Bosnian journal of basic medical sciences最新文献

This study aimed to investigate the programmed cell death-ligand 1 (PD-L1) expression in cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) and its relationship with prognostic factors in tumors that are not in the head and neck region and are therefore relatively less exposed to the sun. This retrospective cross-sectional study included 25 invasive cSCC and 42 BCC cases with a diameter ≥ 2 cm located outside the head and neck region from 2010 to 2018. The biopsy samples were examined based on the membranous PD-L1 (22C3 clone) staining. Staining results were scored as follows: 0, no staining (negative); 1, < 10% PD-L1 positivity of tumor cells; and 2, ≥ 10% PD-L1 positivity of tumor cells. PD-L1 positivity was not seen in any BCC cases, whereas 11 (44%) of cSCC cases were PD-L1 positive. No significant relationship was observed between PD-L1 expression and prognostic parameters, including tumor diameter, tumor depth, and lymphovascular or perineural invasion in the cSCC group. PD-L1 expression was not associated with prognostic factors in the early stages of BCC and SCC located outside the head and neck region. Therefore, investigating the PD-L1 expression seems to be more relevant in patients with advanced-stage disease.

Phospholipase C epsilon 1 (PLCE1) is involved in the pathogenesis of many cancers. However, the biological role of PLCE1 in osteosarcoma (OS) is still poorly understood. The prognostic survival analysis was performed on the PLCE1gene in the TARGET data set and the differential expression of PLCE1 in OS tissue and normal bone tissue on the tissue chip was detected by immunohistochemistry. Spearman's rank correlation coefficient analysis was implemented to explore the relationship between PLCE1 and immune genes. Finally, PLCE1 was silenced to explore its biological function in OS cells. The results of tissue chip immunohistochemistry showed that PLCE1 expression in OS tissue was higher than in normal bone tissue. The survival curve of PLCE1 and its corresponding receiver operating characteristic curve (ROC) showed that PLCE1 had a significant effect on the survival status of patients with OS and that the prognosis of patients with high PLCE1 expression was relatively poor. Spearman's rank correlation coefficient analysis and qRT-PCR assays found that PLCE1 may promote immune escape from OS via CD70-CD27 signaling pathway. Silencing of PLCE1 causes the following biological behaviors of OS cells: it promotes apoptosis, inhibits proliferation of OS cells, and inhibits the ability of cell migration and invasion. PLCE1 is a poor prognostic marker and a potential key factor affecting the immune status of the OS tumor microenvironment.

Coronavirus 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.

Camptothecin (CPT) has attracted much attention due to its potent antitumor activities. However, the undesirable physicochemical properties, including poor water-solubility, unstable lactone ring and severe adverse effects limit its further application. In this study, two water-soluble prodrugs, CPT-lysine (CPTK) and CPT-arginine (CPTR), were designed and synthesized by conjugating lysine or arginine with CPT, improving its solubility, pharmacokinetic properties and tumor penetration. Importantly, the introduction of arginine into CPTR contributed to the mitochondria-specific delivery, which increased mitochondrial reactive oxygen species (ROS) generation, induced mitochondria dysfunction and enhanced cell apoptosis and in vivo anti-cancer effect. This strategy is believed to hold great potential for organelle-specific synergistic anti-tumor therapy.

Coronary artery disease (CAD) is uncommon in young adult patients. However, these patients have different risk factor profiles and high-risk coronary plaques are more common. The aim of this study was to examine the relations between the coronary plaque burden, plaque composition, serum non-high-density lipoprotein cholesterol (non-HDL-C) levels, and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio in young adults. We analyzed a total of 551 patients under age 45 who had undergone coronary computed tomography angiography (CCTA). Coronary plaque characteristics were analyzed using CCTA. Multivariate linear regression analysis was used to assess the predictors of non-calcified plaque (NCB) and calcified plaque (CB) burdens. Serum non-HDL-C levels and TG/HDL-C ratio were higher in the coronary atherosclerosis patient group. Serum non-HDL-C levels and the TG/HDL-C ratio were higher in the obstructive CAD patient group. The plaque burden was positively correlated with non-HDL-C (r = 0.30; p < 0.001), and TG/HDL-C ratio (r = 0.18; p < 0.001).  NCB was positively correlated with age, gender, smoking status, fasting blood glucose, total cholesterol, low-density lipoprotein cholesterol, serum triglycerides, hbA1c, non-HDL-C, and TG/HDL-C ratio. Non-HDL-C (β coefficient = 0.13; p = 0.023) and TG/HDL-C ratio (β = 0.10;  p = 0.042) were independent predictors of NCB. Serum non-HDL-C levels and TG/HDL-C were significantly associated with the presence and burden of coronary plaques. Serum non-HDL-C and TG/HDL-C ratios were independently associated with NCB, suggesting their use as easy-to-compute markers for identifying high-risk groups in young adults.

Coronavirus disease 2019 (COVID-19) was declared a pandemic and has spread around the globe, unsparingly affecting vulnerable populations. Effective prevention measures for pregnant women, who are particularly affected, include early identification of those patients at risk of developing in-hospital complications, and the continuous improvement of maternal-fetal treatment strategies to ensure the efficient use of health resources. The objective of our retrospective study was to determine which patient biomarkers on hospital admission correlate with disease severity as measured by disease course classification, the need for oxygen supplementation and higher demand for oxygen, the need for mechanical ventilation, intensive care unit admission, and length of hospital stay. Analysis of 52 PCR SARS-CoV-2 positive pregnant women revealed that the median date of hospital admission was the 30th gestational week, with dyspnoea, cough, and fever as the leading symptoms. The presence of diabetes and hypertension predisposed pregnant women to the severe course of illness. Lung involvement shown by CT scans on admission correlated with the greater clinical severity. The main laboratory predictors of disease progression were lymphocytopenia, hypocalcemia, low total cholesterol, low total protein levels, and high serum levels of C-reactive protein, ferritin, interleukin-6, glucose, lactate dehydrogenase, procalcitonin, and troponin I. Further research with a larger cohort of pregnant women is needed to determine the utility of these results for everyday practice.

This 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.

Ovarian tumor protease deubiquitinase 5 (OTUD5) has been discussed as a regulator of cancer development. Herein, the current study set out to explore the molecular mechanism of OTUD5 in non-small cell lung cancer (NSCLC) cell proliferation, invasion, and migration. Firstly, the expression patterns of OTUD5, phosphatase and tensin homolog (PTEN), as well as microRNA (miR)-652-3p in cells were detected by qRT-PCR and Western blot. Cell viability, migration, and invasion were assessed with the help of cell-counting kit-8 and Transwell assays, in addition to the measurement of the ubiquitination and protein levels of PTEN. The binding relations between OTUD5 and PTEN, and miR-652-3p and OTUD5 were testified by co-immunoprecipitation or dual-luciferase assays. Cells were further treated with GSK2643943A (inhibitor of deubiquitinase) or miR-652-3p-inhibitor to explore the role of PTEN ubiquitination and miR-652-3p in NSCLC cells. OTUD5 and PTEN were both poorly-expressed, and miR-652-3p was highly-expressed in NSCLC cells. On the other hand, over-expression of OTUD5 suppressed NSCLC cell proliferation, invasion, and migration. OTUD5 deubiquitinated and stabilized PTEN, and miR-652-3p targeted and inhibited OTUD5 expression. Augmenting the ubiquitination levels of PTEN promoted NSCLC cell growth, whereas miR-652-3p inhibition promoted the tumor-suppressing effects of the OTUD5/ PTEN axis in NSCLC. Altogether, our findings highlighted that miR-652-3p restrained the role of OTUD5 in deubiquitinating PTEN to improve PTEN protein level, thereby promoting NSCLC cell proliferation, invasion, and migration.

The gut microbiome and its metabolism may provide crucial insight into the cause of iron deficiency anemia (IDA) in pregnant women. This study aimed to investigate the effect of the gut microbiome and its related metabolites on pregnant women with iron deficiency (ID) and IDA. Maternal cubital venous blood and stool samples were collected from healthy control pregnant women (HC, non-anemic, n=10), pregnant women with ID non-anemia (ID, n=10), and IDA (n=10). All groups were subjected to fecal metagenomics and metabolomics. The composition and function of the gut microbiome were then compared in pregnant women with ID and IDA with HC after excluding the possibility of inflammation and insufficient iron absorption capacity. Whole-genome shotgun libraries were prepared by quantifying metagenomic DNA samples with Quant-iT PicoGreen dsDNA Assay. The levels of 41 microbial species, including 21 Streptococci and ten metabolites (catechol), which could serve as siderophores, were increased. In contrast, 3 Bacteroides and six metabolites were decreased in pregnant women with IDA (p<0.05). The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the bio-pathways, including biosynthesis of siderophore group non-ribosomal peptides (p<0.01), ABC transporters (p<0.05) and membrane transport of the gut microbiota (p<0.01) in IDA patients were expressed differently compared with HC. Correlation analysis also indicates that these increased bacteria formed strong co-occurring relationships with metabolites in the occurrence and development of IDA in pregnant women. The current study identified that streptococci and catechol (fecal metabolite) were significantly increased in pregnant women with IDA. Therefore, adjusting the intestinal homeostasis using long-term living and eating habits on oral Streptococcus in pregnant women with IDA before iron supplementation may be more conducive to iron supplementation, thus providing novel therapies for IDA.

This systematic review and meta-analysis aimed to assess the extent of clinical attachment loss (CAL) as a clinical parameter in the efficacy of antimicrobial photodynamic therapy (aPDT) in non-surgical management of stage II-IV grade C molar-incisor pattern Periodontitis. This review protocol was conducted in accordance with PRISMA statements and is registered in PROSPERO (CRD42022321211). An electronic and manual search was conducted for relevant articles comparing the efficacy of aPDT versus scaling and root planning (SRP) alone or with amoxicillin/metronidazole (AMX/MET) published up until December 2021. The mean clinical attachment loss (CAL), probing depth (PD) reduction, and bleeding on probing (BOP) with a 95% confidence interval (CI) were pooled and compared between the two groups with CAL < and > 7 mm using a random-effect model after 3 and 6 months. To assess the heterogeneity of the findings, the I2 test was applied and Publication bias was evaluated by visual examination of the funnel plot symmetry. Analysis of 9 studies indicated a significant difference in clinical attachment gain in patients with CAL > 7 mm between the aPDT group and the SRP alone (mean difference=0.92, 95% CI=0.01-1.84, P=0.05) and SRP + AMX/MET (mean difference=0.91, 95% CI=-0.14-1.68, P=0.02) control groups. However, this difference was not significant in patients with CAL < 7 mm. Despite the limitations of the included studies, aPDT can be suggested for the improvement of clinical parameters in grade C molar-incisor pattern Periodontitis with CAL > 7 mm. However, its application in milder cases requires further investigation.