Endocan expression is increasingly studied in various human cancers. Experimental evidence showed that human endocan, through its glycan chain, is implicated in various processes of tumor growth. We functionally characterize mouse endocan which is also a chondroitin sulfate proteoglycan but much less glycanated than human endocan. Distant domains from the O-glycanation site, located within exons 1 and 2 determine the glycanation pattern of endocan. In opposite to the human homologue, overexpression of mouse endocan in HT-29 cells delayed the tumor appearance and reduced the tumor growth rate. This tumor growth inhibition is supported by non glycanated form of mouse endocan. Non glycanated human endocan overexpressed in HT-29, A549 or K1000 cells also exhibited an anti-tumor effect. Moreover, systemic delivery of non glycanated human endocan also results in HT-29 tumor growth delay. In vitro, endocan polypeptide did not affect HT-29 cell proliferation, nor cell viability. In tumor tissue sections, a stromal inflammatory reaction was observed only in tumors overexpressing endocan polypeptide, and depletion of CD122+ cells was able to delete partially the anti-tumor effect of endocan polypeptide. These results reveal a novel pathway for endocan in the control of tumor growth, which involves inflammatory cells of the innate immunity.
Dicyclomine is a human muscarinic acetylcholine receptor antagonist used for the treatment of abdominal cramps. We are reporting here that dicyclomine can inhibit the in vitro growth and virulence factors of the human pathogen Candida albicans very effectively. Dicyclomine inhibited adhesion, early biofilm, mature biofilm, and planktonic growth. Yeast to hyphal form transition of C. albicans in various inducer media such as serum, proline, glucose, and N-acetylglucosamine was inhibited. Dicyclomine also could kill C. albicans cells within 15 min of exposure. Dicyclomine appears to inhibit the yeast to hyphal conversion by affecting signal transduction pathway. The expression of selected genes associated with yeast to hyphal form transition in serum in presence of dicyclomine was studied using real-time polymerase chain reaction (RtPCR). The RtPCR analysis showed that dicyclomine targets both cAMP pathway as well as MAPK cascade. Eight genes were upregulated. Out of these, three major upregulated genes were Bcy1, Tup1, and Mig1. Dicyclomine downregulated Ume6, Ece1, and Pde2 genes which are involved in cAMP signaling pathway and also downregulated the DNA binding protein gene, Rfg1. Dicyclomine significantly upregulated the master negative regulator of hyphal formation, Tup1. Based on this study we suggest that the muscarinic acetylcholine receptor antagonist, dicyclomine could be repositioned as a potential anti-Candida albicans as well as anti-virulence agent.
Purpose Campylobacter species are currently the most common cause of bacterial gastroenteritis. In Lebanon, Campylobacter infection occurrence is underdiagnosed owing to the lack of specific culture and rapid test kits, particularly among children. This study aimed to evaluate the prevalence, laboratory findings, and clinical characteristics of Campylobacter infection in hospitalized children with acute gastroenteritis in South Lebanon. Methods We conducted a 6-month retrospective cohort study between January and June 2018, including 291 children aged between 1 month and 12 years, who were admitted to a tertiary healthcare center in South Lebanon. The medical files of the patients were reviewed to retrieve the required clinical information, including clinical and laboratory data. Results The prevalence of campylobacteriosis agents in pediatric patients with acute gastroenteritis is 12.02%. Patients infected with Campylobacter had more severe acute gastroenteritis than Campylobacter -negative patients and often presented with high-grade fever, diarrhea episodes more than six times per day, diarrhea lasting for more than five days, and dehydration. Indeed, children with high-grade fever (≥38.5°C) were five times more likely to test positive for Campylobacter than those with low-grade fever. In addition, the results showed a higher Vesikari score for the majority of Campylobacter -positive patients with severe acute gastroenteritis compared to a moderate profile for Campylobacter -negative patients. Conclusion The present study findings highlight that Campylobacter infection is frequent among children with acute gastroenteritis. Therefore, the detection of Campylobacter should be carried out for the diagnosis of human gastroenteritis in Lebanon, along with the detection of routine enteropathogens.
Dicyclomine is a selective muscarinic M1 receptor antagonist in humans. Dicyclomine targets signal transduction genes and inhibits virulence factors in the human pathogen, Candida albicans. Muscarinic acetylcholine receptors are not known to exist in C. albicans. We carried out a search to identify a muscarinic receptor like proteins in C. albicans. A BLAST protein analysis revealed that a C. albicans protein Rrp9 shares 54% identity and 71% similarity with human muscarinic M1 receptor at 24 amino acids overlap. Global alignment between human muscarinic M1 receptor and C. albicans Rrp9 showed 19% identity and 33% similarity at 570 amino acid residues overlap. Our molecular docking study of dicyclomine with C. albicans, Rrp9, Gpr1, Ste2 and Ste3 showed that dicyclomine could bind only with Rrp9 by forming hydrogen bond interactions with VAL386 and ILE313 amino acid residues in the active site region. Dicyclomine bound with human muscarinic receptor M1 by forming hydrogen bond interaction with ARG123 at the active site region. Our study suggests that Rrp9 may be considered as a potential target for dicyclomine in C. albicans.
Retropharyngeal space swelling is a rare occurrence following minor head and neck trauma. Upper airway obstruction is a potentially life-threatening sequela. The authors present a case of retropharyngeal space haematoma following minor blunt head and neck trauma. Management was conservative with gradual spontaneous resolution of the haematoma. The literature is reviewed and the management and treatment principles presented.
Background: In Candida Albicans, yeast to hyphal form transition can be induced by serum, proline, glucose, and N-acetyl glucosamine. Acetylcholine is a neuromodulator which can stimulate both muscarinic and nicotinic acetylcholine receptors in humans. In this study, we are reporting that acetylcholine can induce yeast to hyphal form transition in C. Albicans. The adenylyl cyclase inhibitor, MDL 12, 330A inhibited this transition indicating the role of cAMP. Muscarinic receptors in C. Albicans did not report yet. We have reported that C. Albicans Rrp9 exhibits identity and similarity with the human muscarinic receptor M1. In humans, activation of muscarinic M1 receptor can produce cAMP through inositol phosphate pathway. The inositol phosphate pathway in C. Albicans is already known. We have carried out the local and global alignment sequences between the proteins of humans and C. Albicans which are involved in inositol phosphate pathway. We found considerable identities and similarities between them. Herein, we hypothesize that acetylcholine may activate Rrp9 which may lead to activation of inositol phosphate signalling pathway in C. Albicans. This study suggests that Rrp9 may have a potential role in yeast to hyphal form transition in C. Albicans.
Background Etiologic diagnosis is important for treatment and consequently for the prognosis of the patient with infectious spondylodiscitis. Unfortunately, this diagnosis can be difficult and the need of a guided discovertebral biopsy (GDVB) could be helpful. Objectives The purpose of this retrospective study was to assess the performance of GDVB to determine the etiology of infectious spondylodiscitis. Methods Patients hospitalized in Rheumatology department, between 1999 to 2012, for suspected diagnosis of infectious spondilodiscitis has been collected. Only patients who had a GDVB for etiologic diagnosis of infectious spondylodiscitis were included in this study. Results 60 patients were included. The accurate arguments diagnosis was obtained in 32 %. Then GDVB was profitable for tuberculosis by: tuberculosis culture, necrosis caseum with giganted cells in 17 % of case; for pyogenes germs it was also profitable in 15% (four cases for staphylococcus aureus one case for brucellosis, one case for Klebsiella oxytoca, one case for Serratia Marcescens, two cases for E.coili ). In 40 % of case the results was no specific with an inflammatory involvement in histopathologic exam: with a definitive diagnosis of tuberculosis in 20 cases and brucellosis in 4 cases. In 28% of case the results was without particularity, non interpretable or non transmitted (major case for tuberculosis, and brucellosis and pyogenes germs for the rest). Conclusions Guided discovertebral biopsy is helpful for the diagnosis of infectious spondylodiscitis and should be done whenever this condition is suspected. The increased rates for no specific inflammatory involvement and no interpretable results could be reduced by respecting the guided discovertebral biopsy technical in order to biopsy the real lesions for different exams. Disclosure of Interest None Declared
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