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Eosinophilic gastroenteritis poses a significant diagnostic challenge, particularly in developing countries, where the awareness of this condition may be limited. Here, the case of a patient in her early 30s, who presented with recurrent episodes of abdominal pain and diarrhea, is reported. Initial standard laboratory investigations revealed normal complete blood counts and elevated total serum immunoglobulin E levels. Upper and lower endoscopic evaluations with systemic biopsies did not reveal any significant abnormalities. However, computed tomography revealed a thickened small intestine wall, halo signs, and mild ascites. Analysis of the ascitic fluid confirmed eosinophilia. These findings prompted a diagnosis of eosinophilic gastroenteritis. The patient responded well to a targeted elimination diet, corticosteroids, and antileukotriene medication. The present case emphasizes the importance of considering eosinophilic gastroenteritis in the differential diagnosis of patients who present with abdominal pain and eosinophilic ascites., Competing Interests: Declaration of conflicting interestThe authors declare that there are no conflicts of interest.

'Drug abuse' has been recognized as one of the most pressing epidemics in contemporary society. Traditional research has primarily focused on understanding how drugs induce neurotoxicity or degeneration within the central nervous system (CNS) and influence systems related to reward, motivation, and cravings. However, recent investigations have increasingly shifted their attention toward the detrimental consequences of drug abuse on the blood-brain barrier (BBB). The BBB is a structural component situated in brain vessels, responsible for separating brain tissue from external substances to maintain brain homeostasis. The BBB's function is governed by cellular interactions involving various elements of the 'neurovascular unit (NVU),' such as neurons, endothelial cells, astrocytes, pericytes, and microglia. Disruption of the NVU is closely linked to serious neurodegeneration. This review provides a comprehensive overview of the harmful effects of psychostimulant drugs on the BBB, highlighting the mechanisms through which drugs can damage the NVU. Additionally, the review proposes novel therapeutic targets aimed at protecting the BBB. By understanding the intricate relationships between drug abuse, BBB integrity, and NVU function, researchers and clinicians may uncover new strategies to mitigate the damaging impact of drug abuse on brain health.

Human sterile α motif and HD domain-containing protein 1 (SAMHD1) has deoxyribonucleoside triphosphohydrolase (dNTPase) activity that allows it to defend against human immunodeficiency virus type I (HIV-1) infections and regulate the cell cycle. Although SAMHD1 mutations have been identified in various cancer types, their role in cancer is unclear. Here, we aimed to investigate the oncogenic role of SAMHD1 in human clear cell renal cell carcinoma (ccRCC), particularly as a core molecule promoting cancer cell migration. We found that SAMHD1 participated in endocytosis and lamellipodia formation. Mechanistically, SAMHD1 contributed to the formation of the endosomal complex by binding to cortactin. Thereafter, SAMHD1-stimulated endosomal focal adhesion kinase (FAK) signaling activated Rac1, which promoted lamellipodia formation on the plasma membrane and enhanced the motility of ccRCC cells. Finally, we observed a strong correlation between SAMHD1 expression and the activation of FAK and cortactin in tumor tissues obtained from patients with ccRCC. In brief, these findings reveal that SAMHD1 is an oncogene that plays a pivotal role in ccRCC cell migration through the endosomal FAK-Rac1 signaling pathway., (© 2023. The Author(s).)

Background: DNA methylation on cytosine in the CpG dinucleotides is one of the most common epigenetic perturbations taking place during cancer initiation, progression, occurrence and resistance therapy. DNA methylation seems to be sufficiently stable epigenetic modification to be utilized as a cancer biomarker in in vitro diagnostic (IVD) settings. Nowadays, the SHOX2 methylation (mSHOX2) is one of the most valuable DNA methylation biomarkers of lung cancer that is the leading cause of cancer death. It is being continuously validated across ethnicities, lifestyles and lifespan. This study focused on characteristics of mSHOX2 in Vietnamese patients with lung cancer since a lack of investigation and evidence of its utility in this country., Methods: The probe and primer sets were designed according to the MethyLight method for quantitative assessment of the mSHOX2 in 214 formalin-fixed paraffin-embedded (FFPE) lung tissues and 57 plasma samples., Results: mSHOX2 in FFPE tissues allowed discriminating benign and malignant lung diseases with 60% (95% CI 50.7-68.8%) sensitivity and 90.4% (95% CI 82.6-95.5%) specificity. Importantly, based on mSHOX2 in plasma, lung cancer could be detected with 83.3% (95% CI 65.3-94.4%) sensitivity and 92.6% (95% CI 75.7-99.1%) specificity, respectively. There were insignificant associations between mSHOX2 with age, cancer stage, EGFR mutation and serum CEA, CYFRA21-1 concentrations except for that gender., Conclusion: Our study indicated that mSHOX2 was satisfactory for distinguishing malignant from benign lung tissue and noninvasively detecting lung cancer., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

The dysregulation of fibroblast growth factor (FGF) signaling has been implicated in tumorigenesis, tumor progression, angiogenesis, and chemoresistance. The small-molecule AZD4547 is a potent inhibitor of FGF receptors. This study was performed to investigate the antitumor effects and determine the mechanistic details of AZD4547 in ovarian cancer cells. AZD4547 markedly inhibited the proliferation and increased the apoptosis of ovarian cancer cells. AZD4547 also suppressed the migration and invasion of ovarian cancer cells under nontoxic conditions. Furthermore, it attenuated the formation of spheroids and the self-renewal capacities of ovarian cancer stem cells and exerted an antiangiogenic effect. It also suppressed in vivo tumor growth in mice. Collectively, this study demonstrated the antitumor effect of AZD4547 in ovarian cancer cells and suggests that it is a promising agent for ovarian cancer therapy.

Arrest defective 1 (ARD1), also known as N(alpha)-acetyltransferase 10 (NAA10) was originally identified as an N-terminal acetyltransferase (NAT) that catalyzes the acetylation of N-termini of newly synthesized peptides. After that, mammalian ARD1/NAA10 expanded its' role to lysine acetyltransferase (KAT) that post-translationally acetylates internal lysine residues of proteins. ARD1/NAA10 is the only enzyme with both NAT and KAT activities. However, recent studies on the role of human ARD1/NAA10 (hARD1/NAA10) in lysine acetylation are contradictory, as crystal structure and in vitro acetylation assay results revealed the lack of KAT activity. Thus, the role of hARD1/NAA10 in lysine acetylation is still debating. Here, we found a clue that possibly explains these complicated and controversial results on KAT activity of hARD1/NAA10. Recombinant hARD1/NAA10 exhibited KAT activity, which disappeared soon in vitro. Size-exclusion analysis revealed that most recombinant hARD1/NAA10 formed oligomers over time, resulting in the loss of KAT activity. While oligomeric recombinant hARD1/NAA10 lost its ability for lysine acetylation, its monomeric form clearly exhibited lysine acetylation activity in vitro. We also characterized the KAT activity of hARD1/NAA10 that was influenced by several experimental conditions, including concentration of reactants and reaction time. Taken together, our study proves that recombinant hARD1/NAA10 exhibits KAT activity in vitro but only under accurate conditions, including reactant concentrations and reaction duration.

Glutathione (GSH) degradation plays an essential role in GSH homeostasis, which regulates cell survival, especially in cancer cells. Among human GSH degradation enzymes, the ChaC2 enzyme acts on GSH to form 5-l-oxoproline and Cys-Gly specifically in the cytosol. Here, we report the crystal structures of ChaC2 in two different conformations and compare the structural features with other known γ-glutamylcyclotransferase enzymes. The unique flexible loop of ChaC2 seems to function as a gate to achieve specificity for GSH binding and regulate the constant GSH degradation rate. Structural and biochemical analyses of ChaC2 revealed that Glu74 and Glu83 play crucial roles in directing the conformation of the enzyme and in modulating the enzyme activity. Based on a docking study of GSH to ChaC2 and binding assays, we propose a substrate-binding mode and catalytic mechanism. We also found that overexpression of ChaC2, but not mutants that inhibit activity of ChaC2, significantly promoted breast cancer cell proliferation, suggesting that the GSH degradation by ChaC2 affects the growth of breast cancer cells. Our structural and functional analyses of ChaC2 will contribute to the development of inhibitors for the ChaC family, which could effectively regulate the progression of GSH degradation-related cancers., Competing Interests: The authors declare no conflicts of interest.

Arrest defective 1 is an acetyltransferase that acetylates N-terminal amino acid or internal lysine residues of its target proteins. By acetylating its target proteins, ARD1 plays roles in many cellular activities, including proliferation, differentiation, autophagy, and apoptosis. In recent years, a number of investigations have emerged reporting the dysregulated expression of ARD1 in different types of cancer, including lung, liver, pancreas, breast, prostate, and colon cancer. Furthermore, the expression level of ARD1 in cancer tissues has been correlated with the progression and metastasis of the cancer and the survival of cancer patients. Consequently, mechanistic studies have revealed that ARD1-mediated protein acetylation plays an important role in modulating several cellular events that are important for cancer development, such as cell cycle progression, cell death, and migration. On the basis of this evidence, targeting of ARD1 has been proposed as a promising avenue for the development of novel cancer therapeutics. This review summarizes the biological functions of ARD1 in different types of cancer and provides a deep insight into the biochemical activities of ARD1 during tumor progression.

The concept of drug repositioning has recently received considerable attention in the field of oncology. In the present study, we propose that paroxetine can be used as a potent anticancer drug. Paroxetine, one of the selective serotonin reuptake inhibitors (SSRIs), has been widely prescribed for the treatment of depression and anxiety disorders. Recently, SSRIs have been reported to have anticancer activity in various types of cancer cells; however, the underlying mechanisms of their action are not yet known. In this study, we investigated the potential anticancer effect of paroxetine in human colorectal cancer cells, HCT116 and HT-29. Treatment with paroxetine reduced cell viability, which was associated with marked increase in apoptosis, in both the cell lines. Also, paroxetine effectively inhibited colony formation and 3D spheroid formation. We speculated that the mode of action of paroxetine might be through the inhibition of two major receptor tyrosine kinases - MET and ERBB3 - leading to the suppression of AKT, ERK and p38 activation and induction of JNK and caspase-3 pathways. Moreover, in vivo experiments revealed that treatment of athymic nude mice bearing HT-29 cells with paroxetine remarkably suppressed tumour growth. In conclusion, paroxetine is a potential therapeutic option for patients with colorectal cancer., (© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Cancer is the second leading cause of death worldwide and has become a global burden. It has long been known that inflammation is related to cancer, as inflammatory components have been identified in the tumor microenvironment and support tumor progression. Among the key inflammatory mediators, leukotrienes were found to be involved in cancer development. In particular, leukotriene B4, which is converted from leukotriene A4 by leukotriene A4 hydrolase (LTA4H), has been implicated in several types of cancer. In addition, LTA4H has attracted attention because of purported roles in inflammation and cancer development. Herein, we review the history of LTA4H, its emerging roles in cancer development, and the development of LTA4H inhibitors in cancer prevention and therapy., (© 2018 New York Academy of Sciences.)

Post-translational modifications (PTMs) are chemical alterations that occur in proteins that play critical roles in various cellular functions. Lysine acetylation is an important PTM in eukaryotes, and it is catalyzed by lysine acetyltransferases (KATs). KATs transfer acetyl-coenzyme A to the internal lysine residue of substrate proteins. Arrest defective 1 (ARD1) is a member of the KAT family. Since the identification of its KAT activity 15 years ago, many studies have revealed that diverse cellular proteins are acetylated by ARD1. ARD1-mediated lysine acetylation is a key switch that regulates the enzymatic activities and biological functions of proteins and influences cell biology from development to pathology. In this review, we summarize protein lysine acetylation mediated by ARD1 and describe the biological meanings of this modification.

SAM domain and HD domain containing protein 1 (SAMHD1) is a deoxynucleotide triphosphohydrolase (dNTPase) that inhibits retroviruses by depleting intracellular deoxynucleotide triphosphates (dNTPs) in non-cycling myeloid cells. Although SAMHD1 is expressed ubiquitously throughout the human body, the molecular mechanisms regulating its enzymatic activity and function in non-immune cells are relatively unexplored. Here, we demonstrate that the dNTPase activity of SAMHD1 is regulated by acetylation, which promotes cell cycle progression in cancer cells. SAMHD1 is acetylated at residue lysine 405 (K405) in vitro and in vivo by an acetylatransferase, arrest defective protein 1 (ARD1). Acetylated SAMHD1 wildtype proteins have enhanced dNTPase activity in vitro , whereas non-acetylated arginine substituted mutants (K405R) do not. K405R mutant expressing cancer cells have reduced G1/S transition and slower proliferation compared to wildtype. SAMHD1 acetylation levels are strongest during the G1 phase, indicating a role during G1 phase. Collectively, these findings suggest that SAMHD1 acetylation enhances its dNTPase activity and promotes cancer cell proliferation. Therefore, SAMHD1 acetylation may be a potent therapeutic target for cancer treatment., Competing Interests: CONFLICTS OF INTEREST We have no conflicts of interest.

Aurora kinase A (AuA) is a prerequisite for centrosome maturation, separation, and mitotic spindle assembly, thus, it is essential for cell cycle regulation. Overexpression of AuA is implicated in poor prognosis of many types of cancer. However, the regulatory mechanisms underlying the functions of AuA are still not fully understood. Here, we report that AuA colocalizes with arrest defective protein 1 (ARD1) acetyltransferase during cell division and cell migration. Additionally, AuA is acetylated by ARD1 at lysine residues at positions 75 and 125. The double mutations at K75/K125 abolished the kinase activity of AuA. Moreover, the double mutant AuA exhibited diminished ability to promote cell proliferation and cell migration. Mechanistic studies revealed that AuA acetylation at K75/K125 promoted cell proliferation via activation of cyclin E/CDK2 and cyclin B1. In addition, AuA acetylation stimulated cell migration by activating the p38/AKT/MMP-2 pathway. Our findings indicate that ARD1-mediated acetylation of AuA enhances cell proliferation and migration, and probably contributes to cancer development., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.