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Early bilirubinemia after allogeneic stem cell transplantation-an endothelial complication.

Hyperbilirubinemia occurs frequently after allogeneic stem cell transplantation. Causes include primary liver damage and endothelial complications as major contributors. Here, we have investigated the impact of early bilirubinemia (EB) on posttransplant outcomes. Maximum total bilirubin levels (days 0-28) were categorized using maximally selected log rank statistics to identify a cut off for the endpoint non-relapse mortality (NRM) in a training cohort of 873 patients. EB above this cut off was correlated with NRM and overall survival (OS) and with pre- and posttransplant Angiopoietin-2, inter

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… As per in-house policy, all patients from the Heidelberg cohort transplanted after 01/2010 routinely received statin-based endothelial protection (SEP): pravastatin (20 mg/d) and ursodeoxycholic acid (UDA) starting at day −1 before alloSCT in order to reduce calcineurin inhibitor-associated cardiovascular … EB early bilirubinemia, SOS/VOD sinusoidal obstruction syndrome/veno-occlusive disease, SEP statin-based endothelial prophylaxis, UDA ursodeoxycholic acid, AML acute myeloid leukemia, ALL acute lymphoblastic leukemia, MDS myelodysplastic syndromes, MPN myeloproliferative neoplasms, MM multiple myeloma …

Polymorphisms in CXCR3 ligands predict early CXCL9 recovery and severe chronic GVHD.

Chronic graft-versus-host disease (cGVHD) is a major cause of mortality and morbidity after allogeneic stem cell transplantation (alloSCT). The individual risk of severe cGVHD remains difficult to predict and may involve CXCR3 ligands. This study investigated the role of single-nucleotide polymorphisms (SNPs) of CXCL4, CXCL9, CXCL10, and CXCL11, and their day +28 serum levels, in cGVHD pathogenesis. Eighteen CXCR3 and CXCL4, CXCL9-11 SNPs as well as peri-transplant CXCL9-11 serum levels were analyzed in 688 patients without (training cohort; n = 287) or with statin-based endothelial protection

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… SEP consists of pravastatin 20 mg/day and ursodeoxycholic acid (UDCA) 3 × 250 mg/day 28 , 29 , and was used as a standard treatment in Heidelberg University Hospital since 01/2010. … Improved survival with ursodeoxycholic acid prophylaxis in allogeneic stem cell transplantation: long-term follow-up of a randomized study. Biol. Blood Marrow Transplant. 2014;20:135–138. doi: 10.1016/j.bbmt.2013.10.014. 49. Amuro H, et al. …

Gut microbiota and microbial metabolites for osteoporosis.

Osteoporosis is an age-related bone metabolic disease. As an essential endocrine organ, the skeletal system is intricately connected with extraosseous organs. The crosstalk between bones and other organs supports this view. In recent years, the link between the gut microecology and bone metabolism has become an important research topic, both in preclinical studies and in clinical trials. Many studies have shown that skeletal changes are accompanied by changes in the composition and structure of the gut microbiota (GM). At the same time, natural or artificial interventions targeting the GM can

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… One study investigated differences in the levels of individual BAs in women with high/low BMDs (65 vs. 71 patients aged 20–40 years) and reported that ursodeoxycholic acid (UDCA) and tauroursodeoxycholic acid (TUDCA) were correlated with a low BMD (OR = 2.69 (1.48–5.41), p = 0.0025; OR = 2.18 (1.3–3.88 … acid Vitamin D receptor Funding Statement This work was supported by the National Key Research and Development Program [2020YFC2009004, 2021YFC2501700], the National Natural Science Foundation of China [82330078, 81874010, 82272554]. …

Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions.

Nuclear receptors (NRs) are a large family of ligand-dependent transcription factors that regulate the expression of a wide range of target genes in response to endogenous and exogenous ligands, including steroid hormones, thyroid hormone, vitamin D, retinoic acid, fatty acids, and oxidative steroids. Upon ligand binding, nuclear receptors form dimer complexes with transcriptional cofactors, which interact with specific DNA sequences in the promoter or enhancer regions of target genes to modulate gene expression. This process plays a crucial role in many physiological processes such as reprodu

Drug reprofiling history and potential therapies against Parkinson's disease.

Given the high whittling down rates, high costs, and moderate pace of new medication, revelation, and improvement, repurposing "old" drugs to treat typical and uncommon illnesses is progressively becoming an appealing proposition. Drug repurposing is the way toward utilizing existing medications in treating diseases other than the purposes they were initially designed for. Faced with scientific and economic challenges, the prospect of discovering new medication indications is enticing to the pharmaceutical sector. Medication repurposing can be used at various stages of drug development, althou

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… acid (UDCA) ( Bell et al. , 2018) | Reduces elevated liver enzyme levels by facilitating bile flow through the liver and protecting liver cells | Secondary bile; it reduces cholesterol absorption and dissolves gallstones | Improves mitochondrial function and redistributes Drp1 in fibroblasts | Phase … Ursodeoxycholic acid improves mitochondrial function and redistributes Drp1 in fibroblasts from patients with either sporadic or familial alzheimer's disease. J. Mol. Biol. 430 (21), 3942–3953. 10.1016/j.jmb.2018.08.019 Bendor J. T., Logan T. P., Edwards R. H. (2013). The function of α-synuclein. …

Vitamin E for people with non-alcoholic fatty liver disease.

RATIONALE: Non-alcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), is … s (IU) to 1000 IU. Co-interventions were lifestyle and low-calorie diet interventions in 13 trials, ursodeoxycholic acid in one trial, unchanged diet and physical activity in one trial, and baseline treatments for type 2 diabetes in one trial. Nine trials had more than two intervention groups, but we used only the groups in which vitamin E alone or vitamin E in combin …

Liver failure due to relapsed myeloma and hepatic iron overload.

Multiple myeloma is a hematologic malignancy that classically manifests with hypercalcaemia, renal insufficiency, anaemia and lytic bone lesions. Liver dysfunction in multiple myeloma is a lesser known complication that occurs through biliary obstruction, liver infiltration by plasma cells, amyloid/light chain deposition or due to liver injury from medications. Although transfusion-related hepatic iron overload-leading to significant liver disease-is a recognised complication in certain hematologic malignancies, little is known about transfusional iron overload in patients with multiple myelom

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… The patient received symptomatic and supportive therapy with ursodeoxycholic acid, diphenhydramine and transfusions, as needed. Given her poor prognosis, goals of care were discussed, and she elected for palliative care/hospice. She died a week after the discharge from the hospital. …

[Chinese experts consensus statement: diagnosis and treatment of cystic fibrosis (2023)].

Cystic fibrosis (CF) is one of the most common autosomal recessive genetic diseases in Caucasians, but CF patients in China are rare, and it … s with CF pancreatic disease(1A).Question 26: How to deal with hepatobiliary disease in CF patients?Ursodeoxycholic acid is not recommended in asymptomatic patients with CF hepatobiliary disease(2B).Question 27: How to deal with gastrointestinal problems such as acid regurgitation in CF patients?Acid suppression is recommended for CF patients with gastrointestinal sym …

Global first-in-class drugs approved in 2023-2024: Breakthroughs and insights.

First-in-class (FIC) drugs are considered the main drivers of new drug discovery and have novel targets and mechanisms. The proportion of FIC drugs among new drugs provides fundamental guidance for both academic and pharmaceutical research. From a global perspective, 81 FIC drugs were approved in 2023 and 2024. Among them, small-molecule drugs account for a greater percentage (51.9%), illustrating the discovery of new chemical entities. Macromolecule drugs (48.1%), which mainly consist of antibody analogs, represent a growing trend as new biotechnology techniques have emerged. In terms of FIC

A Case of Autoimmune Hepatitis Initially Manifesting as Hepatic Encephalopathy.

Autoimmune hepatitis (AIH) is a T-cell-mediated liver disease characterized by elevated transaminases, circulating autoantibodies, hypergammaglobulinemia, and interface hepatitis. A 66-year-old female patient visited our department due to recurrent episodes of altered consciousness, sleep-wake inversion, and asterixis, indicating hepatic encephalopathy (HE). Her liver biopsy results clearly demonstrated interface hepatitis. The patient's severe HE does not parallel her relatively stable liver function and was attributed to a wide retroperitoneal collateral vein shunting blood directly into the

Recent Advances of Acute Kidney Injury in Hematopoietic Cell Transplantation.

Acute kidney injury (AKI) is a common complication of allogeneic hematopoietic cell transplantation (allo-HCT) and is associated with non-relapse mortality (NRM) and quality of life (QOL). Multiple factors may contribute to AKI during allo-HCT and are often present at the same time making it difficult to determine the cause of AKI in each patient. Nephrotoxic drugs, infections, thrombotic microangiopathy (TMA), and sinusoidal obstruction syndrome (SOS) are well described causes of AKI during allo-HCT. Acute graft-versus-host disease (aGVHD) is a major complication of allo-HCT that mainly targe

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… Prophylactic use of ursodeoxycholic acid ( 123 ), defibrotide ( 124 ), and fresh frozen plasma ( 125 ) should be considered in those at high risk of SOS. There is no established treatment for TA-TMA, but potential contributing factors should be eliminated when possible. … Systematic Review of Controlled Clinical Trials on the Use of Ursodeoxycholic Acid for the Prevention of Hepatic Veno-Occlusive Disease in Hematopoietic Stem Cell Transplantation . …

Advances in Drug Delivery and Biomaterials: Facts and Vision.

Drug delivery and biomaterials are different fields of science but, at the same time, are tightly related and intertwined. The 2018 CRS Italy Chapter Annual Workshop aims to explore recent advances in design and development in these areas. Many colleagues from Europe participated to the Workshop, stimulating the discussion. To foster the discussion on recent research and networking opportunities, especially among younger attendees, all poster-presenting authors were asked to provide a short talk. The very friendly and stimulating atmosphere allowed the attendees to explore new frontiers and ta

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… Its conjugation with a bile acid (ursodeoxycholic acid, UDCA) allowed us to obtain a lipophilic prodrug (UDCA-AZT) which is able to elude the AET systems of which it is a substrate [2], with a consequent increase of the uptake in murine macrophages [3]. … Zidovudine and Ursodeoxycholic Acid Conjugation: Design of a New Prodrug Potentially Able to Bypass the Active Efflux Transport Systems of the Central Nervous System. Mol. …

Терапия клеток CAR-T и модуляция микробиоты в мультислерозе: новые терапевтические стратегии и текущие ограничения.

Множественный склероз (MS) — хроническое аутоиммунное воспалительное заболевание центральной нервной системы (CNS), характеризующееся разрушением миелиновой оболочки вокруг нервных клеток. Широкое распространение и серьезные последствия НР свидетельствуют о недостатках существующих методов лечения и о важности разработки новаторских терапевтических подходов. На основе успешных экспериментальных исследований среди пациентов и экспериментальной модели мышью аутоиммунного энцефаломиелита (EAE) клетки CAR-T предлагают новый терапевтический механизм путем непосредственной адресации и ликвидации кле

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… Among BAs, primary BAs such as cholic acid and chenodeoxycholic acid, and secondary BAs, such as lithocholic acid and ursodeoxycholic acid (UDCA), enter the bloodstream from the intestine and are involved in various metabolic processes [ 133 , 134 ]. …

Cardiac amyloidosis: From diagnosis to therapeutics breakthroughs.

Cardiac amyloidosis (CA) is a progressive infiltrative cardiomyopathy resulting from the deposition of misfolded amyloid fibrils in the myocardium and heart valves, with the main forms being amyloid light-chain (AL), transthyretin-related (ATTR) (wild-type or hereditary), and amyloid A amyloidosis. Although historically underdiagnosed, recent advances in non-invasive imaging techniques such as cardiac magnetic resonance imaging and bone scintigraphy have significantly improved its recognition. This review outlines the current diagnostic approaches and therapeutic advancements in CA, emphasizin

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… Effect of doxycycline and ursodeoxycholic acid on transthyretin amyloidosis. Amyloid. 2017;24:78–79. doi: 10.1080/13506129.2016.1269739. 94. Karlstedt E, Jimenez-Zepeda V, Howlett JG, White JA, Fine NM. … Clinical Experience With the Use of Doxycycline and Ursodeoxycholic Acid for the Treatment of Transthyretin Cardiac Amyloidosis. J Card Fail. 2019;25:147–153. doi: 10.1016/j.cardfail.2019.01.006. 95. Fondazione IRCCS Policlinico San Matteo di Pavia. …

Метаболизм желчной кислоты в множестве склероза поражается и связан с риском подтвержденного ухудшения состояния здоровья.

КОЛИЧЕСТВО: Подлые кислоты (БА) стали важными посредниками в нейроинфламмации и нейродегенерации, которые являются важными особенностями множественного склероза (МС). Цель этого исследования состояла в изучении уровней сыворотки БА у недавно диагностировавшихся людей с MS (PwMS) и изучении их связи с ухудшением положения инвалидов. МЕТОДЫ: Исследование включало 907 ПТМС и 907 Сопоставимый контроль со стороны шведской группы ЭИМС, основанной на населении, с клиническими последующими данными шведского регистра MS. Уровни сыворотки BA были проанализированы с использованием масс-спектрометрии жидк

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… Progressive multiple sclerosis People with multiple sclerosis Relapsing-remitting multiple sclerosis Swedish MS Registry Sphingosine-1-phosphate receptor Taurocholic acid Taurochenodeoxycholic acid Taurodeoxycholic acid Taurohyocholic acid Taurolithocholic acid Tauroursodeoxycholic acid Ursodeoxycholic … acid Vitamin D receptor Authors’ contributions The EIMS cohort was conceptualized by IK, TO, AKH, and LA. …

Kidney Disease and Hematopoietic Stem Cell Transplantation.

Hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for patients with hematologic malignancies and certain solid tumors and nonmalignant hematologic conditions. Both AKI and CKD occur commonly after HSCT and are associated with significant morbidity and mortality. AKI and CKD in this setting may result from direct effects of the transplant or be caused by pretransplant bone marrow conditioning regimens and/or nephrotoxic agents administered in the post-transplant period. In this article, we review the epidemiology, risk factors, etiologies, pathophysiology, diagnos

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… acid for prevention are inconclusive; however, prophylactic administration has been associated with less liver toxicity, less aGVHD, and improved survival, supporting use. 66 , 70 The antithrombotic/fibrinolytic agent defibrotide is US Food and Drug Administration approved for the treatment of severe … Ursodeoxycholic acid for the prevention of hepatic complications in allogeneic stem cell transplantation . Blood. 2002 ; 100 ( 6 ): 1977 – 1983 . doi: 10.1182/blood-2001-12-0159 12200355 71. Mohty M Malard F Abecasis M , . …

Adjuvant doxycycline to enhance anti-amyloid effects: Results from the dual phase 2 trial.

BackgroundAlthough, doxycycline use is associated with improved outcomes in amyloidosis in retrospective studies, evidence from clinical trials is limited.MethodsThis phase 2 trial of doxycycline (clinicaltrials.gov: NCT02207556) in newly diagnosed light chain (AL) amyloidosis enrolled 25 patients with systemic AL amyloidosis on treatment with doxycycline for 1 year along with chemotherapy. Outcomes of interest included mortality, organ response, and hematologic response rates at 1 year.FindingsThe median age was 62 years, 64% were male, and 68% had the AL lambda subtype. Patients had Mayo 201

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… Clinical Experience With the Use of Doxycycline and Ursodeoxycholic Acid for the Treatment of Transthyretin Cardiac Amyloidosis. J Card Fail. 2019;25:147–153. doi: 10.1016/j.cardfail.2019.01.006. 19. Comenzo R.L., Reece D., Palladini G. …

Positive Anti-nuclear Antibody in Patients with Polyclonal Hypergammaglobulinemia Suggests the Presence of Multiple Distinct Comorbidities.

Objective Polyclonal hypergammaglobulinemia (PHGG) is a classic problem in internal medicine; however, its conditions and diagnostic procedures have not been well studied. We therefore conducted a retrospective study to characterize the PHGG disease spectrum. Methods We included all patients who underwent serum protein electrophoresis (SPEP) at a hematology tertiary referral center during a five-year period. For these patients, globulin clonality was determined and clinical data were extracted from the records. Results Out of 209 consecutive cases of hypergammaglobulinemia demonstrated by SPEP

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… Liver function was exacerbating, therefore, ursodeoxycholic acid was initiated with clear response, making the PBC diagnosis highly likely. At the same time, she experienced sicca syndrome. …

Liver disease during and after hematopoietic stem cell transplantation in adults: a single-center Egyptian experience.

BACKGROUND: Hepatic complications are a well-known cause of both early and late mortality and morbidity in hematopoietic stem cell transplant (HSCT) recipients. Early diagnosis and management of hepatic complications is important in order to commence appropriate therapy. Conditioning regimens, acute and chronic graft versus host disease, sinusoidal obstruction syndrome, and infections among others represent major hepatic complications for the transplant recipient. We assessed liver function tests, viral markers, polymerase chain reaction, abdominal ultrasound, portal, and hepatic venous duplex

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… Galactomannan in blood samples was performed in suspected cases of neutropenic patients who are not responsive to neutropenic fever protocol ursodeoxycholic acid used as prophylactic agent to prevent liver injury. …

Роль кишечника микробиота-митохондрия в нейродегенерации: основополагающие механизмы и потенциальные методы лечения.

Появляющиеся данные свидетельствуют о том, что микробиота кишечника тесно связана с патологическими проявлениями множественных нейродегенеративных заболеваний через ось кишечника, которая относится к перекрестку между кишечником и центральной нервной системой. Еще важнее то, что митохондрия считается выдающимся посредником взаимодействия между кишечной микробиотой и мозгом. Кишечные микробы могут модифицировать функцию митохондриала в центральной нервной системе, чтобы повлиять на развитие нейродегенеративных заболеваний. Митохондрия необходима для удовлетворения значительных потребностей носи

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… acid Ameliorated neuro–mitochondrial damage Bcl-2/Bax Suppression of neuron death and sensorimotor deficits hd, pd Keene et al., 2001, 2002; Abdelkader et al., 2016 Tauroursodeoxycholic acid Regulated mitochondrial autophagy; Restored mitochondrial structure abnormalities (mitochondrial swelling and … Ursodeoxycholic acid (UDCA), lithocholic acid, and deoxycholic acid are common secondary bile acids. …