State-of-the-Art Liver Cancer Organoids: Modeling Cancer Stem Cell Heterogeneity for Personalized Treatment.

Liver cancer poses a global health challenge with limited therapeutic options. Notably, the limited success of current therapies in patients with primary liver cancers (PLCs) may be attributed to the high heterogeneity of both hepatocellular carcinoma (HCCs) and intrahepatic cholangiocarcinoma (iCCAs). This heterogeneity evolves over time as tumor-initiating stem cells, or cancer stem cells (CSCs), undergo (epi)genetic alterations or encounter microenvironmental changes within the tumor microenvironment.

Diagnostic Accuracy of Furosemide Stress Test and Cystatin-C for Predicting Acute Kidney Injury Progression in Children: A Prospective Cohort Study.

Objectives: To evaluate the predictive ability of furosemide stress test (FST), serum and urine cystatin-C in identifying progressive acute kidney injury (AKI) and the need for kidney replacement therapy (KRT).

Methods: Children aged one month to 18 y admitted in the pediatric intensive care unit (PICU) with Kidney Diseases Improving Global Outcomes (KDIGO) stage-1/2 AKI were enrolled. FST and serum and urine cystatin-C levels were performed and analyzed.

Impact of hemoadsorption with CytoSorb® on meropenem and piperacillin exposure in critically ill patients in a post-CKRT setup: a single-center, retrospective data analysis.

Purpose: CytoSorb® (CS) adsorbent is a hemoadsorption filter for extracorporeal blood purification often integrated into continuous kidney replacement therapy (CKRT). It is primarily used in critically ill patients with sepsis and related conditions, including cytokine storms and systemic inflammatory responses. Up to now, there is no evidence nor recommendation for the use of CS filters in sepsis (22).

Integrating the milk microbiome signatures in mastitis: milk-omics and functional implications.

Mammalian milk contains a variety of complex bioactive and nutritional components and microorganisms. These microorganisms have diverse compositions and functional roles that impact host health and disease pathophysiology, especially mastitis. The advent and use of high throughput omics technologies, including metagenomics, metatranscriptomics, metaproteomics, metametabolomics, as well as culturomics in milk microbiome studies suggest strong relationships between host phenotype and milk microbiome signatures in mastitis.

Interleukin 1 receptor associated kinase 1 gene polymorphism association with risk of rheumatological diseases in Egyptian population.

Background: Interleukin-1 receptor-associated kinase1 (IRAK1) plays a considerable role in the inflammatory signaling pathway. The current study aimed to identify any association between (rs1059703) single nucleotide polymorphism (SNP) and vulnerability to rheumatological diseases in the pediatric and adult Egyptian population.

Patients And Methods: The current study included four patient groups: adult Systemic lupus erythematosus (SLE), Rheumatoid arthritis (RA), juvenile systemic lupus erythematosus (JSLE), and juvenile idiopathic arthritis (JIA).

Nanoparticle innovations in targeted cancer therapy: advancements in antibody-drug conjugates.

Antibody-drug conjugates (ADCs) have emerged as a promising strategy in targeted cancer therapy, enabling the precise delivery of cytotoxic agents to tumor sites while minimizing systemic toxicity. However, traditional ADCs face significant limitations, including restricted drug loading capacity, where an optimal drug-to-antibody ratio (DAR) is crucial; low DARs may lead to insufficient potency, while high DARs can cause rapid clearance and increased toxicity. Additionally, ADCs often suffer from instability in circulation due to the potential for premature release of cytotoxic agents, resulting in off-target effects and reduced therapeutic efficacy.

Natural products and long non-coding RNAs in prostate cancer: insights into etiology and treatment resistance.

Globally, the incidence and death rates associated with cancer persist in rising, despite considerable advancements in cancer therapy. Although some malignancies are manageable by a mix of chemotherapy, surgery, radiation, and targeted therapy, most malignant tumors either exhibit poor responsiveness to early identification or endure post-treatment survival. The prognosis for prostate cancer (PCa) is unfavorable since it is a perilous and lethal malignancy.

Alterations of amino acids in older adults with Alzheimer's Disease and Vascular Dementia.

Metabolomics provide a promising tool for understanding dementia pathogenesis and identifying novel biomarkers. This study aimed to identify amino acid biomarkers for Alzheimer's Disease (AD) and Vascular Dementia (VD). By amino acid metabolomics, the concentrations of amino acids were determined in the serum of AD and VD patients as well as age-matched healthy controls.

Evaluation of the serum level of Lipocalin 2 in vitiligo.

Vitiligo is considered as depigmenting skin disorder where patches of skin losing their pigment. Lipocalin-2 (LCN2) is one of the Inflammatory adipokines that has a potential role in skin disorders and other inflammatory diseases as well. To measure the concentration level of LCN2 in vitiligo patients compared to healthy controls and to investigate its relation to disease activity and other clinical data to evaluate its role in the pathogenesis of the disease.

Fluoxetine exerts anti-proliferative effect in human epidermal keratinocytes.

We have recently shown that fluoxetine (FX) suppressed polyinosinic-polycytidylic acid-induced inflammatory response and endothelin release in human epidermal keratinocytes, via the indirect inhibition of the phosphoinositide 3-kinase (PI3K)-pathway. Because PI3K-signaling is a positive regulator of the proliferation, in the current, highly focused follow-up study, we assessed the effects of FX (14 µM) on the proliferation and differentiation of human epidermal keratinocytes. We found that FX exerted anti-proliferative actions in 2D cultures (HaCaT and primary human epidermal keratinocytes [NHEKs]; 48- and 72-h; CyQUANT-assay) as well as in 3D reconstructed epidermal equivalents (48-h; Ki-67 immunohistochemistry).

Exploring the effect of hsa-miR-19b-3p on IL-1R1 expression and serum levels in alopecia areata.

Alopecia areata (AA) is an autoimmune condition marked by hair loss, linked to inflammatory processes involving the interleukin-1 receptor type 1 (IL-1R1) pathway. This study aims to explore the relationship between IL-1R1 gene expression, serum IL-1R1 levels, and hsa-miR-19b-3p in relation to AA severity. Using a case-control design, we assessed 100 AA patients and 100 healthy controls, measuring serum IL-1R1 through enzyme-linked immunosorbent assay (ELISA) and analyzing IL-1R1 gene and hsa-miR-19b-3p expression levels via quantitative real-time PCR (qRT-PCR).

Comparison of the amyloid plaque proteome in Down syndrome, early-onset Alzheimer's disease, and late-onset Alzheimer's disease.

Down syndrome (DS) is strongly associated with Alzheimer's disease (AD) due to APP overexpression, exhibiting Amyloid-β (Aβ) and Tau pathology similar to early-onset (EOAD) and late-onset AD (LOAD). We evaluated the Aβ plaque proteome of DS, EOAD, and LOAD using unbiased localized proteomics on post-mortem paraffin-embedded tissues from four cohorts (n = 20/group): DS (59.8 ± 4.

Nanoscale Viscometry Reveals an Inherent Mucus Defect in Cystic Fibrosis.

The abnormally viscous and thick mucus is a hallmark of cystic fibrosis (CF). How the mutated CF gene causes abnormal mucus remains an unanswered question of paramount interest. Mucus is produced by the hydration of gel-forming mucin macromolecules that are stored in intracellular granules prior to release.

Lineage-dependence of the neuroblastoma surfaceome defines tumor cell state-dependent and independent immunotherapeutic targets.

Background: Neuroblastoma is a heterogeneous disease with adrenergic (ADRN)- and therapy resistant mesenchymal (MES)-like cells driven by distinct transcription factor networks. Here, we investigate the expression of immunotherapeutic targets in each neuroblastoma subtype and propose pan-neuroblastoma and cell state specific targetable cell-surface proteins.

Methods: We characterized cell lines, patient-derived xenografts, and patient samples as ADRN-dominant or MES-dominant to define subtype-specific and pan-neuroblastoma gene sets.

Unsaturated Fatty Acids Are Decreased in Aβ Plaques in Alzheimer's Disease.

Alzheimer's disease (AD) is characterized by the accumulation of amyloid-beta (Aβ) plaques in the brain, contributing to neurodegeneration. This study investigates lipid alterations within these plaques using a novel, label-free, multimodal approach. Combining infrared (IR) imaging, machine learning, laser microdissection (LMD), and flow injection analysis mass spectrometry (FIA-MS), we provide the first comprehensive lipidomic analysis of chemically unaltered Aβ plaques in post-mortem human AD brain tissue.

Role of Cytokines in Predicting Early Major Bleeding in Patients With Acute Pulmonary Embolism.

Introduction: Anticoagulant therapy is critical for venous thromboembolism (VTE) management, though bleeding remains a major concern, ranging from mild to fatal events. This study aimed to assess the predictive value of cytokines for major bleeding in patients with acute pulmonary embolism (PE).

Methods: In this prospective, observational study, patients aged ≥ 18 years with acute PE were enrolled from April 2021 to September 2022 and followed for 30 days.

Sotatercept in pulmonary hypertension and beyond.

Sotatercept binds free activins by mimicking the extracellular domain of the activin receptor type IIA (ACTRIIA). Additional ligands are BMP/TGF-beta, GDF8, GDF11 and BMP10. The binding with activins leads to the inhibition of the signalling pathway and the deactivation of the bone morphogenic protein (BMP) receptor type 2.

The Functional and Structural Succession of Mesic-Grassland Soil Microbiomes Beneath Decomposing Large Herbivore Carcasses.

Plant detritus is abundant in grasslands but decomposes slowly and is relatively nutrient-poor, whereas animal carcasses are labile and nutrient-rich. Recent studies have demonstrated that labile nutrients from carcasses can significantly alter the long-term soil microbial function at an ecosystem scale. However, there is a paucity of knowledge on the functional and structural response and temporal scale of soil microbiomes beneath large herbivore carcasses.

A Novel Screening System to Characterize and Engineer Quorum Quenching Lactonases.

N-acyl l-homoserine lactones are signaling molecules used by numerous bacteria in quorum sensing. Some bacteria encode lactonases, which can inactivate these signals. Lactonases were reported to inhibit quorum sensing-dependent phenotypes, including virulence and biofilm.

Arrhythmogenic calmodulin variants D131E and Q135P disrupt interaction with the L-type voltage-gated Ca channel (Ca1.2) and reduce Ca-dependent inactivation.

Aim: Long QT syndrome (LQTS) and catecholaminergic polymorphism ventricular tachycardia (CPVT) are inherited cardiac disorders often caused by mutations in ion channels. These arrhythmia syndromes have recently been associated with calmodulin (CaM) variants. Here, we investigate the impact of the arrhythmogenic variants D131E and Q135P on CaM's structure-function relationship.

Data-Driven Equation-Free Dynamics Applied to Many-Protein Complexes: The Microtubule Tip Relaxation.

Microtubules (MTs) constitute the largest components of the eukaryotic cytoskeleton and play crucial roles in various cellular processes, including mitosis and intracellular transport. The property allowing MTs to cater to such diverse roles is attributed to dynamic instability, which is coupled to the hydrolysis of GTP (guanosine-5'-triphosphate) to GDP (guanosine-5'-diphosphate) within the β-tubulin monomers. Understanding the equilibrium dynamics and the structural features of both GDP- and GTP-complexed MT tips, especially at an all-atom level, remains challenging for both experimental and computational methods because of their dynamic nature and the prohibitive computational demands of simulating large, many-protein systems.

Storage and controlled release of fragrances maintaining a constant ratio of volatile compounds.

Controlled fragrance release at the right time, in the right place, depending on the context remains a technological challenge in the areas of psychophysiology, biochemistry and the entertainment industry. In this study, we demonstrate how bulk poly(dimethylsiloxane) (PDMS) templates may effectively take up and retain volatile organic compounds of essential orange oil in the original form without significantly shifting the scent profile. This is done depending on the sampling approach that follows a controllable and slow fragrance release maintaining a constant ratio of volatile compounds in a template-thickness, temperature and time-dependent manner.

Chemical space as a unifying theme for chemistry.

Chemistry has diversified from a basic understanding of the elements to studying millions of highly diverse molecules and materials, which together are conceptualized as the chemical space. A map of this chemical space where distances represent similarities between compounds can represent the mutual relationships between different subfields of chemistry and help the discipline to be viewed and understood globally.

Intercellular TIMP-1-CD63 signaling directs the evolution of immune escape and metastasis in KRAS-mutated pancreatic cancer cells.

Background And Aims: Oncogenic KRAS mutations are present in approximately 90% of pancreatic ductal adenocarcinoma (PDAC). However, Kras mutation alone is insufficient to transform precancerous cells into metastatic PDAC. This study investigates how KRAS-mutated epithelial cells acquire the capacity to escape senescence or even immune clearance, thereby progressing to advanced PDAC.