Iranian Journal of Basic Medical Sciences最新文献

Objectives: Wnt5a, which regulates the activities of osteoblasts and osteoclasts, is reportedly overexpressed in osteoarthritis (OA) tissues. The purpose of this study was to elucidate its role in the development of OA by deleting Wnt5a in osteocalcin (OCN)-expressing cells.

Materials and methods: Knee OA was induced by anterior cruciate ligament transection (ACLT) in OCN-Cre;Wnt5a^fl/fl knockout (Wnt5a-cKO) mice and control littermates. Eight weeks after surgery, histological changes, cell apoptosis, and matrix metabolism of cartilage were evaluated by toluidine blue, TUNEL staining, and im-immunohistochemistry analyses, respectively. In addition, the subchondral bone microarchitecture of mice was examined by micro-computed tomography (micro-CT).

Results: Histological scores show substantial cartilage degeneration occurred in ACLT knees, coupled with decreased collagen type II expression and enhanced matrix metalloproteinase 13 expression, as well as higher proportions of apoptotic cells. Micro-CT results show that ACLT resulted in decreased bone mineral density, bone volume/trabecular volume, trabecular number, and structure model index of subchondral bones in both Wnt5a-cKO and control littermates; although Wnt5a-cKO mice display lower BMD and BV/TV values, no significant difference was observed between Wnt5a-cKO and control mice for any of these values.

Conclusion: Our findings indicate that Wnt5a deficiency in OCN-expressing cells could not prevent an osteoarthritic phenotype in a mouse model of post-traumatic OA.

Lung cancer is one of the leading causes of death among all cancer deaths. This cancer is classified into two different histological subtypes: non-small cell lung cancer (NSCLC), which is the most common subtype, and small cell lung cancer (SCLC), which is the most aggressive subtype. Understanding the molecular characteristics of lung cancer has expanded our knowledge of the cellular origins and molecular pathways affected by each of these subtypes and has contributed to the development of new therapies. Traditional treatments for lung cancer include surgery, chemotherapy, and radiotherapy. Advances in understanding the nature and specificity of lung cancer have led to the development of immunotherapy, which is the newest and most specialized treatment in the treatment of lung cancer. Each of these treatments has advantages and disadvantages and causes side effects. Today, combination therapy for lung cancer reduces side effects and increases the speed of recovery. Despite the significant progress that has been made in the treatment of lung cancer in the last decade, further research into new drugs and combination therapies is needed to extend the clinical benefits and improve outcomes in lung cancer. In this review article, we discussed common lung cancer treatments and their combinations from the most advanced to the newest.

Objectives: Investigating the impact of cadmium (Cd) on annulus fibrosus (AF) cells and its potential mechanism was the purpose of the current study.

Materials and methods: Cd was cultivated in different concentrations (0, 1, 5, 10, and 20 μM) on AF cells and the potential effects of the metal were assessed. Using the CCK-8 method, cell viability and proliferation were identified. Using transcriptome analysis, the annulus fibrosus cells were sequenced both with and without cadmium chloride. The EdU method was used to determine the rate of cell proliferation; senescence-associated β-galactosidase (SA-β-Gal) staining was used to determine the number of positive cells; and western blot, RT-PCR, and immunofluorescence were used to determine the protein and mRNA expression of senescence-associated proteins (p16, p21, and p53) and c-Jun N-terminal kinase (JNK).

Results: According to the findings, Cd has the ability to increase the production of senescence-associated genes (p16 and p21) and senescence-associated secreted phenotype (SASP), which includes IL-1β and IL-6. Through the JNK/p53 signal pathway, Cd exposure simultaneously accelerated AF cell senescence and promoted SASP. Following JNK inhibitor (SP600125) treatment, the expression of p53, JNK, and senescence-associated indices were all down-regulated.

Conclusion: By activating the JNK/p53 signaling pathway, Cd can induce oxidative stress damage and AF cell senescence. These findings could provide a new approach for treating and preventing intervertebral disc degeneration (IVDD) caused by Cd exposure.

Objectives: Sepsis poses a significant threat to human life, rendering it a burdensome medical disease. Despite significant advancements, the current state of medical science still lacks a viable and efficacious cure. Costunolide (COST) is a multifaceted sesquiterpene lactone that exhibits a range of actions, including anti-inflammatory and antioxidant properties. We investigated the potential impacts of COST on a rat sepsis model caused by cecal ligation and puncture (CLP).

Materials and methods: We created an experimental rat model with the following groups: SHAM, CLP, CLP+low dose COST, and CLP+high dose COST. Blood, kidney, and lung samples were collected. Inflammatory mediators such as interleukin-1beta (IL-1β), IL-6, tumor necrosis factor-alpha (TNF- α), and nuclear factor kappa-B (NF-κB) were investigated. In addition, we assessed oxidative stress by measuring 8-Hydroxydeoxyguanosine (8-OHdG) immunopositivity, MDA levels, glutathione (GSH), and superoxide dismutase (SOD) activity. Histopathological and immunohistochemical examinations backed up our findings.

Results: Compared to the CLP group, the COST group showed a reduction in inflammatory and oxidative stress indicators. The expression of inflammatory mediators was suppressed by COST, and histological examinations revealed improvements in kidney and lung tissues in the treatment groups.

Conclusion: Our study highlights the preventive effects of COST against CLP-induced sepsis-related injury. Considering its beneficial effects against many diseases, COST is worthy as to be evaluated against sepsis.

Objectives: Osteoporosis is a significant public health concern due to its association with fragility fractures. Despite experiencing such fractures, many patients remain at high risk of future fractures due to inadequate management and treatment of their underlying osteoporosis. This research presents a comprehensive intervention to enhance osteoporosis management in patients with fragility fractures. The intervention involves a thorough personalized assessment of fracture risk using clinical factors and bone density testing, followed by customized treatment based on the individual's fracture risk level. It also addresses non-compliance through patient education, counseling, reminders, and improved care coordination among acute, primary, and specialty providers.

Materials and methods: The aim is to create and characterize sodium alginate/hydroxyapatite (HA) scaffolds reinforced with zinc oxide nanoparticles (ZnO-NP) for bone tissue engineering. Freeze-drying was used to produce scaffolds with 0-15% ZnO-NP. Analyses confirmed the composite structure, uniform ZnO-NP distribution, and decreasing pore size with higher ZnO-NP content. Mechanical testing showed increased compressive strength with greater ZnO-NP.

Results: The scaffolds exhibited over 70% porosity, neutral pH, and increased apatite deposition and bioactivity with higher ZnO-NP. They also demonstrated decreased swelling and strong antibacterial activity against Escherichia coli and Staphylococcus aureus, making them a promising candidate for bone regeneration.

Conclusion: Additionally, the researchers used an artificial neural network (ANN) to better understand the relationships between various scaffold properties, and the ANN-based predictions showed that changes in pore size and porosity affect the other properties, with acceptable error compared to experimental results.

Objectives: Atrophy of the muscles following denervation can lead to the death of myofibers. This study evaluated the sciatic nerve and tibialis cranialis muscle (TCM) regeneration using scaffold and cells.

Materials and methods: Ninety adult male Wistar rats were divided into six main groups (n=15) and three subgroups (2, 4, and 8 weeks). Groups: control; without surgery, Tr; sciatic nerve transected in silicone tube, S; collagen gel put inside the silicone tube, MC; placed 3×10⁴ mast cells mixed with scaffold, MSC; placed 3×10⁴ mesenchymal stem cells mixed with scaffold, and MC+MSC; 3×10⁴ of each of the mast cell and mesenchymal stem cells along with scaffold. Animals were euthanized and sampled for muscle and nerve histological and nerve immunohistochemical evaluations.

Results: Diameter of muscle fibers, ratio of the muscle fiber's nuclei to the fibrocyte nuclei (mn/fn), ratio of the muscle fibers nuclei number to the muscle fiber's number (mn/mf), and ratio of the blood vessels number to the number of muscle fibers (v/mf) in all treatment groups, especially the MC + MSC group, increased compared to the Tr group but the number of mast cells, the percentage of sarcoplasmolysis, and necrosis fibers decreased. Histomorphometric results of the nerve in its various parts and immunohistochemistry results also showed improved nerve conduction, especially in the MC + MSC group.

Conclusion: In this study, nerve improvement happened mainly for two reasons: cells and time. So, the most obvious improvement occurred in the group with mast and mesenchymal cells in the 8^th week.

Objectives: Baicalein (BAI) is one of the main ingredients of Scutellaria baicalensis georgi. Its pharmacological effects have been widely reported in various cancers. However, the specific molecular mechanism of BAI in gastric cancer (GC) has not been defined. This study investigates BAI's inhibitory effect on gastric cancer and its potential mechanisms.

Materials and methods: Gastric normal (GES-1 cells) and cancer cells (MKN-74 and MGC-803 cells) were treated with different concentrations of BAI. Cell proliferation and migration were assessed by MTT, colony formation, wound healing, and transwell assays. Flow cytometry and Hoechst 33342 staining were used to detect the cell apoptosis. IF and WB tests were employed to detect EMT-related protein. Finally, the anti-tumor effects of BAI were verified in in vivo xenograft models.

Results: Our results show that the cell viability of MKN-74 and MGC-803 cells was significantly decreased in a time- and dose-dependent manner after BAI treatment by MTT assay. The expression levels of p12-LOX genes, which were determined by quantitative RT-PCR and WB, in MKN-74 cells were higher than those in GES-1 cells. As shown by the wound healing assay and Transwell assay, the treatment with BAI also significantly suppressed GC cell migration and invasion. Besides, BAI inhibited the phosphorylation of ERK1/2 and MEK1/2 in GC cells, as revealed by WB. Furthermore, BAI significantly inhibited tumor growth capacities in a xenograft model.

Conclusion: BAI shows a significant anti-tumor effect and inhibition on tumor cell migration and invasion, which is probably through regulation of p12-LOX modulated epithelial-mesenchymal transformation.

Living Donor Liver Transplantation (LDLT) is a promising approach to treating end-stage liver diseases, however, some post-operatory complications such as pneumonia, bacteremia, urinary tract infections, and hepatic dysfunction have been reported. In murine models using partial hepatectomy (PHx), a model that emulates LDLT, it has been determined that the synthesis of hepatic cell proliferation factors that are associated with noradrenaline synthesis are produced in locus coeruleus (LC). In addition, studies have shown that PHx decreases GABA and 5-HT2A receptors, promotes loss of dendritic spines, and favors microgliosis in rat hippocampus. The GABA and serotonin-altered circuits suggest that catecholaminergic neurons such as dopamine and noradrenaline neurons, which are highly susceptible to cellular stress, can also be damaged. To understand post-transplant affections and to perform well-controlled studies it is necessary to know the potential causes that explain as a liver surgical procedure can produce brain damage. In this paper, we review several cellular processes that could induce gliosis in LC after rat PHx.

Objectives: Adipose-derived Mesenchymal stem cells (ASCs) have garnered attention for their regenerative potential; therefore, their cellular senescence-related gene expression remains crucial in therapeutic contexts. Nowadays, combination therapies have shown promising results in reducing senescent cells. This study investigated the effects of vitamin C, doxycycline, and azithromycin co-treatment on the key cellular senescence-associated genes in ASCs.

Materials and methods: Human ASCs were cultured and treated for 24 hr with vitamin C, doxycycline, azithromycin, and a combination of three drugs. Total RNAs were extracted, and the expression of p21, p16, Nanog, Oct4, and Sox2 genes was assessed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Additionally, cell cycle alterations were analyzed via flow cytometry after treatment with these compounds.

Results: Notably, vitamin C treatment resulted in a significant down-regulation of p21 gene expression (P<0.01), implicating the potential role of vitamin C in promoting cell cycle progression. Doxycycline treatment led to a significant up-regulation of p21 and p16 gene expression (P<0.05), as it has previously been shown to induce cell cycle arrest. Similarly, azithromycin treatment predominantly increased p21 expression (P<0.05). Besides, cell cycle analysis revealed that each compound had changed the distribution of cells across different phases of the cell cycle.

Conclusion: The combined use of all three drugs yielded intricate interactions, suggesting a complex yet promising approach to future research. According to our findings, the major difference in the combination drug-treated group (VDA) can be explained by the neutralizing effect of these three components in the environment.

Objectives: Prior research has indicated that hydroxycitric acid (HCA) can impede the formation of calcium oxalate (CaOx) crystals, yet the specific mechanisms underlying its therapeutic effects remain unclear. In this study, we delved into the protective effects of HCA against glyoxylate-induced renal stones in rats and sought to elucidate the underlying metabolic pathways.

Materials and methods: Forty rats were randomly assigned to five groups: control group, model group, L-HCA-treated group, M-HCA-treated group, and H-HCA-treated group. Von Kossa staining was conducted on renal sections, and blood urea nitrogen and serum creatinine were determined by biochemical analysis. Meanwhile, body weight and urine volume were also measured. We subjected urine samples from the rats to analysis using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Next, we employed a metabolomic approach to scrutinize the metabolic profiles of each group.

Results: HCA significantly reduced blood urea nitrogen and serum creatinine, and increased body weight and urine volume. It also reduced CaOx crystal deposition. A total of 24 metabolites, exhibiting a significant reversal pattern following HCA administration, were identified as urine biomarkers indicative of HCA's preventive effects against CaOx crystal-induced renal injury. These metabolites are primarily associated with glycine, serine, and threonine metabolism; phenylalanine metabolism; tricarboxylic acid cycle; taurine and hypotaurine metabolism; and tryptophan metabolism.

Conclusion: It was demonstrated that HCA has a protective effect against CaOx crystal-induced kidney injury in rats by modulating various metabolic pathways. Additionally, results suggest that HCA holds promise as a potential clinical therapeutic drug for both the prevention and treatment of renal stones.