Cystic fibrosis and the clinical biofilm revolution A survey of the Danish CF Center's contribution.

Biofilm infections are chronic infections which are difficult to diagnose. Biofilm infections are tolerant to antibiotics and the defense mechanisms of the host. Patients with the genetic disease cystic fibrosis (CF) produce viscid mucus in the respiratory tract and therefore suffer from chronic biofilm infections in their lungs and paranasal sinuses.

Synthetic approaches and therapeutic applications of FDA-approved antibacterial agents: A comprehensive review from 2003 to 2023.

The increasing threat of antibiotic resistance has necessitated the development of new antibacterial agents. 33 novel antibacterial agents have been approved by the U.S.

The association of HLA-DRB1 allele group but not HLA-B or ERAP1-rs7063 gene polymorphisms with atopic dermatitis.

Atopic dermatitis (AD) is one of the most common dermatoses. According to current data 2.6 % of the world's population suffer from AD.

Cd99l2 regulates excitatory synapse development and restrains immediate-early gene activation.

Cd99 molecule-like 2 (Cd99l2) is a type I transmembrane protein that plays a role in the transmigration of leukocytes across vascular endothelial cells. Despite its high expression in the brain, the role of Cd99l2 remains elusive. We find that Cd99l2 is expressed primarily in neurons and positively regulates neurite outgrowth and the development of excitatory synapses.

Identification of novel PfEMP1 variants containing domain cassettes 11, 15 and 8 that mediate the Plasmodium falciparum virulence-associated rosetting phenotype.

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a diverse family of variant surface antigens, encoded by var genes, that mediates binding of infected erythrocytes to human cells and plays a key role in parasite immune evasion and malaria pathology. The increased availability of parasite genome sequence data has revolutionised the study of PfEMP1 diversity across multiple P. falciparum isolates.

Chromatin landscape alteration uncovers multiple transcriptional circuits during memory CD8+ T cell differentiation.

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells.

Dual Checkpoint Inhibition in M2 Macrophages via Anti-PD-L1 and siRNA-Loaded M1-Exosomes: Enhancing Tumor Immunity through RNA-Targeting Strategies.

The interaction between a cluster of differentiation 47 (CD47) on cancer cells and signal regulatory protein alpha (SIRPα) on macrophages is thought to hinder macrophage phagocytic activity, which can be blocked by combining siRNAs targeting SIRPα (siSIRPα) with simultaneous involvement of activating receptors like FcRs (Fc receptors) anti-programmed death-ligand 1 (anti-PD-L1). For this study, M1 macrophage-derived exosomes were used to deliver the siRNAs, isolated from lipopolysaccharide (LPS)-stimulated RAW264.7 cells and electroporated with siSIRPα.

Aurora kinase B inhibitor AZD1152: repurposing for treatment of lupus nephritis driven by the results of clinical trials.

Background: Lupus nephritis (LN) is one of the most common and severe complications of systemic lupus erythematosus (SLE). Multitarget therapy (MT) achieves a 20% higher complete remission (CR) rate compared to conventional therapy in LN management. Intrigued by its excellent clinical efficacy, we aimed to develop a single-agent therapy with comparable efficacy to MT, offering a simplified treatment regimen.

DNA-binding affinity and specificity determine the phenotypic diversity in BCL11B-related disorders.

BCL11B is a Cys2-His2 zinc-finger (C2H2-ZnF) domain-containing, DNA-binding, transcription factor with established roles in the development of various organs and tissues, primarily the immune and nervous systems. BCL11B germline variants have been associated with a variety of developmental syndromes. However, genotype-phenotype correlations along with pathophysiologic mechanisms of selected variants mostly remain elusive.

The Relationship Between Health Parameters, Body Size, Elements of Lifestyle, and Hand Grip Strength in a Group of Patients with Type 2 Diabetes, Aged 40-98, from Ulaanbaatar, Mongolia.

Decreased muscle strength and lower hand grip strength (HGS) values are observed in patients with type 2 diabetes (T2D). This study aimed to present the values of hand grip strength as a valuable tool in T2D treatment monitoring in the context of body size and lifestyle elements in 347 patients with type 2 diabetes from Ulaanbaatar, Mongolia. A retrospective cross-sectional study was performed at hospitals in Ulaanbaatar, Mongolia.

Association of Serum Polyunsaturated Fatty Acids (PUFAs) and Children's Dietary Inflammatory Index (C-DII) with Recurrent Respiratory Infections in Children: A Cross-Sectional Study.

To assess the associations between serum and dietary polyunsaturated fatty acids (PUFAs), as well as the inflammatory potential of diet measured by the Children's Dietary Inflammatory Index (C-DII), and recurrent respiratory infections (RRIs) in children. We enrolled 44 children aged 3-16 years with RRIs and 44 healthy controls. Dietary intake was assessed using a 7-day food record from which PUFA intake and C-DII were calculated.

Association of Gene Polymorphism and Serum Level of α Klotho Protein with Different Tumor Grades, Overall Survival and Cytokine Profile in Glioma Patients.

Gliomas are the most common and lethal forms of malignant brain tumors. We attempted to identify the role of the aging-suppressor gene and Klotho protein in the immunopathogenesis of gliomas. We examined genetic variants by PCR-RFLP and measured serum Klotho levels using the ELISA method.

Zinc Deficiency Exacerbates Lead-Induced Interleukin-2 Suppression by Regulating CREM Expression.

Lead, a prevalent heavy metal, impairs the immune system by affecting T cell function. Similarly, zinc deficiency adversely affects T cells, with zinc deficiency and lead exposure being linked to reduced interleukin-2 (IL-2) production. Zinc deficiency has been associated with increased expression of the transcription factor CREM 100 kDa, which downregulates IL-2.

4-Pyridone-3-carboxamide-1-β-D-ribonucleoside Reduces Cyclophosphamide Effects and Induces Endothelial Inflammation in Murine Breast Cancer Model.

4-pyridone-3-carboxamide-1-β-D-ribonucleoside (4PYR) is a nicotinamide derivative, considered a new oncometabolite. 4PYR formation induced a cytotoxic effect on the endothelium. Elevated blood 4PYR concentration was observed in patients with cancer.

Comprehensive discovery and functional characterization of the noncanonical proteome.

The systematic identification and functional characterization of noncanonical translation products, such as novel peptides, will facilitate the understanding of the human genome and provide new insights into cell biology. Here, we constructed a high-coverage peptide sequencing reference library with 11,668,944 open reading frames and employed an ultrafiltration tandem mass spectrometry assay to identify novel peptides. Through these methods, we discovered 8945 previously unannotated peptides from normal gastric tissues, gastric cancer tissues and cell lines, nearly half of which were derived from noncoding RNAs.

Optical tuning of polymer functionalized zinc oxide quantum dots as a selective probe for the detection of antibiotics.

Excess consumption of antibiotics leads to antibiotic resistance that hinders the control and cure of microbial diseases. Therefore, it is crucial to monitor the antibiotic levels in the environment. In this proposed research work, an optical nano-sensor was devised that can sense the ultra-low concentration of antibiotics, in samples like tap water using fluorescent zinc oxide quantum dots (ZnO QDs) based nano-sensor.

Cellular interactions in self-directed immune mediated liver diseases.

The lymphocyte population must traverse a complex path throughout their journey to the liver. The signals which these cells must detect, including cytokines, chemokines and other soluble factors, steer their course towards further crosstalk with other hepatic immune cells, hepatocytes and biliary epithelial cells. A series of specific chemokine receptors and adhesion molecules drive not only the recruitment, migration, and retention of these cells within the liver, but also their localisation.

Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature.

Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of -mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons.

Metabolomics-Driven Biomarker Discovery for Breast Cancer Prognosis and Diagnosis.

Breast cancer is a cancer with global prevalence and a surge in the number of cases with each passing year. With the advancement in science and technology, significant progress has been achieved in the prevention and treatment of breast cancer to make ends meet. The scientific intradisciplinary subject of "metabolomics" examines every metabolite found in a cell, tissue, system, or organism from different sources of samples.

From Pseudocyclic to Macrocyclic Ionophores: Strategies toward the Synthesis of Cyclic Monensin Derivatives.

There has been a long search for a simple preparation of new cyclic analogues of ionophore antibiotics. We report a simple and general synthesis of three new cyclic derivatives of polyether ionophore, monensin A (MON). The application of the Huisgen 1,3-dipolar cycloaddition of azides and terminal alkynes to macrocyclization results in a concise, synthetic route to monensin lacton or lactam in only 4 steps.

A signaling molecule from intratumor bacteria promotes trastuzumab resistance in breast cancer cells.

Emerging evidence indicates that intratumor bacteria exist as an active and specific tumor component in many tumor types beyond digestive and respiratory tumors. However, the biological impact and responsible molecules of such local bacteria-tumor direct interaction on cancer therapeutic response remain poorly understood. Trastuzumab is among the most commonly used drugs targeting the receptor tyrosine-protein kinase erbB-2 (ErbB2) in breast cancer, but its resistance is inevitable, severely limiting its clinical effectiveness.

Patient Source of Referral Is a Key Determinant of Subsequent Retention in Care for Young Chronic Hepatitis B Patients.

Hepatitis B elimination objectives can only be realised if new patient linkage to care is matched by long-term patient retention in care. We previously showed in adult chronic hepatitis B (CHB) patients that retention in care was inferior in younger patients and in patients from non-Asian ethnicities. The present study explores further the rates and determinants of loss to follow-up in a cohort of 271 young patients (aged 16-21 years at baseline).

Targeting hyaluronan synthesis enhances the therapeutic effectiveness of biologics in inflammatory bowel disease.

Although biologics have been revolutionizing the treatment of inflammatory bowel diseases (IBD) over the past decade, a significant number of patients still fail to benefit from these drugs. Overcoming the nonresponse to biologics is one of the top challenges in IBD treatment. In this study, we revealed that hyaluronan (HA), an extracellular matrix (ECM) component in the gut, is associated with nonresponsiveness to infliximab and vedolizumab therapy in patients with IBD.

SProtFP: a machine learning-based method for functional classification of small ORFs in prokaryotes.

Small proteins (≤100 amino acids) play important roles across all life forms, ranging from unicellular bacteria to higher organisms. In this study, we have developed SProtFP which is a machine learning-based method for functional annotation of prokaryotic small proteins into selected functional categories. SProtFP uses independent artificial neural networks (ANNs) trained using a combination of physicochemical descriptors for classifying small proteins into antitoxin type 2, bacteriocin, DNA-binding, metal-binding, ribosomal protein, RNA-binding, type 1 toxin and type 2 toxin proteins.