Motility Function Research Articles

Global asymptotic stability in a two-dimensional chemotaxis model arising from tumor invasion

This paper considers the chemotaxis model with density-suppressed motility: ut = ∇·(φ(v)∇u) + ∇·(ψ(v)u∇v) + f(u), vt = Δv + wz, wt = −wz, wt = −wz, zt = Δz − z + u, x ∈ Ω, t > 0 under homogeneous Neumann boundary conditions in a smooth bounded domain Ω⊂R2. Given that the positive motility function φ(v) has the lower-upper bound, we can conclude that the system possesses a unique bounded classical solution. Moreover, it is proved that the global bounded solution (u, v, w, z) will converge to r/μ1α−1,v̄0+w̄0,0,r/μ1α−1 as t → ∞.

Global solutions to a chemotaxis system with singular density-suppressed motility and superlinear consumption

In this paper, we consider a migration-consumption taxis system involving singular density-suppressed motility and superlinear consumption(⋆){ut=Δ(uϕ(v)),vt=Δv−uvm in a bounded smooth domain Ω⊂Rn(n≥2) with no-flux boundary conditions. Here, m≥1 is a constant. The motility function ϕ generalizes the singular prototype given by ϕ(ξ)=ξ−α(ξ>0) with α>0. In Tao and Winkler (2023) [32], Tao and Winkler studied the system (⋆) with m=1 and obtained respectively the global existence of very weak-strong and weak-strong solutions. We study the system (⋆) with m≥1 and prove that a so-called very weak-strong solution can be established for arbitrarily large initial data in W1,∞(Ω). Moreover, under the additional constraints of(⋆⋆)(6−n)α+2m(n+2)−(3n+2)>0, and with an additional assumption on ϕ′, the model (⋆) possesses a global weak-strong solution. In particular, when 2≤n≤5 and m=1, (⋆⋆) is equivalent to α>n−26−n, which consistent with the result of Tao and Winkler. However, our result contains the case n≥6. When n=6, (⋆⋆) is equivalent to m>54 without any requirement for α>0. When n>6, (⋆⋆) is equivalent to m>3n+22n+4 and 0<α<2m(n+2)−(3n+2)n−6.

UNC-45 assisted myosin folding depends on a conserved FX3HY motif implicated in Freeman Sheldon Syndrome

Myosin motors are critical for diverse motility functions, ranging from cytokinesis and endocytosis to muscle contraction. The UNC-45 chaperone controls myosin function mediating the folding, assembly, and degradation of the muscle protein. Here, we analyze the molecular mechanism of UNC-45 as a hub in myosin quality control. We show that UNC-45 forms discrete complexes with folded and unfolded myosin, forwarding them to downstream chaperones and E3 ligases. Structural analysis of a minimal chaperone:substrate complex reveals that UNC-45 binds to a conserved FX3HY motif in the myosin motor domain. Disrupting the observed interface by mutagenesis prevents myosin maturation leading to protein aggregation in vivo. We also show that a mutation in the FX3HY motif linked to the Freeman Sheldon Syndrome impairs UNC-45 assisted folding, reducing the level of functional myosin. These findings demonstrate that a faulty myosin quality control is a critical yet unexplored cause of human myopathies.

Genomic and single-cell analyses reveal genetic signatures of swimming pattern and diapause strategy in jellyfish

Jellyfish exhibit innovative swimming patterns that contribute to exploring the origins of animal locomotion. However, the genetic and cellular basis of these patterns remains unclear. Herein, we generated chromosome-level genome assemblies of two jellyfish species, Turritopsis rubra and Aurelia coerulea, which exhibit straight and free-swimming patterns, respectively. We observe positive selection of numerous genes involved in statolith formation, hair cell ciliogenesis, ciliary motility, and motor neuron function. The lineage-specific absence of otolith morphogenesis- and ciliary movement-related genes in T. rubra may be associated with homeostatic structural statocyst loss and straight swimming pattern. Notably, single-cell transcriptomic analyses covering key developmental stages reveal the enrichment of diapause-related genes in the cyst during reverse development, suggesting that the sustained diapause state favours the development of new polyps under favourable conditions. This study highlights the complex relationship between genetics, locomotion patterns and survival strategies in jellyfish, thereby providing valuable insights into the evolutionary lineages of movement and adaptation in the animal kingdom.

Distribution and ultrastructural characteristics of enteric glial cell in the chicken cecum

Enteric glial cell (EGC) is involved in neuroimmune regulation within the enteric nervous system (ENS); however, limited information exists on the distribution and ultrastructure of EGC in the poultry gut. We aim to investigate the morphological features and distribution of EGC in the chicken cecum. Here, we investigated the distribution and ultrastructural features of chicken cecum EGC using immunohistochemistry (IHC) and transmission electron microscopy (TEM). IHC showed that EGC was widely distributed throughout the chicken cecum. In the mucosal layer, EGC was morphologically irregular, with occasionally interconnecting protrusions that outlined signal-negative neurons. The morphology of EGC in the submucosal layer was also irregular. In the inner circular muscle layer and between the inner circular and outer longitudinal muscle layers, EGC aligned parallel to the circular muscle cells. A small number of EGC with an irregular morphology were found in the outer longitudinal muscle layer. In addition, in the submucosal and myenteric plexus, EGC were aggregated, and the protrusions of the immunoreactive cells interconnected to outline the bodies of nonreactive neurons. TEM-guided ultrastructural characterization confirmed the IHC findings that EGC were morphologically irregular and revealed they developed either a star, bipolar, or fibrous shape. The nucleus was also irregular, with electron-dense heterochromatin distributed in the center of the nucleus or on the nuclear membrane. The cytoplasm contained many glial filaments and vesicle-containing protrusions from neuronal cells; organelles were rare. EGC was in close contact with other cells in their vicinity. These findings suggest that EGC is well-situated to exert influence on intestinal motility and immune functions through mechanical contraction and chemical secretion.

P-076 Role of N-DRC complex in male fertility

Abstract Study question There are many causes of human infertility, what’s the role of Nexin-dynein regulatory complex (N-DRC) in male fertility? Summary answer Many gene mutants in N-DRC components have been identified in infertile men, which affect the assembly of N-DRC complex and cause defects of sperm. What is known already human infertility affects 10–15% of couples, asthenozoospermia accounting for 18% of infertile men and is a common male infertility phenotype. Nexin-dynein regulatory complex (N-DRC) is a large protein complex regulating device in the flagellum and connects adjacent doublets of microtubules (DMTs). Some N-DRC components were reported to be associated with human disease, such as Primary ciliary dyskinesia (PCD). In recent years, more and more studies reported mutants in subunits of N-DRC are related to male infertility. For example, DRC1, DRC5 and DRC3 mutant were identified in patients displayed multiple morphological abnormalities of the flagella (MMAF) and obstructive azoospermia. Study design, size, duration We searched articles about N-DRC and male infertility in pumped and select research studies and the tidied up the gene mutants, gene knock out mouse modals and IVF outcomes of different N-DRC components in infertile men. Besides, we summarized the parameters of semen and ultrastructure of sperm flagella in these patients. Participants/materials, setting, methods We searched articles about N-DRC and male infertility in pumped and select research studies and the tidied up the gene mutants, gene knock out mouse modals and IVF outcomes of different N-DRC components in infertile men. Main results and the role of chance N-DRC is a highly conserved structural complex located in the axoneme of the flagellum and cilium, containing at least 11 different subunits (DRC1∼DRC11). Patients who were diagnosed as MMAF and male infertility carrying homozygous DRC1 mutants. TEM analyses of the patients’ sperm revealed the flagellar axoneme structure is disordered. A frameshift mutant of DRC5 was identified in an infertile male with asthenozoospermia, but the patient’s problem of infertility could be successfully solved by vitro Fertilization (IVF). A recent study identified two bi-allelic DRC3 frameshift variants in two unrelated patients, one patient displayed MMAF and the other present obstructive azoospermia. The sperm flagella function of DRC5 deletion mice was abrogated but flagellum ultrastructure remained normal and the mice behaved as asthenozoospermia and sterile. DRC3, DRC7 and DRC9 knockout mice exhibit MMAF and male infertility, and in DRC7 KO mice, the axoneme of sperm is disorganized and it was difficult to detect the ‘9 + 2’ microtubule structure. DRC1 mutant mice on the C57BL/6 background died before puberty, KO DRC6 in mice neither has no obvious effects on sperm motility function nor destroy the “9 + 2” arrangement of microtubules in cilia, and male mice was fertile. Limitations, reasons for caution More samples of MMAF and asthenozoospermia men to sequence N-DRC gene, and track their assisted reproductive outcomes. Wider implications of the findings The conclusions in our study uncover certain mechanism of N-DRC deficient in MMAF and asthenozoospermia phenotype, which could provide a new basis for diagnosis of male infertility. Trial registration number not applicable

CircRNA ATF6 suppresses bladder cancer cell proliferation and migration via miR-146a-5p/FLNA axis

BackgroundBladder cancer (BCa) is the most common malignancy with increasing morbidity and mortality. Circular RNA (circRNA) ATF6 level was downregulated in BCa after GSE92675 CircRNA microarray dataset was analyzed using GEO2R. However, its function and mechanism in BCa remain largely unknown. MethodsGEO2R and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were used to measure levels of circRNA ATF6, microRNA-146a-5p (miR-146a-5p), and filamin A (FLNA). CircRNA ATF6 stability was assessed by actinomycin D and RNase R assays, while circRNA ATF6 cellular localization was examined by FISH experiments in T24 cells. Cell counting kit-8 (CCK-8), colony formation, wound-healing, and transwell assays were used to study circRNA ATF6’s function in growth, motility, and invasion. By examining luciferase, starBase, RNA pull-down, and RNA immunoprecipitation (RIP) experiments, we anticipated and confirmed miR-146a-5p interactions with circRNA ATF6, as well as miR-146a-5p interactions with FLNA. On tumor-bearing mice, in vivo experiments were conducted. ResultsMiR-146a-5p expression in Bca was elevated, while circRNA ATF6 and FLNA were downregulated. CircRNA ATF6 showed better stability in BCa cells, with its expression primarily in the cytoplasm. Upregulating circRNA ATF6 lowered BCa cell viability, colony numbers, and invasion numbers, but broadened their migratory pattern. MiR-146a-5p was directly sponged up by circRNA ATF6, which also detrimentally affected miR-146a-5p levels in BCa. MiR-146a-5p reduced BCa FLNA expression by targeting FLNA. FLNA silencing abolished circRNA ATF6’s mitigating function in BCa cell proliferation, motility, and invasion. In vivo, overexpression of circRNA ATF6 significantly reduced tumor volume and weight. ConclusionCircRNA ATF6 suppresses BCa cell growth, migration and invasion through the miR-146a-5p/FLNA axis.

An in vitro study of the impact of IL-17A and IL-22 on ciliogenesis in nasal polyps epithelium via the Hippo-YAP pathway

Cilia loss and impaired motile ciliary functions are one of the typical pathological features of chronic rhinosinusitis with nasal polyps (CRSwNP). Interleukin-17A (IL-17A) and interleukin-22 (IL-22) are the canonical cytokines of type 3 inflammation, exhibiting similar functional effects on epithelial cells. In this study, we sought to examine the effects of IL-17A and IL-22 on ciliated cells and investigate the potential involvement of Hippo-Yes-associated protein (YAP) signaling in their influence on ciliogenesis. We assessed both the mRNA and protein expression levels of IL-17A and IL-22 in nasal tissues obtained from patients with CRSwNP and compared them to those from healthy controls. To further explore the impact of IL-17A and IL-22, we established a primary human nasal epithelial cell (hNEC) model using different concentrations (2 ng/mL, 10 ng/mL, 50 ng/mL) for a duration of 28 days in an air-liquid interface (ALI) culture. Additionally, we employed the inhibitor verteporfin (VP) to investigate whether IL-17A andIL-22 exert their effects on ciliated cells via Hippo-YAP pathway. The mRNA and protein levels of IL-17A and IL-22 in CRSwNP were significantly higher than those in healthy controls, revealing a robust correlation between IL-17A and IL-22. YAP was highly expressed in the nucleus of ciliated cells in CRSwNP and displayed a positive correlation with clinical symptoms. Both IL-17A and IL-22 were found to reduce the number of ciliated cells. IL-17A, but not IL-22, suppressed ciliogenesis by disrupting the proper development and docking of the basal body of ciliated cells, resulting in motile ciliary dysfunctions. Furthermore, the expression of YAP within the nucleus of ciliated cells gradually declined as these cells reached the final stage of differentiation. However, this process was obstructed by IL-17A only. YAP inhibitors, such as Verteporfin, markedly reversed the effects of IL-17A by increasing the proportion of ciliated cells, suppressing nuclear YAP expression in these cells, and enhancing ciliary beating frequency. Both IL-17A and IL-22 are overexpressed in nasal epithelium of CRSwNP, which is associated with the impairment of epithelial cell differentiation. Furthermore, IL-17A has been shown to exert a disruptive effect on morphogenesis of motile cilia via activation of YAP.

Effects of substrate availability and mitochondrial disruption on oxidative metabolism and sperm motility in fertile dogs.

In several mammalian species, the measurement of mitochondrial oxygen consumption (MITOX) under different metabolic conditions has demonstrated a positive correlation with sperm motility and may be a sensitive indicator of mitochondrial health. In general, the maintenance of sperm motility and many key sperm functions and fertilizing events are heavily energy-dependent processes, and some species-specific substrate preferences exist. Although canine sperm have been known to undergo capacitation and maintain motility with supplementation of a wide range of energy substrates, the relationship between mitochondrial function, and the maintenance of oxidative metabolism and sperm motility remain unclear. The objective of this study was to explore the metabolic flexibility of canine sperm, and to investigate the relationship between mitochondrial function, and maintenance of motility under differing nutrient conditions. We explored substrate preferences and the bioenergetics underlying maintenance of canine sperm motility by monitoring mitochondrial oxidative function and sperm kinematics in the presence of mitochondrial effector drug treatments: FCCP, antimycin (ANTI), and oligomycin (OLIGO). We hypothesized that canine sperm possess the ability to use compensatory pathways and utilize diverse nutrient sources in the maintenance of motility. Oxygen consumption (change in pO2, oxygen partial pressure) and sperm kinematics (CASA) were measured concurrently (t0-t30) to assess the relationship between oxidative metabolism and maintenance of sperm motility in dogs. Four media were tested: containing glucose, lactate, and pyruvate (GLP), containing glucose (G), fructose (F), or lactate and pyruvate (LP). In the absence of pharmacological inhibition of the electron transport chain, energetic substrate had no effect on sperm kinematics in fertile dogs. Following mitochondrial disruption by ANTI and OLIGO, mitochondrial oxygen consumption was negatively correlated with several sperm motility parameters in GLP, G, F, and LP media. In every media, FCCP treatment quickly induced significantly higher oxygen consumption than in untreated sperm, and spare respiratory capacity, the maximal inducible oxidative metabolism, was high. With respiratory control ratios RCR >1 there was no indication of bioenergetic dysfunction in any media type, indicating that sperm mitochondria of fertile dogs have a high capacity for substrate oxidation and ATP turnover regardless of substrate. Our results suggest MITOX assessment is a valuable tool for assessing mitochondrial functionality, and that canine sperm employ flexible energy management systems which may be exploited to improve sperm handling and storage.

Early versus late closure of protective loop ileostomy: functional significant results in a preliminary analysis.

Protective loop ileostomy (PLI), commonly performed in rectal cancer surgery, is one of the most reliable methods to reduce the risk of sepsis associated with anastomotic complications. The correct timing of PLI closure is not well defined. Recently, most surgeons proposed to close early the PLI. The aim of this study was to evaluate the impact of the timing of stoma closure on postoperative outcomes. We analyzed prospectively data of patients who received PLI anterior resection for rectal cancer between January 2020 to June 2022. Patients were divided into 2 groups according to the timing of stoma closure, until four weeks (EC group) and more than four weeks (LC group). Outpatient clinic follow-up, perioperative data, postoperative complications and evidence of anterior resection syndrome with the Low-Anterior Resection Score (LARS) score were recorded. In the EC group 24 patients were included while 27 patients were considered for LC group. There were no differences between the groups with respect to all parameters, except for recourse to adjuvant therapy, higher for LC group. Perioperative analyzed characteristics were similar among groups. There was no statistically significant difference between the EC group and the LC group for complication rate. LARS score was higher in the LC group for score >20 and >30. Timing of PLI closure was not a significant independent predictor of post-closure complications rate. LARS incidence was significantly related to longer time of closure, with probably late recovery of motility function, but this should be confirmed by randomized studies.

Testing in functional constipation-What's new and what works.

Constipation is among the most common symptoms prompting a consultation with a paediatric gastroenterologist. While most patients will respond to lifestyle and dietary changes and conventional therapy, some may require diagnostic studies. To review the diagnostics studies used to evaluate children with functional constipation. There is no evidence to support the routine use of abdominal X-rays in the evaluation of paediatric constipation. Colon transit by radiopaque markers (ROM) should be indicated when medical history does not match clinical findings, to guide colon manometry (CM) performance and to discriminate between faecal incontinence from functional constipation and non-retentive faecal incontinence. Colon scintigraphy may be useful as an alternative to ROM. Lumbar spine MRI may be indicated to evaluate for spinal abnormalities. The role of defecography has not been properly evaluated in children. Anorectal manometry in children is indicated primarily to evaluate anal resting pressure, presence and quality of the recto-anal inhibitory reflex and simulated defecation manoeuvres. The CM is indicated to guide surgical interventions after failing medical therapy. The goal of these studies is to identify treatable causes of constipation. Most of these studies are designed to evaluate anatomy, transit and/or colon/rectum motility function and are primarily indicated in those who fail to respond to conventional therapy.

Determination of Electrolytes and Trace Elements in Biological Samples from Patients with Altered Semen Parameters: a Correlational Analysis.

The effects of important nutrients such as calcium (Ca), copper (Cu), iron (Fe), magnesium (Mg), selenium (Se), and zinc (Zn) have been investigated in relation to male fertility due to their roles in proper spermatogenesis, sperm maturation, motility, and optimal sperm function. An imbalance between these elements has been associated with several pathologic conditions and male reproductive issues. The purpose of this study was to determine the essential trace and electrolytes elements, such as Ca, Cu, Fe, Mg, Se, and Zn, in human biological samples (blood, serum, and semen) from patients with male infertility. This study used correlational analysis to determine the potential associations between these elements and male fertility. Imbalances in these elements have been linked to various pathological conditions and male reproductive issues. One hundred eighty referent male adults and two hundred twenty-nine patients diagnosed with subtypes of infertility were included in the study, divided into two age groups. Acid digestion was controlled using a microwave oven, and the essential trace elements and electrolytes in the oxidized biological samples were determined using atomic absorption spectrometry. Certified reference materials of blood and serum were used to validate the accuracy of the methodology. The results showed that the concentrations of Ca, Cu, Fe, Mg, Se, and Zn in the blood, serum, and seminal plasma of male adults in all age groups were higher than those in patients with different infertility phenotypes. Essential element deficiency in all biological fluid samples may significantly negatively affect human reproductive health and lead to male infertility. Through a multidimensional approach, our study sought to unravel the intricate biochemical signatures associated with OAT, providing insights that may shape the landscape of diagnostic and therapeutic strategies for male reproductive health.

Information Theory of Chemotactic Agents Using Both Spatial and Temporal Gradient Sensing

Biological cells and small organisms navigate in concentration fields of signaling molecules using two fundamental gradient-sensing strategies: spatial comparison of concentrations measured at different positions on their surface and temporal comparison of concentrations measured at different locations visited along their motion path. It is believed that size and speed dictate which gradient-sensing strategy cells choose, yet this has never been formally proven. Using information theory, we investigate the optimal gradient-sensing mechanism for an ideal chemotactic agent that combines spatial and temporal comparisons. We account for the physical limits of chemosensation: molecule counting noise at physiological concentrations and motility noise inevitable at the microscale. Our simulation data collapse onto an empirical power law that predicts an optimal weighting of information as a function of motility and sensing noise, demonstrating how spatial comparison becomes more beneficial for agents that are large, slow, and less persistent. This refines and quantifies the previous heuristic notion. Our idealized model assuming unlimited information processing capabilities serves as a benchmark for the chemotaxis of biological cells. Published by the American Physical Society 2024

The Effect of Early Mobilization on Incerased Intestinal Peristaltic Post Sectio Caesarea at Grandmed Lubuk Pakam Hospital in 2023

Sectio Caesarea is a surgical process with the aim of removing the fetus through an incision in the abdominal wall which is connected to the autonomic nervous system, so that bowel movements become slow and cause problems. Caesarean section deliveries are increasingly being performed and their success is high, although they are still considered the last solution. Cesarean section operations are common for mothers who are about to give birth. So that post-operative intestinal peristalsis can return immediately, mobilization is necessary. If there is no mobilization, the motility function of the intestines and bladder will take a long time to return to normal so that the mother will have difficulty defecating. This research aims to measure how much mobilization increases intestinal peristalsis in post-caesarean section surgery patients. The research is quantitative research with a One Group pre-post test design. The sample consisted of 25 post-cesarean section mothers with primigravida births. The instruments used are SOP sheets and observations. Data analysis using the Paired T-test with an error of 0.05 showed that the average intestinal peristalsis before the intervention was 7.20 while after the intervention it was 8.04. The results of the Paired T-test show that the p-value is 0.000, which means that there is an effect of mobilization on increasing intestinal peristalsis in post caesarean section patients at GrandMed Lubuk Pakam Hospital. It is recommended that you always implement post caesarean section mobilization measures in accordance with the SOP.

Achilles' heel of male infertility: good LEGO players.

In a recent journal article, Chen et al. identified a germ cell-specific cofactor, STYXL1, associated with male fertility function. Deletion of STYXL1 prevents the LEGO player CCT complex from properly folding key microtubule proteins of the sperm flagellum, which affects sperm motility and male fertility function.

The Possible Synergistic Pharmacological Effect of an Oral Berberine (BBR) and Curcumin (CUR) Complementary Therapy Alleviates Symptoms of Irritable Bowel Syndrome (IBS): Results from a Real-Life, Routine Clinical Practice Settings-Based Study.

Irritable bowel syndrome (IBS) is a prevalent chronic functional gastrointestinal disorder, characterised by recurrent abdominal discomfort and altered bowel movements. IBS cause a significantly negative impact on quality of life (QoL). Growing pharmacological evidence suggests that berberine (BBR) and curcumin (CUR) may mitigate IBS symptoms through multiple complementary synergistic mechanisms, resulting in the attenuation of intestinal inflammation and regulation of bowel motility and gut functions. In the present observational study conducted under real-life routine clinical practice settings, 146 patients diagnosed with IBS were enrolled by general practitioner clinics and pharmacies in Belgium. For the first time, this study assessed the potential synergistic pharmacological effect of a combined oral BBR/CUR supplement (Enterofytol® PLUS, containing 200 mg BBR and 49 mg CUR) (two tablets daily for 2 months), serving as complementary therapy in the management of IBS. Following the 2-month supplementation, significant improvements were observed in the patients' IBS severity index (IBSSI) (47.5%) and all the primary IBS symptoms, such as abdominal discomfort (47.2%), distension (48.0%), intestinal transit (46.8%), and QoL (48.1%) (all p < 0.0001). The improvement in the patients' IBSSI was independent of age, sex, and IBS sub-types. The patients' weekly maximum stool passage frequency decreased significantly (p < 0.0001), and the stool status normalized (p < 0.0001). The patients' need for concomitant conventional IBS treatment decreased notably: antispasmodics by 64.0% and antidiarrhoeals by 64.6%. Minor adverse effects were reported by a small proportion (7.1%) of patients, mostly gastrointestinal. The majority (93.1%) experienced symptom improvement or resolution, with a high satisfaction rate (82.6%) and willingness to continue the supplementation (79.0%). These findings support the potential synergistic pharmacological role of BBR and CUR in IBS, and their co-supplementation may alleviate IBS symptoms and improve QoL.

Planar Cell Polarity in the Multiciliated Epithelial Lining of the Mouse Eustachian Tube.

Planar cell polarity (PCP) signaling, essential for uniform alignment and directional beating of motile cilia, has been investigated in multiciliated epithelia. As a complex structure connecting the middle ear to the nasopharynx, the eustachian tube (ET) is important in the onset of ear-nose-throat diseases. However, PCP signaling, including the orientation that is important for ciliary motility and clearance function in the ET, has not been studied. We evaluated PCP in the ET epithelium. Morphometric examination of the mouse ET. We performed electron microscopy to assess ciliary polarity in the mouse ET, along with immunohistochemical analysis of PCP protein localization in the ET epithelium. We discovered PCP in the ET epithelium. Motile cilia were aligned in the same direction in individual and neighboring cells; this alignment manifested as ciliary polarity in multiciliated cells. Additionally, PCP proteins were asymmetrically localized between adjacent cells in the plane of the ET. The multiciliated ET epithelium exhibits polarization, suggesting novel structural features that may be critical for ET function. NA Laryngoscope, 134:3795-3801, 2024.

Abstract 5694: Elucidating areca nut-induced miRNA-mRNA regulatory networks in head and neck cancer pathogenesis

Abstract Areca nut has been considered a high-risk carcinogen for head and neck cancer (HNC) in Southeast Asia, while its molecular effects, especially on the miRNA regulatory roles, remain elusive. This study characterized miRNA-mRNA networks associated with areca nut-related HNC. We integratively analyzed the areca nut-induced mRNA profile and TCGA-HNSC gene set. A total of 2575 genes were identified, with 1971 upregulated and 604 downregulated in cancers. The KEGG pathway analysis revealed that these genes were enriched in the cellular functions related to motility and stress response. Experimental studies confirmed that arecoline promoted cell migration, invasion, and chemo-radioresistance. We further cross-analyzed the miRNAs induced by areca nut and dysregulated in TCGA-HNSC data and defined 71 molecules affected, with 35 upregulation and 36 downregulation. Using the multimiR tool to map potential mRNA-miRNA interactions, we uncovered that these miRNAs were connected to 2173 genes. These molecules participated in several oncogenic mechanisms, such as ErbB and PI3K-Akt signaling, cell adhesion, and DNA damage response. We endeavored to establish miRNA-mRNA interaction networks with the functions of cellular motility and stress response via the Cytoscape analytical method. Our data revealed nexus comprising 41 miRNAs with 83 mRNAs, and 38 miRNAs with 66 mRNAs, respectively, co-regulate these two malignant functions. A key miRNA, miR-410-3p, downregulated in HNC and decreased following areca nut treatment, was studied. Ectopic expression of miR-410-3p attenuated areca nut-induced cell invasion and exerted modulatory effects on its target oncogenes, CRK. Thus, our study delineates a comprehensive view of the miRNA-mRNA interplay altered by areca nut, illustrating a sophisticated mechanism of carcinogenesis and suggesting new avenues for diagnostic and therapeutic strategies in HNC. Citation Format: Hung-Han Huang, Guo-Rung You, Kai-Hsin Lin, Yin-Ju Chen, Ann-Joy Cheng. Elucidating areca nut-induced miRNA-mRNA regulatory networks in head and neck cancer pathogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5694.

Global boundedness and asymptotic stabilization in a chemotaxis system with density-suppressed motility and nonlinear signal production

In this paper, we study the following chemotaxis model with density-suppressed motility and nonlinear production{ut=Δ(φ(v)u)+ru−μuα,x∈Ω,t>0,vt=Δv−v+wβ,x∈Ω,t>0,wt=Δw−w+uγ,x∈Ω,t>0 under homogeneous Neumann boundary conditions in a bounded domain Ω⊂Rn(n≥2) with smooth boundary, where r∈R,μ,β,γ>0 and α>1. The positive motility function satisfies φ(s)∈C3([0,∞)) and φ′(s)≤0 for all s≥0. It is showed that the system admits a globally bounded and classical solution under some conditions on α,β and γ. Then, under stricter constraints on φ, we obtained that the parameter β has a wider range than before, which is enough to ensure the global boundedness of the solution. Furthermore, if μ is sufficiently large, we proved that the solution converges to ((r+μ)1α−1,(r+μ)βγα−1,(r+μ)γα−1) in L∞(Ω) as t→∞ for all r∈R,μ,β,γ>0 and α>1, where r+:=max⁡{r,0}. Finally, we showed that the convergence is exponential in cases r>0 and r<0.

Relationship of Age and Gender to Motility Test Results and Symptoms in Patients with Chronic Constipation.

Patients with chronic constipation (CC) exhibit symptoms and functional abnormalities upon testing, but their relationship to age and gender is unclear. We assessed age- and gender-related differences in symptoms, colon transit time, and anorectal motility, sensation, and expulsion. Retrospective, post hoc data analysis of patients with CC, who underwent Wireless Motility Capsule (WMC), High-Resolution Anorectal Manometry (HR-ARM), Balloon Expulsion Test (BET) and Rectal Sensory Testing (RST). Clinical assessment was made by questionnaires. Standard WMC criteria for colonic transit time (CTT) and the London classification was used for HR-ARM analyses, and regression plots between age, gender, CTT, HR-HRM, RST and BET were calculated. We studied 75 women and 91 men. Abdominal pain, infrequent defecation, incomplete evacuation, defecatory straining, and multiple motility and anorectal function abnormalities were common. Abdominal pain was least frequently, and straining was most frequently associated with a motility abnormality. For each symptom, the highest prevalence was associated with failed BET. There was a significant increase in CTT with age only in men (p = 0.0006). In men, for each year of age there was a CTT increase of 1.02 h. The prevalence of abdominal pain and incomplete evacuation for females was significantly higher than that for males (both P < 0.05). The prevalence of low anal squeeze pressure for females was significantly higher than that for males, and the prevalence of poor rectal sensation for males was significantly higher than that for females (both P < 0.05). A significant decrease in basal anal and squeeze pressures with age occurred in women (p < 0.0001); an increase in age of one year was associated with a decrease in anal base pressure of 1.2 mmHg. Abnormal CTT and HR-ARM tests were associated with increased symptom frequency, but not severity. There are significant age- and gender-related differences in symptoms, CTT, and HR-HRM parameters, rectal sensation, and expulsion, that may influence the multifaceted management of constipation.