The main function of interstitial cells of Cajal (ICCs) is to regulate gastrointestinal peristalsis by acting as a \"pacemaker\" cell by generating spontaneous slow electrical waves. In 2005, electron microscopy revealed a cell type similar to ICCs (ICC-like) outside the gastrointestinal tract, with contractile activity and c-Kit+ immunohistochemistry shared with ICCs. Among the locations where ICC-like cells have been observed, it is in the uterus where they have a significant functional and pathophysiological role. These cells are involved in obstetric phenomena of contractile action, such as ascending sperm transport, embryo implantation, pregnancy, delivery, and the expulsion of menstrual debris. Within the pathophysiology related to these cells, we find obstetric alterations such as recurrent miscarriages, premature deliveries, abolition of uterine contractions, and failures of embryo implantation, in addition to other common conditions in the fertile age, such as endometriosis and leiomyoma.

Allergic contact dermatitis (ACD) is an occupation-dependent skin disease that afflicts humans with recurrent, non-specific episodes. Telocyte (TC) is a novel interstitial cell discovered in recent years and, together with fibroblasts, constitutes the predominant interstitial cell population in the skin. The purpose of this study was to investigate the morphodynamic changes of interstitial cells, especially TCs, in the skin during the development and treatment of ACD by histological and microscopic scientific methods. Hematoxylin-eosin staining, Masson staining, immunohistochemistry (IHC), immunofluorescence (IF), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) were used to track morphodynamic changes in interstitial cells during the development and treatment in the ACD-involved skin induced by 2,4-dinitrochlorobenzene (DNCB). The results demonstrated that TCs were mainly present around dermal collagen fibers, perivascular (except dermal papillary vascular loop), and skin appendages, which expressed CD34+, Vimentin+, PDGFR-α+, and α-SMA-. The absence of TCs during ACD development and after ACD recovery causes dermal interstitial cell dysregulation. The special anatomical relationships between TCs, immune cells, and follicular stem cells were also revealed, suggesting their potential dermatitis-regulating function. In a nutshell, our results provide morphodynamic evidence for the process of ACD development and recovery and offer potential cytological ideas for ACD treatment.

In traditional Korean medicine, the 16-herb concoction Bojanggunbi-tang (BGT) is used to treat various gastrointestinal (GI) diseases. In this study, we investigated the regulatory mechanism underlying the influence of BGT on the interstitial cells of Cajal (ICCs), pacemaker cells in the GI tract. Within 12 h of culturing ICCs in the small intestines of mice, the pacemaker potential of ICCs was recorded through an electrophysiological method. An increase in the BGT concentration induced depolarization and decreased firing frequency. This reaction was suppressed by cholinergic receptor muscarinic 3 (CHRM3) antagonists, as well as 5-hydroxytryptamine receptor (5HTR) 3 and 4 antagonists. Nonselective cation channel inhibitors, such as thapsigargin and flufenamic acid, along with protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) inhibitors, also suppressed the BGT reaction. Guanylate cyclase and protein kinase G (PKG) antagonists inhibited BGT, but adenylate cyclase and protein kinase A antagonists had no effect. In conclusion, we demonstrated that BGT acts through CHRM3, 5HTR3, and 5HTR4 to regulate intracellular Ca2+ concentrations and the PKC, MAPK, guanylate cycle, and PKG signaling pathways.

UNASSIGNED: This study aims to study the variation in the expression of CD117-positive interstitial cells of Cajal-like cells (ICC-LC) across the upper urinary tract region in children presenting with pelvic-ureteric junction obstruction (PUJO) and its association with renal functional and sonological parameters of patients.
UNASSIGNED: A prospective observational study was done on 20 children with congenital PUJO who underwent dismembered pyeloplasty. All children underwent renal sonography (anteroposterior pelvic diameter [APPD], pelvicalyceal ratio [P/C ratio], Mid polar renal parenchymal diameter [MPPD]) and functional imaging scan (LLEC scan or DTPA scan). Three specimens were taken intraoperatively from above PUJ, at the level of PUJ, and below PUJ. Those were examined immunohistochemically using CD117 to count ICC-LC using standard criteria. Variation in the expression of CD117-positive ICC-LC was correlated with the abovestated parameters.
UNASSIGNED: The number of CD117-positive ICC-LC showed a continuous decreasing trend above downward. P/C ratio and APPD showed a parallel trend with ICC-LC distribution, whereas split renal function (SRF) showed an inverse relationship with the expression of ICC-LC. Children with lesser severity of obstruction (APPD <30 mm and SRF >40%) showed a uniform decreasing trend in the number of CD117-positive ICC-LC across PUJ. Children with more severe obstruction (APPD >30 mm and SRF <40%) showed a decrease in the expression of ICC-LC up to the level of PUJO followed by a sudden relatively increased expression of ICC-LC below the obstruction.
UNASSIGNED: The expression of ICC-LC shows a uniformly decreasing trend across obstruction when the severity of obstruction is less. Resurgence in the number of ICC-LC below PUJ in subjects with severe obstruction hints at the emergence of a new pacemaker area below severely blocked PUJ akin to that seen in complete heart block patients and deserves early attention.

BACKGROUND: Banxia Xiexin Decoction (BXD) is a traditional Chinese medical formula applied to gastrointestinal (GI) motility disorders. Previous studies showed that miR-451-5p was down-regulated in rats with GI motility disorders induced by gastric electrical dysrhythmia. Interstitial cells of Cajal (ICCs) are pacemakers for GI motility, while loss of ICCs is responsible for GI motility disturbance. Thus, the underlying interaction mechanisms for BXD regulating ICCs apoptosis via miR-451-5p remain to be explored.
OBJECTIVE: In this work, the main objectives were to examine the efficacy of BXD on ICCs via miR-451-5p both in GI motility disorders rats model and in vitro, as well as the potential contributions of SCF/c-kit signaling.
METHODS: Rats with gastric electrical dysrhythmia were established in male SD rats by using a single-day diet and a double fasting method (drinking diluted hydrochloric acid water during the period) for 4 weeks. The gastric slow wave (GSW) recording, RT-qPCR, and western blot were performed to examine the effects of BXD on ICCs apoptosis in rats with GED and miR-451-5p expression. In vitro assays included CCK-8, flow cytometry analysis, RT-qPCR, and western blot were applied to investigate the potential molecular mechanism of BXD on ICCs apoptosis via miR-451-5p.
RESULTS: BXD promoted gastric motility, reduced ICCs apoptosis, and elevated miR-451-5p in GED rats. In addition, miR-451-5p was significantly up-regulated in ICCs after BXD treatment compared with that in ICCs with miR-451-5p inhibitor transfection. Meanwhile, high miR-451-5p expression with either BXD treatment or miRNA mimics enhanced ICCs proliferation and inhibit apoptosis. Moreover, overexpression of miR-451-5p can reverse G0/G1 arrest in ICCs by BXD treatment. Further, SCF and c-kit protein levels were detected to demonstrate that modulation of miR-451-5p by BXD treatment was involved in this signaling.
CONCLUSIONS: Through this study, we demonstrated that BXD could promote ICCs proliferation and inhibit apoptosis via miR-451-5p and may involve the modulations of SCF/c-kit signaling, thus suggesting a new therapy basis for GI motility dysfunction from the perspective of modulation of ICCs apoptosis by targeting miR-451-5p.

BACKGROUND: Interstitial cells of Cajal (ICC) are widely distributed in human gastrointestinal (GI) tract, especially in the layer of muscularis externa between neurons and smooth muscles. They play a very important role of coordination of GI tract motility. The aims of this research were to study the morphology and distribution of ICC in the muscularis externa of the GI tract, using immunohistochemistry staining methods, to determine the distribution of immune reactivity of anoctamin 1 (Ano1) compared with c-Kit, and to determine if Ano1 is a reliable marker for ICC in human GI tract.
METHODS: Specimens from the wall of stomach, small intestine, and colon were taken from human cadavers and processed for histological and immunohistochemical study using c-Kit and Ano1 primary antibodies.
RESULTS: Interstitial cells of Cajal appeared as bipolar cells, not forming network, in both the circular and longitudinal muscle layers, while in the myenteric area they appeared as multipolar interconnected cells. They were unevenly distributed in and between the muscle layers of the muscularis externa of human GI tract. They were more numerous in the stomach followed by the colon then the small intestine, and more numerous in the myenteric area followed by the circular muscle layer then the longitudinal muscle layer, in the three organs. Our results also showed that Ano1 is a more reliable marker for human ICC than c-Kit.
CONCLUSIONS: Interstitial cells of Cajal differed in morphology and were unevenly distributed between muscle layers of muscularis externa and between different parts of human GI tract.

Gastric distension is known to affect normal slow-wave activity and gastric function, but links between slow-wave dysrhythmias and stomach function are poorly understood. Low-resolution mapping is unable to capture complex spatial properties of gastric dysrhythmias, necessitating the use of high-resolution mapping techniques. Characterizing the nature of these dysrhythmias has implications in the understanding of postprandial function and the development of new mapping devices. In this two-phase study, we developed and implemented a protocol for measuring electrophysiological responses to gastric distension in porcine experiments. In vivo, serosal high-resolution electrical mapping (256 electrodes; 36 cm2) was performed in anaesthetized pigs (n = 11), and slow-wave pattern, velocity, frequency, and amplitude were quantified before, during, and after intragastric distension. Phase I experiments (n = 6) focused on developing and refining the distension mapping methods using a surgically inserted intragastric balloon, with a variety of balloon types and distension protocols. Phase II experiments (n = 5) used barostat-controlled 500-mL isovolumetric distensions of an endoscopically introduced intragastric balloon. Dysrhythmias were consistently induced in all five gastric distensions, using refined distension protocols. Dysrhythmias appeared 23 s (SD = 5 s) after the distension and lasted 129 s (SD = 72 s), which consisted of ectopic propagation originating from the greater curvature in the region of distension. In summary, our results suggest that distension disrupts gastric entrainment, inducing temporary ectopic slow-wave propagation. These results may influence the understanding of the postprandial stomach and electrophysiological effects of gastric interventions.NEW & NOTEWORTHY This study presents the discovery of temporary dysrhythmic ectopic pacemakers in the distal stomach caused by localized gastric distension. Distension-induced dysrhythmias are an interesting physiological phenomenon that can inform the design of new interventional and electrophysiological protocols for both research and the clinic. The observation of distension-induced dysrhythmias also contributes to our understanding of stretch-sensitivity in the gut and may play an important role in normal and abnormal postprandial physiology.

Minimally invasive therapies for obesity are a bridge between lifestyle interventions and bariatric surgery. We developed a novel device to reduce weight gain rate and evaluated its safety and efficacy in juvenile pigs.
The intragastric satiety-inducing device (ISD) comprises a self-expandable esophageal metal stent connected to a star-shaped disc placed in the stomach fundus. Eight juvenile pigs were randomized into ISD (n = 5) and control (n = 3) groups. Body weight and serum ghrelin hormone were monitored weekly for 6 weeks. One pig was followed up for 4 additional weeks (rebound pig) after ISD removal. Histological examination and immunohistochemistry for the interstitial cells of Cajal (ICCs) were performed.
ISD placement was successful in all pigs. Two ISDs (40%) migrated at 4 and 5 weeks after placement. Weight gain rates were significantly lower in the ISD group than in the control group from week 1 to 6 but were higher in the rebound pig than in a control pig from week 7 to 10. Mean ghrelin hormone level was higher in the control group than in the ISD group from week 1 to 6. ISD induced reversible inflammatory changes in the esophagus and stomach fundus. The number of ICCs was lesser in ISD pigs than in control and rebound pigs.
ISD placement is feasible and safe in juvenile pigs. It decreases weight gain rate but induces reversible inflammatory reaction and tissue hyperplasia. Its mechanism may be related to pressure exertion on the stomach fundus or gastric motility alteration.

OBJECTIVE: In this study, we reviewed GISTs with all morphological and immunohistochemical findings and assessed the prognostic parameters of these tumors.
METHODS: Files of 40 cases with GIST operated between 2002 and 2008 were retrospectively examined in this study. Patients were grouped as patients with and without recurrence within postop 1 year. The patients were grouped based on their localization, gender and age. The cases were stratified as the risk grades based on risk categorization table developed by Fletcher et al. according to the tumor diameter and number of mitoses. The cases were immunohistochemically investigated for CD117, CD34, S100, and Ki-67.
RESULTS: Male/female ratio was 25/15. The mean age was 61.55. Mean tumor diameters were statistically significantly higher in the recurrence (+) group than in the recurrence (-) group (p=0.048). The mean number of mitoses was statistically significantly higher in the recurrence (+) group than in the recurrence (-) group (p=0.038). No statistically significant difference was found in histological distribution of the recurrence (-) and recurrence (+) groups (p=0.8795). No statistically significant difference was found in CD34, S100, and Ki-67 distribution of the recurrence (-) and recurrence (+) groups (p=0.862, p=0.609, and p=0.023, respectively). All patients in the recurrence (+) group were in the high-risk group.
CONCLUSIONS: GISTs are studied in a wide range from benign, incidental tumors to malignant tumors with the risk for recurrence and metastasis concerning biological behaviour. GISTs have prognostic parameters, such as tumor localization, tumor diameter, mitotic index, cellularity, and pleomorphism grade.

Human urine-derived stem cells (hUSCs) show multipotential differentiation ability and can differentiate into mesodermal cell lineages. Interstitial cells of Cajal-like cells (ICC-LCs) are crucial for the pace-making function of spontaneous contraction in the bladder. However, the mechanisms by which hUSCs generate ICC-LCs have not been elucidated. In this study, we developed a strategy for directional differentiation of hUSCs into ICC-LCs. hUSCs were transfected with lentiviral vectors encoding c-Kit, stem cell factor (SCF), hyperpolarization activated cyclic nucleotide gated potassium channel 4 (HCN4), and 5-azacytidine induced 2 (AZI2) genes, and the cells were cultured for an additional 7 days in specific medium. The expression of the surface marker c-Kit on ICC-LCs was determined at 7 days after transfection. hUSCs were successfully expanded and transfected with the four lentiviral vectors. hUSCs transfected with lentiviral-c-Kit, lentiviral-HCN4, and lentiviral-AZI2 showed higher expression of c-Kit 7 days after transfection, but only the lentiviral-HCN4-transfected cells showed morphological alterations in ICC-LCs. These cells also displayed visible HCN current amplitude and density. This approach may provide a new strategy for the treatment of underactive bladder.