Bosnian Journal of Basic Medical Sciences (BJBMS)
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Vancomycin-releasing cross-linked collagen sponges as wound dressings
Get PDFThe study presents a novel vancomycin-releasing collagen wound dressing derived from Cyprinus carpio collagen type I cross-linked with carbodiimide which retarded the degradation rate and increased the stability of the sponge. Following lyophilization, the dressings were subjected to gamma sterilization. The structure was evaluated via scanning electron microscopy images, micro-computed tomography, and infrared spectrometry. The structural stability and vancomycin release properties were evaluated in phosphate buffered saline. Microbiological testing and a rat model of a wound infected with methicillin-resistant Staphylococcus aureus (MRSA) were then employed to test the efficacy of the treatment of the infected wound. Following an initial mass loss due to the release of vancomycin, the sponges remained stable. After 7 days of exposure in phosphate buffered saline (37°C), 60% of the material remained with a preserved collagen secondary structure together with a high degree of open porosity (over 80%). The analysis of the release of vancomycin revealed homogeneous distribution of the antibiotic both across and between the sponges. The release of vancomycin was retarded as proved by in vitro testing and further confirmed by the animal model from which measurable concentrations were observed in blood samples 24 hours after the subcutaneous implantation of the sponge, which was more than observed following intraperitoneal administration. The sponge was also highly effective in terms of reducing the number of colony-forming units in biopsies extracted from the infected wounds 4 days following the inoculation of the wounds with the MRSA solution. The presented sponges have ideal properties to serve as wound dressing for prevention of surgical site infection or treatment of already infected wounds
Long non-coding RNA PVT1 regulates the migration of hepatocellular carcinoma HepG2 cells via miR-3619-5p/MKL1 axis
Get PDFHepatocellular carcinoma (HCC) is the third most common malignant tumor of the digestive system. Plasma cell tumor heterotopic gene 1 (PVT1) is an intergenic long non-coding RNA that is aberrantly expressed in different cancers. Myocardin-related transcription factor A or megakaryoblastic leukemia 1 (MKL1) is a transcriptional coactivator of serum response factor that has been shown to promote cancer cell migration and invasion. In this study, we investigated the relationship between PVT1 and MKL1 as a novel regulatory mechanism underlying HCC progression. We used HepG2 and Cos‑7 cell lines. Transfection experiments with miR-3619-5p mimics/inhibitor, PVT1, siRNA-PVT1, MKL1, or siRNA-MKL1 were performed. RNA and protein levels were analyzed by quantitative reverse transcription PCR and Western blot, respectively. Cell migration was assessed by transwell assay. Luciferase assays, RNA-FISH, RNA immunoprecipitation, and chromatin immunoprecipitation assays were performed to confirm the interaction between PVT1, miR-3619-5p, and MKL1 in HCC cells. Overexpression of PVT1 was positively correlated with MKL1 upregulation, which promoted HepG2 cell migration. miR-3619-5p inhibited MKL1 expression in HCC cells by acting on its 3′-UTR. Furthermore, PVT1 promoted MKL1 expression and migration in HCC cells by directly binding to miR-3619-5p. In a positive feedback loop, MKL1 could activate PVT1 transcription by binding to the CArG box in the promoter region. Our findings may provide a basis for the development of novel targeted therapies in HCC
The value of lymphocyte count in determining the severity of COVID-19 and estimating the time for nucleic acid test results to turn negative
Get PDFPeripheral blood lymphocyte count is shown to be decreased in patients with COVID-19 in the early stage of the disease. The degree of lymphocyte count reduction is related to COVID-19 severity and could be used as an indicator to reflect the disease severity. Our aim was to investigate the value of lymphocyte count in determining COVID-19 severity and estimating the time for SARS-CoV-2 nucleic acid test results to turn negative. We retrospectively analyzed clinical data of 201 patients with severe and critical COVID-19. The patients were admitted to the West Campus of Union Hospital of Tongji Medical College of Huazhong University of Science and Technology. The data included age, gender, chronic disease, lymphocyte count, and SARS-CoV-2 nucleic acid test results. The age of patients in critically ill group was higher than in severely ill group (p = 0.019). The lymphocyte count of critically ill patients was lower than of severely ill patients. The cutoff value of lymphocyte count to distinguish between the critically ill and the severely ill was 0.735 × 109/L (p = 0.001). The cutoff value of lymphocyte count for SARS-CoV-2 nucleic acid test results turning negative in severely and critically ill patients with chronic diseases (hypertension, diabetes, and coronary heart disease) was 0.835 × 109/L (p = 0.017). The cutoff value of lymphocyte count for SARS-CoV-2 nucleic acid test results turning negative in severely and critically ill male patients was 0.835 × 109/L (p < 0.0001). Lymphocyte count could be an effective indicator to predict COVID-19 severity. It may also be useful in determining the time for nucleic acid test results to turn negative in COVID-19 patients with underlying chronic diseases or male COVID-19 patients with severe and critical conditions
The role of cytoreductive nephrectomy in renal cell carcinoma patients with liver metastasis
Get PDFIt is widely accepted that renal cell carcinoma (RCC) with liver metastasis (LM) carries a dismal prognosis. We aimed to explore the value of cytoreductive nephrectomy among these patients. Patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2017. The univariate and multivariate Cox proportional hazards models were conducted to select the prognostic predictors of survival. Patients were divided into nephrectomy and non-nephrectomy groups. Propensity score-matching (PSM) analyses were applied to reduce the above factors’ differences between the groups. Overall survival (OS) was compared by Kaplan–Meier analyses. Data from 683 patients were extracted from the database. The univariate Cox regression and multivariate Cox regression revealed that factors including age, histologic type, T and N stages, lung metastasis, brain metastasis, and nephrectomy were significant predictors of survival in the patients. After the PSM analyses, we found that nephrectomy prolonged OS. Nephrectomy can prolong OS in eligible RCC patients with LM
Cross-sectional imaging and cytologic investigations in the preoperative diagnosis of parotid gland tumors – An updated literature review
Get PDFAn accurate preoperative diagnosis of parotid tumors is essential for the selection and planning of surgical treatment. Various modern cross-sectional imaging and cytologic investigations can support the differential diagnosis of parotid tumors. The aim of this study was to achieve a comprehensive and updated review of modern imaging and cytologic investigations used in parotid tumor diagnosis, based on the latest literature data. This literature review could serve as a guide for clinicians in selecting different types of investigations for the preoperative differential diagnosis of parotid tumors. Magnetic resonance imaging (MRI) with its dynamic and advanced sequences is the first-line imaging investigation used in differentiating parotid tumors. Computed tomography (CT) and positron emission tomography (PET)-CT provide limited indications in differentiating parotid tumors. Fine needle aspiration biopsy and core needle biopsy can contribute with satisfactory results to the cytological diagnosis of parotid tumors. Dynamic MRI with its dynamic contrast-enhanced and diffusion-weighted sequences provides the best accuracy for the preoperative differential diagnosis of parotid tumors. CT allows the best evaluation of bone invasion, being useful when MRI cannot be performed, and PET-CT has value in the follow-up of cancer patients. The dual cytological and imaging approach is the safest method for an accurate differential diagnosis of parotid tumors
Construction and verification of prognostic nomogram for early-onset esophageal cancer
Get PDFThis study aimed to build up nomogram models to evaluate overall survival (OS) and cancer-specific survival (CSS) in early-onset esophageal cancer (EOEC). Patients diagnosed with esophageal cancer (EC) from 2004 to 2015 were extracted from the Surveillance Epidemiology and End Results (SEER) database. Clinicopathological characteristics of younger versus older patients were compared, and survival analysis was performed in both groups. Independent related factors influencing the prognosis of EOEC were identified by univariate and multivariate Cox analysis, which were incorporated to construct a nomogram. The predictive capability of the nomogram was estimated by the concordance index (C-index), calibration plot, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). A total of 534 younger and 17,243 older patients were available from the SEER database. Younger patients were randomly segmented into a training set (n = 266) and a validation set (n = 268). In terms of the training set, the C-index of the OS nomogram was 0.740 (95% CI: 0.707-0.773), and that of the CSS nomogram was 0.752 (95% CI: 0.719-0.785). In view of the validation set, the C-index of OS and CSS were 0.706 (95% CI: 0.671-0.741) and 0.723 (95% CI: 0.690-0.756), respectively. Calibration curves demonstrated the consistent degree of fit between actual and predicted values in nomogram models. From the perspective of DCA, the nomogram models were more beneficial than the tumor-node-metastasis (TNM) and the SEER stage for EOEC. In brief, the nomogram model can be considered as an individualized quantitative tool to predict the prognosis of EOEC patients to assist clinicians in making treatment decisions
Pharmacogenetics of new classes of antidiabetic drugs
Get PDFType 2 diabetes (T2D) has a continuously rising prevalence worldwide. Pharmacogenetics has been recognized as a promising concept for pharmacological treatment of T2D, as antidiabetic drugs are not equally effective and safe for all patients, and the costs of diabetes treatment are increasing. The latest published guidelines on T2D treatment firmly endorse the use of newer antidiabetic drugs, sodium-glucose cotransporter-2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP-IVi), and glucagon-like peptide-1 receptor agonists (GLP-1RA), considering their satisfactory pharmacological effect and good safety profile. Furthermore, SGLT2i and GLP-1RA show protective effects in patients with established atherosclerotic cardiovascular disease and chronic kidney disease. However, there has been growing evidence that the effectiveness and safety of these drug classes could depend on genetic variability. Here, we summarized the results of the published studies on the pharmacogenetic biomarkers for the three drug classes. A number of genetic variations have been investigated so far. The explored candidate genes mostly encode drug targets, drug-metabolizing enzymes, and genes linked to T2D risk. Although many of the results are promising, it is still necessary to obtain more information from larger controlled studies to confirm their clinical significance. This approach may lead towards more personalized treatment for patients with T2D
Cisplatin inhibits the proliferation of Saos-2 osteosarcoma cells via the miR-376c/TGFA pathway
Get PDFThe transforming growth factor alpha (TGFA) gene is involved in the proliferation and metastasis of various tumors, but its role in cell sensitivity to cisplatin chemotherapy is unclear. In this study, we investigated the mechanism underlying inhibitory effects of cisplatin on growth and proliferation of osteosarcoma cells. Osteosarcoma and normal skeletal muscle tissues were collected from 26 patients by biopsy. TGFA was silenced or overexpressed in Saos-2 osteosarcoma cells by transfection with TGFA-shRNA or TGFA ORF clone, respectively. MiR-376c was inhibited or overexpressed by transfection of Saos-2 cells with miR-376c sponge or miR-376c mimics, respectively. Cell growth was analyzed by MTT assay and cell proliferation by BrdU assay. MiR-376c and TGFA mRNA expression was detected by quantitative reverse transcription PCR and TGFA protein expression by Western blot. The target relationship between miR-376c and TGFA was assessed by luciferase reporter assay. Both in osteosarcoma tissues and Saos-2 cells, miR-376c expression was significantly decreased and TGFA mRNA expression was significantly increased compared with control. Transfection of Saos-2 cells with TGFA-shRNA silenced TGFA expression and significantly inhibited cell growth and proliferation. TGFA mRNA and protein expression in Saos-2 cells significantly decreased with increasing cisplatin concentrations (2.5–10 mg/L). Transfection with TGFA ORF clone reversed the inhibitory effects of cisplatin on Saos-2 cell proliferation. Compared with cisplatin (10 mg/L) treatment alone, the combined treatment with cisplatin and miR-376c mimics inhibited the proliferation of Saos-2 cells more significantly. MiR-376c suppressed TGFA expression by directly interacting with its 3\u27 UTR region. Overall, cisplatin inhibited the proliferation of Saos-2 cells by upregulating miR-376c and downregulating TGFA expression
Lessons learned from COVID-19 pandemic in Italy – A commentary
Get PDFSince the COVID-19 outbreak, Italy has been one of the most affected countries in Europe and the second for number of deaths. In this commentary, we discuss some lessons that we learned as health-care providers working in a large public hospital during the pandemic, with a special focus on the importance of infection containment and early diagnosis, the role of swab, serological tests, home isolation and individual protection devices, and the available therapies and management indications to better face a possible new outbreak in the near future. These comments should stimulate a more diffused, efficient, and efficacious management of COVID-19 patients, also reducing the number of admissions to hospital emergency departments and the related spread of the infection
Rapid, multimodal, critical care knowledge-sharing platform for COVID-19 pandemics
No full textIn many areas of the world, critical care providers caring for COVID-19 patients lacked specific knowledge and were exposed to the abundance of new and unfiltered information. With support from the World Health Organization, we created a multimodal tele-education intervention to rapidly share critical care knowledge related to COVID-19 targeting providers in a region of Southeastern Europe. We delivered 60-minute weekly interactive tele-education sessions over YouTubeTM between March 2020 and May 2020, supplemented by a dedicated webpage. The intervention was reinforced using a secure social media platform (ViberTM), providing continuous rapid knowledge exchange among faculty and learners. A high level of engagement was observed, with over 2000 clinicians participating and actively interacting over a 6-week period. Surveyed participants were highly satisfied with the intervention. Tele-education interventions using social media platforms are feasible, low-cost, and effective methods to share knowledge during the COVID-19 pandemic