Artificial intelligence-driven drug repositioning uncovers efavirenz as a modulator of α-synuclein propagation: Implications in Parkinson's disease.

Parkinson's disease (PD) is a complex neurodegenerative disorder with an unclear etiology. Despite significant research efforts, developing disease-modifying treatments for PD remains a major unmet medical need. Notably, drug repositioning is becoming an increasingly attractive direction in drug discovery, and computational approaches offer a relatively quick and resource-saving method for identifying testable hypotheses that promote drug repositioning.

Critical roles of parkin and PINK1 in coxsackievirus B3-induced viral myocarditis.

Viral myocarditis is an inflammatory disease of the myocardium, often leads to cardiac dysfunction and death. PARKIN (PRKN) and PINK1, well known as Parkinson's disease-associated genes, have been reported to be involved in innate immunity and mitochondrial damage control. Therefore, we investigated the role of parkin and PINK1 in coxsackievirus B3 (CVB3)-induced viral myocarditis because the etiology of myocarditis is related to abnormal immune response to viral infection and mitochondrial damage.

Neuronal ApoE Regulates the Cell-to-Cell Transmission of α-Synuclein.

The presence of protein inclusions, called Lewy bodies (LBs) and Lewy neurites (LNs), in the brain is the main feature of Parkinson's disease (PD). Recent evidence that the prion-like propagation of α-synuclein (α-syn), as a major component of LBs and LNs, plays an important role in the progression of PD has gained much attention, although the molecular mechanism remains unclear. In this study, we evaluated whether neuronal ApoE regulates the cell-to-cell transmission of α-syn and explored its molecular mechanism using in vitro and in vivo model systems.

Age-related increase in caveolin-1 expression facilitates cell-to-cell transmission of α-synuclein in neurons.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease, with aging being considered the greatest risk factor for developing PD. Caveolin-1 (Cav-1) is known to participate in the aging process. Recent evidence indicates that prion-like propagation of misfolded α-synuclein (α-syn) released from neurons to neighboring neurons plays an important role in PD progression.

The dual role of c-src in cell-to-cell transmission of α-synuclein.

Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons located in the substantia nigra pars compacta and the presence of proteinaceous inclusions called Lewy bodies and Lewy neurites in numerous brain regions. Increasing evidence indicates that Lewy pathology progressively involves additional regions of the nervous system as the disease advances, and the prion-like propagation of α-synuclein (α-syn) pathology promotes PD progression. Accordingly, the modulation of α-syn transmission may be important for the development of disease-modifying therapies in patients with PD.

Utility of Two Surgical Techniques Using a Lateral Intercostal Artery Perforator Flap after Breast-Conserving Surgery: A Single-Center Retrospective Study.

Background: Immediate partial breast reconstruction after breast-conserving surgery has become a new paradigm in treating breast cancer. Among the volume replacement techniques used for small to moderate-sized breasts, the perforator flap method has many advantages. The authors present anatomical studies and two surgical techniques using lateral intercostal artery perforator flaps.

Effects of Stromal Vascular Fraction on Breast Cancer Growth and Fat Engraftment in NOD/SCID Mice.

Background: To overcome unpredictable fat graft resorption, cell-assisted lipotransfer using stromal vascular fraction (SVF) has been introduced. However, its effect on cancer growth stimulation and its oncological safety are debatable. We investigated the effect of SVF on adjacent breast cancer and transplanted fat in a mouse model.

A murine model of radiation-induced capsule-tissue reactions around smooth silicone implants.

As the availability of breast reconstruction using implants is becoming widespread and many implant recipients undergo radiation therapy, there is an increasing interest in understanding the potential complications associated with capsule-tissue interactions in response to irradiation. Accordingly, our medical institution designed an animal experiment to investigate the effects of irradiation on capsular contracture. A total of 40 mice (C57BL6) were divided into four groups according to whether or not they received irradiation and the time from implantation to irradiation.

Prion-like Propagation of α-Synuclein Is Regulated by the FcγRIIB-SHP-1/2 Signaling Pathway in Neurons.

Recent evidence of prion-like propagation of α-synuclein (α-syn) into neighboring neurons set up a paradigm to elucidate the mechanism of progression of Parkinson's disease (PD) and to develop therapeutic strategies. Here, we show that FcγRIIB expressed in neurons functions as a receptor for α-syn fibrils and mediates cell-to-cell transmission of α-syn. SHP-1 and 2 are activated downstream by α-syn fibrils through FcγRIIB and play an important role in cell-to-cell transmission of α-syn.

The usefulness of pedicled perforator flap in partial breast reconstruction after breast conserving surgery in Korean women.

Background: The emergence of breast-conserving surgery combined with radiotherapy as the treatment of choice for early stage breast cancer has resulted in greater focus on oncoplastic breast surgery. The use of perforator flaps has particularly gained in reputation for its effectiveness in the reconstruction of partial breast defects in Korean women. Herein, we present our experience with the use of thoracodorsal artery perforator (TDAP) and lateral intercostal artery perforator (LICAP) flaps.

Clinical Characteristics of Arteriovenous Malformations of the Head and Neck.

Background: Arteriovenous malformation (AVM) of the head and neck regions show low incidence; hence, studies regarding the causative factors of onset, diagnostic criteria, clinical aspects, treatment methods, and outcomes remain lacking.

Objective: To share the diagnostic and treatment experiences at the center and to understand the treatments' effect through a retrospective analysis of cases in the past 15 years.

Materials And Methods: The authors included 60 patients with AVM in the head and neck area between January 1999 and September 2014 to investigate diagnostic methods, distributions and locations of lesions, clinical stage, and treatment methods by retrospective evaluation.

Factors prognostic for phonetic development after cleft palate repair.

Background: Palatoplasty is aimed to achieve normal speech, improve food intake, and ensure successful maxillary growth. However, the velopharyngeal function is harder to control than other functions. Therefore, many studies on the prognostic factor of velopharyngeal insufficiency have been conducted.

p190RhoGAP and Rap-dependent RhoGAP (ARAP3) inactivate RhoA in response to nerve growth factor leading to neurite outgrowth from PC12 cells.

Rat pheochromocytoma (PC12) cells have been used to investigate neurite outgrowth. Nerve growth factor (NGF) has been well known to induce neurite outgrowth from PC12 cells. RhoA belongs to Ras-related small GTP-binding proteins, which regulate a variety of cellular processes, including cell morphology alteration, actin dynamics, and cell migration.

Hedgehog signaling regulates proliferation of prostate cancer cells via stathmin1.

Hedgehog (Hh) signaling is an essential pathway in embryonic development of prostate. Hh also plays roles in the proliferation of progenitor cells and cancer cells of adult prostate. However, how Hh signaling contributes to carcinogenesis of prostate is poorly understood.

Expression of 4-1BB and 4-1BBL in thymocytes during thymus regeneration.

4-1BB, a member of the tumor necrosis factor receptor (TNFR) superfamily, is a major costimulatory receptor that is rapidly expressed on the surface of CD4(+) and CD8(+) T cells after antigen- or mitogen-induced activation. The interaction of 4-1BB with 4-1BBL regulates immunity and promotes the survival and expansion of activated T cells. In this study, the expression of 4-1BB and 4-1BBL was examined during regeneration of the murine thymus following acute cyclophosphamide- induced involution.

Hedgehog signaling regulates the survival of gastric cancer cells by regulating the expression of Bcl-2.

Gastric cancer is the second most common cause of cancer deaths worldwide. The underlying molecular mechanisms of its carcinogenesis are relatively poorly characterized. Hedgehog (Hh) signaling, which is critical for development of various organs including the gastrointestinal tract, has been associated with gastric cancer.

Regulation of cerebrospinal fluid production by caffeine consumption.

Background: Caffeine is the most commonly consumed psycho-stimulant in the world. The effects of caffeine on the body have been extensively studied; however, its effect on the structure of the brain has not been investigated to date.

Results: In the present study we found that the long-term consumption of caffeine can induce ventriculomegaly; this was observed in 40% of the study rats.

Inhibition of endothelial cell adhesion by the new anti-inflammatory agent alpha-iso-cubebene.

The current study explored if alpha-iso-cubebene, a novel cubebene sesquiterpene compound purified from Schisandra chinensis, could attenuate the activities of adhesion molecules in tumor necrosis factor-alpha (TNF-alpha)-stimulated human umbilical vein endothelial cells (HUVECs). The study was performed on HUVECs that were pretreated with 25 microg/ml of alpha-iso-cubebene before TNF-alpha treatment. Treatment of HUVECs with alpha-iso-cubebene for 6 h significantly inhibited TNF-alpha-induced reactive oxygen species (ROS) formation.

The role of hedgehog signaling during gastric regeneration.

Background: Hedgehog signaling plays critical roles during embryonic development. It is also involved in tissue regeneration and carcinogenesis in various adult tissues. Moreover, it regulates the maintenance of cancer stem cells and adult stem cells.

Reduction of ischemia-induced cerebral injury by all-trans-retinoic acid.

Ischemia-induced cerebral injury evolves over a longer period than previously believed through post-ischemic inflammation. Retinoic acid (RA) has been shown to exert cytoprotective effects on several cells, but its effects on ischemia-induced cerebral injury have been poorly characterized. The aim of the present study was to examine the effects of all-trans-RA on ischemia-induced cerebral injury and elucidate the underlying mechanism.