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Edaravone mitigates hemorrhagic cystitis by modulating Nrf2, TLR-4/NF-κB, and JAK1/STAT3 signaling in cyclophosphamide-intoxicated rats

Research Abstract

Hemorrhagic cystitis is a potentially deadly complication associated with radiation therapy and chemotherapy. This study explored the protective effect of edaravone (ED) on cyclophosphamide (CP)-induced hemorrhagic cystitis, oxidative stress, and inflammation in rats. The animals received 20 mg/kg ED for 10 days and a single injection of 200 mg/kg CP on day 7. CP induced tissue injury manifested by the diffuse necrotic changes, disorganization of lining mucosa, focal hemorrhagic patches, mucosal/submucosal inflammatory cells infiltrates, and edema. CP increased malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor-alpha, and interleukin 6 (IL-6), decreased IL-10, and upregulated toll-like receptor 4 (TLR-4), nuclear factor-kappa B (NF-κB) p65, Janus kinase 1 (JAK1), and signal transducer and activator of transcription 3 (STAT3) in the urinary bladder of rats. ED effectively prevented the histopathological alterations, decreased MDA, NO, and inflammatory mediators, and downregulated TLR-4, NF-κB, JAK1, and STAT3 in CP-induced rats. Treatment with ED upregulated ikβ kinase β, IL-10, nuclear factor-erythroid 2 related factor 2 (Nrf2), and cytoglobin, and boosted glutathione, superoxide dismutase, and glutathione S-transferase. Molecular docking simulations revealed the ability of ED to bind TLR-4, NF-κB, JAK1, and STAT3. In vitro, ED increased the cytotoxic activity of CP against HeLa, Caco-2, and K562 cell lines. In conclusion, ED prevented CP-induced hemorrhagic cystitis in rats by attenuating oxidative stress, suppressing TLR-4/NF-κB, and JAK1/STAT3 signaling and boosted Nrf2, cytoglobin, and antioxidants.

Research Authors
Emad H. M. Hassanein, Marwa A. Ahmed, Ahmed M. Sayed, Eman K. Rashwan, Omnia A. M. Abd El-Ghafar, Ayman M. Mahmoud
Research Date
Research Department
Research Journal
Journal of biochemical and molecular toxicology
Research Publisher
Wiley
Research Year
2021

Nosocomial Bacterial and Fungal Chest Infections in Cirrhotic Patients‎

Research Abstract

Background and aim: For a long time, the connection between liver cirrhosis (LC) and infections ‎had been studied extensively. Because of their weakened immune system, ‎cirrhotic patients are more likely to contract infectious diseases. Cirrhotic ‎patients are more likely to undergo invasive diagnostic or surgical ‎procedures that can change the host's protective barrier, putting them at a ‎higher risk of contracting an infection‎‎. Patients and Methods: ‎The study was conducted over one year duration between January and ‎December 2019 at intensive care unit (ICU). It enrolled all patients with ‎decompensated LC but patients with compensated LC or underlying ‎chronic chest disease were excluded. Baseline evaluation with laboratory ‎data was done in all patients. Blood and sputum cultures were achieved in ‎patients with suspected NCI‎.‎ Results: ‎845 patients with LC were admitted to ICU but 345 of them were excluded ‎so, 500 patients were enrolled in the analysis. NCI occurred in 100 (20%) ‎patients. The most frequent isolated organisms were Klebsiella species ‎‎(32%), Candida albicans (19%), Strept.pneumoniae (12%) and ‎Staph.aureus (10%). All of these infections were in form of pneumoniae.  ‎Up to 65% of patients with NCI were died. Based on the current study the ‎predictors of NCI were; old age spontaneous bacterial peritonitis and low ‎serum albumin‎‎. Conclusion: Patients with liver cirrhosis are liable to infections secondary to ‎dysregulated immunity. NCI in cirrhotic patients has serious outcome. ‎Hospitalized cirrhotic patients should be screened for NCI‎.

Research Authors
Magda Shehata Hassan, Nariman Zaghloul Bekhiet, Mohammed Fawzy Adam, Adnan Ahmed Mohamed
Research Date
Research Journal
Afro-Egyptian Journal of Infectious and Endemic Diseases
Research Member
Research Publisher
Zagazig University, Faculty of Medicine, Endemic and Tropical Medicine Department
Research Year
2021

Amoebiasis in Active Ulcerative Colitis: Epidemiological Aspects, Association and Impact Of Anti-Amoebic Therapy on Disease Severity

Research Authors
Elham Ahmed Hassan, Amany Mohamed Abdel-Hamed,Saad Zaky Mahmoud, Mohamed E Merghany, Asmaa Omar Ahmed, Zainab Geber Mahran
Research Date
Research Journal
Juniper Publishers journal
Research Member

Abstract P6-12-05: Impact of the Middle East unrest on management of breast cancer–A single institution experience

Research Abstract

King Fahad University Hospital of Dammam (KFHU) is a major referral teaching Hospital in the Eastern province in Saudi Arabia. With permission, The Breast Division at KFHU accepts expatriate patients for treatment of breast cancer free of charge. Between Jan 2010 and June 2015 the unit has received 435 new and previously treated breast cancer patients, 35% of them were expatiates. We have noticed that most of these patients had an out of their hand delay in initiating either their investigations for a breast lump or start of active treatment; this has resulted in less than optimum prognosis in many cases. We reported that 75% of these patients had an average of 6-19 months delay before they presented for investigations of a breast mass, 25% had received previous irregular treatment and did not complete their management due to war unrest and travelling. More than 70% of patients who needed radiotherapy …

Research Date
Research Year
2016

Imaging analysis of heart movement for improving the respiration-gated radiotherapy in patients with left sided breast cancer

Research Abstract

[en] Respiration induced heart movement during radiotherapy exposes the heart to the inevitable risks of radio-exposure, and hence radiation injury, in cases of Lt. sided breast cancer. The impact of such a risk is additionally aggravated by the use of radiotherapy in combination with cardiotoxic chemotherapeutic agents. Radio-oncologists pay special attention to the coronary arteries that might be included in this small part of the heart exposed to radiation. The aim of this study was to include the internal heart movement for improving respiration-gated radiotherapy of left sided breast cancer. For 70 patients, all females left sided breast cancer, two planning CT's in inspiration and expiration, and one free breathing scan are performed. The heart motion was analyzed with the clinic-developed software ORAT in the simulator sequence for acquiring information of the cranio-caudal amplitude of heart movements in free breathing (respiration-induced amplitude) and a 15 seconds breath-hold phase (inherent amplitude). The role of inherent heart movement varies from one patient to another which should be taken in consideration during defining the parameters of respiration-gated radiotherapy. The inherent amplitude of the heart motion is the physiological lower limit of the respiration-gating window.

Research Date

Subclinical hypothyroidism in children: updates for pediatricians

Research Abstract

Subclinical hypothyroidism (SH) is defined as serum thyroid-stimulating hormone (TSH) above the upper limit of the reference range in the presence of normal free T4 concentrations. Depending on the degree of TSH elevation, SH could be defined as mild (TSH, 4.5–10 mIU/L) or severe (TSH>10 mIU/L). While there is a general consensus to treat children with serum TSH levels above 10 mU/L, the management of the mild form is uncertain and should be individualized. In this mini-review, we present a brief review of SH in children based on extensive literature review and long-standing clinical experience. This review provides the prevalence, causes, clinical presentation, consequences, investigation, and up-to-date therapeutic approach of SH in children. Generally, the purpose of the review is to provide pediatricians with an update of this common and continuously evolving condition.

Research Authors
Kotb Abbass Metwalley, Hekma Saad Farghaly
Research Date
Research Department
Research File
REVIEW.pdf (204.83 KB)
Research Journal
©2021 Annals of Pediatric Endocrinology & Metabolism
Research Member

Ferritin levels in children and adolescents with type 1 diabetes mellitus: relationship with microvascular complications and glycemic control

Research Abstract

Evaluate ferritin levels in children and adolescents with type 1 diabetes mellitus and its
relation to diabetic microvascular complications, and metabolic control. Subjects and methods: This
study included 180 children and adolescents with type 1 diabetes mellitus (T1DM) with a mean age
of 14.9 ± 3.1 years and 180 apparently normal children matched for age and sex (control group). All
children were evaluated with full history taking, thorough clinical examination, laboratory assessment
of high-sensitivity C-reactive protein and hemoglobin A1c (HbA1c), and evaluation of the presence of
microvascular complications. Serum ferritin levels were measured using electrochemiluminescence
immunoassay. The patients were divided into two groups according to the presence or absence of
microvascular complications. Results: Serum ferritin levels were significantly higher in patients
with T1DM in both groups compared with healthy controls (p < 0.001). Additionally, patients with
microvascular complications had higher serum ferritin concentrations than those without microvascular
complications (p < 0.001). Patients with microalbuminuria showed higher ferritin levels compared with
patients without microalbuminuria (p < 0.05). Stepwise regression analysis revealed that levels of HbA1c
and urinary albumin excretion were independently related to ferritin levels (p < 0.001 for both). On
receiver operating characteristic (ROC) curve analysis, a ferritin cutoff value of 163.6 ng/mL differentiated
patients with microvascular complications from those without microvascular complications with a
sensitivity of 92.1% and specificity of 93.4%. Conclusion: Serum ferritin levels are elevated in T1DM,
particularly in patients with microvascular complications.

Research Authors
Kotb Abbass Metwalley1 Duaa Mohamed Raafat1Deiaaeldin Mohammed Tamer1 Hekma Saad Farghaly1 Ghada Moham
Research Date
Research Department
Research File
FERRITTIN.pdf (139.03 KB)
Research Journal
Arch Endocrinol Metab
Research Year
2020

Association between vascular endothelial dysfunction and the inflammatory marker neopterin in patients with classic congenital adrenal hyperplasia

Research Abstract

Background and aims: Patients with congenital adrenal hyperplasia (CAH) are at increased risk of cardiometabolic
abnormalities. We aimed to evaluate vascular endothelial dysfunction and its association with serum neopterin
(NP) levels in CAH patients.
Methods: The study included 40 patients, with a mean age of 14.8 ± 2.6 years; 28 (70%) subjects were females.
They were compared with 40 healthy controls matched in anthropometric evaluation and measurement of
fasting lipids, glucose, insulin, homeostasis model assessment for insulin resistance [HOMA-IR], and serum NP
levels (nmol/L). Vascular ultrasound was used to measure brachial artery flow-mediated dilation (FMD%) and
carotid intima-media thickness (CA-IMT). According to the degree of control on medical treatment, patients were
classified into poor (n = 12) and good (n = 28) control groups.
Results: Compared to controls, CAH patients had lower brachial FMD% (4.60 ± 2.13 versus 9.31 ± 2.29, p =
0.001), similar CA-IMT (0.44 ± 0.08 versus 0.44 ± 0.06, p = nonsignificant) and higher NP (42.6 ± 11.6 versus
9.2 ± 3.8, p = 0.001). However, differences between poor and good control CAH patients were significant
regarding FMD%, CA-IMT, and NP measurements. FMD% correlated significantly with NP (r = ? 0.54, p =
0.001), high-sensitivity CRP (r = ? 0.53, p = 0.001), HOMA-IR (r = ? 0.31, p = 0.01), CA-IMT (r = ? 0.22, p <
0.05), diastolic blood pressure (r = 0.32, p = 0.01) and systolic blood pressure (r = ? 0.022, p < 0.05). NP was the
most significant independent predictor of FMD%, as determined by linear regression analysis (p = 0.001).
Conclusions: Our study showed that CAH patients had endothelial dysfunction, which is an early process of
vascular affection. This was significantly associated with NP levels, suggesting a crucial role of inflammation in
the pathogenesis of vascular damage. Further studies are needed to confirm our findings and to investigate the
exact role of NP, as either protective or proatherothrombotic.

Research Authors
Hekma Saad Farghaly , Kotb Abbass Metwalley , Duaa Mohamed Raafat , Ghada Mohamed Saied c, Magda Farghali Gabri b, Magdy Algowhary d,*
Research Date
Research Department
Research File
NEOPTERIN.pdf (333.09 KB)
Research Journal
Atherosclerosis
Research Year
2021

Umbelliferone alleviates hepatic ischemia/reperfusion-induced oxidative stress injury via targeting Keap-1/Nrf-2/ARE and TLR4/NF-κB-p65 signaling pathway.

Research Authors
Hassanein, E.H.M., Khader, H.F., Elmansy, R.A., Seleem, H.S., Elfiky, M., Zuhair M Mohammedsaleh, Z.M., Ali F.E.M. and Abd-Elhamid, T.H.
Research Date
Research Department
Research Journal
Environmental Science and Pollution Research
Research Publisher
Springer
Research Website
https://link.springer.com/article/10.1007/s11356-021-15184-8
Research Year
2021

Pretreatment with Coenzyme Q10 combined with aescin protect against sepsis-induced acute lung injury.

Research Authors
Ali F. E. M., Ahmed S. A., Eltrawy A. H., Yousef; R. S., Ali H. S., Mahmoud A. R., Abd-Elhamid T.H.
Research Department
Research Journal
Cells Tissues Organs
Research Publisher
Karger
Research Website
https://www.karger.com/Article/Abstract/516192
Research Year
2021
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