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Expansion and angiogenic potential of mesenchymal stem cells from patients with critical limb ischemia.

BACKGROUND: Critical limb ischemia (CLI) is a life- and limb-threatening condition affecting 1% to 10% of the population with peripheral arterial disease. Traditional revascularization options are not possible for up to 50% of CLI patients, in which case, the use of cellular therapies, such as bone marrow-derived mesenchymal stem cells (MSCs), hold great promise as an alternative revascularization therapy. However, no randomized, controlled phase 3 trials to date have demonstrated an improvement in limb salvage with cellular therapies. This may be due to poor cell quality (ie, inability to gen

Setting up equine embryo gender determination by preimplantation genetic diagnosis in a commercial embryo transfer program.

Preimplantation genetic diagnosis (PGD) allows identifying genetic traits in early embryos. Because in some equine breeds, like Polo Argentino, females are preferred to males for competition, PGD can be used to determine the gender of the embryo before transfer and thus allow the production of only female pregnancies. This procedure could have a great impact on commercial embryo production programs. The present study was conducted to adapt gender selection by PGD to a large-scale equine embryo transfer program. To achieve this, we studied (i) the effect on pregnancy rates of holding biopsied e

Residual Cajal bodies in coilin knockout mice fail to recruit Sm snRNPs and SMN, the spinal muscular atrophy gene product.

Cajal bodies (CBs) are nuclear suborganelles involved in the biogenesis of small nuclear ribonucleoproteins (snRNPs). In addition to snRNPs, they are highly enriched in basal transcription and cell cycle factors, the nucleolar proteins fibrillarin (Fb) and Nopp140 (Nopp), the survival motor neuron (SMN) protein complex, and the CB marker protein, p80 coilin. We report the generation of knockout mice lacking the COOH-terminal 487 amino acids of coilin. Northern and Western blot analyses demonstrate that we have successfully removed the full-length coilin protein from the knockout animals. Some

Hepatoprotective potential of alpha-lipoic acid against gliclazide-induced liver injury in high-glucose-exposed human liver cells and experimental type 2 diabetic rats.

Growing clinical evidence shows that sulfonylurea therapy for patients with type 2 diabetic mellitus (T2DM) contributes to progressive worsening of their liver. The present study presents hepatotoxicity induced by gliclazide, a second-generation sulfonylurea, and alpha-lipoic acid (ALA) as a novel and promising drug for T2DM treatment. Normal human liver cells (HL-7702) were incubated with high-glucose DMEM in the presence or absence of gliclazide and ALA for 72 h, and cell viability and death were measured by flow cytometry. Next, Sprague-Dawley rats were subjected to 12 h of fasting, and fas

Effects of finasteride, a type 2 5-alpha reductase inhibitor, on fetal development in the rhesus monkey (Macaca mulatta).

In genetic male fetuses, dihydrotestosterone (DHT) plays an important role in normal prostatic and external genital differentiation. The enzyme steroid 5-alpha reductase (5 alpha R) catalyzes the conversion of testosterone (T) to DHT. The importance of 5 alpha R in sexual differentiation is evident from the study of human genetic males who congenitally lack this enzyme and consequently develop ambiguous genitalia. These individuals are specifically deficient in the type 2 isozyme, whereas the normal type 1 isozyme activity has been found. The purpose of this study was to determine 1) the suita

Embryologist agreement when assessing blastocyst implantation probability: is data-driven prediction the solution to embryo assessment subjectivity?

STUDY QUESTION: What is the accuracy and agreement of embryologists when assessing the implantation probability of blastocysts using time-lapse imaging (TLI), and can it be improved with a data-driven algorithm? SUMMARY ANSWER: The overall interobserver agreement of a large panel of embryologists was moderate and prediction accuracy was modest, while the purpose-built artificial intelligence model generally resulted in higher performance metrics. WHAT IS KNOWN ALREADY: Previous studies have demonstrated significant interobserver variability amongst embryologists when assessing embryo quality

Incidence risk of bronchopneumonia in newborn calves associated with intrauterine diselementosis.

BACKGROUND AND AIM: Macro- and micro-elements are required to ensure the normal course of biochemical processes in the development of an animal's body. Any excess, deficiency, or imbalance in chemical elements in an animal's body can cause the development of various latent or clinically expressed pathological conditions. Diselementosis in pregnant cows may lead to impaired embryo and fetal development, as well as reduced neonatal viability. The aim of this study was to analyze the content of macroelements and microelements in the blood serum of both calving cows and their calves to evaluate th

The functions of laminins: lessons from in vivo studies.

This series of three short reviews is an attempt to summarize our current knowledge of the in vivo tests of hypotheses of laminin functions. The structures of the laminins have been thoroughly reviewed recently (P. Ekblom and R. Timpl, in press), and I will not attempt to repeat this information here. Instead, I will focus on the recent evidence gathered from gene knock out experiments in mice and from naturally occurring human and mouse gene mutations. The most obvious lesson from the above studies--other than demonstrating the importance of laminins in general--is that the structural diversi

Palmitic acid impairs human and mouse placental function by inhibiting trophoblast autophagy through induction of acyl-coenzyme A-binding protein (ACBP) upregulation.

STUDY QUESTION: Can exposure to palmitic acid (PA), a common saturated fatty acid, modulate autophagy in both human and mouse trophoblast cells through the regulation of acyl-coenzyme A-binding protein (ACBP)? SUMMARY ANSWER: PA exposure before and during pregnancy impairs placental development through mechanisms involving placental autophagy and ACBP expression. WHAT IS KNOWN ALREADY: High-fat diets, including PA, have been implicated in adverse effects on human placental and fetal development. Despite this recognition, the precise molecular mechanisms underlying these effects are not fully

Evaluating endometrial response to human chorionic gonadotropin: alterations in epigenetic regulation and extracellular vesicle cargo of endometrial stromal cells.

STUDY QUESTION: What is the effect of hCG on the epigenetic profile and the expression of other molecular factors in endometrial stromal cells (ESCs)? SUMMARY ANSWER: Our findings suggest that hCG treatment alters the molecular environment of decidualized ESCs, potentially influencing implantation and immune regulation through epigenetic modifications and changes in the levels of secreted proteins and micro-ribonucleic acids (miRNAs). WHAT IS KNOWN ALREADY: Embryo implantation depends not only on the quality of the embryo but also on the receptivity of the endometrium, the specialized lining

Thalassemia.

New developments in the epidemiology, treatment and prognosis of thalassemia have dramatically altered the approach to the care of affected patients, and these developments are likely to have an even greater impact in the next few years. Demographic changes have required an awareness and understanding of the unique features of thalassemia disorders that were previously uncommon in North America but are now seen more frequently in children and recognized more consistently in adults. New methods for measuring tissue iron accumulation and new drugs to remove excessive iron are advancing two of th

Arsenic Sulfide Induces Apoptosis in Myelodysplastic Neoplasm Cells Through the Suppression of ABI2.

BackgroundMyelodysplastic neoplasms (MDS) are a category of myeloid malignancies that can progress to acute myeloid leukemia (AML). Arsenic sulfide (As₂S₂) has demonstrated efficacy in the treatment of MDS. However, further investigation is required to elucidate its specific therapeutic targets.ObjectiveTo examine the influence of ABI2 on MDS and clarify the regulatory role of As₂S₂ on ABI2 within the therapeutic framework of MDS.MethodsTo explore ABI2's role in the expression and prognosis of patients with hematological malignancies, RNA interference was used to reduce ABI2 expression in SKM-

Cancer in pregnancy: FIGO Best practice advice and narrative review.

Cancer during pregnancy is relatively rare. The incidence is underestimated due to the lack of international registries covering both high-income and low- and middle-income countries, and is expected to rise with increasing maternal age and increasing global adoption of cell-free DNA testing for aneuploidy. Physiological changes during pregnancy often make the diagnosis challenging and delayed. Lack of experience and knowledge about this condition may also contribute to late diagnosis, suboptimal management, and occasionally inadvertent fetal and/or maternal harm. The principles of cancer mana

Unleashing the Impact of Exosomes Derived from Human Placental Mesenchymal Stem Cells (hPMSCs) on U-266 Myeloma Cell Line.

Multiple myeloma (MM) is a malignancy of plasma cells, terminally differentiated B cells, with complications like hypercalcemia, renal failure, anemia, and bone disease, which are also known as CRAB criteria. MM develops from monoclonal gammopathy of unknown significance (MGUS), a pre-malignant plasma cell dyscrasia. Over some time, MGUS has the potential to progress into smoldering multiple myeloma (SMM), which can evolve into MM. MM rarely progresses into plasma cell leukemia (PCL), a condition in which malignant plasma cells no longer stay in the bone marrow niche and circulate in the perip

European Medicines Agency review of ixazomib (Ninlaro) for the treatment of adult patients with multiple myeloma who have received at least one prior therapy.

On 21 November 2016, the European Commission issued a marketing authorisation valid throughout the European Union for ixazomib in combination with lenalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. Ixazomib was evaluated in one, randomised, double-blind, phase III study comparing ixazomib plus lenalidomide and dexamethasone (n=360; ixazomib arm) versus placebo plus lenalidomide and dexamethasone (n=362; placebo arm) in adult patients with relapsed and/or refractory multiple myeloma who had received at least one

Совпадение в полном тексте источника
… In the pregnant rat dose range finding study, there were decreases in fetal weights and a trend towards decreased fetal viability and increased post implantation losses; however, these findings were not reproduced in the definitive study (no observed adverse effect level (NOAEL) for rat embryo fetal …

Cancer in Pregnancy: Therapeutic Decisions at the Intersection of Two Lives.

Background: Cancer during pregnancy is a rare but increasingly encountered condition due to delayed childbearing and improved survival of women with cancer. The coexistence of malignancy and pregnancy poses complex diagnostic and therapeutic challenges, requiring careful balance between maternal prognosis and fetal safety. Objective: This review aims to summarize current evidence on the diagnosis and multidisciplinary management of cancer during pregnancy, focusing on the safe use of oncologic therapies, obstetric decision-making, and maternal and fetal outcomes. Methods: A narrative review wa

Совпадение в полном тексте источника
… This approach should take into account the values of the pregnant woman and her family, her tolerance for treatment-related risk, and fetal viability according to gestational age. … For surgical procedures performed after fetal viability, intraoperative fetal heart rate monitoring should be discussed in advance with the patient and conducted in coordination among surgical, obstetric, and neonatal teams to define appropriate management in the event of nonreassuring patterns during …

A pre-in vitro maturation medium containing cumulus oocyte complex ligand-receptor signaling molecules maintains meiotic arrest, supports the cumulus oocyte complex and improves oocyte developmental competence.

STUDY QUESTION: Can a pre-in vitro maturation (pre-IVM) medium containing signaling molecules rather than chemical/pharmaceutical agents, sustain meiotic arrest and improve developmental competence of in vitro matured oocytes in CF1 outbred mice? SUMMARY ANSWER: A short 2 h period of pre-IVM prevents spontaneous meiotic resumption, improves mitochondria activity in subsequently matured oocytes, and increases developmental competence, pregnancy rate and implantation of resulting embryos. WHAT IS KNOWN ALREADY: Spontaneous resumption of meiosis in vitro is detrimental for oocyte developmental

Synergistic silencing of α-globin and induction of γ-globin by histone deacetylase inhibitor, vorinostat as a potential therapy for β-thalassaemia.

β-Thalassaemia is one of the most common monogenic diseases with no effective cure in the majority of patients. Unbalanced production of α-globin in the presence of defective synthesis of β-globin is the primary mechanism for anaemia in β-thalassaemia. Clinical genetic data accumulated over three decades have clearly demonstrated that direct suppression of α-globin and induction of γ-globin are effective in reducing the globin chain imbalance in erythroid cells hence improving the clinical outcome of patients with β-thalassaemia. Here, we show that the histone deacetylase inhibitor drug, vorin

Discovery of a Promising Hydroxyamino-Piperidine HDAC6 Inhibitor via Integrated Virtual Screening and Experimental Validation in Multiple Myeloma.

Background: Histone deacetylase 6 (HDAC6) is a unique class IIb HDAC isozyme characterized by two catalytic domains and a zinc finger ubiquitin-binding domain. It plays critical roles in various cellular processes, including protein degradation, autophagy, immune regulation, and cytoskeletal dynamics. Due to its multifunctional nature and overexpression in several cancer types, HDAC6 has emerged as a promising therapeutic target. Methods: In this study, we employed a ligand-based pharmacophore modeling approach using a structurally diverse set of known HDAC6 inhibitors. This was followed by th