Iranian Journal of Basic Medical Sciences最新文献

Objectives: To investigate the renoprotective effects of Rhein in obesity-related glomerulopathy (ORG) by inhibiting the P2X7 receptor (P2X7R)/NOD-like receptor protein 3 (NLRP3) inflammasome pathway.

Materials and methods: ORG was induced in C57BL/6J mice with a high-fat diet (HFD) for 10 weeks, fol-lowed by oral Rhein treatment (70 or 300 mg/kg/day) for 10 weeks. Renal function, histology, and podocyte injury were assessed. In vitro, leptin-induced podocyte injury was treated with Rhein or P2X7R antagonists (KN-62 or A-438079). P2X7R/NLRP3 activation, inflammation, and oxidative stress were evaluated.

Results: HFD-induced weight gain, dyslipidemia, renal dysfunction, glomerular hypertrophy, and podocyte injury. Rhein reduced serum triglycerides (TG) and total cholesterol (TC), lowered blood urea nitrogen (BUN), improved urinary protein excretion, and alleviated histological damage. Rhein inhibited P2X7R and NLRP3 activation, down-regulated caspase-1, interleukin (IL)-1β, and IL-18, and restored podocyte markers (Nephrin, Podocin). In vitro, Rhein mitigated leptin-induced podocyte injury and inflammasome activation.

Conclusion: Rhein protects against ORG by suppressing the P2X7R/NLRP3 pathway, reducing inflammation and oxidative stress, and preserving podocyte integrity, highlighting its therapeutic potential.

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: 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.

Objectives: One of the most recent cancer treatment methods is cold atmospheric plasma (CAP), which destroys cancer cells without affecting healthy cells. Also, the created photons in the CAP flame can be used to excite a proper photosensitizing agent (PS). Therefore, using nano micelle systems containing a proper photosensitizer may be beneficial in raising the treatment efficacy of CAP. In this study, we utilized molecular dynamics (MD) simulation to optimize a nano micellar system containing methylene blue to take advantage of the induced photodynamic effect of a CAP generator with helium gas on a glioblastoma cell line.

Materials and methods: Some micelle properties were first determined and optimized by MD with GROMACS software. Then, micelles containing methylene blue (Micelle-MB) and free methylene blue (MB) at various concentrations were prepared. Singlet oxygen dosimetry using 1,3-diphenylisobenzofuran (DPBF)was performed in the presence and absence of Micelle-MB and MB. Subsequently, the cytotoxicity of MB and Micelle-MB was evaluated on U87-MG cancer cells, and their half-maximal inhibitory concentrations (IC₅₀) were determined. After 48 hr of treatment, the percentage of cell survival was determined using the MTT test. The experiments were repeated at least three times. The synergy index was selected to compare the results.

Results: Treatment with CAP and MB reduced the survival rate compared to the PS-free group with CAP. Results of singlet oxygen dosimetry showed that Micelle-MB might be more efficient in producing ROS. CAP treatment with Micelle-MB resulted in more cell death than free MB. In addition, cell viability decreased in Micelle-MB groups with increasing irradiation time in the three investigated irradiation times.

Conclusion: Using Micelle-MB in the CAP treatment improves treatment efficiency in the U87-MG cell line.

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: Insufficient breast milk supply is a common reason cited for discontinuing breastfeeding prematurely. Natural galactagogues offer promise as a solution for mothers with low milk production. This study aimed to explore puerarin's potential effects and underlying mechanism on lactation of postpartum hypogalactia mice.

Materials and methods: Postpartum mice were randomly assigned to five groups: control group, agalactosis model group, domperidone group (3.5 mg/kg), low dose puerarin group (18 mg/kg), and high dose puerarin group (72 mg/kg). The effects of puerarin on postpartum hypogalactia mice were evaluated by lactation indicators and pathological morphology. Related hormones and prolactin receptor (PRLR)/Janus kinase 2 (JAK2)/signal transduction and activator (STAT) 5 signaling pathway were also measured.

Results: Puerarin significantly improved lactation yield and stimulated mammary gland development in postpartum hypogalactia mice. Additionally, puerarin increased the expression levels of β-casein, fatty acid synthase (FAS), and glucose transporter 1 (GLUT1). Mechanically, puerarin stimulated secretion of prolactin (PRL), estradiol (E2), and progesterone (P4) in agalactosis mice. Puerarin also substantially increased PRLR, JAK2, and STAT5a expression levels in postpartum hypogalactia mice.

Conclusion: This study suggested that puerarin may promote lactation by stimulating PRL secretion and activating the PRLR/JAK2/STAT5 signaling pathway.

Objectives: Melanoma is one of the most aggressive and deadly skin cancers. Despite advances, effective melanoma treatment is challenging, often requiring a shift from individual therapies to combination approaches. This study explores whether combining dacarbazine (DTIC) and temozolomide (TMZ) with the siRNA approach holds promise for melanoma treatment.

Materials and methods: To determine the IC₅₀ values of DTIC and TMZ, the A375 cell line was treated with different drug concentrations for 24-72 hr. The best exposure time of BRAF siRNA transfection was performed. Subsequently, cell viability (using the MTT assay), apoptosis (by flow cytometry), and gene expression levels of B-Raf proto-oncogene, serine/threonine kinase (BRAF), caspase 3 (CASP3), and phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) genes (by quantitative real-time PCR) were assessed in the treated groups (i.e., control, negative controls, DTIC alone, TMZalone, DTIC+ TMZ, BRAF(V600E)siRNA alone, siRNA+ DTIC, siRNA+ TMZ, and siRNA+ DTIC+ TMZ groups).

Results: Cell viability significantly decreased in the chemotherapy-only and siRNA+drug groups, although no difference was observed between them. The apoptosis percentage in all treated groups indicated a significant difference compared to the control group. The expression of the BRAF gene notably decreased in the BRAF (V600E) siRNA +drug groups compared to the chemotherapy groups. Despite overexpression of CASP3 in the chemotherapy-treated groups, the most effective enhancement was noted in the siRNA+DTIC+TMZ group (P<0.0001). The mean expression of the PIK3R3 gene in siRNA+chemotherapy groups revealed a notable reduction.

Conclusion: These findings suggest that the siRNA-transfected treatment groups have the potential to provide therapeutic effects comparable to those of chemotherapy.

Objectives: Asthma is a complex inflammatory disease of the lungs marked by increased infiltration of leukocytes into the airways, which restricts respiratory function. Proliferator-activated receptor-γ coactivator-1 alpha (PGC-1α) has been recognized as an essential immunomodulator and has the potential as a novel anti-inflammatory target in asthma. The current study aims to investigate the functions of PGC-1α in ovalbumin (OVA)-sensitized asthmatic mice and underlying mechanisms.

Materials and methods: BALB/c mouse asthma model was induced by OVA in vivo. The therapeutic effects of PGC-1α agonist (ZLN005) on asthma were assessed by histological and biochemical analysis. In addition, we integrated real-time qPCR, western blotting, and immunofluorescence analysis to reveal the underlying mechanism.

Results: In the lung tissue of asthmatic mice, PGC-1α levels were down-regulated. Diff-Quik staining indicated that ZLN005 therapy on asthmatic mice reduced the number of inflammatory cells (eosinophilic granulocytes, neutrophils, lymphocytes, and mononuclear macrophages) in bronchoalveolar lavage fluid (BALF), ameliorated pathologic alterations in lung tissues. ZLN005 alleviated airway structure and inflammation, as well as down-regulating the serum immunoglobulin E (IgE), OVA-specific IgE, and T-helper 2 (Th2) cytokines (interleukin (IL)-4, IL-5, and IL-13) expression. Mechanistically, the results showed that ZLN005, through the NF-κB-p65 axis, prominently inhibited the activation of the NLRP3 inflammasome and reduced the levels of the NLRP3 downstream targets IL-1β and IL-18.

Conclusion: PGC-1α agonist (ZLN005) regulated lung inflammation in asthmatic mice by inhibiting the NF-κB-p65/NLRP3 signaling pathway, supporting that ZLN005 may be a candidate for future asthma treatment.

Objectives: To investigate the ameliorative effects of Garcinia kola ethanol extract (EGK) on type 2 diabetes mellitus (T2DM) combined with nonalcoholic fatty liver disease (NAFLD) and to explore its underlying mechanisms.

Materials and methods: In vivo, a T2DM rat model was established using HGHFD/STZ. In vitro, HepG2 cells were induced with FFA to create a model of lipid accumulation. Lipid accumulation (LA), oxidative stress (OS) levels, and inflammatory markers were measured using kit methods. Additionally, the expression of the SREBP-1c pathway was detected by immunohistochemistry and western blot (WB) to further understand the potential mechanism of EGK's protective effect on diabetic liver injury.

Results: In vivo, EGK significantly reduced blood glucose levels (P<0.01), restored body weight (P<0.01), and improved liver LA, OS, and inflammatory levels (P<0.01) in diabetic rats. Histopathological results indicated that EGK effectively ameliorated diabetes-induced liver injury. Immunohistochemistry and WB results revealed that EGK significantly down-regulated the expression of the SREBP-1c pathway (P<0.01). In vitro, EGK markedly improved lipid accumulation, oxidative stress, and inflammation levels in HepG2 cells (P<0.01). Immunofluorescence and WB results showed that EGK significantly reduced the expression of the SREBP-1c pathway (P<0.01).

Conclusion: EGK alleviates T2DM combined with NAFLD by reducing lipid accumulation through the inhibition of oxidative stress, inflammatory responses, and the SREBP-1c signaling pathway.