In vitro and in vivo efficacy studies of an engineered endolysin targeting Gram-negative pathogens.

Endolysins have drawn considerable attention as viable modalities for antibiotic use. The most significant obstacle for Gram-negative targeting endolysins is the presence of the outer membrane barrier. A heterologously expressed endolysin encoded by bacteriophage PBPA90 infecting Pseudomonas aeruginosa exhibited intrinsic antibacterial activity against P.

Controlling tumor progression and recurrence in mice through combined treatment with a PD-L1 inhibitor and a designer strain that delivers GM-CSF.

Combination therapy with checkpoint inhibitors blocks inhibitory immune cell signaling and improves clinical responses to anticancer treatments. However, continued development of innovative and controllable delivery systems for immune-stimulating agents is necessary to optimize clinical responses. Herein, we engineered to deliver recombinant granulocyte macrophage colony stimulating factor (GM-CSF) in a controllable manner for combination treatment with a programmed death-ligand 1 (PD-L1) inhibitor.

Antimicrobial peptide thanatin fused endolysin PA90 (Tha-PA90) for the control of Acinetobacter baumannii infection in mouse model.

Background: This study addresses the urgent need for infection control agents driven by the rise of drug-resistant pathogens such as Acinetobacter baumannii. Our primary aim was to develop and assess a novel endolysin, Tha-PA90, designed to combat these challenges.

Methods: Tha-PA90 incorporates an antimicrobial peptide (AMP) called thanatin at its N-terminus, enhancing bacterial outer membrane permeability and reducing host immune responses.

Bacterial cancer therapy using the attenuated fowl-adapted serovar Gallinarum.

We report here a novel anti-cancer therapy based on an avian-host-specific serotype serovar Gallinarum () deficient in ppGpp synthesis. To monitor the tumor targeting, a bioluminescent ΔppGpp was constructed and injected intravenously into mice bearing syngeneic and human xenograft tumors. Strong bioluminescent signals were detected specifically in all grafted tumors at 2 days post-injection (dpi).

Constitutive Expression of a Cytotoxic Anticancer Protein in Tumor-Colonizing Bacteria.

Bacterial cancer therapy is a promising next-generation modality to treat cancer that often uses tumor-colonizing bacteria to deliver cytotoxic anticancer proteins. However, the expression of cytotoxic anticancer proteins in bacteria that accumulate in the nontumoral reticuloendothelial system (RES), mainly the liver and spleen, is considered detrimental. This study examined the fate of the strain MG1655 and an attenuated strain of serovar Gallinarum ( Gallinarum) with defective ppGpp synthesis after intravenous injection into tumor-bearing mice (~10 colony forming units/animal).

In vivo imaging of invasive aspergillosis with F-fluorodeoxysorbitol positron emission tomography.

Invasive aspergillosis is a critical complication in immunocompromised patients with hematologic malignancies or with viral pneumonia caused by influenza virus or SARS‑CoV‑2. Although early and accurate diagnosis of invasive aspergillosis can maximize clinical outcomes, current diagnostic methods are time-consuming and poorly sensitive. Here, we assess the ability of 2-deoxy-2-F-fluorosorbitol (F-FDS) positron emission tomography (PET) to specifically and noninvasively detect Aspergillus infections.

Lipocalin2 as a potential antibacterial drug against Acinetobacter baumannii infection.

Available antibiotics to treat Acinetobacter baumannii infection is limited due to increasing resistance and the emergence of multiple drug-resistant strains. Hence, discovering effective agents against A. baumannii to reduce the number of infection-related deaths is imperative.

ppGpp signaling plays a critical role in virulence of .

, a major nosocomial pathogen, survives in diverse hospital environments, and its multidrug resistance is a major concern. The ppGpp-dependent stringent response mediates the reprogramming of genes with diverse functions in several bacteria. We investigated whether ppGpp is involved in pathogenesis by examining biofilm formation, surface motility, adhesion, invasion, and mouse infection studies.

Label-Free White Blood Cell Classification Using Refractive Index Tomography and Deep Learning.

. We propose a rapid and accurate blood cell identification method exploiting deep learning and label-free refractive index (RI) tomography. Our computational approach that fully utilizes tomographic information of bone marrow (BM) white blood cell (WBC) enables us to not only classify the blood cells with deep learning but also quantitatively study their morphological and biochemical properties for hematology research.

Lipocalin 2 regulates iron homeostasis, neuroinflammation, and insulin resistance in the brains of patients with dementia: Evidence from the current literature.

Dementia accompanied by memory loss is considered one of the most common neurodegenerative diseases worldwide, and its prevalence is gradually increasing. Known risk factors for dementia include genetic background, certain lifestyle and dietary patterns, smoking, iron overload, insulin resistance, and impaired glucose metabolism in the brain. Here, we review recent evidence on the regulatory role of lipocalin 2 (LCN2) in dementia from various perspectives.

The influence of moderate or deep neuromuscular block status on anesthetic depth monitoring system during total intravenous anesthesia using propofol and remifentanil: A randomized trial.

The neuromuscular block state may affect the electroencephalogram-derived index representing the anesthetic depth. We applied an Anesthetic Depth Monitoring for Sedation (ADMS) to patients undergoing laparoscopic cholecystectomy under total intravenous anesthesia, and evaluated the requirement of propofol according to the different neuromuscular block state. Adult patients scheduled to undergo laparoscopic cholecystectomy were enrolled and randomly assigned to either the moderate (MB) or deep neuromuscular block (DB) group.

Orphan nuclear receptor ERR-γ regulates hepatic FGF23 production in acute kidney injury.

Fibroblast growth factor 23 (FGF23), a hormone generally derived from bone, is important in phosphate and vitamin D homeostasis. In acute kidney injury (AKI) patients, high-circulating FGF23 levels are associated with disease progression and mortality. However, the organ and cell type of FGF23 production in AKI and the molecular mechanism of its excessive production are still unidentified.

Targeted Delivery of the Mitochondrial Target Domain of Noxa to Tumor Tissue via Synthetic Secretion System in .

Targeted delivery of drugs is a key aspect of the successful treatment of serious conditions such as tumors. In the pursuit of accurate delivery with high specificity and low size limit for peptide drugs, a synthetic type 3 secretion system (T3SS) has been repurposed from a native genetic system encoded in pathogenicity island-1 (SPI-1) with no virulence effectors. Here, we tested the potential of synthetic T3SS as drug delivery machinery for peptide-based drugs owing to its modular nature.

Transcriptional regulation of Salmochelin glucosyltransferase by Fur in Salmonella.

Pathogenic bacteria acquire the acquisition of iron from the host to ensure their survival. Salmonella spp. utilizes siderophores, including salmochelin, for high affinity aggressive import of iron.

Epigallocatechin-3-Gallate (EGCG)-Inducible SMILE Inhibits STAT3-Mediated Hepcidin Gene Expression.

Hepatic peptide hormone hepcidin, a key regulator of iron metabolism, is induced by inflammatory cytokine interleukin-6 (IL-6) in the pathogenesis of anemia of inflammation or microbial infections. Small heterodimer partner-interacting leucine zipper protein (SMILE)/CREBZF is a transcriptional corepressor of nuclear receptors that control hepatic glucose and lipid metabolism. Here, we examined the role of SMILE in regulating iron metabolism by inflammatory signals.

Ultrasensitive detection of malignant melanoma using PET molecular imaging probes.

Malignant melanoma has one of the highest mortality rates of any cancer because of its aggressive nature and high metastatic potential. Clinical staging of the disease at the time of diagnosis is very important for the prognosis and outcome of melanoma treatment. In this study, we designed and synthesized the F-labeled pyridine-based benzamide derivatives -(2-(dimethylamino)ethyl)-5-[F]fluoropicolinamide ([F]DMPY2) and -(2-(dimethylamino)ethyl)-6-[F]fluoronicotinamide ([F]DMPY3) to detect primary and metastatic melanoma at an early stage and evaluated their performance in this task.

Transcriptional Regulation of the Outer Membrane Protein A in .

is known for its virulence in severely ill, hospitalized patients and for exhibiting multidrug resistance. infection treatment poses a serious problem in clinical environments. The outer membrane protein A () of the Acinetobacter genus is involved in bacterial virulence.

Lipocalin2 Induced by Bacterial Flagellin Protects Mice against Cyclophosphamide Mediated Neutropenic Sepsis.

Neutropenic sepsis is a fatal consequence of chemotherapy, and septic complications are the principal cause of mortality. Chemotherapy-induced neutropenia leads to the formation of microscopic ulcers in the gastrointestinal epithelium that function as a portal of entry for intraluminal bacteria, which translocate across the intestinal mucosal barrier and gain access to systemic sites, causing septicemia. A cyclophosphamide-induced mouse model was developed to mimic the pathophysiologic sequence of events that occurs in patients with neutropenic sepsis.

Retrospective Comparison between the Effects of Propofol and Inhalation Anesthetics on Postoperative Recurrence of Early- and Intermediate-Stage Hepatocellular Carcinoma.

Objective: Previous studies have reported that propofol has antitumor, anti-inflammatory, and antioxidant effects in addition to its anesthetic properties. To confirm this, a retrospective investigation was conducted to determine whether different anesthetic agents, particularly propofol and inhalation anesthetics, have an effect on the recurrence of hepatocellular carcinoma (HCC) in patients who were diagnosed with primary HCC and underwent laparoscopic hepatectomy.

Subjects And Methods: Patients with Barcelona Clinic Liver Cancer stages 0, A, and B HCC, who underwent laparoscopic hepatic resection, were enrolled in this study.

Development of bacteria as diagnostics and therapeutics by genetic engineering.

Bacteria sense and respond to the environment, communicate, and continuously interact with their surroundings, including host bodies. For more than a century, engineers have been trying to harness the natural ability of bacteria as live biotherapeutics for the treatment of diseases. Recent advances in synthetic biology facilitate the enlargement of the repertoire of genetic parts, tools, and devices that serve as a framework for biotherapy.

The hepcidin-ferroportin axis controls the iron content of Salmonella-containing vacuoles in macrophages.

Macrophages release iron into the bloodstream via a membrane-bound iron export protein, ferroportin (FPN). The hepatic iron-regulatory hormone hepcidin controls FPN internalization and degradation in response to bacterial infection. Salmonella typhimurium can invade macrophages and proliferate in the Salmonella-containing vacuole (SCV).

Cell mass-dependent expression of an anticancer protein drug by tumor-targeted .

Bacterial cancer therapy relies on the properties of certain bacterial species capable of targeting and proliferating within solid malignancies. If these bacteria could be loaded with antitumor proteins, the efficacy of this approach could be greatly increased. However, because most antitumor proteins are also toxic to normal tissue, they must be expressed by bacteria that specifically target and exclusively localize to tumor tissue.

Anti-tumor activity of an immunotoxin (TGFα-PE38) delivered by attenuated Salmonella typhimurium.

The anticancer strategy underlying the use of immunotoxins is as follows: the cancer-binding domain delivers the toxin to a cancer cell, after which the toxin enters and kills the cell. TGFα-PE38 is an immunotoxin comprising transforming growth factor alpha (TGFα), a natural ligand of epidermal growth factor receptor (EGFR), and a modified Pseudomonas exotoxin A (PE38) lacking N terminal cell-binding domain, a highly potent cytotoxic protein moiety. Tumor cells with high level of EGFR undergo apoptosis upon treatment with TGFα-PE38.

Microvasculature remodeling in the mouse lower gut during inflammaging.

Inflammaging is defined as low-grade, chronic, systemic inflammation in aging, in the absence of overt infection. Age-associated deterioration of gastrointestinal function could be ascribed to the inflammaging, although evidence is yet to emerge. Here we show that microvessels in aging mouse intestine were progressively deprived of supportive structures, microvessel-associated pericytes and adherens junction protein vascular endothelial (VE)-cadherin, and became leaky.