Identifying Novel Subtypes of Functional Gastrointestinal Disorder by Analyzing Nonlinear Structure in Integrative Biopsychosocial Questionnaire Data.

Background/Objectives: Given the limited success in treating functional gastrointestinal disorders (FGIDs) through conventional methods, there is a pressing need for tailored treatments that account for the heterogeneity and biopsychosocial factors associated with FGIDs. Here, we considered the potential of novel subtypes of FGIDs based on biopsychosocial information. Methods: We collected data from 198 FGID patients utilizing an integrative approach that included the traditional Korean medicine diagnosis questionnaire for digestive symptoms (KM), as well as the 36-item Short Form Health Survey (SF-36), alongside the conventional Rome-criteria-based Korean Bowel Disease Questionnaire (K-BDQ). Multivariate analyses were conducted to assess whether KM or SF-36 provided additional information beyond the K-BDQ and its statistical relevance to symptom severity. Questions related to symptom severity were selected using an extremely randomized trees (ERT) regressor to develop an integrative questionnaire. For the identification of novel subtypes, Uniform Manifold Approximation and Projection and spectral clustering were used for nonlinear dimensionality reduction and clustering, respectively. The validity of the clusters was assessed using certain metrics, such as trustworthiness, silhouette coefficient, and accordance rate. An ERT classifier was employed to further validate the clustered result. Results: The multivariate analyses revealed that SF-36 and KM supplemented the psychosocial aspects lacking in K-BDQ. Through the application of nonlinear clustering using the integrative questionnaire data, four subtypes of FGID were identified: mild, severe, mind-symptom predominance, and body-symptom predominance. Conclusions: The identification of these subtypes offers a framework for personalized treatment strategies, thus potentially enhancing therapeutic outcomes by tailoring interventions to the unique biopsychosocial profiles of FGID patients.

GPT-4 can pass the Korean National Licensing Examination for Korean Medicine Doctors.

Traditional Korean medicine (TKM) emphasizes individualized diagnosis and treatment. This uniqueness makes AI modeling difficult due to limited data and implicit processes. Large language models (LLMs) have demonstrated impressive medical inference, even without advanced training in medical texts. This study assessed the capabilities of GPT-4 in TKM, using the Korean National Licensing Examination for Korean Medicine Doctors (K-NLEKMD) as a benchmark. The K-NLEKMD, administered by a national organization, encompasses 12 major subjects in TKM. GPT-4 answered 340 questions from the 2022 K-NLEKMD. We optimized prompts with Chinese-term annotation, English translation for questions and instruction, exam-optimized instruction, and self-consistency. GPT-4 with optimized prompts achieved 66.18% accuracy, surpassing both the examination's average pass mark of 60% and the 40% minimum for each subject. The gradual introduction of language-related prompts and prompting techniques enhanced the accuracy from 51.82% to its maximum accuracy. GPT-4 showed low accuracy in subjects including public health & medicine-related law, internal medicine (2), and acupuncture medicine which are highly localized in Korea and TKM. The model's accuracy was lower for questions requiring TKM-specialized knowledge than those that did not. It exhibited higher accuracy in diagnosis-based and recall-based questions than in intervention-based questions. A significant positive correlation was observed between the consistency and accuracy of GPT-4's responses. This study unveils both the potential and challenges of applying LLMs to TKM. These findings underline the potential of LLMs like GPT-4 in culturally adapted medicine, especially TKM, for tasks such as clinical assistance, medical education, and research. But they also point towards the necessity for the development of methods to mitigate cultural bias inherent in large language models and validate their efficacy in real-world clinical settings.

Rikkunshito Depolarizes Pacemaker Potentials of Cultured Interstitial Cells of Cajal through Ghrelin Receptors in Murine Small Intestine.

BACKGROUND: Rikkunshito has been used to treat gastrointestinal (GI) disorders. The purpose of this study was to investigate the effects of Rikkunshito, a traditional Japanese herbal medicine, on the pacemaker potentials of interstitial cells of Cajal (ICCs) from the small intestines of mice. METHODS: We isolated ICCs from the small intestines of mice, and the whole-cell patch-clamp configuration was used to record the pacemaker potentials in cultured ICCs and membrane currents. RESULTS: Rikkunshito depolarized ICC pacemaker potentials in a dose-dependent manner. Pretreatment with GSK1614343 or (D-Lys3)-growth hormone-releasing peptide-6 inhibited Rikkunshito-induced depolarization of pacemaker potentials. Intracellular GDP-ß-S inhibited Rikkunshito-induced effects. In Ca2+-free solution or in the presence of thapsigargin, Rikkunshito did not depolarize pacemaker potentials. Moreover, in the presence of U-73122 or xestospongin C, Rikkunshito-induced effects were inhibited. However, in the presence of staurosporine, Go6976 or Rottlerin, Rikkunshito depolarized pacemaker potentials. Furthermore, Rikkunshito inhibited both transient receptor potentials melastatin 7 (TRPM7) and Ca2+-activated Cl- channels (ANO1) currents. CONCLUSION: Rikkunshito depolarized pacemaker potentials of ICCs via ghrelin receptor and G protein through internal or external Ca2+-, phospholipase C-, and inositol triphosphate-dependent and protein kinase C-, TRPM7-, and ANO1-independent pathways. The study shows that Rikkunshito may alleviate GI motility disorders through its depolarizing effects on ICCs.

Berberine induces pacemaker potential inhibition via cGMP-dependent ATP-sensitive K+ channels by stimulating mu/delta opioid receptors in cultured interstitial cells of Cajal from mouse small intestine.

Berberine is traditionally used to treat gastrointestinal (GI) motility disorders. The interstitial cells of Cajal (ICCs) are the pacemaker cells of the gastrointestinal tract, which are responsible for the production of gut movements. The present study aimed to investigate the effects of berberine on pacemaker potentials (PPs) in cultured ICC clusters from the mouse small intestine, and sought to identify the receptors involved and the underlying mechanisms of action. All experiments were performed on cultured ICCs, and a whole­cell patch­clamp configuration was used to record PPs from ICC clusters (current clamp mode). Under current clamp mode, berberine was shown to decrease the amplitude and frequency of PPs. However, these effects were suppressed by treatment with glibenclamide, a specific ATP­sensitive K+ channel blocker. Nor­binaltorphimine dihydrochloride (a kappa opioid receptor antagonist) did not suppress berberine­induced PP inhibition, whereas ICI 174,864 (a delta opioid receptor antagonist) and CTOP (a mu opioid receptor antagonist) did suppress the inhibitory effects of berberine. Pretreatment with SQ­22536 (an adenylate cyclase inhibitor) or with KT­5720 (a protein kinase A inhibitor) did not suppress the effects of berberine; however, pretreatment with 1H­[1,2,4] oxadiazolo [4,3­a] quinoxalin­1­one (a guanylate cyclase inhibitor) or KT­5823 [a protein kinase G (PKG) inhibitor] did. In addition, berberine stimulated cyclic guanosine monophosphate (cGMP) production in ICCs. These observations indicate that berberine may inhibit the pacemaker activity of ICC clusters via ATP­sensitive K+ channels and the cGMP­PKG­dependent pathway by stimulating mu and delta opioid receptors. Therefore, berberine may provide a basis for the development of novel agents for the treatment of GI motility dysfunction.

Attitudes of Korean and Chinese traditional medical doctors on education of East Asian traditional medicine.

BACKGROUND: The traditional medicine (TRM) of Korea and China share the same cultural tradition for thousands of years, and has experienced modernization process with respect to their distinctive social, cultural, and political influences. The purpose of this study was to analyze the attitude of Korean and Chinese TRM doctors on the current situation and future perspectives of the TRM education. METHODS: We analyzed the recognition on the current educational system, and needed curriculums from Korean (n = 188) and Chinese (n = 118) TRM doctors. The validity of the structured questionnaire was examined with exploratory factor analysis with varimax rotation and reliability with Cronbach α. The differences between Korean and Chinese TRM doctors were examined with t test. RESULTS: Chinese TRM doctors consider their educational system more positively as for the standardization and professional ethics than the Korean. The Korean and Chinese wanted more emphasis on the education of medical humanities, clinical skills, medical classics, and alternative medicine, although it was more prominent with the Chinese. CONCLUSION: This study revealed the attitude of Korean and Chinese TRM doctors on their educational system, and discussed the implication of similarities and differences between them. It would provide foundations for the improvement of the TRM educational curriculums.

The past, present, and future of traditional medicine education in Korea.

Korea has kept the heritage of Korean traditional medicine (KM) during the 19th century harsh modernization, and has established a medical system in parallel with Western medicine. The purpose of this study was to review systematically the history and current system for educating highly qualified traditional medical doctors in Korea. KM produces 750 certified medical doctors every year with a 4-7-year curriculum in 12 universities and their affiliated hospitals. There are 22,074 clinicians along with 2474 clinical specialists in eight departments as of 2014. A national licensing examination and continuing medical education for KM are used for maintaining qualifications of KM doctors, and independent organizations are established for the evaluation of educational institutes. KM has thrived to establish an independent and competitive educational system for KM doctors, equivalent to Western medicine, and has regained a pivotal role for public health in Korea. This study would be useful for cultivating traditional medicine and establishing its educational system in the world.

Effects of Dangkwisoo­san, a traditional herbal medicine for treating pain and blood stagnation, on the pacemaker activities of cultured interstitial cells of Cajal.

The interstitial cells of Cajal (ICCs) are the pacemaker cells in the gastrointestinal (GI) tract. In the present study, the effects of Dangkwisoo­san (DS) on pacemaker potentials in cultured ICCs from the small intestine of the mouse were investigated. The whole­cell patch­clamp configuration was used to record pacemaker potentials from cultured ICCs and the increase in intracellular Ca2+ concentration ([Ca2+i) was analyzed in cultured ICCs using fura­2­acetoxymethyl ester. The generation of pacemaker potentials in the ICCs was observed. DS produced pacemaker depolarizations in a concentration dependent manner in current clamp mode. The 4­diphenylacetoxy­N­methyl­piperidine methiodide muscarinic M3 receptor antagonist inhibited DS­induced pacemaker depolarizations, whereas methoctramine, a muscarinic M2 receptor antagonist, did not. When guanosine 5'­[ß­thio] diphosphate (GDP­ß­S; 1 mM) was in the pipette solution, DS marginally induced pacemaker depolarizations, whereas low Na+ solution externally eliminated the generation of pacemaker potentials and inhibited the DS­induced pacemaker depolarizations. Additionally, the nonselective cation channel blocker, flufenamic acid, inhibited the DS­induced pacemaker depolarizations. Pretreatment with Ca2+­free solution and thapsigargin, a Ca2+­ATPase inhibitor in the endoplasmic reticulum, also eliminated the generation of pacemaker currents and suppressed the DS­induced pacemaker depolarizations. In addition, [Ca2+]i analysis revealed that DS increased [Ca2+]i. These results suggested that DS modulates pacemaker potentials through muscarinic M3 receptor activation in ICCs by G protein­dependent external and internal Ca2+ regulation and external Na+. Therefore, DS were observed to affect intestinal motility through ICCs.

The traditional herbal medicine, Ge-Gen-Tang, inhibits pacemaker potentials by nitric oxide/cGMP dependent ATP-sensitive K(+) channels in cultured interstitial cells of Cajal from mouse small intestine.

ETHNOPHARMACOLOGICAL RELEVANCE: Ge-Gen-Tang (GGT) is a traditional Chinese medicinal formula composed of Puerariae radix (Pueraria lobata Ohwi), Ephedrae Herba (Ephedra sinica Stapf), Cinnamomi Ramulus (Cinnamomum cassia Blume), Paeoniae Radix (Paeonia lactiflora Pallas), Glycyrrhizae Radix preparata (Glycyrrhiza uralensis Fischer), Zingiberis Rhizoma (Zingiber officinale Roscoe), and Zizyphi Fructus (Ziziphus jujuba Mill. var. inermis Rehder) and is widely used to ameoliorate the symptoms of gastrointestinal (GI) disorders related to diarrhea and intestinal mucosal immunity and for anti-cold, antipyretic and analgesic in Eastern Asia. AIM OF THE STUDY: Interstitial cells of Cajal (ICCs) are pacemaker cells in the GI tract that generate rhythmic oscillations in membrane potentials known as slow waves. We investigated the effects of GGT on pacemaker potentials in cultured ICCs from the mouse small intestine, and sought to identify the receptors and the action mechanisms involved. MATERIALS AND METHODS: Enzymatic digestions were used to dissociate ICCs from mouse small intestine tissues. All experiments on ICCs were performed on within 12h after culture. A whole-cell patch-clamp configuration was used to record potentials (current clamp) from cultured ICCs. Intracellular Ca(2+) ([Ca(2+)]i) increase was studied in cultured ICCs using fura-2AM. All of the experiments were performed at 30-32°C. RESULTS: Under the current clamping mode, GGT decreased the amplitude and frequency of pacemaker potentials; however, these effects were blocked by intracellular GDPßS, a G-protein inhibitor, and glibenclamide, a specific ATP-sensitive K(+) channels blocker. Prazosin (α1-adrenoceptor antagonist) and butoxamine (ß2-adrenoceptor antagonist) did not block the GGT-induced effects, whereas atenolol (ß1-adrenoceptor antagonist) blocked the GGT-induced effects. Also, yohimbine (α2-adrenoceptor antagonist) partially blocked the GGT-induced effects. Pretreatment with SQ-22536, an adenylate cyclase inhibitor, did not block the GGT-induced effects, whereas pretreatment with ODQ, a guanylate cyclase inhibitor, or L-NAME, an inhibitor of nitric oxide (NO) synthase, did. Additionally, [Ca(2+)]i analysis showed that GGT decreased [Ca(2+)]i. CONCLUSION: These results suggest that GGT inhibits pacemaker potentials in ICCs in a G protein-, cGMP- and NO-dependent manner through stimulation of α2 and ß1-adrenoceptors.

Characteristics of the cholecystokinin-induced depolarization of pacemaking activity in cultured interstitial cells of Cajal from murine small intestine.

BACKGROUND/AIMS: In this study, we studied the effects of cholecystokinin (CCK) on pacemaker potentials in cultured interstitial cells of Cajal (ICCs) from mouse small intestine using the whole cell patch clamp technique. METHODS: ICCs are pacemaker cells that exhibit periodic spontaneous depolarization, which is responsible for the production of slow waves in gastrointestinal smooth muscle, and generate periodic pacemaker potentials in current-clamp mode. RESULTS: Exposure to CCK (100 nM-5 µM) decreased the amplitudes of pacemaker potentials and depolarized resting membrane potentials. To identify the type of CCK receptors involved in ICCs, we examined the effects of CCK agonists and found that the addition of CCK1 agonist (A-71323, 1 µM) depolarized resting membrane potentials, whereas exposure to CCK2 agonist (gastrin, 1 µM) had no effect on pacemaker potentials. To confirm these results, we examined the effects of CCK antagonists and found that pretreatment with CCK1 antagonist (SR 27897, 1 µM) blocked CCK-induced effects. However, pretreatment with CCK2 antagonist (LY 225910, 1 µM) did not. Furthermore, intracellular GDPßS suppressed CCK-induced effects. To investigate the involvements of phospholipase C (PLC), protein kinase C (PKC), and protein kinase A (PKA) in the effects of CCK in cultured ICCs, we used U-73122 (an active PLC inhibitor), chelerythrine (a PKC inhibitor), SQ-22536 (an inhibitor of adenylate cyclase), or mPKAI (an inhibitor of myristoylated PKA). All inhibitors blocked the CCK-mediated effects on pacemaker potentials. In addition, we found that transient receptor potential classical 5 (TRPC5) channel was involved in CCK-activated currents in cultured ICCs. CONCLUSION: These results suggest that the CCK induced depolarization of pacemaking activity occurs in a G-protein-, PLC-, PKC-, and PKA-dependent manner via CCK1 receptor and TRPC5 channel is a candidate for CCK-activated currents in cultured ICCs in murine small intestine. Therefore, the ICCs are targets for CCK and their interaction can affect intestinal motility.

Effects of Lizhong Tang on cultured mouse small intestine interstitial cells of Cajal.

AIM: To investigate the effects of Lizhong Tang, an herbal product used in traditional Chinese medicine, on mouse small intestine interstitial cells of Cajal (ICCs). METHODS: Enzymatic digestions were used to dissociate ICCs from mouse small intestine tissues. The ICCs were morphologically distinct from other cell types in culture and were identified using phase contrast microscopy after verification with anti c-kit antibody. A whole-cell patch-clamp configuration was used to record potentials (current clamp) from cultured ICCs. All of the experiments were performed at 30-32 °C. RESULTS: ICCs generated pacemaker potentials, and Lizhong Tang produced membrane depolarization in current-clamp mode. The application of flufenamic acid (a nonselective cation channel blocker) abolished the generation of pacemaker potentials by Lizhong Tang. Pretreatment with thapsigargin (a Ca²âº-ATPase inhibitor in the endoplasmic reticulum) also abolished the generation of pacemaker potentials by Lizhong Tang. However, pacemaker potentials were completely abolished in the presence of an external Ca²âº-free solution, and under this condition, Lizhong Tang induced membrane depolarizations. Furthermore, When GDP-ß-S (1 mmol/L) was in the pipette solution, Lizhong Tang still induced membrane depolarizations. In addition, membrane depolarizations were not inhibited by chelerythrine or calphostin C, which are protein kinase C inhibitors, but were inhibited by U-73122, an active phospholipase C inhibitors. CONCLUSION: These results suggest that Lizhong Tang might affect gastrointestinal motility by modulating pacemaker activity in interstitial cells of Cajal.

Effects of histamine on cultured interstitial cells of cajal in murine small intestine.

Interstitial cells of Cajal (ICCs) are the pacemaker cells in the gastrointestinal tract, and histamine is known to regulate neuronal activity, control vascular tone, alter endothelial permeability, and modulate gastric acid secretion. However, the action mechanisms of histamine in mouse small intestinal ICCs have not been previously investigated, and thus, in the present study, we investigated the effects of histamine on mouse small intestinal ICCs, and sought to identify the receptors involved. Enzymatic digestions were used to dissociate ICCs from small intestines, and the whole-cell patch-clamp configuration was used to record potentials (in current clamp mode) from cultured ICCs. Histamine was found to depolarize resting membrane potentials concentration dependently, and whereas 2-PEA (a selective H1 receptor agonist) induced membrane depolarizations, Dimaprit (a selective H2-agonist), R-alpha-methylhistamine (R-alpha-MeHa; a selective H3-agonist), and 4-methylhistamine (4-MH; a selective H4-agonist) did not. Pretreatment with Ca(2+)-free solution or thapsigargin (a Ca(2+)-ATPase inhibitor in endoplasmic reticulum) abolished the generation of pacemaker potentials and suppressed histamine-induced membrane depolarization. Furthermore, treatments with U-73122 (a phospholipase C inhibitor) or 5-fluoro-2-indolyl des-chlorohalopemide (FIPI; a phospholipase D inhibitor) blocked histamine-induced membrane depolarizations in ICCs. On the other hand, KT5720 (a protein kinase A inhibitor) did not block histamine-induced membrane depolarization. These results suggest that histamine modulates pacemaker potentials through H1 receptor-mediated pathways via external Ca(2+) influx and Ca(2+) release from internal stores in a PLC and PLD dependent manner.

Modulation of pacemaker potentials by pyungwi-san in interstitial cells of cajal from murine small intestine: pyungwi-san and interstitial cells of cajal.

OBJECTIVE: Pyungwi-san (PWS) plays a role in a number of physiologic and pharmacologic functions in many organs. Interstitial cells of Cajal (ICCs) are pacemaker cells that generate slow waves in the gastrointestinal (GI) tract. We aimed to investigate the beneficial effects of PWS in mouse small-intestinal ICCs. METHODS: Enzymatic digestion was used to dissociate ICCs from the small intestine of a mouse. The wholecell patch-clamp configuration was used to record membrane potentials from the cultured ICCs. RESULTS: ICCs generated pacemaker potentials in the GI tract. PWS produced membrane depolarization in the current clamp mode. Pretreatment with a Ca(2+) -free solution and a thapsigargin, a Ca(2+) -ATPase, inhibitor in the endoplasmic reticulum, eliminated the generation of pacemaker potentials. However, only when the thapsigargin was applied in a bath solution, the membrane depolarization was not produced by PWS. Furthermore, the membrane depolarizations due to PWS were inhibited not by U-73122, an active phospholipase C inhibitor, but by chelerythrine and calphostin C, protein kinase C inhibitors. CONCLUSIONS: These results suggest that PWS might affect GI motility by modulating the pacemaker activity in the ICCs.

Digestive system-related pathophysiological symptoms of Sasang typology: Systematic review.

The purpose of this study was to review clinical studies on digestive system-related pathophysiological symptoms of each Sasang type to obtain the generalizable typespecific clinical features, which are important for the diagnosis of the Sasang type and subsequent disease treatment. Sasang typology and digestive system symptom-related keywords were used to search through eight domestic and foreign databases up to March 2012. The results were organized and analyzed based on four categories [digestive function, appetite, eating pattern, and body mass index (BMI)] to elucidate type-specific symptoms. Sasang type-specific digestive system-related symptoms were identified by reviewing 30 related articles that were gathered by searching through the databases. The Tae-Eum (TE) type had the highest digestive functions and the So-Eum (SE) type had the lowest. The TE type appeared to have larger volume with fast eating speed compared with the SE type and individuals in the TE category preferred fatty or salty food, which is responsible for the high occurrence rates of organic digestive diseases such as gastritis. Moreover, BMI was higher in the TE type and lower in the SE type. We systematically reviewed previously published clinical reports on digestive functions, which can be used to meet the objective of Sasang-type differentiation and pathophysiological pattern identification.

Involvement of Na(+)-leak channel in substance P-induced depolarization of pacemaking activity in interstitial cells of Cajal.

Interstitial cells of Cajal (ICCs) are the pacemaking cells in the gastrointestinal muscles that generate the rhythmic oscillations in membrane potential known as slow waves. ICCs also mediate or transduce inputs from the enteric nervous system. Substance P (SubP) is a member of the family of mammalian tachykinin peptides that are predominantly released by enteric neurons. This study assessed the relationship of Na(+)-leak channel (NALCN) in the SubP-induced depolarization in pacemaking activity in the gastrointestinal tract. The patch-clamp technique for whole-cell recording was used in cultured cluster and single ICCs. Electrophysiological and pharmacological properties of SubP in ICC pacemaking activity were similar to those of NALCN. Reverse-transcription polymerase chain reaction, Western blotting, and immunohistochemistry all showed abundant and localized expression of NALCN messenger RNA and protein in mouse small intestine. NALCN is involved in the SubP-induced depolarization of intestinal pacemaking activity. The protein is a potential target for pharmacological treatment of motor disorders of the gut.

Effects of ginsenoside on pacemaker potentials of cultured interstitial cells of Cajal clusters from the small intestine of mice.

Ginsenoside, one of the active ingredients of Panax ginseng, has a variety of physiological and pharmacological actions in various organs. However, little is known about the effects of ginsenosides on gastrointestinal (GI) motility. We studied the modulation of pacemaker potentials by ginsenoside in the interstitial cells of Cajal (ICCs) using the whole-cell patch clamp technique in the current clamp mode. Among ginsenosides, we investigated the effects of ginsenoside Rb1, Rg3 and Rf. While externally applied Rb1 and Rg3 had no effects on pacemaker potentials, Rf caused membrane depolarization. The application of flufenamic acid or niflumic acid abolished the generation of pacemaker potentials and inhibited the Rf-induced membrane depolarization. Membrane depolarization induced by Rf was not inhibited by intracellular application of guanosine 5'-[ß-thio]diphosphate trilithium salt. Pretreatment with a Ca(2+)-free solution, thapsigargin, a Ca(2+)-ATPase inhibitor of the endoplasmic reticulum, U-73122, a phospholipase C inhibitor, or 2-APB, an IP3 receptor inhibitor, abolished the generation of pacemaker potentials and suppressed Rfinduced actions. However, treatment with chelerythrine and calphostin C, protein kinase C inhibitors, did not block Rf-induced effects on pacemaker potentials. These results suggest that ginsenoside Rf modulates the pacemaker activities of ICCs and thereby regulates intestinal motility.

The role of transient receptor potential channel blockers in human gastric cancer cell viability.

Transient receptor potential cation channel, subfamily M, receptor 7 (TRPM7) is a ubiquitous divalent-selective ion channel with its own kinase domain. Human gastric cancer cells express the TRPM7 channel, and the presence of this channel is essential for cell survival. Recent studies have suggested that 5-lipoxygenase (5-LOX) inhibitors are potent blockers of the TRPM7 channels. The aim of this study was to show the effects of 5-LOX inhibitors on the growth and survival of gastric cancer cells. Among 5-LOX inhibitors, nordihydroguaiaretic acid (NDGA), 2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone (AA861), and 3-[1-(p-chlorobenzyl)-5-(isopropyl)-3-tert-butylthioindol-2-yl]-2,2-dimethylpropanoic acid (MK886) were potent blockers of TRPM7-like currents in gastric cancer cells and also induced cell death. However, zileuton was ineffective in suppressing TRPM7-like current activity and inducing cell death. Moreover, a specific transient receptor potential cation channel, subfamily C, member 3 (TRPC3) inhibitor, a pyrazole compound (Pyr3), and a specific melastatin TRP (TRPM4) inhibitor, 9-phenanthrol, did not affect TRPM7-like currents or induce cell death. We conclude that TRPM7 has an important role in the growth and survival of gastric cancer cells and a likely potential target for the pharmacological treatment of gastric cancer.

Effects of sophorae radix on human gastric and colorectal adenocarcinoma cells: sophorae radix and cancer cells.

The purpose of this study was to investigate the anti-cancer effects of Sophorae Radix (SR) and doxorubicin (DOX) in human gastric and colorectal adenocarcinoma cells. We used the human gastric and colorectal adenocarcinoma cell lines (MKN-45 and WIDR cells, respectively). We examined cell death by using the MTT(3-[4, 5-dimethylthiazol-2-yl]-2, 5- diphenyltetrazolium bromide) assay and the caspase 3 assay with SR. To examine the inhibitory effects of SR, we performed a cell cycle (sub G1) analysis for the MKN-45 and WIDR cells after three days with SR. The reversibility of SR was examined for one-day to five-day treatments with SR. SR inhibited the growth of MKN-45 and WIDR cells in a dosedependent manner. Also, we showed that SR induced apoptosis in MKN-45 and WIDR cells by using the MTT assay, the caspase 3 assay and the sub-G1 analysis. SR combined with DOX markedly inhibited the growth of MKN-45 and WIDR cells compared to SR or DOX alone. After 3 days of treating MKN-45 and WIDR cells with SR, the fraction of cells in the sub-G1 phase was much higher than that of the control group. Our findings provide insights into unraveling the effects of SR on human gastric and colorectal adenocarcinoma cells and into developing therapeutic agents for use against gastric and colorectal adenocarcinomas.

Effects of imatinib mesylate in interstitial cells of Cajal from murine small intestine.

The interstitial cells of Cajal (ICCs) are pacemakers in the gastrointestinal tract. The possibility of whether imatinib mesylate, a Kit receptor tyrosine kinase inhibitor, modulates pacemaker activities in the ICC was examined using the whole cell patch clamp technique. Imatinib decreased the amplitude of pacemaker potentials in a dose-dependent manner in current-clamp mode. Because the effects of imatinib on pacemaker potentials were the same as those of pinacidil, we examined the effect of glibenclamide on ICC exposed to imatinib. The effects of imatinib on pacemaker potentials were blocked by glibenclamide. To see whether the production of prostaglandins (PGs) is involved in the inhibitory effect of imatinib on pacemaker potentials, we tested the effects of naproxen (a non-selective cyclooxygenase inhibitor) and AH6809 (a prostaglandin EP1 and EP2 receptor antagonist). Naproxen and AH6809 blocked the inhibitory effects of imatinib on ICC. Butaprost (an EP2 receptor agonist) showed the actions on pacemaker potentials in the same manner as imatinib. However, SC 19220 (an EP1 receptor antagonist) has no effects. To investigate the involvement of cAMP and protein kinase A (PKA) in the effects of imatinib on ICC, SQ 22536 (an inhibitor of adenylate cyclase) and mPKAI (an inhibitor of myristoylated PKA) were used. Both SQ-22536 and mPKAI blocked the imatinib-mediated inhibition of pacemaker potentials. However, the protein kinase C (PKC) inhibitors did not block the imatinib-mediated inhibition of pacemaker potentials. These results indicate that imatinib inhibits the pacemaker potentials of ICC by activating ATP-sensitive K(+) channels and PKA-dependent, PKC-independent manner.

Psychological profile of sasang typology: a systematic review.

A systematic review of studies related to the psychological characteristics of Sasang types was conducted with the goal of delineating generalizable psychological profiles based on Sasang typology, a traditional Korean medical typology with medical herbs and acupuncture that is characterized as personalized medicine. Journal articles pertaining to Sasang typology were collected using five electronic database systems in Korea and in the USA. As a result, 64 potentially relevant studies were identified and 21 peer-reviewed research articles that employed psychometric inventories were included. Beginning with the use of the Minnesota Multiphasic Personality Inventory in 1992, Myers-Briggs Type Indicator, NEO-Personality Inventory, Temperament and Character Inventory and other personality assessment tools were employed in the identified studies. Because data synthesis could not be carried out due to the heterogeneity of the studies, the present review article sought to delineate the mutual relevance of the studies based on research results pertaining to the correlation between the aforementioned psychological assessment instruments. Results of the review indicate that two super-factors, Extraversion and Neuroticism, serve as the foundation in regards to delineating personality constructs, such that the So-Yang type scored high on the Extraversion dimension and low on the Neuroticism dimension, while the So-Eum type scored low on the Extraversion dimension and high on the Neuroticism dimension. The present systematic review indicates that Sasang typology shares similarities with the Western psychological tradition.

Analysis of skin humidity variation between sasang types.

The purpose of this study was to examine the relationship between variations in skin humidity (SH) induced by perspiration across Sasang types and to identify novel and effective Sasang classification factors. We also analyzed the responses of each Sasang type to sweating-related QSCC II items. The results revealed a significant difference in SH across gender and significant differences in SH before and after perspiration between Tae-Eum and So-Eum men. In addition, Tae-Eum women showed significant differences in SH compared with women classified as another Sasang type. Furthermore, evaluation of the items related to sweating in the QSCC II and their relationship to each constitution revealed a significant difference between Tae-Eum and other Sasang types. Overall, the results of this study indicate that there is a distinct SH difference following perspiration between Tae-Eum and other Sasang types. Such findings may aid in Sasang typology diagnostic testing with the support of further sophisticated clinical studies.