Bosnian Journal of Basic Medical Sciences (BJBMS)
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Call for emergency action to limit global temperature increases, restore biodiversity, and protect health
Get PDFThe UN General Assembly in September 2021 will bring countries together at a critical time for marshalling collective action to tackle the global environmental crisis. They will meet again at the biodiversity summit in Kunming, China, and the climate conference (COP26) in Glasgow, UK. Ahead of these pivotal meetings, we—the editors of health journals worldwide—call for urgent action to keep average global temperature increases below 1.5°C, halt the destruction of nature, and protect health.
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Inflammatory cells in the ascending aortic aneurysm in patients with type 2 diabetes versus patients with hypertension
Get PDFAortic aneurysms occur relatively frequently in the ascending thoracic aorta, but are rarely seen in patients with type 2 diabetes. Our aim was to evaluate inflammatory cell infiltration in the ascending aortic aneurysm wall in patients with diabetes without arterial hypertension (DM2 group, N=6) versus hypertensive non-diabetic patients (AH group, N=34). For histologic analysis, the sections were stained with hematoxylin-eosin and Movat pentachrome. The immunohistochemical staining was used to analyze the infiltration of pro-inflammatory (CD68) and anti-inflammatory macrophages (CD163), T helper (CD4) and T killer cells (CD8), and B (CD79a) and plasma cells (CD138) in all three layers of aneurysms of both groups. The statistical significance of the differences between groups was evaluated by ANOVA and the Welch test.
In comparison to the AH group, the DM2 group developed less severe infiltration of pro-inflammatory macrophages (P=0.004) and B cells (P=0.025) in the tunica intima, and tunica media (P=0.049, P=0.007, respectively), and fewer plasma cells in the tunica media (P=0.024) and tunica adventitia (P=0.017). We found no significant differences in the number of T helper, T killer cells, and anti-inflammatory macrophages and in the amount of collagen and elastic fibers, ground substance, and smooth muscle cells in all three layers of the vessel wall. Except in tunica adventitia of DM2 group, there were more collagen fibers overall (P=0.025).
Thus, we conclude that the histological structure of the aneurysm in diabetics without hypertension is almost the same as in hypertensive patients without diabetes. Diabetics had significantly less inflammatory infiltration in all three layers of the vessel wall, and more collagen fibers in tunica adventitia
Whole-exome sequencing reveals rare genetic variations in ovarian granulosa cell tumor
Get PDFOvarian granulosa cell tumor (OGCT) is a rare ovarian tumor that accounts for about 2-5% of all ovarian tumors. Despite the low grade of ovarian tumors, high and late recurrences are common in OGCT patients. Even though this tumor usually occurs in adult women with high estrogen levels, the cause of OGCT is still unknown. To screen genetic variants associated with OGCT, we collected normal and matched-tumor formalin-fixed paraffin-embedded (FFPE) from 11 OGCT patients and performed whole-exome sequencing (WES) using Illumina NovaSeq 6000. A total of 1,067,219 single nucleotide polymorphisms (SNPs) and 162,155 insertions/deletions (indels) were identified from 11 pairs of samples. Of these, we identified 44 tumor-specific SNPs in 22 genes and four tumor-specific indels in one gene that were common to 11 patients. We used three cancer databases (TCGA, COSMIC, and ICGC) to investigate genes associated with ovarian cancers. Nine genes (SEC22B, FEZ2, ANKRD36B, GYPA, MUC3A, PRSS3, NUTM2A, OR8U1, and KRTAP10-6) associated with ovarian cancers were found in all three databases. In addition, we identified seven rare variants with MAF ≤ 0.05 in two genes (PRSS3 and MUC3A). Of seven rare variants, five variants in MUC3A are potentially pathogenic. Furthermore, we conducted gene enrichment analysis of tumor-specific 417 genes in SNPs and 106 genes in indels using cytoscape and metascape. In GO analysis, these genes were highly enriched in “selective autophagy”, and “regulation of anoikis”. Taken together, we suggest that MUC3A is implicated in OGCT development, and MUC3A could be used as a potential biomarker for OGCT diagnosis
First-line treatment of patients with HER2-positive metastatic gastric and gastroesophageal junction cancer
Get PDFFluoropyrimidine+cisplatin/oxaliplatin+trastuzumab therapy is recommended for the first-line treatment of HER2-positive metastatic gastric adenocarcinoma. However, there is no comprehensive study on which platinum-based treatment should be preferred. This study aimed to compare the treatment response and survival characteristics of patients with HER2-positive metastatic gastric or gastroesophageal junction (GEJ) cancer who received fluorouracil, oxaliplatin, and leucovorin (mFOLFOX)+trastuzumab or cisplatin and fluorouracil (CF)+trastuzumab as first-line therapy. It was a multicenter, retrospective study of the Turkish Oncology Group, which included 243 patients from 21 oncology centers. There were 113 patients in the mFOLFOX+trastuzumab arm and 130 patients in the CF+trastuzumab arm. The median age was 62 years in the mFOLFOX+trastuzumab arm and 61 years in the CF+trastuzumab arm (P = 0.495). 81.4% of patients in the mFOLFOX+trastuzumab arm and 83.1% in the CF+trastuzumab arm had gastric tumor localization (P = 0.735). The median progression-free survival (PFS) was significantly higher in the mFOLFOX+trastuzumab arm (9.4 months vs. 7.3 months, P = 0.024). The median overall survival (OS) was similar in both groups (18.4 months vs. 15.1 months, P = 0.640). Maintenance trastuzumab was continued after chemotherapy in 101 patients. In this subgroup, the median OS was 23.3 months and the median PFS was 13.3 months. In conclusion, mFOLFOX+trastuzumab is similar to CF+trastuzumab in terms of the median OS, but it is more effective in terms of the median PFS in the first-line treatment of HER2-positive metastatic gastric and GEJ cancer. The choice of treatment should be made by considering the prominent toxicity findings of the chemotherapy regimens
ORM 1 as a biomarker of increased vascular invasion and decreased sorafenib sensitivity in hepatocellular carcinoma
Get PDFThis study aimed to clarify the role of Orosomucoid 1 (ORM1) in the development and therapy resistance in hepatocellular carcinoma (HCC). The mRNA expression level of ORM1 was analyzed via integrative analysis of Gene Express Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets. The protein expression level of ORM1 in our cohort was determined using immunohistochemistry. Correlation analysis was used to investigate the relationship between ORM1 expression and clinical parameters. The Cell Counting Kit-8 assay was used to clarify the role of ORM1 in HCC malignant behaviors, including cell growth and sorafenib sensitivity, in vitro. The results indicated that ORM1 was significantly downregulated in the hepatic cancer cells compared to that in the non-cancerous cells. However, it was upregulated in microvascular invasion samples, especially in the cancer embolus compared to that in the surrounding tumor cells. Though Kaplan-Meier analysis did not show an association of ORM1 expression with the overall survival rates of HCC patients, univariate analysis indicated that ORM1 expression was highly correlated with tumor grade and stage. An in vitro assay also revealed that downregulation of ORM1 led to the suppression of tumor growth and enhancement of sorafenib sensitivity without epithelial-to-mesenchymal transition (EMT) alteration, which was consistent with our bioinformatic analysis. Hence, ORM1 played a key role in HCC tumorigenesis and may serve as a potential target for the development of therapeutics against HCC in the future
Prognostic significance of HDL-C on long-term mortality in patients with COVID-19 pneumonia in the Turkish population: A potential mechanism for population differences
Get PDFCoronavirus disease 2019 (COVID-19) is diagnosed by the evidence of the presence of multiple phenotypes, including thrombosis, inflammation, and alveolar and myocardial damage, which can cause severe illness and mortality. High-density lipoprotein cholesterol (HDL-C) has pleiotropic properties, including anti-inflammatory, anti-infectious, antithrombotic, and endothelial cell protective effects. The aim of this study was to investigate the HDL-C levels and one-year mortality after the first wave of patients with COVID-19 were hospitalized. Data from 101 patients with COVID-19 were collected for this single-center retrospective study. Lipid parameters were collected on the admission. The relationship between lipid parameters and long-term mortality was investigated. The mean age of the non-survivor group (n = 38) was 68.8 ± 14.1 years, and 55% were male. The HDL-C levels were significantly lower in the non-survivors group compared with the survivors (26.9 ± 9.5 vs 36.8 ± 12.8 mg/dl, respectively p < 0.001). Multivariate regression analysis determined that age, C-reactive protein, D-dimer, hypertension, and HDL-C as independent predictors for the development of COVID-19 mortality. HDL-C levels <30.5 mg/dl had 71% sensitivity and 68% specificity to predict one-year mortality after COVID-19. The findings of this study showed that HDL-C is a predictor of one-year mortality in Turkish patients with COVID-19. COVID-19 is associated with decreased lipid levels, and it is an indicator of the inflammatory burden and increased mortality rate. The consequences of long-term metabolic dysregulations in patients that have recovered from COVID-19 still need to be understood
Protocatechuic acid as an inhibitor of the JNK/CXCL1/CXCR2 pathway relieves neuropathic pain in CCI rats
No full textEmerging evidence has shown that protocatechuic acid (PCA) has antioxidant and anti-inflammatory effects. It can alleviate the injury of sciatic nerve, while the mechanism of its therapeutic effect on neuralgia remains unknown . In vivo, chromium bowel ligation was used to establish a chronic constriction injury (CCI) rat model to induce sciatic nerve pain, then two doses of PCA were used to treat CCI rats. In vitro, 10 ng/mL TNF-α was used to stimulate glial satellite cells derived from the dorsal root ganglia (DRG) L4-L6 of the sciatic nerve to simulate sciatic nerve pain. PCA relieved mechanical allodynia and thermal hyperalgesia in CCI rats. CCK-8 assay revealed that PCA inhibited the proliferation of glial satellite cells induced by TNF-α. Moreover, ELISA demonstrated that PCA could improve the inflammatory response of rats caused by CCI and cells induced by TNF-α. Next, RT-qPCR and Western blot assays testified that PCA blocked the c-Jun N-terminal kinase/the chemokine ligand 1/CXC chemokine receptor 2 (JNK/CXCL1/CXCR2) pathway by inhibiting CXCL1 levels in cells induced by TNF-α and DRG of CCI rats. In conclusion, PCA can alleviate neuropathic pain of CCI rats, improve oxidative stress by inhibiting the JNK/CXCL1/CXCR2 signaling pathway, which provides a new perspective for the treatment of neuropathic pain caused by CCI
A novel ferroptosis-related gene signature can predict prognosis and influence immune microenvironment in acute myeloid leukemia
Get PDFAcute myeloid leukemia (AML) is a highly heterogeneous hematopoietic malignancy that strongly correlates with poor clinical outcomes. Ferroptosis is an iron-dependent, non-apoptotic form of regulated cell death which plays an important role in various human cancers. Nevertheless, the prognostic significance and functions of ferroptosis-related genes (FRGs) in AML have not received sufficient attention. The aim of this article was to evaluate the association between FRGs levels and AML prognosis using publicly available RNA-sequencing datasets. The univariate Cox regression analysis identified 20 FRGs that correlate with patient overall survival. The LASSO Cox regression model was used to construct a prognostic 12-gene risk model using a TCGA cohort, and internal and external validation proved the signature efficient. The 12-FRGs signature was then used to assign patients into high- and low-risk groups, with the former exhibiting markedly reduced overall survival, compared to the low-risk group. ROC curve analysis verified the predictive ability of the risk model. Functional analysis showed that immune status and drug sensitivity differed between the 2 risk groups. In summary, FRGs is a promising candidate biomarker and therapeutic target for AML
Tumor protein P63 Regulated 1 contributes to inflammation and cell proliferation of cystitis glandularis through regulating the NF-кB/cyclooxygenase-2/prostaglandin E2 axis
Get PDFCystitis glandularis is characterized by chronic inflammation and hyperproliferation of bladder mucosa, and contributes to progression of bladder adenocarcinoma. TPRG1 (Tumor Protein P63 Regulated 1) is related to cellular inflammatory response, and dysregulation of TPRG1 in tumor tissues is associated with tumor early recurrence. The effect of TPRG1 on cystitis glandularis was investigated in this study. Firstly, bladder specimen were isolated from patients with cystitis glandularis and E. coli-induced cystitis rat. Expression of TPRG1 was found to be up-regulated in the bladder specimen. Moreover, adeno-associated virus (AAV)-mediated silence of TPRG1 was delivered into rat, and data from hematoxylin and eosin (H and E) staining showed that injection with AAV-shTPRG1 ameliorated E. coli-induced histological changes in bladder tissues of rats, and suppressed the inflammatory response. Secondly, TPRG1 was also increased in primary cystitis glandularis cells. Knockdown of TPRG1 decreased cell proliferation of primary cystitis glandularis cells, and suppressed the migration. Thirdly, cyclooxygenase-2 (COX-2) was up-regulated in the bladder specimen isolated from patients with cystitis glandularis and E. coli-induced cystitis rat. Injection with AAV-shTPRG1 reduced protein expression of COX-2, p65 and prostaglandin E2 (PGE2) in the bladder specimen. Lastly, interference of COX-2 attenuated TPRG1 over-expression-induced increase of cell proliferation and migration in the primary cystitis glandularis cells. In conclusion, TPRG1 promoted inflammation and cell proliferation of cystitis glandularis through activation of NF-кB/COX2/PGE2 axis
The association between NOTCH3 expression and the clinical outcome in the urothelial bladder cancer patients
Get PDFDisrupted NOTCH activity is a driving event in urothelial bladder cancer (UBC). After activation by hypoxia, the NOTCH3 receptor participates in tumor cell proliferation, acquisition of the epithelial-mesenchymal transition phenotype, and angiogenesis. The aim was to analyze the association of NOTCH3 expression with histopathological and clinical parameters, and to determine its predictive impact on the clinical outcome in UBC patients. The present research included 614 UBC samples incorporated in paraffin tissue microarrays, evaluated by immunohistochemistry for NOTCH3 expression. The accrual period was four years, while the follow-up period was two years. The membranous expression was semi-quantified (0-3), and the mean degree was 1.81±0.94. Criteria for semi-quantification the NOTCH3 expression were the intensity of the staining and the percentage of positive cells. The samples with negative (0) and weak (1) NOTCH3 immunohistochemical (IHC) score were considered negative, while the samples that showed moderate (2) and strong (3) expression were considered positive. Higher degree of positivity was associated with higher risk of cancer-specific mortality (p<0.001). Independent predictors for cancer-specific mortality were NOTCH3 expression and high stage (p<0.001). NOTCH3 expression was not a statistically significant predictor of recurrence-free survival (p=0.816). This study indicated that NOTCH3 is a predictor of poor outcome, suggesting that the NOTCH3 could be potentially reliable IHC marker for selecting the UBC patients that would require more intensive follow-up, especially if they diagnosed in higher stage, with divergent differentiation in pathological report, and without recurrences which would lead them to more frequent medical assessments