Protective effect of feed additive ferulic acid on respiratory depression and oxidation imbalance of carp induced by pesticide difenoconazole via ROS/NF-κB/NLRP3 axis.

Difenoconazole (DFZ), classified as a "low-toxicity pesticide," has seen widespread application in recent years. Nevertheless, the non-target toxicity of the substance, particularly towards aquatic creatures, has generated considerable apprehension. The anti-inflammatory and antioxidant effects of Ferulic Acid (FA) have attracted considerable study in this particular setting. This study established a chronic exposure model to DFZ and investigated the protective effects of FA on chronic respiratory inhibition leading to gill damage in freshwater carp. Histological analyses via HE staining indicated that FA effectively alleviated gill tissue damage induced by chronic DFZ exposure. The qRT-PCR results showed that the addition of FA reduced the expression of IL-1ß, IL-6 and TNF-α while boosting the expression of IL-10 and TGF-ß1. Biochemical analyses and DHE staining revealed that FA reduced MDA levels and increased CAT and GSH activities, along with T-AOC, decreased ROS accumulation in response to chronic DFZ exposure. The results obtained from Western blotting analysis demonstrated that the addition of FA effectively suppressed the activation of the NF-κB signalling pathway and the NLRP3 inflammasome pathway in the gills subjected to prolonged exposure to DFZ. In summary, FA ameliorated gill tissue inflammation and blocked ROS accumulation in carp exposed to chronic DFZ, mitigating tissue inflammation and restoring redox homeostasis through the NF-κB-NLRP3 signaling pathway. Hence, the application of FA has been found to be efficacious for improving respiratory inhibition and mitigating gill tissue inflammation and oxidative stress resulting from DFZ pollution in aquatic habitats.

Silybin attenuates avermectin-induced oxidative damage in carp respiration by modulating the cGAS-STING pathway and endoplasmic reticulum stress.

Avermectin is a commonly used insect repellent for aquaculture and crops, but it is easy to remain in the aquatic environment, causing organism disorders, inflammation, and even death. This resulted in significant economic losses to the carp aquaculture industry. Silybin has antioxidant, anti-inflammatory, and anti-apoptotic properties. However, it is unclear whether Silybin counteracts gill damage caused by avermectin exposure. Therefore, we modeled avermectin exposure and Silybin intervention by adding 2.404 µg/L avermectin to water and 400 mg/kg of Silybin to feed. Gill tissue was collected and analyzed in depth during a 30-day experimental period. The results showed that avermectin exposure induced structural disorganization of gill filaments and led to increased reactive oxygen species, inhibition of antioxidant functions, induction of inflammatory responses, and endoplasmic reticulum stress in addition to the endogenous apoptotic pathway. In contrast, Silybin effectively alleviated pathological changes and reduced reactive oxygen species levels, thereby attenuating oxidative stress and endogenous apoptosis and inhibiting endoplasmic reticulum stress pathways. In addition, Silybin reduced avermectin-induced gill tissue inflammation in carp, and it is considered that it might modulate the cGAS-STING pathway. In summary, Silybin alleviates avermectin-induced oxidative damage within the carp's respiratory system by modulating the cGAS-STING pathway and endoplasmic reticulum stress. The main goal is to understand how Silybin reduces oxidative damage caused by avermectin in carp gills, offering management strategies. Concurrently, the current study proposes that Silybin can serve as a dietary supplement to reduce the risks brought on by repellent buildup in freshwater aquaculture.

Activation of autophagy and IL-10 production are regulated by Jun N-terminal kinase 1 and 2 and p38 mitogen activated protein kinase signaling pathways during Talaromyces marneffei infection within dendritic cells.

Previous study have shown that Talaromyces marneffei (T. marneffei) induced activation of autophagy. Therefore, we explore signaling pathway that regulates activation of autophagy by intracellular signaling mechanisms during T. marneffei infection. Further, we examine c-Jun N-terminal kinase 1 and 2 (JNK1/2) and p38 signaling pathways that regulate IL-1ß and IL-10 production and activation of autophagy during T. marneffei infection in human dendritic cells (DCs). We found that T. marneffei induced activation of JNK1/2 and p38 in human DCs. Furthermore, the inhibition of JNK1/2 and p38 increased activation of autophagy and decreased the replication of T. marneffei in T. marneffei-infected human DCs. Moreover, IL-1ß secretion in T. marneffei-infected human DCs was dependent on JNK1/2 and autophagy pathways, whereas IL-10 secretion was dependent on JNK1/2, p38 and autophagy pathways. These data suggest that JNK1/2 and p38 pathways play critical roles in activation of autophagy, the multiplication of T. marneffei and subsequent cytokine production during T. marneffei infection.

Down-Regulated CUEDC2 Increases GDNF Expression by Stabilizing CREB Through Reducing Its Ubiquitination in Glioma.

Abnormally high expression of glial cell line-derived neurotrophic factor (GDNF) derived from glioma cells has essential impacts on gliomagenesis and development, but the molecular basis underlying increased GDNF expression in glioma cells remain unclear. This work aimed to study the molecular mechanisms that may explain the accumulation of GDNF in glioma. Firstly, we observed that cAMP response element-binding protein (CREB), known as an important transcription factor for binding of GDNF promoter region, was highly expressed with an apparent accumulation into the nucleus of glioma cells, which may contribute to the transcription of GDNF. Secondly, CUE domain-containing protein 2 (CUEDC2), a ubiquitin-regulated protein, could increase the amount of binding between the E3 ligase tripartite motif-containing 21 (TRIM21) and CREB and affect the CREB level. Like our previous study, it showed that there was a significantly down-regulation of CUEDC2 in glioma. Finally, our data suggest that GDNF expression is indirectly regulated by transcription factor ubiquitination. Indeed, down-regulation of CUEDC2, decreased the ubiquitination and degradation of CREB, which was associated to high levels of GDNF. Furthermore, abundant CREB involved in the binding to the GDNF promoter region contributes to GDNF high expression in glioma cells. Collectively, it was verified the GDNF expression was affected by CREB ubiquitination regulated by CUEDC2 level.

The reversible effects of glial cell line-derived neurotrophic factor (GDNF) in the human brain.

Glial cell line-derived neurotrophic factor (GDNF) is a potent survival factor, and a member of the transforming growth factor ß (TGF-ß) superfamily acting on different neuronal activities. GDNF was originally identified as a neurotrophic factor crucially involved in the survival of dopaminergic neurons of the nigrostriatal pathway and is currently an established therapeutic target in Parkinson's disease. However, GDNF was later reported to be highly expressed in gliomas, especially in glioblastomas, and was demonstrated as a potent proliferation factor involved in the development and migration of gliomas. Here, we review our current understanding and progress made so far by researchers in our laboratories with references to relevant articles to support our discoveries. We present past and recent discoveries on the mechanisms involved in the protection of neurons by GDNF and examine its emerging roles in gliomas, as well as reasons for the abnormal expression in Glioblastoma Multiforme (GBM). Collectively, our work establishes a paradigm by which the ability of GDNF to protect dopaminergic neurons from degradation and its corresponding effects on glioma cells points to an underlying biological vulnerability in the effects of GDNF in the normal brain which can be subverted for use by cancer cells. Hence, presenting novel opportunities for intervention in glioma therapies.

Role of autophagy in regulating the immune response of dendritic cells to Talaromyces marneffei infection.

Autophagy can regulate antimicrobial immunity. However, it is unknown whether autophagy mediates the immune response of dendritic cells (DCs) to Talaromyces marneffei (T. marneffei) infection. Therefore, to explore the relationship between autophagy and multiplication of T. marneffei and investigate whether ERK1/2 signaling pathway regulates activation of autophagy and TNF-α and IFN-γ secretion by intracellular signaling mechanisms during T. marneffei infection in human DCs. DCs were infected with T. marneffei for different times. First, we found that T. marneffei induced activation of autophagy and ERK1/2 in human DCs. Second, the inhibition of ERK1/2 suppressed activation of autophagy in T. marneffei-infected human DCs. Third, the suppression of ERK1/2 and autophagy decreased TNF-α and IFN-γ production and increased the proliferation of T. marneffei. These data suggest that ERK pathway plays vital regulatory roles in activation of autophagy and subsequent cytokine production during T. marneffei infection. Our data further indicate that autophagy is important in the regulation of the DC immune response to T. marneffei infection, thereby extending our understanding of host immune responses to the fungus.

Activation of ERK1/2 and TNF-α production are regulated by calcium/calmodulin signaling pathway during Penicillium marneffei infection within human macrophages.

Previous study have shown that Penicillium marneffei (P. marneffei)-induced TNF-α production via an extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase-dependent mechanism is an important host defence mechanism against P. marneffei in human macrophages. Therefore, we explore signaling pathway that regulates TNF-α secretion and activation of ERK1/2 by intracellular signaling mechanisms during P. marneffei infection. We found that ERK1/2 activation was dependent on the calcium/calmodulin/calmodulin kinase Ⅱ pathway in P. marneffei-infected human macrophages. In contrast, P. marneffei-induced p38 MAPK activation was negatively regulated by calcium/calmodulin/calmodulin kinase Ⅱ signaling pathway. Furthermore, TNF-α production in P. marneffei-infected human macrophages was also dependent on Ca(2+)/calmodulin/calmodulin kinase Ⅱ pathway. These data suggest that Ca(2+)/calmodulin/calmodulin kinase Ⅱ pathway plays vital regulatory roles in macrophage activation and subsequent cytokine production during P. marneffei infection.

Anti-inflammatory activity of atractylenolide III through inhibition of nuclear factor-κB and mitogen-activated protein kinase pathways in mouse macrophages.

To elucidate the anti-inflammatory mechanisms involved, we investigated the effects of atractylenolide III (ATL-III) on cytokine expression, extracellular signal-regulated kinases 1 and 2 (ERK1/2), p38 mitogen-activated protein kinase (p38), C-Jun-N-terminal protein kinase1/2 (JNK1/2) and nuclear factor-κB (NF-κB) pathways in lipopolysaccharide (LPS)-induced RAW264.7 mouse macrophages. Macrophages were incubated with various concentrations (0, 25, 50, 100 µM) of ATL-III and/or LPS (1 µg/mL) for 24 h. The production of nitric oxide (NO) was determined by the Greiss reagent. The production of tumor necrosis factor alpha (TNF-α), prostaglandin E2 (PGE2) and interleukin 6 (IL-6) was determined by enzyme-linked immunosorbent assay (ELISA). Furthermore, macrophages were treated with ATL-III (0, 25, 100 µM) for 1 h and then stimulated by LPS. NF-κB, p38, JNK1/2 and ERK1/2 were determined by western blotting. We found ATL-III showed no inhibitory effect on cell proliferation at concentrations ranging from 1 µM to 100 µM. In addition, ATL-III decreased the release of NO, TNF-α, PGE2 and IL-6 in a dose-dependent manner and showed statistically significant at concentrations of 50 µM and 100 µM as well as cyclooxygenase-2 (COX-2) expression. Furthermore, ATL-III suppressed the transcriptional activity of NF-κB. ATL-III also inhibited the activation of ERK1/2, p38 and JNK1/2 in LPS-treated macrophages and showed statistically significant at concentrations of 25 µM and 100 µM. These data suggest that ATL-III shows an anti-inflammatory effect by suppressing the release of NO, PGE2, TNF-α and IL-6 related to the NF-κB- and MAPK-signaling pathways.

Role of intracellular free calcium in killing Penicillium marneffei within human macrophages.

Increases in cytosolic Ca(2+) concentration ([Ca(2+)]c) promote phagocyte antimicrobial responses. Here, we investigated macrophages stimulated by Penicillium marneffei (P. marneffei). [Ca(2+)]c was determined in macrophages loaded with the fluorescent calcium probe Fura 2/AM as they were stimulated by P. marneffei. We found that P. marneffei induced an increase in [Ca(2+)]c in human macrophages. Further, increased [Ca(2+)]c with the ionophore A23187 promoted phagosomal acidification and maturation and reduced intracellular replication of P. marneffei in P. marneffei-infected human macrophages, whereas decreased [Ca(2+)]c with the chelation MAPTAM decreased TNF-α production, inhibited phagosomal acidification and maturation and increased intracellular replication of P. marneffei. These data indicate that Ca(2+) signaling may play an important role in controlling the replication of P. marneffei within macrophages.

Effect of Jun N-terminal kinase 1 and 2 on the replication of Penicillium marneffei in human macrophages.

Penicillium marneffei (P. marneffei) is a human pathogen which persists in macrophages and threatens the immunocompromised patients. To clarify the mechanisms involved, we evaluated the effect of c-Jun N-terminal kinase 1 and 2 (JNK1/2) on cytokine expression, phagosomal maturation and multiplication of P. marneffei in P. marneffei-stimulated human macrophages. P. marneffei induced the rapid phosphorylation of JNK1/2. Using the specific inhibitor of JNK1/2 (SP600125), we found that the inhibition of JNK1/2 suppressed P. marneffei-induced tumor necrosis factor-α and IL-10 production. In addition, the presence of SP600125 increased phagosomal acidification and maturation and decreased intracellular replication. These data suggest that JNK1/2 may play an important role in promoting the replication of P. marneffei. Our findings further indicate that the pathogen through the JNK1/2 pathway may attenuate the immune response and macrophage antifungal function.

Macrophage activation by polysaccharides from Atractylodes macrocephala Koidz through the nuclear factor-κB pathway.

CONTEXT: Atractylodes macrocephala Koidz is a traditional herb. Atractylodes macrocephalaon polysaccharides (AMP) have been found to enhance immunity and improve heart function. However, the mechanisms of the immunomodulatory effect have not been investigated. OBJECTIVE: We examined whether AMP activated macrophages and explored the mechanisms of activation. MATERIALS AND METHODS: AMP was prepared and evaluated its immunomodulatory activity (25, 50, 100, and 200 µg/mL) by detecting the phagocytosis and the production of tumor necrosis factor-α (TNF-α), IFN-γ, and nitric oxide (NO) in RAW264.7 macrophages. Furthermore, the role of nuclear factor-κB (NF-κB) pathway was examined in regulating TNF-α and NO production. RESULTS: The phagocytosis of macrophages was enhanced by AMP in a dose-dependent manner and the maximal phagocytosis of macrophages occurred at concentrations of 100 and 200 µg/mL. NO, TNF-α, and IFN-γ release was also found to be dose dependent by increasing concentrations of AMP and reached the peak at a concentration of 200 µg/mL. In addition, AMP induced inhibitor kappaB (IκB) degradation and the activation of NF-κB by p65 nuclear translocation, and then the activation of NF-κB in nucleus peaked at a concentration of 200 µg/mL. Besides, NF-κB-specific inhibitor pyrrolidine dithiocarbamate (PDTC) decreased AMP-induced NO and TNF-α production. DISCUSSION AND CONCLUSION: These data suggest that AMP may modulate macrophage activities by stimulating NF-κB or activating NF-κB-dependent mechanisms.

Atractylenolide I inhibits lipopolysaccharide-induced inflammatory responses via mitogen-activated protein kinase pathways in RAW264.7 cells.

Atractylenolide I (ATL-I) is a bioactive component of Rhizoma Atractylodis macrocephalae. Although increasing evidence shows that ATL-I has an anti-inflammatory effect, the anti-inflammatory molecular mechanism of ATL-I is still unknown. In this study, we investigated the effect of ATL-I on cell viability by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and the level of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) by enzyme-linked immunosorbent assay (ELISA) in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Further, we examined the effect of ATL-I on the activation of nuclear factor-kappaB (NF-κB) and phosphorylation of extracellular signal regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (p38) by Western blot. We also investigated the effect of ATL-I on the expression of myeloid differentiation protein-2 (MD-2), CD14, complement receptor 3 (CR3), scavenger receptor class A (SR-A), toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88). We found that ATL-I showed no inhibitory effect on cell viability at concentrations ranging from 1 µM to 100 µM and markedly reduced the release of IL-6 and TNF-α at a concentrate-dependent manner. In addition, ATL-I suppressed the activity of nuclear NF-κB and the phosphorylation of ERK1/2 and p38 in LPS-treated RAW264.7 cells. Further analysis showed that ATL-I inhibited the expression of MD-2, CD14, SR-A, TLR4 and MyD88, but the expression of CR3 was unaffected. These data suggest that ATL-I shows an anti-inflammatory effect by inhibiting TNF-α and IL-6 production. The anti-inflammatory effects of ATL-I may be associated with the inhibition of the NF-κB, ERK1/2 and p38 signaling pathways.

Exosomes released from macrophages infected with Talaromyces marneffei activate the innate immune responses and decrease the replication.

INTRODUCTION: Recent studies have demonstrated that exosomes play roles in pathogenesis and in the treatment of various diseases. We explored the influence of exosomes released from Talaromyces marneffei (T. marneffei)-infected macrophages on human macrophages to determine whether they play a role in the pathogenesis of T. marneffei infection. METHODS: Exosomes derived from macrophages infected with T. marneffei were extracted and characterized by transmission electron microscopy and western blot. Moreover, we examined exosomes that modulated IL-10 and TNF-α secretion and activation of p42 and p44 extracellular signal-regulated kinase 1 and 2 (ERK1/2) and activation of autophagy. RESULTS: We found that exosomes promoted activation of ERK1/2 and autophagy, IL-10 and TNF-α secretion in human macrophages. Further, exosomes decreased the multiplication of T. marneffei in T. marneffei-infected human macrophages. Interestingly, exosomes isolated from T. marneffei-infected but not from uninfected macrophages can stimulate innate immune responses in resting macrophages. CONCLUSION: Our studies are the first to demonstrate that exosomes isolated from T. marneffei-infected macrophages can modulate the immune system to control inflammation, and we hypothesize that exosomes play significant roles in activation of ERK1/2 and autophagy, the replication of T. marneffei and cytokine production during T. marneffei infection.

CTSB Nuclear Translocation Facilitates DNA Damage and Lysosomal Stress to Promote Retinoblastoma Cell Death.

Retinoblastoma (RB) is a pernicious tumor originating from photoreceptor precursor cells that often endangers the lives of children. The purpose of our study was to further investigate the influence of cathepsin B (CTSB) nuclear translocation on RB cell death. Y79 cells were injected into the vitreous cavity of nude mice at a dose of 4 µL/mouse to establish an animal model of RB. Real-time quantitative polymerase chain reaction (RT-qPCR), Western blot analysis, a comet assay, a Cell Counting Kit-8 (CCK-8) assay and flow cytometry were used to measure the levels of the interrelated genes and proteins and to evaluate alterations in autophagy, apoptosis, proliferation, DNA damage and cell cycle arrest. CTSB was found to be expressed at low levels in RB animal model samples and RB cell lines. Functionally, CTSB nuclear translocation promoted DNA damage, cell cycle arrest, ferroptosis and autophagy in Y79 cells and inhibited their proliferation. Downstream mechanistic studies showed that nuclear translocation of CTSB facilitates DNA damage and cell cycle arrest in RB cells by inhibiting breast cancer 1 protein (BRCA1) expression and also activates the signal transducer and activator of transcription 3/stimulator of interferon response cGAMP interactor 1 (STAT3/STING1) pathway to induce lysosomal stress, leading to ferroptosis and autophagy in Y79 cells and alleviating RB. Nuclear translocation of CTSB facilitates DNA damage and cell cycle arrest in RB cells by inhibiting BRCA1 expression and activating the STAT3/STING1 pathway and induces lysosomal stress, which eventually leads to ferroptosis and autophagy and mitigates RB.

Association of Sirtuin Gene Polymorphisms with Susceptibility to Coronary Artery Disease in a North Chinese Population.

AIMS: Coronary artery disease (CAD) represents the leading cause of death worldwide. Accumulating evidence also suggests that sirtuins (SIRTS) have been associated with CAD. The present study was aimed at investigating the association between 12 gene polymorphisms for SIRTs and the development of CAD in a Chinese population. MATERIALS AND METHODS: 12 SNPs (rs12778366 (T > C), rs3758391 (T > C), rs3740051 (A > G), rs4746720 (C > T), rs7895833 (G > A), rs932658 (A > C) for SIRT1, rs2015 (G > T) for SIRT2, rs28365927 (G > A), rs11246020 (C > T) for SIRT3, rs350844 (G > A), rs350846 (G > C), and rs107251 (C > T) for SIRT6) were selected and assessed in a cohort of 509 CAD patients and 552 matched healthy controls for this study. Genomic DNA from whole blood was extracted, and the SNPs were assessed using MassARRAY method. RESULTS: TT genotype for rs3758391 and GG genotype for rs7895833 of SIRT1 were at higher risk of CAD, whereas the CC genotype for rs4746720 of SIRT1 was associated with a significantly decreased risk of CAD. The A allele of the rs28365927 of SIRT3 showed a significant decreased risk association with CAD patient group (P = 0.014). Significant difference in genotypes rs350844 (G > A) (P = 0.004), rs350846 (G > C) (P = 0.002), and rs107251 (C > T) (P ≤ 0.01) for SIRT6 was also found between the CAD patients and the healthy controls. Haplotype CTA significantly increased the risk of CAD (P = 0.000118, OR = 1.497, 95%CI = 1.218-1.840), while haplotype GCG significantly decreases the risk of CAD (P = 0.000414, OR = 1.131, 95%CI = 0.791-1.619). CONCLUSIONS: The SNP rs28365927 in the SIRT3 gene and SNP rs350844, rs350846, and rs107251 in the SIRT6 gene present significant associations with CAD in a north Chinese population. Haplotype CTA and GCG generated by rs350846/rs107251/rs350844 in the SIRT6 might also increase and decrease the risk of CAD, respectively.

A novel subgenotype C6 Enterovirus A71 originating from the recombination between subgenotypes C4 and C2 strains in mainland China.

Recombination plays important roles in the genetic diversity and evolution of Enterovirus A71 (EV-A71). The phylogenetics of EV-A71 in mainland China found that one strain DL71 formed a new subgenotype C6 with unknown origin. This study investigated the detailed genetic characteristics of the new variant. DL71 formed a distinct cluster within genotype C based on the genome and individual genes (5'UTR, VP4, VP1, 2A, 2B, 2C, 3D, and 3'UTR). The average genetic distances of the genome and individual genes (VP3, 2A, 2B, 2C, 3A, 3C, and 3D) between DL71 and reference strains were greater than 0.1. Nine recombination events involving smaller fragments along DL71 genome were detected. The strains Fuyang-0805a (C4) and Tainan/5746/98 (C2) were identified as the parental strains of DL71. In the non-recombination regions, DL71 had higher identities with Fuyang-0805a than Tainan/5746/98, and located in the cluster with C4 strains. However, in the recombination regions, DL71 had higher identities with Tainan/5746/98 than Fuyang-0805a, and located in the cluster with C2 strains. Thus, DL71 was a novel multiple inter-subgenotype recombinant derived from the dominant subgenotype C4 and the sporadic subgenotype C2 strains. Monitoring the emergence of new variants by the whole-genome sequencing remains essential for preventing disease outbreaks and developing new vaccines.

Cross-link regulation of precursor N-cadherin and FGFR1 by GDNF increases U251MG cell viability.

Glial cell line-derived neurotrophic factor (GDNF) is considered to be involved in the development of glioma. However, uncovering the underlying mechanism of the proliferation of glioma cells is a challenging work in progress. We have identified the binding of the precursor of N-cadherin (proN-cadherin) and GDNF on the cell membrane in previous studies. In the present study, we observed increased U251 Malignant glioma (U251MG) cell viability by exogenous GDNF (50 ng/ml). We also confirmed that the high expression of the proN-cadherin was stimulated by exogenous GDNF. Concurrently, we affirmed that lower expression of proN-cadherin correlated with reduced glioma cell viability. Additionally, we observed glioma cell U251MG viability as the phosphorylation level of FGFR1 at Y653 and Y654 was increased after exogenous GDNF treatment, which led to increased interaction between proN-cadherin and FGFR1 (pY653+Y654). Our experiments presented a new mechanism adopted by GDNF supporting glioma development and indicated a possible therapeutic potential via the inhibition of proN-cadherin/FGFR1 interaction.

Identification of COL1A1 as an invasion­related gene in malignant astrocytoma.

Malignant astrocytoma (MA) is the most common and severe type of brain tumor. A greater understanding of the underlying mechanisms responsible for the development of MA would be beneficial for the development of targeted molecular therapies. In the present study, the upregulated differentially expressed genes (DEGs) in MA were obtained from the Gene Expression Omnibus database using R/Bioconductor software. DEGs in different World Health Organization classifications were compared using the Venny tool and 15 genes, including collagen type I α1 chain (COL1A1) and laminin subunit γ1 (LAMC1), were revealed to be involved in the malignant progression of MA. In addition, the upregulated DEGs in MA were evaluated using functional annotations of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes with the Database for Annotation, Visualization, and Integrated Discovery tool. The results indicated that invasion­associated enrichment was observed in 'extracellular matrix' (ECM), 'cell adhesion' and 'phosphoinositide 3­kinase­protein kinase B signaling pathway'. Subsequently, the analysis of the protein­protein interactions was performed using STRING and Cytoscape software, which revealed that the ECM component was the invasion­associated module and its corresponding genes included COL1A1, LAMC1 and fibronectin 1. Finally, survival Kaplan­Meier estimate was conducted using cBioportal online, which demonstrated that COL1A1 expression affected the survival of and recurrence in patients with MA. Moreover, the results of in vitro Transwell assay and western blot analysis revealed that the depleted levels of COL1A1 also decreased the expression of several proteins associated with cell invasion, including phosphorylated­signal transducer and activator of transcription 3, matrix metalloproteinase (MMP)­2, MMP­9 and nuclear factor­κB. On the whole, the present study identified the invasion­related target genes and the associated potential pathways in MA. The results indicated that COL1A1 may be a candidate biomarker for the prognosis and treatment of MA.

Distinct Features of Doublecortin as a Marker of Neuronal Migration and Its Implications in Cancer Cell Mobility.

Neuronal migration is a critical process in the development of the nervous system. Defects in the migration of the neurons are associated with diseases like lissencephaly, subcortical band heterotopia (SBH), and pachygyria. Doublecortin (DCX) is an essential factor in neurogenesis and mutations in this protein impairs neuronal migration leading to several pathological conditions. Although, DCX is capable of modulating and stabilizing microtubules (MTs) to ensure effective migration, the mechanisms involved in executing these functions remain poorly understood. Meanwhile, there are existing gaps regarding the processes that underlie tumor initiation and progression into cancer as well as the ability to migrate and invade normal cells. Several studies suggest that DCX is involved in cancer metastasis. Unstable interactions between DCX and MTs destabilizes cytoskeletal organization leading to disorganized movements of cells, a process which may be implicated in the uncontrolled migration of cancer cells. However, the underlying mechanism is complex and require further clarification. Therefore, exploring the importance and features known up to date about this molecule will broaden our understanding and shed light on potential therapeutic approaches for the associated neurological diseases. This review summarizes current knowledge about DCX, its features, functions, and relationships with other proteins. We also present an overview of its role in cancer cells and highlight the importance of studying its gene mutations.