TY  - JOUR
AB  - Despite recent progress in the diagnosis and treatment of advanced cancers, the overall patient treatment outcome did not substantially improve over the last years. Therefore, developing novel therapies, which may also work synergistically in combination with the conventional therapies is crucial. One promising new therapeutic approach is bacterium-mediated cancer therapy. In the current work, we describe the influence of the gut microbiome and intranasal E. coli Nissle applications on the metabolism in cancer tissues of 4T1 syngeneic tumor bearing mice. Here we found that after gut microbiome depletion and/or E. coli Nissle treatment the ratios of ADMA/Arginine, Putrescine/Ornithine and Kynurenine/Tryptophan as well as the total concentration of Carnosine, Kynurenine and H1 (synonymus for all sugars detectable) are significantly altered in tumor tissues of as the result of treatment. In conclusion, our current data show that E. coli Nissle bacteria facilitating metabolic modulation of tumors, a finding could be important for improved cancer therapy in patients.
AU  - Cecil, A.
AU  - Gentschev, I.*
AU  - Prehn, C.
AU  - Hauck, S.M.
AU  - Witting, M.
AU  - Petrov, I.*
AU  - Ye, M.*
AU  - Othman, E.M.*
AU  - Szalay, A.A.*
C1  - 76049
C2  - 58380
TI  - Endogenous gut microbiome and implanted intranasal E. coli-Nissle modulate cancer tissues metabolism in 4T1 syngeneic tumor bearing mice.
JO  - BIOMED. PHARMACOTHER.
VL  - 193
PY  - 2025
SN  - 1950-6007
ER  - 

TY  - JOUR
AB  - In Wilson disease (WD), excess copper provokes hepatocyte death due to impaired copper excretion, ultimately causing either acute or chronic liver damage. Current therapeutic compounds fail to reduce hepatic copper near to physiological levels, leaving lifelong, several times daily treatment as the only choice for patients. We have previously shown that a bacteria-derived methanobactin, termed ARBM-101, most efficiently depleted excess liver copper in still healthy WD rats. Here we report, for the first time, that mechanistically this is due to endosomal/lysosomal/exosomal trafficking of ARBM-101 in WD hepatocytes, allowing for copper mass excretion via the biliary/fecal route. We further show that such liver copper excretion occurs within minutes in vivo to detect copper-bound ARBM-101 in feces. This efficacy allows for specialized treatment regimen to rescue acute liver failure in WD rats. Moreover, also shown for the first time, it avoids fibrosis development in WD mice. Thus, judging from the results in two rodent species and human hepatocytes, this study advocates the development of ARBM-101 for WD therapy.
AU  - Engler, J.*
AU  - Kim, E.J.*
AU  - Kim, D.*
AU  - Shibata, N.M.*
AU  - Lynderup, E.M.*
AU  - Vendelbo, M.H.*
AU  - Akdogan, B.
AU  - Sailer, J.*
AU  - Fontes, A.
AU  - Eberhagen, C.
AU  - Rieder, T.*
AU  - Reinold, Q.*
AU  - Lee, H.*
AU  - Park, D.*
AU  - Jung, C.*
AU  - Im, W.*
AU  - Wudy, S.I.*
AU  - Kleigrewe, K.*
AU  - Engelhardt, S.*
AU  - DiSpirito, A.A.*
AU  - Sandahl, T.D.*
AU  - Medici, V.*
AU  - Eun, S.Y.*
AU  - Zischka, H.
C1  - 76198
C2  - 58469
TI  - Rapid transcellular hepatic copper depletion by ARBM-101 rescues severe liver damage in Wilson disease rodents.
JO  - BIOMED. PHARMACOTHER.
VL  - 193
PY  - 2025
SN  - 1950-6007
ER  - 

TY  - JOUR
AB  - BACKGROUND: 1,25(OH)2D3 is a fat-soluble vitamin, involved in regulating Ca2+ homeostasis in the body. Its storage in adipose tissue depends on the fat content of the body. Obesity is the result of abnormal lipid deposition due to the prolonged positive energy balance and increases the risk of several cancer types. Furthermore, it has been associated with vitamin D deficiency and defined as a low 25(OH)2D3 blood level. In addition, 1,25(OH)2D3 plays vital roles in Ca2+-Pi and glucose metabolism in the adipocytes of obese individuals and regulates the expressions of adipogenesis-associated genes in mature adipocytes. SCOPE AND APPROACH: The present contribution focused on the VDR mediated mechanisms interconnecting the obese condition and cancer proliferation due to 1,25(OH)2D3-deficiency in humans. This contribution also summarizes the identification and development of molecular targets for VDR-targeted drug discovery. KEY FINDINGS AND CONCLUSIONS: Several studies have revealed that cancer development in a background of 1,25(OH)2D3 deficient obesity involves the VDR gene. Moreover, 1,25(OH)2D3 is also known to influence several cellular processes, including differentiation, proliferation, and adhesion. The multifaceted physiology of obesity has improved our understanding of the cancer therapeutic targets. However, currently available anti-cancer drugs are notorious for their side effects, which have raised safety issues. Thus, there is interest in developing 1,25(OH)2D3-based therapies without any side effects.
AU  - Gupta, V.K.*
AU  - Sahu, L.*
AU  - Sonwal, S.*
AU  - Suneetha, A.*
AU  - Kim, D.H.*
AU  - Kim, J.*
AU  - Verma, H.K.
AU  - Pavitra, E.*
AU  - Raju, G.S.R.*
AU  - Bhaskar, L.*
AU  - Lee, H.U.*
AU  - Huh, Y.S.*
C1  - 70949
C2  - 55896
CY  - 65 Rue Camille Desmoulins, Cs50083, 92442 Issy-les-moulineaux, France
TI  - Advances in biomedical applications of vitamin D for VDR targeted management of obesity and cancer.
JO  - BIOMED. PHARMACOTHER.
VL  - 177
PB  - Elsevier France-editions Scientifiques Medicales Elsevier
PY  - 2024
SN  - 1950-6007
ER  - 

TY  - JOUR
AB  - Sickle cell disease (SCD) is the most severe monogenic hemoglobinopathy caused by a single genetic mutation that leads to repeated polymerization and depolymerization of hemoglobin resulting in intravascular hemolysis, cell adhesion, vascular occlusion, and ischemia-reperfusion injury. Hemolysis causes oxidative damage indirectly by generating reactive oxygen species through various pathophysiological mechanisms, which include hemoglobin autoxidation, endothelial nitric oxide synthase uncoupling, reduced nitric oxide bioavailability, and elevated levels of asymmetric dimethylarginine. Red blood cells have a built-in anti-oxidant system that includes enzymes like sodium dismutase, catalase, and glutathione peroxidase, along with free radical scavenging molecules, such as vitamin C, vitamin E, and glutathione, which help them to fight oxidative damage. However, these anti-oxidants may not be sufficient to prevent the effects of oxidative stress in SCD patients. Therefore, in line with a recent FDA request that the focus to be placed on the development of innovative therapies for SCD that address the root cause of the disease, there is a need for therapies that target oxidative stress and restore redox balance in SCD patients. This review summarizes the current state of knowledge regarding the role of oxidative stress in SCD and the potential benefits of anti-oxidant therapies. It also discusses the challenges and limitations of these therapies and suggests future directions for research and development.
AU  - Pavitra, E.*
AU  - Acharya, R.K.*
AU  - Gupta, V.K.*
AU  - Verma, H.K.
AU  - Kang, H.*
AU  - Lee, J.H.*
AU  - Sahu, T.*
AU  - Bhaskar, L.*
AU  - Raju, G.S.R.*
AU  - Huh, Y.S.*
C1  - 70788
C2  - 55747
CY  - 65 Rue Camille Desmoulins, Cs50083, 92442 Issy-les-moulineaux, France
TI  - Impacts of oxidative stress and anti-oxidants on the development, pathogenesis, and therapy of sickle cell disease: A comprehensive review.
JO  - BIOMED. PHARMACOTHER.
VL  - 176
PB  - Elsevier France-editions Scientifiques Medicales Elsevier
PY  - 2024
SN  - 1950-6007
ER  - 

TY  - JOUR
AB  - BACKGROUND: The immunomodulatory imide drugs (IMiDs) thalidomide, lenalidomide and pomalidomide may exhibit therapeutic efficacy in the prostate. In lower urinary tract symptoms (LUTS), voiding and storage disorders may arise from benign prostate hyperplasia, or overactive bladder. While current therapeutic options target smooth muscle contraction or cell proliferation, side effects are mostly cardiovascular. Therefore, we investigated effects of IMiDs on human detrusor and porcine artery smooth muscle contraction, and growth-related functions in detrusor smooth muscle cells (HBdSMC). METHODS: Cell viability was assessed by CCK8, and apoptosis and cell death by flow cytometry in cultured HBdSMC. Contractions of human detrusor tissues and porcine interlobar and coronary arteries were induced by contractile agonists, or electric field stimulation (EFS) in the presence or absence of an IMID using an organ bath. Proliferation was assessed by EdU assay and colony formation, cytoskeletal organization by phalloidin staining, RESULTS: Depending on tissue type, IMiDs inhibited cholinergic contractions with varying degree, up to 50 %, while non-cholinergic contractions were inhibited up to 80 % and 60 % for U46619 and endothelin-1, respectively, and EFS-induced contractions up to 75 %. IMiDs reduced viable HBdSM cells in a time-dependent manner. Correspondingly, proliferation was reduced, without showing pro-apoptotic effects. In parallel, IMiDs induced cytoskeletal disorganization. CONCLUSIONS: IMiDs exhibit regulatory functions in various smooth muscle-rich tissues, and of cell proliferation in the lower urinary tract. This points to a novel drug class effect for IMiDs, in which the molecular mechanisms of action of IMiDs merit further consideration for the application in LUTS.
AU  - Tamalunas, A.
AU  - Wendt, A.*
AU  - Springer, F.*
AU  - Vigodski, V.*
AU  - Trieb, M.*
AU  - Eitelberger, N.*
AU  - Poth, H.*
AU  - Ciotkowska, A.*
AU  - Rutz, B.*
AU  - Hu, S.*
AU  - Schulz, H.*
AU  - Ledderose, S.*
AU  - Rogenhofer, N.*
AU  - Kolben, T.*
AU  - Nößner, E.
AU  - Stief, C.G.*
AU  - Hennenberg, M.*
C1  - 71085
C2  - 55953
CY  - 65 Rue Camille Desmoulins, Cs50083, 92442 Issy-les-moulineaux, France
TI  - Immunomodulatory imide drugs inhibit human detrusor smooth muscle contraction and growth of human detrusor smooth muscle cells, and exhibit vaso-regulatory functions.
JO  - BIOMED. PHARMACOTHER.
VL  - 177
PB  - Elsevier France-editions Scientifiques Medicales Elsevier
PY  - 2024
SN  - 1950-6007
ER  - 

TY  - JOUR
AB  - BACKGROUND: The intensified search for low-threshold herbal anti-viral drugs would be of great advantage in prevention of early stages of infection. Since the SARS-CoV-2 Omicron variant has prevailed in western countries, the course has only been mild, but there are still no widely available drugs that can alleviate or shorten disease progression and counteract the development of Long-COVID. This study aimed to investigate the antiviral effects of a CO2-extract from Petasites hybridus (Ze 339). METHODS: We analyzed the infection and replication rate of SARS-CoV-2 in primary normal human bronchial epithelial cells (NHBEs) using a GFP-expressing version of the wild-type SARS-CoV-2 virus and live cell imaging. Upon infection with a clinical isolate of the Omicron variant, viral RNA content was quantified, and plaque assays were performed. In addition, the human transcriptome was analyzed after 4- and 24-hours post infection using whole genome microarrays. RESULTS: Ze 339 had a protective effect on primary airway epithelial cells during SARS-CoV-2 infection and impeded SARS-CoV-2 infection and replication in NHBE. Notably, Ze 339 inhibited the expression of infection-induced IFNA10 by 8.6-fold (p < 0.05) and additionally reduced a wide range of other interferons (IFNA6, IFNA7, IFNA8, IFNA21, IFNE, IFNW1). CONCLUSION: Thereby, Ze 339 attenuated epithelial infection by SARS-CoV-2 and modeled the IFN response. In conclusion, this study highlights Ze 339 as a potential treatment option for COVID-19 that limits infection-associated cell intrinsic immune responses.
AU  - Jakwerth, C.A.
AU  - Grass, V.*
AU  - Erb, A.
AU  - Pichlmair, A.*
AU  - Boonen, G.*
AU  - Butterweck, V.*
AU  - Schmidt-Weber, C.B.
C1  - 68937
C2  - 53779
CY  - 65 Rue Camille Desmoulins, Cs50083, 92442 Issy-les-moulineaux, France
TI  - Inhibition of SARS-CoV-2 infection and replication by Petasites hybridus CO2-extract (Ze 339).
JO  - BIOMED. PHARMACOTHER.
VL  - 170
PB  - Elsevier France-editions Scientifiques Medicales Elsevier
PY  - 2023
SN  - 1950-6007
ER  - 

TY  - JOUR
AB  - The phenomenon of autorosette formation was investigated by incubating the peripheral blood mononuclear cells of 5 normal persons with a series of monoclonal antibodies and an FITC-labelled second layer before allowing them to bind to autologous red blood cells. The antibodies used were OKT3, OKT4, OKT5, OKM1 and OKIa1, defining mature T cells, the inducer and suppressor subsets of T cells, monocytes and Ia antigen bearing cells, respectively. By this procedure the percentage of autorosette-forming cells was only slightly decreased. With this double marker analysis, the percentage of fluorescent cells among cells forming autologous rosettes was approximately the same as in the total mononuclear cell population before rosetting. In conclusion we could demonstrate that autologous rosettes in man may be formed by T and probably B lymphocytes as well as by monocytes and that there is no preference for the inducer and suppressor subsets of T lymphocytes.
AU  - Munker, R.
AU  - Stünkel, K.G.E.
AU  - Thierfelder, S.S.
C1  - 41052
C2  - 40461
SP  - 210-212
TI  - Characterization of autologous rosette-forming cells with a series of monoclonal antibodies.
JO  - BIOMED. PHARMACOTHER.
VL  - 36
IS  - 4
PY  - 1982
SN  - 1950-6007
ER  -