Experiences with an Extraperitoneal Transvesicoscopic Repair of a Vesicovaginal Fistula.

Purpose A vesicovaginal fistula (VVF) is a debilitating condition for women in terms of both its personal and social impacts. A reported transperitoneal laparoscopic approach to treatment has some limitations such as risk of intra-peritoneal organ injury and unnecessary bladder dissection. We here report on our experiences with an extraperitoneal transvesicoscopic approach to a VVF repair, which overcomes these drawbacks.

Effects of Puffing, Acid, and High Hydrostatic Pressure Treatments on Ginsenoside Profile and Antioxidant Capacity of Mountain-Cultivated .

The purpose of this study was to investigate the effects of puffing, acid, and high hydrostatic pressure (HHP) treatments on the ginsenoside profile and antioxidant capacity of mountain-cultivated (MCPG) before and after treatments. Puffing and HHP treatments decreased extraction yield and increased crude saponin content. The combination of puffing and HHP treatment showed significantly higher crude saponin content than each single treatment.

Safety assessment of a three-dimensional-printed autologous omentum patch: An application on the kidneys as a new treatment approach.

Recently, the field of regenerative medicine has made great strides in the development of new treatments for various organ dysfunctions. One of the most promising new approaches is the use of three-dimensional (3D) printing and autologous tissues. In this study, we evaluated the safety of a 3D-printed autologous omentum patch to kidneys using large animals.

Neuroprotective Effects of Licochalcone D in Oxidative-Stress-Induced Primitive Neural Stem Cells from Parkinson's Disease Patient-Derived iPSCs.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases caused by the loss of dopaminergic neurons in the substantia nigra pars compacta. Although the etiology of PD is still unclear, the death of dopaminergic neurons during PD progression was revealed to be associated with abnormal aggregation of α-synuclein, elevation of oxidative stress, dysfunction of mitochondrial functions, and increased neuroinflammation. In this study, the effects of Licochalcone D (LCD) on MG132-induced neurotoxicity in primitive neural stem cells (pNSCs) derived from reprogrammed iPSCs were investigated.

Intermediate cells of in vitro cellular reprogramming and in vivo tissue regeneration require desmoplakin.

Amphibians and fish show considerable regeneration potential via dedifferentiation of somatic cells into blastemal cells. In terms of dedifferentiation, in vitro cellular reprogramming has been proposed to share common processes with in vivo tissue regeneration, although the details are elusive. Here, we identified the cytoskeletal linker protein desmoplakin (Dsp) as a common factor mediating both reprogramming and regeneration.

Clinical application of both amniotic membranes and adipose derived mesenchymal stem cells in a cat with a large skin defect.

Surgical procedures on large skin defects can be challenging in the short term due to the size of the lesion, infection, and tissue defect. A regenerative therapy for skin wounds has been applied to promote the healing process. An 8-month-old, Korean domestic short-haired female cat, weighing 3 kg, was rescued with extensive defects on the right flank to right inguinal region caused by bite wounds.

Regulation of Survival Motor Neuron Gene Expression by Calcium Signaling.

Spinal muscular atrophy (SMA) is caused by homozygous () gene deletion, leaving a duplicate gene, , as the sole source of SMN protein. However, a defect in SMN2 splicing, involving exon 7 skipping, results in a low level of functional SMN protein. Therefore, the upregulation of SMN protein expression from the gene is generally considered to be one of the best therapeutic strategies to treat SMA.

Development of a quantitative prediction algorithm for target organ-specific similarity of human pluripotent stem cell-derived organoids and cells.

Human pluripotent stem cell (hPSC)-derived organoids and cells have similar characteristics to human organs and tissues. Thus, in vitro human organoids and cells serve as a superior alternative to conventional cell lines and animal models in drug development and regenerative medicine. For a simple and reproducible analysis of the quality of organoids and cells to compensate for the shortcomings of existing experimental validation studies, a quantitative evaluation method should be developed.

Ciliogenesis is Not Directly Regulated by LRRK2 Kinase Activity in Neurons.

Mutations in the Leucine-rich repeat kinase 2 () gene are the most prevalent cause of familial Parkinson's disease (PD). The increase in LRRK2 kinase activity observed in the pathogenic G2019S mutation is important for PD development. Several studies have reported that increased LRRK2 kinase activity and treatment with LRRK2 kinase inhibitors decreased and increased ciliogenesis, respectively, in mouse embryonic fibroblasts (MEFs) and retinal pigment epithelium (RPE) cells.

The development of a functional human small intestinal epithelium model for drug absorption.

Advanced technologies are required for generating human intestinal epithelial cells (hIECs) harboring cellular diversity and functionalities to predict oral drug absorption in humans and study normal intestinal epithelial physiology. We developed a reproducible two-step protocol to induce human pluripotent stem cells to differentiate into highly expandable hIEC progenitors and a functional hIEC monolayer exhibiting intestinal molecular features, cell type diversity, and high activities of intestinal transporters and metabolic enzymes such as cytochrome P450 3A4 (CYP3A4). Functional hIECs are more suitable for predicting compounds metabolized by CYP3A4 and absorbed in the intestine than Caco-2 cells.

The prediction of need of using ankle-foot orthoses in stroke patients based on findings of a transcranial magnetic stimulation study.

Ankle-foot orthoses (AFOs) are widely prescribed for stroke rehabilitation. We investigated the potential of transcranial magnetic stimulation (TMS) at an early stage, after stroke, to predict the need of using AFOs in stroke patients. We recruited 35 patients who could walk with intermittent support of one person or independently 3 months after onset of stroke.

Case Report: Surgical Treatment of Severe Facial Wounds and Proptosis in a Dog Due to a Traffic Accident.

Although facial wounds caused by traffic accidents in dogs are common, the surgical management of severe facial injuries involving the soft tissue, bone, dentition, nose and orbit are challenging. A 2 year-old Korean Jindo dog was diagnosed with severe skin defects of the face and proptosis caused by a vehicular accident. Along the left lateral maxilla, severe injury involving the overlying skin and platysma muscle occurred, to the extent that the middle part of the sphincter colli profundus pars intermedia muscle was exposed.

Mirabegron for treatment of overactive bladder symptoms in patients with Parkinson's disease: A double-blind, randomized placebo-controlled trial (Parkinson's Disease Overactive bladder Mirabegron, PaDoMi Study).

Aims: This study aimed to investigate the efficacy and safety of mirabegron for Parkinsonism patients with overactive bladder (OAB) symptoms in a randomized, placebo-controlled, multicenter study.

Materials And Methods: Inclusion criteria are Parkinsonism with OAB symptoms for 4 weeks or more, OAB symptom score (OABSS) questionnaire scores greater than 2, and OABSS urgency question scores greater than 1. After a 2-week wash-out period, the patients were randomized into placebo and mirabegron groups at visit 2.

Quantitative Proteomic Analysis of Primitive Neural Stem Cells from LRRK2 G2019S-Associated Parkinson's Disease Patient-Derived iPSCs.

Parkinson's disease (PD) is a common neurodegenerative disease, causing movement defects. The incidence of PD is constantly increasing and this disease is still incurable. Thus, understanding PD pathophysiology would be pivotal for the development of PD therapy, and various PD models have thus been already developed.

Simplified Brain Organoids for Rapid and Robust Modeling of Brain Disease.

Although brain organoids are an innovative technique for studying human brain development and disease by replicating the structural and functional properties of the developing human brain, some limitations such as heterogeneity and long-term differentiation (over 2 months) impede their application in disease modeling and drug discovery. In this study, we established simplified brain organoids (simBOs), composed of mature neurons and astroglial cells from expandable hPSC-derived primitive neural stem cells (pNSCs). simBOs can be rapidly generated in 2 weeks and have more homogeneous properties.

The combination of forskolin and VPA increases gene expression efficiency to the hypoxia/neuron-specific system.

Background: Spinal cord injury (SCI) tends to damage neural tissue and generate a hypoxic environment. Studies have confirmed that single therapy with gene or stem cells is inefficient, but research into combining stem cells and gene therapy in treating tissue damage has been undertaken to overcome the related limitations, which include low gene delivery efficiency and therapeutic outcome. Thus, a combination of stem cells, gene therapy, and a hypoxia-specific system may be useful for the reconstruction of SCI.

Neuroprotective Effects of Cryptotanshinone in a Direct Reprogramming Model of Parkinson's Disease.

Parkinson's disease (PD) is a well-known age-related neurodegenerative disease. Considering the vital importance of disease modeling based on reprogramming technology, we adopted direct reprogramming to human-induced neuronal progenitor cells (hiNPCs) for in vitro assessment of potential therapeutics. In this study, we investigated the neuroprotective effects of cryptotanshinone (CTN), which has been reported to have antioxidant properties, through PD patient-derived hiNPCs (PD-iNPCs) model with induced oxidative stress and cell death by the proteasome inhibitor MG132.

Maturation of human intestinal organoids in vitro facilitates colonization by commensal lactobacilli by reinforcing the mucus layer.

Lactobacilli, which are probiotic commensal bacteria that mainly reside in the human small intestine, have attracted attention for their ability to exert health-promoting effects and beneficially modulate host immunity. However, host epithelial-commensal bacterial interactions are still largely unexplored because of limited access to human small intestinal tissues. Recently, we described an in vitro maturation technique for generating adult-like, mature human intestinal organoids (hIOs) from human pluripotent stem cells (hPSCs) that closely resemble the in vivo tissue structure and cellular diversity.

Cohen Syndrome Patient iPSC-Derived Neurospheres and Forebrain-Like Glutamatergic Neurons Reveal Reduced Proliferation of Neural Progenitor Cells and Altered Expression of Synapse Genes.

Cohen syndrome (CS), a rare autosomal recessive disorder, has been associated with genetic mutations in the gene, which regulates vesicle-mediated protein sorting and transport. However, the cellular mechanism underlying CS pathogenesis in patient-derived human neurons remains unknown. We identified a novel compound heterozygous mutation, due to homozygous variation of biparental origin and heterozygous variation inherited from the father, in the gene in a 20-month-old female patient.

Detection and Assessment of α-Synuclein Oligomers in the Urine of Parkinson's Disease Patients.

Background: α-Synuclein (α-syn) is a major component of Lewy bodies, a pathologic marker of Parkinson's disease (PD) in post-mortem studies. The use of α-syn as a practical PD biomarker has been investigated by numerous researchers. However, reports of differences in α-syn levels in biofluids, such as cerebrospinal fluid, plasma, and saliva, between PD patients and controls are inconsistent.

Iroquois Homeobox Protein 2 Identified as a Potential Biomarker for Parkinson's Disease.

The diagnosis of Parkinson's disease (PD) is initiated after the occurrence of motor symptoms, such as resting tremors, rigidity, and bradykinesia. According to previous reports, non-motor symptoms, notably gastrointestinal dysfunction, could potentially be early biomarkers in PD patients as such symptoms occur earlier than motor symptoms. However, connecting PD to the intestine is methodologically challenging.

Combined Method of Neuronal Cell-Inducible Vector and Valproic Acid for Enhanced Gene Expression under Hypoxic Conditions.

Background: Gene therapy shows the ability to restore neuronal dysfunction via therapeutic gene expression. The efficiency of gene expression and delivery to hypoxic injury sites is important for successful gene therapy. Therefore, we established a gene/stem cell therapy system using neuron-specific enolase promoter and induced neural stem cells in combination with valproic acid to increase therapeutic gene expression in hypoxic spinal cord injury.

CRISPR-mediated gene correction links the ATP7A M1311V mutations with amyotrophic lateral sclerosis pathogenesis in one individual.

Amyotrophic lateral sclerosis (ALS) is a severe disease causing motor neuron death, but a complete cure has not been developed and related genes have not been defined in more than 80% of cases. Here we compared whole genome sequencing results from a male ALS patient and his healthy parents to identify relevant variants, and chose one variant in the X-linked ATP7A gene, M1311V, as a strong disease-linked candidate after profound examination. Although this variant is not rare in the Ashkenazi Jewish population according to results in the genome aggregation database (gnomAD), CRISPR-mediated gene correction of this mutation in patient-derived and re-differentiated motor neurons drastically rescued neuronal activities and functions.