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Elevated Macrophage Migration Inhibitory Factor 1 Is Associated with Left and Right Ventricular Systolic Dysfunction in Heart Failure with Reduced Ejection Fraction.

Background/Objectives: Low-grade systemic inflammation, characteristic of heart failure (HF), is a nonspecific inflammatory syndrome that affects the entire body. Macrophage migration inhibitory factor 1 (MIF-1) is a pro-inflammatory cytokine, a key mediator of the innate immune response, and may serve as a potential biomarker of monocyte homing and activation in HF with reduced and mildly reduced ejection fraction (HFrEF, HFmrEF). Methods: We evaluated 70 hemodynamically stable patients with left ventricular EF (LVEF) < 50% by means of echocardiography and blood sampling. Results: We report s

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… Milatuzumab, an anti-CD74 humanized monoclonal antibody, is currently approved for the treatment of refractory multiple myeloma [ 24 ], while the CD74 receptor antagonist, RTL1000, is under investigation for multiple sclerosis [ 25 ]. …

The impact of pharmaceutical innovation on the burden of disease in Ireland, 2000-2015.

BackgroundWe perform an econometric assessment of the impact that pharmaceutical innovation had on the burden of disease in Ireland.MethodsWe use a difference-in-differences (or two-way fixed effects) research design: we investigate whether diseases for which more new drugs were launched had larger subsequent reductions in mortality. This design controls for the effects of general economic and societal factors (e.g. income, education, and behavioral risk factors), to the extent that those effects are similar across diseases.ResultsNew Chemical Entities launched during 1983-1997 are estimated t

Grading of minor salivary gland immuno-histopathology post-allogenic hematopoietic cell transplantation.

The oral cavity commonly displays mucosal lichenoid lesions and salivary gland dysfunction, which are considered different chronic Graft-versus-Host Disease (cGVHD) pathophysiology's. However, diagnostics of salivary gland (sg-)cGVHD are limited. The objectives of the current study are to evaluate the minor salivary gland (MSG) histo-immunopathological profiles post allogenic hematopoietic cell transplantation based on sg-cGVHD criteria. Design: Histopathology was characterized according to two published grading strategies. Firstly, the National Institute of Health (NIH) assessed peri-ductal/a

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… Dynamic changes in brain mesenchymal perivascular cells associate with multiple sclerosis disease duration, active inflammation, and demyelination. Stem Cells Transl. Med. 2017;6(10):1840–1851. doi: 10.1002/sctm.17-0028. 29. …

Amyloidoses in Onco-Nephrology Practice: A Multidisciplinary Case-Based Conference Report.

Introduction and objectiveAmyloidoses are a heterogeneous group of disorders resulting from deposition of amyloid fibrils into extracellular tissues. While the kidneys are one of the most frequent sites of amyloid deposition, amyloid deposits can also affect a wide range of organ systems, including the heart, liver, gastrointestinal tract, and peripheral nerves. The prognosis of amyloidosis, especially with cardiac involvement, remains poor; however, a collaborative approach applying new tools for diagnosis and management may improve outcomes. In September 2021, the Canadian Onco-Nephrology In

Оценка потребностей в паллиативном уходе у пациентов с повышенными хроническими условиями, не связанными с малиньяном: общий обзор инструментов оценки потребностей.

ЦЕЛИ: Пациенты с повышенными хроническими заболеваниями, не связанными с заболеваниями, испытывают бремя заболеваний и потребности в паллиативном уходе, сопоставимые с потребностями онкологических пациентов, однако паллиативная помощь часто вводится с опозданием. Определение лиц с потенциальными потребностями в паллиативном уходе является сложным делом, и, несмотря на наличие многочисленных инструментов, наиболее подходящий подход к оценке потребностей этой группы населения остается неясным. Цель этого всеобъемлющего обзора заключалась в выявлении и оценке инструментов, используемых для систем

Treatment of Patients with Monoclonal Gammopathy of Clinical Significance.

Monoclonal gammopathy of undetermined significance (MGUS) is defined as the presence of a monoclonal protein (M-protein) produced by a small amount of plasma cells. The majority of patients remain asymptomatic; however, a fraction of them develop clinical manifestations related to the monoclonal gammopathy despite not fulfilling criteria of multiple myeloma or other lymphoproliferative disorder. These patients constitute an emerging clinical issue coined as monoclonal gammopathy of clinical significance (MGCS). The mechanisms involved are poorly understood, and literature is scarce regarding m

Ixazomib decreases the risk of chronic graft-versus-host disease: identification of cGVHD biomarkers.

AbstractChronic graft-versus-host disease (cGVHD) is the leading cause of long-term morbidity and mortality after allogeneic hematopoietic stem cell transplantation. We hypothesize that it is possible to decrease its risk by manipulating the immune response in late phases of transplantation. We performed a prospective randomized trial including 73 patients. Patients in the treatment arm received 4 mg of ixazomib (IXZ) every 28 days from day +100. With a median follow-up of 24 months, the cumulative incidence of moderate/severe cGVHD in the IXZ vs control groups at 1 and 2 years were: 3.23% vs

Pilot clinical and pharmacokinetic study of Δ9-Tetrahydrocannabinol (THC)/Cannabidiol (CBD) nanoparticle oro-buccal spray in patients with advanced cancer experiencing uncontrolled pain.

This pilot study aimed to assess the safety, tolerability, pharmacokinetics and exploratory analgesic effect of a novel water-soluble oro-buccal nanoparticle spray of a cannabis-based medicine (MDCNS-01) in patients with advanced incurable malignancy with unrelieved pain from opioid analgesic. The study was a non-blinded single arm 2 stage study. Stage I was a single escalating dose (n = 5) [2.5 mg Δ9-THC and 2.5 mg CBD) versus a 3-fold escalated dose. Stage II was an up-titrated dose in patients with advanced cancers and intractable pain (n = 25). During Stage I with an increased cannabis-bas

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… Efficacy and safety of cannabinoid oromucosal spray for multiple sclerosis spasticity . J Neurol Neurosurg Psychiatry . 2016 ; 87 ( 9 ): 944 – 51 . …

Analysis of microRNA expression profiles in exosomes derived from acute myeloid leukemia by p62 knockdown and effect on angiogenesis.

ObjectivesIn this study, we aimed to investigate the effect of p62 on angiogenesis and microRNA (miRNA) expression profiles in acute myeloid leukemia (AML) exosomes.MethodsAn Exiqon v19.0 microRNA MicroArray was used to profile miRNAs in exosomes derived from parental and p62-knockdown U937 cells. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to predict the biological functions and potential mechanisms of differentially expressed miRNAs in AML exosomes. Endothelial cell tube formation assays using human umbilical vein endothelial cells (HUVECs) w

The TNF-α/TNFR2 Pathway: Targeting a Brake to Release the Anti-tumor Immune Response.

Newly discovered anti-cancer immunotherapies, such as immune checkpoint inhibitors and chimeric antigen receptor T cells, focus on spurring the anti-tumor effector T cell (Teff) response. Although such strategies have already demonstrated a sustained beneficial effect in certain malignancies, a substantial proportion of treated patients does not respond. CD4+FOXP3+ regulatory T cells (Tregs), a suppressive subset of T cells, can impair anti-tumor responses and reduce the efficacy of currently available immunotherapies. An alternative view that has emerged over the last decade proposes to tackl

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… Exogenous activation of tumor necrosis factor receptor 2 promotes recovery from sensory and motor disease in a model of multiple sclerosis. Brain. Behav. Immun. 81 247–259. 10.1016/j.bbi.2019.06.021 Fischer R., Sendetski M., Del Rivero T., Martinez G. F., Bracchi-Ricard V., Swanson K. … Selective Modulation of TNF-TNFRs Signaling: Insights for Multiple Sclerosis Treatment. Front. Immunol. 9:925. 10.3389/fimmu.2018.00925 Pierik M., Vermeire S., Steen K. V., Joossens S., Claessens G., Vlietinck R., et al. (2004). …

Nephrotoxicity of recent anti-cancer agents.

Cancer patients may develop a variety of kidney lesions that impair not only their immediate survival but also limit the adequate treatment of the underlying malignant process. This review summarizes the nephrotoxic potential of some of the most recently developed anti-cancer drugs, focusing on those interfering with the vascular endothelial growth factor and epidermal growth factor receptor pathways and mammalian target of rapamycin inhibitors. Thrombotic microangiopathy (haemolytic-uraemic syndrome), proteinuria, hypertension and magnesium depletion are the most common side effects. Also the

Immunosenescence: signaling pathways, diseases and therapeutic targets.

Immunosenescence refers to the abnormal activation or dysfunction of the immune system as people age. Inflammaging is a typical pathological inflammatory state associated with immunosenescence and is characterized by excessive expression of proinflammatory cytokines in aged immune cells. Chronic inflammation contributes to a variety of age-related diseases, such as neurodegenerative disease, cancer, infectious disease, and autoimmune diseases. Although not fully understood, recent studies contribute greatly to uncovering the underlying mechanisms of immunosenescence at the molecular and cellul

Derivation and elimination of uremic toxins from kidney-gut axis.

Uremic toxins are chemicals, organic or inorganic, that accumulate in the body fluids of individuals with acute or chronic kidney disease and impaired renal function. More than 130 uremic solutions are included in the most comprehensive reviews to date by the European Uremic Toxins Work Group, and novel investigations are ongoing to increase this number. Although approaches to remove uremic toxins have emerged, recalcitrant toxins that injure the human body remain a difficult problem. Herein, we review the derivation and elimination of uremic toxins, outline kidney-gut axis function and relati

Genetic Regulation of Tryptase Production and Clinical Impact: Hereditary Alpha Tryptasemia, Mastocytosis and Beyond.

Tryptase is a serine protease that is predominantly produced by tissue mast cells (MCs) and stored in secretory granules together with other pre-formed mediators. MC activation, degranulation and mediator release contribute to various immunological processes, but also to several specific diseases, such as IgE-dependent allergies and clonal MC disorders. Biologically active tryptase tetramers primarily derive from the two genes TPSB2 (encoding β-tryptase) and TPSAB1 (encoding either α- or β-tryptase). Based on the most common gene copy numbers, three genotypes, 0α:4β, 1α:3β and 2α:2β, were defi

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… MC degranulation and mediator release have specifically been described in certain clinical settings and diseases, such as asthma, allergy, anaphylaxis, autoimmune diseases (e.g., multiple sclerosis, rheumatoid arthritis and type-1 diabetes) and MC-related disorders (mastocytosis and MC activation syndromes … Tryptase activates peripheral blood mononuclear cells causing the synthesis and release of TNF-alpha, IL-6 and IL-1 beta: Possible relevance to multiple sclerosis. J. Neuroimmunol. 2003;138:115–122. doi: 10.1016/S0165-5728(03)00090-0. 61. Compton S.J., Cairns J.A., Holgate S.T., Walls A.F. …

Early-stage IgM kappa proliferative glomerulonephritis with monoclonal immunoglobulin deposition presenting with atypical renal insufficiency: a case report and literature review.

INTRODUCTION: Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a rare subtype of monoclonal gammopathy of renal significance (MGRS). While the IgG subtype has been well characterized, the IgM-κ variant is extremely rare, with a low detection rate of circulating monoclonal proteins and limited real-world data on its clinical course under conservative management. This case report describes a biopsy-proven IgM-κ PGNMID in an elderly patient with negative hematological screening, to expand the current understanding of this rare entity. PATIENT CONCERNS AND DIAG

Мелатонин за пределами хронобиологии: интеграция фармакокинетики, прогнозирование дозы и клинические данные.

Мелатонин установлен в качестве регулятора времени и сна в циркадиане, в то время как более широкий спектр зависящих от рецептора и независимых от рецептора биологических эффектов вызвал интерес к дополнительным видам терапевтического применения. В этом обзоре критически рассматривается вопрос о том, можно ли интерпретировать эти предлагаемые последствия в фармакологических рамках, основанных на воздействии. Мы интегрируем недавние доклинические и клинические данные с фармакокинетиками перорального и внутривенного мелатонина и с обычным дифференциальном уравнением (ОДВ) - прогнозом воздействия

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… . | Geriatrics/delirium | PMCID PMC12853498 [ 93 ] | Primary progressive multiple sclerosis patients already receiving therapy | MELATOMS-1 safety/efficacy clinical study | Adjunctive high-dose oral melatonin; dose not shown in snippet | Hepatic safety and efficacy signals | Focused on hepatic safety … Sclerosis: Liver Toxicity Findings from a Phase I/II Randomised Clinical Trial (MELATOMS-1). …

Immune mechanisms and immunomodulatory therapies in steroid-resistant nephrotic syndrome.

Steroid-resistant nephrotic syndrome (SRNS) is a complex and refractory kidney disease generally causing chronic kidney dysfunction, characterized by persistent proteinuria despite prolonged corticosteroid therapy. This review comprehensively explores the mechanisms of immunity driving SRNS, mainly focusing on the complex function network within immune cells, pro-inflammatory cytokines, and podocyte injury. Current immunosuppressive therapies show limited efficacy, prompting exploration of precision immunomodulatory strategies. Emerging approaches include IL-17 or low-dose IL-12 modulation, pr

Antibodies to watch in 2023.

In this 14th installment of the annual Antibodies to Watch article series, we discuss key events in commercial monoclonal antibody therapeutics development that occurred in 2022 and forecast events that might occur in 2023. As of mid-November, 12 antibody therapeutics had been granted first approvals in either the United States or European Union (tebentafusp (Kimmtrak), faricimab (Vabysmo), sutimlimab (Enjaymo), relatlimab (Opdualag), tixagevimab/cilgavimab (Evusheld), mosunetuzumab (Lunsumio), teclistamab (TECVAYLI), spesolimab (SPEVIGO), tremelimumab (Imjudo; combo with durvalumab), nirsevim

Emerging Target Discovery Strategies Drive the Decoding of Therapeutic Power of Natural Products and Further Drug Development: A Case Study of Celastrol.

Celastrol (CEL) is a natural pentacyclic triterpenoid demonstrating significant therapeutic properties against various diseases. However, the ambiguity of target information poses a significant challenge in transitioning CEL from a traditional remedy to a modern pharmaceutical agent. Recently, the emerging target discovery approaches of natural products have broadened extensive avenues for uncovering comprehensive target information of CEL and promoting its drug development. Herein, diverse target discovery strategies are overviewed for the pharmacological and toxicological studies of CEL, inc

Unveiling the shared etiology between gastrointestinal disorders and valvular heart diseases through a genome-wide pleiotropy study.

This study explores the genetic link between gastrointestinal disorders and valvular heart disease (VHD), aiming to clarify shared mechanisms through a genome-wide pleiotropy analysis. We assessed the genetic correlation between six gastrointestinal disorders-including GERD, IBS, PUD, IBD, Crohn's disease, and ulcerative colitis-and VHD, employing methods like linkage disequilibrium score regression and pleiotropic analysis under a composite null hypothesis. Our results show significant genetic correlations, particularly with GERD (rg = 0.211), IBS (rg = 0.23), and PUD (rg = 0.21). Fifteen var