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Journal of Ethnopharmacology Apr 2024Dendrobium huoshanense C. Z. Tang et S. J. Cheng (DH) is a traditional medicinal herb with a long history of medicinal use. DH has been recorded as protecting the...
ETHNOPHARMACOLOGICAL RELEVANCE
Dendrobium huoshanense C. Z. Tang et S. J. Cheng (DH) is a traditional medicinal herb with a long history of medicinal use. DH has been recorded as protecting the gastrointestinal function. Modern pharmacology research shows that DH regulates intestinal flora, intestinal mucosal immunity, gastrointestinal peristalsis and secretion of digestive juices. At the same time, some studies have shown that DH has a good therapeutic effect on ulcerative colitis, but its mechanism of action has not been fully elucidated.
AIMS OF THIS STUDY
To investigate the mechanism and effect of Dendrobium huoshanense C. Z. Tang et S. J. Cheng (DH) in the treatment of ulcerative colitis (UC) by combining network pharmacology and in vivo experimental validation.
METHODS
A network pharmacology approach was used to perform component screening, target prediction, PPI network interaction analysis, GO and KEGG enrichment analysis to initially predict the mechanism of DH treatment for UC. Then, the mechanism was validated with the UC mouse model induced by 3% DSS.
RESULTS
Based on the network pharmacological analysis, a comprehensive of 101 active components were identified, with 19 of them potentially serving as the crucial elements in DH's effectiveness against UC treatment. Additionally, the study revealed 314 potential core therapeutic targets along with the top 5 key targets: SRC, STAT3, AKT1, HSP90AA1, and PIK3CA. In experiments conducted on live mice with UC, DH was found to decrease the levels of IL-6 and TNF-α in the blood, while increasing the levels of IL-10 and TGF-β. This led to notable improvements in colon length, injury severity, and an up-regulation of SRC, STAT3, HSP90AA1, PIK3CA, p-AKT1 and PI3K/AKT signaling pathway expression in the colon tissue.
CONCLUSIONS
In this study, the active components and main targets of DH for UC treatment were initially forecasted, and the potential mechanism was investigated through network pharmacology. These findings offer an experimental foundation for the clinical utilization of DH.
Topics: Animals; Mice; Colitis, Ulcerative; Dendrobium; Network Pharmacology; Phosphatidylinositol 3-Kinases; Class I Phosphatidylinositol 3-Kinases; Drugs, Chinese Herbal; Molecular Docking Simulation
PubMed: 38190953
DOI: 10.1016/j.jep.2024.117729 -
Cureus Dec 2023Patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), a mitochondrial disease, develop various types of organ failure,...
Improvement of Intestinal Pseudo-Obstruction by Total Parenteral Nutrition in a Young Woman With Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-Like Episodes: A Case Report.
Patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), a mitochondrial disease, develop various types of organ failure, including intestinal pseudo-obstruction (IPO). We treated a patient with IPO that improved with total parenteral nutrition. A 20-year-old woman with a two-year history of diabetes mellitus was taking sitagliptin but her hemoglobin A1c (HbA1c) levels began increasing. After receiving metformin, she suffered a stroke-like attack and was diagnosed with MELAS. After persistent anorexia, she presented with symptoms of IPO, such as vomiting and gastrointestinal dilatation. After about 10 days of total parenteral nutrition, intestinal peristalsis improved and bowel movements resumed. She was able to resume her normal diet, and glycemic control with insulin glargine has allowed her to return to her daily life without gastrointestinal symptoms for over six months. Total parenteral nutrition may be effective for MELAS with IPO, and good glycemic control can prevent the need for incretin-related drugs, thus reducing the likelihood of recurrent IPO.
PubMed: 38186459
DOI: 10.7759/cureus.50075 -
Science Advances Jan 2024Biologic drugs hold immense promise for medical treatments, but their oral delivery remains a daunting challenge due to the harsh digestive environment and restricted...
Biologic drugs hold immense promise for medical treatments, but their oral delivery remains a daunting challenge due to the harsh digestive environment and restricted gastrointestinal absorption. Here, inspired by the porcupinefish's ability to inflate itself and deploy its spines for defense, we proposed an intestinal microneedle robot designed to absorb intestinal fluids for rapid inflation and inject drug-loaded microneedles into the insensate intestinal wall for drug delivery. Upon reaching the equilibrium volume, the microneedle robot leverages rhythmic peristaltic contraction for mucosa penetration. The robot's barbed microneedles can then detach from its body during peristaltic relaxation and retain in the mucosa for drug releasing. Extensive in vivo experiments involving 14 minipigs confirmed the effectiveness of the intestinal peristalsis for microrobot actuation and demonstrated comparable insulin delivery efficacy to subcutaneous injection. The ingestible peristalsis-actuated microneedle robots may transform the oral administration of biologic drugs that primary relies on parenteral injection currently.
Topics: Animals; Swine; Peristalsis; Biological Products; Robotics; Swine, Miniature; Digestion
PubMed: 38181085
DOI: 10.1126/sciadv.adj7067 -
Biochemical Society Transactions Feb 2024The enteric nervous system (ENS) is a complex series of interconnected neurons and glia that reside within and along the entire length of the gastrointestinal tract. ENS... (Review)
Review
The enteric nervous system (ENS) is a complex series of interconnected neurons and glia that reside within and along the entire length of the gastrointestinal tract. ENS functions are vital to gut homeostasis and digestion, including local control of peristalsis, water balance, and intestinal cell barrier function. How the ENS develops during embryological development is a topic of great concern, as defects in ENS development can result in various diseases, the most common being Hirschsprung disease, in which variable regions of the infant gut lack ENS, with the distal colon most affected. Deciphering how the ENS forms from its progenitor cells, enteric neural crest cells, is an active area of research across various animal models. The vertebrate animal model, zebrafish, has been increasingly leveraged to understand early ENS formation, and over the past 20 years has contributed to our knowledge of the genetic regulation that underlies enteric development. In this review, I summarize our knowledge regarding the genetic regulation of zebrafish enteric neuronal development, and based on the most current literature, present a gene regulatory network inferred to underlie its construction. I also provide perspectives on areas for future zebrafish ENS research.
Topics: Animals; Humans; Zebrafish; Enteric Nervous System; Neurons; Neurogenesis; Gene Expression Regulation, Developmental
PubMed: 38174765
DOI: 10.1042/BST20230343 -
Journal of Neurogastroenterology and... Jan 2024This study aims to evaluate the effects of acute codeine administration on primary and secondary esophageal peristalsis in patients with ineffective esophageal motility...
BACKGROUND/AIMS
This study aims to evaluate the effects of acute codeine administration on primary and secondary esophageal peristalsis in patients with ineffective esophageal motility (IEM).
METHODS
Eighteen IEM patients (8 women; mean age 37.8 years, range 23-64 years) were enrolled in the study. The patients underwent high-resolution manometry exams, consisting of 10 single wet swallows, multiple rapid swallows, and ten 20 mL rapid air injections to trigger secondary peristalsis. All participants completed 2 separate sessions, including acute administration of codeine (60 mg) and placebo, in a randomized order.
RESULTS
Codeine significantly increased the distal contractile integral (566 ± 81 mmHg∙s∙cm vs 247 ± 36 mmHg∙s∙cm, = 0.001) and shortened distal latency (5.7 ± 0.2 seconds vs 6.5 ± 0.1 seconds, < 0.001) for primary peristalsis compared with these parameters after placebo treatment. The mean total break length decreased significantly after codeine treatment compared with the length after placebo ( = 0.003). Codeine significantly increased esophagogastric junction-contractile integral ( = 0.028) but did not change the 4-second integrated relaxation pressure ( = 0.794). Codeine significantly decreased the frequency of weak ( = 0.039) and failed contractions ( = 0.009), resulting in increased frequency of normal primary peristalsis ( < 0.136). No significant differences in the ratio of impaired multiple rapid swallows inhibition and parameters of secondary peristalsis were detected.
CONCLUSIONS
In IEM patients, acute administration of codeine increases contraction vigor and reduces distal latency of primary esophageal peristalsis, but has no effect on secondary peristalsis. Future studies are required to further elucidate clinical relevance of these findings, especially in the setting of gastroesophageal reflux disease with IEM.
PubMed: 38173157
DOI: 10.5056/jnm22131 -
Cureus Dec 2023Rectal duplication is a rare congenital anomaly with many clinical presentations, being mostly asymptomatic. Treatment consists of a surgical approach with a good...
Rectal duplication is a rare congenital anomaly with many clinical presentations, being mostly asymptomatic. Treatment consists of a surgical approach with a good prognosis. We are reporting a case of a full-term female newborn who presented with a mass externalized through the sacral region. The first diagnostic hypothesis was meningomyelocele, but the neurosurgeon verified peristalsis on examination with a surgical microscope. The pediatric surgery team proceeded with the investigation with barium enema, anal electrostimulation, biopsy, and pelvis MRI, confirming presacral rectal duplication. The patient underwent surgery for posterior sagittal surgical excision, with satisfactory evolution. Cases of rectal duplication are rare and we are unaware of reports of its exteriorization through the sacral region. Such presentation may mimic other diagnoses and should be included in the differential diagnosis of meningomyelocele.
PubMed: 38161530
DOI: 10.7759/cureus.51306 -
Frontiers in Pediatrics 2023To explore the expression and clinical implications of protease activated receptors (PARs) in the pathogenesis of children with ureteropelvic junction obstruction (UPJO).
OBJECTIVE
To explore the expression and clinical implications of protease activated receptors (PARs) in the pathogenesis of children with ureteropelvic junction obstruction (UPJO).
MATERIAL AND METHODS
Immunohistochemistry was employed to investigate the distribution of PARs in both normal human ureteropelvic junction (UPJ) and cases of UPJO. Furthermore, PAR gene expression levels were assessed using real-time PCR (RT-PCR), and the patients in the UPJO group were stratified according to the Onen grading system. Subsequently, the clinical implications of PARs in UPJO were explored through RT-PCR analysis.
RESULTS
Immunofluorescence showed robust PAR2 expression in the control group compared with the UPJO group. The results of RT-PCR analysis revealed a significant decrease in the relative mRNA expression of PAR2 in the UPJO group compared to the control group. Notably, the relative RNA expression of PAR1 was significantly lower in the Onen-4 group compared to the control group. Furthermore, the relative mRNA expression of PAR2 exhibited a statistically significant difference among the Onen-3 group, Onen-4 group, and control group.
CONCLUSIONS
PARs are widely distributed throughout the SIP syncytium of the UPJ and play a role in maintaining smooth muscle cells (SMCs) membrane potential by interacting with interstitial cells of Cajal (ICCs), as well as platelet-derived growth factor receptor alpha-positive cells (PDGFR α+ cells). The decreased expression of PAR1 suggests a higher preoperative Onen grade in UPJO patients. Furthermore, the downregulation of PAR2 effects at the UPJ may be involved in the loss of inhibitory neuromuscular transmission, disrupting the rhythmic peristalsis of the UPJ.
PubMed: 38161438
DOI: 10.3389/fped.2023.1286786 -
Open Medicine (Warsaw, Poland) 2023Sepsis can impair gastrointestinal (GI) barrier integrity. Oral probiotics (PT) can maintain the balance of GI microflora and improve GI function. 5-Hydroxytryptamine...
Sepsis can impair gastrointestinal (GI) barrier integrity. Oral probiotics (PT) can maintain the balance of GI microflora and improve GI function. 5-Hydroxytryptamine (5-HT) is a key promoter of GI injury caused by sepsis. However, the mechanism by which PT attenuates sepsis by regulating 5-HT is not fully understood. In this study, C57BL6 mice were intragastric administrated with normal saline (NC) or PT once a day for 4 weeks before cecal ligation and puncture (CLP). Compared with NC-CLP mice, PT-CLP mice had lower clinical score, higher body temperature. The survival rate of PT-CLP mice was significantly improved. The levels of inflammatory cytokines and 5-HT were obviously decreased in PT-CLP mice, and GI peristalsis and barrier function were enhanced. Moreover, sepsis downregulated the expression of tight junction proteins, while PT pretreatment could maintain them at the level of sham operation group. Furthermore, PT pretreatment increased the expression of serotonin transporter and monoamine oxidase A. PT administration could inhibit NF-κB activity, and activate ERK activity. In conclusion, long-term supplementation of PT before CLP can prevent sepsis-induced GI mucosal barrier dysfunction in mice, which may be partially mediated by upregulating the 5-HT degradation pathway via activating ERK signaling.
PubMed: 38152336
DOI: 10.1515/med-2023-0869 -
Communications Biology Dec 2023Assessing gastrointestinal motility lacks simultaneous evaluation of intraluminal pressure (ILP), circular muscle (CM) and longitudinal muscle (LM) contraction, and...
Assessing gastrointestinal motility lacks simultaneous evaluation of intraluminal pressure (ILP), circular muscle (CM) and longitudinal muscle (LM) contraction, and lumen emptying. In this study, a sophisticated machine was developed that synchronized real-time recordings to quantify the intricate interplay between CM and LM contractions, and their timings for volume changes using high-resolution cameras with machine learning capability, the ILP using pressure transducers and droplet discharge (DD) using droplet counters. Results revealed four distinct phases, B, N, D, and A, distinguished by pressure wave amplitudes. Fluid filling impacted LM strength and contraction frequency initially, followed by CM contraction affecting ILP, volume, and the extent of anterograde, retrograde, and segmental contractions during these phases that result in short or long duration DD. This comprehensive analysis sheds light on peristalsis mechanisms, understand their sequence and how one parameter influenced the other, offering insights for managing peristalsis by regulating smooth muscle contractions.
Topics: Animals; Mice; Peristalsis; Gastrointestinal Motility; Muscle Contraction; Intestine, Small
PubMed: 38062160
DOI: 10.1038/s42003-023-05631-2 -
Journal of Family Medicine and Primary... Sep 2023Idiopathic achalasia is a common and well-recognized primary esophageal motility disorder with unknown etiology and is characterized by the abnormality of esophageal...
BACKGROUND
Idiopathic achalasia is a common and well-recognized primary esophageal motility disorder with unknown etiology and is characterized by the abnormality of esophageal body peristalsis associated with an impaired relaxation of the lower esophageal sphincter (LES). The aim of this study is to explore the correlation between and idiopathic achalasia.
METHODS
This study was conducted on 700 patients, with dysphagia, regurgitation, and non-cardiac chest pain (NCCP), who met our inclusion criteria. The mean ± SD age was 39.8 ± 11 (13-80 years), and 60% (420) of the participants were female. Of the participants, 108 had idiopathic achalasia and 105 were normal participants who were placed in the case and control groups, respectively. They were enrolled in the study based on high-resolution manometry. was confirmed by a histological study. In the biopsy, specimens were taken by esophagogastroduodenoscopy.
RESULTS
Our results revealed that 71.3% and 45% of the participants were positive in the case and control groups, respectively. The odds ratio (OR) was 3.3 (95% CI: 1.80-5.99, < 0.05), indicating a statistically significant association between infection and the group classification. The dominant presenting symptoms in achalasia were dysphagia (97.2%) and NCCP (80.5%), but regurgitation (65.7%) was a dominant symptom in the normal participants.
CONCLUSIONS AND INFERENCES
Diverse autoimmune and apoptotic phenomena induced by influence the pathogenesis of idiopathic achalasia, suggesting an underlying link between infection and idiopathic achalasia. This correlation should be confirmed by other clinical and experimental studies.
PubMed: 38024896
DOI: 10.4103/jfmpc.jfmpc_1815_22