Protocol for detecting eDNA in ecological rare fish using RPA-CRISPR-Cas12a technology.

The recombinase polymerase amplification (RPA)-CRISPR-Cas12a-FQ system enables sensitive detection of environmental DNA (eDNA) in rare fish species. Here, we present a protocol for eDNA amplification and Cas12a for target recognition using RPA. We describe steps for identifying a target site, synthesis and purification of CRISPR RNA (crRNA), and RPA isothermal amplification.

Ivermectin Synergizes with Modulated Electro-hyperthermia and Improves Its Anticancer Effects in a Triple-Negative Breast Cancer Mouse Model.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, with limited treatment options. Modulated electro-hyperthermia (mEHT) is a novel adjuvant cancer therapy that induces selective cancer damage. However, mEHT upregulates heat shock protein beta 1 (HSPB1), a cancer-promoting stress chaperone molecule.

Augmentation of the EPR effect by mild hyperthermia to improve nanoparticle delivery to the tumor.

The clinical translation of the nanoparticle (NP)-based anticancer therapies is still unsatisfactory due to the heterogeneity of the enhanced permeability and retention (EPR) effect. Despite the promising preclinical outcome of the pharmacological EPR enhancers, their systemic toxicity can limit their clinical application. Hyperthermia (HT) presents an efficient tool to augment the EPR by improving tumor blood flow (TBF) and vascular permeability, lowering interstitial fluid pressure (IFP), and disrupting the structure of the extracellular matrix (ECM).

Heat shock factor 1 inhibition enhances the effects of modulated electro hyperthermia in a triple negative breast cancer mouse model.

Female breast cancer is the most diagnosed cancer worldwide. Triple negative breast cancer (TNBC) is the most aggressive type and there is no existing endocrine or targeted therapy. Modulated electro-hyperthermia (mEHT) is a non-invasive complementary cancer therapy using an electromagnetic field generated by amplitude modulated 13.

Local Production of Acute Phase Proteins: A Defense Reaction of Cancer Cells to Injury with Focus on Fibrinogen.

This review is intended to demonstrate that the local production of acute phase proteins (termed local acute phase response (lAPR)) and especially fibrin/fibrinogen (FN) is a defense mechanism of cancer cells to therapy, and inhibition of the lAPR can augment the effectiveness of cancer therapy. Previously we detected a lAPR accompanying tumor cell death during the treatment of triple-negative breast cancer (TNBC) with modulated electro-hyperthermia (mEHT) in mice. We observed a similar lAPR in in hypoxic mouse kidneys.

Modulated Electro-Hyperthermia Accelerates Tumor Delivery and Improves Anticancer Activity of Doxorubicin Encapsulated in Lyso-Thermosensitive Liposomes in 4T1-Tumor-Bearing Mice.

Modulated electro-hyperthermia (mEHT) is an adjuvant cancer therapy that enables tumor-selective heating (+2.5 °C). In this study, we investigated whether mEHT accelerates the tumor-specific delivery of doxorubicin (DOX) from lyso-thermosensitive liposomal doxorubicin (LTLD) and improves its anticancer efficacy in mice bearing a triple-negative breast cancer cell line (4T1).

Correction to "Digoxin-Mediated Inhibition of Potential Hypoxia-Related Angiogenic Repair in Modulated Electro-Hyperthermia (mEHT)-Treated Murine Triple-Negative Breast Cancer Model".

[This corrects the article DOI: 10.1021/acsptsci.3c00296.

Neutrophils and NADPH Oxidases Are Major Contributors to Mild but Not Severe Ischemic Acute Kidney Injury in Mice.

Upregulation of free radical-generating NADPH oxidases (NOX), xanthine oxidoreductase (XOR), and neutrophil infiltration-induced, NOX2-mediated respiratory burst contribute to renal ischemia-reperfusion injury (IRI), but their roles may depend on the severity of IRI. We investigated the role of NOX, XOR, and neutrophils in developing IRI of various severities. C57BL/6 and Mcl-1 neutrophil-deficient mice were used.

Digoxin-Mediated Inhibition of Potential Hypoxia-Related Angiogenic Repair in Modulated Electro-Hyperthermia (mEHT)-Treated Murine Triple-Negative Breast Cancer Model.

Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer type with no targeted therapy and hence limited treatment options. Modulated electrohyperthermia (mEHT) is a novel complementary therapy where a 13.56 MHz radiofrequency current targets cancer cells selectively, inducing tumor damage by thermal and electromagnetic effects.

Enhancing therapeutic efficacy in triple-negative breast cancer and melanoma: synergistic effects of modulated electro-hyperthermia (mEHT) with NSAIDs especially COX-2 inhibition in in vivo models.

Triple-negative breast cancer (TNBC) is a leading cause of cancer mortality and lacks modern therapy options. Modulated electro-hyperthermia (mEHT) is an adjuvant therapy with demonstrated clinical efficacy for the treatment of various cancer types. In this study, we report that mEHT monotherapy stimulated interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) expression, and consequently cyclooxygenase 2 (COX-2), which may favor a cancer-promoting tumor microenvironment.

Targeting the heat shock response induced by modulated electro-hyperthermia (mEHT) in cancer.

The Heat Shock Response (HSR) is a cellular stress reaction crucial for cell survival against stressors, including heat, in both healthy and cancer cells. Modulated electro-hyperthermia (mEHT) is an emerging non-invasive cancer therapy utilizing electromagnetic fields to selectively target cancer cells via temperature-dependent and independent mechanisms. However, mEHT triggers HSR in treated cells.

Vascular Endothelial Growth Factor-D (VEGF-D): An Angiogenesis Bypass in Malignant Tumors.

Vascular endothelial growth factors (VEGFs) are the key regulators of vasculogenesis in normal and oncological development. VEGF-A is the most studied angiogenic factor secreted by malignant tumor cells under hypoxic and inflammatory stress, which made VEGF-A a rational target for anticancer therapy. However, inhibition of VEGF-A by monoclonal antibody drugs led to the upregulation of VEGF-D.

Recent Preclinical and Clinical Progress in Liposomal Doxorubicin.

Doxorubicin (DOX) is a potent anti-cancer agent that has garnered great interest in research due to its high efficacy despite dose-limiting toxicities. Several strategies have been exploited to enhance the efficacy and safety profile of DOX. Liposomes are the most established approach.

The Hypertensive Effect of Amphotericin B-Containing Liposomes (Abelcet) in Mice: Dissecting the Roles of C3a and C5a Anaphylatoxins, Macrophages and Thromboxane.

Liposomal amphotericin B (Abelcet) can cause infusion (anaphylactoid) reactions in patients whose mechanism is poorly understood. Here, we used mice to investigate the role of complement (C) receptors and the cellular sources of vasoactive mediators in these reactions. Anesthetized male NMRI and thromboxane prostanoid receptor (TP) or cyclooxygenase-1 (COX-1)-deficient and wild type C57Bl6/N mice were intravenously injected with Abelcet at 30 mg/kg.

A New Role of Acute Phase Proteins: Local Production Is an Ancient, General Stress-Response System of Mammalian Cells.

The prevailing general view of acute-phase proteins (APPs) is that they are produced by the liver in response to the stress of the body as part of a systemic acute-phase response. We demonstrated a coordinated, local production of these proteins upon cell stress by the stressed cells. The local, stress-induced APP production has been demonstrated in different tissues (kidney, breast cancer) and with different stressors (hypoxia, fibrosis and electromagnetic heat).

Divergent regulation of lncRNA expression by ischemia in adult and aging mice.

Elderly patients have increased susceptibility to acute kidney injury (AKI). Long noncoding RNAs (lncRNA) are key regulators of cellular processes, and have been implicated in both aging and AKI. Our aim was to study the effects of aging and ischemia-reperfusion injury (IRI) on the renal expression of lncRNAs.

Initial Renal Function (eGFR) Is a Prognostic Marker of Severe Acute Pancreatitis: A Cohort-Analysis of 1,224 Prospectively Collected Cases.

Acute pancreatitis (AP) is a life-threatening disease. We aimed to explore the prognostic relevance of renal function based on estimated glomerular filtration rate (eGFR). A prospective registry of AP patients was established by the Hungarian Pancreatic Study Group.

Delayed Contralateral Nephrectomy Halted Post-Ischemic Renal Fibrosis Progression and Inhibited the Ischemia-Induced Fibromir Upregulation in Mice.

(1) Background: Ischemia reperfusion (IR) is the leading cause of acute kidney injury (AKI) and results in predisposition to chronic kidney disease. We demonstrated that delayed contralateral nephrectomy (Nx) greatly improved the function of the IR-injured kidney and decelerated fibrosis progression. Our aim was to identify microRNAs (miRNA/miR) involved in this process.

Desensitization of Capsaicin-Sensitive Afferents Accelerates Early Tumor Growth Increased Vascular Leakage in a Murine Model of Triple Negative Breast Cancer.

There is growing interest in the role of nerve-driven mechanisms in tumorigenesis and tumor growth. Capsaicin-sensitive afferents have been previously shown to possess antitumoral and immune-regulatory properties, the mechanism of which is currently poorly understood. In this study, we have assessed the role of these terminals in the triple negative 4T1 orthotopic mouse model of breast cancer.

Modulated Electro-Hyperthermia Induces a Prominent Local Stress Response and Growth Inhibition in Mouse Breast Cancer Isografts.

Modulated electro-hyperthermia (mEHT) is a selective cancer treatment used in human oncology complementing other therapies. During mEHT, a focused electromagnetic field (EMF) is generated within the tumor inducing cell death by thermal and nonthermal effects. Here we investigated molecular changes elicited by mEHT using multiplex methods in an aggressive, therapy-resistant triple negative breast cancer (TNBC) model.

In Vitro and In Vivo Efficacy of a Novel Glucose-Methotrexate Conjugate in Targeted Cancer Treatment.

Methotrexate (MTX) is a commonly used antimetabolite, which inhibits folate and DNA synthesis to be effective in the treatment of various malignancies. However, MTX therapy is hindered by the lack of target tumor selectivity. We have designed, synthesized and evaluated a novel glucose-methotrexate conjugate (GLU-MTX) both in vitro and in vivo, in which a cleavable linkage allows intracellular MTX release after selective uptake through glucose transporter-1 (GLUT1).

Complement-mediated hypersensitivity reactions to an amphotericin B-containing lipid complex (Abelcet) in pediatric patients and anesthetized rats: Benefits of slow infusion.

Intravenous administration of lipid-based nanodrugs can cause hypersensitivity, also known as infusion reactions (IRs), that can be attenuated by slow infusion in adult patients. We studied the role of infusion rate and complement (C) activation in IRs in pediatric patients treated with Abelcet, and also in anesthetized rats. IRs were observed in 6 out of 10 (60%) patients who received Abelcet infusion in 4 h or less, while no patients who received the infusion in 6 h showed C activation or IRs.

Cold Saline Perfusion before Ischemia-Reperfusion Is Harmful to the Kidney and Is Associated with the Loss of Ezrin, a Cytoskeletal Protein, in Rats.

Background: Organ protection for transplantation is perfusion with ice-cold preservation solutions, although saline is also used in animal experiments and living donor transplantations. However, ice-cold perfusion can contribute to initial graft injury. Our aim was to test if cytoskeletal damage of parenchymal cells is caused by saline itself or by the ice-cold solution.

Exhaustion of Protective Heat Shock Response Induces Significant Tumor Damage by Apoptosis after Modulated Electro-Hyperthermia Treatment of Triple Negative Breast Cancer Isografts in Mice.

Modulated electro-hyperthermia (mEHT) is a complementary antitumor therapy applying capacitive radiofrequency at 13.56 MHz. Here we tested the efficiency of mEHT treatment in a BALB/c mouse isograft model using the firefly luciferase-transfected triple-negative breast cancer cell line, 4T1.

Modulated Electro-Hyperthermia-Induced Tumor Damage Mechanisms Revealed in Cancer Models.

The benefits of high-fever range hyperthermia have been utilized in medicine from the Ancient Greek culture to the present day. Amplitude-modulated electro-hyperthermia, induced by a 13.56 MHz radiofrequency current (mEHT, or Oncothermia), has been an emerging means of delivering loco-regional clinical hyperthermia as a complementary of radiation-, chemo-, and molecular targeted oncotherapy.