Effect of Immunoadsorption on clinical presentation and immune alterations in COVID-19-induced and/or aggravated ME/CFS.

Autoreactive antibodies (AAB) are currently being investigated as causative or aggravating factors during post-COVID. In this study we analyze the effect of immunoadsorption therapy on symptom improvement and the relationship with immunological parameters in post-COVID patients exhibiting symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) induced or aggravated by an SARS-CoV-2 infection. This observational study includes 12 post-COVID patients exhibiting a predominance of ME/CFS symptoms alongside increased concentrations of autonomic nervous system receptors (ANSR) autoantibodies and neurological impairments.

The Anti-Obesity Effect of Fish Oil in Diet-Induced Obese Mice Occurs via Both Decreased Food Intake and the Induction of Heat Production Genes in Brown but Not White Adipose Tissue.

Omega-3 (ω-3) polyunsaturated fatty acids in fish oil have been shown to prevent diet-induced obesity in lean mice and to promote heat production in adipose tissue. However, the effects of fish oil on obese animals remain unclear. This study investigated the effects of fish oil in obese mice.

Standardization to Characterize the Complexity of Vessel Network Using the Aortic Ring Model.

Regeneration after ischemia requires to be promoted by (re)perfusion of the affected tissue, and, to date, there is no therapy that covers all needs. In treatment with mesenchymal stem cells (MSC), the secretome acts via paracrine mechanisms and has a positive influence on vascular regeneration via proangiogenic factors. A lack of standardization and the high complexity of vascular structures make it difficult to compare angiogenic readouts from different studies.

Secretome of the Olfactory Ensheathing Cells Influences the Behavior of Neural Stem Cells.

Olfactory ensheathing cell (OEC) transplantation demonstrates promising therapeutic results in neurological disorders, such as spinal cord injury. The emerging cell-free secretome therapy compensates for the limitations of cell transplantation, such as low cell survival rates. However, the therapeutic benefits of the human OEC secretome remain unclear.

Harnessing Mesenchymal Stromal Cells for Advanced Wound Healing: A Comprehensive Review of Mechanisms and Applications.

Chronic wounds and injuries remain a substantial healthcare challenge, with significant burdens on patient quality of life and healthcare resources. Mesenchymal stromal cells (MSCs) present an innovative approach to enhance tissue repair and regeneration in the context of wound healing. The intrinsic presence of MSCs in skin tissue, combined with their roles in wound repair, ease of isolation, broad secretory profile, and low immunogenicity, makes them especially promising for treating chronic wounds.

The Intrinsic Neuronal Activation of the CXCR4 Signaling Axis Is Associated with a Pro-Regenerative State in Cervical Primary Sensory Neurons Conditioned by a Sciatic Nerve Lesion.

CXCL12 and CXCR4 proteins and mRNAs were monitored in the dorsal root ganglia (DRGs) of lumbar (L4-L5) and cervical (C7-C8) spinal segments of naïve rats, rats subjected to sham operation, and those undergoing unilateral complete sciatic nerve transection (CSNT) on post-operation day 7 (POD7). Immunohistochemical, Western blot, and RT-PCR analyses revealed bilaterally increased levels of CXCR4 protein and mRNA in both lumbar and cervical DRG neurons after CSNT. Similarly, CXCL12 protein levels increased, and CXCL12 mRNA was upregulated primarily in lumbar DRGs ipsilateral to the nerve lesion.

Identification of Disease-Relevant, Sex-Based Proteomic Differences in iPSC-Derived Vascular Smooth Muscle Cells.

The prevalence of cardiovascular disease varies with sex, and the impact of intrinsic sex-based differences on vasculature is not well understood. Animal models can provide important insights into some aspects of human biology; however, not all discoveries in animal systems translate well to humans. To explore the impact of chromosomal sex on proteomic phenotypes, we used iPSC-derived vascular smooth muscle cells from healthy donors of both sexes to identify sex-based proteomic differences and their possible effects on cardiovascular pathophysiology.

S6K2 in Focus: Signaling Pathways, Post-Translational Modifications, and Computational Analysis.

S6 Kinase 2 (S6K2) is a key regulator of cellular signaling and is crucial for cell growth, proliferation, and survival. This review is divided into two parts: the first focuses on the complex network of upstream effectors, downstream modulators, and post-translational modifications (PTMs) that regulate S6K2 activity. We emphasize the dynamic nature of S6K2 regulation, highlighting its critical role in cellular homeostasis and its potential as a therapeutic target in diseases like cancer.

The Immunophenotype and the Odontogenic Commitment of Dental Pulp Stem Cells Co-Cultured with Macrophages Under Inflammatory Conditions Is Modulated by Complex Magnetic Fields.

Dental inflammatory diseases remain a challenging clinical issue, whose causes and development are still not fully understood. During dental caries, bacteria penetrate the tooth pulp, causing pulpitis. To prevent pulp necrosis, it is crucial to promote tissue repair by recruiting immune cells, such as macrophages, able to secrete signal molecules for the pulp microenvironment and thus to recruit dental pulp stem cells (DPSCs) in the damaged site.

A 3D-Printed Aqueous Drainage Tube with an Expandable Inner Diameter to Accommodate the Intraocular Pressure (IOP) Fluctuations After Glaucoma Surgery.

Glaucoma treatment involves reducing the intraocular pressure (IOP), which can damage the optic nerve, to a normal range. Aqueous drainage devices may be used for treatment, and a variety of devices have been proposed. However, they have a non-variable and uniform inner diameter, which makes it difficult to accommodate the IOP fluctuations that occur after glaucoma surgery.

CAR-T cell therapy in developing countries: how long should we wait?

Low- and middle-income countries (LMICs) face a significant burden of cancer prevalence and incidence. However, the survival rates for patients with cancer in these regions are notably lower than those in high-income countries, primarily due to late diagnosis and limited access to advanced treatments. Chimeric antigen receptor (CAR) T-cell therapy has demonstrated promising outcomes in certain terminally ill patients with cancer, yet access to this treatment remains limited in LMICs, including Nepal.

Autologous macrophage therapy for liver cirrhosis: a phase 2 open-label randomized controlled trial.

Cirrhosis is a major cause of morbidity and mortality; however, there are no approved therapies except orthotopic liver transplantation. Preclinical studies showed that bone-marrow-derived macrophage injections reduce inflammation, resolve fibrosis and stimulate liver regeneration. In a multicenter, open-label, parallel-group, phase 2 randomized controlled trial ( ISRCTN10368050 ) in n = 51 adult patients with compensated cirrhosis and Model for End-Stage Liver Disease (MELD) score ≥10 and ≤17, we evaluated the efficacy of autologous monocyte-derived macrophage therapy (n = 27) compared to standard medical care (n = 24).

Alpha-synuclein inhibits the secretion of extracellular vesicles through disruptions in YKT6 lipidation.

Parkinson's disease is characterized by the presence of α-synuclein (α-syn) primarily containing Lewy bodies in neurons. Despite decades of extensive research on α-syn accumulation, its molecular mechanisms have remained largely unexplored. Recent studies by us and others have suggested that extracellular vesicles (EVs), especially exosomes, can mediate the release of α-syn from cells, and inhibiting this pathway could result in increased intracellular α-syn levels.

Clinimetric analysis of the numeric pain rating scale, patient-rated tennis elbow evaluation, and tennis elbow function scale in patients with lateral elbow tendinopathy.

Background: Currently, there is conflicting clinimetric data on the patient-rated tennis elbow evaluation (PRTEE) and a paucity of evidence regarding the reliability, validity, and responsiveness of the numeric pain rating scale (NPRS), and tennis elbow function scale (TEFS) in patients with lateral elbow tendinopathy.

Objective: Perform a comprehensive clinimetric analysis of the NPRS, PRTEE, and TEFS in a sample of patients ( = 143) with lateral elbow tendinopathy.

Methods: Establish the reliability, construct validity, responsiveness, meaningful clinically important difference (MCID), and minimal detectable change (MDC) values for the NPRS, PRTEE, and TEFS at the 3-month follow-up.

High fructose levels inhibit the proliferation of cardiomyocytes via the Notch1 signaling pathway.

Fructose, as a natural and simple sugar, is not significantly harmful to the human body when consumed in moderation and can provide energy for the body. High-fructose diets have been linked to an increased risk of a range of metabolic disorders, including hypertriglyceridemia, hypertension, and diabetes mellitus. These conditions are known to be associated with an elevated risk of developing cardiometabolic diseases.

Clinical impact of PTEN rs701848 as a predictive marker for breast cancer.

Background: The incidence of Breast cancer (BC) is currently augmented and it has become the most common malignant cancer in females. Phosphatase and tensin homolog (PTEN) is a tumor suppressor gene as a result of blocking the phosphorylation of PIP3 in PI3K pathway.

Methods: The computational bioinformatics tools were performed to determine the link between PTEN rs701848T/C genetic variants and breast cancer progression.

Tissue Determinants of Antiviral Immunity in the Liver.

The liver is an organ bearing important metabolic and immune functions. Hepatocytes are the main metabolically active cells of the liver and are the target of infection by hepatotropic viruses. Virus-specific CD8 T cells are essential for the control of hepatocyte infection with hepatotropic viruses but may be subject to local regulation of their effector function.

Biofunctionalisation of porous additively manufactured magnesium-based alloys for Orthopaedic applications: A review.

Magnesium (Mg) alloys have gained significant attention as a desirable choice of biodegradable implant for use in bone repair applications, largely owing to their unique material properties. More recently, Mg and Mg-based alloys have been used as load-bearing metallic scaffolds for bone tissue engineering applications, offering promising opportunities in the field. The mechanical properties and relative density of Mg-based alloys closely approximate those of natural human bone tissue, thereby mitigating the risk of stress-shielding effects.

Biological and environmental degradation of two-dimensional materials.

As the use of two-dimensional materials continues to grow, so too does the need to understand the environmental and biological impact of such materials. Degradation is a critical step in the life cycle of any material, but the majority of such knowledge is obtained from test tube and in vitro studies. Therefore, there remains a gap in understanding the degradability of two-dimensional materials in complex systems (in vivo) and in different ambient environments.

Spatial transcriptomic characterization of a Carnegie stage 7 human embryo.

Gastrulation marks a pivotal stage in mammalian embryonic development, establishing the three germ layers and body axis through lineage diversification and morphogenetic movements. However, studying human gastrulating embryos is challenging due to limited access to early tissues. Here we show the use of spatial transcriptomics to analyse a fully intact Carnegie stage 7 human embryo at single-cell resolution, along with immunofluorescence validations in a second embryo.

Vinculin haploinsufficiency impairs integrin-mediated costamere remodeling on stiffer microenvironments.

Vinculin (VCL) is a key adapter protein located in force-bearing costamere complexes, which mechanically couples the sarcomere to the ECM. Heterozygous vinculin frameshift genetic variants can contribute to cardiomyopathy when external stress is applied, but the mechanosensitive pathways underpinning VCL haploinsufficiency remain elusive. Here, we show that in response to extracellular matrix stiffening, heterozygous loss of VCL disrupts force-mediated costamere protein recruitment, thereby impairing cardiomyocyte contractility and sarcomere organization.

Capture primed pluripotency in guinea pig.

Guinea pigs are valuable models for human disease research, yet the lack of established pluripotent stem cell lines has limited their utility. In this study, we isolate and characterize guinea pig epiblast stem cells (gpEpiSCs) from post-implantation embryos. These cells differentiate into the three germ layers, maintain normal karyotypes, and rely on FGF2 and ACTIVIN A signaling for self-renewal and pluripotency.

Oncogenic IDH1 drives robust loss of histone acetylation and increases chromatin heterogeneity.

Malignant gliomas are heterogeneous tumors, mostly incurable, arising in the central nervous system (CNS) driven by genetic, epigenetic, and metabolic aberrations. Mutations in isocitrate dehydrogenase (IDH1/2) enzymes are predominantly found in low-grade gliomas and secondary high-grade gliomas, with IDH1 mutations being more prevalent. Mutant-IDH1/2 confers a gain-of-function activity that favors the conversion of a-ketoglutarate (α-KG) to the oncometabolite 2-hydroxyglutarate (2-HG), resulting in an aberrant hypermethylation phenotype.

infection accelerates postnatal maturation of the intestinal epithelium.

Postnatal establishment of enteric metabolic, host-microbial and immune homeostasis is the result of precisely timed and tightly regulated developmental and adaptive processes. Here, we show that infection with the invasive enteropathogen Typhimurium results in accelerated maturation of the neonatal epithelium with premature appearance of antimicrobial, metabolic, developmental, and regenerative features of the adult tissue. Using conditional Myd88-deficient mice, we identify the critical contribution of immune cell-derived mediators.