Iranian Journal of Basic Medical Sciences最新文献

Objectives: This study aimed to determine the effect of 8-week high-intensity interval training (HIIT) on oxidative stress and apoptosis in the hippocampus of male rats with type 2 diabetes (T2D). The study focused on examining the role of proliferator-activated receptor gamma co-activator 1α (PGC1α)/Kelch-like ECH-associated protein Keap1/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway.

Materials and methods: Twenty-eight 8-week-old Wistar rats were randomly assigned to one of four groups (n=7): control (Con), type 2 diabetes (T2D), exercise (Ex), and exercise + type 2 diabetes (Ex+T2D). The Ex and Ex+T2D groups completed an 8-week exercise program consisting of 80-100% Vmax and 4-10 intervals. The homeostasis model assessment of insulin resistance (HOMA-IR) index was used to assess insulin resistance. The levels of Bcl2, BAX, musculoaponeurotic fibrosarcoma (Maf), Nrf2, Keap1, and PGC1α in the hippocampus were assessed using the western blot method. Additionally, the levels of antioxidant enzymes in the hippocampus were measured using ELISA.

Results: The findings indicated that the T2D group had lower levels of antioxidant enzymes, Maf, Bcl2, PGC1α, and Nrf2, and higher levels of BAX and Keap1 in the hippocampus. Conversely, the HIIT group exhibited increased levels of antioxidant enzymes, Maf, Bcl2, Nrf2, and PGC1α, along with decreased levels of BAX and Keap1 in the hippocampus.

Conclusion: The study demonstrated that 8-week HIIT was effective in reducing hippocampal apoptosis and oxidative stress induced by T2D by activating the PGC1α-Keap1-Nrf2 signaling pathway. The metabolic changes induced by exercise may lead to an increase in PGC1 expression, which is the primary stimulator of the Keap1-Nrf2 signaling pathway.

Objectives: The close relationship of proto-oncogenes to myocardial hypertrophy has long been recognized, and cardiac hypertrophy leads to heart failure (HF). However, whether proviral insertion of Moloney virus 3 kinase (Pim3), a proto-oncogene, contributes to cardiac hypertrophy in diabetes mellitus (DM) remains unknown. This study aims to investigate whether Pim3 is involved in DM-induced cardiac hypertrophy and HF and to elucidate its underlying mechanisms.

Materials and methods: DM was induced in mice by intraperitoneal injection of streptozotocin. Cardiac function was evaluated by echocardiography, and cardiac hypertrophy was determined through histological analysis, quantitative real-time polymerase chain reaction, and western blotting. Silencing RNA transfection and lentivirus-mediated gene knockdown were performed both in vitro and in vivo. Transcriptional activity was analyzed using chromatin immunoprecipitation and luciferase reporter assay.

Results: Compared with C57BL/6J mice, cardiac hypertrophy and dysfunction were observed in mice with DM. Pim3 mRNA and protein expression were significantly up-regulated in diabetic hearts and high glucose-cultured H9C2 cells. Yin Yang 1 (YY1), which translocated from the cytoplasm into the nucleus under hyperglycemia, bound to the Pim3 promoter and enhanced Pim3 transcriptional activity. Pim3 or YY1 knockdown profoundly reduced cell size and inhibited the mRNA and protein expression of cardiac hypertrophy markers, as well as markedly attenuating myocardial hypertrophy and cardiac dysfunction.

Conclusion: Hyperglycemia induced nuclear translocation of YY1, leading to Pim3 up-regulation, eventually developing into cardiac hypertrophy and HF. Targeting YY1-Pim3 signaling may be a promising therapeutic avenue for DM-induced cardiac hypertrophy and HF.

Objectives: Nonalcoholic fatty liver disease (NAFLD) is known to disrupt testicular anti-oxidant capacity, leading to oxidative stress (OS) that can negatively affect male fertility by damaging sperm DNA. Heat shock proteins (HSP70 and HSP90), in association with transitional proteins (TP1 and TP2), play crucial roles in protecting sperm DNA integrity in oxidative conditions. Whiteleg shrimp protein hydrolysates (HPs) exhibit anti-oxidant properties, prompting this study to explore the potential of HPs in ameliorating NAFLD-induced testicular damage.

Materials and methods: The study divided rats into four groups: control, a group subjected to a high-fat diet (HFD) to induce NAFLD without supplementation, and two HFD-induced NAFLD groups receiving HP doses (20 and 300 mg/kg). After 70 days, the testicular total anti-oxidant capacity (TAC), malondialdehyde (MDA), glutathione (GSH), glutathione disulfide (GSSG), HSP70-2a, HSP90 expression, and TP mRNA levels were assessed.

Results: The results showed that HFD-induced NAFLD significantly increased GSH and MDA levels and disrupted the GSH/GSSG ratio (P<0.05) while also reducing HSP70-2a, HSP90, TP1, and TP2 expression (P<0.05). However, HP administration effectively restored testicular redox balance, reduced oxidative stress, and enhanced these protective proteins' expression compared to HFD (P<0.05).

Conclusion: NAFLD negatively affects the testicular redox system and HSP and TP expression, disrupting male fertility potential. In contrast, HP-treated rats showed a marked effect on NAFLD-induced damage by improving testicular anti-oxidant status and regulating the expression of HSPs and TP proteins. These findings suggest a potential therapeutic role for HP in safeguarding male fertility against the damaging effects of NAFLD.

Objectives: Trans-sodium crocetinate (TSC) is one of the crocetin derivations that is more soluble and stable than crocetin and its cis form. It easily crosses the blood-brain barrier. TSC has neuroprotective effects. Bisphenol A (BPA) is an endocrine-mimicking compound that induces Parkinson-like disease by impacting the dopaminergic system. In this research, the effects of TSCs on BPA-induced Parkinson-like symptoms via behavioral and molecular assays have been investigated.

Materials and methods: Male Wistar rats received BPA (75 mg/kg, gavage), TSC (10, 20, and 40 mg/kg), and levodopa (L-dopa) (10 mg/kg) via intraperitoneal injection (IP) for 28 days. Parkinsonian-like motor features were evaluated using bar test, rotarod, and open field experiments. Malondialdehyde (MDA) and glutathione (GSH) levels were also measured as the most important indicators of oxidative stress. Western blotting was performed for the molecular assays of alpha-synuclein (α-syn), Bcl-2, Bax, caspase-3, Beclin, and LC3 I/II proteins.

Results: Our analyses indicated that treatment with TSC at high dose reduces MDA levels and protects GSH reserves. TSC can also increase anti-apoptotic Bcl-2 and decrease pro-apoptotic Bax and caspase-3 proteins. While it does not affect autophagy markers, TSC decreased α-syn protein expression, reduced the catalepsy time, and improved the time spent staying on the rotating bar and the locomotor activity.

Conclusion: Overall, TSC likely ameliorates BPA-mediated Parkinson' s-like symptoms by suppressing oxidative stress inhibition. This leads to reduced α-syn expression, which ultimately results in apoptosis inductions. Therefore, TSC can serve as a promising exploratory target for future research aimed at controlling Parkinson's disease.

Objectives: Both intrinsic and extrinsic factors cause skin aging. Intrinsic aging is characterized by decreased collagen density, particularly collagen types I (COL1A1) and III (COL3A1), and an increase in the COL1/COL3 ratio. Extrinsic aging, primarily due to ultraviolet light exposure, leads to photoaging, which causes collagen fragmentation and reduced production, leading to skin sagging. Thread lifts, a nonsurgical method, aim to tighten the skin and stimulate collagen production using biodegradable monofilament threads such as polydioxanone (PDO), poly-lactic acid (PLLA), and polycaprolactone (PCL). This study compared the effectiveness of PDO, PLLA, and PCL threads in reversing aging by enhancing dermal collagen, reducing the COL1/COL3 ratio, and increasing COL3A1 gene expression in UVB-exposed aging model rats.

Materials and methods: Thirty female Wistar (Rattus norvegicus) rats were divided into six groups, and their back hair was shaved and exposed to 840 mJ/m² UVB for 4 weeks. Skin biopsy specimens were assessed using Sirius Red staining to determine dermal collagen density and the COL1/COL3 ratio. Furthermore, qRT-PCR was used to examine COL3A1 gene expression.

Results: PDO, PLLA, and PCL threads enhanced skin quality, similar to the young negative control group, based on parameters such as dermal collagen density, COL1/COL3 ratio, and COL3A1 gene expression. PCL thread was more active than PDO and PLLA.

Conclusion: Thread implantation may result in a more youthful collagen profile than negative control and may be used to support skin anti-aging. The most effective thread was PCL compared to PDO and PLLA.

Objectives: The lateral periaqueductal gray (lPAG) is involved in regulating cardiovascular activity. As glutamate is present in this region, the effect of glutamatergic receptors on cardiovascular functions in basic and hypotensive hemorrhagic (Hem) rats was investigated.

Materials and methods: In both basic and hemorrhagic animals, saline, L-glutamate (L-Glu), and ionotropic receptor antagonists (MK-801 and GYK as NMDA and non-NMDA receptor antagonists, respectively) with and without L-Glu microinjected into the lPAG. The heart rate (HR), mean arterial pressure (MAP), and systolic blood pressure (SBP) were captured, and those changes (Δ) were calculated and analyzed.

Results: The results showed that in basic conditions, microinjection of MK-801 and GYK alone did not significantly affect cardiovascular parameters, but L-Glu significantly increased all parameters (P<0.001). However, co-injection of GYK and L-Glu significantly attenuated cardiovascular responses induced by L-Glu (P<0.01), whereas MK-801 did not have effects. In Hem hypotensive condition, injection of MK-801 and GYK alone could not significantly change the cardiovascular responses, while L-Glu alone significantly increased these responses (P<0.001). In this condition, Co-injection of L-Glu with GYK attenuates the pressor effect of L-Glu, but MK-801 did not affect it.

Conclusion: Findings suggest an excitatory cardiovascular role of the glutamatergic system of lPAG in normotensive conditions mediated by a non-NMDA receptor. However, in hem hypotensive conditions, the endogenous glutamatergic system of lPAG does not affect hem hypotension, while exogenous glutamate via a non-NMDA receptor could improve cardiovascular responses in this condition.

Objectives: Insulin resistance (IR) is a critical component of metabolic syndrome, primarily linked to obesity. It contributes to impaired glucose metabolism, beta-cell dysfunction, and the onset of type 2 diabetes. This study aimed to develop a DNAsome nanocarrier designed for the targeted delivery of small interfering RNA (siRNA) to inhibit mRNA of Transforming growth factor beta-like Stimulated Clone 22 D4 (TSC22D4), thereby enhancing insulin sensitivity in hepatocytes.

Materials and methods: The DNAsome was constructed using Y-DNA building blocks derived from three distinct DNA oligonucleotides. Its structural characteristics were analyzed through atomic force microscopy (AFM). The functional efficacy of the DNAsome in delivering siRNA was evaluated by measuring its cellular uptake and ability to down-regulate TSC22D4 expression in HepG2 cells via real-time PCR. Additionally, the cytotoxicity and safety of both the DNAsome and the DNAsome-siRNA complexes were assessed using the MTT assay on HepG2 cells.

Results: Findings indicated successful fabrication of the DNAsome nanocarriers, although aggregation was observed at higher concentrations, yielding nanoparticle sizes between 116 and 740 nm. Real-time PCR results confirmed effective siRNA targeting, significant cellular uptake of the nanocomplexes, and successful silencing of TSC22D4 expression.

Conclusion: This study suggests that DNAsome-based siRNA delivery systems hold promise for improving insulin sensitivity and addressing IR associated with obesity and metabolic syndrome.

Objectives: Knee osteoarthritis (KOA) is a persistent degenerative disease affecting the joints, significantly reducing the quality of life for individuals afflicted. This study explores the therapeutic effects of total saponin Achranthes (TSA) on KOA rats and its underlying mechanism.

Materials and methods: Forty-eight rats were randomly assigned to six experimental groups: a blank control group, a model group, a sham-operated group, and a TSA treatment group (low, medium, and high dose), with eight rats in each group. The rats were treated continuously for four weeks. The degree of joint swelling was quantified, and the Lequesne MG score was evaluated. Network pharmacology approaches were employed to pinpoint potential TSA targets and related pathways for managing KOA. Additionally, histopathological examinations were conducted on the knee cartilage of the rats. Serum levels of TNF-α and IL-1β were assessed through the ELISA assay.

Results: The network pharmacology results indicate that TSA may effectively treat KOA through the MAPK and PI3K/Akt signaling pathways. Moreover, TSA significantly decreased the serum concentrations of pro-inflammatory cytokines such as TNF-α and IL-1β, and TSA down-regulated the P38 MAPK, PI3K/Akt, and NF-κB pathways, whereas the KOA model showed up-regulation. The treatment also significantly reduced MMP-9, MMP-13, and ADAMTS-5 protein levels.

Conclusion: TSA can potentially ameliorate inflammation, safeguard knee cartilage tissue, and alleviate symptoms of KOA by inhibiting the MAPK/Akt/NF-κB signaling pathway.

Obesity remains a significant worldwide health concern, and further research into other strategies, including herbal weight-loss medications, is necessary. By reviewing clinical trials, this study aims to evaluate the effectiveness of herbal medicines for weight loss or obesity. A comprehensive search was conducted using multiple databases. Clinical trials evaluating the effects of herbal medicines on weight loss or obesity management were included. Relevant data, such as study design, intervention details, and outcome measures, were extracted and analyzed. The use of herbal medicines exhibited varying efficacy in promoting weight loss or managing obesity. Some herbal interventions significantly reduced body weight, body mass index (BMI), and waist circumference. Notably, these interventions led to decreases in fasting blood glucose (FBG) and homeostatic model assessment of insulin resistance (HOMA-IR), regulating insulin levels while increasing levels of catalase (CAT) and glutathione (GSH). Additionally, reductions in inflammatory markers such as high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor-alpha (TNF-α) were observed, indicating a potential anti-inflammatory effect. Mechanisms of action included appetite regulation, fat oxidation, increased satiety, enhanced insulin sensitivity, and modulation of lipid metabolism. However, it is important to note that these herbal interventions' efficacy and safety profiles may vary among different population groups. The findings suggest that certain herbal medicines hold promise as adjunctive therapies for weight loss and obesity management. However, comprehensive and targeted research efforts are warranted to determine these herbal interventions' optimal use, dosages, and long-term effects in specific population subgroups.

Objectives: Hydatid cysts are typically treated with albendazole. Nevertheless, this drug has side effects and limited bioavailability. In this study, we aimed to explore a nanoemulsion of black seed oil to enhance the therapeutic efficacy of albendazole in mice with hydatid cysts.

Materials and methods: The size of the prepared nanoemulsions was characterized using a Zetasizer analyzer. Additionally, the stability of the nanoemulsions was assessed after 45 days. MTT assay was used to compare the cytotoxicity of free albendazole, nanoemulsion containing albendazole, and nanoemulsion without albendazole. Furthermore, infected mice were treated with these preparations, euthanized, and subjected to autopsy examination. Cysts obtained from mice were examined for histopathological features.

Results: ALB-NE (albendazole-loaded nanoemulsion) DLS results were obtained from black seed oil. Freshly prepared ALB-NE showed (d50 = 170 nm), PDI: 0.323, ALB-NE after 45 days storage at 25 ºC were (d50 = 92.4 nm), and ALB-NE after 45 days storage at 45 ºC revealed (d50 = 118 nm). The cytotoxicity of albendazole was reduced when loaded into the nanoemulsion. Moreover, the group treated with nanoemulsion containing albendazole showed a significant decrease in size and number of cysts compared to those receiving free albendazole or nanoemulsion without the drug. Additionally, after 60 days, the nanoemulsion containing albendazole showed 100% survival, while the survival rate was 50% for free albendazole, 75% for nanoemulsion without albendazole, and 37.5% for PBS.

Conclusion: The nanoemulsion containing albendazole can be a promising treatment for hydatid cysts.