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Evidence for a causal link between adaptor protein PDZK1 downregulation and Na⁺/H⁺ exchanger NHE3 dysfunction in human and murine colitis.

A dysfunction of the Na(+)/H(+) exchanger isoform 3 (NHE3) significantly contributes to the reduced salt absorptive capacity of the inflamed intestine. We previously reported a strong decrease in the NHERF family member PDZK1 (NHERF3), which binds to NHE3 and regulates its function in a mouse model of colitis. The present study investigates whether a causal relationship exists between the decreased PDZK1 expression and the NHE3 dysfunction in human and murine intestinal inflammation. Biopsies from the colon of patients with ulcerative colitis, murine inflamed ileal and colonic mucosa, NHE3-tra

Taurodeoxycholate modulates apical Cl-/OH- exchange activity in Caco2 cells.

Bile acid malabsorption has been shown to be associated with diarrhea in cases such as ileal resection Crohn's disease of the ileum, and radiation enteritis. The mechanisms of bile acid-induced diarrhea are not fully understood. Although the induction of colonic chloride secretion in response to bile acids has been extensively investigated, to date the direct effect of bile acids on intestinal chloride absorption has not been well defined. Therefore, the current studies were undertaken to investigate the effect of bile acids on the apical Cl(-)/OH(-) exchange process utilizing Caco2 monolayers

Dysbiosis and zonulin upregulation alter gut epithelial and vascular barriers in patients with ankylosing spondylitis.

BACKGROUND: Dysbiosis has been recently demonstrated in patients with ankylosing spondylitis (AS) but its implications in the modulation of intestinal immune responses have never been studied. The aim of this study was to investigate the role of ileal bacteria in modulating local and systemic immune responses in AS. METHODS: Ileal biopsies were obtained from 50 HLA-B27+ patients with AS and 20 normal subjects. Silver stain was used to visualise bacteria. Ileal expression of tight and adherens junction proteins was investigated by TaqMan real-time (RT)-PCR and immunohistochemistry. Serum level

Therapeutic siRNAs Targeting the JAK/STAT Signalling Pathway in Inflammatory Bowel Diseases.

Background and aimsInflammatory bowel diseases are highly debilitating conditions that require constant monitoring and life-long medication. Current treatments are focused on systemic administration of immunomodulatory drugs, but they have a broad range of undesirable side-effects. RNA interference is a highly specific endogenous mechanism that regulates the expression of the gene at the transcript level, which can be repurposed using exogenous short interfering RNA [siRNA] to repress expression of the target gene. While siRNA therapeutics can offer an alternative to existing therapies, with a

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… CACO-2 cells were reverse transfected using 10 5 cells per well seeded on a 12-well plate, except for transcriptomic analysis, where 10 6 CACO-2 cells were seeded in 10-cm-diameter dishes. … Comparative analysis of JAK -targeting siRNA and Jakinibs on JAK/STAT signalling in CACO-2 cells. Western blot analysis of JAK/STAT signalling in CACO-2 cells transfected at 10 nM siRNA using lipofectamine RNAiMAX for 48 h. …

Оптимизация доставки каннабидиол: повышение растворимости и проницаемости воды посредством фосфолипидной комплексации.

Каннабидиол (КБР) продемонстрировал терапевтический потенциал в лечении эпилепсии, множественного склероза, болезни Альцгеймера, Паркинсона и Крона. Несмотря на ее многообещающие последствия и анальгетические, антивоспалительные и аксиолитические свойства, полный потенциал КБР сдерживается низкой растворимостью воды (0,7-10 мкг/мл), низкой проницаемостью и химической нестабильностью. Цель этого исследования состояла в том, чтобы повысить проницаемость кишечника (GI) в результате распада, стабильности и проницаемости кишечника КБР путем создания комплекса КБР-фосфолипид (CBD-PLC). Мы предположи

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… The Caco-2 cell line was kindly provided by Anthony Wignall, University of South Australia. 3.2. Quantification of CBD by HPLC Method The HPLC method was conducted under the conditions previously studied and optimised by Abdella et al. [ 67 ]. … Assessment of Cell Viability in Caco-2 Cells Caco-2 cells were cultured in DMEM, enriched with 10% ( v / v ) Fetal Bovine Serum (FBS), 1% ( v / v ) L-glutamine, and 1% ( v / v ) penicillin/streptomycin. …

Pectin: A Bioactive Food Polysaccharide with Cancer Preventive Potential.

Pectin is an acidic heteropolysaccharide found in the cell walls and the primary and middle lamella of land plants. To be authorized as a food additive, industrial pectins must meet strict guidelines set forth by the Food and Agricultural Organization and must contain at least 65% polygalacturonic acid to achieve the E440 level. Fruit pectin derived from oranges or apples is commonly used in the food industry to gel or thicken foods and to stabilize acid-based milk beverages. It is a naturally occurring component and can be ingested by dietary consumption of fruit and vegetables. Preventing lo

Conservative therapy is associated with worse clinical features and biochemical derangements than renal replacement therapy: a retrospective study in Kumasi, Ghana.

BACKGROUND: The incidence of end stage kidney disease (ESKD) is increasing in Ghana as with the rest of the world. This study compared the sociodemographic, diagnostic characteristics (clinical, biochemical and imaging) and clinical outcomes of ESKD patients who chose either renal replacement therapy (RRT) or conservative therapy as well as the factors that influenced their choice. METHODS: We retrospectively reviewed the records of 382 ESKD patient from 2006 to 2018. The data was collected from the Nephrology Clinic at the Komfo Anokye Teaching Hospital (KATH). Sociodemographic, diagnostic (

Nostoc commune-derived scytonemin induced mitochondrial cell death in leukemia models.

Cyanobacteria have long attracted scientific interest through their potential application in the development of new therapeutic approaches, particularly those related to the treatment of cancer. In this study, the antiproliferative effects of Nostoc commune extract (NOS) and the cyanobacterial compound scytonemin (SCY) were evaluated against a variety of in vitro cancer models, including cervix, colon, breast, lung, and leukemia cell lines, using resazurin assays. Both of the studied compounds were found to have inhibited metabolic activity in a dose-dependent manner, with IC50 values ranging

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… Caco-2 cells were cultured in high-glucose DMEM (GE Healthcare, Piscataway, NJ, USA) supplemented with 10% FBS, penicillin (100 IU/mL), and streptomycin (100 μg/mL) (all obtained from Invitrogen, Carlsbad, CA, USA). …

Bone targeted nano-drug and nano-delivery.

There are currently no targeted delivery systems to satisfactorily treat bone-related disorders. Many clinical drugs consisting of small organic molecules have a short circulation half-life and do not effectively reach the diseased tissue site. This coupled with repeatedly high dose usage that leads to severe side effects. With the advance in nanotechnology, drugs contained within a nano-delivery device or drugs aggregated into nanoparticles (nano-drugs) have shown promises in targeted drug delivery. The ability to design nanoparticles to target bone has attracted many researchers to develop n

Innovative Biomaterials for the Treatment of Bone Cancer.

Bone cancer is a demanding challenge for contemporary medicine due to its high frequency of presentation and significant heterogeneity of malignant lesions developing within the bone. To date, available treatments are rarely curative and are primarily aimed at prolonging patients' survival and ameliorating their quality of life. Furthermore, both pharmacological and surgical therapies are aggravated by a consistent burden of adverse events and subsequent disability due to the loss of healthy bone structural and functional properties. Therefore, great research efforts are being made to develop

Targeting Metal Ion Homeostasis for Regulated Cell Death-Amplified Tumor Nanomedicine.

Amidst escalating global health challenges, neoplastic diseases remain a predominant cause of morbidity and mortality, exerting complex and far-reaching effects on human health and societal well-being. The advent of precision medicine has ushered in an era of tailored therapeutic strategies, leveraging individual genetic profiles, tumor microenvironmental features, and exogenous factors to redefine oncology care. Central to these advances is the understanding of cell death, a fundamental biological process encompassing both programmed and non-programmed forms. Programmed cell death is orchestr

Omega-3 Fatty Acids and Cancer Cell Cytotoxicity: Implications for Multi-Targeted Cancer Therapy.

Cancer is a major disease worldwide. Despite progress in cancer therapy, conventional cytotoxic therapies lead to unsatisfactory long-term survival, mainly related to development of drug resistance by tumor cells and toxicity towards normal cells. n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), can exert anti-neoplastic activity by inducing apoptotic cell death in human cancer cells either alone or in combination with conventional therapies. Indeed, n-3 PUFAs potentially increase the sensitivity of tumor cells to conventional therapies, poss

Bone cements for percutaneous vertebroplasty and balloon kyphoplasty: Current status and future developments.

Osteoporotic vertebral compression fractures (OVCFs) have gradually evolved into a serious health care problem globally. In order to reduce the morbidity of OVCF patients and improve their life quality, two minimally invasive surgery procedures, vertebroplasty (VP) and balloon kyphoplasty (BKP), have been developed. Both VP and BKP require the injection of bone cement into the vertebrae of patients to stabilize fractured vertebra. As such, bone cement as the filling material plays an essential role in the effectiveness of these treatments. In this review article, we summarize the bone cements

Bioactivities and Mechanisms of Action of Sinomenine and Its Derivatives: A Comprehensive Review.

Sinomenine, an isoquinoline alkaloid extracted from the roots and stems of Sinomenium acutum, has been extensively studied for its derivatives as bioactive agents. This review concentrates on the research advancements in the biological activities and action mechanisms of sinomenine-related compounds until November 2023. The findings indicate a broad spectrum of pharmacological effects, including antitumor, anti-inflammation, neuroprotection, and immunosuppressive properties. These compounds are notably effective against breast, lung, liver, and prostate cancers, exhibiting IC50 values of appro

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… Liu et al. reported that SIN (500 mM) boosted the cytotoxic effect of adriamycin on Caco-2 and multidrug resistance (MDR)-Caco-2 cells. SIN decreased PGE2 in MDR-Caco-2 cells and inhibited P-gp/MDR1 and COX-2 by obstructing the NF-κB pathway [ 56 ]. The following year, X. … SIN also reduced TEER and increased FD-4 flux in Caco-2 cell monolayers [ 218 ]. Additionally, in 2019, W.C. Xu et al. found that SIN enhanced the immunosuppressive effect of methylprednisolone (MP), decreasing the IC 50 value of MP. …

Computational study of SENP1 in cancer by novel natural compounds and ZINC database screening.

Introduction: Sentrin-specific protease 1 (SENP1) is a protein whose main function is deSUMOylation. SENP1 inhibits apoptosis, and increases angiogenesis, estrogen and androgen receptor transcription and c-Jun transcription factor, proliferation, growth, cell migration, and invasion of cancer. The in vivo and in vitro studies also demonstrated which natural compounds, especially phytochemicals, minerals, and vitamins, prevent cancer. More than 3,000 plant species have been reported in modern medicine. Natural compounds have many anti-cancerous andanti-turmeric properties such as antioxidative,

β-caryophyllene and β-caryophyllene oxide-natural compounds of anticancer and analgesic properties.

Natural bicyclic sesquiterpenes, β-caryophyllene (BCP) and β-caryophyllene oxide (BCPO), are present in a large number of plants worldwide. Both BCP and BCPO (BCP(O)) possess significant anticancer activities, affecting growth and proliferation of numerous cancer cells. Nevertheless, their antineoplastic effects have hardly been investigated in vivo. In addition, both compounds potentiate the classical drug efficacy by augmenting their concentrations inside the cells. The mechanisms underlying the anticancer activities of these sesquiterpenes are poorly described. BCP is a phytocannabinoid wit

Efficacy of Polymer-Based Nanocarriers for Co-Delivery of Curcumin and Selected Anticancer Drugs.

Cancer remains a heavy health burden resulting in a high rate of mortality around the world. The presently used anticancer drugs suffer from several shortcomings, such as drug toxicity, poor biodegradability and bioavailability, and poor water solubility and drug resistance. Cancer is treated effectively by combination therapy whereby two or more anticancer drugs are employed. Most of the combination chemotherapies result in a synergistic effect and overcome drug resistance. Furthermore, the design of polymer-based nanocarriers for combination therapy has been reported by several researchers t

Non-Curcuminoids from Turmeric and Their Potential in Cancer Therapy and Anticancer Drug Delivery Formulations.

Over the past decades curcuminoids have been extensively studied for their biological activities such as antiulcer, antifibrotic, antiviral, antibacterial, antiprotozoal, antimutagenic, antifertility, antidiabetic, anticoagulant, antivenom, antioxidant, antihypotensive, antihypocholesteremic, and anticancer activities. With the perception of limited toxicity and cost, these compounds forms an integral part of cancer research and is well established as a potential anticancer agent. However, only few studies have focused on the other bioactive molecules of turmeric, known as non-curcuminoids, wh

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… The bioavailability of curcumin could be significantly increased by (α, ar) turmerones as explained by Yue et al. in human intestinal epithelial colorectal adenocarcinoma Caco-2 cells. … The role of turmerones on curcumin transportation and P-glycoprotein activities in intestinal Caco-2 Cells J. Med. Food 2012 15 242 252 10.1089/jmf.2011.1845 22181075 PMC3282471 36. Sun P.Y. Young K.H. …

SLAMF7 regulates goblet cell mucus production and negatively impacts gut homeostasis and commensalism.

Crosstalk between the intestinal mucosal barrier and the gut microbiota contributes to maintaining intestinal homeostasis. Accumulating evidence suggests that diverse mechanisms are involved in maintaining intestinal homeostasis. Any disturbance in these pathways can compromise gut homeostasis and trigger chronic inflammatory diseases such as inflammatory bowel disease (IBD). However, how host factors regulate the intestinal mucosal barrier and change the gut microbiome has not been well defined. Here, we discovered that disruption of SLAMF7 protects against intestinal inflammation. SLAMF7 def

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… Compared with macrophages from WT mouse intestines, macrophages from slamf7 -/- mouse intestines induced Caco-2 cells to secrete significantly more mucin ( Figure 4(e) ). …

Organelle-oriented nanomedicines in tumor therapy: Targeting, escaping, or collaborating?

Precise tumor therapy is essential for improving treatment specificity, enhancing efficacy, and minimizing side effects. Targeting organelles is a key strategy for achieving this goal and is a frontier research area attracting a considerable amount of attention. The concept of organelle targeting has a significant effect on the structural design of the nanodrugs employed. Most notably, the intricate interactions among different organelles in a tumor cell essentially create a unified system. Unfortunately, this aspect might have been somewhat overlooked when existing organelle-targeting nanodru