Purpose: Subretinal (SR) injection in porcine models is a promising avenue for preclinical evaluation of cell and gene therapies. Targeting of the subretinal fluid compartment (bleb) is critical to the procedure, especially if treatment of the cone-rich area centralis is required (i.e.
View Article and Find Full Text PDFHeart failure (HF) and type 2 diabetes mellitus (DM2) are global health problems that often lead to muscle atrophy. These conditions are associated with increased autophagy and apoptosis in the muscle cells, resulting in decreased muscle mass. Physical exercise associated with photobiomodulation (PBM) seems promising to attenuate the skeletal muscle changes caused by HF and DM2, due to its direct effects on mitochondria, which may result in an increase in antioxidant capacity.
View Article and Find Full Text PDFObjective: To evaluate the effectiveness and safety of tofacitinib in patients with ulcerative colitis (UC) in clinical practice in Lebanon.
Design: This was a retrospective cross-sectional study. The data were collected from hospital records.
Hemophilia A, a severe hereditary hemorrhagic disorder characterized by a deficiency in blood clotting factors, imposes a significant economic burden on individuals, healthcare systems, and society, with inhibitors exacerbating the socioeconomic impact. The detrimental impact on the quality of life for patients and caregivers, including functional limitations, is particularly pronounced during bleeding episodes and in the presence of inhibitors. The increasing prevalence of Hemophilia A across the MENA region is evident, marked by the approval of various therapies and intensified research and development efforts focusing on treatment innovations.
View Article and Find Full Text PDFThe investigation of triggers causing the onset and intensification of Northern Hemisphere Glaciation (NHG) during the late Pliocene is essential for understanding the global climate system, with important implications for projecting future climate changes. Despite their critical roles in the global climate system, influences of land-ocean interactions on high-latitude ice sheets remain largely unexplored. Here, we present a high-resolution Asian dust record from Ocean Drilling Program Site 1208 in the North Pacific, which lies along the main route of the westerlies.
View Article and Find Full Text PDFIntroduction: Cardiovascular diseases are the leading cause of morbidity and mortality worldwide. Ischemic heart disease is one of the most harmful conditions to cellular structure and function. After reperfusion treatment, a spectrum of adverse effects becomes evident, encompassing altered cell viability, heightened oxidative stress, activated autophagy, and increased apoptosis.
View Article and Find Full Text PDFIntroduction: Orthotopic cardiac xenotransplantation has seen notable improvement, leading to the first compassionate use in 2022. However, it remains challenging to define the clinical application of cardiac xenotransplantation, including the back-up strategy in case of xenograft failure. In this regard, the heterotopic thoracic technique could be an alternative to the orthotopic procedure.
View Article and Find Full Text PDFExpert Rev Pharmacoecon Outcomes Res
October 2024
Introduction: Multiple sclerosis (MS) is a persistent condition characterized by immune-mediated processes in the central nervous system, affecting around 2.8 million individuals globally. While historically less prevalent in the Middle East and North Africa (MENA) region, recent trends mirror the global rise in MS.
View Article and Find Full Text PDFTo date 11 patients with Coffin-Siris syndrome type 7 (OMIM 618027) have been described since the first literature report. All reported patients carried de novo variants with presumed dominant negative effect, which localized in the PHD1/PHD2 domains of DPF2. Here we report on the first familial case of Coffin-Siris syndrome type 7.
View Article and Find Full Text PDFSepsis survivors exhibit immune dysfunction, hematological changes, and increased risk of infection. The long-term impacts of sepsis on hematopoiesis were analyzed using a surgical model of murine sepsis, resulting in 50% survival. During acute disease, phenotypic hematopoietic stem and progenitor cells (HSPCs) were reduced in the bone marrow (BM), concomitant with increased myeloid colony-forming units and extramedullary hematopoiesis.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Cell Res
April 2024
Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance (PVR), right ventricular (RV) failure and premature death. Compounds with vasodilatory characteristics, such as β-caryophyllene, could be promising therapeutics for PAH. This study aimed to determine the effects of free and nanoemulsified β-caryophyllene in lung oxidative stress and heart function in PAH rats.
View Article and Find Full Text PDFObjective: The present study aimed to explore the relationship between objective physical activity and sedentary behaviour with seasonality among a sample of older adults living in four European countries.
Methods: A sample of 169 older adults living in Croatia, Greece, Portugal, and Poland (mean age = 72.2 ± 6.
Background: Orthotopic cardiac xenotransplantation has seen substantial advancement in the last years and the initiation of a clinical pilot study is close. However, donor organ overgrowth has been a major hurdle for preclinical experiments, resulting in loss of function and the decease of the recipient. A better understanding of the pathogenesis of organ overgrowth after xenotransplantation is necessary before clinical application.
View Article and Find Full Text PDFDuchenne muscular dystrophy (DMD) is a fatal X-linked disease caused by mutations in the gene, leading to complete absence of dystrophin and progressive degeneration of skeletal musculature and myocardium. In DMD patients and in a corresponding pig model with a deletion of exon 52 (Δ52), expression of an internally shortened dystrophin can be achieved by skipping of exon 51 to reframe the transcript. To predict the best possible outcome of this strategy, we generated Δ51-52 pigs, additionally representing a model for Becker muscular dystrophy (BMD).
View Article and Find Full Text PDFEngineered heart tissue (EHT) transplantation represents an innovative, regenerative approach for heart failure patients. Late preclinical trials are underway, and a first clinical trial started recently. Preceding studies revealed functional recovery after implantation of in vitro-matured EHT in the subacute stage, whereas transplantation in a chronic injury setting was less efficient.
View Article and Find Full Text PDFDomestic pigs () share many genetic, anatomical, and physiological traits with humans and therefore constitute an excellent preclinical animal model. Fundamental understanding of the cellular and molecular processes governing early porcine cardiogenesis is critical for developing advanced porcine models used for the study of heart diseases and new regenerative therapies. Here, we provide a detailed characterization of porcine cardiogenesis based on fetal porcine hearts at various developmental stages and cardiac cells derived from porcine expanded pluripotent stem cells (pEPSCs), i.
View Article and Find Full Text PDFThe end of the Middle Pleistocene Transition (MPT, ~ 800-670 thousand years before present, ka) was characterised by the emergence of large glacial ice-sheets associated with anomalously warm North Atlantic sea surface temperatures enhancing moisture production. Still, the direction and intensity of moisture transport across Eurasia towards potential ice-sheets is poorly constrained. To reconstruct late MPT moisture production and dispersal, we combine records of upper ocean temperature and pollen-based Mediterranean forest cover, a tracer of westerlies and precipitation, from a subtropical drill-core collected off South-West Iberia, with records of East Asia summer monsoon (EASM) strength and West Pacific surface temperatures, and model simulations.
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