Iranian Journal of Basic Medical Sciences最新文献

This review focuses on identifying the primary limitations affecting the oral administration of biologics and evaluates current strategies designed to improve their bioavailability. It also incorporates a bibliometric mapping approach to assess ongoing research trends in this field. A detailed literature survey was performed alongside a bibliometric analysis using VOSviewer to illustrate keyword relationships and the evolution of research activity in oral biologic delivery. Barriers such as enzymatic degradation, restricted epithelial transport, and rapid systemic elimination hinder effective oral delivery of biologics. Innovative approaches including nanocarrier systems, enteric coatings, PEGylation, lipidation, protease inhibitors, and mucoadhesive formulations have been developed to address these issues. Advances like receptor targeted ligand systems and pH sensitive nanocarriers show promise for more efficient absorption. Emerging therapies, including GLP-1 receptor agonists and orally delivered monoclonal antibodies, are highlighted. The review also touches upon therapeutic applications beyond oncology, such as neurodegenerative diseases. Case studies on oral insulin provide valuable clinical development insights. Scaleup production and regulatory challenges are discussed, along with future directions for formulation improvement. Although oral delivery of biologics presents significant obstacles, technological advancements are steadily transforming the landscape. Future research focusing absorption mechanisms and innovative formulation strategies will be crucial for the successful development of effective oral biologic therapies.

Objectives: Cryopreservation of immature testicular tissue (ITT) is currently the only technique available for restoring fertility in adolescent boys with cancer. Preclinical investigations assessing the development of human transplanted ITT using a nude mouse model have revealed a notable decrease in spermatogonial stem cells.

Materials and methods: We transplanted ITT from neonatal male NMRI mice (3-5 days old), either embedded in a chitosan (CS) scaffold or without it, into the epididymal fat pad (Epi.fat) and back skin of mature (6-8 weeks old) male NMRI mice. Grafts were recovered 14 days post-transplantation. We evaluated scaffold cytotoxicity, morphology, in vivo degradation, tissue integrity, seminiferous tubule morphometry, and germ cell survival.

Results: The diameters of the seminiferous tubules did not differ significantly between grafted groups. However, the height of the seminiferous epithelium in the Epi.fat + S group was significantly greater than in the Back + S group. The total seminiferous tubule area ratio in the Epi.fat, Epi.fat + S, and Back groups were significantly lower compared to the Back + S group. The number of PLZF-positive cells per seminiferous tubule section was significantly higher in the Back + S group than in the Epi.fat group.

Conclusion: Allotransplantation of ITT embedded in a CS scaffold enhanced spermatogonial survival and tissue integrity in both the Epi.fat and subcutaneous back skin. Among the two transplantation sites, the subcutaneous back skin yielded more favorable outcomes.

Objectives: Acute liver failure (ALF) is a life-threatening condition marked by rapid hepatocellular damage. This study investigates the therapeutic efficacy of human umbilical cord-derived mesenchymal stem cells (hUCMSCs) in a rat model of ALF.

Materials and methods: ALF was induced using D-galactosamine and lipopolysaccharide in rats. hUCMSCs were administered intravenously at different time points and dosages. Liver function, inflammatory cytokine levels, histopathology, neutrophil infiltration, and survival rates were evaluated. Additionally, biodistribution was tracked using 89Zr-labeled hUCMSCs, and fresh versus cryopreserved cells were compared.

Results: Administration of hUCMSCs, especially at the prog-2h time point, significantly improved survival and liver histology. Treatment reduced ALT and AST levels and modulated pro- and anti-inflammatory cytokines. Neutrophil infiltration was alleviated by both fresh and cryo-preserved hUCMSCs. Biodistribution data revealed hepatic enrichment of hUCMSCs peaking at 24 hr post-injection.

Conclusion: hUCMSCs exhibit strong immunomodulatory and hepatoprotective properties in ALF, offering promise for clinical translation. Timing and dosage significantly influence therapeutic efficacy, and cryopreserved cells maintain functionality comparable to that of fresh cells.

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: 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.

Objectives: Melanoma, a lethal form of skin cancer, is closely linked to mutations in melanocytes. Due to increased resistance to chemotherapy, innovative strategies, including gene and combination therapies, are being explored. This study evaluates the effects of trehalose (TRE) and hydroxychloroquine (HCQ) in enhancing the efficacy of BRAF (V600E)-siRNA in A375 cells.

Materials and methods: The A375 cells were treated, and changes in cell viability were assessed using MTT assays. Apoptosis was evaluated using flow cytometry. Additionally, gene expression analysis of B-Raf proto-oncogene, serine/threonine kinase (BRAF), Caspase 3 (CASP3), and Phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) was performed using quantitative RT-PCR.

Results: HCQ treatment reduced cell viability and increased apoptosis compared to both control cells and cells treated with TRE. Gene expression analysis showed a significant down-regulation of BRAF expression in cells treated with HCQ and BRAF (V600E)-siRNA compared to siRNA-only treated cells. CASP3 expression was significantly up-regulated in cells treated with combined HCQ and siRNA, indicating a stronger apoptotic response. PIK3R3 expression showed no significant change in the transfected groups.

Conclusion: TRE, either alone or combined with siRNA, showed limited efficacy and may counteract the apoptotic benefits of HCQ. Conversely, HCQ, whether used alone or in combination with siRNA, enhanced apoptosis, suggesting promise as a potential treatment for melanoma.

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.