Bosnian Journal of Basic Medical Sciences (BJBMS)
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Retracted: MicroRNA-573 inhibits cell proliferation, migration and invasion and is downregulated by PICSAR in cutaneous squamous cell carcinoma
No full textThis article has been retracted: https://doi.org/10.17305/bjbms.2022.8232
Retraction: "MicroRNA-573 functions as a tumor suppressor and is downregulated by PICSAR in cutaneous squamous cell carcinoma" by Yanhua Wang, Shengjian Tang and Jianping Lv, Bosn J Basic Med Sci. 2022 Apr 1;22(2):229-237. (doi: 10.17305/bjbms.2021.6301). This article has been withdrawn at the request of the authors. The authors voluntarily requested the retraction of this paper. The additional experiments they conducted could not confirm the role of microRNA-573 functions in cutaneous squamous cell carcinoma reported in the BJBMS article (vol. 22(2):229-237). All authors signed and agreed on the retraction of the article. The Bosnian Journal of Basic Medical Sciences apologizes to the readers and scientific community for the inconveniences caused by this retraction
Altered fecal microbial and metabolic profile reveals potential mechanisms underlying iron deficiency anemia in pregnant women in China
Get PDFThe 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
The α7 nicotinic acetylcholine receptor agonist PNU-282987 ameliorates sepsis-induced acute kidney injury through CD4+CD25+ regulatory T cells in rats
Get PDFThe ameliorative effects of α7 nicotinic acetylcholine receptor (α7nAChR) agonists have been demonstrated in acute kidney injury (AKI) caused by multiple stimulations. However, the ameliorative effect of α7nAChR on sepsis-induced acute kidney injury (SAKI) in the cecal ligation and puncture (CLP) model is unclear. Previous studies have demonstrated that α7nAChR is highly expressed on the surface of CD4+CD25+ regulatory T cells (Tregs). However, the role of Tregs in SAKI is unclear. We hypothesized that Tregs might play a role in the ameliorative effect of α7nAChR on SAKI. Hence, in this study, we determined the effects of PNU-282987 (a selective α7nAchR agonist) on SAKI and evaluated whether PNU-282987 would attenuate SAKI via regulating Tregs. Our study showed that immediate administration of PNU-282987 after CLP surgery in rats improved renal function, reduced levels of systemic inflammatory factors (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), etc.), inflammatory cell infiltration and tubular apoptosis in renal tissues, and increased forkhead/winged helix transcription factor p3 (Foxp3) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression indicating activated Tregs. Moreover, in in vitro experiments, isolated Tregs co-cultured with PNU-282987 also displayed enhanced expression of CTLA-4 and Foxp3. Furthermore, Tregs were co-cultured with PNU-282987 for 24 hours and then reinfused into rats through the tail vein immediately after CLP surgery, and a significant renal protective effect was observed 24 hours postoperatively. These results demonstrate that PNU-282987 exerts its renal protective effects on SAKI through activation of Tregs
Predictors of COVID-19 severity among pregnant patients
Get PDFCoronavirus 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
The prognostic value of MKL1 in predicting breast cancer immune infiltrates and chemosensitivity
Get PDFMegakaryocytic leukemia 1 (MKL1) acts as a transcription factor in the regulation of the immune system and is associated with cancer biology. However, its function in the infiltrating immune cells in breast cancer has not been explored. Our study aimed to analyze the expression of MKL1 in The Cancer Genome Atlas (TCGA) breast cancer dataset. The aim of this study was to evaluate the correlations between MKL1 expression, infiltrating immune cells, and immune control genes. Enriched signaling pathways and drug sensitivity analyses were also performed. Our results indicate that high MKL1 expression could predict better survival in breast cancer patients. MKL1 expression was associated with the expression and function of different immune cells, including T cells, B cells, natural killer (NK) cells, macrophages, neutrophils and dendritic cells (DCs). The chromatin modifying enzymes, cellular senescence, epigenetic regulation of gene expression, estrogen-dependent gene expression, and chromosome maintenance were differentially enriched in MKL1 low expression phenotype. Patients in the high MKL1 expression group showed sensitivity to paclitaxel, while those in the low expression group showed potential sensitivity for cisplatin and docetaxel. In conclusion, MKL1 might act as a potential biomarker of prognostic value for immune infiltration and drug sensitivity in breast cancer
Attributes of intestinal microbiota composition and their correlation with clinical primary non-response to anti-TNF-α agents in inflammatory bowel disease patients
Get PDFThe largest microbial aggregation in the human body exists in the gastrointestinal tract. The microbiota in the host gastrointestinal tract comprises a diverse ecosystem, and the intestinal microbiota plays a vital role in maintaining gut homeostasis. This study aims to examine whether the gut microbiota influences unresponsiveness to anti-TNF-α treatments in primary nonresponder patients, and consequently identify the responsible microbes as biomarkers of unresponsiveness. Stool samples were collected from a cohort of patients with an established diagnosis of IBD, either ulcerative colitis (UC) or Crohn’s disease (CD), following completion of the induction phase of anti TNF therapy. 16S rRNA sequencing analysis was used to examine the pattern of microbiota communities in fecal samples. The quality and quantity of fecal microbiota were compared in responder and primary nonresponder IBD patients following anti-TNF-α therapy. As per our hypothesis, a difference in gut microbiome composition between the two patient subgroups was observed. A decreased abundance of short-chain fatty acid (SCFA)-producing bacteria, including Anaerostipes, Coprococcus, Lachnospira, Roseburia, and Ruminococcus, was detected in non-responsive patients, which was the hallmark of dysbiosis. Biomarkers of dysbiosis that were identified as predictors of clinical nonresponse, included Klebsiella, Eubacteriaceae, RF32, Bifidobacterium_animalis, and Muribaculaceae—previously known as S24-7. Signature biomarkers showed dramatic alteration in the composition of gut microbiota in patients who demonstrated primary nonresponse to anti-TNF-α agents. Dysbiosis, with features including a dropped biodiversity, augmentation in opportunistic pathogenic microbiota, and a lack of SCFA-producing bacteria, is a prominent feature of the microbiome of primary nonresponders to anti-TNF-α therapy
Global DNA methylation and chondrogenesis of rat limb buds in a three-dimensional organ culture system
Get PDFAlthough DNA methylation epigenetically regulates development, data on global DNA methylation during development of limb buds (LBs) are scarce. We aimed to investigate the global DNA methylation developmental dynamics in rat LBs cultivated in a serum-supplemented (SS) and in chemically defined serum- and protein-free (SF) three-dimensional organ culture. Fischer rat front- and hind-LBs at 13th and 14th gestation days (GD) were cultivated at the air-liquid interface in Eagle\u27s Minimal Essential Medium (MEM) or MEM with 50% rat serum for 14 days, as SF and SS conditions, respectively. The methylation of repetitive DNA sequences (SINE rat ID elements) was assessed by pyrosequencing. Development was evaluated by light microscopy and extracellular matrix glycosaminoglycans staining by Safranin O. Upon isolation, weak Safranin O staining was present only in more developed GD14 front-LBs. Chondrogenesis proceeded well in all cultures towards day 14, except in the SF-cultivated GD13 hind-LBs, where Safranin O staining was almost absent on day 3. That was associated with a higher percentage of DNA methylation than in SF-cultivated GD13 front-LBs on day three. In SF-cultivated front-LBs, a significant methylation increase between the 3rd and 14th day was detected. In SS-cultivated GD13 front-LBs, methylation increased significantly on day three and then decreased. In older GD14 SS-cultivated LBs, there was no increase of DNA methylation, but they were significantly hypomethylated relative to the SS-cultivated GD13 at days 3 and 14. We confirmed that the global DNA methylation increase is associated with less developed limb organ primordia that strive towards differentiation in vitro, which is of importance for regenerative medicine strategies
Novel insights into the pathological development of dyslipidemia in patients with hypothyroidism
Get PDFAccording to the previous reports, hypothyroidism has been shown to be strongly correlated with increased circulating concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). Notably, thyroid hormones are confirmed to modulate the production, clearance, and transformation process of cholesterol within circulation of mammals. Moreover, emerging evidence suggests that the thyroid-stimulating hormone could also participate in modulating serum lipid metabolism independently of thyroid hormones, which further induces the pathological development of dyslipidemia. However, the underlying mechanism is still not fully elucidated. Recently, several research studies have demonstrated that the pathogenic progression of hypothyroidism-related dyslipidemia might be correlated with the decreased serum concentrations of thyroid hormones and the increased serum concentrations of thyroid-stimulating hormones. Thus, this indicates that hypothyroidism could induce dyslipidemia and its related cardio-metabolic disorder diseases. In addition, several newly identified modulatory biomarkers, such as proprotein convertase subtilisin/kexin type 9 (PCSK9), angiopoietin-like protein (ANGPTLs), and fibroblast growth factors (FGFs), might play an important role in the regulation of dyslipidemia induced by hypothyroidism. Furthermore, under the status of hypothyroidism, significantly dysfunctional HDL particles could also be observed. In the current review, we summarized the recent knowledge of the relationship between the development of hypothyroidism with dyslipidemia. We also discussed the updated understanding of the mechanisms whereby hypothyroidism induces the risk and the development of dyslipidemia and cardio-metabolic diseases. 
Mechanism of OTUD5 in non‐small cell lung cancer cell proliferation, invasion, and migration
Get PDFOvarian 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
Serum microRNAs as biomarkers for the diagnosis of papillary thyroid carcinoma: a meta-analysis
Get PDFPapillary thyroid carcinoma (PTC) is the most common form of thyroid cancer. Several studies have proposed serum microRNAs (miRNAs) as novel biomarkers for diagnosing PTC. In this study, we conducted a meta-analysis aiming to investigate the overall diagnostic accuracy of serum miRNAs in PTC detection. Three online databases including PubMed, EMBASE and Cochrane Library were searched up to 1 May 2021. We systematically reviewed studies evaluating the value of serum miRNAs in diagnosing PTC, and then summarized the area under receiver operating characteristics curve (AUROC), sensitivity, specificity, and diagnostic odds ratio to assess the accuracy of serum miRNAs for the discrimination between patients with PTC and patients with benign thyroid nodules and healthy controls. We included 32 studies from 6 articles. Overall, there were 463 PTC patients, 334 patients with benign thyroid nodules, and 104 healthy controls. The results showed that the summary sensitivity and specificity were 76% (95% confidence interval [CI]: 68%‒83%) and 86% (95% CI: 80%‒91%), respectively, and that the summary AUROC was 0.89 (95% CI: 0.86‒0.91), when serum miRNAs were used for discriminating between PTC patients and those with benign nodules. On the other hand, the summary sensitivity and specificity of serum miRNAs for discriminating between PTC patients and healthy controls were 82% (95% CI: 77%‒86%) and 84% (95% CI: 76%‒90%), respectively, and the summary AUROC was 0.89 (95% CI: 0.86‒0.92). We found that serum miRNAs have good diagnostic performance for the discrimination between patients with PTC and patients with benign nodules and healthy controls, and thus have considerable potential as novel minimally invasive tools for detecting PTC