonin reduces the viability of
bladder cancer cell lines derived from different stages of human bladder cancer, and acts synergistically with
apoptosis-inducing agents such as docetaxel and flavokawain A. Our results support a novel anti-bladder cancer
mechanism by yangonin and further studies are needed to assess the potential use of yangonin for bladder cancer
prevention and treatment
Automatic diagnosis tool helps physicians to evaluate capsule endoscopic examinations faster and more accurate.
The purpose of this study was to evaluate the validity and reliability of an automatic post-processing method for
identifying and classifying wireless capsule endoscopic images, and investigate statistical measures to differentiate
normal and abnormal images. The proposed technique consists of two main stages, namely, feature extraction and
classification. Primarily, 32 features incorporating four statistical measures (contrast, correlation, homogeneity and
energy) calculated from co-occurrence metrics were computed. Then, mutual information was used to select features
with maximal dependence on the target class and with minimal redundancy between features. Finally, a trained
classifier, adaptive neuro-fuzzy interface system was implemented to classify endoscopic images into tumor, healthy
and unhealthy classes. Classification accuracy of 94.2% was obtained using the proposed pipeline. Such techniques
are valuable for accurate detection characterization and interpretation of endoscopic images.
Liver injury represents a continuum of pathophysiological processes involving a complex interplay between
hepatocytes, macrophages, and hepatic stellate cells. The mechanism whereby these intercellular interactions
contribute to liver injury and fibrosis is not completely understood. We report here that angiogenic factor with G patch
and FHA domains 1 (Aggf1) was downregulated in the livers of cirrhotic patients compared to healthy controls and in
primary hepatocytes in response to carbon tetrachloride (CCl4) stimulation. Overexpression of Aggf1 attenuated
macrophage chemotaxis. Aggf1 interacted with NF-κB to block its binding to the Ccl2 gene promoter and repressed
Ccl2 transcription in hepatocytes. Macrophages cultured in the conditioned media collected from Aggf1-
overexpressing hepatocytes antagonized HSC activation. Taken together, our data illustrate a novel role for Aggf1 in
regulating hepatic inflammation and provide insights on the development of interventional strategies against cirrhosis.
Sex steroids, also known as gonadal steroids, are oxidized with hydroxylation by cytochrome P450,
glucuronidation by UDP-glucuronosyltransferase, sulfation by sulfotransferase, and O-methylation by catechol Omethyltransferase. Thus, it is important to determine the process by which inflammation influences metabolism of
gonadal hormones. Therefore, we investigated the mechanism of metabolic enzymes against high physiologic
inflammatory response in vivo to study their biochemical properties in liver diseases. In this study, C57BL/6N mice
were induced with hepatic inflammation by diethylnitrosamine (DEN) exposure. We observed upregulation of
Cyp19a1, Hsd17b1, Cyp1a1, Sult1e1 in the DEN-treated livers compared to the control-treated livers using real time
PCR. Moreover, the increased Cyp19a1 and Hsd17b1 levels support the possibility that estrogen biosynthesis from
androgens are accumulated during inflammatory liver diseases. Furthermore, the increased levels of Cyp1a1 and
Cyp1b1 in the hydroxylation of estrogen facilitated the conversion of estrogen to 2- or 4-hydroxyestrogen,
respectively. In addition, the substantial increase in the Sult1e1 enzyme levels could lead to sulfate conjugation of
hydroxyestrogen. The present information supports the concept that inflammatory response can sequester sulfate
conjugates from the endogenous steroid hormones and may suppress binding of sex steroid hormones to their
receptors in the whole body.
Unbalanced brain serotonin (5-HT) levels have implications in various behavioral abnormalities and
neuropsychiatric disorders. The biosynthesis of neuronal 5-HT is regulated by the rate-limiting enzyme, tryptophan
hydroxylase-2 (TPH2). In the present study, the clustered regularly interspaced short palindromic repeat (CRISPR)/
CRISPR-associated (Cas) system was used to target the Tph2 gene in Bama mini pig fetal fibroblasts. It was found
that CRISPR/Cas9 targeting efficiency could be as high as 61.5%, and the biallelic mutation efficiency reached at
38.5%. The biallelic modified colonies were used as donors for somatic cell nuclear transfer (SCNT) and 10 Tph2
targeted piglets were successfully generated. These Tph2 KO piglets were viable and appeared normal at the birth.
However, their central 5-HT levels were dramatically reduced, and their survival and growth rates were impaired
before weaning. These Tph2 KO pigs are valuable large-animal models for studies of 5-HT deficiency induced
behavior abnomality.
Difructose dianhydride IV (DFA-IV) is produced from levan, which is a natural polysaccharide that belongs to the
fructan family, through the activity of levan fructotransferase (LF) derived from microorganisms. Recently, DFA-IV
has been expected to have diverse applications in the food and medical industry. Here, we examined the potential
application of DFA-IV for in vitro fertilization (IVF) in pigs. In the assessment of acrosomal integrity during
incubation, intact acrosomal or viable spermatozoa were highly sustained in 0.1% or 0.25% DFA-IV (69.8%-70.8%,
P < 0.05). Reactive oxygen species (ROS) levels during sperm incubation decreased following the addition of DFAIV, and 0.1%-0.5% DFA-IV in particular significantly decreased ROS production relative to that seen with no addition
or 0.75% DFA-IV. Total fertilization (mono + polyspermic oocyte) rate was significantly higher in the addition of
0.1% DFA-IV (94.2%) than with other concentrations (71.8%-86.7%, P < 0.05). When using reduced IVF times and
lower sperm numbers, we found that addition of 0.1%–0.5% DFA-IV significantly increased the fertilization rate
(P < 0.05). Fertilized oocytes treated with 0.1% DFA-IV exhibited higher embryonic development and blastocyst
formation than those treated with other concentrations (P < 0.05). Consequently, the addition of DFA-IV during IVF
improved fertilization and embryonic development, suggesting the possible use of novel sugars for enhancement of
assisted reproductive technology (ART) in mammals.
2017, 31(5): 462-465.
doi: 10.7555/JBR.31.20160159
We describe a case of right ilio-psoas abscess caused by stump appendicitis 14 years after open appendectomy.
Stump appendicitis is a rare complication of appendectomy. Right ilio-psoas abscess was diagnosed in an immunecompetent patient and treated by ultrasound guided percutaneous drainage twice without identifying the cause of the
abscess. The patient did not improve until diagnostic laparoscopy was performed revealing a long stump appendicitis
to be the origin of infection. It was treated by completion appendectomy. Surgical exploration may be necessary in
persistent or recurrent ilio-psoas abscesses. We identified 4 reported cases of post-appendectomy ilio-psoas abscess
but without recognizing the cause of the abscess and its relation to appendectomy. This is the first reported case of
ilio-psoas abscess that developed as a complication of stump appendicitis.
Authors and Reviewers
