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Glycosaminoglycans modulate activation, activity, and stability of tripeptidyl-peptidase I in vitro and in vivo.

Tripeptidyl-peptidase I (TPP I, CLN2 protein) is a lysosomal exopeptidase that sequentially removes tripeptides from the N termini of polypeptides and shows a minor endoprotease activity. Mutations in TPP I lead to classic late-infantile neuronal ceroid lipofuscinosis, a neurodegenerative lysosomal storage disease. TPP I proenzyme is converted in lysosomes into a mature enzyme with the assistance of another protease and is able to autoactivate in acidic pH in vitro via a unimolecular mechanism. Because autoactivation in vitro at the pH values reported for lysosomes generated inactive enzyme, w

Glucocorticoids-based prodrug design: Current strategies and research progress.

Attributing to their broad pharmacological effects encompassing anti-inflammation, antitoxin, and immunosuppression, glucocorticoids (GCs) are extensively utilized in the clinic for the treatment of diverse diseases such as lupus erythematosus, nephritis, arthritis, ulcerative colitis, asthma, keratitis, macular edema, and leukemia. However, long-term use often causes undesirable side effects, including metabolic disorders-induced Cushing's syndrome (buffalo back, full moon face, hyperglycemia, etc.), osteoporosis, aggravated infection, psychosis, glaucoma, and cataract. These notorious side e

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… CIA: collagen-induced arthritis; LPS: lipopolysaccharide; SDS: sodium dextran sulfate. Prodrug types | Prodrug name | Carrier | Linker | Route of administration | Applications and Advantages | Ref. … In another study, Ren et al. injected HPMA-Dex prodrugs intravenously to treat sodium dextran sulfate-induced ulcerative colitis mice [63] . …

[Mechanism of vitamin K2 in modulating matrix Gla protein to inhibit tumor growth in inflammation-associated colorectal cancer model mice].

Objective: To explore the mechanism of vitamin K2 (VitK2) regulating matrix Gla protein (MGP) in inhibiting tumor growth in inflammation-associated colorectal cancer (CAC) model mice. Methods: Twenty-six C57BL/6 male mice, 6-8 weeks old and weighing 20-25 g, were divided into 4 groups according to the random number table method (each group received different treatments): normal group (treated with olive oil gavage and physiological saline intraperitoneal injection) (n=5), model group [treated with olive oil gavage, azoxymethane (AOM) intraperitoneal injection, and dextran sulfate sodium (DSS) …

Methyl deficient diet aggravates experimental colitis in rats.

Inflammatory bowel diseases (IBD) result from complex interactions between environmental and genetic factors. Low blood levels of vitamin B12 and folate and genetic variants of related target enzymes are associated with IBD risk, in population studies. To investigate the underlying mechanisms, we evaluated the effects of a methyl-deficient diet (MDD, folate, vitamin B12 and choline) in an experimental model of colitis induced by dextran sodium sulphate (DSS), in rat pups from dams subjected to the MDD during gestation and lactation. Four groups were considered (n = 12-16 per group): C DSS(-) (

How autophagy controls the intestinal epithelial barrier.

Macroautophagy/autophagy is a cellular catabolic process that results in lysosome-mediated recycling of organelles and protein aggregates, a … T3: DNA damage inducible transcript 3; DEPTOR: DEP domain containing MTOR interacting protein; DSS: dextran sulfate sodium; EGF: epidermal growth factor; EGFR: epidermal growth factor receptor; EIF2A: eukaryotic translation initiation factor 2A; EIF2AK3: eukaryotic translation initiation factor 2 alpha kinase 3; EIF2AK4/GCN2: eukaryotic translation initiation fac …

Iron Sucrose: A Wealth of Experience in Treating Iron Deficiency.

Iron deficiency and iron-deficiency anemia are associated with increased morbidity and mortality in a wide range of conditions. In many patient populations, this can be treated effectively with oral iron supplementation; but in patients who are unable to take or who do not respond to oral iron therapy, intravenous iron administration is recommended. Furthermore, in certain conditions, such as end-stage kidney disease, chronic heart failure, and inflammatory bowel disease, intravenous iron administration has become first-line treatment. One of the first available intravenous iron preparations i

When Iron Bites Back: Severe Thrombocytopenia After Intravenous Iron Sucrose Therapy (Venofer).

Iron deficiency anemia (IDA) commonly presents with normal or elevated platelet counts, while thrombocytopenia is rare. Intravenous iron sucrose (Venofer) is widely used and generally well tolerated. We report the case of a 71-year-old female with chronic IDA who developed severe thrombocytopenia following iron sucrose therapy. Baseline hemoglobin was 6.3 g/dL with a platelet count of 229 × 10³/µL. After two doses of intravenous iron, hemoglobin improved to 9.3 g/dL, but platelets rapidly declined to 11 × 10³/µL. Extensive workup excluded thrombotic microangiopathy, autoimmune disease, infecti

The 'speck'-tacular oversight of the NLRP3-pyroptosis pathway on gastrointestinal inflammatory diseases and tumorigenesis.

The NLRP3 inflammasome is an intracellular sensor and an essential component of the innate immune system involved in danger recognition. An important hallmark of inflammasome activation is the formation of a single supramolecular punctum, known as a speck, per cell, which is the site where the pro-inflammatory cytokines IL-1β and IL-18 are converted into their bioactive form. Speck also provides the platform for gasdermin D protein activation, whose N-terminus domain perforates the plasma membrane, allowing the release of mature cytokines alongside with a highly inflammatory form of cell death

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… In vivo data showed that IL-18 inhibition, or IL-18R abrogation from intestinal epithelial cells (IECs), protects mice from Dextran Sulfate Sodium (DSS)-induced colitis [ 57 ]. However, like IL-1β, specific IL-18 targeting raises concerns. … Akkermansia muciniphila alleviates dextran sulfate sodium (DSS)-induced acute colitis by NLRP3 activation. Microbiol Spectr. 2021;9(2):e0073021. doi: 10.1128/Spectrum.00730-21. 79. Tong L, Hao H, Zhang Z, Lv Y, Liang X, Liu Q, et al. …

Histone deacetylase in inflammatory bowel disease: novel insights.

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is characterized by chronic nonspecific intestinal inflammation. Despite considerable efforts, IBD remains a heavy burden on society and human health, with increasing morbidity. Posttranslational modification, especially histone acetylation, is a key process in controlling DNA transcriptional activity. Histone deacetylases (HDACs) play a vital role in the mechanism of IBD pathogenesis through histone and nonhistone protein deacetylation. Herein, we present a summary of different categories of HDACs as well as H

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… BMDM, bone marrow-derived macrophages; CPT1, carnitine palmitoyltransferase 1; DSS, dextran sulfate sodium; FBA, N-(1-carbamoyl-2-phenylethyl) butyramide; HCEC, human colon epithelial cells; HDAC, histone deacetylase; HDACi, HDAC inhibitor; IBD, inflammatory bowel disease; iTreg, inducible regulatory … Macrophagic HDAC3 inhibition ameliorates Dextran Sulfate Sodium induced inflammatory bowel disease through GBP5-NLRP3 pathway. Int J Med Sci 2024; 21(8): 1385–1398. 105. Kapralov AA, Yang Q, Dar HH, et al. …

Unveiling the Role of CCL3: A Driver of CIPN in Colon Cancer Patients?

Cancer neuroscience is an emerging field revealing how malignancies interact with the nervous system to shape disease progression and symptom burden. In colorectal cancer (CRC), increasing evidence suggests a direct interplay between tumor cells and peripheral sensory neurons, contributing not only to cancer progression but also to chemotherapy-induced side effects such as peripheral neuropathy. Chemokines, particularly CCL3, appear to be key players in this bidirectional communication. This literature review aims to critically examine the role of CCL3 in CRC and chemotherapy-induced periphera

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… The study by Sasaki et al., demonstrated that mice deficient in CCL3 or CCR5 exhibited reduced tumor formation following azoxymethane (AOM) and dextran sulfate sodium (DSS) induction [ 31 ]. … Dysplasia and carcinoma development in a repeated dextran sulfate sodium-induced colitis model. J. Gastroenterol. Hepatol. 2002;17:1078–1083. doi: 10.1046/j.1440-1746.2002.02853.x. 34. …

[Effects of electroacupuncture at changbing fang on autophagy of colonic cells and gut microbiota in ulcerative colitis of rats].

OBJECTIVE: To observe the effects of electroacupuncture (EA) at changbing fang (prescription for intestinal disease) on autophagy of colonic cells and gut microbiota in rats with ulcerative colitis (UC), and to explore the mechanism of EA in the treatment of UC. METHODS: Thirty-two SD male rats were randomly divided into a control group, a model group, an EA group and a sham-EA group, with 8 rats in each group. Except the control group, the UC rat model was established by free drinking of 5% dextran sulfate sodium solution for 7 days in the other groups. In the EA group, changbing fang was ad…

Роли глюкагонового пептида 1 Агонисты-рецепторы в биологии иммунных клеток и аутоиммунных/аутоинфлампмидативных заболеваниях.

Глукагон-подобный peptide-1 (В тыс.GLP-1) — гормон, полученный кишечником, необходимый для поддержания глюкозы гомеостаза через многочисленные физиологические пути: инсулина, ингибирующего секрецию глюкагонов, замедляющего опустошение желудочков, усиливающего чувство полноты и подавляющего аппетит. С тех пор GLP-1 может разлагаться при помощи дипептидила пептидаза 4, GLP-1 рецепторные агонисты (GLP-1RAs) были разработаны для решения этой проблемы деградации. В настоящее время GLP-1RAs стали высокоэффективными методами лечения для управления типом 2 сахарный диабет и ожирение. Помимо их хорошо

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… ILC3s have been recognized to exert a protective function in both adoptive T-cell transfer-induced colitis and dextran sulfate sodium (DSS)-provoked colitis through their production of IL-22. Conversely, blocking IL-22 production has been shown to worsen the condition of colitis [ 183 , 184 ]. … Dulaglutide db/db mice, diabetic mice; IBD, inflammatory bowel disease; DSS, dextran sulfate sodium; EAE, experimental autoimmune encephalitis; LAMP3, lysosome-associated membrane protein; RA, rheumatoid arthritis; MS, multiple sclerosis; SS, Sjögren’s syndrome Presently, there is a scarcity of research …

Identification of iron metabolism-related predictive markers of endometriosis and endometriosis-relevant ovarian cancer.

Endometriosis is associated with ovarian cancers, mainly endometrioid and clear-cell carcinomas. Iron metabolism has been shown to play a role in endometriosis. Therefore, it is vital to explore the relationship between iron metabolism and ovarian cancer and to identify novel markers for diagnostics and therapeutics. The endometriosis dataset GSE51981 and the ovarian cancer dataset GSE26712 were obtained from the gene expression omnibus database, and differentially expressed genes were identified. Iron metabolism genes were obtained from molecular signatures database, and hub genes from the 3

Molecular mechanisms underlying methotrexate-induced intestinal injury and protective strategies.

Methotrexate (MTX) is a folic acid reductase inhibitor that manages various malignancies as well as immune-mediated inflammatory chronic diseases. Despite being frequently prescribed, MTX's severe multiple toxicities can occasionally limit its therapeutic potential. Intestinal toxicity is a severe adverse effect associated with the administration of MTX, and patients are significantly burdened by MTX-provoked intestinal mucositis. However, the mechanism of such intestinal toxicity is not entirely understood, mechanistic studies demonstrated oxidative stress and inflammatory reactions as key fa

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… Significantly, it was documented that berberine prevented ulcerative colitis provoked by dextran sulfate sodium (Zhu et al. 2019 ). … Endocrine-related Cancer 26:R369–R380 Khor TO, Huang M-T, Kwon KH, Chan JY, Reddy BS, Kong A-N (2006) Nrf2-deficient mice have an increased susceptibility to dextran sulfate sodium–induced colitis. …

Indications and recent evidence for apheresis in children and adults with kidney diseases: a comprehensive review.

IntroductionPlasmapheresis has been a therapeutic option in kidney diseases to eliminate disease-causing autoantibodies, circulating factors, and abnormal components involved in complement pathways. We aim to systematically review the effectiveness and adverse events associated with plasmapheresis and related apheresis therapies in treating kidney diseases in paediatric and adult populations.MethodsWe searched databases including EMBASE, CINAHL, PubMed, and Cochrane Central for studies from 2010 to October 2023. The search terms included terms related to glomerulonephritis treated with plasmap

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… Lipoprotein apheresis (LDL-A) can be performed using the double filtration system, heparin-induced LDL precipitation, LDL adsorption through dextran sulfate, the DALI hemoperfusion system, and the Liposorber D system [ 63 ]. … The other approaches bind LDL based on negatively charged polyacrylate or dextran sulfate anions or antibodies to the lipoprotein [ 64 ]. Acute decreases in LDL-cholesterol after each procedure range from 60% to 80%, depending upon the volume of blood or plasma treated [ 65 ]. …

Immunomodulatory Nanosystems.

Immunotherapy has emerged as an effective strategy for the prevention and treatment of a variety of diseases, including cancer, infectious diseases, inflammatory diseases, and autoimmune diseases. Immunomodulatory nanosystems can readily improve the therapeutic effects and simultaneously overcome many obstacles facing the treatment method, such as inadequate immune stimulation, off-target side effects, and bioactivity loss of immune agents during circulation. In recent years, researchers have continuously developed nanomaterials with new structures, properties, and functions. This Review provi

Bioabsorbable polymers in cancer therapy: latest developments.

Cancer is a devastating disease, being responsible for 13 % of all deaths worldwide. One of the main challenges in treating cancer concerns the fact that anti-cancer drugs are not highly specific for the cancer cells and the "death" of healthy cells in the course of chemotherapy treatment is inevitable. In this sense, the use of drug delivery systems (DDS) can be seen as a powerful tool to minimize or overcome this very important issue. DDS can be designed to target specific tissues in order to mitigate side effects. Bioabsorbable polymers, due to their inherent characteristics, and because th

Influence of gut microbial metabolites on tumor immunotherapy: mechanisms and potential natural products.

In recent years, tumor immunotherapy has made significant breakthroughs in the treatment of malignant tumors. However, individual differences in efficacy have been observed in clinical practice. There is increasing evidence that gut microbial metabolites influence the efficacy of distal tumor immunotherapy via the gut-liver axis, the gut-brain axis and the gut-breast axis, a process that may involve modulating the expression of immune cells and cytokines in the tumor microenvironment (TME). In this review, we systematically explore the relationship between gut microbial metabolites and tumor i

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… Dextran sulfate sodium (DSS) can break down the intestinal mucosal barrier, leading to intestinal inflammation and ulcers. Previous studies have shown that BBR can ameliorate the bile acid imbalance induced by DSS in both the liver and the intestine. …

Effects of Expanded Hemodialysis with Medium Cut-Off Membranes on Maintenance Hemodialysis Patients: A Review.

Kidney failure is associated with high morbidity and mortality. Hemodialysis, the most prevalent modality of renal replacement therapy, uses the principle of semipermeable membranes to remove solutes and water in the plasma of patients with kidney failure. With the evolution of hemodialysis technology over the last half century, the clearance of small water-soluble molecules in such patients is adequate. However, middle molecules uremic toxins are still retained in the plasma and cause cardiovascular events, anemia, and malnutrition, which significantly contribute to poor quality of life and h

The Effects of Artificial Sweeteners on Intestinal Nutrient-Sensing Receptors: Dr. Jekyll or Mr. Hyde?

The consumption of artificial and low-calorie sweeteners (ASs, LCSs) is an important component of the Western diet. ASs play a role in the pathogenesis of metabolic syndrome, dysbiosis, inflammatory bowel diseases (IBDs), and various inflammatory conditions. Intestinal nutrient-sensing receptors act as a crosstalk between dietary components, the gut microbiota, and the regulation of immune, endocrinological, and neurological responses. This narrative review aimed to summarize the possible effects of ASs and LCSs on intestinal nutrient-sensing receptors and their related functions. Based on the

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… In mice with dextran sulfate sodium (DSS)-induced colitis (an animal model of IBD), high protein intake caused an increased expression of inflammatory cytokines through the modulation of CaSR [ 56 ], while L-tryptophan, L-valine, and glutamyl dipeptides inhibited CaSR-dependent pro-inflammatory cytokine … In an animal model involving dextran sulfate sodium-induced colitis mice, Stevia inhibited the activation of NFKB and MAPK signaling and might mimic probiotic action. It could modify the microbiome of the intestine, but the results are controversial [ 115 ] and further studies are needed. …