Muscle Motility Research Articles

Orbital emphysema and medial orbital wall fracture after nose-blowing: a case report and review of literature

Nose-blowing is commonly known as the harmless act of expelling nasal mucus by exhaling forcefully through the nose. We report a case of orbital emphysema in a 49-year-old female patient, who suffered from fractures of the medial orbital wall after forcefully blowing her nose. The patient presented to our emergency department with acute right sided periorbital swelling and pain as well as an unremarkable endoscopic examination of the nose. Prior to the event, a common cold with signs of acute sinusitis had been reported. A trauma to the eye was credibly denied, which is consistent with the medical imaging pattern. A CT-scan confirmed the diagnosis and showed air trapped into the orbit as well as multiple fractures of the lamina papyracea with displaced bone fragments. Visual acuity and extraocular muscle motility were intact. The patient was treated conservatively with prophylactic antibiotics and was instructed not to blow her nose. Follow-up examination after seven days showed a complete remission.

Immunohistochemical characterization of interstitial cells and their spatial relationship to motor neurons within the mouse esophagus.

Interstitial cells of Cajal (ICC) and PDGFRα+ cells regulate smooth muscle motility in the gastrointestinal (GI) tract, yet their function in the esophagus remains unknown. The mouse esophagus has been described as primarily skeletal muscle; however, ICC have been identified in this region. This study characterizes the distribution of skeletal and smooth muscle cells (SMCs) and their spatial relationship to ICC, PDGFRα+ cells, and intramuscular motor neurons in the mouse esophagus. SMCs occupied approximately 30% of the distal esophagus, but their density declined in more proximal regions. Similarly, ANO1+ intramuscular ICC (ICC-IM) were distributed along the esophagus, with density decreasing proximally. While ICC-IM wereclosely associated with SMCs, they were also present in regions of skeletal muscle. Intramuscular, submucosal, and myenteric PDGFRα+ cells were densely distributed throughout the esophagus, yet only intramuscular PDGFRα+ cells in the lower esophageal sphincter (LES) and distal esophagus expressed SK3. ICC-IM and PDGFRα+ cells were closely associated with intramuscular nNOS+, VIP+, VAChT+, and TH+ neurons and GFAP+ cells resembling intramuscular enteric glia. These findings suggest that ICC-IM and PDGFRα+ cells may have roles in regulating esophageal motility due to their close proximity to each other and to skeletal muscle and SMCs, although further functional studies are needed to explore their role in this region. The mixed muscular composition and presence of interstitial cells in the mouse distal esophagus is anatomically similar to the transitional zone found in the human esophagus, and therefore, motility studies in the mouse may be translatable to humans.

Effects of live transport methods on the survivability, physiological responses, and flesh quality of turbot (Scophthalmus maximus)

AbstractWaterless transport is an alternative method for live aquatic products. However, the changes that occur in the fish body after transportation are not known. Herein, the effects of different transport methods on quality of turbot (Scophthalmus maximus) were investigated. Fish were divided into four groups: Group A (water, 17°C), Group B (waterless, 3°C), Group C (water, 3°C), and Group D (control, 17°C). In the case of 100% survival, the maximum transport time was 40 h for Group A, 55 h for Group B, and 90 h for Group C. Both crude protein and crude fat decreased significantly (p < 0.05) in the treatment groups compared with the control group. Compared with control group, lactic dehydrogenase (LDH), lactic acid (LA), and serum cortisol (COR) increased significantly (p < 0.05) in all treatment groups. After fish recovered, LDH, LA, and COR values were all significantly (p < 0.05) lower than their corresponding non‐recovered group. Compared with the control group, the expression of proteins related to muscle motility and stress capacity both decreased in the low‐temperature, waterless group. Together, obvious damage may occur to flesh quality, liver, and heart of turbot when the transport time is >40 h, regardless of the transport method.

Outcomes of inferior oblique muscle myectomy with tucking into Tenon’s capsule, cohort prospective study

ABSTRACT Background: Inferior oblique muscle overaction (IOOA) is a prevalent ocular muscle motility disorder. This study aimed to investigate the outcomes and impact of IO muscle myectomy with and without tucking the proximal end of the muscle into Tenon’s capsule in two surgical groups as a treatment for IOOA. Methods: Randomized cohort study that involves two surgical groups. A total of 33 patients (55 eyes). Patients were randomly divided into two groups: first group underwent myectomy without tucking the proximal end of the muscle, whereas the second group underwent myectomy with tucking of the proximal end of the muscle. Each patient had four visits. During each visit, each patient had a comprehensive ophthalmic examination. Surgical success was defined as IOOA grade range of 0 to + 1 and correction of hypertropia in primary gaze. Results: The median age was 6 years. Sixteen (48.5%) patients underwent IO muscle myectomy with tucking, while 17 (51.5%) had an IO myectomy without tucking. Both the tucking and without tucking groups showed reductions in the angles of deviations, but there was no significant difference between the groups at baseline or postoperatively at 6 months. The success rate was 92.85% for the tucking group and 92.59% for the without tucking group. Conclusion: The study suggests that both surgical techniques are effective in correcting IOOA and associated HT, without any clear benefits of the addition of tucking. Ultimately, the two surgical techniques are equally effective, and the choice of surgical technique remains a personal preference of the surgeon.

The Posterior Insular Cortex is Necessary for Feeding-Induced Jejunal Myoelectrical Activity in Male Rats

The gastrointestinal tract exhibits coordinated muscle motility in response to food digestion, which is regulated by the central nervous system through autonomic control. The insular cortex is one of the brain regions that may regulate the muscle motility. In this study, we examined whether, and how, the insular cortex, especially the posterior part, regulates gastrointestinal motility by recording jejunal myoelectrical signals in response to feeding in freely moving male rats. Feeding was found to induce increases in jejunal myoelectrical signal amplitudes. This increase in the jejunal myoelectrical signals was abolished by vagotomy and pharmacological inhibition of the posterior insular cortex. Additionally, feeding induced a decrease and increase in sympathetic and parasympathetic nervous activities, respectively, both of which were eliminated by posterior insular cortical inhibition. These results suggest that the posterior insular cortex regulates jejunal motility in response to feeding by modulating autonomic tone.

Immunohistochemical characterization of interstitial cells and their relationship to motor neurons within the mouse esophagus.

Interstitial cells of Cajal (ICC) and PDGFRα+ cells regulate smooth muscle motility in the gastrointestinal (GI) tract. However, their role(s) in esophageal motility are still unclear. The mouse esophagus has traditionally been described as almost entirely skeletal muscle in nature though ICC have been identified along its entire length. The current study evaluated the distribution of skeletal and smooth muscle within the esophagus using a mouse selectively expressing eGFP in smooth muscle cells (SMCs). The relationship of SMCs to ICC and PDGFRα+ cells was also examined. SMCs declined in density in the oral direction however SMCs represented ~ 25% of the area in the distal esophagus suggesting a likeness to the transition zone observed in humans. ANO1+ intramuscular ICC (ICC-IM) were distributed along the length of the esophagus though like SMCs, declined proximally. ICC-IM were closely associated with SMCs but were also found in regions devoid of SMCs. Intramuscular and submucosal PDGFRα+ cells were densely distributed throughout the esophagus though only intramuscular PDGFRα+ cells within the LES and distal esophagus highly expressed SK3. ICC-IM and PDGFRα+ cells were closely associated with nNOS+, VIP+, VAChT+ and TH+ neurons throughout the LES and distal esophagus. GFAP+ cells resembling intramuscular enteric glia were observed within the muscle and were closely associated with ICC-IM and PDGFRα+ cells, occupying a similar location to c. These data suggest that the mouse esophagus is more similar to the human than thought previously and thus set the foundation for future functional and molecular studies using transgenic mice.

Epidemiology of thyroid-stimulating immunoglobulin in recent-onset symptomatic thyroid eye disease.

This study aims to report correlations between thyroid-stimulating immunoglobulin (TSI) and both clinical and radiological parameters in recent-onset symptomatic thyroid eye disease (TED) patients. A prospective cohort study of TED patients managed at the Chinese University of Hong Kong from January 2014 to May 2022. Serum TSI levels were determined with the functional assay. Outcomes included the Clinical Activity Score (CAS), marginal reflex distance1 (MRD1), extraocular muscle motility restriction (EOMy), exophthalmos, and diplopia. The radiological assessment included cross-sectional areas and signal of extraocular muscles on STIR-sequence MRI. A total of 255 (197 female) treatment-naive patients, with an average onset age of 50 ± 14 years (mean ± s.d.), were included. Elevated pre-treatment TSI level was observed in 223 (88%) patients. There was a weak positive correlation between TSI and CAS (r = 0.28, P = 0.000031), MRD1 (r = 0.17, P = 0.0080), and the size of the levator palpebrae superioris/superior rectus complex (r = 0.25, P = 0.018). No significant correlation existed between TSI and STIR signals. The AUC and optimal cut-off value for clinical active TED were 0.67 (95% CI: 0.60-0.75) and 284% (specificity: 50%, sensitivity: 85%). In total, 64 patients received intravenous methylprednisolone (IVMP) during the study interval, and they had a higher baseline TSI level than those who did not have IVMP (P = 0.000044). Serial post-IVMP TSI among the 62 patients showed a significant reduction compared to the baseline level (P < 0.001). Both the baseline and post-IVMP TSI levels, and percentages of TSI changes were comparable between patients who responded and did not respond to the first course of IVMP. TSI can be a serum biomarker for the diagnosis, prognosis, and treatment response of TED. Further validation should be warranted.

Orbital radiotherapy with combined intravenous methylprednisolone and mycophenolate mofetil in moderate-to-severe thyroid eye disease

PurposeTo report the clinical outcomes of orbital radiotherapy (ORT) with combined intravenous methylprednisolone (IVMP) and mycophenolate mofetil (MMF) in thyroid eye disease (TED) patients with restrictive myopathy. DesignProspective comparative case series of patients managed at The Chinese University of Hong Kong from 2015 to 2021. MethodsThe primary outcome was the change in Gorman diplopia score at 52 weeks. Secondary outcomes were the changes in extraocular muscle motility (EOMy), area of extraocular muscle (EOM) on MRI, exophthalmos, and marginal reflex distance (MRD) 1 and MRD2 at 52 weeks. ResultsA total of 40 (29 females) TED patients, medium age 56 years, were treated with the double regimen: combined IVMP and MMF (17) or triple regimen: IVMP, MMF, and ORT (23). The triple group has a higher age (P = 0.028). Sex, smoking history, thyroid, and pre-treatment orbital status were comparable between the 2 groups. EOMy improved more after the triple regimen(P = 0.026). Nine patients from the triple group showed a significant reduction in the size of the inferior rectus (both eyes: P < 0.05), while five from the double group showed no significant reduction of any EOM on MRI. The improvement of CAS, diplopia score, exophthalmos, MRD1, and MRD2 were similar. No patient reported any severe or organ-threatening side effects from IVMP, MMF, or ORT requiring discontinuation of treatment. ConclusionThe triple regimen demonstrates better structural and functional outcomes in TED-related restrictive myopathy. Future randomized clinical trials are warranted to clarify the adjuvant role of ORT in this specific indication of TED management.

Cerium Oxide Nanozymes Improve Skeletal Muscle Function in Gestational Diabetic Offspring by Attenuating Mitochondrial Oxidative Stress.

Gestational diabetes mellitus (GDM) is a significant complication during pregnancy that results in abnormalities in the function of multiple systems in the offspring, which include skeletal muscle dysfunction and reduced systemic metabolic capacity. One of the primary causes behind this intergenerational effect is the presence of mitochondrial dysfunction and oxidative stress in the skeletal muscle of the offspring due to exposure to a high-glucose environment in utero. Cerium oxide (CeO2) nanozymes are antioxidant agents with polymerase activity that have been widely used in the treatment of inflammatory and aging diseases. In this study, we synthesized ultrasmall particle size CeO2 nanozymes and applied them in GDM mouse offspring. The CeO2 nanozymes demonstrated an ability to increase insulin sensitivity and enhance skeletal muscle motility in GDM offspring by improving mitochondrial activity, increasing mitochondrial ATP synthesis function, and restoring abnormal mitochondrial morphology. Furthermore, at the cellular level, CeO2 nanozymes could ameliorate metabolic dysregulation and decrease cell differentiation in adult muscle cells induced by hyperglycemic stimuli. This was achieved through the elimination of endogenous reactive oxygen species (ROS) and an improvement in mitochondrial oxidative respiration function. In conclusion, CeO2 nanozymes play a crucial role in preserving muscle function and maintaining the metabolic stability of organisms. Consequently, they serve to reverse the negative effects of GDM on skeletal muscle physiology in the offspring.

Novel 18-norspirostane steroidal saponins: Extending lifespan and mitigating neurodegeneration through promotion of mitophagy and mitochondrial biogenesis in Caenorhabditis elegans

Pharmacological strategies to delay aging and combat age-related diseases are increasingly promising. This study explores the anti-aging and therapeutic effects of two novel 18-norspirostane steroidal saponins from Trillium tschonoskii Maxim, namely deoxytrillenoside CA (DTCA) and epitrillenoside CA (ETCA), using Caenorhabditis elegans (C. elegans). Both DTCA and ETCA significantly extended the lifespan of wild-type N2 worms and improved various age-related phenotypes, including muscle health, motility, pumping rate, and lipofuscin accumulation. Furthermore, these compounds exhibited notable alleviation of pathology associated with Parkinson's disease (PD) and Huntington's disease (HD), such as the reduction of α-synuclein and poly40 aggregates, improvement in motor deficits, and mitigation of neuronal damage. Meanwhile, DTCA and ETCA improved the lifespan and healthspan of PD- and HD-like C. elegans models. Additionally, DTCA and ETCA enhanced the resilience of C. elegans against heat and oxidative stress challenges. Mechanistic studies elucidated that DTCA and ETCA induced mitophagy and promoted mitochondrial biogenesis in C. elegans, while genetic mutations or RNAi knockdown affecting mitophagy and mitochondrial biogenesis effectively eliminated their capacity to extend lifespan and reduce pathological protein aggregates. Together, these compelling findings highlight the potential of DTCA and ETCA as promising therapeutic interventions for delaying aging and preventing age-related diseases.

Esophageal anatomy and physiology vary across spastic and non-spastic phenotypes of disorders of esophagogastric junction outflow.

Pathophysiologic mechanisms of disorders of esophagogastric junction (EGJ) outflow are poorly understood. We aimed to compare anatomic and physiologic characteristics among patients with disorders of EGJ outflow and normal motility. We retrospectively evaluated adult patients with achalasia types 1, 2, 3, EGJ outflow obstruction (EGJOO) or normal motility on high-resolution manometry who underwent endoscopic ultrasound (EUS) from January 2019 to August 2022. Thickened circular muscle was defined as ≥1.6 mm. Characteristics from barium esophagram (BE) and functional lumen imaging probe (FLIP) were additionally assessed. Of 71 patients (mean age 56.2 years; 49% male), there were 8 (11%) normal motility, 58 (82%) had achalasia (5 (7%) type 1, 32 (45%) classic type 2, 21 (30%) type 3 [including 12 type 2 with FEPs]), and 7 (7%) had EGJOO. A significantly greater proportion of type 3 achalasia had thickened distal circular muscle (76.2%) versus normal motility (0%; p < 0.001) or type 2 achalasia (25%; p < 0.001). Type 1 achalasia had significantly wider mean maximum esophageal diameter on BE (57.8 mm) compared to type 2 achalasia (32.8 mm), type 3 achalasia (23.4 mm), EGJOO (15.9 mm), and normal motility (13.5 mm). 100% type 3 achalasia versus 0% type 1 achalasia/normal motility had tertiary contractions on BE. Mean EGJ distensibility index on FLIP was lower for type 3 achalasia (1.2 mmHg/mm2 ) and EGJOO (1.2 mmHg/mm2 ) versus type 2 (2.3 mmHg/mm2 ) and type 1 achalasia (2.9 mmHg/mm2 ). Our findings suggest distinct pathologic pathways may exist: type 3 achalasia and EGJOO may represent a spastic outflow phenotype consisting of a thickened, spastic circular muscle, which is distinct from type 1 and 2 achalasia consisting of a thin caliber circular muscle layer with more prominent esophageal dilation.

Age-dependent effects of the β3 adrenoceptor agonist CL316,243 on human and rat detrusor muscle strips

Motility of detrusor smooth muscle includes adrenergic relaxation and cholinergic contraction. Since the latter may be deregulated in overactive bladder (OAB) pathophysiology, anticholinergics are the standard therapy but occasionally less tolerated due to side effects such as dry mouth and constipation. β3 adrenoceptor agonists also alleviate OAB symptoms by relaxing the detrusor muscle. Their age dependence, however, is far from understood. To address this issue, we induced contractions with KCl (60 mM) and carbachol (from 10 nM to 100 μM) in the presence of the β3 adrenoceptor agonist CL316,243 (from 0.1 to 10 μM) in both human and rat muscle strips. Our results confirmed that both contractions were attenuated by β3 adrenoceptor activation in both species, but with differing age dependence. In humans, specimens from mid-life subjects showed a significantly more pronounced effect of CL316,243 in attenuating carbachol-induced contractions than those from aged subjects (Cohen’s d of maximal attenuation: 1.82 in mid-life versus 0.13 in aged) without altering EC50. Conversely, attenuation of KCl responses by CL316,243 increased during ageing (Spearman correlation coefficient = -0.584, P<0.01). In rats, both KCl- and carbachol-induced contractions were significantly more attenuated by CL316,243 in samples from adolescent as compared to aged samples. Immunohistochemistry in human detrusor sections proved β3 adrenoreceptor abundance to remain unaltered during ageing. In conclusion, our findings suggest differential age-dependent changes in human β3 adrenoceptor-dependent attenuation of detrusor contraction in terms of electromechanical versus pharmacomechanical coupling; they may help understand the differential responsiveness of OAB patients to β3 agents.

Teprotumumab and Orbital Decompression for the Management of Proptosis in Patients With Thyroid Eye Disease.

To compare outcomes of patients with thyroid eye disease treated with teprotumumab or orbital decompression, or both in sequence. Patients with thyroid eye disease and treated with decompression, teprotumumab, or both were included. Four groups were defined: decompression only, teprotumumab only, teprotumumab first with decompression later, and decompression first with teprotumumab later. The primary outcome was change in exophthalmometry. Secondary outcomes included change in extraocular muscle motility, strabismus, diplopia, and side effects. One hundred and thirty-nine patients were included. The mean duration for early follow-up was 1.2 months for both decompression and teprotumumab groups. The mean late follow-up was 14.4 and 8.2 months for the decompression and teprotumumab groups respectively. Mean change in exophthalmometry was significantly greater for the decompression group (3.5 mm) compared with teprotumumab (2.0 mm) at late follow-up. Improvement in total extraocular muscle restriction was significantly greater in the teprotumumab group (14.7 degrees) than in the decompression group (2.6 degrees). The teprotumumab group had a significantly higher percentage of patients with diplopia score >1 at baseline and late follow-up ( p < 0.01) compared with the decompression group. Additional treatment with teprotumumab or decompression when previously treated with the opposite had similar proptosis reduction effect as that therapy alone. Surgical decompression has a greater proptosis reduction effect than teprotumumab, whereas teprotumumab better improves extraocular muscle motility. The addition of teprotumumab or decompression to a previous course of the opposite adds a similar effect to the supplemental treatment alone.

Orbital Trapdoor Fracture With Extraocular Muscle Entrapment in Adults: A Case Series.

To report adult patients with an orbital trapdoor fracture with extraocular muscle entrapment. We retrospectively reviewed 566 adult patients (>18 years) with a pure orbital fracture who were referred to us from January 2016 to May 2023. The following data were collected: age, sex, affected side, causes of injury, concomitant ocular injury and nasal bone fracture, presence or absence of oculocardiac reflex and infraorbital nerve hypesthesia, period from injury to surgery, follow-up period, and pre- and postoperative limitation of extraocular muscle motility and fields of a binocular single vision. We found 5 patients (0.9%) with an orbital trapdoor fracture with extraocular muscle entrapment (age range, 19-47 years; all males; 2 right and 3 left). Causes of injury included performing a bench press, fall, assault, boxing, and bicycle accident. Entrapment of the inferior and medial recti muscles was seen in 2 and 3 patients, respectively. None of the patients had any sign of oculocardiac reflex. After surgical reduction, the field of binocular single vision became normal in 3 patients and was incompletely recovered in 2 patients, in whom consultation with us was delayed. Adults with extraocular muscle entrapment may not present with an oculocardiac reflex. Urgent release of an entrapped muscle is, however, still recommended to avoid permanent limitation of extraocular muscle motility.

Mural Serum Response Factor (SRF) Deficiency Provides Insights into Retinal Vascular Functionality and Development.

Serum response factor (SRF) controls the expression of muscle contraction and motility genes in mural cells (MCs) of the vasculature. In the retina, MC-SRF is important for correct angiogenesis during development and the continuing maintenance of the vascular tone. The purpose of this study was to provide further insights into the effects of MC SRF deficiency on the vasculature and function of the mature retina in SrfiMCKO mice that carry a MC-specific deletion of Srf. Retinal morphology and vascular integrity were analyzed in vivo via scanning laser ophthalmoscopy (SLO), angiography, and optical coherence tomography (OCT). Retinal function was evaluated with full-field electroretinography (ERG). We found that retinal blood vessels of these mutants exhibited different degrees of morphological and functional alterations. With increasing severity, we found vascular bulging, the formation of arteriovenous (AV) anastomoses, and ultimately, a retinal detachment (RD). The associated irregular retinal blood pressure and flow distribution eventually induced hypoxia, indicated by a negative ERG waveform shape. Further, the high frequency of interocular differences in the phenotype of individual SrfiMCKO mice points to a secondary nature of these developments far downstream of the genetic defect and rather dependent on the local retinal context.

Efficacy and Safety of 6-Weekly versus 12-Weekly Intravenous Methylprednisolone in Moderate-to-Severe Active Thyroid-Associated Ophthalmopathy.

To compare the efficacy and safety of 6-weekly and 12-weekly intravenous methylprednisolone (IVMP) regimens in moderate-to-severe, active thyroid-associated orbitopathy (TAO) patients. Retrospective comparative study of patients who received IVMP between January 2011 and July 2021 at the Thyroid Eye Clinic, the Chinese University of Hong Kong. Outcome measures included the 7-item clinical activity score (CAS), exophthalmos, extraocular muscle motility (EOMy), marginal reflex distance (MRD), best corrected visual acuity (BCVA), intraocular pressure (IOP), the requirement of additional treatment, and complications. A total of 65 (63% (41/65) females) moderate-to-severe, active TAO patients aged 50 ± 13 (25-74) years received 6-weekly (n = 22) or 12-weekly (n = 43) IVMP. Sex, age, smoking status, and Graves' disease status were comparable in the two groups (all p > 0.05). CAS at week 6 (p = 0.0279), 12 (p = 0.00228), and 52 (p = 0.0228) were lower at each time for the 12-weekly group. Exophthalmos improved more at week 6 (p = 0.0453) and 12 (p = 0.0347) in the 12-weekly group. The improvement of diplopia, MRD1, MRD2, and EOMy were comparable between the two groups. More patients in the 6-weekly group (p = 0.00169) required additional treatments including IVMP+/-ORT. Patients in the 6-weekly group who did not require additional treatment had a lower presenting CAS (p = 0.0193) than those who required additional treatment. The total numbers of adverse events were comparable between the two groups.

Slow myosin heavy chain 1 is required for slow myofibril and muscle fibre growth but not for myofibril initiation

Slow myosin heavy chain 1 (Smyhc1) is the major sarcomeric myosin driving early contraction by slow skeletal muscle fibres in zebrafish. New mutant alleles lacking a functional smyhc1 gene move poorly, but recover motility as the later-formed fast muscle fibres of the segmental myotomes mature, and are adult viable. By motility analysis and inhibiting fast muscle contraction pharmacologically, we show that a slow muscle motility defect persists in mutants until about 1 month of age. Breeding onto a genetic background marking slow muscle fibres with EGFP revealed that mutant slow fibres undergo terminal differentiation, migration and fibre formation indistinguishable from wild type but fail to generate large myofibrils and maintain cellular orientation and attachments. In mutants, initial myofibrillar structures with 1.67 ​μm periodic actin bands fail to mature into the 1.96 ​μm sarcomeres observed in wild type, despite the presence of alternative myosin heavy chain molecules. The poorly-contractile mutant slow muscle cells generate numerous cytoplasmic organelles, but fail to grow and bundle myofibrils or to increase in cytoplasmic volume despite passive movements imposed by fast muscle. The data show that both slow myofibril maturation and cellular volume increase depend on the function of a specific myosin isoform and suggest that appropriate force production regulates muscle fibre growth.

Flavonoids in Amomum tsaoko Crevost et Lemarie Ameliorate Loperamide-Induced Constipation in Mice by Regulating Gut Microbiota and Related Metabolites.

Amomum tsaoko (AT) is a dietary botanical with laxative properties; however, the active ingredients and mechanisms are still unclear. The active fraction of AT aqueous extract (ATAE) for promoting defecation in slow transit constipation mice is the ethanol-soluble part (ATES). The total flavonoids of ATES (ATTF) were the main active component. ATTF significantly increased the abundance of Lactobacillus and Bacillus and reduced the dominant commensals, such as Lachnospiraceae, thereby changing the gut microbiota structure and composition. Meanwhile, ATTF changed the gut metabolites mainly enriched in pathways such as the serotonergic synapse. In addition, ATTF increased the serum serotonin (5-HT) content and mRNA expression of 5-hydroxytryptamine receptor 2A (5-HT2A), Phospholipase A2 (PLA2), and Cyclooxygenase-2 (COX2), which are involved in the serotonergic synaptic pathway. ATTF increased Transient receptor potential A1 (TRPA1), which promotes the release of 5-HT, and Myosin light chain 3(MLC3), which promotes smooth muscle motility. Notably, we established a network between gut microbiota, gut metabolites, and host parameters. The dominant gut microbiota Lactobacillus and Bacillus, prostaglandin J2 (PGJ2) and laxative phenotypes showed the most significant associations. The above results suggest that ATTF may relieve constipation by regulating the gut microbiota and serotonergic synaptic pathway and has great potential for laxative drug development in the future.

Case Report on Achalasia Cardia

Motor dysphagia has a number of frequent causes, including achalasia. The failure of the lower esophageal sphincter to relax results in achalasia, a condition of esophageal smooth muscle motility. The gastroesophageal junction becomes functionally blocked as a result of this disease. The actual pathophysiology of this disorder is still unknown, despite the fact that the disease was originally recorded more than 300 years ago. Loss of the inhibitory ganglion in the myenteric plexus of the oesophagus can be the pathophysiological aetiology of achalasia cardia. In the esophageal myenteric plexus, there is a loss of inhibitory neurons that produce VIP and nitric oxide synthase, but in extreme situations, it also affects cholinergic neurons. Despite numerous possibilities being put forth, the specific cause of this deterioration remains unknown. The autoimmune phenomenon, viral infection, and genetic predisposition are some of these hypotheses. Read more...

Motor Dysfunction of Gastric Antral Smooth Muscle in Diabetic Rats: Contribution of ATP-Dependent Potassium Channels.

The goal of the current research was to further elucidate the role of adenosine triphosphate (ATP)-sensitive potassium (KATP) channels in the motility and contractility force of gastric smooth muscle of diabetic rats. Male Wistar rats (190-230 g) were grouped into control and streptozotocin (STZ)-induced diabetes (55 mg/kg) rats. Thirty days later, gastric muscle contractility was measured using a myograph and a force transducer of antral segments immersed in a tissue bath. Gastric emptying response was measured through feeding of standard pellet. Furthermore, the expression of KATP channel subunits in antral smooth muscle was determined by western blot technique. The amplitude of KCl-evoked twitch contractions of diabetic antral strips was about 25% more than control (P < 0.05). Application of minoxidil, a KATP channel opener, dose dependently decreased the force of twitch contractions in both normal and diabetic antral strips. Application of 10 μM glibenclamide, a KATP channel blocker, did not antagonize the minoxidil-induced relaxation of antral strips. Diabetic gastric emptying was faster than normal, although not significant. Despite the relaxant effect of minoxidil on gastric emptying rate in normal rats (P < 0.05), this effect was not observed in diabetic rats. Also, glibenclamide increased gastric emptying and antagonized minoxidil-induced relaxation in normal rats (P < 0.05). Furthermore, the expression of KATP Kir6.1 and SUR2B subunits was substantially reduced in antral smooth muscle in diabetic condition (P < 0.01). These results propose that KATP channels may contribute to the development of gastric motility disorders in diabetes.