Iranian Journal of Basic Medical Sciences最新文献

Objectives: Increased nuclear factor (NF-kβ) and carbonyl stress due to decreased glyoxalase-1 activity (Glo-I) contribute significantly to insulin resistance and vascular complications. Therefore, we aimed to study the impact of the combination of thiamine and niacin on hepatic NF-kβ signaling, metabolic profile, and Glo-I activity in male rats with type-2 diabetes (T2DM).

Materials and methods: Forty male rats were divided equally into five groups: control, diabetic, diabetic treated with thiamine (180 mg/l in drinking water), niacin (180 mg/l), and a combination of both. The treated groups received the treatments daily in drinking water for two months. T2DM was induced using a combination of nicotinamide and alloxan. Metabolic profile and renal dysfunction parameters were assessed. Additionally, various glycation, oxidative stress, and inflammatory markers were measured.

Results: The treated group with both vitamins showed the lowest blood sugar and insulin resistance indices, cardiovascular indices, renal dysfunction parameters, hepatic NF-kβ expression, oxidative stress, inflammatory and glycation markers, and the highest anti-oxidant and anti-glycation markers, β cell activity, and insulin sensitivity. Thiamine exhibited more anti-inflammatory activity than niacin in diabetic rats, while niacin demonstrated stronger anti-oxidant activity (P<0.001).

Conclusion: The combined use of vitamins had a more beneficial impact on macro and microvascular complications in diabetes than each alone, attributed to their higher anti-oxidant, anti-inflammatory, and anti-glycation characteristics. The vitamins also had a more corrective effect on glucose-lipid metabolism, insulin sensitivity, and renal function through a stronger lowering effect on hepatic NF-kβ expression.

Objectives: The key ingredient in Nigella sativa, thymoquinone (TQ), has several beneficial (antioxidant and anti-inflammatory) properties. This study aimed to investigate the vitamin D metabolism in insulin resistance and the effects of TQ.

Materials and methods: Male Wistar albino rats were used. TQ was administered as a therapy, and prophylaxis and treatment with metformin were set up for the groups in which insulin resistance had been developed. The gene groups implicated in vitamin D metabolism underwent RT-PCR gene expression analysis and western blot protein analysis.

Results: The analysis shows that the application of TQ reduced HOMA-IR (a sign of insulin resistance). The expression of the VDR gene may be responsible for TQ's effect on treating insulin resistance.

Conclusion: It has been demonstrated that using TQ for therapeutic and preventive reasons is advantageous for improving insulin resistance metrics. Serum vitamin D level was also found to be impacted, which was found to be directly related to the expression of several genes involved in vitamin D metabolism in the liver. However, some of these genes were found to be relatively ineffective in the present study.

Objectives: Acute lung injury (ALI) is characterized by severe hypoxia and alveolar damage, often caused by oxidative stress, endoplasmic reticulum stress (ERS), and apoptosis. Fluvoxamine (FLV), an antidepressant, has tissue-protective properties through various intracellular mechanisms. This study investigates the anti-inflammatory effects of FLV used as an antidepressant in a lipopolysaccharide (LPS)-induced ALI model.

Materials and methods: Thirty-two female Wistar Albino rats aged 14-16 weeks and weighing 300-350 g, with 8 animals in each group, were divided into four groups: control, LPS, LPS+FLV, and FLV. After LPS administration, rats were euthanized, and histopathological analysis, immunohistochemistry for tumor necrosis factor-α (TNF-α) and caspase-3 (Cas-3), ELISA for oxidative stress markers, and PCR for CHOP, Cas-12, and Cas-9 gene expressions were conducted.

Results: In the LPS group, lung tissue damage, increased inflammatory cell infiltration, increased Cas-3 and TNF-α expressions, increased oxidative stress markers, and increased CHOP, Cas-9, and Cas-12 mRNA expressions were observed compared to the control group. FLV treatment in the LPS+FLV group significantly reversed these effects in the LPS group.

Conclusion: FLV exhibits protective effects against ALI by mitigating inflammation, ERS, and apoptosis via the CHOP/Cas-9/Cas-12 pathway. Further studies are needed to explore additional pathways and potential clinical applications of FLV.

Objectives: Reducing the immune response to inflammation is vital for successful transplantation, yet chronic graft rejection remains a major issue despite immunosuppressive drugs. This study explored the effect of bone marrow mesenchymal stem cell-derived exosomes on the survival of skin allografts in mice.

Materials and methods: C57BL/6 and BALB/c mice underwent skin allograft surgery, followed by intraperitoneal injection of exosomes, which were compared with groups receiving dexamethasone and no treatment group.

Results: On day 3, mild signs of graft rejection appeared in both control groups, while none were seen in the exosome-treated group. By day 14, the grafts were completely rejected in the control groups but showed mild rejection in the treatment group. Histopathology revealed severe rejection signs in the control groups, including epithelial necrosis and inflammation, while the treatment group showed signs of angiogenesis and graft acceptance. Additionally, inflammatory cytokine levels (TNF-α, IL-1β, and IL-6) were lower in the treatment group than in the positive control group, particularly on days 3 and 14.

Conclusion: The findings suggest that exosomes can prevent graft rejection and may offer a promising therapeutic approach for solid organ transplantation, though further research is needed to standardize exosome methods and evaluate cost-effectiveness.

Objectives: Sexual dimorphism in blood pressure regulation has been extensively noted in humans, but the underlying mechanisms remain to be fully understood. Our research aims to investigate the possible correlation between gender-associated differences in blood pressure and renal sodium transport.

Materials and methods: We measured male and female mice's blood pressure, urine, and plasma sodium concentration when fed a regular or high-Na⁺ diet. After that, their renal sodium transporters were assessed by western blot and immunofluorescence. For further investigation, male mice were castrated to observe the differences in blood pressure and renal sodium transporters compared to normal mice.

Results: Male mice exhibited higher blood pressure and lower renal sodium excretion than female littermates. Furthermore, the blood pressure of male mice exhibited a more significant and rapid increase relative to female mice when the diet was switched from control sodium to high sodium. Western blot and immunofluorescent staining revealed that in male mice, the sodium transporters epithelial sodium channel (ENaC) and the upstream kinases SPAK (Ste20-related proline/alanine-rich kinase), OSR1 (oxidative stress response kinase 1), and WNK4 (Lysine-Deficient Protein Kinase 4) were elevated. Beyond that, male mice exhibited lowered blood pressure and reduced abundance of ENaC (α, β, and γ) after castration.

Conclusion: ENaC plays a significant role in gender-associated differences in blood pressure and renal sodium reabsorption.

Objectives: Osteoclasts drive bone resorption under inflammation, with cytokines promoting osteoclastogenesis. The role of proline enzymes like dipeptidyl peptidase-8 and 9 (DPP-8/9) in this process remains unclear. This study aimed to explore the DPP-8/9 involvement in inflammation-driven osteoclastogenesis using the RAW264.7 macrophage model.

Materials and methods: Receptor activator of nuclear factor-κB ligand (RANKL) and lipopolysaccharide (LPS) induced osteoclastogenesis, raising interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and IL-23 levels. Using RAW264.7 cells, DPP-8/9 protein and tartrate-resistant acid phosphatase (TRAPc) were assayed. Antibodies for cluster of differentiation (CD86 and CD206) were used to analyze macrophage polarization, while molecular docking was used to assess flavonoid binding to DPP-8/9. Western blot confirmed DPP-8/9 expression in treated macrophages.

Results: Administering RANKL and LPS increased IL-6 and TNF-α levels, significantly promoting osteoclastogenesis in RAW264.7 macrophages. This treatment also elevated the levels of the inflammatory macrophage marker IL-23. Osteoclast formation was confirmed by measuring TRAPc levels in the culture. Analysis of the cell supernatant revealed elevated DPP-8/9 levels in the RANKL+LPS group. Inhibition of DPP-8/9 with 1G244 decreased inflammatory cytokines and TRAPc levels in the cell culture. Molecular docking analysis of various flavonoids identified chrysin as a potential molecule with sufficient binding energy against DPP-8/9, a finding confirmed by blotting assay.

Conclusion: This study emphasizes the involvement of DPP-8/9 in inflammatory osteoclastogenesis in RAW264.7 macrophages. Inhibition of DPP-8/9 reduced osteoclastogenesis markers and inflammatory cytokines levels, indicating decreased osteoclast formation. Additionally, chrysin demonstrated potential as an anti-DPP-8/9 agent, highlighting its possible role in future therapeutic strategies targeting inflammation-induced osteoclastogenesis.

Objectives: For designing a suitable hydrogel, two crosslinked Alginate/ Carboxymethyl cellulose (Alg/CMC) hydrogel, using calcium chloride (Ca²⁺) and glutaraldehyde (GA) as crosslinking agents were synthesized and compared.

Materials and methods: All samples were characterized by Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Blood compatibility (BC), Blood clotting index (BCI), weight loss (WL), water absorption (WA), pH, and Electrochemical Impedance Spectroscopy (EIS). Cell viability and cell migration were investigated using the MTT assay and the wound scratch test, respectively. Besides, the wound healing potential of prepared hydrogels was evaluated on the rat models with full-thickness skin excision. To further investigation, TGF β1, IGF-I, COL1, ACT-A (alfa-SMA), and GAPDH expression levels were also reported by RT-PCR.

Results: Water absorption and weight loss properties were compared between different crosslinker agents, and the most nontoxic crosslinker concentration was determined. We have shown that GA (20 µl/ml) and Ca²⁺ (50 or 75 mM) enhanced the physical stability of Alg-CMC hydrogel, and they are nontoxic and suitable crosslinkers for wound dressing applications. Although in vivo assessments indicated that the GA (20 µl/ml) had a cytotoxic effect on tissue repair, Ca²⁺ (75 mM) boosted the wound healing process. Further, RT-PCR results revealed that TGF β1, IGF-I, COL1, ACT-A (alfa-SMA), and GAPDH expression levels were increased in GA (20 µl/ml). Moreover, this trend is the opposite in the Ca²⁺ (75 mM) treatment groups.

Conclusion: This research shows that Ca²⁺ (75 mM) boosts tissue regeneration and wound healing process.

Objectives: Echinacoside (ECH) is an anti-fibrotic phenylethanoid glycoside derived from the Cistanche plant that protects against cardiac dysfunction by mitigating apoptosis, oxidative stress, and fibrosis. Nevertheless, ECH's precise function and mechanisms in addressing cardiac fibrosis are still not fully understood.

Materials and methods: In our current investigation, we induced cardiac fibrosis in mice by administering Angiotensin II (Ang II) and subsequently assessed the effects of ECH treatment four weeks post-fibrosis induction. Additionally, in an in vitro setting, we exposed cardiac fibroblasts (CFs) to Ang II to prove the anti-fibrotic mechanisms of ECH.

Results: ECH treatment effectively reversed cardiac fibrosis in the mice model. ECH treatment significantly reduced the levels of fibrosis-related genes, such as α-SMA, Collagen I, and Collagen III (all, P<0.001). Moreover, it reduced the number of apoptotic cells and regulated the expression of apoptosis-related genes, such as BAX and BCL-2 (all, P<0.001). ECH treatment also positively affected serum levels of markers associated with cardiac fibrosis, including LDH, CK-MB, ANP, BNP, CTnl, and CTnT (all, P<0.001), in the in vivo experiments. In the in vitro studies, ECH pretreatment alleviated cardiac fibroblast apoptosis and reduced cell migration, collagen deposition, and MMP expression (all, P<0.001). In our in vivo and in vitro investigations, we observed that ECH treatment reversed the down-regulation of SIRT1 and up-regulation of IL-11 following cardiac fibrosis. The results suggest that the protective effects of ECH may involve regulating the SIRT1/IL-11 pathway.

Conclusion: ECH may protect against Ang II-induced cardiac fibrosis via the SIRT1/IL-11 pathway.

Objectives: This study investigated the effects of young plasma therapy (YPT) compared to estrogen therapy (E2T) on motor and cognitive impairments in aged ovariectomized (OVX) rats.

Materials and methods: Sixty female Wistar rats were divided as follows: 1). 2-3 months control young group. Five 22-24 months old groups: 1) Control, 2) Sham, 3) OVX, 4) OVX.E2, and 5) OVX.YP. Young plasma (1 ml plasma, through the tail vein, 3 days weekly for 4 weeks) and E2 (30 mg/kg, SC, 5 days weekly for 4 weeks) were administrated to OVX rats. The open field, elevated plus maze, and Barne's maze were used to assess the behaviors. Then, miR-134 and miR-124 (RT- RCR), SIRT1, CREB, and BDNF (western blot), and anti-oxidants/oxidants markers (Photometry) levels were assessed in the rat's hippocampal tissues.

Results: OVX caused up-regulated hippocampal miR-134 and miR-124 expression levels (P<0.001) while down-regulated SIRT1, CREB, and BDNF protein expressions (P<0.001). Also, ovariectomy Increased TOS, OSI, and MDA (P<0.001) while decreasing TAC (P<0.001) compared to sham. Treatment with both E2T and YPT significantly improved all oxidative stress indexes (P<0.0.001) and increased p-CREB, BDNF, and SIRT1 protein levels (P<0.05, P<0.01) while decreasing the expression of miR-134 and miR-124 (P<0.001).

Conclusion: YPT is a non-pharmacological therapeutic as much as or more than E-2T, which can exhibit anti-oxidative and anti-inflammatory potential in the hippocampal tissue and improve cognitive deficits in aged OVX rats without unknown side effects.

Objectives: Three physiological processes interact: sleep, learning, and stress. It is essential to understand how stress affects and interacts with the link between sleep, learning, and memory since it has long been recognized that sleep plays a crucial role in memory consolidation and learning. Through naloxone injection in the baso lateral amygdala (BLA), this study intends to shed light on the interactions between stress, learning, and sleep, as well as the function of the opioid system and its impact on brain-derived neurotrophic factor (BDNF) production in the hippocampus.

Materials and methods: Male Wistar rats (n=77) in eleven groups were implanted with electroencephalogram (EEG) and electromyography (EMG) recording electrodes, and the BLA area was bilaterally cannulated. Recordings of Rapid Eye Movement (REM) and Non-Rapid Eye Movement (NREM) sleep and wakefulness steps were made for the three hours prior to and three hours following the implementation of the immobility stress protocol and learning with the Barnes maze for three consecutive days. Also, the animals' memory was tasted 48 hr later. Before the stress and learning procedure, naloxone was injected into each BLA three times in a row at a dosage of 0.05 μg or 0.1 μg in a volume of 0.5 μl. A molecular biomarker of learning and stress, BDNF, was also examined.

Results: The study demonstrated that the immobility stress model lowers REM and NREM sleep. On the other hand, putting the learning technique into practice results in more REM and NREM sleep, and stress situations do not stop this rise after learning. Naloxone injections in the BLA region also enhance learning and memory, preventing stress-related REM and NREM sleep loss. Additionally, stress lowers BDNF expression in the hippocampal region. BDNF expression rises in the hippocampus throughout the learning process, and naloxone administration in the BLA area also raises BDNF expression in the hippocampus.

Conclusion: Stress generally reduces REM, NREM, and BDNF expression in the hippocampal region. Under stress, using the learning protocol increases REM, NREM sleep, and BDNF. Naloxone injection in BLA improves memory and learning, reducing stress-induced memory loss.