Iranian Journal of Basic Medical Sciences最新文献

Objectives: Cannabinoids, derivatives of Cannabis sativa L., can activate the endocannabinoid system via two endogenous receptors, CB1 and CB2. This system is crucial in regulating folliculogenesis, fertility, and reproductive function. This study investigated the potential effects of cannabinoid agonists and antagonists on ovarian health and function in female mice.

Materials and methods: 80 NMRI mice were divided into 10 groups. Treatment groups received CB1 or CB2 agonists, antagonists, or their combinations for five days. The animals were then sacrificed, the ovaries were excised and weighed, and their volume was measured. Total RNA was extracted from the left ovary for qPCR analysis, while the right ovary was fixed in Bouin's solution for histological evaluation following H&E staining.

Results: Treatment with CB1/CB2 agonist+CB1 antagonist (W102+AM251) decreased the level of NAPE-PLD (a key factor in the production of endocannabinoids in cells) and increased the level of FAAH (responsible for cannabinoid degradation) genes compared to all groups. CB2 antagonist (AM630) increased the number of primary, preantral, and antral follicles, the volume and weight of ovaries, and estrogen levels. Meanwhile, the CB1 antagonist (AM251) significantly increased microvascular density in the ovaries.

Conclusion: Cannabinoids modulate ovarian physiology and folliculogenesis, with CB2 receptors playing a particularly significant role. Antagonism at CB2 appeared to differentially affect cannabinoid-metabolizing enzymes in ovarian follicles and differentially affect their maturation. However, our preliminary novel findings in mice require human studies before clinical application.

Objectives: This study examines the temporal dynamics of ferroptosis following cerebral ischemia-reperfusion injury (CIRI) to establish a theoretical framework for innovative therapies that enhance neuronal survival by mitigating ferroptosis.

Materials and methods: An experimental CIRI model was established in mice via middle cerebral artery occlusion and reperfusion (MCAO/R). Behavioral assessments were conducted, and blood-brain barrier (BBB) integrity was evaluated using transmission electron microscopy. Immunoblotting and ELISA were performed to determine ferroptosis dynamics post-MCAO/R. Additionally, CIRI mice received intraperitoneal injections of Ferrostain-1 (10 mg/kg/d) and Erastin (30 mg/kg/d). The effects of ferroptosis on CIRI were further verified through 2,3,5-Triphenyltetrazolium chloride and hematoxylin-eosin staining.

Results: MCAO/R induced BBB disruption, and was associated with a reduction in GSH activity (at 1, 3, and 5 days), elevated Fe(2+) levels (at 1 day), as well as decreased MDA levels (at 3 days). Concurrently, ferroptosis markers, including NRF2, xCT, and GPX4, were significantly down-regulated on day 1, reaching their nadir by day 3, whereas HO-1 exhibited an inverse trend. Notably, Ferrostatin-1 pretreatment conferred a protective effect against CIRI, in contrast to the MCAO and Erastin groups.

Conclusion: This study elucidates the temporal dynamics of ferroptosis markers in the early stages of stroke, highlighting a therapeutic window for ferroptosis-related CIRI. These findings underscore the importance of targeting ferroptosis to improve neuronal survival and inform future CIRI therapies.

Objectives: Our study aimed to demonstrate the therapeutic effects of sacubitril (an inhibitor of neprilysin) and/or valsartan (an ARB) in an experimentally induced polycystic ovary syndrome (PCOS) model and in PCOS-induced insulin resistance.

Materials and methods: After 21 days of letrozole 1 mg/kg administration, rats were confirmed to have PCOS by the vaginal smear method. Following PCOS induction, the experiment was terminated after 15 days of drug treatment. Metformin 300 mg/kg, sacubitril 30 mg/kg, and valsartan 31 mg/kg were administered orally every 15 days. Fasting insulin levels and oral glucose tolerance test (OGTT) were performed to measure insulin resistance and calculate homeostatic model assessment - insulin resistance (HOMA-IR). At the end of the experiment, biochemical analyses were performed on blood samples, and histological studies were conducted on tissue samples.

Results: The sacubitril and valsartan combination significantly improved impaired glucose tolerance and HOMA-IR. Serum neprilysin (NEP) levels were found to be significantly higher in the PCOS group than in the healthy group, while atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels were found to be significantly lower. The sacubitril+valsartan combination provided the greatest improvement in PCOS-related changes in serum NEP, ANP, BNP, angiotensin II (ANGII), hormone, and lipid levels. The application of sacubitril+valsartan provided an important treatment for insulin resistance due to PCOS by increasing the expression of insulin resistance (IR), insulin receptor substrate 1 (IRS-1), and insulin receptor substrate 2 (IRS-2).

Conclusion: Sacubitril and valsartan combination has been shown to have significant therapeutic benefits for PCOS. It markedly reduces cystic follicles and PCOS-associated insulin resistance, improves serum lipid levels, and is supported by pathological findings.

Objectives: The protective effects of acupuncture on myocardial injury have been identified in clinical trials. However, there is still a lack of comprehensive understanding of its fundamental mechanism. This research aimed to clarify the roles of plasma exosomes in the cardioprotection of acupuncture.

Materials and methods: Myocardial infarcted rats were divided into control group, acupuncture group, and acupuncture plus GW4869 group. The rats without the performance of a myocardial infarction were divided into a sham group. Acupuncture was performed at bilateral PC6.

Results: The results showed that the effects of acupuncture on increasing the thickness of the left ventricular infarct wall and inhibiting apoptosis of the damaged heart tissue were significantly reversed by GW4869. Among the five miRNAs of plasma exosomes increased by acupuncture, miR-142-3p was the unique miRNA up-regulated in myocardial tissue. Overexpressing miR-142-3p retarded oxidative damage of H9c2 by anti-apoptosis. miR-142-3p directly bound to and suppressed the expression of Cofilin 2 (CFL2). In vivo CFL2 expression was down-regulated by acupuncture and up-regulated by GW4869.

Conclusion: Our results suggest that plasma exosomes transfer cardio-protective signals of acupuncture to the injured heart and confer cardioprotective effects, and miR-142-3p emerges as a prominent exosomal miRNA in the inhibition of myocardial apoptosis by targeting CFL2.

Objectives: This study investigates the ability of astaxanthin (ASTX), a powerful anti-oxidant, to protect kidney tissue from oxidative and cellular damage resulting from bisphenol A (BPA) toxicity, a widespread global toxin associated with chronic kidney disease.

Materials and methods: We used 32 male Wistar Albino rats, 16 weeks old, and weighing 250-300 g. The rats were randomly divided into four groups: Control, Sham, BPA, and BPA+ASTX. Following the experiment, serum samples were assessed for Paraoxonase 1 (PON1), Arylesterase (ARE), urea, and creatinine levels. Changes in kidney tissue induced by BPA were examined using histopathological methods. Also, the levels of apoptosis and collagen content were evaluated.

Results: ASTX treatment reversed the BPA-induced inhibition of PON1 and ARE levels, restoring them to control levels, and reduced the BPA-induced increase in urea levels. Creatinine levels showed no significant differences across the groups. BPA exposure in kidney tissue caused vacuolization, congestion, tubular dilatation, desquamation, infiltration, and increased collagen around glomeruli and blood vessels. However, ASTX treatment significantly improved these pathological findings. While BPA induced apoptosis as indicated by Bax and Bcl-2 analysis, ASTX treatment partially inhibited this process.

Conclusion: These findings indicate that ASTX may protect against BPA-induced renal injury. However, the study's limitations include the use of a single dose and a focus solely on kidney tissue. Additionally, the lack of dose-response data and evaluations of other organs or long-term effects are significant drawbacks. Future research should explore multiple doses and longer observation periods for a better understanding of ASTX's protective efficacy.

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.