CRE

Therapeutic options for managing Pancreatic ductal adenocarcinoma (PDAC), one of the deadliest types of aggressive malignancies, are limited and disappointing. Therefore, despite suboptimal clinical effects, gemcitabine (GEM) remains the first-line chemotherapeutic drug in the clinic for PDAC treatment. The therapeutic limitations of GEM are primarily due to poor bioavailability and the development of chemoresistance resulting from the addiction of mutant-K-RAS/AKT/ERK signaling-mediated desmoplastic barriers with a hypoxic microenvironment...

The CTC1-STN1-TEN1 (CST) complex is a single-strand DNA-binding protein complex that plays an important role in genome maintenance in various model eukaryotes. Dysfunction of CST is the underlying cause of the rare genetic disorder known as Coats plus disease. In addition, down regulation of STN1 promotes colorectal cancer development in mice. While prior studies have utilized RNAi to knock down CST components in mammalian cells, this approach is associated with off-target effects. Attempts to employ CRISPR/Cas9-based knockout of CST components in somatic cell lines have been unsuccessful due to CST's indispensable role in DNA replication and cell proliferation...

Precision-cut lung slices (PCLS), ex vivo 3D lung tissue models, have been widely used for various applications in lung research. PCLS serve as an excellent intermediary between in vitro and in vivo models because they retain all resident cell types within their natural niche while preserving the extracellular matrix environment. This protocol describes the TReATS (TAT-Cre recombinase-mediated floxed allele modification in tissue slices) method that enables rapid and efficient gene modification in PCLS derived from adult floxed animals...

BACKGROUND: The channel-forming protein Pannexin1 (Panx1) has been implicated in both human studies and animal models of chronic pain, but the underlying mechanisms remain incompletely understood. METHODS: Wild-type (WT, n = 24), global Panx1 KO (n = 24), neuron-specific Panx1 KO (n = 20), and glia-specific Panx1 KO (n = 20) mice were used in this study at Albert Einstein College of Medicine. The von Frey test was used to quantify pain sensitivity in these mice following complete Freund's adjuvant (CFA) injection (7, 14, and 21 d)...

UNLABELLED: Pancreatic ductal adenocarcinoma (PDAC) therapeutic resistance is largely attributed to a unique tumor microenvironment embedded with an abundance of cancer-associated fibroblasts (CAF). Distinct CAF populations were recently identified, but the phenotypic drivers and specific impact of CAF heterogeneity remain unclear. In this study, we identify a subpopulation of senescent myofibroblastic CAFs (SenCAF) in mouse and human PDAC. These SenCAFs are a phenotypically distinct subset of myofibroblastic CAFs that localize near tumor ducts and accumulate with PDAC progression...

PDAC therapeutic resistance is largely attributed to a unique tumor microenvironment embedded with an abundance of cancer associated fibroblasts (CAFs). Distinct CAF populations were recently identified, but the phenotypic drivers and specific impact of CAF heterogeneity remain unclear. In this study, we identify a subpopulation of senescent myofibroblastic CAFs (SenCAFs) in mouse and human PDAC. These SenCAFs are a phenotypically distinct subset of myofibroblastic CAFs that localize near tumor ducts and accumulate with PDAC progression...

BACKGROUND: Essential tremor patients may find that low alcohol amounts suppress tremor. A candidate mechanism is modulation of α6β3δ extra-synaptic GABAA receptors, that in vitro respond to non-intoxicating alcohol levels. We previously found that low-dose alcohol reduces harmaline tremor in wild-type mice, but not in littermates lacking δ or α6 subunits. Here we addressed whether low-dose alcohol requires the β3 subunit for tremor suppression. METHODS: We tested whether low-dose alcohol suppresses tremor in cre-negative mice with intact β3 exon 3 flanked by loxP, and in littermates in which this region was excised by cre expressed under the α6 subunit promotor...

BACKGROUND: Acute pancreatitis (AP) encompasses a spectrum of pancreatic inflammatory conditions, ranging from mild inflammation to severe pancreatic necrosis and multisystem organ failure. Given the challenges associated with obtaining human pancreatic samples, research on AP predominantly relies on animal models. In this study, we aimed to elucidate the fundamental molecular mechanisms underlying AP using various AP models. AIM: To investigate the shared molecular changes underlying the development of AP across varying severity levels...

OBJECTIVE: Infections caused by Carbapenem-resistant Enterobacterales (CRE) have high treatment costs, high mortality and few effective therapeutic agents. This study aimed to determine the risk factors for progression from intestinal colonization to infection in hematological patients and the risk factors for 30-day mortality in infected patients. METHODS: A retrospective case-control study was conducted in the Department of Hematology at Shandong Provincial Hospital affiliated to Shandong First Medical University from April 2018 to April 2022...

BACKGROUND: Crossed renal ectopia (CRE) occurs when one kidney crosses the midline from the primary side to the contralateral side while the ureter remains on the primary side. Rectal cancer, one of the most common malignant tumors of the digestive tract, refers to cancer from the dentate line to the rectosigmoid junction. The concurrent presentation of CRE alongside rectal cancer is an uncommon clinical observation. CASE SUMMARY: Herein, we report a 69-year-old male patient with rectal cancer who was diagnosed with CRE via computed tomography during hospitalization...

The cystic fibrosis transmembrane conductance regulator (CFTR) gene encodes an anion-selective channel found in epithelial cell membranes. Mutations in CFTR cause cystic fibrosis (CF), an inherited disorder that impairs epithelial function in multiple organs. Most men with CF are infertile due to loss of intact genital ducts. Here we investigated a novel epididymis-selective cis-regulatory element (CRE), located within a peak of open chromatin at -9.5 kb 5' to the CFTR gene promoter. Activation of the -9...

Drug dependence is characterized by a switch in motivation wherein a positively reinforcing substance can become negatively reinforcing. Put differently, drug use can transform from a form of pleasure-seeking to a form of relief-seeking. Ventral tegmental area (VTA) GABA neurons form an anatomical point of divergence between two double dissociable pathways that have been shown to be functionally implicated and necessary for these respective motivations to seek drugs. The tegmental pedunculopontine nucleus (TPP) is necessary for opiate conditioned place preferences (CPP) in previously drug-naïve rats and mice, whereas dopaminergic (DA) transmission in the nucleus accumbens (NAc) is necessary for opiate CPP in opiate-dependent and withdrawn (ODW) rats and mice...

Mastitis is the most common disease of dairy cattle and can be manifested in clinical and subclinical forms. The overuse of antimicrobials in the treatment and prevention of mastitis favours antimicrobial resistance and milk can be a potential route of dissemination. This study aimed to evaluate the biological quality of bulk tank milk (BTM) and the microbiological quality and signs of mastitis of freshly milked raw milk. In addition, to evaluate antimicrobial resistance in Enterobacteriaceae and Staphylococcus spp...

Smad4, a critical mediator of TGF-β signaling, plays a pivotal role in regulating various cellular functions, including immune responses. In this study, we investigated the impact of Smad4 knockout specifically in macrophages on anti-tumor immunity, focusing on lung metastasis of B16 melanoma cells. Using a mouse model with Smad4 knockout in macrophages established via Lyz2-cre mice and Smad4 flox/flox mice, we demonstrated a significant inhibition of B16 metastasis in the lungs. Interestingly, the inhibition of tumor growth was found to be independent of adaptive immunity, as no significant changes were observed in the numbers or activities of T cells, B cells, or NK cells...

OBJECTIVE: Uncoupling protein 1 (UCP1), a mitochondrial protein responsible for nonshivering thermogenesis in adipose tissue, serves as a distinct marker for thermogenic brown and beige adipocytes. Ucp1-Cre mice are thus widely used to genetically manipulate these thermogenic adipocytes. However, evidence suggests that UCP1 may also be expressed in non-adipocyte cell types. In this study, we investigated the presence of UCP1 expression in different mouse tissues that have not been previously reported...

Cellular retinaldehyde-binding protein (CRALBP) supports production of 11-cis-retinaldehyde and its delivery to photoreceptors. It is found in the retinal pigment epithelium (RPE) and Müller glia (MG), but the relative functional importance of these two cellular pools is debated. Here, we report RPE- and MG-specific CRALBP knockout (KO) mice and examine their photoreceptor and visual cycle function. Bulk visual chromophore regeneration in RPE-KO mice is 15-fold slower than in controls, accounting for their delayed rod dark adaptation and protection against retinal phototoxicity, whereas MG-KO mice have normal bulk visual chromophore regeneration and retinal light damage susceptibility...

In lactic acid bacteria, the global transcriptional regulator CcpA regulates carbon metabolism by repressing and activating the central carbon metabolism pathway, thus decreasing or increasing the yield of certain metabolites to maximize carbon flow. However, there are no reports on the deregulation of the inhibitory effects of CcpA on the metabolism of secondary metabolites. In this study, we identified a single-base mutant strain of Lactococcus lactis N8-2 that is capable of metabolizing 2,3-butanediol. It has been established that CcpA dissociates from the catabolite responsive element ( cre) site due to a mutation, leading to the activation of derepression and expression of the 2,3-butanediol dehydrogenase gene cluster ( butB and butA )...

INTRODUCTION: Increased antimicrobial use during the COVID-19 pandemic has raised concerns about the spread of resistant bacteria. This study analyzed the frequency of device-associated infections (DAI) caused by resistant bacteria, the predictors of these infections, and 30-day all-cause mortality in patients with and without COVID-19. METHODS: A retrospective cohort study was conducted on DAI patients admitted to the ICU (intensive care unit) in 20 hospitals in Medellin, Colombia (2020-2021)...

According to previous studies, the median raphe region (MRR) is known to contribute significantly to social behavior. Besides serotonin, there have also been reports of a small population of dopaminergic neurons in this region. Dopamine is linked to reward and locomotion, but very little is known about its role in the MRR. To address that, we first confirmed the presence of dopaminergic cells in the MRR of mice (immunohistochemistry, RT-PCR), and then also in humans (RT-PCR) using healthy donor samples to prove translational relevance...

Neuroinflammation is the major cause of neurodegenerative disorders such as Alzheimer's and Parkinson's disease. Currently available drugs present relatively low efficacy and are not capable of modifying the course of the disease or delaying its progression. Identifying well-tolerated and brain-penetrant agents of plant origin could fulfil the pressing need for novel treatment techniques for neuroinflammation. Attention has been drawn to a large family of flavonoids in citrus fruits, which may function as strong nutraceuticals in slowing down the development and progression of neuroinflammation...