Abnormal Migration Research Articles

Chronic Kidney Disease Is Characterized by Expansion of a Distinct Proinflammatory Intermediate Monocyte Subtype and by Increased Monocyte Adhesion to Endothelial Cells.

CKD is accompanied by abnormal inflammation, which contributes to progressive loss of functional renal tissue and accelerated cardiovascular disease. Although studies have documented that dysregulation of monocyte maturation and function is associated with CKD and its complications, it is not well characterized. This study reveals that a distinctive human monocyte subtype with high propensity for releasing proinflammatory mediators and activating endothelial cells is increased in adults with CKD compared with adults with high cardiovascular risk and normal kidney function. It also demonstrates that human monocyte adhesion to endothelial layers and responses to specific inflammatory migration signals are enhanced in CKD. These findings offer insights into the mechanisms of CKD-associated intravascular and localized inflammation and may suggest potential targets for therapeutic interventions. Cardiovascular disease (CVD) in patients with CKD is associated with increased circulating intermediate monocytes (IMs). Dysregulation of monocyte maturation and function is associated with CKD and its complications, but it is incompletely characterized. To explore monocyte repertoire abnormalities in CKD, we studied properties of monocyte subpopulations, including IM subpopulations distinguished by HLA-DR expression level, in individuals with or without CKD. Using flow cytometry, we profiled monocyte populations in blood samples from adults with CKD, healthy volunteers (HVs), and patient controls (PCs) with high CVD risk. Monocyte subpopulations were also derived from single-cell RNA-sequencing profiles of paired blood and biopsy samples from kidney transplant recipients. We quantified intracellular cytokine production, migration, and endothelial adhesion in ex vivo assays of PBMCs. Of four predefined blood monocyte subpopulations, only HLA-DR hi IMs were increased in individuals with CKD compared with HVs and PCs. In HVs and patients with CKD, LPS-stimulated HLA-DR hi IMs isolated from blood produced higher amounts of TNF and IL-1 β than other monocyte populations. Single-cell analysis revealed four monocyte clusters common to blood and kidneys, including an HLA-DR hi IM-like cluster that was enriched in kidneys versus blood. Migration toward CCL5 and CX3CL1 and adhesion to primary endothelial cell layers were increased in monocyte subpopulations in individuals with CKD compared with HVs. Monocyte adhesion to endothelial cells was partly dependent on CX3CR1/CX3CL1 interaction. CKD is associated with an increased number of a distinctive proinflammatory IM subpopulation and abnormalities of monocyte migration and endothelial adhesion. Dysregulated monocyte maturation and function may represent targetable factors contributing to accelerated CVD in CKD.

Enhanced Local Delivery of microRNA-145a-5P into Mouse Aorta via Ultrasound-Targeted Microbubble Destruction Inhibits Atherosclerotic Plaque Formation.

Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) play a key role in the formation and rupture of atherosclerotic plaques. Previous studies have confirmed that microRNA-145 (miR-145) is involved in the phenotypic regulation of VSMCs and reduction of atherosclerosis. At present, seeking safe and effective gene delivery remains a key problem restricting the development of gene therapy. In recent years, ultrasound-targeted microbubble destruction (UTMD) has become a safe and effective transfection method that is widely used in the basic research of gene therapy for heart and tumor diseases. Here, we synthesized cationic microbubbles to encapsulate miR-145 and targeted their release into VSMCs in vitro and in vivo using ultrasound. The feasibility of this gene therapy was verified by fluorescence microscopy and an in vivo imaging system. The results showed that treatment with miR-145 delivered via UTMD considerably improved the gene transfection efficiency and promoted the contraction phenotype of VSMCs in vitro. In vivo, this treatment reduced the atherosclerotic plaque area by 48.04% compared with treatment with free miR-145. Therefore, UTMD-mediated miRNA therapy may provide a new targeted therapeutic approach for atherosclerotic plaques.

Inhibition of Foxp4 Disrupts Cadherin-based Adhesion of Radial Glial Cells, Leading to Abnormal Differentiation and Migration of Cortical Neurons in Mice.

Heterozygous loss-of-function variants of FOXP4 are associated with neurodevelopmental disorders (NDDs) that exhibit delayed speech development, intellectual disability, and congenital abnormalities. The etiology of NDDs is unclear. Here we found that FOXP4 and N-cadherin are expressed in the nuclei and apical end-feet of radial glial cells (RGCs), respectively, in the mouse neocortex during early gestation. Knockdown or dominant-negative inhibition of Foxp4 abolishes the apical condensation of N-cadherin in RGCs and the integrity of neuroepithelium in the ventricular zone (VZ). Inhibition of Foxp4 leads to impeded radial migration of cortical neurons and ectopic neurogenesis from the proliferating VZ. The ectopic differentiation and deficient migration disappear when N-cadherin is over-expressed in RGCs. The data indicate that Foxp4 is essential for N-cadherin-based adherens junctions, the loss of which leads to periventricular heterotopias. We hypothesize that FOXP4 variant-associated NDDs may be caused by disruption of the adherens junctions and malformation of the cerebral cortex.

BAFF Promotes FLS Activation Through BAFFR-Mediated Non-canonical NF-κB Pathway and the Effects of CP-25.

B cell activating factor (BAFF) has been shown to play a key role in regulating B cell function, but little is known about whether BAFF affects the function of fibroblast-like synoviocyte (FLS), an effector cell of rheumatoid arthritis (RA). CP-25, a new ester derivative of paeoniflorin, could alleviate the arthritis symptoms of collagen-induced arthritis (CIA) mice by inhibiting BAFF-mediated abnormal activation of B cells. In this study, we aimed to understand the mechanism by which BAFF activates FLS and the effect of CP-25 on FLS function. Therefore, the proliferation and migration abilities of FLS and key proteins on the non-canonical NF-κB pathway were examined. The results showed that compared with the FLS of normal rats/OA patients, the expression of BAFF-R, TRAF2, NIK, p-IKKα, P100, and P52 was higher in the FLS of AA rats/RA patients, while the expression of TRAF3 was lower. And, BAFF promotes FLS activation by activating the non-canonical NF-κB signaling pathway. Meanwhile, BAFFR-siRNA inhibited the proliferation of FLS and the activation of non-canonical NF-κB signaling in FLS induced by BAFF. Additionally, CP-25 could inhibit abnormal proliferation and migration of FLS by regulating non-canonical NF-κBsignaling. We concluded that BAFF may act as an important role in facilitating the function of FLS through the BAFFR-mediated non-canonical NF-κB pathway, which would be useful for revealing the pathological mechanism of RA. And CP-25 may become a potential new drug for the treatment of RA, providing a scientific basis for the development of new drugs to treat RA.

Pubic Accessory Scrotum: a Case Report of a Rare Position

Scrotum shows multiple congenital anomalies which could be explained by embryological abnormalities in migration of labioscrotal swelling. Our case was a neonate who had an accessory scrotum in the pubic area at delivery which is a rare position. Ultrasound scan and voiding cystourethrography showed adequate capacity, shouldering and smooth outline with insignificant mild residual urine of bladder, and dilated posterior urethra. Magnetic resonance imaging revealed a pubic accessory scrotum with thickened skin and subcutaneous tissue with no detectable internal contents or pelvic connection; however, pelvicalyceal system was dilated suggesting pelviureteric junction obstruction. Excision of accessory scrotum was discussed with parents but they refused. Ultrasound follow-up of the associated congenital hydronephrosis revealed improvement of hydronephosis.

The Dyslexia-associated gene KIAA0319L is involved in neuronal migration in the developing chick visual system.

The gene KIAA0319-Like (KIAA0319L) is thought to confer susceptibility for developmental dyslexia. Dyslexia may be caused by alterations in neuronal migration, and in utero knockdown of KIAA0319L in rats indicated migration errors. However, studies carried out with KIAA0319L knockout mice did not reveal an altered neuronal migration phenotype. Gene knockout may activate compensatory mechanisms to buffer against genetic mutations during development. Here we assessed the role of KIAA0319L on migrating neurons in the chick developing tectum. Whole mount in situ hybridization was performed for KIAA0319L on embryonic day (E)3 - E5 chick embryos and in situ hybridization on sections was performed at later stages. The specificity and efficiency of engineered microRNA (miRNA) constructs targeting KIAA0319L for knocking down KIAA0319L were verified. miRNAs were electroporated into E5 chick optic tecta. Our studies demonstrate that KIAA0319L is expressed in the developing chick visual system, as well as in the otic vesicles. Knockdown of KIAA0319L in the optic tectum results in abnormal neuronal migration, strengthening the argument that KIAA0319L is involved in this developmental process.

Hypoxia-induced endothelial cell-derived exosome stimulates vascular smooth muscle cell proliferation and migration.

This study mainly used human VSMCs and ECs cultured in vitro to investigate whether exosomes (Exos) are involved in the communication between ECs and VSMCs under hypoxia, and to explore the role and mechanism of ECs-derived exosomes in the abnormal proliferation of VSMCs. VSMCs proliferation and migration were assessed by a series of cell function assays after culturing VSMCs alone or co-culturing ECs under hypoxia or normoxia. Next, exosomes were extracted from ECs under hypoxia or normoxia and characterized. We then introduced ECs-Exos to observe their effects on VSMCs proliferation and migration, and further evaluated the expression of transforming growth factor-beta receptor 1 (TGFBR1) pathway-related proteins. Finally, the effect of ECs-Exos on VSMCs function was evaluated after knocking down TGFBR1 in ECs. VSMCs treated with ECs-Exos exhibited increased proliferation and migration ability in hypoxic environment, and the expression of TGFBR1 pathway-related proteins was upregulated. Administration of ECs-Exos with TGFβ1 knockdown conspicuously reversed the promoting effects of ECs-Exos on cell proliferation and migration under hypoxia. In summary, hypoxia affected the secretion of extracellular vesicles by endothelial cells, which can be internalized by VSMCs and accelerate the abnormal proliferation and migration of VSMCs by delivering TGFBR1.

Rastreio de heterotopia nodular periventricular com ultrassom transfontanelar em paciente assintomático com fator de risco: relato de caso

Periventricular nodular heterotopia (PH) results from abnormal neuronal migration during the genesis of the central nervous system, especially in the fetal period. It is asymptomatic in the neonatal period, however, is often characterized as epileptiform focus that is difficult to control throughout life, impacting the neuropsychomotor development and the quality of life of the child and his caregiver. Because it is related to genetic abnormality, often derived from a hereditary pattern, it can be predicted that affected parents may generate offspring with such a clinical condition. In this context, however, the use of transfontanellar ultrasonography (USTF) in the neonatal period, to screen PH in patients who have a positive family history for the clinical condition, is not yet consensus in the current literature. Thereby, we sought to report the case of PH diagnosed at random, in asymptomatic neonate, but with epileptic parent with the same condition, not known during prenatal care. The child showed signs suggestive of neuronal ectopy in requested USTF due to the risk of periventricular hemorrhage, which was later confirmed with brain magnetic resonance.

Clinical Value of Long Non-Coding RNA HOTAIR in Carotid Artery Stenosis and Its Role in Vascular Smooth Muscle Cell Proliferation.

This study investigated the clinical role of HOTAIR in patients with carotid artery stenosis (CAS) and its mechanism in vascular smooth muscle cells (VSMCs). Patients with CAS were collected. The expression of HOTAIR was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The clinical importance of HOTAIR was revealed by the receiver operating characteristic curve. Overexpression and knockdown of HOTAIR were achieved by transfecting pCDNA3.1-HOTAIR plasmid and si-HOTAIR respectively. CCK-8 assay or Transwell assay were used to analyze the changes in cell viability or migration after transfection treatments. Double luciferase reporter gene assay confirmed the targeted relationship between HOTAIR and miR-148b-3p. The levels of miR-148b-3p in VSMCs and patients were detected by qRT-PCR. Pearson analysis was used to analyze the relationship between HOTAIR and miR-148b-3p in patients with CAS. The expression of HOTAIR in patients with CAS was significantly higher than that in healthy individuals. HOTAIR appeared to discriminate CAS patients from healthy people. The overexpression of HOTAIR increased the viability and migration of VSMCs. Silenced HOTAIR restricted the abnormal viability and migration of VSMCs. A double luciferase reporter revealed a region of complementary binding between HOTAIR and miR-148b-3p. The expression of miR-148b-3p in VSMCs was regulated by the levels of HOTAIR. Reduction of miR-148b-3p expression was substantiated in CAS patients. Pearson analysis exhibited that the expression of HOTAIR was negatively relative to the levels of miR-148b-3p. The long noncoding RNA HOTAIR might be a diagnostic biomarker for CAS patients, and it was involved in the activity of vascular smooth muscle cells.

PS-B01-8: MALAYSIAN TUALANG HONEY INHIBITS PDGF-INDUCED HUMAN VASCULAR SMOOTH MUSCLE CELLS PROLIFERATION AND MIGRATION

Introduction and Objective: Cardiovascular diseases (CVD) are the leading cause of death globally. Atherosclerosis is a common CVD which can lead to the deadliest heart failure. Increasing evidence showed that abnormal vascular smooth muscle cells (VSMC) proliferation and migration constitute the main pathological basis of atherosclerosis. These events are potently stimulated by platelet-derived growth factor (PDGF), causing phenotypic switching of VSMC from a mature, quiescent phenotype to a proliferative, migratory phenotype which is commonly observed in the development of atherosclerosis. Furthermore, study have revealed that PDGF elevates the concentration of reactive oxygen species (ROS) which stimulates VSMC proliferation and migration. Pharmacological treatment for atherosclerosis is often an ongoing, long-term regimen that may have adverse effect to an individual. Thus, alternative therapy based on natural products can potentially be the frontier in atherosclerosis treatment. Interestingly, previous study revealed that Malaysian Tualang Honey (MTH) is capable of protecting vascular endothelial cells from inflammation. However, little is known on the effect of MTH on the PDGF-induced VSMC proliferation and migration. Therefore, the present study aimed to determine the antioxidant, anti-proliferative and anti-migratory effects of MTH in PDGF-induced VSMC. Methodology: VSMC were treated with increasing concentrations of MTH (0.001–10%) for 24 hours and the cell viability were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cells were then be treated with non-cytotoxic concentrations of MTH and induced with 20ng/mL PDGF for 72 hours to determine the proliferation rate via MTT assay. The intracellular ROS were measured in these cultured cells by dichlorodihydrofluorescein diacetate (DCFH-DA) assay. Wound healing assay were used to determine the anti-migration activities on PDGF-induced VSMC treated with MTH. Results: Our data showed that MTH concentrations ranging from 0.01% to 1.00% showed no cytotoxic effect to VSMC. Co-culture of the cells with MTH significantly inhibits the proliferation and migration of PDGF-stimulated VSMC in a concentration-dependent manner. Pre-treatment of cells with MTH prior to culturing in 20ng/mL PDGF showed a significant decrease in the production of ROS. Conclusion: This study demonstrates that MTH inhibits VSMC proliferation and migration by suppressing the production of ROS which constitute the pharmacological basis of anti-atherosclerotic action. Therefore, MTH potentially can be a promising therapeutic agent in the treatment of atherosclerosis.

A rare case of abnormal epithelial migration in the external auditory canal secondary to cotton bud abuse

The outer third of external auditory canal is cartilaginous and contains pilosebaceous glands and hair follicles. The medial two third is bony, and the skin is devoid of these skin appendages and its secretions. It also has outward migratory property which makes the ear self-cleansing. Here we present an exceeding rare case of hair in the tympanic membrane causing distressing symptom of scratchy sensation, tinnitus, and otalgia. We hypothesize, it is the distortion of migratory pattern medially due to repeated otitis externa caused by abuse of cotton bud that led to presence of hair in the tympanic membrane.

Satisfying outcome of vagus nerve stimulation applied in the treatment of a patient with drug-resistant epilepsy caused by periventricular nodular heterotopia

Introduction. Periventricular nodular heterotopia (PNH) is a developmental malformation of the cerebral cortex characterized by abnormal migration of neurons into the cortical plate and is often associated with drug-resistant focal epilepsy. Case report. A 33-year-old female patient suffered from drug-resistant epilepsy, which was predominantly characterized by focal seizures, with occasional seizures that had a focal onset and progressed into bilateral tonic-clonic seizures. Magnetic resonance imaging showed bilateral heterotopic nodules in the occipital horns of the lateral brain ventricles. 18-Fluoro-deoxyglucose positron emission tomography ? FDG-PET scan demonstrated a zone of reduced glucose metabolism on the right temporal region. Electroencephalogram suggested focal electrocortical activity on the temporo-parieto-occipital regions, predominantly on the right temporal side. The woman was treated with polytherapy (valproic acid, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, clobazam, and lacosamide), but it did not affect the seizure frequency. Due to the bilateral localization of the heterotopic nodules, surgical treatment was not recommended. After a multidisciplinary assessment, we decided on vagus nerve stimulation (VNS) and achieved satisfying seizure control. Conclusion. Patients with PNH require multidisciplinary assessment and treatment, while in this report we have a case of a patient in whom satisfying control of drug-resistant epilepsy was achieved after the implantation of the VNS device.

KIF26A is mutated in the syndrome of congenital hydrocephalus with megacolon.

Human disorders of the enteric nervous system (ENS), e.g., Hirschsprung's disease, are rarely associated with major central nervous system involvement. We describe two families each segregating a different homozygous truncating variant in KIF26A with a unique constellation of severe megacolon that resembles Hirschsprung's disease but lacks aganglionosis as well as brain malformations that range from severe to mild. The intestinal phenotype bears a striking resemblance to that observed in Kif26a-/- mice where KIF26A deficiency was found to cause abnormal GDNF-Ret signaling resulting in failure to establish normal neuronal networks despite myenteric neuronal hyperplasia. Very recently, a range of brain developmental phenotypes were described in patients and mice with KIF26A deficiency and were found to result from abnormal radial migration and increased apoptosis. Our report, therefore, reveals a recognizable autosomal-recessive human KIF26A deficiency phenotype characterized by severe ENS dysfunction and a range of brain malformations.

Cell migration is impaired in XPA-deficient cells.

Xeroderma pigmentosum (XP) is a hereditary disorder characterized by photosensitivity, predisposition to skin cancers, and neurological abnormalities including microcephaly and progressive neurodegeneration. A lack of nucleotide excision repair (NER) in patients with XP can cause hypersensitivity to the sun, leading to skin cancer, whereas the etiology of the neuronal symptoms of XP remains ambiguous. There are various neurological disorders that perturb neuronal migration, causing mislocalization and disorganization of the cortical lamination. Here, we investigated the role of the XP group-A (Xpa) gene in directed cell migration. First, we adopted an in utero electroporation method to transduce shRNA vectors into the murine embryonic cerebral cortex for the in vivo knockdown of Xpa. Xpa-knockdown neurons in the embryonic cerebral cortex showed abnormal cell migration, cell cycle exit, and differentiation. The genotype-phenotype relationship between the lack of XPA and cell migration abnormalities was confirmed using both a scratch assay and time-lapse microscopy in XP-A patient-derived fibroblasts. Unlike healthy cells, these cells showed impairment in overall mobility and the direction of motility. Therefore, abnormal cell migration may explain neural tissue abnormalities in patients with XP-A.

In Situ Visualization of Epidermal Growth Factor Receptor Nuclear Translocation with Circular Bivalent Aptamer.

Epidermal growth factor receptor (EGFR) nuclear translocation correlates with the abnormal proliferation, migration, and anti-apoptosis of tumor cells. Monitoring EGFR nuclear translocation provides insights into the molecular mechanisms underlying cancers. EGFR nuclear translocation includes two processes, EGFR phosphorylation and phosphorylated EGFR translocation to the nucleus. With the help of aptamers, probes that can achieve the first step of anchoring phosphorylated EGFR have been developed. However, the EGFR nuclear translocation can last for hours, posing a challenge to monitor the entire nuclear translocation in living cells. Herein, we designed a circular bivalent aptamer-functionalized optical probe with greatly enhanced stability for long-term visualization of EGFR nuclear translocation in situ. The results of cell experiments show that the probe could monitor the entire nuclear translocation of EGFR. The findings of tissue and in vivo experiments demonstrate that the probe can evaluate the development and progression of tumors by imaging EGFR nuclear translocation in situ. The proposed approach allows us to monitor EGFR nuclear translocation in the long term, indicating its great potential in investigating the mechanisms of cancers and guiding for tumor treatment.

Resveratrol Inhibits Insulin-Induced Vascular Smooth Muscle Cell Proliferation and Migration by Activating SIRT1.

Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are essential for the development of hypertension. Insulin has been identified to promote VSMC proliferation and migration; resveratrol has been shown to have protective effects against cardiovascular diseases. This study aimed to investigate the effect of resveratrol on insulin-induced VSMC proliferation and migration and its potential mechanism. VSMC proliferation was measured by Cell Counting Kit-8 (CCK-8), cell counting method, and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay. Cell migration was detected by wound healing assay and transwell method. Expression of silent information regulator of transcription 1 (SIRT1) and phosphorylation levels of signaling molecules, such as phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt), in VSMCs were detected by Western blotting. Resveratrol (25-150 μM) was found to inhibit insulin-induced VSMC proliferation. Pretreatment with 100 μM resveratrol reduced insulin (100 nM)-mediated VSMC migration. LY294002, an inhibitor of PI3K, inhibited the stimulatory effect of insulin (100 nM) on the proliferation of VSMCs. Treatment with resveratrol also decreased insulin-induced stimulatory effect on PI3K and Akt phosphorylation levels. Moreover, resveratrol treatment increased SIRT1 protein expression in VSMCs. A SIRT1 inhibitor, EX527, reversed the inhibitory effect of resveratrol on insulin-induced VSMC proliferation and migration and activation of PI3K and Akt phosphorylation levels. In conclusion, our study revealed that treatment with resveratrol inhibited insulin-mediated VSMC proliferation and migration, possibly by activating SIRT1 and downregulating the PI3K/AKT pathway.

The regulatory role of endoplasmic reticulum chaperone proteins in neurodevelopment.

The endoplasmic reticulum (ER) is the largest tubular reticular organelle spanning the cell. As the main site of protein synthesis, Ca2+ homeostasis maintenance and lipid metabolism, the ER plays a variety of essential roles in eukaryotic cells, with ER molecular chaperones participate in all these processes. In recent years, it has been reported that the abnormal expression of ER chaperones often leads to a variety of neurodevelopmental disorders (NDDs), including abnormal neuronal migration, neuronal morphogenesis, and synaptic function. Neuronal development is a complex and precisely regulated process. Currently, the mechanism by which neural development is regulated at the ER level remains under investigation. Therefore, in this work, we reviewed the recent advances in the roles of ER chaperones in neural development and developmental disorders caused by the deficiency of these molecular chaperones.

Nuciferine attenuates atherosclerosis by regulating the proliferation and migration of VSMCs through the Calm4/MMP12/AKT pathway in ApoE(-/-) mice fed with High-Fat-Diet

BackgroundAtherosclerosis (AS) is the pathological basis of multiple cardiovascular diseases. The pathogenesis of AS is closely related to the abnormal proliferation and migration of vascular smooth muscle cells (VSMCs). Nuciferine, an aporphine alkaloid from lotus leaf, has various pharmacological activities. However, the effect and mechanism of nuciferine on regulating proliferation and migration of VSMCs against AS is still unclear. PurposeTo elucidate the pharmacological effect and molecular mechanism of nuciferine on AS in ApoE(-/-) mice fed with High-Fat-Diet (HFD). Study DesignHFD-fed ApoE(-/-) mice and 3% fetal bovine serum (FBS) induced mouse aortic vascular smooth muscle cells (MOVAS) were used to investigate the protective effect and mechanism of nuciferine on AS. MethodsOil red O staining was used to detect the atherosclerotic lesions. Western blotting and immunofluorescence were used to determine calmodulin 4 (Calm4) expression and localization. CCK-8 assay, transwell and wound-healing assays were used to measure the migration and proliferation of MOVAS cells. ResultsNuciferine at 40 mg/kg significantly ameliorated the aortic lesion and vascular plaque in AS model, which was equal to the effect of the positive control drug (atorvastatin). In addition, nuciferine attenuated the migration and proliferation of VSMCs in vivo and in vitro. Importantly, nuciferine down-regulated the increase of Calm4 induced by HFD-fed in ApoE(-/-) mice or 3% FBS induced MOVAS cells. However, the inhibitory effect of nuciferine on the migration and proliferation of MOVAS cells was blocked when Calm4 was overexpressed. Furthermore, we found that nuciferine suppressed MMP12 and PI3K/Akt signaling pathway via Calm4. ConclusionOur results illustrated that Calm4 promoted the proliferation and motility of MOVAS by activating MMP12/Akt signaling pathway in AS. Nuciferine has a significant anti-atherogenic effect by regulating the proliferation and migration of VSMCs through the Calm4/MMP12/AKT signaling pathway. Thus, Calm4 could potentially be a new target for AS therapy, and nuciferine could be a potential drug against AS.

Reduced Expression of SFRP1 is Associated with Poor Prognosis and Promotes Cell Proliferation in Breast Cancer: An Integrated Bioinformatics Approach

PurposeBreast carcinoma is the most frequent form of malignancy in women globally. Exploration of the breast cancer genome tiled the way for the validation of novel cancer biomarkers and to explore various mechanisms involved in the progression of carcinogenesis. The purpose of the research is to find an identification of potential gene linked to breast cancer (BC) progression and prognosis. MethodsThree datasets (GSE71053, GSE61724, and GSE36295) were downloaded from the Gene Expression Omnibus (GEO) database. An integrated analysis of several gene expression profile datasets was used to find differentially expressed genes (DEGs) in BC and normal breast tissue samples. Protein–protein interaction (PPI) network was used to verify hub genes associated with the pathogenesis and prognosis of BC. The functional enrichment and pathway analysis was performed by FunRich and cBioPortal. The expression pattern was assessed using COSMIC, GEPIA2, and BC-GenExMiner. ResultsThe results revealed that among the hub genes, Secreted Frizzled-related protein 1 (SFRP1) was a negative regulator of the Wnt pathway in breast cancer. Loss of SFRP1 may result in abnormal cellular proliferation, migration, and invasion, which may trigger cancer cells, leading to progression of the disease, poor prognosis, and therapy resistance. Lastly, the Kaplan–Meier plotter online database demonstrated that expression levels of the SFRP1 gene were related to lower survival. ConclusionThe findings of this research would provide some directive significance for further investigating the diagnostic and prognostic biomarker to facilitate the molecular targeting therapy of breast cancer; SFRP1 expression may be effective as a novel prognostic biomarker in early breast cancer.

Effects of Different Intervention Factors on Vascular Endothelial Growth Factor-Induced Human Airway Smooth Muscle Cell Migration.

Background Asthma airway remodeling is closely related to the abnormal migration of human airway smooth muscle cells (ASMCs), and vascular endothelial growth factor (VEGF) is involved in the pathophysiological process of asthma. This study aimed to investigate the effect of VEGF on ASMC migration through in vitro cell experiments and to intervene in ASMC migration with different asthma drugs and signaling pathway inhibitors to provide a basis for screening effective drugs for airway remodeling. Methods The effect of VEGF on the proliferation of ASMCs was detected by the CCK-8 method, and the effect of VEGF on the migration of ASMCs was proven by scratch and transwell assays. Different asthma drugs and signaling pathway inhibitors were used to interfere with the migration of ASMCs. The number of migrating cells was compared between the intervention and nonintervention groups. Results Our results showed that VEGF induction enhanced ASMC migration; pretreatment with the commonly used asthma drugs (salbutamol, budesonide, and ipratropium bromide) significantly attenuated VEGF-induced ASMC migration; and inhibitors SB203580, LY294002, and Y27632 blocked the VEGF-induced activation of p38 MAPK, PI3K, and ROCK signaling pathway targets in ASMCs and inhibited migration. Conclusion This study shows that the current commonly used asthma drugs salbutamol, budesonide, and ipratropium have potential value in the treatment of airway remodeling, and the p38 MAPK, PI3K, and ROCK signaling pathway targets are involved in the VEGF-induced ASMC migration process. Signaling pathway inhibitor drugs may be a new way to treat asthma-induced airway remodeling in asthma patients in the future. However, the related mechanism and safety profile still need further research.