Potassium channels and transporters maintain potassium homeostasis and play significant roles in several different biological actions via potassium ion regulation. In previous decades, the key revelations that potassium channels and transporters are involved in the production of gastric acid and the regulation of secretion in the stomach have been recognized. Drugs used to treat peptic ulceration are often potassium transporter inhibitors. It has also been reported that potassium channels are involved in ulcerative colitis. Direct toxicity to the intestines from nonsteroidal anti-inflammatory drugs has been associated with altered potassium channel activities. Several reports have indicated that the long-term use of the antianginal drug Nicorandil, an adenosine triphosphate-sensitive potassium channel opener, increases the chances of ulceration and perforation from the oral to anal regions throughout the gastrointestinal (GI) tract. Several of these drug features provide further insights into the role of potassium channels in the occurrence of ulceration in the GI tract. The purpose of this review is to investigate whether potassium channelopathies are involved in the mechanisms responsible for ulceration that occurs throughout the GI tract.
Adenosine ; Channelopathies* ; Colitis, Ulcerative ; Gastric Acid ; Gastrointestinal Tract ; Homeostasis ; Intestines ; Nicorandil ; Peptic Ulcer ; Potassium Channels ; Potassium* ; Stomach ; Ulcer*

Potassium channels and transporters maintain potassium homeostasis and play significant roles in several different biological actions via potassium ion regulation. In previous decades, the key revelations that potassium channels and transporters are involved in the production of gastric acid and the regulation of secretion in the stomach have been recognized. Drugs used to treat peptic ulceration are often potassium transporter inhibitors. It has also been reported that potassium channels are involved in ulcerative colitis. Direct toxicity to the intestines from nonsteroidal anti-inflammatory drugs has been associated with altered potassium channel activities. Several reports have indicated that the long-term use of the antianginal drug Nicorandil, an adenosine triphosphate-sensitive potassium channel opener, increases the chances of ulceration and perforation from the oral to anal regions throughout the gastrointestinal (GI) tract. Several of these drug features provide further insights into the role of potassium channels in the occurrence of ulceration in the GI tract. The purpose of this review is to investigate whether potassium channelopathies are involved in the mechanisms responsible for ulceration that occurs throughout the GI tract.
Adenosine ; Channelopathies* ; Colitis, Ulcerative ; Gastric Acid ; Gastrointestinal Tract ; Homeostasis ; Intestines ; Nicorandil ; Peptic Ulcer ; Potassium Channels ; Potassium* ; Stomach ; Ulcer*

Purpose: Brain metastasis rarely occurs in soft tissue sarcoma (STS). Here, we present five cases of STS with brain metastases with genetic profiles. Materials and Methods: We included five patients from Seoul National University Hospital who were diagnosed with STS with metastasis to the brain. Tissue from the brain metastasis along with that from the primary site or other metastases were used for DNA and RNA sequencing to identify genetic profiles. Gene expression profiles were compared with sarcoma samples from The Cancer Genome Atlas. Results: The overall survival after diagnosis of brain metastasis ranged from 2.2 to 34.3 months. Comparison of mutational profiles between brain metastases and matched primary or other metastatic samples showed similar profiles. In two patients, copy number variation profiles between brain metastasis and other tumors showed several differences including MYCL, JUN, MYC, and DDR2 amplification. Gene ontology analysis showed that the group of genes significantly highly expressed in the brain metastasis samples was enriched in the G-protein coupled receptor activity, structural constituent of chromatin, protein heterodimerization activity, and binding of DNA, RNA, and protein. Gene set enrichment analysis showed enrichment in the pathway of neuroactive ligand-receptor interaction and systemic lupus erythematosus. Conclusion The five patients had variable ranges of clinical courses and outcomes. Genomic and transcriptomic analysis of STS with brain metastasis implicates possible involvement of complex expression modification and epigenetic changes rather than the addition of single driver gene alteration.

BACKGROUND: The essential oil of Ocimum basilicum (EOOB) has a pleasant aroma and is known to have antimicrobial and insecticidal activities. In addition, it is used as a pain reliever in folk medicine. However, there are few reports on the antinociceptive activities of EOOB. METHODS: This study examined the antinociceptive effects of EOOB using formalin and a plantar test in mice. In the formalin test, EOOB (50 mg/kg, 100 mg/kg, 150 mg/kg) was administered intraperitoneally and the licking time of the mice was measured. In the plantar test, intraperitoneal EOOB (50 mg/kg, 100 mg/kg) was administered and the withdrawal latency was measured using the Hargreaves method. RESULTS: In the formalin test, EOOB (50 mg/kg, IP) showed significant decreases in licking time in the second phase. On the other hand, in the plantar test, there were no significant effects in any of the groups examined. CONCLUSIONS: These results support the traditional use of EOOB for the treatment of painful conditions. However, there is a need for more research to determine the active chemical constituents and the precise mechanism.
Animals ; Formaldehyde ; Hand ; Medicine, Traditional ; Mice ; Ocimum ; Ocimum basilicum ; Pain Measurement

OBJECTIVES: Mental health disorders and suicide are an important and growing public health concern in Korea. Evidence has shown that both globally and in Korea, obesity is associated with an increased risk of developing some psychiatric disorders. Therefore, we examined the association between distorted body weight perception (BWP) and suicidal ideation. METHODS: Data were obtained from the 2007-2012 Korea National Health and Nutritional Evaluation Survey (KNHANES), an annual cross-sectional nationwide survey that included 14 276 men and 19 428 women. Multiple logistic regression analyses were conducted to investigate the associations between nine BWP categories, which combined body image (BI) and body mass index (BMI) categories, and suicidal ideation. Moreover, the fitness of our models was verified using the Akaike information criterion. RESULTS: Consistent with previous studies, suicidal ideation was associated with marital status, household income, education level, and perceived health status in both genders. Only women were significantly more likely to have distorted BWP; there was no relationship among men. In category B1 (low BMI and normal BI), women (odds ratio [OR], 2.25; 95% confidence interval [CI], 1.48 to 3.42) were more likely to express suicidal ideation than women in category B2 (normal BMI and normal BI) were. Women in overweight BWP category C2 (normal BMI and fat BI) also had an increased OR for suicidal ideation (OR, 2.25; 95% CI, 1.48 to 3.42). Those in normal BWP categories were not likely to have suicidal ideation. Among women in the underweight BWP categories, only the OR for those in category A2 (normal BMI and thin BI) was significant (OR, 1.34; 95% CI, 1.13 to 1.59). CONCLUSIONS: Distorted BWP should be considered an important factor in the prevention of suicide and for the improvement of mental health among Korean adults, especially Korean women with distorted BWPs.
Adult ; Aged ; Body Image/*psychology ; *Body Mass Index ; Body Weight ; Cross-Sectional Studies ; Demography ; Female ; Health Status ; Humans ; Income ; Interviews as Topic ; Logistic Models ; Male ; Marital Status ; Mental Health ; Middle Aged ; Nutrition Surveys ; Obesity/psychology ; Odds Ratio ; Sex Factors ; Social Class ; Socioeconomic Factors ; Suicidal Ideation ; Young Adult

BACKGROUND: Previous studies suggest that systemic administration of agmatine, endogenous ligand for imidazoline receptors has anti-hypernociceptive effects in experimental animal. However the peripheral effects of agmatine on inflammatory pain have not yet been elucidated. Here we examined the effects of intra-articular injection of agmatine in the induction and maintenance phase of arthritic pain. In addition, we sought to determine the potential contribution of imidazoline and alpha(2)-adrenergic receptors to the antinociceptive effects using clonidine which is mixed alpha(2)-adrenoceptor and imidazoline receptor agonist. METHODS: To induce arthritis in rats, 2% lambda-carrageenan (50microliter, in saline) was injected into the joint of the right hind limb under enflurane anesthesia. Either agmatine (10, 50, 100microgram/40microliter) or clonidine (10, 50, 100microgram/40microliter) was injected into the knee joint cavity immediately before or 4 hr after carrageenan injection. Weight load tests were performed to measure pain-related behavior in freely walking rats. RESULTS: The intraarticular injection of agmatine into the knee joint had no effects in the both phase of induction and maintenance of arthritic pain at any dose tested. However, injection of clonidine reversed arthritic pain, when injected 4 h after carrageenan injection. CONCLUSIONS: In rats, agmatine has no peripheral effect on inflammatory pain and imidazoline receptors in the periphery may not contribute to the anti-inflammatory pain.
Agmatine ; Anesthesia ; Animals ; Arthritis ; Carrageenan ; Clonidine ; Enflurane ; Extremities ; Imidazoline Receptors ; Inflammation ; Injections, Intra-Articular ; Joints ; Knee ; Knee Joint ; Rats ; Walking

Many intracellular proteins and signaling cascades contribute to the sensitivity of N-methyl-D-aspartate receptors (NMDARs). One such putative contributor is the serine/threonine kinase, protein kinase C (PKC). Activation of PKC by phorbol 12-myristate 13-acetate (PMA) causes activation of extracellular signal-regulated kinase (ERK) and promotes the formation of new spines in cultured hippocampal neurons. The purpose of this study was to examine which PKC isoforms are responsible for the PMA-induced augmentation of long-term potentiation (LTP) in the CA1 stratum radiatum of the hippocampus in vitro and verify that this facilitation requires NMDAR activation. We found that PMA enhanced the induction of LTP by a single episode of theta-burst stimulation in a concentration-dependent manner without affecting to magnitude of baseline field excitatory postsynaptic potentials. Facilitation of LTP by PMA (200 nM) was blocked by the nonspecific PKC inhibitor, Ro 31-8220 (10microM); the selective PKCdelta inhibitor, rottlerin (1microM); and the PKCepsilon inhibitor, TAT-epsilonV1-2 peptide (500 nM). Moreover, the NMDAR blocker DL-APV (50microM) prevented enhancement of LTP by PMA. Our results suggest that PMA contributes to synaptic plasticity in the nervous system via activation of PKCdelta and/or PKCepsilon, and confirm that NMDAR activity is required for this effect.
2-Amino-5-phosphonovalerate ; Acetophenones ; Benzopyrans ; Excitatory Postsynaptic Potentials ; Hippocampus ; Indoles ; Long-Term Potentiation ; Nervous System ; Neurons ; Phorbols ; Phosphotransferases ; Protein Isoforms ; Protein Kinases ; Proteins ; Receptors, N-Methyl-D-Aspartate ; Spine

Nephronophthisis-related ciliopathy (NPHP-RC) is a common genetic cause of end-stage renal failure during childhood and adolescence and exhibits an autosomal recessive pattern of inheritance. Genetic diagnosis is quite limited owing to genetic heterogeneity in NPHP-RC. We designed a novel approach involving the step-wise screening of Sanger sequencing and targeted exome sequencing for the genetic diagnosis of 55 patients with NPHP-RC. First, five NPHP-RC genes were analyzed by Sanger sequencing in phenotypically classified patients. Known pathogenic mutations were identified in 12 patients (21.8%); homozygous deletions of NPHP1 in 4 juvenile nephronophthisis patients, IQCB1/NPHP5 mutations in 3 Senior–Løken syndrome patients, a CEP290/NPHP6 mutation in 1 Joubert syndrome patient, and TMEM67/MKS3 mutations in 4 Joubert syndrome patients with liver involvement. In the remaining undiagnosed patients, we applied targeted exome sequencing of 34 ciliopathy-related genes to detect known pathogenic mutations in 7 (16.3%) of 43 patients. Another 18 likely damaging heterozygous variants were identified in 13 NPHP-RC genes in 18 patients. In this study, we report a variety of pathogenic and candidate mutations identified in 55 patients with NPHP-RC in Korea using a step-wise application of two genetic tests. These results support the clinical utility of targeted exome sequencing to resolve the issue of allelic and genetic heterogeneity in NPHP-RC.
Adolescent ; Diagnosis* ; Exome* ; Genetic Heterogeneity* ; Humans ; Kidney Failure, Chronic ; Korea ; Liver ; Mass Screening ; Wills

Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world. Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis. Results: NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs. Conclusion Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world. Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis. Results: NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs. Conclusion Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.