Iranian Journal of Basic Medical Sciences最新文献

Objectives: Ellagic acid (EA) is a natural polyphenol with anti-cancer, anti-oxidant, anti-inflammatory, antibacterial, and other effects. However, the role of EA in cerebral ischemia/reperfusion injury (CIRI) remains unclear. This study aims to investigate the neuroprotective effects of EA in CIRI.

Materials and methods: Forty male Wistar rats (260-300 g) were randomly divided into four groups with 10 rats per group: 1) Sham+Veh: Rats underwent I/R surgery, except that they were not inserted with thread plugs, and received solute treatment at the same time. 2) MCAO/R+Veh. 3) MCAO/R+EA: Rats were administered 200 mg/kg EA before undergoing MCAO. 4) MCAO/R+Nim: Rats were administered Nim before undergoing MCAO.

Results: Cerebral MCAO/R damaged brain tissue, elevated neurological deficit score (P<0.01), cerebral infarction volume (P<0.01), inflammatory cell infiltration (P<0.01), NLRP6, ASC, caspase-1 and GSDMD mRNA level (P<0.01 and P<0.001), NLRP6, caspase-1, GSDMD-N and IL-1β protein level (P<0.01 and P<0.001), and inflammatory cytokines in brain tissue (P<0.01). Prophylactic administration of EA also significantly improved brain tissue damage, reduced neurological deficit score (P<0.01), cerebral infarction volume (P<0.01), inflammatory cell number (P<0.05), NLRP6, caspase-1, GSDMD-N mRNA and protein level (P<0.05 and P<0.01), ASC mRNA level and IL-1β protein level (P<0.01), and IL-1β and IL-18 level in brain tissue (P<0.01) compared to positive control.

Conclusion: EA may serve as a potential drug for the treatment of brain I/R, which may exert an anti-inflammatory effect by inhibiting the activation of the inflammasome.

Objectives: While ketone bodies are not the main heart fuel, exercise may increase their uptake. Objectives: This study aimed to investigate the effect of 6-week endurance training and Pyruvate dehydrogenase kinase 4 )PDK4( inhibition on ketone bodies metabolism in the heart of diabetic rats with emphasis on the role of Peroxisome proliferator-activated receptor-gamma coactivator PGC-1alpha (PGC-1α).

Materials and methods: Sixty male Wistar rats were divided into eight groups: healthy control group (CONT), endurance training group (TRA), diabetic group (DM), DM + EX group, Dichloroacetate (DCA) group, DM + DCA group, TRA + DCA group, and DM + TRA + DCA group. Diabetes was induced using streptozotocin (STZ). The animals in training groups ran on the treadmill for six weeks (30-50 min running at 20-30 m/min). After the training period, molecular markers for mitochondrial biogenesis and ketone metabolism were assessed in the heart. Circulating ß-hydroxybutyrate (ßOHB) and Acetylacetonate (AcAc) levels were also measured.

Results: Our results showed that 6-week endurance training increased the cardiac expression of PGC-1α, 3-oxoacid CoA-transferase 1 (OXCT1), and Acetyl-CoA Acetyltransferase 1 (ACAT1) and reduced beta-hydroxybutyrate dehydrogenase1 (BDH1) expression (P≤0.05). In addition, exercise and DCA usage significantly decreased PDK4 gene expression, ßOHB, and AcAc blood levels (P≤0.05). Furthermore, the combination of 6-week endurance training and DCA supplementation led to more reduction in PDFK4 gene expression, ßOHB, and AcAc blood levels.

Conclusion: Six-week endurance training and DCA supplementation could safely improve ketone body metabolism in the heart, ultimately reducing hyperketonemia/ketoacidosis in diabetic rats.

Objectives: Cisplatin (DDP) resistance remains a primary cause of chemotherapy failure and recurrence of non-small cell lung cancer (NSCLC). Abnormal high microsomal glutathione transferase 1 (MGST1) expression has been found in DDP-resistant NSCLC cells. This study aimed to explore the function and mechanism of MGST1 in DDP resistance of NSCLC cells.

Materials and methods: The expression levels of target molecules were assessed by quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting. Cell proliferation was evaluated by cell counting kit-8 (CCK-8) and colony formation assays. Ferroptosis was determined by malondialdehyde (MDA), glutathione (GSH), Fe²⁺, and reactive oxygen species (ROS) levels. The interaction between proteins was confirmed by Co-immunoprecipitation (Co-IP). The effect of MGST1 on DDP resistance was evaluated using the tumor xenograft assay in vivo. Immunohistochemical staining was performed to measure Ki-67 and p-H2A.X expression in tumor tissues.

Results: MGST1 expression was higher, while arachidonate lipoxygenase 5 (ALOX5) expression was lower in DDP-resistant NSCLC patients and cells. MGST1 ablation sensitized NSCLC cells to DDP therapy through inducing ferroptosis. MGST1 protein directly interacted with ALOX5 protein to restrain ALOX5-triggered ferroptosis. Ferroptosis inhibitor or sh-ALOX5 reversed the promotive effect of MGST1 silencing on the DDP sensitivity of NSCLC cells. Finally, MGST1 depletion sensitized NSCLC cells to DDP therapy in nude mice in vivo.

Conclusion: MGST1 high expression contributed to DDP resistance of NSCLC cells by inhibiting ALOX5-induced ferroptosis. Our results provide a potential therapeutic target for overcoming DDP resistance in NSCLC patients.

Metabolic syndrome is a clustering of metabolic abnormalities and anthropometric factors that increase the risk of cardiovascular disease and type 2 diabetes mellitus. As the search for effective treatments intensifies, attention has turned towards natural substances with potential medicinal benefits. Among them, vanillic acid, a phenolic acid present in many plants, has attracted some attention due to its wide range of biological activities. This review aimed to provide an in-depth summary of the potential therapeutic use of vanillic acid in metabolic syndrome. The potential mechanisms of action of vanillic acid, including its anti-oxidant, anti-inflammatory, and hypolipidemic properties, are discussed. The effect of vanillic acid on glucose homeostasis, insulin sensitivity, and adipocyte activity is also addressed. The effect of vanillic acid on lipid metabolism, including the control of lipid synthesis, breakdown, and transport, is also reviewed. The emerging evidence for the beneficial effects of vanillic acid in animal models, in vitro studies, and preliminary clinical studies is also highlighted. The data suggests that vanillic acid has the potential to ameliorate metabolic syndrome. However, further preclinical and clinical research is needed to determine the specific mechanisms of action, appropriate dose, and subsequent advantages of vanillic acid. A more comprehensive understanding of the therapeutic potential of vanillic acid could pave the way for developing innovative techniques for preventing and treating metabolic syndrome and its implications.

Objectives: The present study investigated the protective effect of melittin (MEL) against bleomycin (BLM)- induced pulmonary fibrosis (PF) in mice and the mechanism underlying this effect.

Materials and methods: A mouse model of PF was established by intratracheal injection of 3.5 mg/kg BLM. Twenty-four hours after the model was established, the mice in the treatment groups were intraperitoneally injected with MEL, and specimens were collected 28 days later. The body weight, survival rate, and pulmonary index (PI) of the mice were determined. Haematoxylin and eosin (HE) staining, Masson's trichrome staining, immunohistochemical staining, kit assays, and Western blot (WB) analysis were performed.

Results: Our study indicated that MEL significantly increased the body weight and survival rate, reduced PI, and improved lung histopathology in mice. In addition, MEL inhibited epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) deposition. Attenuated mitochondrial damage and reduced oxidative stress (OS) were also observed in MEL-treated mice. We further showed that MEL inhibited the TGF-β1/Smad2/3 pathway and activated the AMPK/SIRT1/PGC-1α pathway.

Conclusion: MEL is a promising future therapeutic agent for PF. Its multifaceted and complex mechanism of action inhibits both EMT and ECM production by modulating the TGF-β1/Smad2/3 pathway. It also improves mitochondrial function and reduces OS at least partially through the activation of the AMPK/SIRT1/PGC-1α signaling pathway.

Cancers are extremely dynamic diseases that can actively cause refractorines to be gained from applied therapies, which is why they are at the forefront of deaths worldwide. In this literature review, we covered the most recent and important discoveries regarding the influence of human microbiota, including tumor bacteriome, on the development and treatment of cancer. Advances in research on microbial communities have enabled us to discover the role of the human microbiome in the development and course of this disease, helping us understand neoplasms better and design new potential therapies. As we show through our findings, by immunomodulation and the secretion of certain chemical substances, the correct bacteriome of the intestinal tract, respiratory system, or skin can protect humans against cancer development and help during the treatment process. Bacteria also reside inside tumors, forming part of the tumor microenvironment (TME), where they interact with immunological and cancer cells in many complex ways. Some bacteria, such as Pseudomonas aeruginosa or Akkermansia muciniphila, can stimulate anticancer cell-mediated immune responses or even directly lead to cancer cell death. We also present the clinical possibilities of using some live, usually modified bacteria to develop bacteriotherapies. Modifying the gut microbiome to stimulate standard treatment is also important. Research on the microbiome and cancer remains a challenging topic in microbiology, having a great potential for advancements in cancer therapy in the future, and is continuously becoming a more and more popular field of research, as shown by our statistical analysis of PubMed data.

Objectives: Adjuvants are some of the most important components used for vaccine formulation. In addition, the efficacy of vaccines is highly dependent on the nature of the adjuvants used. Therefore, new adjuvant formulations may help develop more potent vaccines. In the present study, the potency of an in-house and water-in-oil adjuvant (Yavar-70A) was compared with Montanide ISA 206 and Montanide ISA 266 in an HPV-16E7d vaccine model.

Materials and methods: Three HPV-16 E7d vaccines were formulated using three different adjuvants, Montanide ISA 206, Montanide ISA 266, and Yavar-70A, with standard protocols. Afterward, each formulation containing 10 μg of the E7d protein was administered thrice at two-week intervals to C57BL/6 mice. Serum levels of IFN-γ and IL-4 cytokines secreted from spleen cells, total IgG, and specific IgG1 and IgG2a isotypes were assessed using ELISA two weeks after the last immunization. Lymphocyte proliferative responses were also evaluated using the BrdU method.

Results: The results indicated that the vaccine formulated using the Yavar-70A adjuvant showed the highest lymphocyte proliferation responses compared with other groups and higher IFN-γ cytokine release compared with that formulated using Montanide ISA 206. However, the vaccine formulated using Montanide ISA 206 induced the highest total IgG responses compared with other groups. Importantly, the vaccine formulated using Yavar-70A decreased IL-4 secretion compared with other vaccinated groups.

Conclusion: The present study demonstrated that Yavar-70A induces cellular and humoral immunologic parameters against the HPV-16 E7d vaccine model comparable to commercialized oil-based adjuvants.

Objectives: Traumatic brain injury (TBI) is a significant cause of mortality and disability worldwide. TBI has been associated with factors such as oxidative stress, neuroinflammation, and apoptosis, which are believed to be mediated by the N-methyl-D-aspartate (NMDA)-type glutamate receptor. Two NMDA receptor antagonists, ketamine and memantine, have shown potential in mitigating the pathophysiological effects of TBI.

Materials and methods: To conduct the study, a controlled cortical impact model was used to induce TBI in rats. The rats with TBI were then divided into three groups: a group receiving only TBI, a group receiving TBI along with memantine, and a group receiving TBI along with ketamine. After 24 hr, the levels of oxidative stress markers (such as SOD, MDA, and total thiol) in the brain tissue were measured. Immunohistochemical staining was also performed seven days after TBI to assess the activation of glial cells and the TLR-4/NF-κB neuroinflammatory pathway.

Results: The results indicated that treatment with memantine led to a reduction in MDA levels and an increase in SOD and total thiol levels. Memantine also decreased astrogliosis and down-regulated the TLR-4/NF-κB pathway. On the other hand, ketamine increased the levels of anti-oxidant markers but did not significantly affect the MDA level. Additionally, ketamine decreased the expression of NF-κB seven days after TBI.

Conclusion: The findings suggest that NMDA receptor antagonists, such as ketamine and memantine, may have therapeutic effects on TBI by inhibiting oxidative stress and inflammatory responses.

Adipogenesis, the process of proliferation of adipocyte progenitor cells and their differentiation into mature adipocytes, plays a critical role in the development of obesity. In this context, exploring the effects of phytochemicals on adipogenesis is very promising, as nowadays, they are widely used as food, drink, or supplement and can significantly impact general health and obesity control. This systematic review attempts to evaluate new findings regarding the molecular mechanisms of different phytochemicals on adipogenesis in in vitro models. Between 2010 and July 2023, a comprehensive systematic search of PubMed and Scopus databases was conducted. The following keywords were used: ("adipogenic") AND ("inhibit" OR "suppress" OR "reduce" OR "anti" OR "decrease") AND ("cell" OR "cell line" OR "adipocyte") AND ("phytochemical" OR "plant" OR "herb"). In this review, 109 studies were comprehensively analyzed, which provided important insights into the process of adipogenesis. Among the numerous transcription factors studied, PPARγ, C/EBPα, and SREBP1c were found to be the most important regulators actively involved in adipocyte differentiation. These results highlight the critical role of these factors in the control of adipogenesis and suggest that they represent promising targets for therapeutic interventions aimed at reducing the excessive lipid accumulation associated with obesity. This study provides a compelling rationale for further exploring phytochemicals as potential therapeutics for treating obesity. The potential benefits of using natural products to influence adipogenesis are evident, and future studies should focus on translating these findings into clinical applications.

Objectives: In our study, the neuroprotective efficacy of pre- and post-traumatic applications of boric acid (BA) in rats with experimentally induced spinal cord injury (SCI) was investigated.

Materials and methods: The experimental animals were divided into four groups: control group (C), SCI group (SCI), BA-treated group before SCI (BA+SCI), and BA-treated group after SCI (SCI+BA). Forty-eight hours after SCI, biochemical levels of malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), and cytochrome c (Cytc) and caspase-3 (Casp3) expressions were measured in the spinal cord tissues and were examined histologically.

Results: After SCI, oxidative stress markers, such as MDA, TOS, and OSI, and apoptosis markers Cytc and Casp3 showed an increase in levels compared to Group C. The oxidative stress markers that increased after SCI decreased with BA+SCI application, while Cytc level, one of the apoptosis markers that increased after SCI, decreased in both groups with BA application. Cell, myelin, ependymal damage, and hemorrhage levels increased after SCI compared to Group C. These histological markers increased after SCI and decreased after BA+SCI. BA was found to reduce SCI-induced oxidative stress and oxidative stress-induced apoptosis.

Conclusion: BA administered before SCI was shown to be more effective in protecting neural damage.