UNASSIGNED: The significance of interstitial cells of Cajal (ICC) in the gastrointestinal tract has garnered increasing attention. In recent years, approximately 80 articles on ICC have been published annually in various journals. However, no bibliometric study has specifically focused on the literature related to ICC. Therefore, we conducted a comprehensive bibliometric analysis of ICC to reveal dynamic scientific developments, assisting researchers in exploring hotspots and emerging trends while gaining a global perspective.
UNASSIGNED: We conducted a literature search in the Web of Science Core Collection (WoSCC) from January 1, 2013, to December 31, 2023, to identify relevant literature on ICC. We employed bibliometric software, namely VOSviewer and CiteSpace, to analyze various aspects including annual publication output, collaborations, research hotspots, current status, and development trends in this domain.
UNASSIGNED: A total of 891 English papers were published in 359 journals by 928 institutions from 57 countries/regions. According to the keyword analysis of the literature, researchers mainly focused on \"c-Kit,\" \"expression,\" \"smooth muscle,\" and \"nitric oxide\" related to ICC over the past 11 years. However, with \"SIP syncytium,\" \"ANO1,\" \"enteric neurons,\" \"gastrointestinal stromal tumors (GIST),\" and \"functional dyspepsia (FD),\" there has been a growing interest in the relationship between ANO1, SIP syncytium, and ICC, as well as the role of ICC in the treatment of GIST and FD.
UNASSIGNED: Bibliometric analysis has revealed the current status of ICC research. The association between ANO1, SIP syncytium, enteric neurons and ICC, as well as the role of ICC in the treatment of GIST versus FD has become the focus of current research. However, further research and collaboration on a global scale are still needed. Our analysis is particularly valuable to researchers in gastroenterology, oncology, and cell biology, providing insights that can guide future research directions.

Constipation is common in the diseases of the digestive system in clinics. With the change in diet structure and the increase in life pressure, the prevalence rate increases year by year. In traditional Chinese medicine (TCM), the location of the disease of constipation is in the large intestine, which is related to the dysfunction of lung, spleen, liver, kidney and other viscera. Its pathogenesis is conductive dysfunction of large intestine. Based on the theory, Shouhui Tongbian Capsule (SHTB) is composed of eight traditional Chinese medicines, including Polygoni multiflori Radix (Heshouwu in Chinese), Aloe (Luhui in Chinese), Cassiae Semen (Juemingzi in Chinese), Ginseng Radix et Rhizoma (Renshen in Chinese), Lycii Fructus (Gouqizi in Chinese), Asini Corii Colla (Ejiao in Chinese), Aurantii Fructus Immaturus (Zhishi in Chinese), and Atractylodis Macrocephalae Rhizoma (Baizhu in Chinese), which could help to release excessive turbid, and nourishing yin and supplementing qi in the treatment. This study has been carried out to review the latest advances of SHTB in the treatment of constipation. The results showed that significant effect of SHTB was found in the treatment of constipation, such as functional constipation, and constipation associated with tumor chemotherapy, colitis, type 2 diabetes and chronic cardiac failure. Besides, obvious adverse reactions were not observed. SHTB could effectively treat five types of constipation, provide direction for the future exploration of SHTB in the treatment of other types of constipation.

Diabetic gastroparesis (DGP) is a common complication of diabetes mellitus, marked by gastrointestinal motility disorder, a delayed gastric emptying present in the absence of mechanical obstruction. Clinical manifestations include postprandial fullness and epigastric discomfort, bloating, nausea, and vomiting. DGP may significantly affect the quality of life and productivity of patients. Research on the relationship between gastrointestinal dynamics and DGP has received much attention because of the increasing prevalence of DGP. Gastrointestinal motility disorders are closely related to a variety of factors including the absence and destruction of interstitial cells of Cajal, abnormalities in the neuro-endocrine system and hormone levels. Therefore, this study will review recent literature on the mechanisms of DGP and gastrointestinal motility disorders as well as the development of prokinetic treatment of gastrointestinal motility disorders in order to give future research directions and identify treatment strategies for DGP.

Aurantii Fructus Immaturus total flavonoids (AFIF) is the main effective fraction extracted from AFI, which has a good effect on promoting gastrointestinal motility. This study aimed to investigate AFIF which regulates miR-5100 to improve constipation symptoms in mice by targeting Frizzled-2 (Fzd2) to alleviate interstitial cells of Cajal (ICCs) calcium ion balance and autophagy apoptosis. The constipated mouse model was induced by an antibiotic suspension, and then treated with AFIF. RNA-seq sequencing, luciferase assay, immunofluorescence staining, transmission electron microscopy, ELISA, flow cytometry, quantitative polymerase chain reaction (PCR), and Western blot were applied in this study. The results showed that AFIF improved constipation symptoms in antibiotic-induced constipated mice, and decreased the autophagy-related protein Beclin1 levels and the LC3-II/I ratio in ICCs. miR-5100 and its target gene Fzd2 were screened as key miRNAs and regulator associated with autophagy. Downregulation of miR-5100 caused increased expression of Fzd2, decreased proliferation activity of ICCs, increased apoptotic cells, and enhanced calcium ion release and autophagy signals. After AFIF treatment, miR-5100 expression was upregulated and Fzd2 was downregulated, while autophagy-related protein levels and calcium ion concentration decreased. Furthermore, AFIF increased the levels of SP, 5-HT, and VIP, and increased the expression of PGP9.5, Sy, and Cx43, which alleviated constipation by improving the integrity of the enteric nervous system network. In conclusion, AFIF could attenuate constipation symptoms by upregulating the expression of miR-5100 and targeting inhibition of Fzd2, alleviating calcium overload and autophagic death of ICCs, regulating the content of neurotransmitters, and enhancing the integrity of the enteric nervous system network.

BACKGROUND: Chaihu Shugan Powder (CHSGP) has significant clinical efficacy in the treatment of functional dyspepsia (FD), but the specific mechanism requires further study.
OBJECTIVE: The aim of this study was to investigate the therapeutic effect of CHSGP on FD rats and the underlying mechanism of the effect on interstitial cells of cajal (ICC) mitophagy.
METHODS: The tail-clamping stimulation method was utilized to establish an FD rat model in vivo. Gastric emptying rate and small intestinal propulsion rate test, H&E staining, and Immunohistochemistry were conducted to evaluate the therapeutic effects of CHSGP on FD rats. In vitro, the regulatory effect of CHSGP on CCCP-mediated ICC mitophagy was further investigated by CCK8, Transmission electron microscope, immunofluorescence co-staining, Quantitative polymerase chain reaction and Western blot to reveal the potential mechanisms of CHSGP inhibited ICC mitophagy.
RESULTS: Animal experiments provided evidence that CHSGP promoted gastric motility, increased ICC numbers, reduced Parkin expression, and elevated USP30 expression in FD rats. In vitro, further mechanism research demonstrated that CHSGP decreased LC3Ⅱ/LC3Ⅰ、PINK1、Parkin、PHB2 protein expression and increased USP30 protein expression. Furthermore, CHSGP increased Mfn2 protein expression by suppressing activation of the PINK1/Parkin pathway when USP30 is knocked down, consequently reducing CCCP-induced ICC mitophagy.
CONCLUSIONS: These results suggest that CHSGP may treat FD against CCCP-induced ICC mitophagy by the up-regulation of via PINK1/Parkin pathway.

[This corrects the article DOI: 10.3389/fphar.2022.864598.].

OBJECTIVE: Functional dyspepsia (FD) is one of the most common gastrointestinal diseases, with a global prevalence of 10%-30%. However, the specific pathogenesis of FD has not yet been determined. As such, the aim of this study was to investigate the effects of saikosaponin D (SSD) administration on the apoptosis, autophagy, and morphological structure of the intestinal cells of Cajal (ICCs) in FD.
METHODS: A rat model of FD was constructed by stimulating the rat tail with a sponge clamp at one-third of the distal tail length. An autophagy model was constructed for ICCs using glutamate. The apoptosis rate in each group of cells was determined using flow cytometry. The expressions of ghrelin and substance P (SP) were detected using ELISA.
RESULTS: The body weight and food intake of male and female rats in the SSD group were consistently higher than those in the model group. The SSD group showed substantial improvement compared with the model group, with no inflammatory cell infiltration and normal gastric mucosal structures. After intervention with SSD, the ultrastructure of the ICCs considerably improved and was clear. Compared with the model group, the expressions of LC3 I/II, ghrelin, and SP proteins in the SSD group were significantly upregulated, and the apoptosis rate was significantly reduced.
CONCLUSIONS: The administration of SSD improved ICC morphology and structure, inhibited excessive autophagy, and improved FD, a gastrointestinal motility disorder, by regulating ghrelin and SP levels.

BACKGROUND: Children with refractory constipation experience intense and persistent symptoms that greatly diminish their quality of life. However, the underlying pathophysiological mechanism responsible for this condition remains uncertain. Our objective was to evaluate characteristics of colonic motor patterns and interstitial cells of Cajal (ICCs) to refractory constipation children, as well as intestinal microbiota compositions.
METHODS: Colonic manometry (CM) was conducted on a cohort of 30 patients with refractory constipation to assess colonic motility, and 7 of them underwent full-thickness colon biopsy specimens. Another 5 colonic specimens from nonconstipation patients were collected to identify the ICCs by immunohistochemistry. Fecal samples from 14 children diagnosed with refractory constipation and subjecting 28 age-matched healthy children to analysis using high-throughput sequencing of 16S rRNA.
RESULTS: According to CM results, dividing 30 children with refractory constipation into 2 groups: normal group (n = 10) and dysmotility group (n = 20). Dysmotility subjects showed lower colonic motility. Antegrade propagating pressure waves, retrograde propagating pressure waves, and periodic colonic motor activity were common in normal subjects and rare in dysmotility subjects (32.7 ± 8.9 vs 20.7 ± 13.0/17 h, P < 0.05, 11.5 ± 2.3 vs 9.6 ± 2.3/17 h, P < 0.05, and 5.2 ± 8.9 vs 3.5 ± 6.8 cpm, P < 0.005, respectively), whereas periodic rectal motor activity was more common in dysmotility subjects (3.4 ± 4.8 vs 3.0 ± 3.1 cpm, P < 0.05). Dysmotility subjects exhibited a significantly greater number of preprandial simultaneous pressure waves compared to the normal subjects (32.3 ± 25.0 vs 23.6 ± 13.2/1 h, P < 0.005). Dysmotility subjects displayed a notable decrease in postprandial count of antegrade propagating pressure waves and high amplitude propagating pressure waves when compared to normal subjects (3.9 ± 2.9 vs 6.9 ± 3.5/1 h and 2.3 ± 1.5 vs 5.4 ± 2.9/1 h, respectively, P < 0.05). The number, distribution, and morphology of ICCs were markedly altered in refractory constipation compared children to the controls (P < 0.05). Children diagnosed with refractory constipation displayed a distinct dissimilarity in composition of their intestinal microbiota comparing with control group (P < 0.005). In genus level, Bacteroidetes represented 34.34% and 43.78% in the refractory constipation and control groups, respectively. Faecalibacterium accounted for 3.35% and 12.56%, respectively (P < 0.005). Furthermore, the relative abundances of Faecalibacterium (P < 0.005), Lachnospira (P < 0.05), and Haemophilus (P < 0.05) significantly decreased, whereas those of Parabacteroides (P < 0.05), Alistipes (P < 0.005), Prevotella_2 (P < 0.005), [Ruminococcus]_torques_group (P < 0.005), Barnesiella (P < 0.05), Ruminococcaceae_UCG-002 (P < 0.005), and Christensensenellaceae_R-7_group (P < 0.05) were markedly increased in children with refractory constipation.
CONCLUSIONS: Dysmotility subjects showed lower colonic motility and an impaired postprandial colonic response. The decreased number and abnormal morphology of colonic ICCs may contribute to the pathogenesis of refractory constipation. Children with refractory constipation exhibited significant variations in microbiota composition across various taxonomic levels compared to the healthy control group. Our findings contribute valuable insights into pathophysiological mechanism underlying refractory constipation and provide evidence to support the exploration of novel therapeutic strategies for affected children.

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.

Telocytes (TCs), a novel type of interstitial cells, are characterized by their smaller cellular body and extremely long, thin processes which are called telopodes (Tps). They have been described in multiple organs from diverse animals. Currently, the existence of TCs in rat pars distalis (PD) has remained unexplored. This investigation was undertaken to visualize the distribution and structural features of TCs in the PD using immunofluorescence (IF) and further validated by transmission electron microscopy (TEM). HE staining revealed the presence of interstitial cells in the peri-sinusoidal vessels spaces of the PD. Using IF, CD34/vimentin double-positive interstitial cells were identified as TCs in accordance with identification standards. TEM further verified the presence of TCs based on their unique ultrastructural features. TCs exhibited communication structures including cell connections and extracellular vesicles (EVs). Interestingly, TCs were in close proximity to the nerves. Most importantly, Tps extended toward the nerves, blood vessels, and glandular cells. TCs could be the structural foundation of a third regulatory system in rat PD according to the tight connections of TCs with sinusoid vessels, glandular cells, EVs and most crucially the nerves. Taken together, these morphological and structural findings demonstrate that TCs are vital components of the rat PD.