Diagnostic Role of Bile Pigment Components in Biliary Tract Cancer

Bile pigment, bilirubin, and biliverdin concentrations may change as a results of biliary tract cancer (BTC) altering the mechanisms of radical oxidation and heme breakdown. We explored whether changes in bile pigment components could help distinguish BTC from benign biliary illness by evaluating alterations in patients with BTC. We collected bile fluid from 15 patients with a common bile duct stone (CBD group) and 63 individuals with BTC (BTC group). We examined the bile fluid’s bilirubin, biliverdin reductase (BVR), heme oxygenase (HO-1), and bacterial taxonomic abundance. Serum bilirubin levels had no impact on the amounts of bile HO-1, BVR, or bilirubin. In comparison to the control group, the BTC group had considerably higher amounts of HO-1, BVR, and bilirubin in the bile. The areas under the curve for the receiver operating characteristic curve analyses of the BVR and HO-1 were 0.832 (p<0.001) and 0.891 (p<0.001), respectively. Firmicutes was the most prevalent phylum in both CBD and BTC, according to a taxonomic abundance analysis, however the Firmicutes/Bacteroidetes ratio was substantially greater in the BTC group than in the CBD group. The findings of this study showed that, regardless of the existence of obstructive jaundice, biliary carcinogenesis impacts heme degradation and bile pigmentation, and that the bile pigment components HO-1, BVR, and bilirubin in bile fluid have a diagnostic significance in BTC. In tissue biopsies for the diagnosis of BTC, particularly for distinguishing BTC from benign biliary strictures, bile pigment components can be used as additional biomarkers.

Efficient Generation of Dopaminergic Neurons from Mouse Ventral Midbrain Astrocytes

Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by tremors, bradykinesia, and rigidity. PD is caused by loss of dopaminergic (DA) neurons in the midbrain substantia nigra (SN) and therefore, replenishment of DA neurons via stem cell-based therapy is a potential treatment option. Astrocytes are the most abundant non-neuronal cells in the central nervous system and are promising candidates for reprogramming into neuronal cells because they share a common origin with neurons. The ability of neural progenitor cells (NPCs) to proliferate and differentiate may overcome the limitations of the reduced viability and function of transplanted cells after cell replacement therapy. Achaete-scute complex homolog-like 1 (Ascl1) is a wellknown neuronal-specific factor that induces various cell types such as human and mouse astrocytes and fibroblasts to differentiate into neurons. Nurr1 is involved in the differentiation and maintenance of DA neurons, and decreased Nurr1 expression is known to be a major risk factor for PD. Previous studies have shown that direct conversion of astrocytes into DA neurons and NPCs can be induced by overexpression of Ascl1 and Nurr1 and additional transcription factors genes such as superoxide dismutase 1 and SRY-box 2. Here, we demonstrate that astrocytes isolated from the ventral midbrain, the origin of SN DA neurons, can be effectively converted into DA neurons and NPCs with enhanced viability. In addition, when these NPCs are inducted to differentiate, they exhibit key characteristics of DA neurons. Thus, direct conversion of midbrain astrocytes is a possible cell therapy strategy to treat neurodegenerative diseases.

Circulating microRNAs as biomarkers in bile-derived exosomes of cholangiocarcinoma

Purpose@#In this pilot study, using next-generation sequencing and integrated messenger RNA (mRNA) sequencing, we investigated circulating microRNA (miRNA) expression profiling from bile-derived exosomes to identify dysregulated miRNA signatures and oncogenic pathways and determine their effects on targeted mRNAs in cholangiocarcinoma (CCA).Moreover, we explored the possibility that genetic analysis using bile-derived exosomes may replace gene analysis using tissue. @*Methods@#Bile was collected from a patient with perihilar CCA before curative resection. As a control, bile was collected from a patient with a common bile duct stone. Exosomes were isolated from the bile, and we performed next-generation miRNA sequencing using isolated exosomes. To evaluate miRNA-mRNA interactions, mRNA sequencing was performed using bile fluid in both patients. @*Results@#We identified 22 differentially expressed miRNAs. More than 65% of the predicted mRNA targets of those miRNAs were actually differentially expressed between control and CCA bile samples. In functional pathway analysis, targets of 22 miRNAs were primarily enriched in mitogen-activated protein kinase, platelet derived growth factor, vascular endothelial growth factor, epidermal growth factor receptor, and p53 signaling. In particular, in the functional assessment of miRNAmRNA interactions, RAS pathways, including downstream pathways (PI3K-AKT-mTOR and RAS-RAF-MEK-ERK), were determined to be enriched. @*Conclusion@#Circulating miRNAs in bile-derived exosomes provide new information for the development of miRNA analysis in CCA. These miRNAs may represent the oncogenic characteristics of CCA tissue, enabling them to be used instead of tissue samples for the diagnosis of CCA. Further research investigating circulating miRNAs in bile exosomes may lead to more rational, targeted approaches to treatment.

Circulating microRNAs as biomarkers in bile-derived exosomes of cholangiocarcinoma

Purpose@#In this pilot study, using next-generation sequencing and integrated messenger RNA (mRNA) sequencing, we investigated circulating microRNA (miRNA) expression profiling from bile-derived exosomes to identify dysregulated miRNA signatures and oncogenic pathways and determine their effects on targeted mRNAs in cholangiocarcinoma (CCA).Moreover, we explored the possibility that genetic analysis using bile-derived exosomes may replace gene analysis using tissue. @*Methods@#Bile was collected from a patient with perihilar CCA before curative resection. As a control, bile was collected from a patient with a common bile duct stone. Exosomes were isolated from the bile, and we performed next-generation miRNA sequencing using isolated exosomes. To evaluate miRNA-mRNA interactions, mRNA sequencing was performed using bile fluid in both patients. @*Results@#We identified 22 differentially expressed miRNAs. More than 65% of the predicted mRNA targets of those miRNAs were actually differentially expressed between control and CCA bile samples. In functional pathway analysis, targets of 22 miRNAs were primarily enriched in mitogen-activated protein kinase, platelet derived growth factor, vascular endothelial growth factor, epidermal growth factor receptor, and p53 signaling. In particular, in the functional assessment of miRNAmRNA interactions, RAS pathways, including downstream pathways (PI3K-AKT-mTOR and RAS-RAF-MEK-ERK), were determined to be enriched. @*Conclusion@#Circulating miRNAs in bile-derived exosomes provide new information for the development of miRNA analysis in CCA. These miRNAs may represent the oncogenic characteristics of CCA tissue, enabling them to be used instead of tissue samples for the diagnosis of CCA. Further research investigating circulating miRNAs in bile exosomes may lead to more rational, targeted approaches to treatment.

Pachymic Acid Enhances Pentobarbital-Induced Sleeping Behaviors via GABA(A)-ergic Systems in Mice

This study was investigated to know whether pachymic acid (PA), one of the predominant triterpenoids in Poria cocos (Hoelen) has the sedative-hypnotic effects, and underlying mechanisms are mediated via gamma-aminobutyric acid (GABA)-ergic systems. Oral administration of PA markedly suppressed locomotion activity in mice. This compound also prolonged sleeping time, and reduced sleep latency showing synergic effects with muscimol (0.2 mg/kg) in shortening sleep onset and enhancing sleep time induced by pentobarbital, both at the hypnotic (40 mg/kg) and sub-hypnotic (28 mg/kg) doses. Additionally, PA elevated intracellular chloride levels in hypothalamic primary cultured neuronal cells of rats. Moreover, Western blotting quantitative results showed that PA increased the amount of protein level expression of GAD65/67 over a broader range of doses. PA increased alpha- and beta-subunits protein levels, but decreased gamma-subunit protein levels in GABA(A) receptors. The present experiment provides evidence for the hypnotic effects as PA enhanced pentobarbital-induced sleeping behaviors via GABA(A)-ergic mechanisms in rodents. Taken together, it is proposed that PA may be useful for the treatment of sleep disturbed subjects with insomnia.

The Effect of Botulium Toxin in Chemical Brow Lift

The object of this study was to determine whether brow elevation occurs as a result of paralysis of brow depressors after botulinum toxin injection. This prospective study was designed with pretreatment and posttreatment outcome evaluation with statistical analysis. Twenty-seven consecutive patients were injected into brow depressor muscle directly. Botulinum toxin was injected into the glabellar area (5U), the supralateral eyebrow (2.5Ux2), the crow's feet (4Ux2). All patients were evaluated 2 weeks after treatment. The outcomes were measured by change in brow elevation; 1) brow to medial canthus, 2) brow to midpupil, 3) brow to lateral canthus, 4) interbrow distance, 5) brow to hairline. The average brow elevation were noted from the medial canthus (0.92mm+/-0.58mm, p<0.001), midpupil (1.42mm+/-0.61mm, p<0.001), lateral canthus(1.37mm+/-0.79mm, p<0.001). The average change were increased in interbrow distance(0.7mm+/-0.46mm, p<0.001) and decreased in brow to hairline(0.69mm+/-0.81mm, p<0.001). Botulinum toxin is a safe and effective treatment for chemical brow lift. The elevation in the medial, central and lateral brow can produce an aesthetically pleasing female brow with desirable shape and height. Although the endoscopic brow lift is more effective and able to predict the change of the brow shape and height, this procedure may be considered a simple and safe alternative to surgical brow elevation.

Correction of Deep Nasolabial Fold using Dermofat Graft of Rhytidectomy Skin

One of the techniques for improvement of the nasolabial fold is the insertion of a fat or dermis fat graft. Guyuron introduced the dermis fat graft from the suprapubic area or the groin region. We innovated a procedure of rhytidectomy and dermis fat graft from rhytidectomy skin to the nasolabial fold area. In casse of a 48-year-old man a conventional cervicofacial flap was elevated from the preauricular and cervico-postauricular regeon to the nasolabial fold. The excess excised skin from the preauricular area was deepithehialized, contoured, and grafted to the nasolabial fold. Three pull-out suture were placed at the medial margin of the dermis fat graft to secure its position. This procedure have several advantages. First, a dermis fat graft under the nasolabial crease not only thickens the soft tissue but also provides a shield to prevent reattachment of the fibrous band to the dermis, which are causative of a recurrent crease. Second, it has no donor site morbidity. Third, the subcutaneous tissue of the preauricular area has much fascial component which survives better than fat injection of strip fat graft. Last, under the direct vision surgeon could place the graft in position he wants. This technique could be used in Asian whose skin is thick and whose maxilla is protruded.