Heba Fikry

Neurodegenerative diseases, which afflict millions worldwide and threaten public health, have no cure. Neurodegenerative diseases lack effective therapies, burdening society and the economy. Over the past 20 years, regenerative cell therapy (stem cell therapy) has advanced, opening novel neurodegenerative disease treatments. Thus, the current review aimed to systematically highlight experimental and clinical studies of potentially effective therapeutic strategies for stem cells and report histological, cellular, or ultrastructural outcomes following stem cell interventions in neurodegenerative diseases. PRISMA‐compliant computerized literature searches of PubMed, Scopus, and Web of Science identified studies on embryonic, induced pluripotent, mesenchymal, or neural stem cells (NSCs) in neurodegenerative disease models and histological and tissue‐level outcomes. Search terms included nervous system diseases, histology, neuron regeneration, stem cells, stem cell treatment, and transplantation. Peer‐reviewed articles published between 2000 and 2025 were selected. Experimental animal and clinical studies that reported histological or tissue‐level results after stem cell treatments were included. Eighty‐six studies met the eligibility criteria, covering models of Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and Huntington's disease. Across these studies, stem cell therapies were linked to improved neuron survival, better synaptic structure, diminished gliosis, and some restoration of tissue structure. These effects depended on the type of stem cell used, the disease model, and how the treatment was given. Overall, the evidence suggests that stem cell therapies can lead to significant histological and tissue‐level improvements in neurodegenerative diseases, supporting their potential for regeneration. Further standardized and translational studies are needed to clarify the underlying mechanisms and improve treatment strategies.

Gastric ulcer (GU) and Alzheimer's disease (AD) are prevalent age-associated disorders frequently accompanied by systemic oxidative stress and inflammation. Emerging evidence suggests that gastrointestinal dysfunction and inflammatory signaling may aggravate neurodegenerative processes. Curcumin (Cur) exhibits well-established antioxidant, anti-inflammatory, neuroprotective, and gastroprotective properties; however, its therapeutic utility is limited by poor bioavailability. The present study aimed to formulate and characterize Curcumin- encapsulated chitosan nanoparticles (Cur-CSNPs) and evaluate their dual protective effects in a clinically relevant comorbid rat model combining scopolamine-induced AD-like pathology and ethanol-induced GU. Male Wistar rats were divided into six groups: control, Cur-CS-NPs alone, GU, AD, GU + AD, and GU + AD treated with Cur-CSNPs. Behavioral assessments, biochemical analyses, histopathological evaluation, and immunohistochemical investigations were performed on brain and gastric tissues. GU + AD rats exhibited cognitive deficits, neuronal degeneration, amyloid-β accumulation, astrocyte activation, gastric mucosal injury, increased oxidative stress, NF-κB activation, elevated inflammatory cytokines, and enhanced apoptotic signaling. Cur-CSNP treatment significantly improved cognitive performance, reduced oxidative stress and inflammation, suppressed NF-κB signaling, decreased amyloid-β deposition, inhibited apoptosis, and restored gastric mucosal integrity. In conclusion, Cur-CSNPs exert concurrent neuroprotective and gastroprotective effects in a comorbid AD and GU model through coordinated modulation of oxidative stress, inflammation, amyloidogenic activity, and apoptotic pathways. These findings demonstrate that Cur-CSNPs exert dual neuroprotective and gastroprotective effects by modulating oxidative stress, inflammation, amyloidogenic pathways, and apoptosis, highlighting nano-curcumin as a promising therapeutic strategy for gut-brain axis-related disorders. Further investigations are warranted to elucidate the detailed molecular mechanisms and to explore the clinical applicability of nano-formulated curcumin as a therapeutic strategy for disorders involving concurrent gastrointestinal and neurodegenerative pathology.

Diabetes mellitus (DM) induces endocrine and exocrine dysfunction, including salivary gland impairment. While the sublingual gland (SLG) contributes to saliva production, its involvement in diabetes remains understudied. Agmatine (AGM), a naturally occurring polyamine, exhibits antioxidant and anti‐inflammatory properties; however, its protective effects on the SLG and pancreas in diabetes have remained largely uninvestigated. This study introduces new insights into SLG injury in diabetes and the dose‐dependent protective benefits of AGM through multi‐level analysis. Male Wistar rats were rendered diabetic by a single intraperitoneal STZ injection (65 mg/kg) and treated with either low‐dose (40 mg/kg) or high‐dose (100 mg/kg) AGM for two weeks. SLGs and the pancreas were analyzed by histological, immunohistochemical, and biochemical methods. Mucin secretion (MUC‐5B) was measured, oxidative stress markers and pro‐inflammatory cytokines were quantified, and structural changes were evaluated using H&E, Alcian Blue/PAS, and Mallory's trichrome staining. Immunohistochemistry included α‐SMA and CK17 for SLG and insulin receptor for the pancreas. STZ‐induced diabetes resulted in a substantial reduction in MUC‐5B, increased oxidative stress and pro‐inflammatory markers, damage to acinar and myoepithelial cells, and injury to pancreatic β‐cells. Agmatine administration enhanced these parameters in a dose‐dependent manner, with high‐dose treatment reinstating mucin secretion, regulating oxidative and inflammatory indicators, and maintaining histological and immunohistochemical integrity in both the sublingual gland and pancreas. AGM confers dose‐dependent protection against SLG dysfunction and pancreatic damage in diabetic rats via antioxidant, anti‐inflammatory, and cytoprotective mechanisms. These findings highlight the therapeutic potential of AGM in preventing salivary gland dysfunction and maintaining pancreatic function in diabetes.

Background: The most noticeable consequence of paraquat (PQ) toxicity is pulmonary fibrosis. Mesenchymal stem cells have the remarkable ability to self-renew and differentiate into many cell types. One such type is adipose tissue-derived Mesenchymal Stem Cells (AT-MSCs), which are derived from adipose tissue. Thus, the purpose of this study was to compare the effects of AT-MSCs and rapamycin on paraquat-induced acute lung injury and pulmonary fibrosis in a mouse model. Methods: Fifty female mice were randomly allocated to four groups. Group I (control group) received the drug solvent using the same route of administration for the same duration as the corresponding experimental groups. Group II (pulmonary fibrosis group) lung injury was induced by injection of PQ at a dosage of 40 mg/kg. Group III (AT-MSCs group) received 1.0 × 10⁵ cells/mouse of male AT-MSCs. Group IV (rapamycin group) received 2.5 mg/kg/day diluted in 1% Dimethyl sulfoxide orally for two weeks. Lung tissue was harvested at the end of the experiment and analyzed by light and electron microscopy in addition to immunohistochemistry evaluation of p53. Samples were also taken to -80 for identification of the Y chromosome (SRY gene) and biochemical testing in the lung tissue. The injured lung was improved with AT-MSCs. Just like the control group, they restored p53 levels. Results: Following injection with AT-MSCs, there was an increase in Y-chromosome expression levels. Treatment with AT-MSCs also reduced malondialdehyde levels in the lung tissues while increasing superoxide dismutase and reduced glutathione levels. The results showed that pulmonary fibrosis may be mitigated following AT-MSCs transplantation in PQ-poisoned mice by suppressing the synthesis of pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-alpha) in the lung tissues of the animals. The SRY gene’s expression was significantly upregulated in the AT-MSCs treatment group. Conclusion: This study provides more evidence that the immunomodulatory effects of AT-MSC transplantation can alleviate pulmonary inflammatory and fibrotic alterations more effectively than rapamycin. As a result, these cells are a very promising pharmacological therapy for acute lung injury and pulmonary fibrosis induced by PQ poisoning.

The metabolic syndrome, or MetS, is currently a global health concern. The anti-inflammatory, anti-proliferative, and antioxidant properties of luteolin are some of its advantageous pharmacological characteristics. This research was designed to establish a MetS rat model and investigate the possible protective effect of luteolin on cardiovascular, hepatic, and metabolic changes in diet-induced metabolic syndrome in rats. Forty adult male albino rats were split into four groups: a negative control group, a group treated with luteolin, a group induced MetS (fed 20% fructose), and a group treated with luteolin (fed 20% fructose and given luteolin). Following the experiment after 8 weeks, biochemical, histological (light and electron), and immunohistochemistry analyses were performed on liver and heart tissues. Serum levels of cTnI, CK-MB, and LDH were significantly elevated in response to the cardiovascular effect of MetS. Furthermore, compared to the negative control group, the MetS group showed a marked increase in lipid peroxidation in the cardiac and hepatic tissues, as evidenced by elevated levels of MDA and a decline in the antioxidant defense system, as demonstrated by lower activities of GSH and SOD. The fatty liver-induced group exhibited histological alterations, including disrupted hepatic architecture, dilated and congested central veins, blood sinusoids, and portal veins. In addition to nuclear structural alterations, most hepatocytes displayed varying degrees of cytoplasmic vacuolation, mitochondrial alterations, and endoplasmic reticulum dilatation. These alterations were linked to inflammatory cellular infiltrations, collagen fiber deposition, active hepatic stellate cells, and scattered hypertrophied Kupffer cells, as demonstrated by electron microscopy and validated by immunohistochemical analysis. It is interesting to note that eosinophils were seen between the liver cells and in dilated blood sinusoids. Moreover, the biochemical (hepatic and cardiac) and histological (liver) changes were significantly less severe in luteolin-treated rat on a high-fructose diet. These results suggested that luteolin protects against a type of metabolic syndrome that is produced experimentally.

Status epilepticus (SE), the most severe form of epilepsy, leads to brain damage. Uncertainty persists about the mechanisms that lead to the pathophysiology of epilepsy and the death of neurons. Overloading of intracellular iron ions has recently been identified as the cause of a newly recognized form of controlled cell death called ferroptosis. Inhibiting ferroptosis has shown promise as a treatment for epilepsy, according to recent studies. So, the current study aimed to assess the possible antiepileptic impact of CoQ10 either alone or with the standard antiepileptic drug sodium valproate (SVP) and to evaluate the targeted effect of COQ10 on hippocampal oxidative stress and ferroptosis in a SE rat model. Using a lithium-pilocarpine rat model of epilepsy, we evaluated the effect of SVP, CoQ10, or both on seizure severity, histological, and immunohistochemical of the hippocampus. Furthermore, due to the essential role of oxidative stress and lipid peroxidation in inducing ferroptosis, we evaluated malonaldehyde (MDA), reduced glutathione (GSH), glutathione peroxidase 4 (GPX4), and ferritin in tissue homogenate. Our work illustrated that ferroptosis occurs in murine models of lithium-pilocarpine-induced seizures (epileptic group). Nissl staining revealed significant neurodegeneration. A significant increase in the number of astrocytes stained with an astrocyte-specific marker was observed in the hippocampus. Effective seizure relief can be achieved in the seizure model by administering CoQ10 alone compared to SVP. This was accomplished by lowering ferritin levels and increasing GPX4, reducing MDA, and increasing GSH in the hippocampus tissue homogenate. In addition, the benefits of SVP therapy for regulating iron stores, GPX4, and oxidative stress markers were amplified by incorporating CoQ10 as compared to SVP alone. It was concluded that CoQ10 alone has a more beneficial effect than SVP alone in restoring histological structures and has a targeted effect on hippocampal oxidative stress and ferroptosis. In addition, COQ10 could be useful as an adjuvant to SVP in protecting against oxidative damage and ferroptosis-related damage that result from epileptic seizures.

. Introduction. Acute exacerbation-idiopathic pulmonary fibrosis (AE-IPF) is a life-threatening condition. In the treatment of AE-IPF, corticosteroid medication is commonly utilized. However, there is insufficient evidence to justify its usage. Pirfenidone (PFD) has recently been discovered to be effective in the treatment of AE-IPF patients. However, regenerative therapy, such as stem cell therapy or tissue engineering, is necessary due to ineffective and limited therapies. Combining MSC transplantation with pharmacological therapy may also give additional benefits; nevertheless, its use must be proven experimentally. As a result, the goal of this study was to assess the therapeutic effects of adipose-derived mesenchymal stem cells (AD-MSCs) on corticosteroid resistance in an animal model of AE-IPF caused by bleomycin compared to PFD. Materials and methods. Seventy C57BL/6J male mice were randomly divided into seven groups, control, BLM, methylprednisolone (MP), PFD, AD-MSCs, PFD +MP, and AD-MSCs +MP. Results. In terms of survival, collagen deposition, the acute lung injury score (ALI), and the Ashcroft score, AD-MSCs exceeded PFD. AD-MSCs + MP provided protection and preserved the lung's architecture in BLM-induced AE. In addition, AD-MSCs successfully decreased chemokine (CC motif) ligand-2 (CCL2) positive cells and lower pro-fibrotic and pro -inflammatory cytokines. Conclusions. AD-MSCs enhanced histological structure, Ashcroft and ALI scores, lung collagen deposition, survival, and cytokines in an animal model of AE-IPF. As a result, we believe that AD-MSCs may be more therapeutically helpful for AE-IPF than presently available therapies, either alone or in conjunction with MP.

Aims: Parkinson's disease (PD) is the second most prevalent age‐related neurodegenerative disorder. The cerebellum plays a role in PD pathogenesis. Curcumin has numerous medicinal uses, mostly attributed to its potent antioxidant properties. This study investigated the potential protective influence of curcumin on the cerebellum of albino rats with rotenone‐induced PD.Methods: Forty adult male albino rats were randomized into four treatment groups: vehicle (group I); rotenone 3 mg/kg/day i.p. injection (group II); rotenone 3 mg/kg/day plus curcumin 30 mg/kg/day i.p. injection (group III); and curcumin 30 mg/kg/day i.p. injection (group IV).Results: Compared to group I, group II exhibited marked degenerative changes in hematoxylin & eosin‐stained sections and a reduction in Nissl granules in the Purkinje cells of the cerebellum. In group III, the neurotoxic effects in the cerebellum were reduced. Furthermore, the degenerated Purkinje and GFAP‐positive cells increased considerably in group II and were partially reduced in group III versus group II. Compared to group I, rats in group II showed reduced rotarod motor activity, partially restored in group III. Acetylcholine esterase, glutathione, and superoxide dismutase were significantly reduced, and malondialdehyde was significantly increased in group II compared to group I and was partially increased in group III.Conclusion: Curcumin attenuated neurotoxic effects and degenerative histological changes and alleviated induced oxidative stress in the cerebellar cortex of a PD rat model. Therefore, curcumin dietary supplementation may have neuroprotective effects against the development of cerebellum‐related PD symptoms.

Background: Olfactory ensheathing cells (OECs) are highly specialized glial cells that guide olfactory receptor axons from nasal mucosa to olfactory bulb. Olfactory ensheathing cells (OECs) are attractive candidates for transplantation-mediated repair of injured nervous system owing to their neuroregenerative properties.Aim of the work: To evaluate the neuroregenerative role of OECs in a model of sciatic nerve crush injury in rats.Materials and Methods: OECs were isolated from the olfactory mucosa of 15 male albino rats (100 gm). Thirty adult female albino rats (200-250 gm) were used and divided into three groups of 10 rats each. Group I (control group) underwent sham operation. Group II underwent crush injury of sciatic nerve. Group III underwent sciatic nerve crush injury then injected with single dose of 3×104 OECs at the lesion site. All rats were sacrificed after 3 weeks from the onset of the experiment.Results: Histological examination of sciatic nerves of group II rats showed discontinuity of nerve fibers with vacuolated axoplasm. OECs transplantation in group III revealed restoration of the normal histological architecture of the sciatic nerves. A significant decrease in the diameter of myelinated nerve fibers and myelin sheath thickness was recorded in group II compared to the control group. However, group III revealed a significant increase in the previous parameters compared to group II.Conclusions: Olfactory ensheathing cells (OECs) have neuroregenerative properties which might represent a new vision in human cell based therapy.