Platelet-rich plasma enhances remodeling of combined gastrocnemius muscle and Achilles tendon injuries in rat model: Reducing fibrosis, modulating gene (MMP9, Bax, HMGB1, and IGF) expression, and restoring histopathological and ultrastructural changes

Article

Author: Alhegaili, Alaa S ; Mahfouz, Hala ; Alsulimani, Ahmad ; Abdo, Walied ; Elmahallawy, Ehab Kotb ; Morsy, Manal Mohammad ; Salah, Basma ; Abouzed, Tarek Kamal ; Alnasser, Sulaiman Mohammed ; Hulail, Mohey E E ; Abdel-Kareem, Mona A ; Hakami, Zaki H

Muscle and tendon injuries are prevalent occurrences during sports activities. Platelet-rich plasma (PRP) is known for its rich content of factors essential for wound healing, inflammation reduction, and tissue repair. Despite its recognized benefits, limited information is available regarding PRP's effectiveness in addressing combined surgical injuries to the gastrocnemius muscle and Achilles tendon. The effects of PRP on muscle and tendon injury in rats were assessed through a set of biochemical markers, histopathological examinations, and immunohistochemistry analyses of muscular myogenin, desmin, and tendinous type I collagen. Additionally, mRNA expression levels of Matrix metalloproteinase-9 (MMP-9), Pro-apoptotic Bcl-2 Associated-X-protein (BAX), Insulin-like growth factor (IGF), and High mobility group box 1 protein (HMGB1) genes were evaluated. Induction of muscle and tendon injuries was associated with elevated levels of serum biomarkers such as C-reactive protein (CRP), Aspartate aminotransferase (AST), Lactate dehydrogenase A (LDH), and Creatine Kinase MB (CK-MB), delayed collagen fiber remodeling, and structural abnormalities in myofibrils. Furthermore, there was overexpression of MMP9, Bax, and HMGB1 genes, along with decreased expression of the IGF gene in this group. Treatment with PRP resulted in significant improvement of these reported findings, including enhanced collagen fiber remodeling, elevated levels of desmin and myogenin in muscle tissues, and increased expression of collagen type I in tendons. Additionally, PRP treatment led to reduced expression levels of MMP9, Bax, and HMGB1 genes, while the expression of the IGF gene increased. Overall, PRP treatment demonstrated substantial enhancement of the healing process in both muscle and tendon tissues in a surgical model of gastrocnemius skeletal muscle and Achilles tendon-induced injury. These findings suggest that PRP therapy may offer advantages in the treatment of physical-related injuries.

01 Mar 2025·Journal of Molecular Structure

New S- and N-alkyl functionalized bis-1,2,4-Triazolyl-based derivatives as potential dual EGFRWT and EGFRT790M inhibitors: Synthesis, anti-proliferative evaluation, molecular docking study and ADMET studies

Author: Ezelarab, Hend A. A. ; Aboelez, Moustafa O. ; Hassan, Abdelfattah ; Khodairy, Ahmed ; Salah, Hanan ; User, Marium Abo ; Ahmed, Abdelraheem M.

A new series of 2-(s-triazolylsulfanyl) moiety connected with N-arylacetamides, 1-aryl ethanones, acetate, acetonitrile, and 2-propane were synthesized via the reaction of 5,5-(butane-1,4-diyl)bis(4-phenyl-4H-1,2,4-triazole-3-thiol) with 2-chloro-N-arylacetamides, phenacyl bromides, Et chloroacetate, chloroacetonitrile, or 2-bromopropane under PTC conditions.Mannich bases were synthesized by reacting 5,5'-(butane-1,4-diyl)bis(4- phenyl-4H-1,2,4-triazole-3-thiol) with formaldehyde and morpholine or piperidine.The structure of the new products has been characterized by IR, NMR and their elemental analyses.These newly designed scaffolds were designed as efficient anti-proliferative EGFR^WT and EGFRT^790M kinase inhibitory agents.Scaffolds 4-nitro substituted N-arylacetamide/1-aryl ethanone and iso-Pr substituted propane were established as the most potent anti-proliferative derivatives on various tested cancer cell panels with highly remarkable IC₅₀ values compared to the reference drugs erlotinib and doxorubicin.Moreover, 4-nitro substituted N-arylacetamide/1-aryl ethanone and iso-Pr substituted propane demonstrated a favorable safety profile when tested against the normal WI-38 line, besides their exceptional selectivity as a dual kinase inhibitor, particularly targeting EGFR^WT and EGFRT^790M, where they were more potent than erlotinib and gefitinib, with IC₅₀ values of (0.30 and 11.47μM), (0.38 and 11.57μM), (0.33 and 13.12μM), and (0.37 and 21.56μM), resp.Furthermore, its apoptotic triggering capability was investigated by evaluating apoptotic markers: Caspases-3, Caspases-9, Bcl-2, Bax, and Bax/Bcl-2 ratio expression levels.The docking outcomes of the designed scaffolds 4-nitro substituted N-arylacetamide/1-aryl ethanone, and iso-Pr substituted propane in the ATP-binding sites of both EGFR^WT and EGFRT^790M agreed with the in-vitro results.Besides, Mol. dynamics simulations via iMODs server evaluated the stability of protein-8c complexes.Also, the in silico ADME properties examination of the most promising EGFR inhibitory 4-nitro substituted N-arylacetamide/1-aryl ethanone and iso-Pr substituted propane via the egg-boiled method clarified acceptable lipophilicity, GIT absorption and blood-brain barrier penetration.So, our designed analogs, specifically 4-nitro substituted N-arylacetamide/1-aryl ethanone, and iso-Pr substituted propane own prospective anti-proliferative and dual EGFR^WT and EGFRT^790M kinases inhibitory properties, making them efficient candidates for further therapeutic amelioration in the future.

01 Mar 2025·International Journal of Biological Macromolecules

Design, synthesis, and in-Silco ADME prediction of some novel bis(1,3,4-thiadiazoles) encapsulated lipid-chitosan nano capsule decorative with magnetic nanoparticles and their potential anti-helicobacter pylori activity

Article

Author: Selim, Abdelfattah M ; Hashem, Hamada ; Radwan, Ibrahim Taha ; Hassaneen, Hamdi M ; Elwahy, Ahmed H M ; Bagato, Noha ; Salem, Mostafa E

Helicobacter pylori (H. pylori) is an extremely prevalent human pathogen globally that leads to severe illnesses. Sadly, the worldwide issue of H. pylori's resistance to antimicrobial medications persists. In this context, creating an anti-H. pylori vaccine that can deliver a satisfactory eradication rate with fewer side effects would be highly beneficial. In this regard, a new series of bis(1,3,4-thiadiazoles) was synthesized and assessed for antimicrobial activity against H. pylori. Combining two bioactive 1,3,4-thiadiazole portions within a single molecule to create a new bis-heterocycle represents an efficient strategy to produce powerful compounds and address issues of resistance and effectiveness. Every synthesized compound showed outstanding inhibition results. Compounds 5c and 8 exhibited the lowest MIC values, recorded at 7.5 and 15.6 μg/mL, respectively. Theoretical predictions were employed to evaluate ADME, leading to outcomes of low solubility, stability, and bioavailability. The effective agents aimed at H. pylori were encapsulated in an appropriate newly developed nanocarrier to tackle challenges related to low bioavailability and stability. Further tests were carried out to evaluate the efficacy of antimicrobials against H. pylori, resulting in promising results. Additionally, the MIC values decreased by 4 and 2 times relative to their original synthetic versions. The activity of the enzyme urease was assessed before nanoencapsulation, showing an IC₅₀ value of 8.99 μg/mL, which was reduced to 7.8 μg/mL after nanoencapsulation.

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