Hanan Hassan Fouad

Gastrointestinal (GI) diseases have become a global health issue and an economic burden due to their wide distribution, late prognosis, and the inefficacy of recent available medications. Therefore, it is crucial to search for new strategies for their management. In the recent decades, mesenchymal stem cells (MSCs) therapy has attracted attention as a viable option for treating a myriad of GI disorders such as hepatic fibrosis (HF), ulcerative colitis (UC), acute liver injury (ALI), and non-alcoholic fatty liver disease (NAFLD) due to their regenerative and paracrine properties. Importantly, recent studies have shown that MSC-derived extracellular vesicles (MSC-EVs) are responsible for most of the therapeutic effects of MSCs. In addition, EVs have revealed several benefits over their parent MSCs, such as being less immunogenic, having a lower risk of tumour formation, being able to cross biological barriers, and being easier to store. MSC-EVs exhibited regenerative, anti-oxidant, anti-inflammatory, anti-apoptotic, and anti-fibrotic effects in different experimental models of GI diseases. However, a key issue with their clinical application is the maintenance of their stability and efficacy following in vivo transplantation. Preconditioning of MSC-EVs or their parent cells is one of the novel methods used to improve their effectiveness and stability. Herein, we discuss the application of MSC-EVs in several GI disorders taking into account their mechanism of action. We also summarise the challenges and restrictions that need to be overcome to promote their clinical application in the treatment of various GI diseases as well as the recent developments to improve their effectiveness. A representation of the innovative preconditioning techniques that have been suggested for improving the therapeutic efficacy of MSC-EVs in GI diseases. The pathological conditions in various GI disorders (ALI, UC, HF and NAFLD) create a harsh environment for EVs and their parents, increasing the risk of apoptosis and senescence of MSCs and thereby diminishing MSC-EVs yield and restricting their large-scale applications. Preconditioning with pharmacological agents or biological mediators can improve the therapeutic efficacy of MSC-EVs through their adaption to the lethal environment to which they are subjected. This can result in establishment of a more conducive environment and activation of numerous vital trajectories that act to improve the immunomodulatory, reparative and regenerative activities of the derived EVs, as a part of MSCs paracrine system. ALI, acute liver injury; GI diseases, gastrointestinal diseases; HF, hepatic fibrosis; HSP, heat shock protein; miRNA, microRNA; mRNA, messenger RNA; MSC-EVs, mesenchymal stem cell-derived extracellular vesicles; NAFLD, non-alcoholic fatty liver disease; UC, ulcerative colitis.

Growing evidence points to impaired autophagy as one of the major factors implicated in the pathophysiology of Parkinson's disease (PD). Autophagy is a downstream target of adenosine monophosphate-activated protein kinase (AMPK). Inosine has already demonstrated a neuroprotective effect against neuronal loss in neurodegenerative diseases, mainly due its anti-inflammatory and antioxidant properties. We, herein, aimed at investigating the neuroprotective effects of inosine against rotenone-induced PD in rats and to focus on the activation of AMPK-mediated autophagy. Inosine successfully increased p-AMPK/AMPK ratio in PD rats and improved their motor performance and muscular co-ordination (assessed by rotarod, open field, and grip strength tests, as well as by manual gait analysis). Furthermore, inosine was able to mitigate the rotenone-induced histopathological alterations and to restore the tyrosine hydroxylase immunoreactivity in PD rats' substantia nigra. Inosine-induced AMPK activation resulted in an autophagy enhancement, as demonstrated by the increased striatal Unc-S1-like kinase1 and beclin-1 expression, and also by the increment light chain 3II to light chain 3I ratio, along with the decline in striatal mammalian target of rapamycin and p62 protein expressions. The inosine-induced stimulation of AMPK also attenuated neuronal apoptosis and promoted antioxidant activity. Unsurprisingly, these neuroprotective effects were antagonized by a preadministration of dorsomorphin (an AMPK inhibitor). In conclusion, inosine exerted neuroprotective effects against the rotenone-induced neuronal loss via an AMPK activation and through the restoration of the imbalance between autophagy and apoptosis. These findings support potential application of inosine in PD treatment.

Growing evidence points to impaired autophagy as one of the major factors implicated in the pathophysiology of Parkinson's disease (PD). Autophagy is a downstream target of adenosine monophosphate-activated protein kinase (AMPK). Inosine has already demonstrated a neuroprotective effect against neuronal loss in neurodegenerative diseases, mainly due its anti-inflammatory and antioxidant properties. We, herein, aimed at investigating the neuroprotective effects of inosine against rotenone-induced PD in rats and to focus on the activation of AMPK-mediated autophagy. Inosine successfully increased p-AMPK/AMPK ratio in PD rats and improved their motor performance and muscular co-ordination (assessed by rotarod, open field, and grip strength tests, as well as by manual gait analysis). Furthermore, inosine was able to mitigate the rotenone-induced histopathological alterations and to restore the tyrosine hydroxylase immunoreactivity in PD rats' substantia nigra. Inosine-induced AMPK activation resulted in an autophagy enhancement, as demonstrated by the increased striatal Unc-S1-like kinase1 and beclin-1 expression, and also by the increment light chain 3II to light chain 3I ratio, along with the decline in striatal mammalian target of rapamycin and p62 protein expressions. The inosine-induced stimulation of AMPK also attenuated neuronal apoptosis and promoted antioxidant activity. Unsurprisingly, these neuroprotective effects were antagonized by a preadministration of dorsomorphin (an AMPK inhibitor). In conclusion, inosine exerted neuroprotective effects against the rotenone-induced neuronal loss via an AMPK activation and through the restoration of the imbalance between autophagy and apoptosis. These findings support potential application of inosine in PD treatment.

OBJECTIVES: To describe the inside out surgical anatomy of the superior laryngeal artery and to resolve the ambiguities in the nomenclature of its main branches.

STUDY DESIGN: Endoscopic dissection of the superior laryngeal artery in the paraglottic space of larynges of fresh frozen cadavers and a review of the literature.

SETTING: A center for anatomy encompassing facilities for latex injection into the cervical arteries of human donor bodies and a laryngeal dissection station equipped with a video-guided endoscope and a 3-dimensional camera.

METHODS: Video-guided endoscopic dissection of 12 hemilarynges in fresh frozen cadavers whose cervical arteries were injected with red latex. Description of the inside-out surgical anatomy of the superior laryngeal artery and its main branches. Review of the previous reports describing the anatomy of the superior laryngeal artery.

RESULTS: From inside the larynx, the artery was exposed upon its entry through the thyrohyoid membrane or through the foramen thyroideum. It was traced ventrocaudally in the paraglottic space exposing its branches to the epiglottis, the arytenoid, and the laryngeal muscles and mucosa. Its terminal branch was followed until it left the larynx through the cricothyroid membrane. Branches of the artery, previously described under different names, appeared to supply the same anatomical domains.

CONCLUSION: Mastering the inside out anatomy of the superior laryngeal artery is mandatory to control any intraoperative or postoperative hemorrhage during transoral laryngeal microsurgery or during transoral robotic surgery. Naming the artery's main branches according to their domain of supply would resolve the ambiguities resulting from various nomenclatures.

{Due to their low cost, toxicity, and health risks, medicinal plants have come to be seen as useful products and sources of biologically active compounds. Mangifera indica L., a medicinal plant with a long history, has a high bioactive metabolites content. Mangiferin (C19H18O11) is primary isolated from M. indica’s leaves, which has many pharmacological benefits. In this investigation, ultrasonic-assisted extraction with ethanol as the extraction solvent was applied to obtain mangiferin from a local type of M. indica leaves. HPLC was performed after a dichloromethane-ethyl acetate liquid–liquid fractionation method. Further, UV–vis, FTIR, and NMR spectroscopy were utilized to elucidate the structure. Interestingly, purified mangiferin displayed promising antimicrobial efficacy against a diverse variety of fungal and bacterial pathogens with MICs of 1.95–62.5 and 1.95–31.25 µg/mL, respectively. Time–kill patterns also showed that mangiferin had both bactericidal and fungicidal action. Furthermore, it exhibited strong radical dosage-dependent scavenging activity (IC50 = 17.6 μg/mL) compared to vitamin C (Vc

Both gallic and citrate are well-established antioxidants that show promise as new selective anti-cancer drugs. Gold nanoparticles (AuNPs) as well can be developed as flexible and nontoxic nano-carriers for anti-cancer drugs. This article evaluating the efficiency and biocompatibility of gallic acid and citrate capping gold nanoparticles to be used as anti-cancer drug. The biosafety and therapeutic efficiency of prepared nano-formulations were tested on Hela and normal BHK cell line. Gold nanospheres coated with citrate and gallate were synthesized via wet chemical reduction method. The prepared nano-formulations, citrate and gallate coated gold nanospheres (Cit-AuNPs and Ga-AuNPs), were characterized with respect to their morphology, FTIR spectra, and physical properties. In addition, to assess their cytotoxicity, cell cycle arrest and flow cytometry to measure biological response were performed. Cit-Au NPs and Ga-Au NPs were shown to significantly reduce the viability of Hela cancer cells. Both G0/G cell cycle arrest and comet assay results showed that genotoxic effect was induced in Hela cells by Cit-Au NPs and Ga-Au NPs. The results of this study showed that Cit-Au NPs and Ga-AuNPs inhibit the growth of metastatic cervical cancer cells, which could have therapeutic implications.