Iranian Journal of Basic Medical Sciences最新文献

Objectives: Myocardial ischemia/reperfusion injury (MIRI) is the primary pathological injury following ischemic cardiomyocyte therapy, but there are few effective treatments available for MIRI. Apigenin (API) is an active ingredient of herbal medicine. Our study aims to verify whether API regulates autophagy and apoptosis against MIRI via miR-448/Sirtuin-1 (SIRT1) axis.

Materials and methods: MTT, SOD, and LDH assays were used to measure cell viability, oxidative stress injury, and cell damage, respectively. RT-qPCR, western blot, and ELISA were used to measure RNA and protein expression levels.

Results: Compared with the control group, cell viability and SOD levels in the cells of the OGD/R group were significantly decreased, LDH release in the cells was significantly increased, the level of miR-448 in the cells was significantly increased, the levels of SIRT1 mRNA and protein in the cells were significantly increased, the expression of LCII/I and Bcl-2 proteins in the cells were significantly down-regulated, and the expression of p62, Bax proteins in the cells and caspase-3 protein in the cell supernatant were significantly up-regulated. Compared with the OGD/R group, the above indicators were significantly reversed in the OGD/R+API group and the OGD/R+miR-448 inhibitor group. Compared to the OGD/R+miR-448 inhibitor group, the above indicators were significantly reversed in the OGD/R+miR-448 inhibitor+EX527 (SIRT1 inhibitor) group. Compared to the OGD/R+API group, the above indicators were significantly reversed in the OGD/R+API+miR-448 mimic group, OGD/R+API+EX527 group, and OGD/R+API+CA-5f (autophagy inhibitor) group.

Conclusion: API regulates autophagy and apoptosis via the miR-448/SIRT1 axis against MIRI.

Objectives: Type 2 diabetes (T2D) represents a complex and multifactorial disorder, and efforts to discover its treatment are necessary. Browning of white adipose tissue (WAT) as a therapeutic target for diabetes seems to be induced by exercise through neuropeptide FF (NPFF) signaling in the hypothalamus and adipose tissue. This study aimed to explore the role of endurance training on the browning of WAT by assessing the expression of the gene and protein of NPFF and its receptors in the hypothalamus and adipose tissue.

Materials and methods: Forty adult male Wistar rats were assigned into four groups: control, exercise, diabetic control, and diabetic exercise. The serum levels of lipid profile, insulin, and glucose, along with the expression of gene and protein of NPFF and its receptors (NPFFR1 and NPFFR2), were evaluated in the hypothalamus and adipose tissue. A histological examination was performed to evaluate the browning of WAT.

Results: Metabolic parameters notably increased in the diabetic group. The gene and protein expression of NPFF and its receptors significantly decreased in the hypothalamus and fat tissue in the diabetic group. However, these changes in the hypothalamus, not in the adipose tissue, were significantly improved in the diabetic-exercise group compared to the diabetic group. The high WAT content in diabetic rats was decreased by exercise, leading to an increase in the browning of WAT.

Conclusion: Endurance progressive training could centrally, not peripherally, promote the browning of WAT in diabetic rats by enhancing the expression of gene and protein of NPFF and its receptors in the hypothalamus.

Objectives: Recent studies have increasingly focused on applying nanotechnology to treat neurodegenerative diseases. In this study, we compared the effects of the monoterpene linalool and linalool-loaded chitosan nanoparticles on key pathological features of Alzheimer's disease (AD), including oxidative stress, neuroinflammation, neuronal death, amyloid plaque deposition, alterations in tryptophan metabolism, and memory deficit in a rat model of AD.

Materials and methods: An intracerebroventricular injection of Aβ₄₂ (10 µg) was used to induce the AD model. Linalool (25 mg/kg) and nano-linalool (25 mg/kg) were administered orally once daily for 30 consecutive days.

Results: Both linalool and nano-linalool significantly reduced malondialdehyde levels and enhanced superoxide dismutase activity in the hippocampus. They also decreased the mRNA levels of monocyte chemoattractant protein-1, inhibited the up-regulation of beta-secretase, reduced amyloid plaque deposition, and attenuated pyramidal neuron death in the CA1 region. Additionally, treatment with both compounds down-regulated indoleamine 2,3-dioxygenase, lowered kynurenine levels, and increased serotonin concentrations in the hippocampus. Although both treatments improved learning and spatial memory in Aβ-injected rats, nano-linalool's effectiveness was more significant than that of linalool in modulating the molecular, biochemical, and histological parameters.

Conclusion: Encapsulating linalool in chitosan nanoparticles enhances its effectiveness in improving molecular, biochemical, and histological changes in the hippocampus of rat models of AD.

Objectives: Psoriasis is an autoimmune disease that mainly affects the skin and joints, which is mediated via T-cells. Several factors contribute to its pathogenesis, including genetic and environmental triggers, as well as intrinsic immune processes that lead to an autoimmune response. Silymarin, a flavonoid complex extracted from Silybum marianum, exhibits anti-inflammatory, immunostimulatory, and anti-oxidant properties, rendering it a viable candidate for treating psoriasis. This study aimed to investigate the effect of silymarin on imiquimod (IMQ) induced psoriasis-like skin lesions in male mice applied as a cream for seven consecutive days (1 mg per mouse).

Materials and methods: Thirty-five male mice were assigned to seven groups (n=5 per group): (I) control group, (II) IMQ group, (III-V) oral silymarin groups (30, 60, and 120 mg/kg), (VI) topical betamethasone group, and (VII) topical silymarin 2% group.

Results: Silymarin, both orally and topically, significantly reduces erythema, thickness, and scaling induced by IMQ after seven days of treatment. The treatment also reversed the increase in spleen weight/body weight ratio. Immunofluorescence analysis revealed that silymarin reduced the expression of nuclear factor κB (NF-κB) (P<0.01) and toll-like receptor 4 (TLR4) (P<0.01) compared to the IMQ group.

Conclusion: These findings suggest that silymarin effectively alleviates psoriasis lesions by reducing inflammation and modulating the TLR4/ NF-κB signaling pathway.

Objectives: Pathomechanisms of sulfur mustard (SM) are not fully understood, and no specific medical countermeasures exist to prevent SM-induced pulmonary injury. This study aimed to evaluate the apoptosis following SM-induced acute pulmonary injury.

Materials and methods: Acute pulmonary injury models were established using SM at an equivalent toxicity dose (1 LD50), administered via intraperitoneal injection or intratracheal instillation. Protein expression levels and mRNA expressions of apoptosis-related markers, including cellular inhibitor of apoptosis proteins-1 and -2 (cIAP-1, cIAP-2), Fas, Bcl-2-associated death promoter (Bad), second mitochondria-derived activator of caspases (Smac), and survivin (BIRC5), were analyzed using immunohistochemistry and polymerase chain reaction.

Results: The intraperitoneal SM group exhibited significantly higher levels of apoptotic cells in the alveolar septa and increased protein and mRNA expression of cIAP-1, cIAP-2, Fas, Bad, Smac, and BIRC5 compared to the intratracheal SM group. These changes displayed a time-dependent increase in both protein and gene expression levels.

Conclusion: SM-induced pulmonary injury involves both extrinsic (Fas, cIAP-1, cIAP-2) and intrinsic (Bad, Smac) pathways as well as caspase-dependent pathways (BIRC5). These findings provide valuable insights into the underlying mechanisms of SM toxicity and may facilitate the development of targeted therapeutic strategies.

Objectives: Different Cannabis sativa chemovars produce diverse pharmacological and behavioral effects. With the widespread use of cannabis in Nigeria, detailed toxicological effects of Nigerian chemovars are lacking. This study aimed to identify phytocannabinoids and investigate the toxic effects of an indigenous C. sativa.

Materials and methods: The plant samples were air-dried, powdered, extracted with ethanol, and characterized (phytochemical screening, Fourier Transformed Infrared Spectroscopy (FTIR), and Gas Chromatography-Mass Spectrometry (GC-MS)). Acute and subacute toxicity tests were done following Organisation for Economic Co-operation and Development (OECD) protocols.

Results: Screening showed appreciable levels of alkaloids, tannins, saponins, cardiac glycosides, and phenol. FTIR analysis indicated functional groups and chemical linkages like alcohols, fatty acids, alkynes, ketones, and esters, and 11 phytocannabinoids with delta-9-tetrahydrocannabinol in abundance (35.78%) reported by GC-MS. Acute toxicity test indicated an oral lethal dose (LD₅₀) value of ˃5000 mg/kg, a no-observed-adverse-effect-level (NOAEL) dose of ≤300 mg/kg, and a significant (P<0.05) decrease in the weight of animals in the 2000 mg/kg treatment group. The sub-acute toxicity test showed significantly (P<0.05) decreased ALP and ALT levels at 25 mg/kg body weight, and significantly lower triglyceride (P<0.01) and LDL (P<0.05) levels. Urea and some haematological parameters were significantly (P<0.05) higher in the 250 mg/kg group. Also, we observed mild to moderate necrosis in the excised pancreas and liver, and mild tubular changes in the kidney.

Conclusion: This suggests that our indigenous variety of C. sativa may be considered safe following oral consumption.

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.