Iranian Journal of Basic Medical Sciences最新文献

Objectives: This study aims to design and fabricate innovative polymer-ceramic-metal scaffolds for bone tissue engineering, utilizing 3D printing and freeze-drying techniques to enhance bone repair.

Materials and methods: Stainless steel scaffolds were produced via selective laser melting (SLM) and coated with varying weight percentages (0, 5, 10, 15) of polyvinylpyrrolidone (PVP), carboxymethyl chitosan (CMC), and forsterite using freeze-drying. The scaffolds were characterized through Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscopy (SEM) to assess functional groups, phase purity, porosity, and pore size. Biological assessments included bioactivity, ion emission tests (ICP-AES), and wettability evaluations. Artificial neural networks (ANN) were employed to predict mechanical and biological properties.

Results: The analysis revealed that scaffolds with 15% forsterite exhibited optimal mechanical and biological performance, enhancing the scaffold's potential for clinical applications in bone repair.

Conclusion: This study introduces a novel scaffold design that significantly improves bone tissue regeneration processes. The integration of advanced materials and predictive modeling through ANN paves the way for future research in the field of bone tissue engineering.

Objectives: Parthenolide (PTL) has significant anti-inflammatory and immunomodulatory effects, but its regulatory mechanisms in endometriosis (EMs) remain unclear. This study aimed to systematically evaluate the effects of PTL on cellular models and a murine EMs model, with a focus on its regulatory roles in autophagy and the NLRP3 inflammasome pathway.

Materials and methods: Human monocytic leukemia THP-1 cells, murine immortalized bone marrow-derived macrophages, and 30 female C57BL/6 mice were used. Autophagy-related proteins (Beclin1, LC3, p62) and inflammasome components (NLRP3, ASC, caspase-1) were detected by Western blotting, and the activation of the AMPK/ULK1 signaling pathway was assessed after treating with PTL at a concentration of 10 mg/ml for 1 hr. A murine EMs model was established by peritoneal implantation, followed by intraperitoneal injections of PTL (10 mg/ml). Immunohistochemical staining was performed to detect the expression of NLRP3, caspase-1, IL-1β, and GSDMD in ectopic lesions.

Results: In vitro, PTL (10 mg/ml) significantly inhibited the activation of NLRP3, caspase-1-p20, IL-1β, and GSDMD, while increasing the phosphorylation levels of Beclin1 and AMPK/ULK1, and decreasing the expression of p62 and LC3, indicating enhanced autophagic flux. In vivo, PTL treatment markedly reduced the number, surface area, and weight of ectopic lesions in mice, and significantly suppressed the expression of inflammatory proteins in the lesions.

Conclusion: PTL exerts its therapeutic effect on EMs by simultaneously activating autophagy through the AMPK/ULK1 signaling pathway and inhibiting the NLRP3 inflammasome and its downstream effectors.

Objectives: Dysphania botrys (L.) Mosyakin & Clemants (Basionym: Chenopodium botrys L.), belonging to the Amaranthaceae family, has been used for the treatment of inflammation, bacterial and viral infections, and diabetes. In this study, we aimed to evaluate the potential cytotoxic, anti-oxidant, and apoptotic activities of methanol (MeOH) extract and petroleum ether (PE) and dichloromethane (DCM) fractions of D. botrys against B16F10 and MCF-7 cell lines.

Materials and methods: The anti-oxidant activities of fractions were measured using FRAP, DPPH, and β-carotene assays. The cytotoxicity of extracts and the intracellular ROS content were assessed using resazurin and DCFH-DA assays, respectively. A flow cytometry assay using PI staining was performed to measure the apoptotic activity of the fractions. Total phenolic and flavonoid content was determined using spectrophotometric methods.

Results: The DCM fraction of D. botrys exhibited the highest anti-oxidant activity in FRAP, DPPH, and β-carotene assays, which also showed the highest amount of phenolic and flavonoid content compared to the MeOH extract and PE fraction. Cell viability and intracellular ROS content were significantly decreased following the treatment of B16F10 and MCF-7 cells with 100 and 200 µg/ml DCM and PE fractions. Treatment with 200 µg/ml DCM and PE fractions increased apoptosis in B16F10 cells.

Conclusion: DCM fraction of D. botrys had significant anti-oxidant effects that may be associated with its phenolic and flavonoid compounds. It seems that terpenoid compounds are responsible for cytotoxic effects. Hence, complementary studies are needed to assess other bioactive compounds of D. botrys and their protective mechanisms.

Metabolic syndrome is characterized by obesity, insulin resistance, dyslipidemia, and hypertension. Withania somnifera, commonly known as ashwagandha or Indian winter cherry, belongs to the Solanaceae family. W. somnifera, particularly its powdered root, is a fundamental component of traditional Indian medicine. W. somnifera (Ashwagandha) exhibits pharmacological activities, including immunomodulatory, anti-stress, and neuroprotective effects in animal models. Also, preclinical and clinical studies demonstrate its anti-inflammatory and antiviral properties. In rodent studies, ashwagandha regulates apoptosis and modulates reactive oxygen species (ROS) levels as well as mitochondrial activity. Additionally, it improves endothelial function in rats, dogs, and human brain endothelial cells. Research conducted in both living organisms and controlled laboratory conditions has demonstrated that W. somnifera alleviates the symptoms of metabolic syndrome. It positively affects diabetes by inhibiting dipeptidyl peptidase-4 (DPP-4), α-glucosidase, and α-amylase, while simultaneously increasing pancreatic insulin secretion and improving insulin sensitivity in organs. It has a vasodilatory and diuretic effect. Ashwagandha reduces the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. It modulates the gene expression of peroxisome proliferator-activated receptor (PPAR)-γ. It regulates the gene expression of sterol regulatory element-binding protein (SREBP)-1c and CYP7A1. It increases the secretion of bile acids that eliminate excess cholesterol. It reduces oxidative stress and inflammation while protecting the body from the harmful effects of elevated cholesterol. This study aims to compile a variety of research findings on the effectiveness of ashwagandha in managing metabolic syndrome.

Objectives: This study aimed to develop and evaluate decellularized bovine bone (DBB) scaffolds and investigate their potential to promote osteogenic differentiation when combined with Crocin and Alendronate.

Materials and methods: Bovine bone was decellularized using a combination of physical (freeze-thaw cycles, sonication), chemical (sodium dodecyl sulfate), and enzymatic (deoxyribonuclease I) treatments to preserve native bone architecture. Scaffold properties were assessed by evaluating extracellular matrix (ECM) integrity and compressive strength. Biocompatibility was confirmed through cytotoxicity and hemolysis assays. In vitro osteogenesis was analyzed using alizarin red staining and qRT-PCR (quantitative real-time polymerase chain reaction) to quantify expression of osteogenic markers RUNX2, osteocalcin, osteopontin, and osteonectin following treatment with crocin (Cr 5 mg/ml), Alendronate (ALN 1 mg/ml), and their combination (Cr/ALN 5 mg/ml).

Results: DBB scaffolds-maintained ECM structure and compressive strength (14.56 ± 0.82 MPa), comparable to native bovine bone (17.86 ± 0.14 MPa). No cytotoxic or hemolytic effects were observed. Crocin, Alendronate, and Cr/ALN treatments significantly enhanced RUNX2 expression (70%, 60%, and 65%, respectively), while Osteocalcin expression increased in Cr (50%) and Cr/ALN (25%) groups. Osteopontin and osteonectin expression also rose in Cr and Cr/ALN groups, supporting enhanced osteogenic differentiation.

Conclusion: Based on in vitro findings, DBB scaffolds demonstrate favorable mechanical and biological properties, and loading the scaffolds with crocin and Alendronate enhanced osteogenic differentiation and matrix mineralization, indicating potential for bone-regeneration applications.

Objectives: Cholestasis, a hepatic disorder characterized by impaired bile secretion, drives progressive liver damage, fibrosis, failure, and even death. This study explores how amarogentin (AG) ameliorates cholestatic liver injury in rats induced by α-naphthylisothiocyanate (ANIT).

Materials and methods: The bile flow rate, a visual indicator of the degree of intrahepatic cholestasis, was measured to assess the model's success. Liver function was evaluated by analyzing the serum levels of enzymes (ALP, ALT, AST, TBIL, DBIL, and TBA), as well as indicators of oxidative damage (SOD, MDA, and GSH-Px), in the liver tissue, and by examining liver histopathology. Additionally, Western blot analysis was utilized to assess the protein levels of the FXR and Nrf2 signaling pathways in the liver tissue of cholestatic rats both before and after AG treatment, to understand the underlying protective mechanism.

Results: AG was administered intragastrically to ANIT-treated cholestatic rats, which significantly decreased the plasma concentrations of AST, ALT, ALP, TBIL, DBIL, and TBA, and alleviated ANIT-induced liver injury. AG could also significantly improve the bile flow rate and suppress oxidative stress. Western blot analysis revealed that AG could enhance ANIT-induced cholestasis by modulating the anti-oxidative system via activation of the PI3K/Akt/Nrf2 pathway and by regulating bile acid metabolism.

Conclusion: This study demonstrated that AG may mitigate ANIT-induced cholestatic liver damage by improving the bile flow rates, decreasing the concentrations of liver function markers and serum enzyme levels, enhancing liver histology, activating Nrf2 via the PI3K/Akt signaling pathway, and controlling bile acid transport.

Psoriasis is a long-lasting inflammatory skin condition that impacts millions globally. The occurrence of this disorder differs significantly across various areas, resulting from a complex interplay of genetic and environmental influences. In psoriasis, the pathogenesis represents a complex interaction of innate and adaptive immunity that plays a significant role in the disease manifestation process. Many genetic factors predispose to psoriasis, which is considered a polygenic disease. Several genes concerning pathways like NF-κB and PI3K/Akt that modulate the amplification of inflammatory response and keratinocyte dysregulation have been elaborated in the light of their differential expression, susceptibility loci, and polymorphisms. Such genetic insights could open a whole new avenue for precision medicine in which biomarkers and gene-targeting therapies are promising options for personalized treatment. This review emphasizes the need for complex investigations into psoriasis, from molecular mechanisms to clinical manifestations, to bridge the gap between basic research and therapeutic development by furthering the understanding of psoriasis and paving the way for innovative treatments addressing skin lesions and systemic effects.

Objectives: Annona muricata" (soursop) is a medicinal plant with diverse ornamental, consumptive, and pharmacological importance. This study was designed for its anti-amnesic potential in mice.

Materials and methods: The crude extract was fractionated with n-hexane, ethyl acetate, and aqueous methanol. The crude and fractions were tested in vitro for the anti-oxidant radical scavenging activity (DPPH), total flavonoid and phenolic content, and their acetylcholinesterase inhibitory activity. Thin-layer chromatography was used to determine the phytochemicals contained in the fractions and their purity. Neurobehavioral models like the Open Field Test, Novel Object Recognition Test, Y-Maze, and Morris Water Maze were used to evaluate the action of AMME (Annona muricata methanol extract) and AMAMF (Annona muricata aqueous methanol fraction).

Results: The AMME and AMAMF significantly reduced the serum levels of myeloperoxidase and arginine (P<0.05). They also modulate the hippocampal and prefrontal acetylcholinesterase and glutamic acid decarboxylase activities (P<0.05). The 25 mg/kg AMAMF significantly affected short-term memory (P<0.05). The AMAMF and AMME significantly enhanced the prefrontal and hippocampal tissue levels of glutathione and superoxide dismutase. During the in vitro AchE assay on all fractions, the AMME and AMAMF consistently showed the greatest percentage of inhibitory activity. They inhibited 50% of the AchE enzymes with the lowest concentration.

Conclusion: The study showed the neuroprotective effects of AMME and AMAMF in memory impairment models. The extracts showed potent AChE inhibition and positive effects on memory and anti-oxidant enzyme levels.

Gliomas are the most common lethal tumors of the brain associated with a poor prognosis and increased resistance to chemo-radiotherapy. Circular RNAs (circRNAs), newly identified noncoding RNAs, have appeared as critical regulators of therapeutic resistance among multiple cancers and gliomas. Since circRNAs are aberrantly expressed in glioma and may act as promoters or inhibitors of therapeutic resistance, we categorized alterations of these specific RNAs expression in therapy resistant-glioma in three different classes, including chemoresistance, radioresistance, and glioma stem cell (GSC)-regulation. circRNAs act as competing endogenous RNA, sponging target microRNA and consequently affecting the expression of genes related to glioma tumorigenesis and resistance. By doing so, circRNAs can modulate the critical cellular pathways and processes regulating glioma resistance, including DNA repair pathways, GSC, epithelial-mesenchymal transition, apoptosis, and autophagy. Considering the poor survival and increased resistance to currently approved treatments for glioma, it is crucial to increase the knowledge of the resistance regulatory effects of circRNAs and their underlying molecular mechanisms. Herein, we conducted a comprehensive search and discussed the existing knowledge regarding the important role eof circRNAs in the emergence of resistance to therapeutic interventions in glioma. This knowledge may serve as a basis for enhancing the effectiveness of glioma therapeutic strategies.

Objectives: Alzheimer's disease (AD) is one of the most common neurodegenerative diseases in people over 65. The present research aimed to investigate the potential of different dietary supplements (DS) in preventing AD in an experimental animal model and in silico study.

Materials and methods: Three DS containing a mixture of wheat-germ oil and black pepper extract/or turmeric extract were prepared. Total phenolic content, HPLC-phenolic profile, phytosterols content, fatty-acids profile, and anti-oxidant activity were evaluated in all DS. The protective effect of the prepared DS was assessed through their impact on cholinergic neurotransmission and the gene expression of GSK3β, APP, and Akt. Oxidative stress and inflammatory markers were evaluated. The inhibition activities against acetylcholinesterase (AChE) and reduction of amyloid-β aggregation of the major phytochemicals present in the studied DS were evaluated using in silico molecular docking study.

Results: Molecular docking revealed that rosmarinic acid and β-Sitosterol exhibited the strongest binding affinities for AChE and Amyloid-β, respectively. The results showed that all DS reduced cholinergic neurotransmission, decreased TNF-α as an inflammatory marker, and improved oxidative stress status. All DS down-regulated the expression of GSK3β and APP while significantly up-regulating the expression of the Akt gene.

Conclusion: The present study concluded that all DS enhanced cholinergic neurotransmission, reduced inflammation, and improved oxidative stress status by impacting the expression of GSK3β, Akt, and APP genes. Rosmarinic acid and β-sitosterol showed promising effects for treating AD, according to an in silico molecular docking study. The studied dietary supplements were considered promising candidates for the prevention of AD.