Cinnamamide derivatives with 4-hydroxypiperidine moiety enhance effect of doxorubicin to cancer cells and protect cardiomyocytes against drug-induced toxicity through CBR1 inhibition mechanism.

Doxorubicin (DOX) is classified by World Health Organization (WHO) as an essential medicine for cancer. However, its clinical application is limited due to resistance development and cardiotoxicity. Many attempts have been made to address these issues with some focused on finding a potential adjuvant therapy.

Effect of Growth Hormone Treatment on the Concentration of Selected Metabolic Markers in Girls With Turner Syndrome.

Background: As Turner syndrome (TS) predisposes to obesity and metabolic disorders, and their complications, such as cardiovascular diseases, are the main causes of shortened life expectancy in patients with TS, new metabolic markers that could serve as early predictors of dysmetabolic state are sought.

Objective: Assessment of MMP-1 (matrix metalloproteinase-1), MMP-2 (matrix metalloproteinase-2), MMP-9 (matrix metallopeptidase-9), BDNF (brain-derived neurotrophic factor), GDNF (glial cell line-derived neurotrophic factor), and VEGF (vascular endothelial growth factor) before the onset of growth hormone (GH) therapy and then during GH treatment as well as markers assessment during GH medication in girls with TS to establish marker stability and repeatability, and the impact of GH on markers concentration.

Method: The concentrations of circulating MMP-1, MMP-2, MMP-9, BDNF, GDNF, and VEGF were measured in nine girls with TS before the onset of GH therapy and then after at least 3 months of treatment period.

SARS-CoV-2 infects an model of the human developing pancreas through endocytosis.

Recent studies showed that SARS-CoV-2 can infect adult human pancreas and trigger pancreatic damage. Here, using human fetal pancreas samples and 3D differentiation of human pluripotent cells into pancreatic endocrine cells, we determined that SARS-CoV-2 receptors ACE2, TMPRSS2, and NRP1 are expressed in precursors of insulin-producing pancreatic β-cells, rendering them permissive to SARS-CoV-2 infection. We also show that SARS-CoV-2 enters and undergoes efficient replication in human multipotent pancreatic and endocrine progenitors .

Does a Multiple Myeloma Polygenic Risk Score Predict Overall Survival of Patients with Myeloma?

Background: Genome-wide association studies (GWAS) of multiple myeloma in populations of European ancestry (EA) identified and confirmed 24 susceptibility loci. For other cancers (e.g.

Amelanotic Uveal Melanomas Evaluated by Indirect Ophthalmoscopy Reveal Better Long-Term Prognosis Than Pigmented Primary Tumours-A Single Centre Experience.

(1) Background: There is a constant search for new prognostic factors that would allow us to accurately determine the prognosis, select the type of treatment, and monitor the patient diagnosed with uveal melanoma in a minimally invasive and easily accessible way. Therefore, we decided to evaluate the prognostic role of its pigmentation in a clinical assessment. (2) Methods: The pigmentation of 154 uveal melanomas was assessed by indirect ophthalmoscopy.

Anticancer potential of alkaloids: a key emphasis to colchicine, vinblastine, vincristine, vindesine, vinorelbine and vincamine.

Cancer, one of the leading illnesses, accounts for about 10 million deaths worldwide. The treatment of cancer includes surgery, chemotherapy, radiation therapy, and drug therapy, along with others, which not only put a tremendous economic effect on patients but also develop drug resistance in patients with time. A significant number of cancer cases can be prevented/treated by implementing evidence-based preventive strategies.

Complement Levels at Admission Reflecting Progression to Severe Acute Kidney Injury (AKI) in Coronavirus Disease 2019 (COVID-19): A Multicenter Prospective Cohort Study.

Background: Dysregulation of complement system is thought to be a major player in development of multi-organ damage and adverse outcomes in patients with coronavirus disease 2019 (COVID-19). This study aimed to examine associations between complement system activity and development of severe acute kidney injury (AKI) among hospitalized COVID-19 patients.

Materials And Methods: In this multicenter, international study, complement as well as inflammatory and thrombotic parameters were analyzed in COVID-19 patients requiring hospitalization at one US and two Hungarian centers.

Albumin Binds Doxorubicin via Self-Assembling Dyes as Specific Polymolecular Ligands.

Congo red (CR) type self-assembled ribbon-like structures (SRLS) were previously shown to interact with some proteins, including albumin. SRLS also complex with some drugs with a flat, ring-shaped structure with aromatic characteristics, intercalating them into their ribbon structure. The combination of interaction with proteins and drug binding by SRLS enables the use of such systems for immunotargeting.

The Seroprevalence of SARS-CoV-2 Antibodies among HealthCare Workers in University Hospital in Krakow before the Era of Vaccination.

Background: Knowledge of occupational health is crucial to the safety of healthcare workers in the pandemic period. The aim of our study was the rating of SARS-CoV-2 seroprevalence in connection with selected demographic, social, and organizational factors, as well as the identification of key elements determining the safety of HCWs and patients of the University Hospital in Krakow.

Methods: This was a non-interventional, uncontrolled, open, single-center, cross-sectional online survey on the preparedness for the COVID-19 epidemic and the seroprevalence of medical and non-medical HCWs and students.

Heme Oxygenase-1 Has a Greater Effect on Melanoma Stem Cell Properties Than the Expression of Melanoma-Initiating Cell Markers.

Melanoma-initiating cells (MICs) contribute to the tumorigenicity and heterogeneity of melanoma. MICs are identified by surface and functional markers and have been shown to display cancer stem cell (CSC) properties. However, the existence of MICs that follow the hierarchical CSC model has been questioned by studies showing that single unselected melanoma cells are highly tumorigenic in xenotransplantation assays.

Immune-instructive copolymer scaffolds using plant-derived nanoparticles to promote bone regeneration.

Background: Age-driven immune signals cause a state of chronic low-grade inflammation and in consequence affect bone healing and cause challenges for clinicians when repairing critical-sized bone defects in elderly patients.

Methods: Poly(L-lactide-co-ɛ-caprolactone) (PLCA) scaffolds are functionalized with plant-derived nanoparticles from potato, rhamnogalacturonan-I (RG-I), to investigate their ability to modulate inflammation in vitro in neutrophils and macrophages at gene and protein levels. The scaffolds' early and late host response at gene, protein and histological levels is tested in vivo in a subcutaneous rat model and their potential to promote bone regeneration in an aged rodent was tested in a critical-sized calvaria bone defect.

Secretory leukocyte protease inhibitor regulates nerve reflex-mediated skin barrier function in psoriasis.

Background: Secretory leukocyte protease inhibitor (SLPI), a ~12 kDa protein is an important regulator of innate and adaptive immunity and a component of tissue regenerative programmes. SLPI expression is markedly elevated in chronically inflamed skin, including that of individuals suffering from psoriasis. However, the role of SLPI in these diseases remains elusive.

The Effect of Dietary Polyphenols on Vascular Health and Hypertension: Current Evidence and Mechanisms of Action.

The aim of this review was to explore existing evidence from studies conducted on humans and summarize the mechanisms of action of dietary polyphenols on vascular health, blood pressure and hypertension. There is evidence that some polyphenol-rich foods, including berry fruits rich in anthocyanins, cocoa and green tea rich in flavan-3-ols, almonds and pistachios rich in hydroxycinnamic acids, and soy products rich in isoflavones, are able to improve blood pressure levels. A variety of mechanisms can elucidate the observed effects.

Active factor XI is associated with the risk of cardiovascular events in stable coronary artery disease patients.

Background And Aims: Tissue factor (TF) and activated factor XI (FXIa) have been associated with acute coronary syndrome, ischemic stroke and venous thromboembolism. Their predictive value in stable coronary artery disease (CAD) is unclear. We investigated whether active TF and FXIa were associated with clinical outcomes in CAD patients in long-term observation.

Pharmacokinetic/Pharmacodynamic Assessment of Selective Phosphodiesterase Inhibitors in a Mouse Model of Autoimmune Hepatitis.

Autoimmune hepatitis (AIH) is a life-threatening disorder currently treated with nonspecific immunosuppressive drugs. It is postulated that phosphodiesterase (PDE) inhibitors, as agents exerting anti-inflammatory and immunomodulatory activities, may constitute a possible treatment of autoimmune disorders. This study develops a pharmacokinetic/pharmacodynamic (PK/PD) model to assess the effects of PDE-selective inhibitors, namely, cilostazol (PDE3), rolipram (PDE4), and BRL-50481 (PDE7), in a mouse model of AIH.

Effect of Brazil Nuts on Selenium Status, Blood Lipids, and Biomarkers of Oxidative Stress and Inflammation: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Tree nuts, including Brazil nuts, have been hypothesized to impact cardiovascular health through the modulation of oxidative stress and inflammation. Nonetheless, a quantitative analysis of these effects has not been performed. Therefore, the aim of this study was to systematically revise and quantify the effect of Brazil nut intervention on selenium status, blood lipids, and biomarkers of oxidative stress and inflammation using a meta-analytical approach.

Changes in the Composition of Oral and Intestinal Microbiota After Sleeve Gastrectomy and Roux-En-Y Gastric Bypass and Their Impact on Outcomes of Bariatric Surgery.

Background: We aimed to assess the changes in composition of bacterial microbiota at two levels of the digestive tract: oral cavity and large intestine in patients 6 months after bariatric surgery.

Methods: This was a prospective cohort study including patients undergoing bariatric surgery. Before surgery and 6 months after the procedure, oral swabs were obtained and stool samples were provided.

Effects of non-steroidal anti-inflammatory drugs and other eicosanoid pathway modifiers on antiviral and allergic responses: EAACI task force on eicosanoids consensus report in times of COVID-19.

Non-steroidal anti-inflammatory drugs (NSAIDs) and other eicosanoid pathway modifiers are among the most ubiquitously used medications in the general population. Their broad anti-inflammatory, antipyretic, and analgesic effects are applied against symptoms of respiratory infections, including SARS-CoV-2, as well as in other acute and chronic inflammatory diseases that often coexist with allergy and asthma. However, the current pandemic of COVID-19 also revealed the gaps in our understanding of their mechanism of action, selectivity, and interactions not only during viral infections and inflammation, but also in asthma exacerbations, uncontrolled allergic inflammation, and NSAIDs-exacerbated respiratory disease (NERD).

GPR18-Mediated Relaxation of Human Isolated Pulmonary Arteries.

GPR18 receptor protein was detected in the heart and vasculature and appears to play a functional role in the cardiovascular system. We investigated the effects of the new GPR18 agonists PSB-MZ-1415 and PSB-MZ-1440 and the new GPR18 antagonist PSB-CB-27 on isolated human pulmonary arteries (hPAs) and compared their effects with the previously proposed, but unconfirmed, GPR18 ligands NAGly, Abn-CBD (agonists) and O-1918 (antagonist). GPR18 expression in hPAs was shown at the mRNA level.

Alcohol Consumption, Bone Mineral Density, and Risk of Osteoporotic Fractures: A Dose-Response Meta-Analysis.

Excess alcohol consumption is known to be detrimental to human health. However, the role of light-to-moderate alcohol intake is under investigation for potential certain health benefits-mostly related to the cardiovascular system. Nevertheless, there is no univocal agreement on this matter, and research is still ongoing to clarify whether there might be other potential outcomes affected by alcohol intake.

Relationship Between Anti-DFS70 Autoantibodies and Oxidative Stress.

Background: The anti-DFS70 autoantibodies are one of the most commonly and widely described agent of unknown clinical significance, frequently detected in healthy individuals. It is not known whether the DFS70 autoantibodies are protective or pathogenic. One of the factors suspected of inducing the formation of anti-DFS70 antibodies is increased oxidative stress.

The Role of the Western Diet and Oral Microbiota in Parkinson's Disease.

The type of diet not only affects the composition of the oral microflora but is also one of the more critical factors associated with an increased risk of Parkinson's disease, PD. This study compared diet preferences and oral microbiota profiles in patients with PD vs. healthy controls.

Liver Injury in Patients with COVID-19 without Underlying Liver Disease.

Unlabelled: SARS-CoV-2 shows a high affinity for the ACE-2 receptor, present on the epithelial cells of the upper and lower respiratory tract, within the intestine, kidneys, heart, testes, biliary epithelium, and-where it is particularly challenging-on vascular endothelial cells. Liver involvement is a rare manifestation of COVID-19.

Material And Methods: We reviewed 450 patients admitted due to the fact of SARS-CoV-2 infection (COVID-19) including 88 with liver injury.