Bosnian Journal of Basic Medical Sciences (BJBMS)
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Regulatory role and molecular mechanism of METTL14 in vascular endothelial cell injury in preeclampsia
Get PDFPreeclampsia (PE) is a pregnancy-related disease characterized by vascular endothelial cell injury. This study aimed to investigate the role of methyltransferase-like protein 14 (METTL14) in vascular endothelial cell injury in PE. A PE cell model was established by treating human umbilical vein endothelial cells (HUVECs) with tumor necrosis factor-alpha (TNF-α) in vitro. METTL14 and forkhead box protein 1 (FOXP1) were silenced, and miR-34a-5p was overexpressed in HUVECs to evaluate their effects. HUVEC viability, apoptosis, and levels of intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and endothelin-1 were measured. The N6-methyladenosine (m6A) modification of pri-miR-34a-5p was quantified. The interactions between miR-34a-5p, DiGeorge syndrome critical region 8, and m6A enrichment in miR-34a-5p were analyzed. The relationship between miR-34a-5p and FOXP1 was also verified. The results showed the expressions of METTL14, FOXP1, and miR-34a-5p. METTL14 expression was elevated in the TNF-α-induced HUVEC injury model. Silencing METTL14 improved HUVEC viability, inhibited apoptosis, and reduced endothelial inflammation. METTL14 promoted miR-34a-5p expression through m6A modification. Overexpression of miR-34a-5p or silencing FOXP1 reversed the protective effects of METTL14 silencing on cell injury in the PE model. In conclusion, METTL14 mediated m6A modification to promote miR-34a-5p expression, leading to FOXP1 inhibition, which aggravated endothelial cell damage in the PE cell model
Concurrent intra-aortic balloon pump and veno-arterial extracorporeal membrane oxygenation for acute coronary syndrome-related cardiogenic shock: A meta-analysis of multivariate studies
Get PDFConcurrent intra-aortic balloon pump (IABP) use has been suggested to reduce mortality in patients with acute coronary syndrome (ACS)-related cardiogenic shock (CS) on veno-arterial extracorporeal membrane oxygenation (ECMO). However, this observation is primarily based on small-scale univariate studies. The aim of this meta-analysis was to evaluate whether concurrent IABP and ECMO were independently associated with reduced mortality in patients with ACS-related CS. We searched Medline, Web of Science, and Embase for studies published up to May 28, 2024. The inclusion criteria were longitudinal observational studies comparing concurrent IABP and ECMO to ECMO alone in ACS-related CS patients, reporting all-cause mortality with multivariate adjustments. The primary outcome was the risk ratio (RR) of short-term mortality. A random-effects model incorporating heterogeneity was used to pool the results. Seven cohort studies, involving 5467 patients, were included. Concurrent IABP and ECMO were associated with a significant reduction in short-term mortality (adjusted RR: 0.64; 95% CI: 0.48–0.87, P = 0.005; I² = 83%). Sensitivity analyses confirmed the robustness of these results. Meta-regression indicated that the proportion of men in each study significantly influenced the outcomes, fully explaining the heterogeneity (I² residual = 0%). Subgroup analyses showed consistent results across various study designs, patient ages, observational durations, and study quality scores. In conclusion, concurrent IABP and ECMO are independently associated with reduced short-term mortality in ACS-related CS patients, particularly in studies with higher proportions of men. These findings support the potential benefits of combined mechanical support in this high-risk population
HLA-DRB1*01 predicts treatment outcome in juvenile idiopathic arthritis: A retrospective-prospective cohort study
Get PDFJuvenile idiopathic arthritis (JIA) is the most common chronic inflammatory autoimmune disease in childhood, significantly contributing to both short- and long-term disability. While certain human leukocyte antigen (HLA) class II alleles are known to be associated with specific subgroups of JIA, emerging evidence suggests a strong correlation between these alleles and treatment response. This study involved 143 JIA patients diagnosed according to International League of Associations for Rheumatology criteria. Each patient underwent HLA class II typing, including HLA-B27, as well as tests for rheumatoid factor (RF) and antinuclear antibodies (ANA). Comprehensive rheumatological assessments were conducted at diagnosis, with follow-ups at three and six months post-onset. After six months of methotrexate (MTX) treatment, patients were categorized as responders or non-responders. Responders achieved clinically inactive disease based on the American College of Rheumatology Provisional Criteria for Defining Clinical Inactive Disease and Clinical Remission. Non-responders, who did not reach clinically inactive disease after six months of treatment, required the addition of another non-biological disease-modifying antirheumatic drug (DMARD) or a biological DMARD. Our analysis revealed that the HLA-DRB1*01 allele is a significant prognostic marker for therapeutic response, predicting therapeutic resistance (P=0.01). The most prevalent HLA-DRB1 alleles in the treatment-resistant group were HLA-DRB1*08:11 (11.3%), HLA-DRB1*01:01 (8.5%), HLA-DRB1*01:13, HLA-DRB1*04:11 (7%), HLA-DRB1*08:13, and HLA-DRB1*08:15 (4.2%). These findings highlight the critical role of HLA class II alleles in pediatric rheumatology, particularly in relation to treatment response and disease prognosis. In the era of personalized medicine, understanding the genetic contributions to treatment response and outcomes in JIA patients is essential. A key limitation of this study was the lack of comparison of treatment responses across different JIA subtypes. Future studies should prioritize evaluating MTX efficacy within specific JIA subgroups to enable a more tailored understanding of its effectiveness
Hidden benefits of snail mucus: A natural skincare marvel
Get PDFDear Editor,From a scientific perspective, snail mucus, or snail secretion filtrate (SSF), has emerged as a significant discovery in dermatology and regenerative medicine. Several studies on mucus composition have illuminated its features in recent years, yet much remains unexplored. High-quality snail mucus contains adequate levels of active substances (e.g., allantoin, glycolic acid, proteins, glycosaminoglycans, and polyphenols). It comprises a complex mixture of proteins, enzymes, peptides, and trace minerals produced both externally and internally, which improves skin hydration, flexibility, and smoothness. This makes it an ideal ingredient for anti-aging creams, moisturizers, and serums. The beauty and pharmaceutical industries popularize commercial SSF products due to their natural composition and scientifically proven performance as a promising dermatological treatment. These products offer synergistic therapeutic effects, including cell signaling, tissue growth, tissue repair, wound healing, hydration, anti-aging properties, and exfoliation.
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Identification of potential hub genes associated with recurrent miscarriage through combined transcriptomic and proteomic analysis
Get PDFRecurrent miscarriage (RM) is currently difficult to prevent and treat due to a lack of comprehensive understanding of its molecular mechanisms. The aim of this study was to identify genes potentially involved in the pathogenesis of RM and to observe their expression in the decidual tissues of RM patients. A total of 1823 differentially expressed genes (DEGs) and 148 differentially expressed proteins (DEPs) in decidual tissues between RM and control groups were identified. Subsequently, DCN, DPT, LUM, MFAP4, and ISG15 were identified from the DEGs/DEPs as RM-related hub genes through systematic bioinformatics analysis. Bioinformatics analysis of the single-cell dataset GSE214607 revealed that the expression of these five hub genes in the decidual stromal cells (DSCs) of RM patients appeared to be upregulated, while the RT-qPCR assay showed that their decidual expression levels were significantly increased in RM patients. Uterine Isg15 expression was significantly increased, whereas the uterine expression of Dcn, Dpt, Lum, and Mfap4 was decreased in LPS-induced early pregnancy loss (EPL) mice. MiR-16-5p, -21-3p, -27a-3p, and -941 were identified as potentially involved in the regulation of these five hub genes, and their decidual expression levels were significantly decreased in RM patients. The abnormally increased ISG15 expression in the decidual tissues of RM patients and uterine tissues of LPS-induced mice was validated by WB analysis. ISG15 expression was significantly reduced during the in vitro decidualization of human endometrial stromal cells (hESCs). Collectively, DCN, DPT, LUM, MFAP4, and ISG15 were identified as RM-related hub genes, and their expression in the decidual tissues of RM patients was significantly increased. The decidualization of hESCs was accompanied by reduced ISG15 expression, suggesting that increased decidual ISG15 expression might lead to EPL by disrupting the decidualization process
The association of plasma homocysteine levels with short-term mortality in sepsis patients: A meta-analysis
Get PDFThe association between plasma homocysteine (Hcy) levels and short-term mortality in sepsis patients remains unclear. This meta-analysis aimed to clarify this potential relationship. Following PRISMA 2020 and Cochrane Handbook guidelines, we conducted a comprehensive literature search in the PubMed, Embase, and Web of Science databases up to June 24, 2024. We included cohort studies that assessed the association between plasma Hcy levels and all-cause mortality in adult sepsis patients. Standardized mean differences (SMDs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model to account for potential heterogeneity. Nine cohort studies involving 771 sepsis patients were included. Overall, no significant difference in plasma Hcy levels was observed between survivors and non-survivors (SMD: -0.23, 95% CI: -0.84 to 0.37, P = 0.45), with substantial heterogeneity (I² = 86%). Subgroup analysis revealed lower plasma Hcy levels among survivors in Chinese patients (SMD: -1.56, 95% CI: -1.98 to -1.13, P < 0.001) but not in non-Asian patients. Plasma Hcy levels were not significantly associated with all-cause mortality (OR per 1-unit increment: 1.03, 95% CI: 0.95 to 1.11, P = 0.51), with notable heterogeneity (I² = 72%). However, a significant association was found in Chinese patients (OR: 1.09, 95% CI: 1.03 to 1.15, P = 0.003), but not in non-Asian patients. In conclusion, plasma Hcy levels were not generally associated with short-term mortality in sepsis patients. However, significant associations were observed in Chinese patients, suggesting potential ethnic differences that warrant further investigation
Camel milk-derived exosomes as novel nanocarriers for curcumin delivery in lung cancer
Get PDFCancer remains a leading cause of mortality, with non-small cell lung cancer (NSCLC) being a primary contributor to cancer-related deaths. Traditional treatment strategies such as chemotherapy, radiation, and hormone therapy often present challenges, including severe side effects, drug resistance, and toxicity. Recent advancements in nanotechnology aim to enhance the effectiveness of cancer therapies by targeting drugs selectively and specifically to tumor cells. Among these innovations, exosomes, or small extracellular vesicles (sEVs), have emerged as promising carriers for drug delivery due to their natural origin and ability to encapsulate both small molecules and biologics. This study explores the use of exosomes derived from camel milk in Hail, Saudi Arabia, as a vehicle for delivering curcumin (CUR), a polyphenol with known chemopreventive properties but limited bioavailability. Camel milk was processed to isolate exosomes through differential centrifugation, followed by characterization using dynamic light scattering, zeta potential measurements, and Western blot analysis to confirm exosomal markers. The encapsulation of CUR into camel milk-derived exosomes demonstrated a 20% loading efficiency as analyzed by UPLC. In vitro antiproliferative assays revealed that the exosomal formulation of CUR (ExoCUR) significantly enhanced cytotoxicity against drug-sensitive (A549) and taxol-resistant (A549TR) lung cancer cells compared to free CUR. Molecular docking studies and molecular dynamics simulations indicated that CUR has a strong binding affinity for the epidermal growth factor receptor (EGFR), comparable to the established drug gefitinib. Furthermore, CUR effectively downregulated EGFR and STAT3 expression in lung cancer cells, suggesting its potential to disrupt key signaling pathways involved in tumor progression. Our findings highlight the potential of camel milk-derived exosomes as an effective and biocompatible delivery system for CUR, offering a promising strategy to overcome the limitations of current cancer therapies and enhance the therapeutic efficacy of chemopreventive agents
PF4 inhibits ferroptosis-mediated intracerebral hemorrhage through modulating the CXCR3/AKT1/SLC7A11 signaling pathway
Get PDFFerroptosis plays a crucial role in the secondary pathophysiological damage to brain tissue surrounding hematomas after intracerebral hemorrhage (ICH). While platelet factor 4 (PF4) is known to promote regeneration following peripheral nerve injury, its role in brain tissue repair after cerebral hemorrhage remains unclear. In this study, Hemin-induced PC12 cells were treated with various inhibitors and assessed for viability, oxidative stress, and ferroptosis using a combination of assays, including CCK-8 (Cell Counting Kit-8), EdU (5-Ethynyl-2’-deoxyuridine), flow cytometry, and immunofluorescence. ICH cells were also treated with recombinant PF4 (Rm-PF4) and a CXCR3 antagonist (AMG487) to investigate the mechanism by which Rm-PF4 influences Hemin-induced PC12 cell injury and inflammation. Subsequently, ICH mouse models were established via collagenase injection. Neurological function in these mice was evaluated using the Cylinder and Corner tests. Histopathological damage to brain tissue was analyzed through HE, TUNEL, and Nissl staining, as well as immunohistochemistry, to further explore the role of Rm-PF4 in controlling neuroinflammation in vivo. Results showed that Rm-PF4 inhibited Hemin-mediated ferroptosis-induced PC12 cell damage and inflammation by activating the CXCR3/AKT1/SLC7A11 signaling pathway. Blocking the CXCR3/AKT1/SLC7A11 pathway partially reversed PF4\u27s protective effects on Hemin-induced PC12 cells.In ICH mice, pro-inflammatory marker CD16 (3rd day) and anti-inflammatory marker Arg1 (7th day) were significantly decreased and increased, respectively (p<0.05). IL-6, TNF-α, and IL-1β levels were down-regulated in brain tissues after Rm-PF4 injection, which was significantly reversed by AMG487. PF4 inhibits ferroptosis after ICH reduced PC12 cell damage and the inflammatory response via activating the CXCR3/AKT1/SLC7A11 pathway
Surgical approach and recurrence risk in struma ovarii: A retrospective and systematic analysis
Get PDFStruma ovarii (SO) represents a rare subset of ovarian germ cell tumors, with approximately 5% transforming into malignant SO (MSO). This study retrospectively analyzed clinical data from 23 SO patients treated at the Cancer Hospital of the Chinese Academy of Medical Sciences between January 2013 and December 2023, including 17 benign SO and 6 MSO cases. Additionally, a systematic review of 164 cases of MSO confined to the ovary, reported in the literature from 1946 to 2024, was conducted. Data on pathological type, treatment, and prognosis were extracted, and univariate and multivariate Cox regression analyses were performed to identify risk factors for recurrence in stage I MSO. The median age at diagnosis was higher for benign SO compared to MSO (58 vs. 42.5 years), with 70.6% of patients being postmenopausal. Benign SO commonly presented with abdominal distension or mass, with more than half having ascites, while MSO patients were asymptomatic and lacked ascites. Cox regression analyses revealed that ovarian cystectomy was adversely associated with recurrence risk in stage I MSO, likely due to surgically induced capsular rent and potential tumor spillage. Significantly lower recurrence risks were observed in patients who underwent unilateral or bilateral salpingo-oophorectomy (HR = 0.36, P = 0.019; HR = 0.19, P = 0.004, respectively). This study highlights the importance of the surgical approach in the management of stage I MSO. A thorough preoperative discussion of the benefits and risks of different surgical approaches is recommended for patients desiring fertility preservation. Postoperative adjuvant therapy has not been shown to have a significant impact on prognosis. For the treatment of recurrent MSO, selecting appropriate surgical and adjuvant therapeutic strategies is essential to improve the long-term prognosis of MSO patients
PF4 regulates neuronal ferroptosis in cerebral hemorrhage through CXCR3/PI3K/AKT/Nrf2 pathway
Get PDFInhibiting ferroptosis represents a promising strategy for managing neuronal injury caused by intracerebral hemorrhage (ICH). Platelet factor 4 (PF4), a chemokine with diverse biological functions, has an unclear role in ICH and its impact on neuronal ferroptosis. To investigate this, a hemin-induced injury model was established in PC12 cells in vitro, and an ICH model was created in vivo using IV collagenase injection. Hemin-treated PC12 cells were co-cultured with recombinant mouse PF4 (Rm-PF4) protein to examine the effects of PF4 on ferroptosis. Additionally, Rm-PF4 was administered intraperitoneally to ICH mice, and its influence on neurological dysfunction, brain edema, and neuronal ferroptosis was evaluated. Western blot analysis was employed to assess PF4 levels, CXCR3/phosphatidylinositol 3-kinase (PI3K)/AKT/nuclear factor erythroid-2-related factor 2 (Nrf2) pathway activation, and ferroptosis-related protein expression. PF4 levels were found to be reduced in both perihematomal brain tissues of ICH mice and hemin-treated PC12 cells. Treatment with Rm-PF4 decreased ferrous ion, malondialdehyde (MDA), and reactive oxygen species (ROS) levels, effectively inhibiting ferroptosis in PC12 cells. Furthermore, Rm-PF4 administration alleviated neurological dysfunction, neuronal damage, and brain edema while suppressing neuronal ferroptosis in ICH mice. Mechanistically, Rm-PF4 activated the CXCR3/PI3K/AKT/Nrf2 pathway, and this protective effect was diminished by a CXCR3 antagonist in both ICH mice and hemin-treated PC12 cells. In conclusion, PF4 mitigates ICH-induced neuronal ferroptosis in mouse models and PC12 cells by activating the CXCR3/PI3K/AKT/Nrf2 pathway