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Exploring the top 30 drugs associated with drug-induced constipation based on the FDA adverse event reporting system.

ObjectiveThis project aims to identify the top 30 drugs most commonly associated with constipation and their signal values within the FDA Adverse Event Reporting System database.MethodsWe extracted adverse drug events (ADEs) related to constipation from the FAERS database spanning from January 1, 2004, to September 30, 2023. We compiled the 30 most frequently reported drugs based on the frequency of constipation events. We employed signal detection methodologies to ascertain whether these drugs elicited significant signals, including reporting odds ratio, proportional reporting ratio, multi-it

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… Efficacy and safety of lipase inhibitor orlistat in Japanese with excessive visceral fat accumulation: 24-week, double-blind, randomized, placebo-controlled study. Adv. Ther. 36, 86–100. 10.1007/s12325-018-0835-5 Shore N. D., Chowdhury S., Villers A., Klotz L., Siemens D. …

RXR Agonists Enhance Lenalidomide Anti-Myeloma Activity and T Cell Functions while Retaining Glucose-Lowering Effect.

Retinoid X receptor (RXR) heterodimerizes with the PPAR nuclear hormone receptor and regulates its downstream events. We investigated the effects of RXR agonists (LG100754, bexarotene, AGN194204, and LG101506) on lenalidomide's anti-myeloma activity, T cell functions, and the level of glucose and lipids in vivo. Genetic overexpression and CRISPR/Cas9 knockout experiments were conducted in multiple myeloma (MM) cell lines and Jurkat T cell lines to determine the roles of CRBN in RXR-agonist mediated effects. A xenograft mouse model of MM was established to determine the combination effect of LG

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… Consistent with our data, CS018 induced the expression of PPAR γ target genes, CD36 , and lipoprotein lipase ( LPL ) and significantly reduced animal blood glucose levels in vivo. Bexarotene is an FDA-approved RXR agonist. …

Biotechnological Innovations from Ocean: Transpiring Role of Marine Drugs in Management of Chronic Disorders.

Marine drugs are abundant in number, comprise of a diverse range of structures with corresponding mechanisms of action, and hold promise for the discovery of new and better treatment approaches for the management of several chronic diseases. There are huge reserves of natural marine biological compounds, as 70 percent of the Earth is covered with oceans, indicating a diversity of chemical entities on the planet. The marine ecosystems are a rich source of bioactive products and have been explored for lead drug molecules that have proven to be novel therapeutic targets. Over the last 70 years, m

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… This compound decreases the expression of fatty acid synthase and increases the activity of adipose triglyceride lipase, further leading to the production and phosphorylation of hormones that are sensitive to lipolysis. …

Current landscape of clinical development and approval of advanced therapies.

Advanced therapy medicinal products (ATMPs) are innovative therapies that mainly target orphan diseases and high unmet medical needs. The uncertainty about the product's benefit-risk balance at the time of approval, the limitations of nonclinical development, and the complex quality aspects of those highly individualized advanced therapies are playing a key role in the clinical development, approval, and post-marketing setting for these therapies. This article reviews the current landscape of clinical development of advanced therapies, its challenges, and some of the efforts several stakeholde

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… Moreover, performance and socialization at school age around 5–6 years was suggested by the experts as long-term data to be captured relating to efficacy. 37 , 78 For those patients with lipoprotein lipase (LPL) deficiency, the most severe associated complication is pancreatitis. …

Emerging treatment options for the management of Hodgkin's lymphoma: clinical utility of nivolumab.

Classical Hodgkin's lymphoma (cHL) is a B-cell malignancy comprised of pathologic Reed Sternberg cells with a surrounding immune-tolerant inflammatory milieu. RS cells evade immune recognition in part through programmed death ligand 1 (PD-L1) overexpression, which is genetically programmed through copy number alterations, polysomy, and amplification of the 9p24.1 locus encoding PD-L1. By engaging with PD-1+ T-cells, PD-L1 delivers a potent immune suppressive signal promoting immunologic escape of the tumor cell. Enhancing antitumor immune response by targeting PD-1 with the monoclonal antibody

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… Drug-related grade 3 AEs included neutropenia (5%), increased lipase (3%), increased AST/ALT (3%), abdominal pain (3%), and rash (1%). 65 Two patients discontinued treatment due to AEs believed to be drug related; 1 patient with newly diagnosed autoimmune hepatitis, and 1 patient with increased AST/ALT …

63rd Annual Conference of the Indian Society of Gastroenterology, ISGCON 2022-January 5th - 8th, 2023 in Jaipur.

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TGF-β in hematologic malignancies: molecular functions and clinical applications.

Transforming growth factor-β (TGF-β) represents a family of multifunctional cytokines, primarily secreted by megakaryocytes, monocytes, T lymphocytes, bone marrow stromal cells, and other cell types. TGF-β plays an essential role in various physiological processes, including the regulation of cell proliferation, differentiation, apoptosis, and immune homeostasis. As a key immunoregulatory cytokine, TGF-β contributes to an immunosuppressive network within the microenvironment of hematologic malignancies by modulating the functions of both adaptive and innate immune cells. Current studies have s

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… Additionally, grade 4 bilirubin elevation was seen in 5% of patients, and another 5% experienced grade 4 lipase elevation, underscoring the need to monitor potential hepatobiliary effects ( 126 ). Galunisertib (LY2157299), developed by Eli Lilly and Company, is another TβRI kinase inhibitor. …

Prevalence of symptomatic toxicities for novel therapies in adult oncology trials: a scoping review.

BackgroundPatients' self-report of their symptoms can provide important data for the evaluation of treatment benefit and tolerability of oncology drugs. Contemporary treatment approaches, including immunotherapy and molecular targeted therapies, have unique toxicities based on their novel mechanisms of action. This scoping review aimed to summarize evidence from existing reviews and clinical practice guidelines to examine the type and prevalence of toxicities including symptomatic adverse events (sympAEs) for adult cancer patients to inform clinical care and therapeutic trials.MethodsA systema

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… , patidegib, taladegib) | GI: dysgeusia (38%-68%), nausea (33%-47%), vomiting (32%), diarrhea (24%), ↓ appetite (19%-63%) Pain: HA (15%), myalgia (19%), arthralgia (13%) Sleep/Wake: fatigue (29%-54%), asthenia (3%) Skin: alopecia (38%-66%) Misc: muscle spasms (23%-71%), weight loss (9%-27%) | GI: ↑ lipase …

Contemporary treatment patterns of overweight and obesity: insights from the Mass General Brigham health care system.

ObjectiveThe objective of this study was to describe the prevalence of obesity, obesity-related conditions (ORCs), and antiobesity medication (AOM) eligibility and prescribing practice among eligible patients in a large health care system.MethodsIn this cross-sectional analysis of the multicenter Mass General Brigham health care system (Boston, Massachusetts) spanning 2018 to 2022, adults eligible for AOMs (BMI ≥ 30 kg/m2 or BMI 27-29.9 kg/m2 with ≥1 ORC) were identified. Among those AOM-eligible, the prevalence of prescriptions for AOMs approved for long-term weight management was evaluated.R

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… Triglycerides, mg/dL | 122.09 ± 86.05 | 97.47 ± 62.87 | 114.20 ± 76.64 | 128.42 ± 87.56 | 141.59 ± 98.49 | 149.4 ± 101.89 | 149.10 ± 102.43 | <0.001 NT‐proBNP, pg/mL | 1108.21 ± 1864.16 | 1468.4 ± 2157.79 | 1165.75 ± 1915.04 | 1041.24 ± 1783.59 | 889.06 ± 1608.31 | 787.26 ± 1515.97 | 753.18 ± 1475.67 | <0.001 Lipase …

Pharmacomicrobiomics in Anticancer Therapies: Why the Gut Microbiota Should Be Pointed Out.

Anticancer treatments have shown a variable therapeutic outcome that may be partly attributable to the activity of the gut microbiota on the pathology and/or therapies. In recent years, microbiota-drug interactions have been extensively investigated, but most of the underlying molecular mechanisms still remain unclear. In this review, we discuss the relationship between the gut microbiota and some of the most commonly used drugs in oncological diseases. Different strategies for manipulating the gut microbiota layout (i.e., prebiotics, probiotics, antibiotics, and fecal microbiota transplantati

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… Similarly, a triple-layered nanogel DOX-loaded nanoparticle has been developed to be degraded by bacterial lipases, releasing DOX into the tumor, thereby allowing for better tissue specificity, targeted anticancer action and a reduction in side effects [ 125 ]. …

Peroxisome Proliferator-Activated Receptors (PPAR)γ Agonists as Master Modulators of Tumor Tissue.

In most clinical trials, thiazolidinediones do not show any relevant anti-cancer activity when used as mono-therapy. Clinical inefficacy contrasts ambiguous pre-clinical data either favoring anti-tumor activity or tumor promotion. However, if thiazolidinediones are combined with additional regulatory active drugs, so-called 'master modulators' of tumors, i.e., transcriptional modulators, metronomic low-dose chemotherapy, epigenetically modifying agents, protein binding pro-anakoinotic drugs, such as COX-2 inhibitors, IMiDs, etc., the results indicate clinically relevant communicative reprogram

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… PPARγ Agonists and IMiDs In an animal model, pomalidomide enhances the expression of PPARγ and CCAAT/enhancer binding protein α (C/EBPα), as well as the activity of lipoprotein lipase (LPL) and fatty acid synthetase (FAS). …

Posttransplant complications: molecular mechanisms and therapeutic interventions.

Posttransplantation complications pose a major challenge to the long-term survival and quality of life of organ transplant recipients. These complications encompass immune-mediated complications, infectious complications, metabolic complications, and malignancies, with each type influenced by various risk factors and pathological mechanisms. The molecular mechanisms underlying posttransplantation complications involve a complex interplay of immunological, metabolic, and oncogenic processes, including innate and adaptive immune activation, immunosuppressant side effects, and viral reactivation.

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… metabolic disorders | Increased insulin resistance occurs in peripheral tissues | 172 , 175 Direct damage occurs to pancreatic β‐cells | 173 , 174 Dyslipidemia | Key enzymes are upregulated in the cholesterol biosynthesis process | 177 LDL receptor binding to LDL is interfered with, and lipoprotein lipase … coenzyme A (HMG‐CoA) reductase, thereby enhancing the synthesis of very low‐density lipoprotein (VLDL) cholesterol. 177 Second, cyclosporine can also impair the body's ability to remove low‐density lipoprotein (LDL) and VLDL by interfering with LDL receptor binding to LDL and decreasing lipoprotein lipase …

Late Breaking Orals.

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… Inactivation of bacterial lipoprotein and lipopolysaccharide (LPS) from EVs was performed using lipoprotein lipase and polymyxin B, respectively. … Osteoclastogenic effects of EVs from P. gingivalis and T. forsythia were reduced by both lipoprotein lipase and polymyxin B, while osteoclastogenic effects of EVs from S. oralis and F. alocis were reduced by lipoprotein lipase alone. …

Myokines in cancer: bridging molecular mechanisms to biomarker discovery and therapeutic innovation.

Exercise can regulate the physiological functions of the body by inducing the secretion of myokines, which are bioactive factors mainly secreted by muscle cells. This review classifies myokines based on their functional characteristics, including metabolic regulation (such as myostatin, interleukin-6), neuroregulation (brain-derived neurotrophic factor), cell proliferation/differentiation regulation (myogenic proteins), immune regulation (tumor necrosis factor- alpha), and factors involved in angiogenesis and extracellular matrix remodeling (such as connective tissue growth factor).Cancer, as

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… Free fatty acid (FFA) release is also increased by IL-6(Lima 11 ).By stimulating hormone-sensitive lipase (HSL) in fat cells, it converts triglycerides into FFA and glycerol, raising blood levels of FFA and giving muscles and other tissues a source of energy ( 12 ).Furthermore, IL-6 might also have an …

Barriers to Treg therapy in Europe: From production to regulation.

There has been an increased interest in cell based therapies for a range of medical conditions in the last decade. This explosion in novel therapeutics research has led to the development of legislation specifically focused on cell and gene based therapies. In Europe, the European medicines agency (EMA) designates any medicines for human use which are based on genes, tissues, or cells as advanced therapy medicinal products or advanced therapy medicinal products (ATMPs). In this article we discuss the hurdles to widespread adoption of ATMPs in Europe, with a focus on regulatory T cells (Tregs).

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… | Notes | Chondrocelect | TEP | Autologous chondrocyte implantation for the treatment of cartilaginous lesions in the knee | 5/10/09 | No | MA withdrawn in 2016 | NCT00414700 Glybera | GTMP | Adenovirus vector delivery of human lipoprotein lipase to treat LPL deficiency | 25/10/12 | Yes | MA not renewed …

Shutting off the fuel supply to target metabolic vulnerabilities in multiple myeloma.

Pathways that govern cellular bioenergetics are deregulated in tumor cells and represent a hallmark of cancer. Tumor cells have the capacity to reprogram pathways that control nutrient acquisition, anabolism and catabolism to enhance their growth and survival. Tumorigenesis requires the autonomous reprogramming of key metabolic pathways that obtain, generate and produce metabolites from a nutrient-deprived tumor microenvironment to meet the increased bioenergetic demands of cancer cells. Intra- and extracellular factors also have a profound effect on gene expression to drive metabolic pathway

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… Fatty acid synthase (FASN) | Orlistat | Inhibits lipases and induces apoptosis in myeloma cells ( 43 , 85 ). The HK isoform HKII is the rate-limiting step in aerobic glycolysis and is overexpressed in many cancers including MM ( 87 , 88 ). …

Potential Approaches Versus Approved or Developing Chronic Myeloid Leukemia Therapy.

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of patients with chronic myeloid leukemia (CML). However, continued use of these inhibitors has contributed to the increase in clinical resistance and the persistence of resistant leukemic stem cells (LSCs). So, there is an urgent need to introduce additional targeted and selective therapies to eradicate quiescent LSCs, and to avoid the relapse and disease progression. Here, we focused on emerging BCR-ABL targeted and non-BCR-ABL targeted drugs employed in clinical trials and on alternative CML treatments, including antioxidan

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… Adverse effects seen after Ponatinib-treatment are rash, abdominal pain, dryness of the skin, thrombocytopenia and increased lipase levels ( 39 ), thrombosis and other cardiovascular problems ( 54 ). …

Systemic Lupus Erythematosus in Primary Care: An Update and Practical Messages for the General Practitioner.

Systemic Lupus Erythematosus (SLE) is a complex chronic autoimmune disease that manifests a wide range of organ involvement. Traditionally, the diagnosis and management of SLE is provided at secondary and tertiary centers to ensure prompt initiation of treatment, adequate control of flares and prevention of irreversible organ damage. Notwithstanding, the role of primary care in SLE is also emerging as there are still significant unmet needs such as the diagnostic delay at the community level and the high burden of therapy- and disease-related comorbidities. In the present review, we summarize

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… Numerous mechanisms are implicated in its pathogenesis, including antibodies against lipoprotein lipase as well as cytokines that affect the balance and content of lipoproteins ( 134 ). Prevalence of diabetes ranges from 2.7 to 7% and increases over time after diagnosis reaching up to 14% ( 135 ). …

The cGAS-STING pathway in senescence and aging-related diseases: mechanisms and therapeutic opportunities.

The cGAS-STING pathway acts as a critical molecular hub connecting genomic instability with cellular senescence. Functioning as a key regulator of the innate immune system, this pathway detects aberrant cytoplasmic DNA to activate downstream inflammatory responses, thereby playing a pivotal role in aging-related diseases. This review systematically explores the core mechanisms by which the cGAS-STING pathway regulates cellular senescence, emphasizing its role in triggering senescence through the recognition of DNA damage signals (e.g., oxidative stress, telomere dysfunction) and promoting para

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… However, the SASP is subject to contextual regulation; for example, monoacylglycerol lipase (MGLL) overexpression in senescent prostate tumor cells suppresses NF-κB-driven SASP, thereby attenuating both autocrine and paracrine tumor-promoting effects [ 76 ]. …

61st Annual Conference of Indian Society of Gastroenterology, Virtual Diamond Jubilee ISGCON 2020, 19-20th December 2020.

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