Iranian Journal of Basic Medical Sciences最新文献

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.

Dyspnea, a distressing symptom characterized by difficult or labored breathing, can be caused by a variety of underlying processes, including respiratory and cardiovascular problems. Despite advancements in medicine, a need remains for more effective dyspnea therapies. Herbal therapy has emerged as a viable approach in this field, with potential therapeutic benefits. The purpose of this narrative review is to assess the efficacy of herbal medication in reducing dyspnea. A comprehensive search was undertaken without time constraints utilizing Google Scholar, PubMed, and Scopus databases up to December 2024 to collect relevant clinical trials. Herbal medicine (Allium sativum L., Carum copticum (L.) Benth. & Hook.f., Crocus sativus L., Curcuma longa L., Eucalyptus globulus Labill., Mentha × piperita L., Nigella sativa L., Rosmarinus officinalis L., Thymus vulgaris L., and Zataria multiflora Boiss.) and their main components have been shown to reduce dyspnea through multiple mechanisms of disease, including anti-inflammatory, bronchodilatory, and anti-oxidant properties. The findings indicate that herbal remedies may be a useful complement or alternative therapy for managing dyspnea. It could be concluded that herbal therapy offers an effective approach to managing dyspnea, providing a natural and potentially beneficial option for people experiencing respiratory distress. More research and clinical trials are needed to understand the exact mechanisms of action and maximize the use of herbal therapies in the treatment of dyspnea.

Objectives: Sodium valproate (VPA) has harmful effects on the male reproductive system. The present study aimed to investigate the influence of curcumin (CUR) in mitigating the VPA-induced reproductive toxicity in male mice.

Materials and methods: The male mice (mean weight 20 g and 8 weeks old) were divided into six groups (n=6): control, VPA only (500 mg/kg, IP), VPA plus different doses of CUR (25, 50, and 100 mg/kg, IP), CUR alone (100 mg/kg, IP). After treatment for eight consecutive weeks, the mice were sacrificed, testicle tissues were separated, and mitochondria were isolated with different centrifuge techniques. Various biomarkers were evaluated in testis tissue, including the concentration of lipid peroxidation, glutathione, protein carbonyl, nitric oxide, IL-6, and TNF-alpha. Also, mitochondrial toxicity, swelling, and membrane potential were assessed. Furthermore, sperm analysis and histopathological examination were done on testicular tissue.

Results: VPA injection increased the amount of nitric oxide, inflammatory factors, mitochondrial toxicity, and oxidative stress markers (P<0.05). Also, histopathological and sperm analysis showed significant damage to testis tissue and a significant reduction in sperm count, motility, and normal morphology after VPA administration. CUR led to a substantial reduction of the inflammatory and oxidative stress parameters(P<0.05), restored the VPA-induced testis toxicity, and increased sperm count and motility (P<0.05).

Conclusion: Our study demonstrates CUR's ameliorative effects on mitochondrial oxidative damage and inflammation caused by VPA-induced reproductive toxicity, which can be suggested as a strategy for reducing the side effects caused by VPA.

Objectives: Insulin resistance is the primary trigger of metabolic syndrome, carbonyl stress, and vitamin B6 deficiency, while the nuclear factor (NF-κB) pathway is a pivotal factor in its development. Hence, we investigated the impact of pyridoxal phosphate (PLP) on liver and kidney functions, carbonyl stress, and inflammatory markers in serum and liver tissue.

Materials and methods: The study involved four groups of rats, each consisting of eight rats: untreated normal rats (N), rats induced to have metabolic syndrome (MetS), and rats treated with PLP, labeled as N (PLP) and MetS (PLP), respectively. Metabolic syndrome was induced in rats by administering a concentrated sucrose solution for four months. The treated groups received daily PLP at 180 mg/l in their drinking water. Subsequently, the metabolic profile, NF-κB expression, indicators of gly-oxidation, inflammation, and organ function markers were evaluated.

Results: PLP significantly reduced gly-oxidation, carbonyl stress, and inflammatory indicators (in both serum and liver tissue) as well as NF-κB expression, glycation, carbonyl stress, liver fat levels, glycemia, insulin resistance, and body weight (P<0.001). The treatment also prevented acute hepatitis.

Conclusion: PLP had beneficial effects in the metabolic syndrome rat model, showing anti-obesity and hepato-renal protective effects. It improved metabolism and organ (liver and kidney) functions by modulating NF-κB expression, glutathione metabolism, carbonyl stress, and oxidative stress.

Objectives: Classical Hodgkin lymphoma (cHL) is identified by the appearance of Hodgkin and Reed-Sternberg cells. A20 and CYLD are deubiquitinating enzymes involved in negatively regulating NF-κB-mediated immune response. Vincristine (Vinc) and doxorubicin (Dox) are classical antitumor drugs, in which Dox serves a key role in chemotherapy against cHL and Vinc induces disruption of microtubule function that inhibits mitosis of cancer cells. Little is known about the roles of A20/CYLD in regulating macrophage function from cHL patients upon treatment with Vinc or Dox. This study, therefore, asked whether A20/CYLD expression affects function of macrophages in cHL cases.

Materials and methods: Macrophages from cHL patients differentiated from bone marrow cells were exposed to Vinc or Dox. Gene expression levels were determined by real time-qPCR, cell maturation, apoptosis and phagocytosis by flow cytometry, and cytokine release by ELISA.

Results: Dox induced maturation, apoptosis, and phagocytosis of macrophages in cHL cases. Moreover, the percentage of CD68⁺CD40⁺, but not CD68⁺CD86⁺ cells as well as levels of IL-1β were further enhanced when exposed to A20 siRNA, whereas the absence of CYLD unaltered macrophage function in cHL patients. Importantly, the increased numbers of A20-sensitive CD68⁺CD40⁺ and Annexin V^-PI⁺ cells as well as enhanced levels of caspase 3 were abolished in the presence of mTOR inhibitor Everolimus.

Conclusion: The present study indicates that Dox-induced macrophage maturation and apoptosis are dependent on A20 expression through mTOR signaling. Moreover, inhibition of Dox-induced macrophage maturation in the patients with low A20 expression by Everolimus might represent a promising therapy for A20-sensitive cHL cases.

Objectives: Wound healing requires effective biomaterials to overcome the limitations of conventional treatments, especially for full-thickness injuries. This study introduces an innovative hydrogel composed of carboxymethyl cellulose (CMC), carboxymethyl chitosan (CMCS), and gelatin (Gel), enhanced with extracts from Arthrospira platensis (AP) and Chlorella vulgaris (CV). The matrix is further integrated with decellularized amniotic membranes to enhance therapeutic effects.

Materials and methods: Hydrogels were formulated, crosslinked using 1-Ethyl-3-(3-Dimethylaminopropyl)carbodiimide (EDAC), and incorporated with 1% of either AP, CV, or both extracts. The scaffold was subjected to in vitro cell viability, red blood cell hemolysis, blood clotting index, and in vivo assays. The physical and chemical properties of the scaffolds were also evaluated using weight loss, swelling ratio, scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, and nuclear magnetic Resonance (NMR) spectroscopy. To analyze wound healing under in vivo conditions, 36 male Wistar rats were used, and histopathological analysis was performed using hematoxylin and eosin staining.

Results: In vitro studies demonstrated that AP-loaded hydrogels exhibited faster degradation and a higher release profile (85.25%) compared to CV (68.32%), consistent with AP's anti-oxidant properties. In vivo assessments on Wistar rats demonstrated that CV hydrogels achieved faster wound closure and better collagen synthesis, reaching 88 ± 2.5 % closure at 14 days versus 81 ± 2.64 % for AP (P<0.05). The CMC/CMCS/Gel/AP 1%/CV 1% hydrogels showed synergistic effects, achieving a 92 ± 2.1 % closure rate (P<0.01).

Conclusion: The hydrogels demonstrated strong potential for skin repair, exhibiting good biocompatibility and controlled release; further refinement of the extracts and materials is suggested.

Objectives: Endometriosis carries remarkable social, public health, and financial consequences. Based on two theories of retrograde menstruation and stem cells, menstrual blood-derived stem cells (MenSCs) play a significant role in endometriosis since key genes of critical cellular processes are differentially expressed in the MenSCs of endometriosis and non-endometriosis women (E- and NE-MenSCs, respectively). In this study, E-MenSCs were isolated from the menstrual blood of women with various endometriosis subtypes. We tried to find the proper microRNA (miRNA) and assayed the effects of exosome-encapsulated miRNA on modulating the gene expression profile and functional pattern of E-MenSCs.

Materials and methods: After in silico selection of miR-149-3p using publicly accessible algorithm-based databases, E- and NE-MenSCs were cultured as controls, and the other experimental groups were as follows: E-MenSCs transfected with empty and miRNA vectors (E-MenSC+BB and E-MenSC+miR), and E-MenSCs treated with exosomes derived from non-transfected and miRNA-transfected NE-MenSCs (E-MenSC+Exo and E-MenSC+T-Exo). Then, the expression level of selected genes, the level of interleukins (ILs) and oxygen reactive species (ROS), the protein level of β-catenin and Ki-67, and the migratory ability were assessed through real-time PCR, ELISA, western blot, and scratching tests, respectively.

Results: Although both E-MenSCs+T-Exo and E-MenSC+miR showed down-regulation of IL-6, -8, and -10, neither had decreased IL-1β, vascular endothelial growth factor, IDO1, and KRAS levels. Furthermore, only the IL-6 protein level was significantly decreased in the E-MenSC+miR group, but the levels of IL-6, IL-8, ROS, β-catenin, and Ki67 were significantly lower in the E-MenSCs+T-Exo group compared to the E-MenSCs.

Conclusion: The potential of exosomes as miRNA carriers could be considered in developing novel endometriosis therapies.