Laser Acupuncture as a Treatment Option for Carpal Tunnel Syndrome Management: a Case Series

Limanjaya Iwan,Haris Salim,Nareswari Irma 사단법인약침학회 2022 Journal of Acupuncture & Meridian Studies Vol.15 No.3

Carpal tunnel syndrome (CTS) is disease that gives burdens for many countries, with a few choices for the management such as drugs or surgery, each has side effects that decrease the quality of life. Acupuncture is proven to be an effective treatment for pain and can restore nerve functions, and laser acupuncture is one of the modalities. This study aims to assess the effectiveness of laser acupuncture with total sample of 3 patients (6 wrists) mostly with tingling sensations and the outcomes are Boston questionnaire (BCTQ), visual analogue scale (VAS), Tinel sign, Phalen sign, and parameters of nerve conduction study (NCS). Acupuncture points used here are PC6, PC7, EXUE9, and LI4. The results show a decrease in NCS grades for 3 wrists, all wrists have BCTQ score improvements, a decrease in VAS, but no significant improvement in Tinel and Phalen signs. It is concluded that laser acupuncture can be used as a treatment option for the management of carpal tunnel syndrome.

The anti-Alzheimer compounds from tempeh oil in LPS-induced neuronal Schwann cells

Limanjaya Eileen C.,SUBALI DIONYSIUS,Yanti Yanti 한국식품연구원 2022 Journal of Ethnic Foods Vol.9 No.-

Tempeh is a traditional fermented Indonesian food from white soybean. Tempe has better nutritional value than non-fermented white soybean. The aim of this study was to extract tempeh oil and analyze the inhibitory potency of Alzheimer-related gene expression in LPS-induced neuronal Schwann cells. Tempeh oil was extracted with Bligh Dyer method and was analyzed with PUFA identification, anticholinesterase activity, antioxidant activity, and quantitative PCR. Tempeh oil had a total yield of 7.14%, and PUFA identification found 8.37% omega-3. The anti-acetylcholinesterase activity showed that tempeh oil 25 µg/mL had the highest activity and 500 µg/mL in anti-butyrylcholinesterase activity. The quantitative PCR showed that tempeh oil had downregulated the gene expression of PSEN1, Gsk3b, cdk5,andTNF. From this study, tempeh oil may have the potential to lower the risk of Alzheimer’s disease by regulating certain gene traits.

Gene expression profiling of mouse cavernous endothelial cells for diagnostic targets in diabetes-induced erectile dysfunction

윤국남,옥지연,최민지,Anita Limanjaya,Kalyan Ghatak,송강문,권미혜,서준규,류지간 대한비뇨의학회 2021 Investigative and Clinical Urology Vol.62 No.1

Purpose: To investigate potential target genes associated with the diabetic condition in mouse cavernous endothelial cells (MCECs) for the treatment of diabetes-induced erectile dysfunction (ED). Materials and Methods: Mouse cavernous tissue was embedded into Matrigel, and sprouted cells were subcultivated for other studies. To mimic diabetic conditions, MCECs were exposed to normal-glucose (NG, 5 mmoL) or high-glucose (HG, 30 mmoL) conditions for 72 hours. An RNA-sequencing assay was performed to evaluate gene expression profiling, and RT-PCR was used to validate the sequencing data. Results: We isolated MCECs exposed to the two glucose conditions. MCECs showed well-organized tubes and dynamic migration in the NG condition, whereas tube formation and migration were significantly decreased in the HG condition. RNA-sequencing analysis showed that MCECs had different gene profiles in the NG and HG conditions. Among the significantly changed genes, which we classified into 14 major gene categories, we identified that aging-related (9.22%) and angiogenesis-related (9.06%) genes were changed the most. Thirteen genes from the two gene categories showed consistent changes on the RNA-sequencing assay, and these findings were validated by RT-PCR. Conclusions: Our gene expression profiling studies showed that Cyp1a1, Gclm, Igfbp5, Nqo1, Il6, Cxcl5, Olr1, Ctgf, Hbegf, Serpine1, Cyr61, Angptl4, and Loxl2 may play a critical role in diabetes-induced ED through aging and angiogenesis signaling. Additional research is necessary to help us understand the potential mechanisms by which these genes influence diabetes-induced ED.

Three-Dimensional Reconstruction of Neurovascular Network in Whole Mount Preparations and Thick-Cut Transverse Sections of Mouse Urinary Bladder

Nguyen Nhat Minh,Song Kang-Moon,Choi Min-Ji,Ghatak Kalyan,Limanjaya Anita,Kwon Mi-Hye,Chung Doo Yong,Ock Jiyeon,Yin Guo Nan,Park Chang-Shin,Suh Jun-Kyu,Ryu Ji-Kan 대한남성과학회 2021 The World Journal of Men's Health Vol.39 No.1

Purpose: Proper functional and structural integrity of nervous and vascular system in urinary bladder plays an important role in normal bladder function and the disruption of these structures is known to be related to lower urinary tract symptoms. Here, we present an immunohistochemical staining method that delineates neurovascular structures in the mouse urinary bladder by using immunohistochemical staining with three-dimensional reconstruction. Materials and Methods: The urinary bladder was harvested from 8-week-old C57BL/6 male mouse. Lamina propria and detrusor muscle layer were dissected for whole mount staining, and thick-cut (60-μm) sections were prepared for full-thickness bladder staining. Immunofluorescent staining of bladder tissue was performed with antibodies against CD31 (an endothelial cell marker), smooth muscle α-actin (a smooth muscle cell marker), NG2 (a pericyte marker), and βIII-tubulin (a neuronal marker). We reconstructed three-dimensional images of bladder neurovascular system from stacks of two-dimensional images. Results: Three-dimensional images obtained from thick-cut sections clearly provided good anatomic information about neurovascular structures in the three layers of bladder, such as urothelium, lamina propria, and detrusor muscle layer. Whole mount images of lamina propria and detrusor muscle layer also clearly delineated spatial relationship between nervous and vascular systems. The microvessel density was higher in the lamina propria than in the detrusor muscle layer. Nerve fibers were evenly innervated into the lamina propria and detrusor muscle. Conclusions: This study provides comprehensive insight into three-dimensional neurovascular structures of mouse urinary bladder. Our technique may constitute a standard tool to evaluate pathologic changes in a variety of urinary bladder diseases.

Establishment of in vitro model of erectile dysfunction for the study of high-glucose-induced angiopathy and neuropathy

Yin, G. N.,Park, S.-H.,Song, K.-M.,Limanjaya, A.,Ghatak, K.,Minh, N. N.,Ock, J.,Ryu, J.-K.,Suh, J.-K. Wiley (Blackwell Publishing) 2017 Andrology Vol.5 No.2

<P>Penile erection requires complex interaction between vascular endothelial cells, smooth muscle cells, pericytes, and autonomic nerves. Diabetes mellitus is one of the most common causes of erectile dysfunction (ED) and multiple pathogenic factors, such as cavernous angiopathy and autonomic neuropathy, are associated with diabetic ED. Although a variety of animal models of diabetic ED play an important role in understanding pathophysiologic mechanisms of diabetes-induced ED, these animal models have limitations for addressing the exact cellular or molecular mechanisms involved in ED. Therefore, we established an in vitro model of ED for the study of high-glucose-induced angiopathy and neuropathy. We successfully isolated and cultivated mouse cavernous endothelial cells (MCECs) and mouse cavernous pericytes (MCPs). The cells were exposed to the normal-glucose (5 mmoL) or highglucose (30 mmoL) condition for 48 h. In vitro matrigel assay revealed impairments in tube formation in primary cultured MCECs or MCPs exposed to high-glucose condition. To study cellular interaction between MCECs and MCPs, co-culture systems including indirect contact, indirect non-contact, and direct mixed co-culture system, were established. We observed impaired tube formation and increased permeability in MCECs-MCPs co-culture exposed to high-glucose condition. To evaluate the effect of high-glucose on neurite sprouting, the mouse major pelvic ganglion (MPG) tissue was harvested and cultivated in matrigel. Neurite outgrowth and nNOS-positive nerve fibers were significantly lower in MPG tissues exposed to the high-glucose condition than in the tissues exposed to the normal-glucose condition. We believe that in vitro model of ED will aid us to understand the role of each cellular component in the pathogenesis of diabetic ED, and also be a useful tool for determining the efficacy of candidate therapeutics targeting vascular or neuronal function. This model would present a new avenue for drug discovery and development of novel therapeutic modalities for erectile dysfunction.</P>

Pericyte-Derived Dickkopf2 Regenerates Damaged Penile Neurovasculature Through an Angiopoietin-1-Tie2 Pathway

Yin, Guo Nan,Jin, Hai-Rong,Choi, Min-Ji,Limanjaya, Anita,Ghatak, Kalyan,Minh, Nguyen Nhat,Ock, Jiyeon,Kwon, Mi-Hye,Song, Kang-Moon,Park, Heon Joo,Kim, Ho Min,Kwon, Young-Guen,Ryu, Ji-Kan,Suh, Jun-Kyu American Diabetes Association 2018 Diabetes Vol.67 No.6

<P>Penile erection requires well-coordinated interactions between vascular and nervous systems. Penile neurovascular dysfunction is amajor cause of erectile dysfunction (ED) in patients with diabetes, which causes poor response to oral phosphodiesterase-5 inhibitors. Dickkopf2 (DKK2), a Wnt antagonist, is known to promote angiogenesis. Here, using DKK2-Tg mice or DKK2 protein administration, we demonstrate that the overexpression of DKK2 in diabetic mice enhances penile angiogenesis and neural regeneration and restores erectile function. Transcriptome analysis revealed that angiopoietin-1 and angiopoietin-2 are target genes for DKK2. Using an endothelial cell-pericyte co-culture system and ex vivo neurite sprouting assay, we found that DKK2-mediated juxtacrine signaling in pericyte-endothelial cell interactions promotes angiogenesis and neural regeneration through an angiopoietin-1-Tie2 pathway, rescuing erectile function in diabetic mice. The dual angiogenic and neurotrophic effects of DKK2, especially as a therapeutic protein, will open new avenues to treating diabetic ED.</P>

Penile neurovascular structure revisited: immunohistochemical studies with three-dimensional reconstruction

Yin, G. N.,Park, S. H.,Choi, M. J.,Limanjaya, A.,Ghatak, K.,Minh, N. N.,Ock, J.,Song, K. M.,Ryu, J. K.,Suh, J. K. John Wiley Sons Ltd 2017 Andrology Vol.5 No.5

Vactosertib, a Novel, Orally Bioavailable Activin Receptor-Like Kinase 5 Inhibitor, Promotes Regression of Fibrotic Plaques in a Rat Model of Peyronie’s Disease

Kang-Moon Song,Doo Yong Chung,Min Ji Choi,Kalyan Ghatak,Nguyen Nhat Minh,Anita Limanjaya,Mi-Hye Kwon,옥지연,Guo Nan Yin,Dae-Kee Kim,Ji-Kan Ryu,Jun-Kyu Suh 대한남성과학회 2020 The World Journal of Men's Health Vol.38 No.4

Purpose: To examine the therapeutic effect of Vactosertib, a small molecule inhibitor of transforming growth factor-β (TGF-β) type I receptor (activin receptor-like kinase-5, ALK5), in an experimental model of Peyronie’s disease (PD) and determining anti-fibrotic mechanisms of Vactosertib in primary fibroblasts derived from human PD plaques. Materials and Methods: Male rats were randomly divided into three groups (n=6 per group); control rats without treatment; PD rats receiving vehicle; and PD rats receiving Vactosertib (10 mg/kg). PD-like plaques were induced by administering 100 μL of each of human fibrin and thrombin solutions into the tunica albuginea on days 0 and 5. Vactosertib was given orally five times a week for 2 weeks. On day 30, we performed electrical stimulation of the cavernous nerve to measure erectile function, and the penis was obtained for histological examination. Fibroblasts isolated from human PD plaques were used to determine the anti-fibrotic effects of Vactosertib in vitro. Results: Vactosertib induced significant regression of fibrotic plaques in PD rats in vivo through reduced infiltration of inflammatory cells and reduced expression of phospho-Smad2, which recovered erectile function. Vactosertib also abrogated TGF- β1-induced enhancement of extracellular matrix protein production and hydroxyproline content in PD fibroblasts in vitro by hindering the TGF-β1-induced Smad2/3 phosphorylation and nuclear translocation, and fibroblast-to-myofibroblast transdifferentiation. Conclusions: In view of the critical role of TGF-β and the Smad pathway in the pathogenesis of PD, inhibition of this pathway with an ALK5 inhibitor may represent a novel, targeted therapy for PD.

Effectiveness of Intracavernous Delivery of Recombinant Human Hepatocyte Growth Factor on Erectile Function in the Streptozotocin-Induced Diabetic Mouse

Das, Nando Dulal,Yin, Guo Nan,Choi, Min Ji,Song, Kang-Moon,Park, Jin-Mi,Limanjaya, Anita,Ghatak, Kalyan,Minh, Nguyen Nhat,Ock, Jiyeon,Park, Soo-Hwan,Kim, Ho Min,Ryu, Ji-Kan,Suh, Jun-Kyu BLACKWELL PUBLISHING LTD 2016 JOURNAL OF SEXUAL MEDICINE Vol.13 No.11

<P>Introduction: Diabetic erectile dysfunction is a disease mostly of vascular origin and men with diabetic erectile dysfunction respond poorly to oral phosphodiesterase-5 inhibitors. Hepatocyte growth factor (HGF) is a pleiotropic factor that plays an essential role in the regulation of cell proliferation, survival, and angiogenesis. Aim: To determine the effectiveness of recombinant human (rh)-HGF in restoring erectile function in diabetic mice. Methods: Four groups of mice were used: control non-diabetic mice and streptozotocin-induced diabetic mice receiving two successive intracavernous injections of phosphate buffered saline (days -3 and 0), a single intracavernous injection of rh-HGF (day 0), or two successive intracavernous injections of rh-HGF (days -3 and 0). We also examined the effect of rh-HGF in primary cultured mouse cavernous endothelial cells and in major pelvic ganglion culture in vitro, which was incubated under a normal-glucose (5 mmol/L) or a high-glucose (30 mmol/L) condition. Main Outcome Measures: Two weeks after treatment, we measured erectile function by electrical stimulation of the cavernous nerve and the penis was harvested for histologic studies. Results: Repeated intracavernous injections of rh-HGF protein induced significant restoration of erectile function in diabetic mice (89-100% of control values), whereas a single intracavernous injection of rh-HGF protein elicited modest improvement. Rh-HGF significantly induced phosphorylation of its receptor c-Met, increased the content of endothelial cells and smooth muscle cells, and decreased the generation of reactive oxygen species (superoxide anion and peroxynitrite) and extravasation of oxidized low-density lipoprotein in diabetic mice. Under the high-glucose condition, rh-HGF protein also promoted tube formation in mouse cavernous endothelial cells and enhanced neurite sprouting in major pelvic ganglion culture in vitro. Conclusion: The dual angiogenic and neurotrophic effects of HGF could open a new avenue through which diabetic erectile dysfunction can be treated. Copyright (C) 2016, International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.</P>

Latrophilin-2 is a novel receptor of LRG1 that rescues vascular and neurological abnormalities and restores diabetic erectile function

Yin Guo Nan,Kim Do-Kyun,Kang Ji In,Im Yebin,Lee Dong Sun,Han Ah-reum,옥지연,Choi Min-Ji,Kwon Mi-Hye,Limanjaya Anita,Jung Saet-Byel,Yang Jimin,Min Kwang Wook,Yun Jeongwon,Koh Yongjun,Park Jong-Eun,Hwang D 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by inappropriate hyperglycemia, which causes endothelial dysfunction and peripheral neuropathy, ultimately leading to multiple complications. One prevalent complication is diabetic erectile dysfunction (ED), which is more severe and more resistant to treatment than nondiabetic ED. The serum glycoprotein leucine-rich ɑ-2-glycoprotein 1 (LRG1) is a modulator of TGF-β-mediated angiogenesis and has been proposed as a biomarker for a variety of diseases, including DM. Here, we found that the adhesion GPCR latrophilin-2 (LPHN2) is a TGF-β-independent receptor of LRG1. By interacting with LPHN2, LRG1 promotes both angiogenic and neurotrophic processes in mouse tissue explants under hyperglycemic conditions. Preclinical studies in a diabetic ED mouse model showed that LRG1 administration into the penile tissue, which exhibits significantly increased LPHN2 expression, fully restores erectile function by rescuing vascular and neurological abnormalities. Further investigations revealed that PI3K, AKT, and NF-κB p65 constitute the key intracellular signaling pathway of the LRG1/LPHN2 axis, providing important mechanistic insights into LRG1-mediated angiogenesis and nerve regeneration in DM. Our findings suggest that LRG1 can be a potential new therapeutic option for treating aberrant peripheral blood vessels and neuropathy associated with diabetic complications, such as diabetic ED.