Search

Honey, considered a functional food with a complex chemical composition, has been revered since ancient times for its nutritional and therapeutic properties. In addition to its high sugar content, honey contains a wide variety of bioactive components, especially phenolic acids and flavonoids, which gives it a high antioxidant and anti-inflammatory activity. In addition, results obtained by in vitro and in vivo testing of different types of honey have demonstrated the potential effects of this product in the prevention, progression and therapy of cancer. The antitumor effects of honey are generally attributed to different mechanisms, such as blocking the cell cycle, activating the mitochondrial pathway, permeabilizing the outer mitochondrial membrane, inducing apoptosis and, on the other hand, modulating oxidative stress, ameliorating inflammation and inhibiting angiogenesis. These aspects have demonstrated excellent preclinical potential in a variety of conditions and physiological systems, an aspect that can guide future research in thoroughly delving into the mechanisms of action of this proven "superfood" that can be optimized for the benefit of humanity.

The biological activity of important honey, one of the most characteristics, which distinguishes it from other natural products and makes it important for the medical and therapeutic field. Its potential health benefits can be influenced both by its composition, which varies between different types of honey, and by the bioavailability of various phytochemical components and how they are absorbed and metabolized. It was found that a series of compounds contained in honey such as phenolic compounds, especially flavonoids, have an inhibitory effect against a wide spectrum of bacterial species, Gram-positive (G+) and Gram-negative (G-), but also an important antifungal and antiviral action. These important properties of honey are due both to the quality of the polyphenols contained, which is more important than their quantity, but also to the high osmolarity, acidity, H2O2 content and the composition of non-peroxidic components.

Objectives: The aim of this study was to evaluate the variation in the size of periapical lesions in patients with ENT cancer before and after radiotherapy by using the imaging examination represented by CT. Materials and methods: our study included 35 cancer patients-34 men and one female, with ENT cancer, under treatment at the Regional Institute of Oncology, Iasi. They were examinated by four endodontist, two radiologists and an ENT doctor. We measured the size of the periapical lesions before and after radiotherapy. Results: We found the change in the dimensions of periapical lesions: their maximum overall size was initially 5.4591 ± 3.88509 mm; after radiotherapy the global maximum size reached 7.0000 ± 3.37510, reaching 14.00 mm. The observed difference was statistically significant, so it could be stated that radiotherapy accentuates the severity of periapical lesions systematically. Before radiotherapy, the most extensive periapical lesions were observed in the case of laryngeal neoplasm ( with an average of 6.6778 ± 4.17246 mm) and nasopharyngeal neoplasm ( with an average of 6.000 ± 2.82843 mm) and the lowest ones were found in the case of the neoplasm of the oropharynx (with an average of 4.0000 ± 3.74166 mm). After radiotherapy, we found an increase in the size of the periapical lesions in the case of all five types of neoplasm investigated. The most extensive lesions were observed in the case of the neoplasm of the oropharynx, with an average of 7.6000 ± 3.84708 mm, followed by the neoplasm of the larynx, with an average of 7.4000 ± 3.33999 and the neoplasm of the oral cavity, with an average of 7.4000 ± 4.33590 mm. Disscusions: In terms of expectancy and quality of life of patients can only be achieved through a multidisciplinary approach. As soon as the dentist diagnoses a pontetially malignant disorder in the ENT sphere, patients should undergo an ENT screening complete for detecting lesions in any area of the upper aerodigestive tract. After radiotherapy an increase in the size of the periapical lesions is observed. The ENT doctor must encourage the patients with ENT cancer to extract their teeth with periapical lesions before the implementation of radiotherapy to avoid the risk of postradiotherapy osteoradionecrosis. Conclusions: By using CT, the increase in the size of periapical lesions after radiotherapy is observed in patients with cancer in the ENT sphere.

Objectives: Our aim was to demonstrate the occurrence of post-radiotherapy side effects- even in the case of using intensively modulated therapy (IMRT) in patients with ENT cancer as its are: radiomucositis, dental caries, osteoradionecrosis, the increase in the size of the existing periapical lesions before radiotherapy, dysphagia, dysgeusia. Materials and methods: Our study included 35 cancer patients age between 32-81 years old with ENT cancer- neoplasm of larynx, oropharynx, oral cavity, nasopharynx, hypopharynx, sinuses; under treatment at the Regional Institute of Oncology, Iasi. They were examinated by one dental generalist, two endodontist, one radiologist, one doctor specialized in radiotherapy and an ENT doctor before and after radiotherapy. We used as irradiation dose between 50-70 Gy. Results: All patients suffered from various forms of cancer; the majority (40%) presented a neoplasm of the larynx, 8 patients (22,9%) presented a neoplasm of oropharynx, 6 patients (17,1%) presented a neoplasm of the oral cavity. Other forms of neoplasm found were nasopharynx, hypopharynx and respectively sinus neoplasm (1 case). The vast majority of the patients presented radiomucositis grade 2 (34,3%) and 3 (45,7%). The distribution of the localization of periapical lesions changed before and after radiotherapy. Osteoradionecrosis was initially diagnosed in 3 of the 35 patients (8,6%); after radiotherapy osteoradionecrosis was diagnosed in 6 patients (17,1%). We did not identify a statistically significant relationship between the dose of radiation administered and the degree of radiomucositis. Disscusions: Our retrospective study reported a frequency of 40% cancer of the larynx, 22,9% cancer of the oropharynx and 17,1% neoplasm of the oral cavity, followed by cancer of the nasopharynx, hypopharynx and sinus neoplasm out of a total of 35 patients taken into account. Taking into account the fact that the patients received an irradiation dose between 70 Gy (65,7%)- 66 Gy (22,9%), the degree of radiomucositis was mainly 2 (34,3%) or 3 (45,7%). We observed an increase in the diameter of the periapical lesions after radiotherapy associated with the dose of radiation administered. Areas with osteoradionecrosis revealed the same tendency of increase in their comparative analysis after the applied irradiation doses. Conclusions: The management of the side effects of radiotherapy can be managed favorably for the oncological patient through a close collaboration between the general dentist, ENT and the radiotherapist.

Acromegaly is a rare endocrine disorder characterized by the excessive production of growth hormone (GH) in adulthood. Currently, it is understood that certain pituitary neuroendocrine tumors (PitNETs) exhibit a hereditary predisposition. These tumors’ genetic patterns fall into two categories: isolated and syndromic tumors. The isolated forms are characterized by molecular defects that predispose exclusively to PitNETs, including familial isolated pituitary adenomas (FIPAs) and sporadic genetic defects not characterized by hereditary predisposition. All the categories involve either germline or somatic mutations, or both, each associated with varying levels of penetrance and different phenotypes. This highlights the importance of genetic testing and the need for a more comprehensive view of the whole disease. Despite the availability of multiple treatment options, diagnosis often occurs after several years, and management is still difficult. Early detection and intervention are crucial for preventing complications and enhancing the quality of life for affected individuals. This review aims to elucidate the molecular, clinical, and histological characteristics of GH-secreting PitNETs, providing insights into their prevalence, treatment nuances, and the benefits of genetic testing for each type of genetic disorder associated with acromegaly.

Background: Plants have long been recognized for their potential to influence neurological health, with both neuroprotective and neurotoxic properties. This review explores the dual nature of plant-derived compounds and their impact on the human brain. Discussion: Numerous studies have highlighted the neuroprotective effects of various phytoconstituents, such as those found in Ginkgo biloba, Centella asiatica, Panax ginseng, Withania somnifera, and Curcuma longa. The neuroprotective compounds have demonstrated antioxidant, anti-inflammatory, and cognitive-enhancing properties, making them promising candidates for combating neurodegenerative diseases and improving brain function. Polyphenolic compounds, triterpenic acids, and specific phytocompounds like the ones from EGb 761 extract have shown interactions with key enzymes and receptors in the brain, leading to neuroprotective outcomes. However, this review also acknowledges the neurotoxic potential of certain plants, such as the Veratrum species, which contains steroidal alkaloids that can cause DNA damage and disrupt neurological function, or Atropa belladonna, which interfere with the normal functioning of the cholinergic system in the body, leading to a range of symptoms associated with anticholinergic toxicity. Conslusions: This review also emphasizes the need for further research to elucidate the complex mechanisms underlying the neuroprotective and neurotoxic effects of plant-derived compounds, as well as to identify novel phytoconstituents with therapeutic potential. Understanding the complex relationship between plants and the human brain is crucial for harnessing the benefits of neuroprotective compounds while mitigating the risks associated with neurotoxic substances. This review provides a comprehensive overview of the knowledge on the neurological properties of plants and highlights the importance of continued research in this field for the development of novel therapeutic strategies targeting brain health and neurological disorders.

The nasal route of administration can bypass the blood–brain barrier in order to obtain a higher concentration in the brain, thus offering a feasible alternative route of administration for diseases associated with the central nervous system. The advantages of the intranasal administration and the potential favorable therapeutic effects of intranasally administered insulin led to the formulation of carboxymethyl chitosan (CMC) and sodium hyaluronate (NaHA) hydrocolloidal systems with insulin for nasal administration, targeting nose-to-brain delivery and the initial assessment of these systems. The influence of the formulation variables on the response parameters defined as surface properties, rheology, and in vitro release of insulin were analyzed using experimental design and statistical programs (Modde and Minitab software). The systems recorded good wetting and adhesion capacity, allowing the spread of the hydrocolloidal systems on the nasal mucosa. The samples had a pseudoplastic flow and the rapid release of the insulin was according to our objective. According to the physico-chemical characterization and preliminary assessment, these formulations are appropriate for administration on the nasal mucosa, but further studies are necessary to demonstrate the beneficial therapeutic actions and the safety of using intranasal insulin.

Chronic threatening limb ischemia of the inferior limbs (CLTI) is the final stage of peripheral arterial disease (PAD) and is one of the most feared atherosclerotic manifestations because if left untreated, in time, it can lead to amputation. Although there are currently numerous treatment techniques, both open and endovascular, it is a pathology that has no underlying treatment. Therefore, current studies are very much focused on new therapeutic possibilities that can be applied in the early stages of the atherosclerotic process. In numerous studies in the literature, miRNAs have been identified as important markers of atherosclerosis. The present study aims to identify the expression of three miRNAs—miR-199a, miR-20a, and miR-30c—in patients with chronic limb-threatening ischemia in the pre- and post-revascularization periods. The aim of the study is to identify whether these three markers play a role in critical ischemia and whether they have the potential for future use in new treatments of this pathology.

Background: Acromegaly is a rare disorder caused by excessive growth hormone (GH) secreted from a pituitary tumor. High levels of GH and insulin growth factor-1 can lead to renal hypertrophy, as well as to diabetes mellitus and hypertension, which negatively impact kidney function. It is believed that high GH may also be involved in the onset of diabetic nephropathy, the main cause of end-stage kidney disease in developed countries. Material and methods: This case–control study was conducted on 23 acromegalic patients and on a control group represented by 21 healthy subjects. The following parameters were determined for all the subjects: serum creatinine, serum urea, estimated glomerular filtration rate (eGFR), urinary albumin/creatinine ratio (UACR), nephrin and kidney injury molecule 1 (KIM-1). Results: Patients with acromegaly showed higher levels of UACR and lower levels of eGFR as compared to healthy subjects. No significant correlations were found between clinical or biochemical parameters associated with acromegaly and nephrin or KIM-1. Conclusions: There was no glomerular or proximal tubular damage at the time of the study, as proven by the normal levels of the biomarkers nephrin and KIM-1. Studies including more patients with uncontrolled disease are needed to clarify the utility of nephrin and KIM-1 for the detection of early kidney involvement in acromegalic patients.

Worldwide, breast cancer (BC) is one of the most common cancers in women and is responsible for the highest number of cancer-related deaths among women, with a special clinical behavior and therapy response. Triple-negative breast cancer (TNBC) is seen as a highly invasive BC, characterized by a short survival, higher mortality, recurrence, and metastasis when it is compared to the other BC subtypes. The molecular subtyping of TNBC based on mRNA expression levels does not accurately reflect protein expression levels, which impacts targeted therapy effectiveness and prognostic predictions. Most TNBC cases exhibit a high frequency of homologous recombination (HR) DNA repair deficiency (HRD) signatures and are associated with a complex genomic profile. Biomarker research in TNBC includes investigating genetic mutations, gene expression patterns, immune system-related markers, and other factors that can provide valuable information for diagnosis, treatment selection, and patient outcomes. Additionally, these biomarkers are often crucial in the development of personalized and precision medicine approaches, where treatments are customized to each patient’s unique characteristics. This ongoing research is essential for improving the management and outcomes of TNBC, which is a challenging and heterogeneous form of breast cancer. The findings of this research have practical implications for refining treatment strategies, particularly in selecting appropriate systemic therapies and integrating traditional treatment modalities like surgery and radiotherapy into comprehensive care plans for TNBC patients.

The aim of the present study was to formulate new variants of synthetic and animal-source bone materials coated with different biopolymers, containing antibiotics (ampicillin and oxacillin) and alendronate drugs. Validation consists in establishing mixtures that do not present interactions between components. These materials should act as a drug delivery system alongside the bone base. Natural polymers such as chitosan, alginate, and kappa-carrageenan have been shown to be optimal materials for drug delivery due to their intrinsic biocompatibility. Binary, ternary, and quaternary mixtures between components are analyzed by FT-IR spectroscopy, UV-Vis analysis, thermogravimetry (TGA), and scanning electron microscopy (SEM). The analysis led to the validation of materials suitable for the controlled release of active substances, which have the greatest chance of increasing the speed of bone regeneration, as well as helping in the local administration of antibiotics, which currently must be administered in the form of oral formulations or an injection. According to the FTIR, thermogravimetry, UV-Vis, SEM, and cytotoxicity tests performed in this study, it can be said that it is quite easy to obtain materials that can be used in dental practice that facilitate bone reconstruction through local treatment. At the same time, it was found that both active substances can be incorporated into the material together with Alg and Chit, thus limiting the adverse effects and maximizing the local beneficial effects.

Epicardial adipose tissue (EAT) is a unique fat depot located around the heart, intimately associated with the myocardium and coronary arteries. The secretion of bioactive molecules and their interaction with neighbouring cardiac tissues makes it an active organ with important implications in cardiovascular health and disease. In recent years, omics technologies have provided valuable insights into the molecular characteristics and functional relevance of EAT in patients with coronary atherosclerosis, myocardial infarction, atrial fibrillation and associated metabolic disorders. This review aims to summarize the current understanding of EAT biology through the lens of genomics, transcriptomics, proteomics and lipidomics approaches. We discuss key findings from omics studies on EAT, including gene expression profiles, metabolic activity, signalling pathways and regulatory network, in order to explore in depth the disease mechanisms, possible therapeutic strategies, and cardiovascular risk assessment. Further advances in this field and integrating data from multiple omics platforms hold promise for unlocking personalized cardiometabolic profiles with EAT as a possible biomarker and therapeutic target in cardiovascular disease.

Background: Chronic limb-threatening ischemia (CLTI), the advanced stage of peripheral arterial disease, is diagnosed in the presence of ischemic rest pain, non-healing ulcers, or gangrene. Several studies have demonstrated that inflammation and endothelial dysfunction are some of the main substrates of CLTI. Methods: A narrative review was conducted and reported according to PRISMA guidelines. Three databases were searched—Web of Science, Medline, and EMBASE—for the studies assessing CLTI and the biological markers related to it. Results: We included 22 studies, and all the markers identified (C-reactive protein, D-dimers, fibrinogen, cytokines, IL-6, TNF-α, ICAM-1 (Intracellular Adhesion Molecule-1), VCAM-1 (Vascular Cell Adhesion Molecule-1), neutrophile-to-lymphocytes ratio (NLR), IL-8, Pentraxin-3, neutrophil gelatinase-associated lipocalin (NGAL), calprotectin, E-selectin, P-selectin, neopterin, High-Mobility Group Box-1 protein (HGMB-1), Osteoprotegerin (OPG) and Sortilin) were positively associated with advanced CLTI, with major limb or major cardiovascular events in these patients. Conclusions: All the studied markers had increased values in patients with CLTI, especially when associated with diabetes mellitus, proving a very important association between diabetes and major limb or cardiovascular events in these patients. There is a need for more studies to validate these markers in terms of diagnosis or prognosis in CLTI patients and in trying to find new medical strategies that target inflammation or endothelial dysfunction in these patients.

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-β-(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.

Background: Breast cancer is the most frequently diagnosed cancer among women, responsible for the highest number of cancer-related deaths worldwide. There is limited data available related to serum tumor markers in breast cancer and other blood parameters or other glandular laboratory parameters. This study aims to evaluate the correlation of tumor-specific markers for breast cancer with other blood parameters and how these correlations could impact clinical management. Material and Method: This retrospective study represents a data analysis from 1 January 2020 to 31 May 2023, in the County Hospital of Timisoara, Romania. We reviewed all the cases where, in the laboratory analyses, the serum tumor specific biomarkers for breast cancer were analyzed. Results: A statistical analysis was performed in order to identify a possible relationship between CA 15-3 and the various biomarkers and blood parameters included in the present study. Values were classified according to reference ranges. The tests revealed no statistically significant associations between CA 15-3 values and the levels of CA125 (χ2(1) = 1.852, p = 0.174), CEA (χ2(1) = 1.139, p = 0.286), AFP (Fisher’s exact test, p = 0.341), fT4 (Fisher’s exact test, p = 0.310), TSH (Fisher’s exact test, p = 0.177), or PTH (Fisher’s exact test, p = 0.650). Conclusion: The findings indicate a lack of strong correlation between CA 15-3 and CA125, CEA, AFP, thyroid function markers, or PTH within this cohort.

We describe the survey design and science goals for One-hundred-deg ^2 DECam Imaging in Narrowbands (ODIN), a NOIRLab survey using the Dark Energy Camera (DECam) to obtain deep (AB ∼ 25.7) narrowband images over an unprecedented area of sky. The three custom-built narrowband filters, N 419, N 501, and N 673, have central wavelengths of 419, 501, and 673 nm and respective FWHM of 7.5, 7.6, and 10.0 nm, corresponding to Ly α at z = 2.4, 3.1, and 4.5 and cosmic times of 2.8, 2.1, and 1.4 Gyr, respectively. When combined with even deeper, public broadband data from the Hyper Suprime-Cam, DECam, and in the future, the Legacy Survey of Space and Time, the ODIN narrowband images will enable the selection of over 100,000 Ly α -emitting (LAE) galaxies at these epochs. ODIN-selected LAEs will identify protoclusters as galaxy overdensities, and the deep narrowband images enable detection of highly extended Ly α blobs (LABs). Primary science goals include measuring the clustering strength and dark matter halo connection of LAEs, LABs, and protoclusters, and their respective relationship to filaments in the cosmic web. The three epochs allow for the redshift evolution of these properties to be determined during the period known as Cosmic Noon, where star formation was at its peak. The narrowband filter wavelengths are designed to enable interloper rejection and further scientific studies by revealing [O ii ] and [O iii ] at z = 0.34, Ly α and He ii 1640 at z = 3.1, and Lyman continuum plus Ly α at z = 4.5. Ancillary science includes similar studies of the lower-redshift emission-line galaxy samples and investigations of nearby star-forming galaxies resolved into numerous [O iii ] and [S ii ] emitting regions.

Background: Hepatic encephalopathy (HE) caused by cirrhosis has severe consequences on an individual’s lifespan, leading to long-term liver complications and potentially life-threatening outcomes. Despite recent interest in this condition, the effectiveness of secondary prophylaxis involving rixafimin, lactulose, or L-ornithine L-aspartate (LOLA) may be hindered by the unique microbial profiles each patient possesses. Methods: Thus, in this manuscript, we aimed to search, identify, and gather all randomized controlled trials (RCTs) published between 2000–2023 (November) in four major academic databases such as PubMed, ISI Web of Science, Scopus, and ScienceDirect by using a controlled terminology and web strings that reunite six main keywords. We complementarily retrieved data on the ongoing RCTs. Results: Regardless of the relatively high number of results displayed (n = 75), 46.66% (n = 35) were initially deemed eligible after the first evaluation phase after removing duplicates, n = 40 (53.34%). At the second assessment stage, we eliminated 11.42% (n = 4) studies, of which n = 22 finally met the eligibility criteria to be included in the main body of the manuscript. In terms of RCTs, otherwise found in distinct stages of development, n = 3 target FMT and n = 1 probiotics. Conclusions: Although we benefit from the necessary information and technology to design novel strategies for microbiota, only probiotics and synbiotics have been extensively studied in the last decade compared to FMT.

Aim of the study The aim of the study is to present a particular case of Gorlin-Goltz syndrome (GGS) and to assess the importance of both clinical and radiological findings in the management of this rare disease. Material and methods We studied a GGS case from our hospital and integrated his clinical and radiological findings in order to assess the importance of conventional radiography, computer tomography (CT), magnetic resonance imaging (MRI) and cone beam computer tomography (CB-CT). Results In this particular case we illustrate the role of MRI and CT examination in determining facial BCC extension and respectively GGS skeletal features. Conclusions Even if GGS is a rare chronic condition, if not periodically and properly investigated, it can lead to invasive basal cell carcinomas (BCCs) or other complication like facial deformities, mandibular fractures caused by keratocystic odontogenic cyst (OKCs).

Zinc (Zn), copper (Cu), iron (Fe), manganese (Mn), cadmium (Cd), and lead (Pb) levels were measured in the Bor City water supply system (control) and two watercourses exposed to mining wastewaters, i.e., the Lutarica River (one site) and the Kriveljska River (two sites). The same parameters were determined in the brain, heart, lungs, stomach, liver, spleen, kidneys, and testes of male Wistar rats given water from these sources for 2 months. Water Cu, Fe, Cd, and Pb were outside the safe range, excepting the reference site. Significant impacts on intra-organ metal homeostasis were detected, especially in the brain, stomach, kidneys, and testes. The dynamics and magnitude of these changes (versus controls) depended on the target organ, analyzed metal, and water origin. The greatest number of significant intra-organ associations between essential and non-essential metals were found for Cd-Zn, Cd-Cu, and Cd-Mn. A regression analysis suggested the kidneys as the most relevant organ for monitoring water manganese, and the stomach and brain for lead. These results highlight the environmental risks associated with mining wastewaters from the Bor area and could help scientists in mapping the spatial distribution and severity of trace metal contamination in water sources.

Nowadays, worldwide neoplastic pathology is a major public health problem. Despite the many therapeutic strategies currently available in chemotherapy and radiotherapy, the number of new cancer cases and cancer deaths is increasing. An inexpensive alternative without adverse effects is the development of therapeutic strategies using herbal compounds obtained from various natural sources. On the other hand, the development of therapeutic alternatives involves testing their cytotoxic effects on healthy human cells. In this study, we tested Ocimum basilicum extracts (in butanol and acetonitrile), in concentrations between 5mg/ml and 40mg/ml, in order to evaluate the cytotoxic potential on colon (Caco2), liver (HepG2) and blood cancer (K-562). We analysed the biocompatibility of the products in vitro on healthy cell lines (MSC-mesenchymal STEM cells and HDFA- human fibroblasts). Cell proliferation was analyzed by the MTT assay. The obtained results revealed that the tested extracts do not significantly modify the multiplication of healthy human cells. Instead, it causes a decrease in the cell growth rate for liver and colon neoplastic cells, and less so for leukemic cells.

Numerous studies have reported positive associations between certain biologically active compounds, with pharmacological properties, such as nutraceuticals, contained in some foods and various pathologies. The term "nutraceutical" currently varies from country to country, referring to a number of valuable molecules, derived from organic sources (plants) or foods such as polyphenols, essential amino acids, antioxidants, soluble fiber, polyunsaturated fatty acids ( PUFA), prebiotics, prebiotics, which act at the cellular level, in combating oxidative stress and inflammatory processes and / or in altering the expression of some genes. The discovery of the many benefits attributed to these products and the ever-changing lifestyle have contributed to increasing consumer confidence in nutraceutical and functional foods around the world, and there is a growing interest in improving the quality of life and adopting a healthy lifestyle. to prevent or reduce the risk of disease. Based on these considerations, this paper aims to review some scientific evidence obtained from in vitro / in vivo studies, which supports the beneficial effects of some nutraceuticals and their medical implications in various pathologies.

The milk intended for human consumption must meet the terms of safety and human security. The purpose of this paper was to evaluate the raw milk quality from the food markets of Timisoara, in relation with pasteurized milk. The microbiological studies included the following assays: total number of germs (TNG) and coliform bacteria. From milk samples were made dilutions which later were distributed on the surface of the solid medium poured in Petri dishes. The incubation was carried out at 37º C for 48 h, after which it was determined the number of colony forming units. The obtained values for each sample were compared with the values in existing legislation noticing that the total number of germs is within normal values but towards the upper limit of normality, except the milk samples from Sacos village where UFC/ml exceed the maximum value admitted (300.000 UFC/ml milk). In coliform bacteria case is observed that in all analyzed milk samples the values obtained exceed the maximum values admitted (0.1 UFC/ml) indicating the existence of inappropriate sanitary and hygienic conditions of milking, transporting and marketing.

Due to the fact that, for a few years now, our focus is more and more concentrated on safety and security of meat and vegetable products, this study’s aim is to evaluate the quality of certain well - known meat products (sausages, dry salami, and half-dried salami), purchased in a supermarket, from Timisoara. Microbiological tests were made especially on sanitary microbiological indicators (Escherichia, Enterobacter, Klebsiella). These tests emphasize hygiene in processing ang handling of products. In some cases, it higtlights how various heat treatments (pasteurization type) apply to food products. It also establishes the microbial load on the microscopic field and the colony forming units, by a culture method in plates, at 37º C for 48 hours. Based on the obtained results, it has been established that, concerning the microbial load and the presence or absence of coliform bacteria, studied products fall into the quality permitted by applicable law.

Silybin is a flavonoid extracted from the herb Armurariu (Silybum marianum) and has the potential efficacy in the treatment of liver disease. The aims of this study were to investigate the effect of alcohol and CCl4 on liver histology and the capacity of silybin to ameliorate the hepatotoxicity. Thirty adult male Wistar rats were used in the study. Liver toxicity was induced by dietary alcohol administration and CCl4 intra-peritoneal injection. The protective effect of silibin was investigated by co-administration of silybin with these toxic agents. Hepatocellular and extracellular matrix integrity was determined by histopathological and immunohistochemical study. Hematoxylin-Eosin and trichrome stains sections were studied in each case. For immunohistochemistry we used monoclonal anti-collagen IV primary antibody. Light microscopic evaluation of liver tissues shows that control and silibin treated groups has normal liver structure. In the toxicity groups, HE and trichromic staining showed hepatocellular necrosis, inflammatory infiltrate and proliferating collagen fibers. Immunoexpression of collagen IV was variable. In the control group, we found negative expression. Collagen IV displays positive immunoreaction in hepatotoxicity groups, at the level of the areas rich in inflammatory infiltrate and with degenerative aspect. After this study, we can conclude that silybin, in rats, has protective effects.

Background: Helicobacter pylori antibiotic resistance has increased worldwide and affects the effectiveness of current therapies. The recommended first-line empiric treatment should be tailored to the local clarithromycin resistance rate. This study aimed to determine the pediatric patient profile and rate of clarithromycin resistance for patients diagnosed with Helicobacter pylori by gastric biopsy. Methods: We studied 84 positive gastric samples for Helicobacter pylori. Positive results were confirmed by a rapid urease test and histopathological examination, with the type of gastritis established according to the Sydney System. Gastric biopsy samples were stored in RNA saver. Clarithromycin resistance was determined by a real-time polymerase chain reaction-based molecular assay after RNA-DNA extraction. Results: Of the 84 biopsy samples analyzed, 35 (41.6%) were resistant to clarithromycin. Clarithromycin resistance was found mainly in girls (80%) with a mean age of 15 years (range 6–17 years). The history of prior exposure to clarithromycin was 91.6%. The concordance between the histopathological examination and the PCR test was 100%. Conclusions: One in 2.4 children infected with Helicobacter pylori had a strain resistant to clarithromycin. This resistant strain may be a reason for treatment failure in Romanian children, yet this is uninvestigated. The high rate of bacterial resistance to this antibiotic among children indicates the need for susceptibility testing before therapy.

The delivery of nucleosides represents an interesting research trend in recent years due to their application in various viral infections. The main aims of this study were to develop and to characterize polyurethane particles that are intended to be used for the transport of nucleosides. Three samples have been prepared using aliphatic diisocyanates, a mixture of polyethylene glycol, polycaprolactone, and diols, respectively. The samples were characterized through refractivity measurements, drug loading efficacy, release and penetration rate investigations, FTIR and Raman spectroscopy, thermal analyses, Zetasizer, SEM, HDFa cells viability, and irritation tests on mice skin. The results indicate the obtaining of particles with sizes between 132 and 190 nm, positive Zeta potential values (28.3–31.5 mV), and a refractivity index around 1.60. A good thermal stability was found, and SEM images show a medium tendency to agglomerate. The samples’ color, pH, and electrical conductivity have changed only to a small extent over time, and the evaluations indicate an almost 70% encapsulation efficacy, a prolonged release, and that around 70% of particles have penetrated an artificial membrane in the first 24 h. The synthesized products should be tested in further clinical trials, and the current tests on cell cultures and mice skin revealed no side effects.

The ionic liquids have attracted a great of attention in the scientific community due to their potential pharmaceutical such as antimicrobial. In this paper, the main objective was the assessment of the cytotoxic effect of tetrabutylammonium chloride against HCT 8 human colon carcinoma cell line. The cells were cultured in 75 cm2 culture flasks using RPMI medium supplemented with 10% inactivated fetal bovine serum (FBS), penicillin (100 IU/mL) and streptomycin (100 μg/mL) and maintained at 37 °C and 5% CO2. Before achieving viability test, the cells were harvested using trypsin solution (0.25%). Then, the cells were seeded in 24 – well plates at a density of 5 x 105 cells/mL in 100 µL medium/well in order to reach confluence. After 24 h, the medium was replaced with fresh medium containing different concentrations of ionic liquid, respectively, 0.085, 0.17, 0.34, 0.68 and 1.36 mg /mL. Control group contained cells without treatment. Cell proliferation kinetics have been studied at 24 and 48 h after IL treatment, following trypsinization and counting total cells per plate by using a Trypan blue dye and a hemocytometer. Data obtained from the growth kinetics assay shows that the tetrabutylammonium chloride (TBAC) had an inhibitory effect on the growth of cells in a concentration dependent manner. The maximum inhibitory effect on HCT 8 cells it was obtained at 1.36 mg TBAC/mL.

Sulfonylurea herbicides are frequently used in agricultural crops even if they determine quantitative and qualitative changes in soil microbial communities. In this study it was used increasing doses of two sulfonylurea herbicides, tribenuron-methyl and nicosulfuron, in order to establish their effect on actinomyces communities from soil under laboratory conditions. Using nutritive gelose with soil extract and Gause medium the main species of actinomyces were identified: Streptomyces albus, Streptomyces aureus and Streptomyces chrysomallus. Streptomyces albus is the most abundant species, which could indicate a resistance to used herbicides. Sulfonylurea herbicides, tribenuron-methyl and nicosulfuron, point out a lower value, inhibiting the actinomycete communities from soil.

Liver regeneration after loss of important cell population is a complex process involving all mature liver cell types. We study the response of hepatocytes in 24h and 48h after partial hepatectomy by microscopic and morphometric analysis. Thirty adult male NMRI, 8 week old mice were used in the study. Liver regeneration after partial hepatectomy (68%) in mice is a complex process that is performed on account differentiated mature hepatocyte proliferation, as evidenced by the presence of nuclei hypertrophy, binucleate cells or polyploidy, and numerous mitotic figures. Morphometrical analysis of cell size showed increases in average dimension of the control compared to the experimental groups. After this study, we can conclude that liver regeneration after partial hepatectomy is marked by the proliferation of liver cell population, while reducing the apoptotic process.

Medicinal plants are used in poultry feed due to their beneficial effects on the intestinal microflora, digestibility of nutrients, intestinal morphology, aspects that are found in the quality of meat and eggs. Currently, due to its characteristics, coriander is widely used in the food, pharmaceutical and medical industry, in the cosmetics and perfume industry, but also in the zootechnical field, as an alternative to antibiotics, in raising young animals and birds. In this context, the aim of this study was to evaluate the additional effects of the diet of chickens with coriander powder on intestinal and liver morphology. The study was performed on a number of 24 broilers (ROS 308 hybrids), male, divided into two groups, each group with two replications, 6 individuals / group: Control group (CG) fed only by the basic diet and the experimental group (CoG) in which the basic diet was supplemented with 1% coriander powder. The duration of the experiment was 42 days. Supplementation of the basic diet of chickens with 1% coriander powder led to an increase in the analyzed histomorphometric parameters, the differences compared to the control group (CG) being significant (p0.05) for the width of the villi. In addition, at the hepatic level, dietary supplementation with coriander powder led to vascular hypertrophy, the presence of perivascular leukocyte infiltrates and the manifestation of cytoplasmic vacuolation of hepatocytes in the perilobular territories. Histomorphometric analysis of the data obtained in this study and histological changes in the liver provide new information on the use of coriander seed powder in broiler feed, as a potential promoter of their growth.

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.

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-β-(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.

The diagnosis and management of fragile X syndrome (FXS) have significantly improved in the last three decades, although the current diagnostic techniques are not yet able to precisely identify the number of repeats, methylation status, level of mosaicism, and/or the presence of AGG interruptions. A high number of repeats (>200) in the fragile X messenger ribonucleoprotein 1 gene (FMR1) results in hypermethylation of promoter and gene silencing. The actual molecular diagnosis is performed using a Southern blot, TP-PCR (Triplet-Repeat PCR), MS-PCR (Methylation-Specific PCR), and MS-MLPA (Methylation-Specific MLPA) with some limitations, with multiple assays being necessary to completely characterise a patient with FXS. The actual gold standard diagnosis uses Southern blot; however, it cannot accurately characterise all cases. Optical genome mapping is a new technology that has also been developed to approach the diagnosis of fragile X syndrome. Long-range sequencing represented by PacBio and Oxford Nanopore has the potential to replace the actual diagnosis and offers a complete characterization of molecular profiles in a single test. The new technologies have improved the diagnosis of fragile X syndrome and revealed unknown aberrations, but they are a long way from being used routinely in clinical practice.

Mitochondria are subcellular organelles involved in essential cellular functions, including cytosolic calcium regulation, cell apoptosis, and reactive oxygen species production. They are the site of important biochemical pathways, including the tricarboxylic acid cycle, parts of the ureagenesis cycle, or haem synthesis. Mitochondria are responsible for the majority of cellular ATP production through OXPHOS. Mitochondrial dysfunction has been associated with metabolic pathologies such as diabetes, obesity, hypertension, neurodegenerative diseases, cellular aging, and cancer. In this article, we describe the pathophysiological changes in, and mitochondrial role of, metabolic disorders (diabetes, obesity, and cardiovascular disease) and their correlation with oxidative stress. We highlight the genetic changes identified at the mtDNA level. Additionally, we selected several representative biomarkers involved in oxidative stress and summarize the progress of therapeutic strategies.

Abstract Background Familial hypercholesterolemia(FH) is one of the most frequent and important monogenic cholesterol pathologies. Traditional and non-traditional cardiovascular risk factors increase the prevalence of atherosclerotic cardiovascular disease(ASCVD) in this population. The aims of the study were: (a) to identify FH patients in the North-Eastern part of Romania and to analyze demographic, clinical and paraclinical data (b) to evaluate the risk of new cardiovascular events at follow-up in FH patients stratified by lipid-lowering agents. Methods This first prospective study in the North-Eastern part of Romania was carried out between October 2017 and October 2019; out of 980 patients with dyslipidemia evaluated with the Dutch Lipid Network(DLCN) and Simon Broome(SM) scores, 61 patients with DLCN score above 3 and possible/probable FH(SM score) were included. Results Nine hundred-eighty patients were examined and 61 (6.2%) were received the clinical diagnosis of FH. The mean age was 48.5±12.5 years, with more female patients than male patients (63.9% versus 36%). Hypertension was the main cardiovascular risk factor for both genders, followed by physical inactivity and obesity for the female group and active smoking for the male group. The measured DLCN score recorded: “possible” FH identified in 39.4%, “probable” FH in 45.9% and “definite” FH in 14.7%. The effective lipid-lowering drugs used were statin alone and statin in association with fenofibrate, which improved both the lipid profile values and the subclinical atherosclerosis markers (ankle-brachial index, carotid intima-media thickness and high-sensitivity C-reactive protein). New ASCVDs that emerged during the study were most commonly represented by coronary heart disease and stroke. At the same time, the new cardiovascular events were delayed in patients receiving the lipid-lowering drugs, without significant differences between them. Conclusions In patients with suspected FH, the lipid-lowering agents during the follow-up period delayed the new cardiovascular events, yet failed to reach the goals proposed by the guidelines.

Over the past 40 years, the 5-years-overall survival rate of pediatric cancer reached 75–80%, and for acute lymphoblastic leukemia (ALL), exceeded 90%. Leukemia continues to be a major cause of mortality and morbidity for specific patient populations, including infants, adolescents, and patients with high-risk genetic abnormalities. The future of leukemia treatment needs to count better on molecular therapies as well as immune and cellular therapy. Advances in the scientific interface have led naturally to advances in the treatment of childhood cancer. These discoveries have involved the recognition of the importance of chromosomal abnormalities, the amplification of the oncogenes, the aberration of tumor suppressor genes, as well as the dysregulation of cellular signaling and cell cycle control. Lately, novel therapies that have already proven efficient on relapsed/refractory ALL in adults are being evaluated in clinical trials for young patients. Tirosine kinase inhibitors are, by now, part of the standardized treatment of Ph+ALL pediatric patients, and Blinatumomab, with promising results in clinical trials, received both FDA and EMA approval for use in children. Moreover, other targeted therapies such as aurora-kinase inhibitors, MEK-inhibitors, and proteasome-inhibitors are involved in clinical trials that include pediatric patients. This is an overview of the novel leukemia therapies that have been developed starting from the molecular discoveries and those that have been applied in pediatric populations.

As the progenitors of present-day galaxy clusters, protoclusters are excellent laboratories to study galaxy evolution. Since existing observations of protoclusters are limited to the detected constituent galaxies at UV and/or infrared wavelengths, the details of how typical galaxies grow in these young, pre-virialized structures remain uncertain. We measure the total stellar mass and star formation within protoclusters, including the contribution from faint undetected members by performing a stacking analysis of 211 z = 2–4 protoclusters selected as Planck cold sources. We stack Wide-field Infrared Survey Explorer and Herschel/SPIRE images to measure the angular size and the spectral energy distribution of the integrated light from the protoclusters. The fluxes of protoclusters selected as Planck cold sources can be contaminated by line-of-sight interlopers. Using the WebSky simulation, we estimate that a single protocluster contributes 33% ± 15% of the flux of a Planck cold source on average. After this correction, we obtain a total star formation rate of 7.3 ± 3.2 × 10 ^3 M _⊙ yr ^−1 and a total stellar mass of 4.9 ± 2.2 × 10 ^12 M _⊙ . Our results indicate that protoclusters have, on average, 2× more star formation and 4× more stellar mass than the total contribution from individually detected galaxies in spectroscopically confirmed protoclusters. This suggests that much of the total flux within z = 2–4 protoclusters comes from galaxies with luminosities lower than the detection limit of SPIRE ( L _IR < 3 × 10 ^12 L _⊙ ). Lastly, we find that protoclusters subtend a half-light radius of 2.′8 (4.2–5.8 cMpc), which is consistent with simulations.

Background and objectives: The postpartum maternal physical and psychological state played a fundamental role in the mother–child relationship at the beginning of the COVID-19 pandemic. The aim of the study is to analyze the influence of maternal psychological manifestations on the mother–child couple through three objectives (briefly expressed): (I) Determination of the main acute and chronic conditions of newborns/infants. (II) Verification of the hypothesis of the existence of a link between the following neonatal variables: gestational age, birth weight, number of days of hospitalization, and specific neonatal therapies (oxygen, surfactant, and blood products’ transfusion). (III) Verification of the influence of postpartum maternal psychological status on the mother–child couple through three hypotheses. Materials and methods: This cross-sectional study was conducted in two hospitals in Timișoara, Romania, between 1 March and 1 September 2020, and included 165 mothers and their 175 newborns. Mothers answered the Edinburgh Postnatal Depression Scale, Spielberger’s Inventory of State-Trait Anxiety, and the Collins and Read Revised Adult Attachment Scale. Results: (I) The acute and chronic pathology of the infants in the study group was polymorphic. (II) Large correlations were identified between the following infant variables: gestational age with birth weight, and number of hospitalization days with birth weight, gestational age, and use of blood product transfusion (all p < 0.001). (III) (1) State anxiety was the only significant predictor of number of hospitalization days (p = 0.037), number of acute disorders (p = 0.028), and number of infant chronic diseases (p = 0.037). (2) Maternal depressive symptoms were the only predictor of postpartum maternal attachment (p = 0.018). (3) Depressive symptoms, state, and trait anxiety were non-significant in all models studied (all p > 0.05). Conclusions: Postpartum maternal physical and psychological state plays a fundamental role on the mother–child relationship in the new social and complex family conditions.

Parkinson’s disease (PD) is an enigmatic neurodegenerative disorder that is currently the subject of extensive research approaches aiming at deepening the understanding of its etiopathophysiology. Recent data suggest that distinct compounds used either as anticonvulsants or agents usually used as dopaminergic agonists or supplements consisting of live active lactic acid bacteria strains might alleviate and improve PD-related phenotypes. This is why we aimed to elucidate how the administration of rotenone (ROT) disrupts homeostasis and the possible neuroactive potential of valproic acid (VPA), antiparkinsonian agents (levodopa and carbidopa – LEV+CARB), and a mixture of six Lactobacillus and three Bifidobacterium species (PROBIO) might re-establish the optimal internal parameters. ROT causes significant changes in the central nervous system (CNS), notably reduced neurogenesis and angiogenesis, by triggering apoptosis, reflected by the increased expression of PARKIN and PINK1 gene(s), low brain dopamine (DA) levels, and as opposed to LRRK2 and SNCA compared with healthy zebrafish. VPA, LEV/CARB, and PROBIO sustain neurogenesis and angiogenesis, manifesting a neuroprotective role in diminishing the effect of ROT in zebrafish. Interestingly, none of the tested compounds influenced oxidative stress (OS), as reflected by the level of malondialdehyde (MDA) level and superoxide dismutase (SOD) enzymatic activity revealed in non-ROT-exposed zebrafish. Overall, the selected concentrations were enough to trigger particular behavioral patterns as reflected by our parameters of interest (swimming distance (mm), velocity (mm/s), and freezing episodes (s)), but sequential testing is mandatory to decipher whether they exert an inhibitory role following ROT exposure. In this way, we further offer data into how ROT may trigger a PD-related phenotype and the possible beneficial role of VPA, LEV+CARB, and PROBIO in re-establishing homeostasis in Danio rerio.

With the onset of the COVID-19 pandemic, enormous efforts have been made to understand the genus SARS-CoV-2. Due to the high rate of global transmission, mutations in the viral genome were inevitable. A full understanding of the viral genome and its possible changes represents one of the crucial aspects of pandemic management. Structural protein S plays an important role in the pathogenicity of SARS-CoV-2, mutations occurring at this level leading to viral forms with increased affinity for ACE2 receptors, higher transmissibility and infectivity, resistance to neutralizing antibodies and immune escape, increasing the risk of infection and disease severity. Thus, five variants of concern are currently being discussed, Alpha, Beta, Gamma, Delta and Omicron. In the present review, a comprehensive summary of the following critical aspects regarding SARS-CoV-2 has been made: (i) the genomic characteristics of SARS-CoV-2; (ii) the pathological mechanism of transmission, penetration into the cell and action on specific receptors; (iii) mutations in the SARS-CoV-2 genome; and (iv) possible implications of mutations in diagnosis, treatment, and vaccination.

Background and Objectives: Hepatic diseases are an important public health problem. All patients with chronic hepatitis C virus (HCV) infection receive treatment, regardless of hepatic fibrosis severity. However, evaluation of hepatic fibrosis and steatosis is still useful in assessing evolution, prognosis and monitoring of hepatic disease, especially after treatment with direct-acting antivirals (DAAs). The aim of this study was to assess the link between patatin-like phospholipase domain-containing 3 (PNPLA3) polymorphism and the degree of hepatic steatosis and fibrosis in patients with chronic HCV infection, as well as changes in steatosis and fibrosis three monthsafter obtaining a sustained viral response (SVR). Materials and Methods:Ourstudy included 100 patients with chronic hepatitis C (CHC) infection and compensated cirrhosis who received DAA treatment and who were evaluated using Fibromax prior to and 3 months after SVR. The influence of PNPLA3 (CC, CG, GG) genotype among these patients on the degree of post-treatment regression of steatosis and fibrosis was assessed. Results: Regression was noticed in the degree of both hepatic steatosis and hepatic fibrosis post-DAA treatment (three months after SVR). Analysis of the correlation between PNPLA3 genotype and fibrosis indicated that the average level of fibrosis (F) before DAA treatment was higher in patients with the GG genotype than in patients with the CC or CG genotype. Three months after SVR, the average level of fibrosis decreased; however, it remained significantly increased in GG subjects compared to that in CC or CG patients. The degree of hepatic steatosis before treatment was not significantly different among patients with different PNPLA3 genotypes, and no significant correlations were observed three months after SVR. Conclusions: The genetic variants of PNPLA3 influence the evolution of hepatic fibrosis. The GG subtype plays an important role in the degree of hepatic fibrosis both before and after treatment (three months after SVR)and could be a prognostic marker for assessment of post-SVR evolution.

Wolf–Hirschhorn syndrome (WHS), a rare disorder determined by distal 4p deletion, is characterized by a pre and postnatal growth retardation, hypotonia, intellectual disability, epilepsy, craniofacial dysmorphism, and congenital fusion anomalies. The clinical aspects are dependent on the deletion’ size. Our aim was to identify rare specific characteristics in a cohort of seven cases with 4p deletion and to assess the utility of Multiplex ligation-dependent probe amplification (MLPA) (cheap and sensitive test)—combined kits—as a diagnostic test and selection tool for cases that require other investigations (chromosomal microarray analysis—CMA, karyotype). For all cases we conducted a clinical examination with the main features identified: facial dysmorphism, intellectual disability, postnatal development delay, cardiac defects and hypotonia. In some cases, we observed seizures, structural brain abnormalities, immunodeficiencies, and renal anomalies. Prenatal growth retardation was detected in a relatively small number of cases, but postnatal growth failure was a constant feature. In all cases, the clinical diagnosis was confirmed by genetic analyses: karyotype and/or MLPA. In conclusion, renal and brain defects, as well as immunodeficiency are rare manifestations and should be looked for. Although CMA is the standard test, in our experience, MLPA is also a reliable screening method as the identified cases were either confirmed by MLPA or selected for further investigations.

Abstract Aim The study assessed mRNA expression of podocyte-associated molecules in urinary sediments of patients with type 2 diabetes mellitus (DM) in relation to urinary podocytes, biomarkers of podocyte injury and of proximal tubule (PT) dysfunction. Methods A total of 76 patients with type 2 DM and 20 healthy subjects were enrolled in a cross-sectional study, and assessed concerning urinary podocytes, urinary mRNA of podocyte-associated genes, urinary biomarkers of podocyte damage and of PT dysfunction. Results We found significant differences between urinary mRNA of podocyte-associated molecules in relation with albuminuria stage. In multivariable regression analysis, urinary mRNA of nephrin, podocin, alpha-actinin-4, CD2-associated protein, glomerular epithelial protein 1 (GLEPP1), ADAM 10, and NFκB correlated directly with urinary podocytes, albuminuria, urinary alpha1-microglobulin, urinary kidney-injury molecule-1, nephrinuria, urinary vascular endothelial growth factor, urinary advanced glycation end-products (AGE), and indirectly with eGFR (p

Objective. Our research aims to assess a possible connection between tumour localization and histological subtypes of grade II meningiomas. Material and methods. 143 patients with grade II WHO meningiomas underwent surgical resection in "Prof. Dr. N. Oblu" Emergency Clinical Hospital Iași between 1990 and 2015. The collected data included: patient age, gender, tumour localization and histopathological diagnosis (atypical, clear cells and chordoid meningioma). Results. 135 (94.4%) of all 143 patients with grade II meningiomas were atypical meningiomas, 6 (4.2%) were cell clear meningiomas and only 2 (1.4%) were chordoid meningiomas. As concerns their distribution by gender, 79 (55.2%) were female and 64 (44.8%) were male. Grade II meningiomas were most commonly located at convexity 49.7% (n=71), followed by skull base in 30.8% (n=44) of the cases and parasagittal/falcine in 14.7% (n=21) of the patients. Conclusions. The most common localization of grade II meningiomas was convexity, followed by skull base, parasagittal/falcine and intraventricular areas. We have also noticed that convexity meningiomas are more frequent in women, unlike the other anatomical localizations in which the male-female ratio is almost equal. Therefore, further research is necessary to determine the role of embryological, anatomopathological and genetic factors in underlying the connection between meningioma grade and anatomical localization.

Purpose. Nontraditional cardiovascular risk factors as apolipoprotein A (ApoA), apolipoprotein B (ApoB), and the proprotein convertase subtilisin/kexin type 9 (PCSK9) increase the prevalence of cardiovascular mortality in chronic kidney disease (CKD) or in end-stage renal disease (ESRD) through quantitative alterations. This review is aimed at establishing the biomarker (ApoA, ApoB, and PCSK9) level variations in uremic patients, to identify the studies showing the association between these biomarkers and the development of cardiovascular events and to depict the therapeutic options to reduce cardiovascular risk in CKD and ESRD patients. Methods. We searched the electronic database of PubMed, Scopus, EBSCO, and Cochrane CENTRAL for studies evaluating apolipoproteins and PCSK9 in CKD and ESRD. Randomized controlled trials, observational studies (including case-control, prospective or retrospective cohort), and reviews/meta-analysis were included if reference was made to those keys and cardiovascular outcomes in CKD/ESRD. Results. 18 studies met inclusion criteria. Serum ApoA-I has been significantly associated with the development of new cardiovascular event and with cardiovascular mortality in ESRD patients. ApoA-IV level was independently associated with maximum carotid intima-media thickness (cIMT) and was a predictor for sudden cardiac death. The ApoB/ApoA-I ratio represents a strong predictor for coronary artery calcifications, cardiovascular mortality, and myocardial infarction in CKD/ESRD. Plasma levels of PCSK9 were not associated with cardiovascular events in CKD patients. Conclusions. Although the “dyslipidemic status” in CKD/ESRD is not clearly depicted, due to different research findings, ApoA-I, ApoA-IV, and ApoB/ApoA-I ratio could be predictors of cardiovascular risk. Serum PCSK9 levels were not associated with the cardiovascular events in patients with CKD/ESRD. Probably in the future, the treatment of dyslipidemia in CKD/ESRD will be aimed at discovering new effective therapies on the action of these biomarkers.

The tumor microenvironment (TME) influences cancer progression. Therefore, engineered TME models are being developed for fundamental research and anti-cancer drug screening. This paper reports the biofabrication of 3D-printed avascular structures that recapitulate several features of the TME. The tumor is represented by a hydrogel droplet uniformly loaded with breast cancer cells (106 cells/mL); it is embedded in the same type of hydrogel containing primary cells—tumor-associated fibroblasts isolated from the peritumoral environment and peripheral blood mononuclear cells. Hoechst staining of cryosectioned tissue constructs demonstrated that cells remodeled the hydrogel and remained viable for weeks. Histological sections revealed heterotypic aggregates of malignant and peritumoral cells; moreover, the constituent cells proliferated in vitro. To investigate the interactions responsible for the experimentally observed cellular rearrangements, we built lattice models of the bioprinted constructs and simulated their evolution using Metropolis Monte Carlo methods. Although unable to replicate the complexity of the TME, the approach presented here enables the self-assembly and co-culture of several cell types of the TME. Further studies will evaluate whether the bioprinted constructs can evolve in vivo in animal models. If they become connected to the host vasculature, they may turn into a fully organized TME.

Excessive use of antimicrobials and inadequate infection control practices has turned antimicrobial resistance (AMR) into a global, public health peril. We studied the expression of qnrA, qnrB, and qnrS plasmid in ciprofloxacin (CIP)-resistant strains of Escherichia coli in swine and humans from Romania, using the Polymerase Chain Reaction (PCR) technique. Antibiotic Susceptibility Testing (AST) for human subjects (H) on 147 samples and 53 swine (S) was ascertained as well as the isolation of bacterial DNA (E. coli) as follows: bacteriolysis, DNA-binding, rinsing, elution, amplification, and nucleic acids’ migration and U.V. visualization stages. From 24 samples of E. coli resistant to CIP collected from H subjects and 15 from S, for PCR analysis, 15 H and 12 S were used, with DNA purity of 1.8. The statistically analyzed results using the Crosstabs function (IBM SPSS Statistics-Ver. 2.1.), revealed the qnrS (417 bp) gene in 13 human subjects (52.0%), as well as in all swine samples studied. The qnrB (526 bp) gene was exposed in 9 of the human patients (36.0%) and in all swine isolates, and the qnrA (516 bp) gene was observed only in 3 of the isolates obtained from human subjects (12.0%) and was not discovered in pigs (p > 0.05). The presence of plasmids qnrA, qnrB, and qnrS in the human samples and of qnrB and qnrS in swine, facilitates the survival of pathogens despite the CIP action. The long-term use of CIP could cause a boost in the prevalence of qnr resistance genes, and resistance in the pigs destined for slaughter, a perturbing fact for public health and the human consumer.

In an attempt to develop drug delivery systems that bypass the blood–brain barrier (BBB) and prevent liver and intestinal degradation, it was concluded that nasal medication meets these criteria and can be used for drugs that have these drawbacks. The aim of this review is to present the influence of the properties of chitosan and its derivatives (mucoadhesion, permeability enhancement, surface tension, and zeta potential) on the development of suitable nasal drug delivery systems and on the nasal bioavailability of various active pharmaceutical ingredients. Interactions between chitosan and proteins, lipids, antigens, and other molecules lead to complexes that have their own applications or to changing characteristics of the substances involved in the bond (conformational changes, increased stability or solubility, etc.). Chitosan and its derivatives have their own actions (antibacterial, antifungal, immunostimulant, antioxidant, etc.) and can be used as such or in combination with other molecules from the same class to achieve a synergistic effect. The applicability of the properties is set out in the second part of the paper, where nasal formulations based on chitosan are described (vaccines, hydrogels, nanoparticles, nanostructured lipid carriers (NLC), powders, emulsions, etc.).

Blunt carotid artery injury is a relatively rare but potentially lethal injury that predominantly occurs in high-impact mechanisms such as motor-vehicle collision. Any simptoms or neurological deficits following a multiple trauma patient mandates a thorough evaluation and consideration of BCI. This is a case report on two young patients with neurologic simptoms developed after blunt trauma in the cervical region. Both patients had left internal carotid artery dissection diagnosed on a CT-angiography, followed by middle cerebral artery territory infarction. Although it can be a delayed onset with no signs of vascular demage, we believe that, by implementing a protocol with additional imaging for early detection, we can prevent a devastating outcome.

The authors present the case of a little girl aged 5 years and 6 months presenting a minor erythema multiforme bullosum. The diagnosis was established on clinical criteria (erytemato – papulous, vesiculobullous tegument lesions resulting from the expose of the skin with apparition of liquid when exfoliating the papules) at a child with a good general condition. It was established a possible etiology due to a staphylococcus evidentiating the existence of the staphylococcus aureus in the gathering of papules liquid. It was discussion about the differential diagnosis of the bullous dermatitis. Unlike simple cases with autolimitative evolution, when the treatment is useless, the respective case had a particularly prolonged evolution and required a general and local treatment.