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).

Sepsis subtypes and differential treatment response to vitamin C: biological sub-study of the LOVIT trial.

Purpose: We hypothesised that the biological heterogeneity of sepsis may highlight sepsis subtypes with differences in response to intravenous vitamin C treatment in the Lessening Organ Dysfunction with VITamin C (LOVIT) trial. Our aims were to identify sepsis subtypes and to test whether sepsis subtypes have differences in treatment effect to vitamin C and describe putative biological effects of vitamin C treatment.

Methods: We measured biomarkers of inflammation, at baseline and at 7 days post-randomisation, in 457/863 (53.

Typical development of synaptic and neuronal properties can proceed without microglia in the cortex and thalamus.

Brain-resident macrophages, microglia, have been proposed to have an active role in synaptic refinement and maturation, influencing plasticity and circuit-level connectivity. Here we show that several neurodevelopmental processes previously attributed to microglia can proceed without them. Using a genetically modified mouse that lacks microglia (Csf1r), we find that intrinsic properties, synapse number and synaptic maturation are largely normal in the hippocampal CA1 region and somatosensory cortex at stages where microglia have been implicated.

A multi-level analysis of motor and behavioural dynamics in 9-month-old preterm and term-born infants during changing emotional and interactive contexts.

Computational analysis of infant movement has significant potential to reveal markers of developmental health. We report two studies employing dynamic analyses of motor kinematics and motor behaviours, which characterise movement at two levels, in 9-month-old infants. We investigate the effect of preterm birth (< 33 weeks of gestation) and the effect of changing emotional and social-interactive contexts in the still-face paradigm.

Host hepatocyte senescence determines the success of hepatocyte transplantation in a mouse model of liver injury.

Background & Aims: Hepatocyte transplantation has shown promise for genetic diseases of the hepatocytes but to date has shown limited efficacy for non-genetic forms of severe liver injury. Limited cell engraftment and poor function of donor hepatocytes in recipient livers impacts the clinical utility of hepatocyte cell therapy. The mechanisms underpinning this are poorly understood.

Licensing and niche competition in spermatogenesis: mathematical models suggest complementary regulation of tissue maintenance.

To maintain and regenerate adult tissues after injury, division and differentiation of tissue-resident stem cells must be precisely regulated. It remains elusive which regulatory strategies prevent exhaustion or overgrowth of the stem cell pool, whether there is coordination between multiple mechanisms, and how to detect them from snapshots. In Drosophila testes, somatic stem cells transition to a state that licenses them to differentiate, but remain capable of returning to the niche and resuming cell division.

Endothelial cells as key players in cerebral small vessel disease.

Cerebral small vessel disease (SVD) is a vascular disorder that increases the risk of stroke and dementia and is diagnosed through brain MRI. Current primary prevention and secondary treatment of SVD are focused on lifestyle interventions and vascular risk factor control, including blood pressure reduction. However, these interventions have limited effects, a proportion of individuals with sporadic SVD do not have hypertension, and SVD shows strong familial and genetic underpinnings.

IFNγ and TNFα drive an inflammatory secretion profile in cancer-associated fibroblasts from human non-small cell lung cancer.

Cancer-associated fibroblasts (CAFs) are the dominant nonmalignant component of the tumour microenvironment (TME). CAFs demonstrate a high level of inter- and intra-tumour heterogeneity in solid tumours, though the drivers of CAF subpopulations are not fully understood. Here, we demonstrate that non-small cell lung cancer (NSCLC) patient-derived CAFs upregulate the secretion of inflammatory cytokines (IL6, LIF, IL33, GM-CSF, IL1ra) and chemokines (CCL2, CCL3, CCL4, CCL20, CXCL8, CXCL9, CXCL10, CXCL11) in response to in vitro co-culture with anti-CD3/anti-CD28-stimulated peripheral blood mononuclear cells (PBMCs) via IFNγ and TNFα.

Alternative splicing expands the antiviral IFITM repertoire in Chinese rufous horseshoe bats.

Species-specific interferon responses are shaped by the virus-host arms race. The human interferon-induced transmembrane protein (IFITM) family consists of three antiviral IFITM genes that arose by gene duplication. These genes restrict virus entry and are key players in antiviral interferon responses.

Invasive or Non-invasive Vagus Nerve Stimulation Modulation of Brain Function and Remodeling After Stroke: a Review.

Background: The main reason restricting stroke patients from reintegrating into society is neurological deficits. Of particular interest is the potential Vagus Nerve Stimulation (VNS) potentially offers for sustaining improvement in neurological deficits. The goal of the present study is to provide a summary of the findings from research that has been carried out to elucidate the mechanisms and demonstrate the efficacy and safety of the clinical application of VNS, as well as to identify research gaps in the field, in order to offer references for subsequent further research and application.

A novel human pluripotent stem cell gene activation system identifies IGFBP2 as a mediator in the production of haematopoietic progenitors in vitro.

A major challenge in the stem cell biology field is the ability to produce fully functional cells from induced pluripotent stem cells (iPSCs) that are a valuable resource for cell therapy, drug screening, and disease modelling. Here, we developed a novel inducible CRISPR-mediated activation strategy (iCRISPRa) to drive the expression of multiple endogenous transcription factors (TFs) important for in vitro cell fate and differentiation of iPSCs to haematopoietic progenitor cells. This work has identified a key role for IGFBP2 in developing haematopoietic progenitors.

snRNA-seq stratifies multiple sclerosis patients into distinct white matter glial responses.

Poor understanding of the cellular and molecular basis of clinical and genetic heterogeneity in progressive multiple sclerosis (MS) has hindered the search for new effective therapies. To address this gap, we analyzed 632,000 single-nucleus RNA sequencing profiles from 156 brain tissue samples of MS and control donors to examine inter- and intra-donor heterogeneity. We found distinct cell type-specific gene expression changes between MS gray and white matter, highlighting clear pathology differences.

3D Super-Resolution Imaging of PSD95 Reveals an Abundance of Diffuse Protein Supercomplexes in the Mouse Brain.

PSD95 is an abundant scaffolding protein that assembles multiprotein complexes controlling synaptic physiology and behavior. Confocal microscopy has previously shown that PSD95 is enriched in the postsynaptic terminals of excitatory synapses and two-dimensional (2D) super-resolution microscopy further revealed that it forms nanoclusters. In this study, we utilized three-dimensional (3D) super-resolution microscopy to examine the nanoarchitecture of PSD95 in the mouse brain, characterizing the spatial arrangement of over 8 million molecules.

Clinical predictors of treatment response to gabapentin in women with unexplained chronic pelvic pain.

Introduction: Chronic pelvic pain affects up to 24% of women worldwide and for up to 55% of these there is no associated pathology. Despite this there are no established treatments in this cohort. This is a secondary analysis of a randomised-controlled trial (GaPP2) to explore if there are measures which enable us to predict treatment outcome.

Generation of an inducible dCas9-SAM human PSC line for endogenous gene activation.

The CRISPR/Cas9 system has transformed genome editing by enabling precise modifications for diverse applications. Recent advancements, including base editing and prime editing, have expanded its utility beyond conventional gene knock-out and knock-in strategies. Additionally, several catalytically dead Cas9 (dCas9) proteins fused to distinct activation domains have been developed to modulate endogenous gene expression when directed to their regulatory regions by specific single-guide RNAs.

Monkeypox: A comprehensive review on mutation, transmission, pathophysiology, and therapeutics.

Monkeypox virus (MPXV) is the causative agent of the monkeypox (Mpox) disease, belongs to the Orthopoxvirus genus of the Poxviridae family. Due to the recent re-emergence of Mpox in 2024, this is the second time when the World Health Organization (WHO) declared Mpox as a Public Health Emergency of International Concern (PHEIC). This review intends to offer an in-depth analysis of Mpox, including its key characteristics, epidemiological, mutation, pathophysiology, transmission, and therapeutics.

Harmonizing multisite neonatal diffusion-weighted brain MRI data for developmental neuroscience.

Large diffusion-weighted brain MRI (dMRI) studies in neonates are crucial for developmental neuroscience. Our aim was to investigate the utility of ComBat, an empirical Bayes tool for multisite harmonization, in removing site effects from white matter (WM) dMRI measures in healthy infants born at 37 gestational weeks+ 0 days-42 weeks+ 6 days from the Theirworld Edinburgh Birth Cohort (n = 86) and Developing Human Connectome Project (n = 287). Skeletonized fractional anisotropy (FA), mean, axial and radial diffusivity (MD, AD, RD) maps were harmonized.

Evidence-based guideline: premature ovarian insufficiency.

Study Question: How should premature/primary ovarian insufficiency (POI) be diagnosed and managed based on the best available evidence from published literature?

Summary Answer: The current guideline provides 145 recommendations on symptoms, diagnosis, causation, sequelae, and treatment of POI.

What Is Known Already: Premature ovarian insufficiency (POI) presents a significant challenge to women's health, with far-reaching implications, both physically and emotionally. The potential implications include adverse effects on quality of life; fertility; and bone, cardiovascular, and cognitive health.

The Scottish Hepatology Access Research Partnership (SHARP) improving access to liver services throughout Scotland.

Background And Aims: Scotland has the highest rate of deaths from chronic liver disease (CLD) in the UK. Socioeconomic and geographic isolation represent significant challenges to delivery of care. The multidisciplinary Scottish Hepatology Access Research Partnership (SHARP) aimed to identify and break down barriers to diagnosing and treating liver disease in Scotland.

A prognostic molecular signature of hepatic steatosis is spatially heterogeneous and dynamic in human liver.

Hepatic steatosis is a central phenotype in multi-system metabolic dysfunction and is increasing in parallel with the obesity pandemic. We use a translational approach integrating clinical phenotyping and outcomes, circulating proteomics, and tissue transcriptomics to identify dynamic, functional biomarkers of hepatic steatosis. Using multi-modality imaging and broad proteomic profiling, we identify proteins implicated in the progression of hepatic steatosis that are largely encoded by genes enriched at the transcriptional level in the human liver.

Evidence-based guideline: Premature Ovarian Insufficiency.

Study Question: How should premature/primary ovarian insufficiency (POI) be diagnosed and managed, based on the best available evidence from published literature?

Summary Answer: The current guideline provides 145 recommendations on symptoms, diagnosis, causation, sequelae and treatment of POI.

What Is Known Already: Premature ovarian insufficiency (POI) presents a significant challenge to women's health, with far-reaching implications, both physically and emotionally. The potential implications include adverse effects on quality of life; fertility; and bone, cardiovascular and cognitive health.

Evidence-based guideline: premature ovarian insufficiency.

Study Question: How should premature/primary ovarian insufficiency (POI) be diagnosed and managed, based on the best available evidence from published literature?

Summary Answer: The current guideline provides 145 recommendations on symptoms, diagnosis, causation, sequelae and treatment of POI.

What Is Known Already: POI presents a significant challenge to women's health, with far-reaching implications, both physically and emotionally. The potential implications include adverse effects on quality of life, on fertility and on bone, cardiovascular and cognitive health.