Mitochondrial DNA and Inflammation Are Associated with Cerebral Vessel Remodeling and Early Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus.

Cerebrovascular disease accounts for major neurologic disabilities in patients with type 2 diabetes mellitus (DM). A potential association of mitochondrial DNA (mtDNA) and inflammation with cerebral vessel remodeling in patients with type 2 DM was evaluated. A cohort of 150 patients and 30 healthy controls were assessed concerning urinary albumin/creatinine ratio (UACR), synaptopodin, podocalyxin, kidney injury molecule-1 (KIM-1), N-acetyl-ß-(D)-glucosaminidase (NAG), interleukins IL-17A, IL-18, IL-10, tumor necrosis factor-alpha (TNFα), intercellular adhesion molecule-1 (ICAM-1). MtDNA-CN and nuclear DNA (nDNA) were quantified in peripheral blood and urine by qRT-PCR. Cytochrome b (CYTB) gene, subunit 2 of NADH dehydrogenase (ND2), and beta 2 microglobulin nuclear gene (B2M) were assessed by TaqMan assays. mtDNA-CN was defined as the ratio of the number of mtDNA/nDNA copies, through analysis of the CYTB/B2M and ND2/B2M ratio; cerebral Doppler ultrasound: intima-media thickness (IMT)-the common carotid arteries (CCAs), the pulsatility index (PI) and resistivity index (RI)- the internal carotid arteries (ICAs) and middle cerebral arteries (MCAs), the breath-holding index (BHI). The results showed direct correlations of CCAs-IMT, PI-ICAs, PI-MCAs, RI-ICAs, RI-MCAs with urinary mtDNA, IL-17A, IL-18, TNFα, ICAM-1, UACR, synaptopodin, podocalyxin, KIM-1, NAG, and indirect correlations with serum mtDNA, IL-10. BHI correlated directly with serum IL-10, and serum mtDNA, and negatively with serum IL-17A, serum ICAM-1, and NAG. In neurologically asymptomatic patients with type 2 DM cerebrovascular remodeling and impaired cerebrovascular reactivity may be associated with mtDNA variations and inflammation from the early stages of diabetic kidney disease.

Cystic Echinococcosis in Hospitalized Adult Patients from Western Romania: 2007-2022.

Cystic echinococcosis (CE) is a neglected parasitic disease caused by the tapeworm Echinococcus granulosus. The aim of this study was to assess the epidemiological features of human cystic echinococcosis in patients from Western Romania. We retrospectively investigated the medical records of patients hospitalized with CE between 1 January 2007 and 1 September 2022. A total of 366 patients (range 18-90 years) were recorded. The number of hospitalized individuals was higher in patients aged 50-59 years (83/366, 22.7%), in females (194/366, 53%), and in residents of rural areas (225/366, 61.5%). The liver was the most common localization of the cysts (302/366, 82.5%). Ninety-eight patients (26.8%) presented complications, including biliary fistula, allergies, and infection of the cyst. Patients with complications had a longer mean hospital stay (15.7 ± 8.3 days) compared to patients without complications (11.5 ± 7.3 days) (p < 0.001). The results of this study revealed that patients diagnosed with CE required hospitalization and extended medical care, indicating that this zoonotic disease remains a significant public health problem in Western Romania. Public health authorities should enhance CE surveillance by implementing control programs and mandatory notification of new cases.

Metabolites Potentially Derived from Gut Microbiota Associated with Podocyte, Proximal Tubule, and Renal and Cerebrovascular Endothelial Damage in Early Diabetic Kidney Disease in T2DM Patients.

Complications due to type 2 diabetes mellitus (T2DM) such as diabetic kidney disease (DKD) and cerebral small vessel disease (CSVD) have a powerful impact on mortality and morbidity. Our current diagnostic markers have become outdated as T2DM-related complications continue to develop. The aim of the investigation was to point out the relationship between previously selected metabolites which are potentially derived from gut microbiota and indicators of endothelial, proximal tubule (PT), and podocyte dysfunction, and neurosonological indices. The study participants were 20 healthy controls and 90 T2DM patients divided into three stages: normoalbuminuria, microalbuminuria, and macroalbuminuria. Serum and urine metabolites were determined by untargeted and targeted metabolomic techniques. The markers of endothelial, PT and podocyte dysfunction were assessed by ELISA technique, and the neurosonological indices were provided by an ultrasound device with high resolution (MYLAB 8-ESAOTE Italy). The descriptive statistical analysis was followed by univariable and multivariable linear regression analyses. In conclusion, in serum, arginine (sArg), butenoylcarnitine (sBCA), and indoxyl sulfate (sIS) expressed a biomarker potential in terms of renal endothelial dysfunction and carotid atherosclerosis, whereas sorbitol (sSorb) may be a potential biomarker of blood-brain barrier (BBB) dysfunction. In urine, BCA and IS were associated with markers of podocyte damage, whereas PCS correlated with markers of PT dysfunction.

Quantitative, Targeted Analysis of Gut Microbiota Derived Metabolites Provides Novel Biomarkers of Early Diabetic Kidney Disease in Type 2 Diabetes Mellitus Patients.

Diabetic kidney disease (DKD) is one of the most debilitating complications of type 2 diabetes mellitus (T2DM), as it progresses silently to end-stage renal disease (ESRD). The discovery of novel biomarkers of early DKD becomes acute, as its incidence is reaching catastrophic proportions. Our study aimed to quantify previously identified metabolites from serum and urine through untargeted ultra-high-performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (UHPLC-QTOF-ESI+-MS) techniques, such as the following: arginine, dimethylarginine, hippuric acid, indoxyl sulfate, p-cresyl sulfate, L-acetylcarnitine, butenoylcarnitine and sorbitol. The study concept was based on the targeted analysis of selected metabolites, using the serum and urine of 20 healthy subjects and 90 T2DM patients with DKD in different stages (normoalbuminuria-uACR < 30 mg/g; microalbuminuria-uACR 30-300 mg/g; macroalbuminuria-uACR > 300 mg/g). The quantitative evaluation of metabolites was performed with pure standards, followed by the validation methods such as the limit of detection (LOD) and the limit of quantification (LOQ). The following metabolites from this study resulted as possible biomarkers of early DKD: in serum-arginine, dimethylarginine, hippuric acid, indoxyl sulfate, butenoylcarnitine and sorbitol and in urine-p-cresyl sulfate.

Metabolomic Investigation of Blood and Urinary Amino Acids and Derivatives in Patients with Type 2 Diabetes Mellitus and Early Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease; however, few biomarkers of its early identification are available. The aim of the study was to assess new biomarkers in the early stages of DKD in type 2 diabetes mellitus (DM) patients. This cross-sectional pilot study performed an integrated metabolomic profiling of blood and urine in 90 patients with type 2 DM, classified into three subgroups according to albuminuria stage from P1 to P3 (30 normo-, 30 micro-, and 30 macroalbuminuric) and 20 healthy controls using high-performance liquid chromatography and mass spectrometry (UPLC-QTOF-ESI* MS). From a large cohort of separated and identified molecules, 33 and 39 amino acids and derivatives from serum and urine, respectively, were selected for statistical analysis using Metaboanalyst 5.0. online software. The multivariate and univariate algorithms confirmed the relevance of some amino acids and derivatives as biomarkers that are responsible for the discrimination between healthy controls and DKD patients. Serum molecules such as tiglylglycine, methoxytryptophan, serotonin sulfate, 5-hydroxy lysine, taurine, kynurenic acid, and tyrosine were found to be more significant in the discrimination between group C and subgroups P1-P2-P3. In urine, o-phosphothreonine, aspartic acid, 5-hydroxy lysine, uric acid, methoxytryptophan, were among the most relevant metabolites in the discrimination between group C and DKD group, as well between subgroups P1-P2-P3. The identification of these potential biomarkers may indicate their involvement in the early DKD and 2DM progression, reflecting kidney injury at specific sites along the nephron, even in the early stages of DKD.

Mitochondrial DNA Changes in Blood and Urine Display a Specific Signature in Relation to Inflammation in Normoalbuminuric Diabetic Kidney Disease in Type 2 Diabetes Mellitus Patients.

Mitochondrial dysfunction is an important mechanism contributing to the development and progression of diabetic kidney disease (DKD). Mitochondrial DNA (mtDNA) levels in blood and urine were evaluated in relation to podocyte injury and proximal tubule (PT) dysfunction, as well as to a specific inflammatory response in normoalbuminuric DKD. A total of 150 type 2 diabetes mellitus (DM) patients (52 normoalbuminuric, 48 microalbuminuric, and 50 macroalbuminuric ones, respectively) and 30 healthy controls were assessed concerning the urinary albumin/creatinine ratio (UACR), biomarkers of podocyte damage (synaptopodin and podocalyxin), PT dysfunction (kidney injury molecule-1 (KIM-1) and N-acetyl-ß-(D)-glucosaminidase (NAG)), and inflammation (serum and urinary interleukins (IL-17A, IL-18, and IL-10)). MtDNA-CN and nuclear DNA (nDNA) were quantified in peripheral blood and urine via qRT-PCR. MtDNA-CN was defined as the ratio of the number of mtDNA/nDNA copies via analysis of the CYTB/B2M and ND2/B2M ratio. Multivariable regression analysis provided models in which serum mtDNA directly correlated with IL-10 and indirectly correlated with UACR, IL-17A, and KIM-1 (R2 = 0.626; p < 0.0001). Urinary mtDNA directly correlated with UACR, podocalyxin, IL-18, and NAG, and negatively correlated with eGFR and IL-10 (R2 = 0.631; p < 0.0001). Mitochondrial DNA changes in serum and urine display a specific signature in relation to inflammation both at the podocyte and tubular levels in normoalbuminuric type 2 DM patients.

Seroprevalence of Anti-Echinococcus granulosus Antibodies and Risk Factors for Infection in Blood Donors from Western Romania.

Cystic echinococcosis is a worldwide-distributed zoonotic parasitic disease. This cross-sectional study aimed to assess the seroprevalence and risk factors potentially associated with Echinococcus granulosus in healthy blood donors from Timis County, an endemic region in Western Romania. Serum samples were collected from 1347 Romanian blood donors. Serologic tests to determine the presence of anti-Echinococcus antibodies were performed using an anti-Echinococcus-ELISA immunoassay. Anti-Echinococcus antibodies were detected in 38 blood donors, indicating an overall seroprevalence of 2.8%. The seropositivity rate was 3.7% in females and 3.1% in blood donors residing in urban areas. The highest seropositivity was found in the age group of 31-40 years (3.6%). There were no significant differences between Echinococcus seropositivity and gender, area of residence, age, contact with dogs, or raising sheep. This serologic survey evaluated for the first time the presence of Echinococcus antibodies in healthy blood donors from Western Romania and the potential risk factors associated with echinococcosis. Our results suggest that this zoonotic infection might evolve asymptomatically in apparently healthy individuals. Further studies should be conducted in the general population to estimate the true extent of human echinococcosis and its risk factors.

Metabolite Profiling of the Gut-Renal-Cerebral Axis Reveals a Particular Pattern in Early Diabetic Kidney Disease in T2DM Patients.

Type 2 diabetes mellitus (T2DM) represents an important microvascular disease concerning the kidney and the brain. Gut dysbiosis and microbiota-derived metabolites may be in relation with early pathophysiological changes in diabetic kidney disease (DKD). The aim of the study was to find new potential gut-derived biomarkers involved in the pathogenesis of early DKD, with a focus on the complex interconnection of these biomarkers with podocyte injury, proximal tubule dysfunction, renal and cerebrovascular endothelial dysfunction. The study design consisted of metabolite profiling of serum and urine of 90 T2DM patients (subgroups P1-normoalbuminuria, P2-microalbuminuria, P3-macroalbuminuria) and 20 healthy controls (group C), based on ultra-high-performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry analysis (UHPLC-QTOF-ESI+-MS). By multivariate and univariate analyses of serum and urine, which included Partial Least Squares Discriminant Analysis (PLSDA), Variable Importance Plots (VIP), Random Forest scores, One Way ANOVA and Biomarker analysis, there were discovered metabolites belonging to nitrogen metabolic pathway and retinoic acid signaling pathway which differentiate P1 group from P2, P3, C groups. Tyrosine, phenylalanine, indoxyl sulfate, serotonin sulfate, and all-trans retinoic acid express the metabolic fingerprint of P1 group vs. P2, P3, C groups, revealing a particular pattern in early DKD in T2DM patients.

Evaluation of FIB-4, NFS, APRI and Liver Function Tests as Predictors for SARS-CoV-2 Infection in the Elderly Population: A Matched Case-Control Analysis.

Several investigations have revealed that COVID-19 causes a significant death rate due to acute respiratory distress syndrome, alterations in the quantity of ACE2 receptor expression, or the intensity of cytokine storm. Similarly, patients with hepatic impairment that are co-infected with SARS-CoV-2 are more likely to display upregulations of ACE2 receptors and cytokine storm overload, which exacerbates hepatic impairment, potentially increasing the death rate. Moreover, it is expected that the aging population develops a higher degree of hepatic fibrosis in association with other comorbid conditions that are likely to influence the course of COVID-19. Therefore, this research was developed to describe the differences in liver test parameters in elderly individuals with COVID-19 in relation to other inflammatory markers and outcomes. This current observational single-center research followed a case-control design of elderly patients hospitalized for SARS-CoV-2 infection. The research was conducted at a tertiary emergency hospital in western Romania during a two-year period. There were 632 patients included in the analysis that were split into two equal groups matched 1:1 based on gender and body mass index. Three hundred sixteen patients made the group of cases with COVID-19 patients older than 65 years, while the other half were the 316 patient controls with COVID-19 that were younger than 65 years old. Disease outcomes showed a higher prevalence of ICU admissions (22.8% vs. 12.7%, p-value < 0.001) and in-hospital mortality (17.1% vs. 8.9%, p-value = 0.002) in the group of cases. Specific and non-specific liver biomarkers were identified as risk factors for mortality in the elderly, such as ALP (OR = 1.26), LDH (OR = 1.68), AST (OR = 1.98), and ALT (OR = 2.34). Similarly, patients with APRI and NFS scores higher than 1.5 were, respectively, 2.69 times and, 3.05 times more likely to die from COVID-19, and patients with FIB-4 scores higher than 3.25 were 3.13 times more likely to die during hospitalization for SARS-CoV-2 infection. Our research indicates that abnormally increased liver biomarkers and high liver fibrosis scores are related to a worse prognosis in SARS-CoV-2 infected individuals.

In Vitro and In Ovo Evaluation of the Potential Hepatoprotective Effect of Metformin.

Background and Objectives: Metformin is currently the leading drug of choice for treating type 2 diabetes mellitus, being one of the most widely used drugs worldwide. The beneficial effects of Metformin, however, extend far beyond the reduction of blood glucose. Therefore, this study aimed to evaluate Metformin's effects both in vitro and in ovo. Materials and Methods: Metformin has been tested in five different concentrations in human hepatocytes -HepaRG, in terms of cell viability, morphology, structure and number of nuclei and mitochondria, as well as the effect on cell migration. Through the application of HET-CAM, the biocompatibility and potential anti-irritant, as well as protective effects on the vascular plexus were also assessed. Results: According to the results obtained, Metformin increases cell viability without causing morphological changes to cells, mitochondria, or nuclei. Metformin displayed an anti-irritant activity rather than causing irritation at the level of the vascular plexus. Conclusions: In conclusion, Metformin enhances cell viability and proliferation and, has a protective effect on the vascular plexus. Nonetheless, more studies are required to clarify the mechanism of hepatoprotective effect of metformin.

Cardiovascular Risk Prediction Parameters for Better Management in Rheumatic Diseases.

The early detection of cardiovascular disease (CVD) serves as a key element in preventive cardiology. The risk of developing CVD in patients with rheumatic disease is higher than that of the general population. Thus, the objective of this narrative review was to assess and describe updated risk-prediction parameters for CVD in patients suffering from rheumatic diseases, and, additionally, to evaluate therapeutic and risk management possibilities. The processes of recognizing CVD risk factors in rheumatic diseases, establishing diagnoses, and discovering CV risk assessments are currently displeasing in clinical practice; they have a limited clinical impact. A large number of references were found while screening PUBMED, Scopus, and Google scholar databases; the 47 most relevant references were utilized to build up this study. The selection was limited to English language full text articles, RCTs, and reviews published between 2011 and 2021. Multiple imaging techniques, such as ECG, ultrasound, and cIMT, as well as biomarkers like osteoprotegerin cytokine receptor and angiopoietin-2, can be beneficial in both CV risk prediction and in early subclinical diagnosis. Physical exercise is an essential non-pharmacological intervention that can maintain the health of the cardiovascular system and, additionally, influence the underlying disease. Lipid-lowering drugs (methotrexate from the non-biologic DMARDs family as well as biologic DMARDs such as anti-TNF) were all associated with a lower CV risk; however, anti-TNF medication can decrease cardiac compliance and promote heart failure in patients with previously diagnosed chronic HF. Although they achieved success rates in reducing inflammation, glucocorticoids, NSAIDs, and COX-2 inhibitors were correlated with an increased risk of CVD. When taking all of the aforementioned points into consideration, there appears to be a dire need to establish and implement CVD risk stratification models in rheumatic patients.

Phytochemical Analysis and In Vitro Cytotoxic Activity against Colorectal Adenocarcinoma Cells of Hippophae rhamnodies L., Cymbopogon citratus (D.C.) Stapf, and Ocimum basilicum L. Essential Oils.

Colorectal carcinoma (CRC) is one of the most frequently diagnosed cancer types with current deficient and aggressive treatment options, but various studied alternative therapies are able to efficiently contribute to its management. Essential oils (EOs) contain valuable compounds, with antibacterial, anti-inflammatory, and anticancer properties, which might serve as effective solutions in CRC prophylaxis or treatment. The aim of the present work was to evaluate the phytochemical composition and in vitro biological activity of essential oils derived from Hippophae rhamnoides (Hr_EO), Cymbopogon citratus (Cc_EO), and Ocimum basilicum (Ob_EO) species on HT-29 and Caco-2 human colorectal adenocarcinoma cell lines. The main compounds identified by GC-MS analysis were estragole (Hr_EO, Ob_EO), alpha- and beta-citral (Cc_EO). All tested EOs exerted a dose-dependent cytotoxicity on both cell lines by reducing the cell viability, especially in the case of Cc_EO, where at 75 µg/mL the viability percentages reached the values of 62.69% (Caco-2) and 64.09% (HT-29), respectively. The nuclear morphology evaluation highlighted significant dysmorphologies on both lines after their treatment with EOs at 75 µg/mL.

Experimental Models of Hepatocellular Carcinoma-A Preclinical Perspective.

Hepatocellular carcinoma (HCC), the most frequent form of primary liver carcinoma, is a heterogenous and complex tumor type with increased incidence, poor prognosis, and high mortality. The actual therapeutic arsenal is narrow and poorly effective, rendering this disease a global health concern. Although considerable progress has been made in terms of understanding the pathogenesis, molecular mechanisms, genetics, and therapeutical approaches, several facets of human HCC remain undiscovered. A valuable and prompt approach to acquire further knowledge about the unrevealed aspects of HCC and novel therapeutic candidates is represented by the application of experimental models. Experimental models (in vivo and in vitro 2D and 3D models) are considered reliable tools to gather data for clinical usability. This review offers an overview of the currently available preclinical models frequently applied for the study of hepatocellular carcinoma in terms of initiation, development, and progression, as well as for the discovery of efficient treatments, highlighting the advantages and the limitations of each model. Furthermore, we also focus on the role played by computational studies (in silico models and artificial intelligence-based prediction models) as promising novel tools in liver cancer research.

Plant-Derived Anticancer Compounds as New Perspectives in Drug Discovery and Alternative Therapy.

Despite the recent advances in the field of chemically synthetized pharmaceutical agents, nature remains the main supplier of bioactive molecules. The research of natural products is a valuable approach for the discovery and development of novel biologically active compounds possessing unique structures and mechanisms of action. Although their use belongs to the traditional treatment regimes, plant-derived compounds still cover a large portion of the current-day pharmaceutical agents. Their medical importance is well recognized in the field of oncology, especially as an alternative to the limitations of conventional chemotherapy (severe side effects and inefficacy due to the occurrence of multi-drug resistance). This review offers a comprehensive perspective of the first blockbuster chemotherapeutic agents of natural origin's (e.g. taxol, vincristine, doxorubicin) mechanism of action using 3D representation. In addition is portrayed the step-by-step evolution from preclinical to clinical evaluation of the most recently studied natural compounds with potent antitumor activity (e.g. resveratrol, curcumin, betulinic acid, etc.) in terms of anticancer mechanisms of action and the possible indications as chemotherapeutic or chemopreventive agents and sensitizers. Finally, this review describes several efficient platforms for the encapsulation and targeted delivery of natural compounds in cancer treatment.

Impact of Dietary Restriction Regimens on Mitochondria, Heart, and Endothelial Function: A Brief Overview.

Caloric restriction (CR) and intermittent fasting (IF) are strategies aimed to promote health beneficial effects by interfering with several mechanisms responsible for cardiovascular diseases. Both dietary approaches decrease body weight, insulin resistance, blood pressure, lipids, and inflammatory status. All these favorable effects are the result of several metabolic adjustments, which have been addressed in this review, i.e., the improvement of mitochondrial biogenesis, the reduction of reactive oxygen species (ROS) production, and the improvement of cardiac and vascular function. CR and IF are able to modulate mitochondrial function via interference with dynamics (i.e., fusion and fission), respiration, and related oxidative stress. In the cardiovascular system, both dietary interventions are able to improve endothelium-dependent relaxation, reduce cardiac hypertrophy, and activate antiapoptotic signaling cascades. Further clinical studies are required to assess the long-term safety in the clinical setting.

Tetracyclic and Pentacyclic Triterpenes with High Therapeutic Efficiency in Wound Healing Approaches.

Wounds are among the most common skin conditions, displaying a large etiological diversity and being characterized by different degrees of severity. Wound healing is a complex process that involves multiple steps such as inflammation, proliferation and maturation and ends with scar formation. Since ancient times, a widely used option for treating skin wounds are plant- based treatments which currently have become the subject of modern pharmaceutical formulations. Triterpenes with tetracyclic and pentacyclic structure are extensively studied for their implication in wound healing as well as to determine their molecular mechanisms of action. The current review aims to summarize the main results of in vitro, in vivo and clinical studies conducted on lupane, ursane, oleanane, dammarane, lanostane and cycloartane type triterpenes as potential wound healing treatments.

Thermosensitive Betulinic Acid-Loaded Magnetoliposomes: A Promising Antitumor Potential for Highly Aggressive Human Breast Adenocarcinoma Cells Under Hyperthermic Conditions.

PURPOSE: Breast cancer presents one of the highest rates of prevalence around the world. Despite this, the current breast cancer therapy is characterized by significant side effects and high risk of recurrence. The present work aimed to develop a new therapeutic strategy that may improve the current breast cancer therapy by developing a heat-sensitive liposomal nano-platform suitable to incorporate both anti-tumor betulinic acid (BA) compound and magnetic iron nanoparticles (MIONPs), in order to address both remote drug release and hyperthermia-inducing features. To address the above-mentioned biomedical purposes, the nanocarrier must possess specific features such as specific phase transition temperature, diameter below 200 nm, superparamagnetic properties and heating capacity. Moreover, the anti-tumor activity of the developed nanocarrier should significantly affect human breast adenocarcinoma cells. METHODS: BA-loaded magnetoliposomes and corresponding controls (BA-free liposomes and liposomes containing no magnetic payload) were obtained through the thin-layer hydration method. The quality and stability of the multifunctional platforms were physico-chemically analysed by the means of RAMAN, scanning electron microscopy-EDAX, dynamic light scattering, zeta potential and DSC analysis. Besides this, the magnetic characterization of magnetoliposomes was performed in terms of superparamagnetic behaviour and heating capacity. The biological profile of the platforms and controls was screened through multiple in vitro methods, such as MTT, LDH and scratch assays, together with immunofluorescence staining. In addition, CAM assay was performed in order to assess a possible anti-angiogenic activity induced by the test samples. RESULTS: The physico-chemical analysis revealed that BA-loaded magnetoliposomes present suitable characteristics for the purpose of this study, showing biocompatible phase transition temperature, a diameter of 198 nm, superparamagnetic features and heating capacity. In vitro results showed that hyperthermia induces enhanced anti-tumor activity when breast adenocarcinoma MDA-MB-231 cells were exposed to BA-loaded magnetoliposomes, while a low cytotoxic rate was exhibited by the non-tumorigenic breast epithelial MCF 10A cells. Moreover, the in ovo angiogenesis assay endorsed the efficacy of this multifunctional platform as a good strategy for breast cancer therapy, under hyperthermal conditions. Regarding the possible mechanism of action of this multifunctional nano-platform, the immunocytochemistry of the MCF7 and MDA-MB-231 breast carcinoma cells revealed a microtubule assembly modulatory activity, under hyperthermal conditions. CONCLUSION: Collectively, these findings indicate that BA-loaded magnetoliposomes, under hyperthermal conditions, might serve as a promising strategy for breast adenocarcinoma treatment.

Urinary Microbiota-Are We Ready for Prime Time? A Literature Review of Study Methods' Critical Steps in Avoiding Contamination and Minimizing Biased Results.

Within the last few years, there have been an increased number of clinical studies involving urinary microbiota. Low-biomass microbiome sequencing (e.g., urine, lung, placenta, blood) is easily biased by contamination or cross-contamination. So far, a few critical steps, from sampling urine to processing and analyzing, have been described (e.g., urine collection modality, sample volume size, snap freezing, negative controls usage, laboratory risks for contamination assessment, contamination of negative results reporting, exploration and discussion of the impact of contamination for the final results, etc.) We performed a literature search (Pubmed, Scopus and Embase) and reviewed the published articles related to urinary microbiome, evaluating how the aforementioned critical steps to obtain unbiased, reliable results have been taken or have been reported. We identified different urinary microbiome evaluation protocols, with non-homogenous reporting systems, which can make gathering results into consistent data for similar topics difficult and further burden the already so complex emerging field of urinary microbiome. We concluded that to ease the progress in this field, a joint approach from researchers, authors and publishers would be necessary in order to create mandatory reporting systems which would allow to recognize pitfalls and avoid compromising a promising field of research.

Right hepatectomy extended to segments I and IVa and segmental colectomy performed in the same operative time - case presentation.

Colorectal cancer remains an important cause of morbidity and mortality worldwide. We present the case of a 58-year-old male patient admitted in Timisoara Hepato-Biliary-Pancreatic Surgical Center, Romania, with transverse colon cancer and synchronous liver metastases, who underwent a major hepatectomy and a segmental colon resection performed in the same operative time. The patient had a postoperative outcome without major complications and with no signs of local or distant recurrence at 15 months postoperatively. Conclusions: The synchronous approach of both the primary tumor and liver metastases in colorectal cancer is a possible therapeutic method, even in the case of major hepatectomies.

Left internal carotid artery agenesis associated with communicating arteries anomalies. A case report.

Agenesis, aplasia and hypoplasia of the internal carotid artery are rare congenital malformations. They are usually asymptomatic and incidentally discovered through ultrasound or imagistic tests. The aim of this study is to improve their management in our Departments. We report here the case of a 39-year-old woman addressed to our ambulatory in 2013 for benign symptoms like dizziness and headache. Imagistic findings (magnetic resonance imaging of the brain, and cervical spine, and magnetic resonance angiography of the head and neck) indicated a very rare condition: left internal carotid artery agenesis accompanied by the absence of the pre-communicant part of the left anterior cerebral artery and of the right posterior communicating artery. Internal carotid artery agenesis is an uncommon congenital anomaly and it could be misdiagnosed as stenosis/occlusion of this artery. This condition is important to be recognized due to the associated hemodynamic changes and in order to discover and evaluate other accompanying vascular malformations (aneurysms, collateral channels) and their life threatening potential risks (subarachnoid hemorrhage or ischemia). Also, it has a special importance in case of planning carotid or trans-sphenoidal hypophyseal surgery.