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Valproate attenuates neuroinflammation and glial activation in a rat model of fibromyalgia: Evidence for antioxidant and nociceptive modulation

Research Abstract

Fibromyalgia syndrome (FMS) is a chronic, multidimensional musculoskeletal condition distinguished by severe nociceptive dysfunction, persistent fatigue, sleep disruptions, cognitive deficits, and emotional instability. Although valproic acid (VPA) has been used to treat epilepsy and bipolar disorder, its efficacy in altering neuropathic pain pathways remains unclear. In this investigation, we assessed the neuromodulatory characteristics of VPA (300 mg/kg, intraperitoneally) in an established FMS rat model, with a focus on neuroinflammation, oxidative stress, and glial activation. Behavioral evaluations for thermal hyperalgesia (paw withdrawal latency, PWL) and mechanical allodynia (paw withdrawal threshold, PWT) were performed at baseline (day 0), after induction (day 5), and at various intervals following VPA administration. Neurochemical evaluations demonstrated that VPA markedly diminished FMS-induced elevations in malondialdehyde (MDA), nitric oxide (NO), and pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and interleukin (IL)-6, while restoring antioxidant defenses, such as glutathione (GSH) and superoxide dismutase (SOD). Histopathological examination demonstrated reduced neuronal degeneration and decreased immunoreactivity of glial fibrillary acidic protein (GFAP). These findings indicate that VPA reduces FMS-related pain and neuroinflammatory characteristics through antioxidative and glial-modulating mechanisms, indicating its potential for therapeutic repurposing in neuropathic pain syndromes.

Research Authors
Esraa A. Ahmed a , Rasha B. Abd-ellatief a , Marwa F. Ali b , Ahmed M. Abd-Eldayem
Research Date
Research Department
Research Journal
Brain Research
Research Pages
12
Research Publisher
Elsevier
Research Rank
international
Research Vol
1869
Research Website
www.elsevier.com/locate/brainres
Research Year
2025

Valproate attenuates neuroinflammation and glial activation in a rat model of fibromyalgia: Evidence of antioxidant and nociceptive modulation

Research Authors
Esraa A.Ahmed, Rasha B.Abd-ellatief, Marwa F.Ali, Ahmed M.Abd-eldayem
Research Date
Research Journal
Brain Research

Role of cAMP/pCREB and GSK-3β/NF-κB p65 signaling pathways in the renoprotective effect of mirabegron against renal ischemia-reperfusion injury in rats

Research Abstract

Acute kidney injury and other renal disorders are thought to be primarily caused by renal ischemia-reperfusion (RIR). Cyclic adenosine monophosphate (cAMP) has plenty of physiological pleiotropic effects and preserves tissue integrity and functions. This research aimed to examine the potential protective effects of the β3-adrenergic receptors agonist mirabegron in a rat model of RIR and its underlying mechanisms. Male rats enrolled in this work were given an oral dose of 30 mg/kg mirabegron for two days before surgical induction of RIR. Renal levels of kidney injury molecule-1 (KIM-1), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), Interleukin-10 (IL-10), cAMP, cAMP-responsive element binding protein (pCREB), and glycogen synthase kinase-3 beta (GSK-3β) were assessed along with blood urea nitrogen and serum creatinine. Additionally, caspase-3 and nuclear factor-kappa B (NF-κB) p65 were explored by immunohistochemical analysis. Renal specimens were inspected for histopathological changes. RIR led to renal tissue damage with elevated blood urea nitrogen and serum creatinine levels. The renal KIM-1, MCP-1, TNF-α, and GSK-3β were significantly increased, while IL-10, cAMP, and pCREB levels were reduced. Moreover, upregulation of caspase-3 and NF-κB p65 protein expression was seen in RIR rats. Mirabegron significantly reduced kidney dysfunction, histological abnormalities, inflammation, and apoptosis in the rat renal tissues. Mechanistically, mirabegron mediated these effects via modulation of cAMP/pCREB and GSK-3β/NF-κB p65 signaling pathways. Mirabegron administration could protect renal tissue and maintain renal function against RIR.

Research Authors
Marwa A. Ahmed a , Esam O. Kamel b , Ahmed M. Abd-Eldayem a c
Research Date
Research Department
Research Journal
European Journal of Pharmacology
Research Year
2024

Exploring the role of chitosan and curcumin-loaded chitosan nanoparticles against chronic toxoplasma infection in experimental mice

Research Abstract

Toxoplasma gondii infection remains a significant global health concern, promoting the urgent need
for effective therapeutic strategies. This study aimed to evaluate the therapeutic potential of chitosan
nanoparticles (CSNPs) and curcumin-loaded chitosan nanoparticles (Cur-CSNPs) against the chronic
Toxoplasma gondii (ME49 strain) in an experimental mouse model. This achieved by investigating
their ability to reduce parasitic load, oxidative stress, histopathological lesion, and to enhance the
host immune response. Sixty female BALB/c mice were divided into five groups: infected untreated
group, Spiramycin®-treated group, CSNPs-treated group, Cur-CSNPs-treated group, and negative
control group. The Cur-CSNPs-treated group exhibited the lowest brain cyst counts, along with
significant reductions in cyst size. Hematological indices revealed no significant reduction in total
white blood cell (WBC) counts or in the percentage of neutrophils, monocytes, and eosinophils in
both the CSNPs and Cur-CSNPs treated groups, compared to the infected untreated group and
Spiramycin-treated group. However, both nanoparticle-treated groups exhibited a significant decrease
in the percentage of lymphocytes compared to the infected untreated group. Significant differences
in total antioxidant capacity (TAC) and malondialdehyde (MDA) levels were observed, with the
Cur-CSNPs treated group displaying values comparable to the negative control. Histopathological
examination revealed substantial improvements in the brain, liver, and spleen tissues of Cur-CSNPstreated
animals, characterized by preserved tissue architecture and reduced inflammatory lesions.
Immunohistochemical analysis further revealed reduced expression of IL-6 and TNF-α, indicating a
mitigated inflammatory response. These findings highlight the promising therapeutic role of Cur-
CSNPs in controlling chronic T. gondii infection and suggest their potential as a novel strategy for
developing effective antiparasitic treatments.
Keywords Toxoplasma, Curcumin, Chitosan nanoparticles, Oxidative stress, TNF-α, Histopathological
lesions

Research Authors
AHMED K. DYAB
Research Date
Research Department
Research Journal
Scientific Reports
Research Member
Research Pages
25252-5.
Research Publisher
PMC
Research Rank
q1
Research Vol
15
Research Website
https://pubmed.ncbi.nlm.nih.gov/41285946/
Research Year
2025

PATHOGENESIS OF DIARRHEA AMONG INFANTS AND CHILDREN: AN OVERVIEW

Research Abstract

is frequent, loose, or watery bowel movements (BMs) that differ from a child's normal
pattern, as is a very common problem, leading cause of child mortality and morbidity worldwide.
In children acute watery diarrhea (several hours or days), acute bloody diarrhea (dysentery), and
persistent diarrhea, which lasts 14 days or longer. Gastroenteritis most common symptoms regardless
of cause, are vomiting, diarrhea, and sometimes abdominal cramps, fever, and poor appetite.
The risky complication of gastroenteritis is dehydration. The dehydrated children become listless,
irritable, or sluggish (lethargic), but dehydrated infants develop serious side effects with hospitalized
medical care. The causative agents of diarrhea in children are viruses, particularly rotavirus
(preventable with a vaccine) and norovirus, as well as adenovirus and arbovirus, bacteria
like E. coli, salmonella and cholera. Protozoal parasites causing diarrhea as Cryptosporidium, Entamoeba,
Giardia, Balantidium coli and Cystoisospora belli as well as helminths as Strongyloides,
Schistosoma and Trichuris may cause chronic diarrhea especially in immunocompromised individuals.
Apart from microorganism agents, diet, antibiotics and others can cause children diarrhea.
Key words: Children, Diarrhea, Pathogenesis, Bacteria, Parasites, Viruses, Others

Research Authors
AHMED K. DYAB
Research Date
Research Department
Research Journal
Journal of the Egyptian Society of Parasitology
Research Member
Research Pages
379-390
Research Publisher
the Egyptian Society of Parasitology,
Research Vol
53
Research Website
https://jesp.journals.ekb.eg/article_472231.html
Research Year
2025

Pelvic Nodal Irradiation in Muscle Invasive Bladder Cancer (MIBC)

Research Abstract

Background: Bladder cancer preservation treatment achieved 5/10-year overall survival rates comparable to those of radical cystectomy. Bladder-preserving trials have recommended coverage of pelvic lymph nodes (LN) in radiation portals (micrometastases in pelvic LN 25 to 44%). Gemcitabine-based radiotherapy did not include the pelvic LN in the radiation portals to minimize bowel toxicity. However, the pelvic LN irradiation debate has been highlighted. The present study aimed to evaluate the role of pelvic LN irradiation in negative node, bladder cancer.
 
Method: A prospective study was conducted from October 2017 to February 2020 at the South Egypt Cancer Institute. Bladder cancer Patients with cT1-3, N0, and M0 underwent maximum TURBT and were then randomized into two arms: Group A: Bladder-only irradiation (52.5 GY/20 frs); Group B: Pelvic nodal irradiation with weekly gemcitabine 100mg/m2 
Statistical analysis: SPSS Statistics (version 26.0, IBM), descriptive (means and SD), chi-square test for qualitative variables, independent student t-test, and survival analysis (Kaplan-Meier). 
Results: Patients aged 37 to 76 years old and 32 to 82 years old in groups A and B, respectively. Cases were Stage III in groups A, II, and III in B. Both groups showed similar local control rates (90% and 92%, respectively). Favorable toxicity profile group A schedule emphasizes high local control with low-grade intestinal toxicity (no G3 enteritis). Unexpectedly, Group A showed significantly higher progression free survival (PFS over Group B (P < 0.034).
Conclusion: Bladder-only chemoradiation has non-inferior local control of node-negative bladder cancer with significantly higher PFS. The pelvic nodal radiation field has an unfavorable toxicity profile (higher G2 enteritis).

Highlights

Keywords

Main Subjects

Research Authors
noha Ali abdelmalik & wageeh ali abdelhafeez

Utility of Bowel Ultrasound and Elastography in assessment of Ulcerative Colitis activity and response to treatment

Research Abstract
Background Ulcerative colitis (UC) is a chronic remittent gastrointestinal disease affecting the colon. Ileocolonoscopy and histopathology are the mainstay tools for diagnosis and monitoring response to treatment which are invasive. There is unmet need for non-invasive tools for diagnosis and monitoring UC patients.
Objectives:  Bowel Ultrasound (BUS) and elastography are a promising non-invasive tool for this issue. We studied the validity of BUS in UC diagnosis and prediction of response to treatment.
Patients and methods 48 participants were included, classified into 18 patients with active UC, 15 UC patients in remission and another 15 participants as a control group. BWT, WLS, CDS, pericolic lymph nodes presence and pericolic fat echogenicity had revealed a clinical significance in UC diagnosis and prediction of response to treatment.
Results: BWT had a perfect agreement at UC diagnosis and prediction of response to treatment at a cut off point 0.3 cm with 94.0% accuracy, 94.4% sensitivity, 93.3% specificity, 94.4% PPV and 93.3% NPV with P value <0.001. bowel shear wave elastography showed a clinical significance in UC diagnosis. Using shear wave elastography E1 comparing active UC patients vs. patients in remission with cut off value 1 kPa had 0.750 AUC, 95% CI with 88.9% sensitivity, 53.3% specificity, 69.6% PPV and 80.0% NPV with P value 0.004, but SR didn’t show any significance either in diagnosis or monitoring UC patients.
Conclusion: BUS can be used in diagnosis and monitoring UC patients instead of or beside ileocolonoscopy and histopathology to decrease the burden of the disease. Further research is needed to study shear wave elastography to get its benefit and to use in scoring systems for diagnosis and disease monitoring.

Keywords

Main Subjects

Research Authors
Ghada M. Abdelrazek 1 Yahya Almansoury 2 Muhammad Abdel-Gawad 3 Mohammed Tag-Adeen 2 Zainelabdeen Ahmed 4 Wageeh A. Ali
Research Date

Adenosine Deaminase Activity and ADA G22A single nucleotide Polymorphism in Patients with Acute Coronary Syndrome

Research Authors
Alaa Ahmed Mostafa c , Yousry Lotfy Sharkawy Bakryb , Ahmed G. Hassana M Ahmed a* , Tahia H. Saleem
Research Date
Research Department
Research Journal
SVU-IJMS
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