Synthesis and biological evaluation of 4,7,9-trisubstituted benzoxazepines as antileishmanial agents.

Herein we report a series of antileishmanial analogues derived from 4-[(3,5-dimethyl-4-isoxazolyl)acetyl]-9-[(1-methyl-3-piperidinyl)methoxy]-7-(5-methyl-2-thienyl)-2,3,4,5-tetrahydro-1,4-benzoxazepine (1), which was identified through a previously reported high-throughput phenotypic screen. The analogue series was designed, synthesized, and evaluated for antileishmanial activity to establish pharmacophore elements and preliminary structure-activity relationships as key steps in validating the series for further optimization. This study led to identification of the early lead compound 46, which exhibited sub-micromolar proliferation inhibitory activity against intra-macrophage L.

Hydroxysteroid 17-β dehydrogenase 14 (HSD17B14) is an L-fucose dehydrogenase, the initial enzyme of the L-fucose degradation pathway.

L-Fucose (6-deoxy-L-galactose), a monosaccharide abundant in glycolipids and glycoproteins produced by mammalian cells, has been extensively studied for its role in intracellular biosynthesis and recycling of GDP-L-fucose for fucosylation. However, in certain mammalian species, L-fucose is efficiently broken down to pyruvate and lactate in a poorly understood metabolic pathway. In the 1970s, L-fucose dehydrogenase, an enzyme responsible for the initial step of this pathway, was partially purified from pig and rabbit livers and characterized biochemically.

Crystal structure of L-2-keto-3-deoxyfuconate 4-dehydrogenase reveals a unique binding mode as a α-furanosyl hemiketal of substrates.

L-2-Keto-3-deoxyfuconate 4-dehydrogenase (L-KDFDH) catalyzes the NAD-dependent oxidization of L-2-keto-3-deoxyfuconate (L-KDF) to L-2,4-diketo-3-deoxyfuconate (L-2,4-DKDF) in the non-phosphorylating L-fucose pathway from bacteria, and its substrate was previously considered to be the acyclic α-keto form of L-KDF. On the other hand, BDH2, a mammalian homolog with L-KDFDH, functions as a dehydrogenase for cis-4-hydroxy-L-proline (C4LHyp) with the cyclic structure. We found that L-KDFDH and BDH2 utilize C4LHyp and L-KDF, respectively.

The Iron Metabolism with a Specific Focus on the Functioning of the Nervous System.

Iron is the micronutrient with the best-studied biological functions. It is widely distributed in nature, and its involvement in the main metabolic pathways determines the great importance of this metal for all organisms. Iron is required for cellular respiration and various biochemical processes that ensure the proper functioning of cells and organs in the human body, including the brain.

Bone Marrow Nucleated Cells and Bone Marrow-Derived CD271+ Mesenchymal Stem Cell in Treatment of Encephalopathy and Drug-Resistant Epilepsy.

The broad spectrum of brain injuries in preterm newborns and the plasticity of the central nervous system prompts us to seek solutions for neurodegeneration to prevent the consequences of prematurity and perinatal problems. The study aimed to evaluate the safety and efficacy of the implantation of autologous bone marrow nucleated cells and bone marrow mesenchymal stem cells in different schemes in patients with hypoxic-ischemic encephalopathy and immunological encephalopathy. Fourteen patients received single implantation of bone marrow nucleated cells administered intrathecally and intravenously, followed by multiple rounds of bone marrow mesenchymal stem cells implanted intrathecally, and five patients were treated only with repeated rounds of bone marrow mesenchymal stem cells.

Higher perfusion pressure and pump flow during cardiopulmonary bypass are beneficial for kidney function-a single-centre prospective study.

Kidneys play an essential role in the circulatory system, regulating blood pressure and intravascular volume. They are also set on maintaining an adequate filtration pressure in the glomerulus. During the CPB, a decrease in systemic blood pressure and hemoglobin concentration may lead to renal ischemia and subsequent acute kidney injury.

Translation and cross-cultural adaptation of the Get Active Questionnaire for Pregnancy (kwestionariusz "Badź Aktywna w Ciąży") to support physical activity among pregnant women in Poland.

Introduction: Physical activity during pregnancy is established to derive clinically meaningful improvements in pregnancy, childbirth, and postpartum health outcomes. Evidence-based pre-screening tools have been developed to support the implementation of physical activity programmes, and enhance communication between health care providers, exercise professionals and pregnant women. The Get Active Questionnaire for Pregnancy (GAQ-P) and the Health Care Provider Consultation Form for Prenatal Physical Activity (HCPCF) empower pregnant women to identify whether they require additional counselling from their obstetric health care provider in terms of physical activity.

Intrauterine deaths - an unsolved problem in Polish perinatology.

Objectives: The Polish criteria for "intrauterine death" include fetal demise after 22 weeks of gestation, weighing > 500 g and body length at least 25 cm, when the gestational age is unknown. The rate of fetal death in Poland in 2015 is 3:10,000. In 2020, 1,231 stillbirths were registered.

Predicting the WHO Grading of Pediatric Brain Tumors Based on Their MRI Appearance: A Retrospective Study.

The treatment of central nervous system (CNS) tumors constitutes a significant part of a pediatric neurosurgeon's workload. The classification of such neoplasms spans many entities. These include low- and high-grade lesions, with both occurring in the population of patients under 18 years of age.

Preoperative Serum Levels of PDGF-AB, PDGF-BB, TGF-α, EGF and ANG-2 in the Diagnosis of Endometrial Cancer.

(1) Background: It is relevant to find new diagnostic biomarkers for endometrial cancer. This study aimed to investigate whether PDGF-AB, PDGF-BB, TGF-α, EGF and ANG-2 could be considered new useful markers for diagnosis and survival of endometrial cancer. (2) Methods: A total of 93 women diagnosed with endometrial cancer (EC) and 66 patients with non-cancerous endometrial lesions (NCEL) were included in this study.

Thermally cross-linkable fluorene-based hole transporting materials: synthesis, characterization, and application in perovskite solar cells.

Perovskite solar cells are among the most promising photovoltaic technologies in academia and have the potential to become commercially available in the near future. However, there are still a few unresolved issues regarding device lifetime and fabrication cost of perovskite solar cells in order to be competitive with existing technologies. Herein, we report small organic molecules with introduced vinyl groups as hole transporting materials, which are capable of undergoing thermal polymerization, forming solvent-resistant 3D networks.

From Biomarkers to the Molecular Mechanism of Preeclampsia-A Comprehensive Literature Review.

Preeclampsia (PE) is a prevalent obstetric illness affecting pregnant women worldwide. This comprehensive literature review aims to examine the role of biomarkers and understand the molecular mechanisms underlying PE. The review encompasses studies on biomarkers for predicting, diagnosing, and monitoring PE, focusing on their molecular mechanisms in maternal blood or urine samples.

Screening for Preeclampsia and Fetal Growth Restriction in the First Trimester in Women without Chronic Hypertension.

Background: Nowadays, it is possible to identify a group at increased risk of preeclampsia (PE) and fetal growth restriction (FGR) using the principles of the Fetal Medicine Foundation (FMF). It has been established for several years that acetylsalicylic acid (ASA) reduces the incidence of PE and FGR in high-risk populations. This study aimed to evaluate the implementation of ASA use after the first-trimester screening in a Polish population without chronic hypertension, as well as its impact on perinatal complications.

Comparative Analysis of the Results of Stroke Treatment With Multiple Administrations of Wharton's Jelly Mesenchymal Stem Cells-Derived HE-ATMP and Standard Conservative Treatment: Case Series Study.

Stroke remains still the leading cause of long-term disability worldwide. Although interventions such as early reperfusion, intravenous thrombolysis, and endovascular revascularization have shown neurological benefit in stroke patients, there is still lack of effective treatment enabling regeneration of nervous tissue after cerebral ischemic episodes. Cell therapy is an evolving opportunity for stroke survivors with residual neurological deficits.

Preoperative Oral Carbohydrate (CHO) Supplementation Is Beneficial for Clinical and Biochemical Outcomes in Patients Undergoing Elective Cesarean Delivery under Spinal Anaesthesia-A Randomized Controlled Trial.

Background: Preoperative fasting and surgery cause metabolic stress, insulin resistance with ketosis, and postoperative nausea and vomiting (PONV). Oral carbohydrate loading strategy (CHO) improves outcomes in labor and general surgery. We aimed to compare the effectiveness of CHO with standard fasting in patients undergoing elective cesarean delivery (CD) under spinal anesthesia.

Prospective, Long-Term Functional Outcomes of Extra-Osseous Talotarsal Stabilization (EOTTS) Using HyProCure in Adult Patients with Talotarsal Joint Instability: Assessment of Physical Activity and Patient Satisfaction.

Background: The partial dislocation of the talus from the calcaneus and navicular bones is a primary factor leading to a prolonged overpronation during weightbearing. This study aimed to assess the possibility of returning to physical activity and long-term patient satisfaction after an extra-osseous talotarsal stabilization (EOTTS) procedure with a HyProCure sinus tarsi implant for partial talotarsal joint dislocation (TTJ).

Methods: A total of 41 adult patients (61 feet), with an average age of 46.

Influence of hsCRP Parameter on the Occurrence of Metabolic Syndrome in Patients with Polycystic Ovary Syndrome.

PCOS (polycystic ovary syndrome) is a common endocrine disorder that affects 8-13% of women of reproductive age. Increased body weight and insulin resistance may be associated with chronic inflammation, which increases the risk of cardiovascular complications. CRP (C-reactive protein) tests may be use to assess persistent inflammation.

Evidence of Placental Aging in Late SGA, Fetal Growth Restriction and Stillbirth-A Systematic Review.

During pregnancy, the placenta undergoes a natural aging process, which is considered normal. However, it has been hypothesized that an abnormally accelerated and premature aging of the placenta may contribute to placenta-related health issues. Placental senescence has been linked to several obstetric complications, including abnormal fetal growth, preeclampsia, preterm birth, and stillbirth, with stillbirth being the most challenging.

The Role of Selenium and Manganese in the Formation, Diagnosis and Treatment of Cervical, Endometrial and Ovarian Cancer.

Selenium (Se) and manganese (Mn) are essential micronutrients that are important elements of cell metabolism. They are involved in the composition of enzyme systems and regulate enzyme activity. Disturbances in the homeostasis of these micronutrients affect the development of many diseases and carcinogenesis, which can be linked to increased levels of oxidative stress and impaired antioxidant properties of many enzymes.

Low-Dose Aspirin after ASPRE-More Questions Than Answers? Current International Approach after PE Screening in the First Trimester.

Preeclampsia (PE) is a multi-factorial disorder of pregnancy, and it continues to be one of the leading causes of fetal and maternal morbidity and mortality worldwide. Aspirin is universally recommended for high-risk women to reduce preeclampsia risk. The purpose of this review is to summarize the recommendations of various scientific societies on predicting preeclampsia and their indications for the inclusion of acetylsalicylic acid (ASA) prophylaxis.

Emergency cerclage using double-level versus single-level suture in the management of cervical insufficiency (Cervical Occlusion double-level Stitch Application, ): study protocol for a multicentre, non-blinded, randomised controlled trial.

Introduction: Cervical insufficiency accounts for 15% of recurrent pregnancy losses between 16 and 28 weeks of gestation. The aim of the study is to verify the effectiveness of emergency double-level cerclage with vaginal progesterone in cervical insufficiency treatment in terms of the prevention of preterm delivery before 34 weeks of gestation.

Methods And Analysis: This trial is a multicentre, non-blinded, randomised study with 1:1 allocation ratio.

The Trace Element Concentrations and Oxidative Stress Parameters in Afterbirths from Women with Multiple Pregnancies.

The aim of this study was to evaluate the intensity of oxidative stress by measuring the concentrations of lipid peroxidation products (LPO) in fetal membrane, umbilical cord, and placenta samples obtained from women with multiple pregnancies. Additionally, the effectiveness of protection against oxidative stress was assessed by measuring the activity of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione reductase (GR). Due to the role of iron (Fe), copper (Cu), and zinc (Zn) as cofactors for antioxidant enzymes, the concentrations of these elements were also analyzed in the studied afterbirths.