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A Case of Light Chain Deposition Disease Leading to Acute Liver Failure and Review of Literature.

Light chain deposition disease (LCDD) is a monoclonal immunoglobulin deposition disease characterized by light chain deposition in soft tissues and viscera, causing systemic organ dysfunction with an underlying lymphoproliferative disorder. While the kidney is the most affected organ, cardiac and hepatic involvement is also seen with LCDD. Hepatic manifestation can range from mild hepatic injury to fulminant liver failure. Herein, we are presenting a case of an 83-year-old woman with a monoclonal gammopathy of undetermined significance (MGUS), who presented to our institution with acute liver

The Problem of Molecular Target Choice for CAR-T Cells in Acute Myeloid Leukemia Therapy.

Recently, the chimeric antigen receptor (CAR)-T approach represented a breakthrough in the treatment of B-cell malignancies, encouraging the application of the approach for other hematological diseases, such as acute myeloid leukemia (AML). Heterogeneity and antigen variation in the pathological cell population hinder the choice of molecular targets in the case of AML. In this review, the critical aspects were described that are usually considered when selecting molecular targets for the new CAR genetic constructs. The role of AML-associated antigens in AML progression was covered. In conclusi

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… Additionally, this marker is synthesized by neutrophils, NK cells, B cells, and Kupffer cells in the liver [ 36 ]. The transmembrane protein Siglec-3 carries an intracellular inhibitory ITIM (immunoreceptor tyrosine-based inhibition motif) domain [ 35 ]. … Interestingly, hepatotoxicity was not observed despite the CD33 expression by Kupffer cells. Thereby one can propose the lack of CAR-T cell tissue infiltration. 4.3. …

Aptamer Therapeutics in Cancer: Current and Future.

Aptamer-related technologies represent a revolutionary advancement in the capacity to rapidly develop new classes of targeting ligands. Structurally distinct RNA and DNA oligonucleotides, aptamers mimic small, protein-binding molecules and exhibit high binding affinity and selectivity. Although their molecular weight is relatively small-approximately one-tenth that of monoclonal antibodies-their complex tertiary folded structures create sufficient recognition surface area for tight interaction with target molecules. Additionally, unlike antibodies, aptamers can be readily chemically synthesize

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… Infiltration of mononuclear cells and hypertrophy of Kupffer cells in the liver as well as basophilic granules in the cytoplasm of tubular epithelial cells in the kidneys were reported [ 71 , 72 , 73 ]. Liver metabolism of oligonucleotides may result in hepatotoxicity. … Kang et al. reported no definitive evidence of sinusoidal dilation, Kupffer cell hypertrophy, or perivascular inflammatory infiltrate in the liver after intravenous bolus injection of E-selectin antagonistic thioaptamer (ESTA) at a dose up to 500 μg twice weekly for 4 weeks, compared to saline injected …

Диметилфумарат уменьшает травму от печени ишемии и реперуляции путем подавления сигнала CGAS-STING.

Повреждение печени во время периоперационной фазы операции на печени часто происходит в результате печени. Неправильная активация сигнала СТИНГ может вызвать чрезмерную воспламенение реакции на усугубление печени. Диметилфумарат (DMF) — разрешенный УЛХ иммунодулятор, используемый для лечения множественного склероза и псориаза в силу его заметных свойств против воспаления. Однако механизм и целевые показатели ДМФ в области иммуномодуляции остаются неясными. Здесь мы обнаружили, что DMF подавляет активацию CGAS-STING, индуцируемую HSV-1, ДНК яичек и митохондриальная ДНК в различных клетках. DMF

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… Previous research has shown that Kupffer cells and hepatocytes play a crucial role in liver I/R injury. 13 , 34 Emerging studies suggest that the cGAS‐STING pathway is intimately linked to hepatic I/R injury and may serve as a promising therapeutic target for its management and prevention. …

Glycoprotein YKL-40: a novel biomarker of chronic graft-vs-host disease activity and severity?

AimTo investigate whether increased YKL-40 levels positively correlate with graft-vs-host disease (cGVHD) activity and severity and if YKL-40 could serve as a disease biomarker.MethodsThis case-control study was conducted at the University Hospital Centre Zagreb from July 2013 to October 2015. 56 patients treated with hematopoietic stem cell transplantation (HSCT) were included: 35 patients with cGVHD and 21 without cGVHD. There was no difference between groups in age, sex, median time from transplant to study enrollment, intensity of conditioning, type of donor, or source of stem cells. Blood

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… Scand J Clin Lab Invest 2004 64 57 62 10.1080/00365510410004092 15025429 39 Malaguarnera L Di Rosa M Zambito AM dell’Ombra N Nicoletti F Malaguarnera M Chitotriosidase gene expression in Kupffer cells from patients with non-alcoholic fatty liver disease. …

Dynamic roles of inflammasomes in inflammatory tumor microenvironment.

The inflammatory tumor microenvironment has been known to be closely connected to all stages of cancer development, including initiation, promotion, and progression. Systemic inflammation in the tumor microenvironment is increasingly being recognized as an important prognostic marker in cancer patients. Inflammasomes are master regulators in the first line of host defense for the initiation of innate immune responses. Inflammasomes sense pathogen-associated molecular patterns and damage-associated molecular patterns, following recruitment of immune cells into infection sites. Therefore, dysreg

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… Kupffer cells (resident macrophages in liver) and HCC cells have been known as major sources of IL-1β secretion in HCV-mediated progression of HCC 78 , 79 . … HCV-induced NLRP3 inflammasome activation in Kupffer cells led to increased serum levels of IL-1β in HCV-infected patients 78 , 79 . Necrotic debris of HCC cells formed under hypoxic conditions also induced secretion of IL-1β from macrophages in the HCC microenvironment 80 . …

Profile of eliglustat tartrate in the management of Gaucher disease.

Gaucher disease (GD) is a lysosomal storage disorder caused by the deficient activity of acid beta glucosidase, with consequent accumulation of glucosylceramide in the spleen, liver, bone marrow, and various organs and tissues. Currently, the gold standard for GD treatment is enzyme replacement therapy (ERT). The efficacy of ERT in improving or stabilizing the visceral and hematological symptoms of GD is well-proven. However, since ERT has to be administered by frequent intravenous infusions, this therapeutic approach has an important impact on the patient's quality of life. Eliglustat tartrat

Anticancer and cardio-protective effects of liposomal doxorubicin in the treatment of breast cancer.

Breast cancer (BC) is a highly prevalent disease, accounting for the second highest number of cancer-related mortalities worldwide. The anthracycline doxorubicin (DOX), isolated from Streptomyces peucetius var. caesius, is a potent chemotherapeutic drug that is successfully used to treat various forms of liquid and solid tumors and is currently approved to treat BC. DOX exerts its effects by intercalation into DNA and inhibition of topoisomerases I and II, causing damage to DNA and the formation of reactive oxygen species (ROS), resulting in the activation of caspases, which ultimately leads t

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… In addition, PEGylation of liposomes decreases their opsonization by immunoglobulin/ complement proteins and their uptake by phagocytic cells of the MPS (eg, Kupffer cells and splenic macrophages), thus prolonging the agent’s plasma circulation time. …

"Complimenting the Complement": Mechanistic Insights and Opportunities for Therapeutics in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and a leading cause of death in the US and worldwide. HCC remains a global health problem and is highly aggressive with unfavorable prognosis. Even with surgical interventions and newer medical treatment regimens, patients with HCC have poor survival rates. These limited therapeutic strategies and mechanistic understandings of HCC immunopathogenesis urgently warrant non-palliative treatment measures. Irrespective of the multitude etiologies, the liver microenvironment in HCC is intricately associated with chronic

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… Correspondingly, CCL5 promotes fibrogenic responses via resident Kupffer cells, bone marrow-derived macrophages, and HSCs ( 100 ) necessary for development of HCC. … Complement activation within the liver may therefore contribute to the development of HCC by several mechanisms, for example, via activation of NF-κB in Kupffer cells and STAT3 in hepatocytes. …

Advanced Diagnostic Techniques

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Полнотрансформатная ретиноидальная кислота в гематологическое расстройство: не только острая промиелоцитическая лейкемия.

Всетранс-ретиноиновая кислота (ATRA) играет определенную роль в развитии тканей, нейронной функции, воспроизводстве, зрение, росте и дифференциации клеток, иммунитете от опухоли и апоптозе. АТРА может действовать, вызывая автофагическую сигнализацию, ангиогенез, клеточную дифференциацию, апоптоз и иммунную функцию. В крови ATRA впервые с большим успехом использовалась в острой промиелоцитической лейкемии (APL), где ATRA дифференцировала клетки лейкемии на зрелые гранулоциты. АТРА может играть определенную роль не только в ППН, но и в других гематоологических заболеваниях, таких, как иммунная т

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… ATRA-mediated crosstalk between hepatic stellate cells and Kupffer cells promotes the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) activation, inhibits autophagy, and aggravates acute liver injury ( Yu et al., 2022 ). … ATRA-mediated-crosstalk between stellate cells and Kupffer cells inhibits autophagy and promotes NLRP3 activation in acute liver injury. Cell. Signal. 93, 110304. 10.1016/j.cellsig.2022.110304 Zhang W., Zhou F., Cao X., Cheng Y., He A., Liu J., et al. (2006). …

Glycoprotein Non-Metastatic Protein B: An Emerging Biomarker for Lysosomal Dysfunction in Macrophages.

Several diseases are caused by inherited defects in lysosomes, the so-called lysosomal storage disorders (LSDs). In some of these LSDs, tissue macrophages transform into prominent storage cells, as is the case in Gaucher disease. Here, macrophages become the characteristic Gaucher cells filled with lysosomes laden with glucosylceramide, because of their impaired enzymatic degradation. Biomarkers of Gaucher cells were actively searched, particularly after the development of costly therapies based on enzyme supplementation and substrate reduction. Proteins selectively expressed by storage macrop

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… In LDLR, -/- mice fed a HCD a 300-fold induction of Gpnmb was found in liver, most likely in Kupffer cells [ 166 ]. Interestingly, GPNMB was also found to be increased in human subjects with fatty liver disease. … In the liver, a less pronounced induction of GPNMB was detected in Kupffer cells. Consistently, increased lysosomal volume occurs in obese adipose macrophages [ 169 ]. Also in human obese adipose tissue, GPNMB expression was found to be increased [ 132 ]. …

Twenty-five years of type I interferon-based treatment: a critical analysis of its therapeutic use.

The clinical exploitation of type I interferon (IFN) as an antiviral and antineoplastic agent is based on the properties originally attributed to this cytokine family, with schedules reflecting only their antiviral and antiproliferative activities. Nevertheless, type I IFN has emerged as a central activator of the innate immunity. As current schedules of treatment for chronic hepatitis C and for hematological and solid tumors, based on the continuous administration of recombinant type I IFN or pegylated formulations, disregard viral resistance, host genetic variants predicting treatment outcom

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… The up-regulation of ISGs in liver-derived biopsies of chronically HCV infected patients is largely sustained by hepatocytes [86] , although Kupffer cells can be a local source of IFN that promoted basal expression of ISG in hepatocytes of non-responders [87] . … Innate immune tolerance and the role of kupffer cells in differential responses to interferon therapy among patients with HCV genotype 1 infection Gastroenterology 144 2013 402 413 e12 23123437 10.1053/j.gastro.2012.10.044 PMC3822610 88 Bolen C.R. Ding S. Robek M.D. Kleinstein S.H. …

Amino acid metabolism in immune cells: essential regulators of the effector functions, and promising opportunities to enhance cancer immunotherapy.

Amino acids are basic nutrients for immune cells during organ development, tissue homeostasis, and the immune response. Regarding metabolic reprogramming in the tumor microenvironment, dysregulation of amino acid consumption in immune cells is an important underlying mechanism leading to impaired anti-tumor immunity. Emerging studies have revealed that altered amino acid metabolism is tightly linked to tumor outgrowth, metastasis, and therapeutic resistance through governing the fate of various immune cells. During these processes, the concentration of free amino acids, their membrane bound tr

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… Tissue-resident macrophages have various names tied to their specific function including microglia, Kupffer cells, alveolar macrophages, and osteoclasts [ 190 - 193 ]. In physiological conditions, tissue-resident macrophages play an important role in tissue homeostasis and organ development. … As for homeostasis, Kupffer cells efficiently phagocytize pathogens entering from the portal or arterial circulation [ 191 ], and are essential for cholesterol transport to link lipid metabolism in the liver [ 196 ]. …

Exosomes and organ-specific metastasis.

The transmission of information between tumor cells and other cell types in the tumor microenvironment plays an important role in tumor metastasis and is critically modulated by exosomes and other mediators. Tumor-derived exosomes can promote epithelial-mesenchymal transition, angiogenesis, immune escape, formation of the pre-metastatic microenvironment, and transmission of drug-resistant molecules, thereby promoting tumor growth, invasion, and metastasis. Integrins are important regulatory molecules on exosomes that can locate metastatic cells at the initial stage of metastasis and show good

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… Second, macrophage MIF, an important component of pancreatic cancer exosomes, promotes fibrotic cytokine secretion after fusion with Kupffer cells, activates fibrotic pathways, and ultimately establishes a pro-inflammatory environment for metastasis. … cells and increase liver metastasis. …

Novel Insights into the Links between N6-Methyladenosine and Regulated Cell Death in Musculoskeletal Diseases.

Musculoskeletal diseases (MSDs), including osteoarthritis (OA), osteosarcoma (OS), multiple myeloma (MM), intervertebral disc degeneration (IDD), osteoporosis (OP), and rheumatoid arthritis (RA), present noteworthy obstacles associated with pain, disability, and impaired quality of life on a global scale. In recent years, it has become increasingly apparent that N6-methyladenosine (m6A) is a key regulator in the expression of genes in a multitude of biological processes. m6A is composed of 0.1-0.4% adenylate residues, especially at the beginning of 3'-UTR near the translation stop codon. The m

Burden, Outcome, and Comorbidities of Extrahepatic Manifestations in Hepatitis B Virus Infections.

Hepatitis B virus (HBV) infections affect approximately 296 million people around the world, and the prevalence of any past or present HBV infection during the years 2015-2018 was as high as 4.3%. Acute HBV infection often presents with nonspecific symptoms and is usually self-limited, but 5% of patients can have persistent infections leading to chronic HBV infection and the risk of turning into chronic HBV infection is significantly higher in babies with vertical transmission (95%). Patients with chronic HBV infection are usually asymptomatic, but 15 to 40% of chronic HBV carriers develop cir

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… The CD8 Kupffer cells detected in liver biopsies in HAAA patients may be the mediator of this condition [ 38 ]. Treatment of this disorder includes both supportive treatment and definitive treatment. Supportive treatment comprises specific blood product transfusion. … Hepatitis associated with aplastic anemia: Do CD8(+) kupffer cells have a role in the pathogenesis? Dig. Dis. Sci. 2007;52:2438–2443. doi: 10.1007/s10620-006-9280-4. 44. Patel K.R., Bertuch A., Sasa G.S., Himes R.W., Wu H. Features of Hepatitis in Hepatitis-associated Aplastic Anemia. J. Pediatr. …

Advances in the Study of Denosumab Treatment for Osteoporosis and Sarcopenia in the Chinese Middle-Aged and Elderly Population.

Osteosarcopenia (OS) is a geriatric syndrome characterized by the concurrent presence of osteoporosis and sarcopenia, predominantly affecting the elderly population. Osteoporosis (OP) is a systemic skeletal disorder characterized by decreased bone mass, compromised bone microarchitecture, and heightened bone fragility, substantially elevating fracture risk. Sarcopenia (SP) is defined by decreased muscle mass, strength, and/or functional capacity. Both conditions are age-related degenerative diseases with overlapping pathophysiological mechanisms, commonly co-occurring in elderly individuals an

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… Conversely, exposure to RANKL in primary hepatocytes directly stimulates the NF-κB pathway, resulting in the upregulation of pro-inflammatory genes and activation of Kupffer cells. …

Gaucher: A Systematic Review on Oral and Radiological Aspects.

Background and Objectives: Gaucher disease (GD) is a lysosomal storage disorder with the genetic autosomal recessive transmission. Bone involvement is a prevalent finding in Gaucher disease. It causes deformity and limits daily activities and the quality of life. In 75% of patients, there is bone involvement. This review aims to evaluate the principal findings in the jaw by a Cone-beam computed tomography (CBTC) and X-ray orthopantomography; Materials and Methods: PubMed, Web of Science, Lilacs and Scopus were systematically searched until 31 December 2022. In addition, a manual search was per

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… The most affected organs in Gaucher disease are the liver and spleen, which increased in volume due to macrophage accumulation in Kupffer cells [ 11 ]. Nevertheless, portal hypertension is rare due to cirrhosis and fibrosis [ 4 ]. …

TAM-ing the CIA-Tumor-Associated Macrophages and Their Potential Role in Unintended Side Effects of Therapeutics for Cancer-Induced Anemia.

Cancer-induced anemia (CIA) is a common consequence of neoplasia and has a multifactorial pathophysiology. The immune response and tumor treatment, both intended to primarily target malignant cells, also affect erythropoiesis in the bone marrow. In parallel, immune activation inevitably induces the iron-regulatory hormone hepcidin to direct iron fluxes away from erythroid progenitors and into compartments of the mononuclear phagocyte system. Moreover, many inflammatory mediators inhibit the synthesis of erythropoietin, which is essential for stimulation and differentiation of erythroid progeni

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… In situations when this capacity of RPM to take up damaged RBC (dRBC) and to recycle iron is overwhelmed, such as in massive hemolysis, Kupffer cells (KC) in the liver take over RBC uptake and degradation as a back-up mechanism. … Erythropoietin enhances Kupffer cell number and activity in the challenged liver. Sci Rep (2017) 7(1):10379. 10.1038/s41598-017-11082-7 183. Li X, Yao W, Yuan Y, Chen P, Li B, Li J, et al. …