Bosnian Journal of Basic Medical Sciences (BJBMS)
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Single-cell transcriptomic analysis of radiation-induced lung injury in rat
Get PDFRadiation-induced lung injury (RILI) frequently occurs as a complication following radiotherapy for chest tumors like lung and breast cancers. However, the precise underlying mechanisms of RILI remain unclear. In this study, we generated RILI models in rats treated with a single dose of 20 Gy and examined lung tissues by single-cell RNA sequencing (scRNA-seq) 2 weeks post-radiation. Analysis of lung tissues revealed 18 major cell populations, indicating an increase in cell-cell communication following radiation exposure. Neutrophils, macrophages, and monocytes displayed distinct subpopulations and uncovered potential for pro-inflammatory effects. Additionally, endothelial cells exhibited a highly inflammatory profile and the potential for reactive oxygen species (ROS) production. Furthermore, smooth muscle cells (SMC) showed a high propensity for extracellular matrix (ECM) deposition. Our findings broaden the current understanding of RILI and highlight potential avenues for further investigation and clinical applications
VIRMA promotes the progression of head and neck squamous cell carcinoma by regulating UBR5 mRNA and m6A levels
Get PDFHead and neck squamous cell carcinoma (HNSCC) is a globally prevalent and lethal cancer form which precise mechanisms remain incompletely understood. Increasing evidence suggests that N6-methyladenosine (m6A) plays a crucial role in cancer progression. This study aimed to explore the biological function of m6A modification and vir-like m6A methyltransferase associated (VIRMA) inHNSCC. We conducted an analysis of VIRMA expression in HNSCC cells using The Cancer Genome Atlas (TCGA) database and employed reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting to assess its expression levels in HNSCC cell lines. Additionally,m6A levels in HNSCC cells were quantified, and the correlation between VIRMA expression levels and the clinical and pathological features of other genes was analyzed. Upon knocking down VIRMA levels, we assessed HNSCC cell proliferation, migration, and invasion and validated downstream genes using RT-qPCR and western blot. Our findings suggested that VIRMA, as an m6A-related regulator, may significantly influence HNSCC progression by regulating ubiquitin protein ligase E3 component N-recognin 5 (UBR5) through m6A modification. Therefore, VIRMA may serve as a prognostic biomarker
Probiotics for the prevention of gestational diabetes mellitus: A meta-analysis of randomized controlled trials
Get PDFChanges of intestinal microbiota have been shown to be involved in the development of gestational diabetes mellitus (GDM). We performed a meta-analysis to systematically evaluate the potential role of probiotics for the prevention of GDM. Systematic literature search was performed in electronic databases including PubMed, Cochrane library, Embase, Web of Science, Wanfang, and China National Knowledge Infrastructure (CNKI) to obtain relevant randomized controlled studies. A random-effects model was used to pool the results by incorporating the impact of the potential heterogeneity. Meta-regression and subgroup analyses were conducted to evaluate the source of heterogeneity. Fourteen studies involving 3527 pregnant women were included. Results showed that probiotics significantly reduced the incidence of GDM as compared to control (risk ratio [RR]: 0.71, 95% confidence interval [CI]: 0.52–0.96, P = 0.03) with significant heterogeneity (I2 = 73%). The meta-regression showed that body mass index (BMI) of women was positively associated with the RR for the effect of probiotics on GDM (coefficient = 0.084, P = 0.01). The results of subgroup analyses also suggested that probiotics significantly reduced the risk of GDM in women with BMI < 26 kg/m2, but not in those with BMI ≥ 26 kg/m2 (P for subgroup difference = 0.001). In addition, the preventative efficacy of probiotics on GDM was remarkable in women < 30 years, but not in those ≥ 30 years (P for subgroup difference < 0.001). In conclusion, probiotics may be effective in reducing the risk of GDM, particularly for women with lower BMI and younger age
Predominance of OXA-48 carbapenemase-producing Klebsiella pneumoniae strains in tertiary hospital in Sarajevo, Bosnia and Herzegovina
Get PDFKlebsiella pneumoniae, a member of the Enterobacteriaceae family, demonstrates an increasing trend of resistance to carbapenems and is a common cause of both hospital- and community-acquired infections. The current study provides insights into the genetic characterization of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates circulating during 2022 in a Sarajevo tertiary hospital. Among the 87 CRKP strains analyzed, real-time polymerase chain reaction (rtPCR) results showed that 85 (97.7%) tested positive for the carbapenem resistance gene. The oxacillinase-48 (OXA-48) gene was detected in 83 (95.4%) isolates, while the Klebsiella pneumoniae carbapenemase (KPC) and the New Delhi metallo-beta-lactamase (NDM) genes were detected in one isolate each. No Verona integron-encoded-metallo-beta-lactamase (VIM) or imipenemase-metallo-beta-lactamase 1 (IMP-1) genes were found in any of the tested isolates. The multilocus sequence typing (MLST) analysis of sequence types (STs) revealed that ST101, an emerging high-risk clone exhibiting extensive drug resistance, was the most prevalent, whereas ST307 was detected in only one isolate. Phylogenetic analysis of the ten CRKP isolates indicated the presence of three clusters that could constitute an outbreak. A comparison of the results of the utilized phenotypic test (the combined-disk test [CDT]) and rtPCR showed high concordance, suggesting that the phenotypic assay may be useful for the early detection of resistance mechanisms as part of routine susceptibility testing. With the increased affordability of next-generation sequencing (NGS), its application in hospital settings has proven highly beneficial, aiding in the implementation of infection control and prevention measures. Given the significant resistance demonstrated by the CRKP isolates to most tested antibiotics, it is imperative to establish effective methods to restrict the spread of these isolates, as well as to carefully monitor the use of carbapenems in clinical practice
Serum C-reactive protein to albumin ratio as a reliable marker of diabetic neuropathy in type 2 diabetes mellitus
Get PDFIn various diseases characterized by inflammation, the C-reactive protein to albumin ratio (CAR) serves as a marker of inflammation. Type 2 diabetes mellitus (T2DM) is frequently complicated by diabetic neuropathy (DN) and timely diagnosis is crucial for treatment and potential reversal of this complication. Since both DN and T2DM are associated with chronic, low-grade inflammation, our study aimed to evaluate CAR levels in type 2 diabetic subjects with DN and compare them to those in subjects without DN. Patients presenting to our institutional outpatient clinics were divided into two groups based on the presence of DN. Data on characteristics and laboratory measures, including CAR,were compared between the DN and non-DN groups. The median CAR in the DN and non-DN groups was 2.19% (range 0.2%–49%) and 0.56% (range 0.02%–5.8%), respectively (P < 0.001). CAR showed significant positive correlations with weight (r = 0.19, P = 0.01), body mass index (BMI) (r = 0.11, P = 0.03), waist circumference (r = 0.10, P = 0.046), fasting glucose (r = 0.14, P = 0.004), serum creatinine (r = 0.25, P < 0.001), triglyceride (r = 0.17, P < 0.001), and LDL-cholesterol (r = 0.13, P = 0.001) levels, and an inverse correlation with estimated glomerular filtration rate (eGFR) (r = −0.16, P < 0.001). Additionally, CAR demonstrated a sensitivity of 78% and specificity of 73% for predicting DN at a threshold of 1.02% (area under curve [AUC] 0.84, 95% confidence interval [CI] 0.82–0.87, P < 0.001). High CAR levels were independently associated with an increased risk of DN (odds ratio [OR] 1.34, 95% CI 1.08–1.62, P < 0.001). Elevated CAR levels may thus be considered a potential marker for DN in T2DM patients
Impact of RANGAP1 SUMOylation on Smad4 nuclear export by bioinformatic analysis and cell assays
Get PDFSmall Ubiquitin-like Modifier (SUMOylation) regulates a variety of cellular activities, and its dysregulation has been associated with glioma etiology. The aim of this research was to clarify the function of SUMOylation-related genes in glioma and determine relevant prognostic markers. The Cancer Genome Atlas (TCGA) Glioma and GSE16011 datasets were analyzed through bioinformatics to identify Ran GTPase activating protein 1 (RANGAP1) as the hub gene for further study. Experimental validation consisted of quantitative real-time polymerase chain reaction (qRT-PCR), western blotting (WB), and immunoprecipitation (IP) to evaluate RANGAP1 expression, function, and interaction with SUMO1. To assess the role of RANGAP1 knockdown and SUMOylation in glioma cells, various assays were conducted, including cell proliferation, migration, invasion, and apoptosis. In addition, cell cycle analysis and immunofluorescence were performed. Through bioinformatics, RANGAP1 was identified as a crucial prognostic gene for glioma. Experimental studies confirmed the downregulation of RANGAP1 in glioma cells and verified that RANGAP1 repair impedes tumor growth. When it comes to RANGAP1 silencing, it enhanced cell proliferation, invasion and migration. Additionally, SUMO1 was identified as a specific SUMO molecule coupled to RANGAP1, affecting the location of Sma and Mad related protein 4 (Smad4) in the nucleocytoplasm and the transforming growth factor (TGF)-β/Smad signaling pathway. The functional impact of RANGAP1 SUMOylation on cell proliferation and migration was further confirmed through experiments using a SUMOylation-impairing mutation (K524R). Our findings suggest that RANGAP1 may be a potential prognostic marker in gliomas and could play a role in regulating cell proliferation, migration, and invasion. SUMOylation of RANGAP1 is responsible for regulating the TGF-β/Smad signaling pathway, which is crucial for the progression of tumors. Further investigations and experiments are necessary to confirm these results
Treatment outcome of elderly patients (≥ 78 years) with head and neck squamous cell carcinoma: A single center experience
Get PDFPatients older than the expected age of the local population generally have limited life expectancy. The optimal treatment approach for very elderly patients with head and neck cancer remains uncertain. This study retrospectively analyzed patients over 78 years old, the expected age in 2019 for Chinese individuals, who underwent treatment for head and neck cancer at a tertiary cancer center in China. The study compared the overall survival rates among different treatment groups. The findings revealed that among patients eligible for surgery, radical resection yielded better outcomes compared to radiotherapy-based treatments, with a hazard ratio of 0.362 (95% CI 0.160-0.819, P = 0.015). Among patients who received radiotherapy, those who received a total dose exceeding 60 Gy had a significantly longer survival compared to those who received palliative doses, with median survival time of 31 months versus 14 months (P = 0.003). Among 78 patients who underwent conventional fractionated radiotherapy (CFRT), 15 patients (19.23%) experienced unscheduled treatment breaks with a median duration of 12 days. However, these treatment breaks did not appear to impact survival (P > 0.1). The study also suggested that altered fractionated radiotherapy, including hypofractionated radiotherapy (hypo-RT), could be a viable alternative to CFRT, offering similar survival outcomes with reduced treatment duration. In conclusion, eligible patients should be treated with curative intent, even if they are older than the expected age of the local population. When radiotherapy is indicated, altered fractionation, particularly hypo-RT, may be a favorable option to consider
PRODIGY score predicts respiratory depression in the post-anesthesia care unit: A post-hoc analysis
Get PDFSurgical patients who experience respiratory depressive episodes (RDEs) during their post-anesthesia care unit (PACU) admission are at a higher risk of developing subsequent respiratory complications in general care wards. A risk assessment tool for PACU RDEs has not been previously assessed. The PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) score is an assessment tool that uses baseline patient variables to categorize patients into low, intermediate, or high risk groups for RDEs in general care wards. This study assessed whether PRODIGY groups are associated with PACU RDEs. This analysis utilized data from a previous observational trial of PACU RDEs detected by capnography. PRODIGY scores were retrospectively calculated, and the number and duration of respiratory alerts were compared among PRODIGY groups. Twenty-six (29.9%) patients were classified as low risk, 29 (33.3%) as intermediate risk, and 32 (36.8%) as high risk. A total of 3,580 alerts were recorded in the PACU, 47% of which were apnea episodes lasting ≥ 10 seconds. The total number and duration of alerts were highest in high risk group patients (median 56 [IQR 12 – 87] alerts per patient vs 22 [9 – 37] in low risk and 26 [13 – 42] in intermediate risk patients, P = 0.035; 303 [123 – 885] seconds vs 177 [30 – 779] in low risk and 301 [168 – 703] in intermediate risk patients, P = 0.042). Poisson regression analysis indicated that the rate of RDEs in the high PRODIGY risk group was higher than in the intermediate (rate ratio estimate = 2.01 [95% CI 1.86 – 2.18], P < 0.001) and low (rate ratio estimate = 2.25 [95% confidence interval 2.07 – 2.45], P < 0.001) risk groups. This analysis suggests that the PRODIGY score may be useful in assessing the risk of PACU RDEs. Trial Registration: https://www.clinicaltrials.gov/ct2/show/NCT02707003
Neuroimaging in the diagnosis and treatment of cerebral toxoplasmosis in children with severe β-thalassemia after allo-HSCT
Get PDFChildren with severe β-thalassemia major (β-TM) are at high risk of developing toxoplasmosis after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The aim of this study was to identify the neuroimaging findings of cerebral toxoplasmosis in pediatric patients with β-TM for early diagnosis and treatment of cerebral toxoplasmosis. We performed a retrospective assessment of clinical and neuroimaging data of children with severe β-TM who had cerebral toxoplasmosis after allo-HSCT. Additionally, we reviewed and summarized the literature on cerebral toxoplasmosis in patients with other underlying conditions. This case series identified three children who had severe β-TM and had subsequent cerebral toxoplasmosis after allo-HSCT. In addition, we identified 23 patients from literature who had toxoplasmosis and had underlying conditions other than β-TM. We found that the most common clinical symptom among the patients from our series and the patients from literature was fever upon presentation. We identified the typical neuroimaging findings including brain lesions with ring enhancement and eccentric/central nuclear target-like enhancement, which should facilitate early diagnosis and treatment of cerebral toxoplasmosis
Association between serum neuron-specific enolase at admission and the risk of delayed neuropsychiatric sequelae in adults with carbon monoxide poisoning: A meta-analysis
Get PDFDelayed neuropsychiatric sequelae (DNS) significantly impact the quality of life in patients following acute carbon monoxide poisoning (COP). This systematic review and meta-analysis aimed to assess the relationship between serum neuron-specific enolase (NSE) levels at admission and the risk of DNS in adults after acute COP. Relevant observational studies with longitudinal follow-up were identified through searches in PubMed, Embase, Web of Science, Wanfang, and China National Knowledge Infrastructure databases. The random-effects model was used to aggregate results, accounting for potential heterogeneity. Nine cohort studies, including 1501 patients, were analyzed, with 254 (16.9%) developing DNS during follow-up. The pooled data indicated that elevated serum NSE in the early phase was linked to a higher risk of subsequent DNS (odds ratio per 1 ng/mL increase in NSE: 1.10, 95% confidence interval: 1.06 to 1.15, P < 0.001). Moderate heterogeneity (I2 = 46%) among the studies was entirely attributed to one study with the longest follow-up duration (22.3 months; I2 = 0% after excluding this study). Subgroup analyses based on country, study design, sample size, age, sex, admission carboxyhemoglobin levels, DNS incidence, follow-up duration, and quality score yielded consistent results (P for subgroup differences all > 0.05). In summary, high serum NSE levels in the early phase of acute COP are associated with an increased risk of developing DNS during follow-up