Molecular Biology Reports最新文献

Objectives: This study aimed to investigate the effects of andiz extract on wound healing and compare it with saline and chlorhexidine gluconate. Microbial DNA load was used to evaluate its antibacterial effects, and gene expression methods were used to assess its contribution to cytokine release and wound healing.

Methods and results: A standardized wound site was created with a 3 mm diameter punch on 32 male Wistar albino rats. The rats were divided into four groups: Control (n = 5), Saline (n = 9), Chlorhexidine gluconate (n = 9), and Andiz extract (n = 9). Five rats in the control group were euthanised without any treatment. Irrigations of the Saline, Chlorhexidine, and Extract groups were provided regularly. After the tissue samples were taken in the 1st week, 2nd week, and 3rd week, three rats were euthanized each week for each group. The total bacterial DNA load on the samples taken was determined by a nano spectrophotometer. β-actin was chosen as housekeeping, and target gene primers were created for TGF-β and IL-1β. Expression amounts of target genes were measured by Real-Time PCR with the application of the created primers. There is a significant difference between the Extract group and the other groups regarding total bacterial DNA load. The whole bacterial load was 185% less than the initial values. TGF-β and IL-1β genes evaluated regarding gene expression were measured at the highest value in the Extract group.

Conclusions: This study showed the antibacterial effects of the Extract and its positive contributions to wound healing.

Background: The objective of this study was to evaluate the levels of Vascular Peroxidase 1 (VPO1), humanin, and MOTS-c in relation to miR-200c expression in untreated preeclamptic pregnancies, and to compare these findings with endoglin levels.

Methods and results: In this study, blood samples were collected from preeclamptic patients presenting to the clinic prior to the initiation of treatment. The levels of endoglin, VPO1, humanin, and MOTS-c were measured using enzyme-linked immunosorbent assay (ELISA), while miR-200c expression was quantified using reverse transcription polymerase chain reaction (RT-PCR). Receiver operating characteristic (ROC) analysis was performed to assess diagnostic accuracy. Statistical significance was determined at p < 0.05. The levels of endoglin, VPO1, and miR-200c were found to be significantly elevated in the preeclampsia group compared to the control group (p < 0.05), whereas MOTS-c levels were significantly reduced (p < 0.05). No significant difference was observed in humanin levels between the two groups. A positive correlation was identified between endoglin levels and VPO1 (r = 0.943, p < 0.001), humanin (r = 0.421, p < 0.01), and uric acid (r = 0.314, p = 0.02) in the preeclamptic group.

Conclusions: Our findings suggest that the elevation of VPO1 and miR-200c levels, along with the reduction of humanin and MOTS-c levels, may contribute to the increased endoglin levels and subsequent endothelial dysfunction observed in preeclampsia. These changes may be associated with the pathogenesis and severity of the disease.

Background: Acute myeloid leukemia (AML) is a common hematological tumor, but it is difficult to treat. DNMT1 is a DNA methyltransferase whose main function is to maintain stable DNA methylation during the DNA replication process. DNMT1 also plays an important role in AML, but its function in cytokine-induced memory-like natural killer (CIML NK) cell activity remains unclear.

Methods and results: In this study, we isolated primary NK cells from the peripheral blood of healthy volunteers and AML patients and treated them with 10 ng/mL IL-12, 50 ng/mL IL-15 and 50 ng/mL IL-18 to promote their differentiation into CIML NK cells. The activity of CIML NK cells was evaluated by RT‒qPCR, western blotting, ELISAs, and flow cytometry. DNMT1 was highly expressed in NK cells from AML patients. Knocking down DNMT1 significantly increased the expression of CD25, CD137, CD107a, IFN-γ, and TNF-α and increased the activity of CIML NK cells. Mechanistically, knocking down DNMT1 promoted autophagy by activating the AMPK/mTOR signaling pathway, thereby enhancing the activity of CIML NK cells and alleviating the progression of AML.

Conclusions: Our study revealed that the downregulation of DNMT expression may be a new target for the treatment of AML.

Introduction: The changes in histone modifications are linked to the progression of benign and normal tissue to malignancy. Thus, numerous findings suggest that targeting epigenetic factors might be a focus for anti-cancer treatment. In this study, we tested the hypothesis that telomerase activator might be a potential epigenetic regulator in combatting skin cancer cell proliferation.

Methods: Melanoma cell line A375 cells were treated with telomerase activator TA-65. Cell senescence assay was done to evaluate the senescence induction. Morphological changes and differences in expression of HDACs and hTERT genes were studied. Further, hyaluronidase and anti-oxidant assays were also performed. Additionally, telomerase enzyme and 20S proteasome activity was also studied.

Results: Morphological changes were observed in treated cells and it is evident that telomerase activator induced cellular senescence in high concentrations. From our results, it is evident that HDAC8 and  HDAC10 expression was upregulated, whereas hTERT gene expression was downregulated in treated groups. This suggests that the telomerase activator has a regulatory role in skin cancer cells proliferation by targeting the epigenetic factors.

Conclusion: Targeting HDACs and hTERT in the treatment of melanoma is a prominent concern. In our current study, we highlight the most recent research, although in its initial stage, involving various epigenetic factors involved in melanoma cells proliferation.

Background: Oleuropein (OLE) has the potential to reduce oxidative stress and inflammation. So, in the present investigation, we explored the protective effect of OLE on brain aging induced by d-galactose (D-Gal) in a rat model.

Methods and results: 40 Wister male adult rats were categorized into 5 groups. Group 1 received normal saline; group 2 was given 100 mg/kg of D-Gal intraperitoneally (IP). The rats in groups 3 to 5 were given D-Gal (100 mg/kg, IP) along with different doses of OLE (20, 40, and 80 mg/kg, respectively) orally. All administrations were performed daily for 8 weeks. 24 h after last treatment motor activity and memory impairment were evaluated. Then, the rats were euthanized and brain samples were collected for evaluating the levels of malondialdehyde (MDA), Brain-Derived Neurotrophic Factor (BDNF), protein carbonyl (PC), glutathione (GSH), glutathione peroxidase (GPX), catalase (CAT), Superoxide dismutase (SOD), Tumor necrosis factor alpha (TNF-α), interleukin 1 beta ( IL-1β), as well as Sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1) gene expression. The results showed that D-Gal significantly reduced motor activity and memory performance (P < 0.05). It also significantly reduced the GPX, CAT and SOD activities, GSH and BDNF levels as well as SIRT1 and PGC1 expression, and, significantly increased PC, MDA TNF-α and IL-1β levels in the brain tissue (P < 0.05). Administration of OLE restored all of the above parameters close to control group.

Conclusion: The findings demonstrated that OLE, through its antioxidant and anti-inflammatory properties, improved motor activity, memory impairment, and age-related neurological dysfunction.

Wound management is a major global health problem. With the rising incidence of diabetic wounds, accidents, and other injuries, the demand for prompt wound treatment has become increasingly critical. Millions of people suffer from serious, large wounds resulting from major accidents, surgeries, and wars. These wounds require considerable time to heal and are susceptible to infection. Furthermore, chronic wounds, particularly in elderly and diabetic patients, often require frequent medical interventions to prevent complications. Consequently, wound management imposes a significant economic burden worldwide. The complications arising from wound infections can vary from localized issues to systemic effects. The most severe local complication of wound infection is the non-healing, which results from the disruption of the wound-healing process. This often leads to significant pain, discomfort, and psychological trauma for the patient. Systemic complications may include cellulitis, osteomyelitis, and septicemia. Mesenchymal stem cells are characterized by their high capacity for division, making them suitable candidates for the treatment of tissue damage. Additionally, they produce antimicrobial peptides and various cytokines, which enhance their antimicrobial activity. Evidence shows that phages are effective in treating wound-related infections, and phage therapy has proven to be highly effective for patients when administered correctly. The purpose of this article is to explore the use of bacteriophages and mesenchymal stem cells in wound healing and infection management.

Background: The treatment of metastatic castration-resistant prostate cancer (mCRPC) is still challenging clinically. Due to the refractor and highly metastatic phenotype of mCRPC, novel therapy strategies need to be investigated. Luteolin, a promising anticancer agent with various biological targets in many cancer types, also has a pro-oxidant effect that selectively triggers ROS and apoptosis. In recent years, among its ROS-mediated mechanisms, the inhibitory effect of luteolin on the nuclear factor-E2-related factor 2 (Nrf2), the main ROS scavenger protein in cancer cells, has been reported. However, no evidence exists that luteolin potentially regulates the Nrf2 or its regulator signaling pathway, Nrf2-Keap1-Cul3 axis, concerning its pro-oxidant effects associated with ROS-triggered apoptosis in any PCa cells or tumor model.

Methods and results: In the present study, we investigated for the first time whether the anticancer effect of luteolin is associated with pro-oxidant activity via the regulation of the Nrf2-Keap1-Cul3 redox signaling in PC3 and DU145 mCRPC cells. The results showed that luteolin significantly caused more cytotoxic, apoptotic, and pro-oxidant effects in a dose-dependent manner in mCRPC cells than in WPMY-1 normal prostate fibroblast cells for 72 h. Moreover, significant inhibition of Nrf2-Keap1-Cul3 redox signaling has occurred in response to increasing doses of luteolin in mCRPC cells.

Conclusions: The current study put forth the potential pro-oxidant inhibitory effect of luteolin on the Nrf2-Keap1-Cul3 axis in mCRPC cells for the first time. Thus, luteolin might be an attractive therapy strategy with an inhibitory effect on the cytoprotective Nrf2-Keap1-Cul3 redox signaling for treating mCRPC.

Background: Analysis of the content of the gut of fish helps in the understanding of their inter- and intra-specific interactions, fish behaviour, condition and energy intake. The stomach contents of the commercially important neritic tuna species of Sri Lanka, kawakawa (Euthynnus affinis), frigate tuna (Auxis thazard) and bullet tuna (Auxis rochei) were analysed to determine their feeding habits and to identify prey species.

Methods and results: The weighed stomachs of fish were dissected to reveal the types of prey found within. The prey was categorised into prey categories and each prey species was identified morphologically. Prey items which were partially digested were identified using DNA barcoding. The main prey category was small fish, followed by crustaceans and cephalopods. While the highest occurring prey category for E. affinis and A. rochei was fish, crustaceans dominated the A. thazard diet. DNA barcoding identified 11 prey items that were partially digested, which could not be identified to species-level morphologically. Of the prey items identified by DNA barcoding, four species of fish, three species of cephalopod and four species of crustaceans were identified. These prey item identifications confirmed that E. affinis, A. thazard and A. rochei are all nonspecific feeders.

Conclusions: This exhibits the value of molecular tools in the identification of species which have lost their distinguishable features due to digestion. Further, it illustrates the predator-prey relationships between these species, aiding in the management of prey and predator populations, ensuring that both populations remain stable, helping in the maintenance of the balance of the ecosystem.

Background: The progression of leukemia is substantially associated with the interactions of leukemic cells with surrounding cells within the bone marrow microenvironment (BMM), and these interactions were facilitated using exosomes as vital mediators. The current study aimed to examine the proliferative effects of exosomes derived from the HL-60 cell line, a representative of acute myeloblastic leukemia (AML), on the cell cycle progression of human bone marrow mesenchymal stromal cells (hBM-MSCs), a key element of the BMM.

Methods and results: hBM-MSCs were treated with different concentrations of AML-derived exosomes from the HL-60 cell line. The results were obtained from MTT, cell proliferation, cell cycle, and RT-qPCR evaluations. In the current study, we found that the proliferation effects of AML-derived exosomes relied on the dose and the time, and the optimal effects of exosomes were seen in 50 μg/ml, 48 h treatment. Flow cytometry analysis revealed a significant increase in the G1 phase, showing a 1.6-fold change compared to the control group (p value < 0.0001). RT-qPCR results demonstrated a significant upregulation of CCND1 (3.3-fold, p value < 0.0001), CDK4 (3.7-fold, p value < 0.0001), CDK6 (3.3-fold, p value < 0.0001), RAS (3.2-fold, p value < 0.0001), and Erk (3.4-fold, p value < 0.0001) expression levels, along with increased Ki-67 (2.6-fold, p value < 0.0001) levels. Moreover, treatment with 50 μg/ml, 48 h of AML-derived exosomes resulted in a notable reduction in BM-MSC apoptosis both in early (p value < 0.0001) and late (p value < 0.0001) apoptosis rate compared to control group.

Conclusions: The findings will be of interest to AML-derived exosomes, which were able to potentiate the activation of the signaling pathways involved in the survival and proliferation of hBM-MSCs. Our findings suggest their specific targeting as a potential therapeutic strategy against cancer progression and metastasis.

Fibromyalgia (FM) is a complex, chronic pain syndrome characterized by widespread musculoskeletal pain, fatigue, and cognitive disturbances. Despite its prevalence, the pathophysiology of FM remains poorly understood, with current treatments often providing limited relief. Recent studies have suggested that metformin, a widely used antidiabetic drug, may have potential therapeutic benefits for chronic pain conditions, including FM. This review aims to provide current insights into the role of metformin in FM pathophysiology, focusing on its neurotransmitter-modulating and anti-inflammatory effects. Metformin has been shown to mitigate neuroinflammation, protect neural tissues, and modulate key neurotransmitters involved in pain and mood regulation. These effects are particularly evident in animal models, where metformin has been observed to reduce pain sensitivity, improve mood-related behaviors, and decrease levels of pro-inflammatory cytokines like interleukin 1-beta (IL-1β). Additionally, the ability of metformin to influence serotonin, norepinephrine, and glutamate levels suggests a potential mechanism for its analgesic and mood-stabilizing effects. However, the current evidence is largely preclinical, and further research is needed to confirm these findings in human studies. This review aims to encourage researchers to explore the association between metformin and FM more deeply, with the hope of uncovering new therapeutic strategies that could offer relief to FM patients.