TY  - JOUR
A1  - Meyer, Malin Tordis
A1  - Watermann, Christoph
A1  - Dreyer, Thomas
A1  - Ergün, Süleyman
A1  - Karnati, Srikanth
T1  - 2021 update on diagnostic markers and translocation in salivary gland tumors
JF  - International Journal of Molecular Sciences
N2  - Salivary gland tumors are a rare tumor entity within malignant tumors of all tissues. The most common are malignant mucoepidermoid carcinoma, adenoid cystic carcinoma, and acinic cell carcinoma. Pleomorphic adenoma is the most recurrent form of benign salivary gland tumor. Due to their low incidence rates and complex histological patterns, they are difficult to diagnose accurately. Malignant tumors of the salivary glands are challenging in terms of differentiation because of their variability in histochemistry and translocations. Therefore, the primary goal of the study was to review the current literature to identify the recent developments in histochemical diagnostics and translocations for differentiating salivary gland tumors.
KW  - salivary gland tumors
KW  - epithelial salivary gland
KW  - adenoid cystic carcinoma (ACC)
KW  - pleomorphic adenoma
KW  - mucoepidermoid carcinoma
KW  - diagnostic markers
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-261057
SN  - 1422-0067
VL  - 22
IS  - 13
ER  - 
TY  - JOUR
A1  - Kleefeldt, Florian
A1  - Bömmel, Heike
A1  - Broede, Britta
A1  - Thomsen, Michael
A1  - Pfeiffer, Verena
A1  - Wörsdörfer, Philipp
A1  - Karnati, Srikanth
A1  - Wagner, Nicole
A1  - Rueckschloss, Uwe
A1  - Ergün, Süleyman
T1  - Aging‐related carcinoembryonic antigen‐related cell adhesion molecule 1 signaling promotes vascular dysfunction
JF  - Aging Cell
N2  - Aging is an independent risk factor for cardiovascular diseases and therefore of particular interest for the prevention of cardiovascular events. However, the mechanisms underlying vascular aging are not well understood. Since carcinoembryonic antigen‐related cell adhesion molecule 1 (CEACAM1) is crucially involved in vascular homeostasis, we sought to identify the role of CEACAM1 in vascular aging. Using human internal thoracic artery and murine aorta, we show that CEACAM1 is upregulated in the course of vascular aging. Further analyses demonstrated that TNF‐α is CEACAM1‐dependently upregulated in the aging vasculature. Vice versa, TNF‐α induces CEACAM1 expression. This results in a feed‐forward loop in the aging vasculature that maintains a chronic pro‐inflammatory milieu. Furthermore, we demonstrate that age‐associated vascular alterations, that is, increased oxidative stress and vascular fibrosis, due to increased medial collagen deposition crucially depend on the presence of CEACAM1. Additionally, age‐dependent upregulation of vascular CEACAM1 expression contributes to endothelial barrier impairment, putatively via increased VEGF/VEGFR‐2 signaling. Consequently, aging‐related upregulation of vascular CEACAM1 expression results in endothelial dysfunction that may promote atherosclerotic plaque formation in the presence of additional risk factors. Our data suggest that CEACAM1 might represent an attractive target in order to delay physiological aging and therefore the transition to vascular disorders such as atherosclerosis.
KW  - aging
KW  - anti‐aging
KW  - cytokines
KW  - inflammation
KW  - mouse
KW  - reactive oxygen species
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201231
VL  - 2019
IS  - 18
ER  - 
TY  - JOUR
A1  - Karnati, Srikanth
A1  - Seimetz, Michael
A1  - Kleefeldt, Florian
A1  - Sonawane, Avinash
A1  - Madhusudhan, Thati
A1  - Bachhuka, Akash
A1  - Kosanovic, Djuro
A1  - Weissmann, Norbert
A1  - Krüger, Karsten
A1  - Ergün, Süleyman
T1  - Chronic Obstructive Pulmonary Disease and the Cardiovascular System: Vascular Repair and Regeneration as a Therapeutic Target
JF  - Frontiers in Cardiovascular Medicine
N2  - Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide and encompasses chronic bronchitis and emphysema. It has been shown that vascular wall remodeling and pulmonary hypertension (PH) can occur not only in patients with COPD but also in smokers with normal lung function, suggesting a causal role for vascular alterations in the development of emphysema. Mechanistically, abnormalities in the vasculature, such as inflammation, endothelial dysfunction, imbalances in cellular apoptosis/proliferation, and increased oxidative/nitrosative stress promote development of PH, cor pulmonale, and most probably pulmonary emphysema. Hypoxemia in the pulmonary chamber modulates the activation of key transcription factors and signaling cascades, which propagates inflammation and infiltration of neutrophils, resulting in vascular remodeling. Endothelial progenitor cells have angiogenesis capabilities, resulting in transdifferentiation of the smooth muscle cells via aberrant activation of several cytokines, growth factors, and chemokines. The vascular endothelium influences the balance between vaso-constriction and -dilation in the heart. Targeting key players affecting the vasculature might help in the development of new treatment strategies for both PH and COPD. The present review aims to summarize current knowledge about vascular alterations and production of reactive oxygen species in COPD. The present review emphasizes on the importance of the vasculature for the usually parenchyma-focused view of the pathobiology of COPD.
KW  - COPD
KW  - emphysema
KW  - pulmonary hypertension
KW  - hypoxia
KW  - oxidative stress
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235631
SN  - 2297-055X
VL  - 8
ER  - 
TY  - JOUR
A1  - Gredic, Marija
A1  - Karnati, Srikanth
A1  - Ruppert, Clemens
A1  - Guenther, Andreas
A1  - Avdeev, Sergey N.
A1  - Kosanovic, Djuro
T1  - Combined pulmonary fibrosis and emphysema: when Scylla and Charybdis ally
JF  - Cells
N2  - Combined pulmonary fibrosis and emphysema (CPFE) is a recently recognized syndrome that, as its name indicates, involves the existence of both interstitial lung fibrosis and emphysema in one individual, and is often accompanied by pulmonary hypertension. This debilitating, progressive condition is most often encountered in males with an extensive smoking history, and is presented by dyspnea, preserved lung volumes, and contrastingly impaired gas exchange capacity. The diagnosis of the disease is based on computed tomography imaging, demonstrating the coexistence of emphysema and interstitial fibrosis in the lungs, which might be of various types and extents, in different areas of the lung and several relative positions to each other. CPFE bears high mortality and to date, specific and efficient treatment options do not exist. In this review, we will summarize current knowledge about the clinical attributes and manifestations of CPFE. Moreover, we will focus on pathophysiological and pathohistological lung phenomena and suspected etiological factors of this disease. Finally, since there is a paucity of preclinical research performed for this particular lung pathology, we will review existing animal studies and provide suggestions for the development of additional in vivo models of CPFE syndrome.
KW  - CPFE
KW  - lung fibrosis
KW  - emphysema
KW  - animal models
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-313571
SN  - 2073-4409
VL  - 12
IS  - 9
ER  - 
TY  - JOUR
A1  - Meyer, Malin Tordis
A1  - Watermann, Christoph
A1  - Dreyer, Thomas
A1  - Wagner, Steffen
A1  - Wittekindt, Claus
A1  - Klussmann, Jens Peter
A1  - Ergün, Süleyman
A1  - Baumgart-Vogt, Eveline
A1  - Karnati, Srikanth
T1  - Differential expression of peroxisomal proteins in distinct types of parotid gland tumors
JF  - International Journal of Molecular Sciences
N2  - Salivary gland cancers are rare but aggressive tumors that have poor prognosis and lack effective cure. Of those, parotid tumors constitute the majority. Functioning as metabolic machinery contributing to cellular redox balance, peroxisomes have emerged as crucial players in tumorigenesis. Studies on murine and human cells have examined the role of peroxisomes in carcinogenesis with conflicting results. These studies either examined the consequences of altered peroxisomal proliferators or compared their expression in healthy and neoplastic tissues. None, however, examined such differences exclusively in human parotid tissue or extended comparison to peroxisomal proteins and their associated gene expressions. Therefore, we examined differences in peroxisomal dynamics in parotid tumors of different morphologies. Using immunofluorescence and quantitative PCR, we compared the expression levels of key peroxisomal enzymes and proliferators in healthy and neoplastic parotid tissue samples. Three parotid tumor subtypes were examined: pleomorphic adenoma, mucoepidermoid carcinoma and acinic cell carcinoma. We observed higher expression of peroxisomal matrix proteins in neoplastic samples with exceptional down regulation of certain enzymes; however, the degree of expression varied between tumor subtypes. Our findings confirm previous experimental results on other organ tissues and suggest peroxisomes as possible therapeutic targets or markers in all or certain subtypes of parotid neoplasms.
KW  - peroxisomes
KW  - parotid gland
KW  - salivary
KW  - tumors
KW  - pleomorphic adenoma
KW  - mucoepidermoid carcinoma
KW  - acinic cell carcinoma
KW  - differential expression
KW  - immunohistochemistry
KW  - mRNA
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-261047
SN  - 1422-0067
VL  - 22
IS  - 15
ER  - 
TY  - JOUR
A1  - Rajendran, Ranjithkumar
A1  - Böttiger, Gregor
A1  - Dentzien, Niklas
A1  - Rajendran, Vinothkumar
A1  - Sharifi, Bischand
A1  - Ergün, Süleyman
A1  - Stadelmann, Christine
A1  - Karnati, Srikanth
A1  - Berghoff, Martin
T1  - Effects of FGFR tyrosine kinase inhibition in OLN-93 oligodendrocytes
JF  - Cells
N2  - Fibroblast growth factor (FGF) signaling is involved in the pathogenesis of multiple sclerosis (MS). Data from neuropathology studies suggest that FGF signaling contributes to the failure of remyelination in MS. In MOG\(_{35–55}\)-induced EAE, oligodendrocyte-specific deletion of FGFR1 and FGFR2 resulted in a less severe disease course, reduced inflammation, myelin and axon degeneration and changed FGF/FGFR and BDNF/TrkB signaling. Since signaling cascades in oligodendrocytes could not be investigated in the EAE studies, we here aimed to characterize FGFR-dependent oligodendrocyte-specific signaling in vitro. FGFR inhibition was achieved by application of the multi-kinase-inhibitor dovitinib and the FGFR1/2/3-inhibitor AZD4547. Both substances are potent inhibitors of FGF signaling; they are effective in experimental tumor models and patients with malignancies. Effects of FGFR inhibition in oligodendrocytes were studied by immunofluorescence microscopy, protein and gene analyses. Application of the tyrosine kinase inhibitors reduced FGFR1, phosphorylated ERK and Akt expression, and it enhanced BDNF and TrkB expression. Furthermore, the myelin proteins CNPase and PLP were upregulated by FGFR inhibition. In summary, inhibition of FGFR signaling in oligodendrocytes can be achieved by application of tyrosine kinase inhibitors. Decreased phosphorylation of ERK and Akt is associated with an upregulation of BDNF/TrkB signaling, which may be responsible for the increased production of myelin proteins. Furthermore, these data suggest that application of FGFR inhibitors may have the potential to promote remyelination in the CNS.
KW  - multiple sclerosis
KW  - oligodendrocytes
KW  - dovitinib
KW  - AZD4547
KW  - FGFR signaling
KW  - myelin
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239600
SN  - 2073-4409
VL  - 10
IS  - 6
ER  - 
TY  - JOUR
A1  - Kustiati, Ulayatul
A1  - Ergün, Suleyman
A1  - Karnati, Srikanth
A1  - Nugrahaningsih, Dwi Aris Agung
A1  - Kusindarta, Dwi Liliek
A1  - Wihadmadyatami, Hevi
T1  - Ethanolic extract of Ocimum sanctum Linn. Inhibits cell migration of human lung adenocarcinoma cells (A549) by downregulation of integrin αvβ3, α5β1, and VEGF
JF  - Scientia Pharmaceutica
N2  - Adenocarcinoma lung cancer is a type of non-small cell lung carcinoma (NSCLC), which accounts for 85% of lung cancer incidence globally. The therapies that are being applied, both conventional therapies and antibody-based treatments, are still found to have side effects. Several previous studies have demonstrated the ability of the ethanolic extract of Ocimum sanctum Linn. (EEOS) as an ethnomedicine with anti-tumor properties. The aim of this study was to determine the effect of Ocimum sanctum Linn. ethanolic extract in inhibiting the proliferation, angiogenesis, and migration of A549 cells (NSCLC). The adhesion as well as the migration assay was performed. Furthermore, enzyme-linked immunosorbent assay (ELISA) was used to measure the expression of αvβ3 integrins, α5β1 integrins, and VEGF. The cells were divided into the following treatment groups: control (non-treated/NT), positive control (AP3/inhibitor β3 80 µg/mL), cisplatin (9 µg/mL), and EEOS at concentrations of 50, 70, 100, and 200 µg/mL. The results showed that EEOS inhibits the adhesion ability and migration of A549 cells, with an optimal concentration of 200 µg/mL. ELISA testing showed that the group of A549 cells given EEOS 200 µg/mL presented a decrease in the optimal expression of integrin α5β1, integrin αvβ3, and VEGF.
KW  - EEOS
KW  - A549 cell line
KW  - integrin α5β1
KW  - integrin αvβ3
KW  - VEGF
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-290540
SN  - 2218-0532
VL  - 90
IS  - 4
ER  - 
TY  - JOUR
A1  - Rajendran, Ranjithkumar
A1  - Böttiger, Gregor
A1  - Stadelmann, Christine
A1  - Karnati, Srikanth
A1  - Berghoff, Martin
T1  - FGF/FGFR pathways in multiple sclerosis and in its disease models
JF  - Cells
N2  - Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system (CNS) affecting more than two million people worldwide. In MS, oligodendrocytes and myelin sheaths are destroyed by autoimmune-mediated inflammation, while remyelination is impaired. Recent investigations of post-mortem tissue suggest that Fibroblast growth factor (FGF) signaling may regulate inflammation and myelination in MS. FGF2 expression seems to correlate positively with macrophages/microglia and negatively with myelination; FGF1 was suggested to promote remyelination. In myelin oligodendrocyte glycoprotein (MOG)\(_{35–55}\)-induced experimental autoimmune encephalomyelitis (EAE), systemic deletion of FGF2 suggested that FGF2 may promote remyelination. Specific deletion of FGF receptors (FGFRs) in oligodendrocytes in this EAE model resulted in a decrease of lymphocyte and macrophage/microglia infiltration as well as myelin and axon degeneration. These effects were mediated by ERK/Akt phosphorylation, a brain-derived neurotrophic factor, and downregulation of inhibitors of remyelination. In the first part of this review, the most important pharmacotherapeutic principles for MS will be illustrated, and then we will review recent advances made on FGF signaling in MS. Thus, we will suggest application of FGFR inhibitors, which are currently used in Phase II and III cancer trials, as a therapeutic option to reduce inflammation and induce remyelination in EAE and eventually MS.
KW  - FGF
KW  - FGFR
KW  - multiple sclerosis
KW  - EAE
KW  - ERK
KW  - Akt
KW  - BDNF
KW  - LINGO-1
KW  - SEMA3A
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236594
SN  - 2073-4409
VL  - 10
IS  - 4
ER  - 
TY  - JOUR
A1  - Rajendran, Ranjithkumar
A1  - Rajendran, Vinothkumar
A1  - Gupta, Liza
A1  - Shirvanchi, Kian
A1  - Schunin, Darja
A1  - Karnati, Srikanth
A1  - Giraldo-Velásquez, Mario
A1  - Berghoff, Martin
T1  - Interferon beta-1a versus combined interferon beta-1a and oligodendrocyte-specific FGFR1 deletion in experimental autoimmune encephalomyelitis
JF  - International Journal of Molecular Sciences
N2  - Recombinant beta interferons-1 (IFNβ-1) are used as first line therapies in patients with relapsing multiple sclerosis (MS), a chronic inflammatory and neurodegenerative disease of the CNS. IFNβ-1a/b has moderate effects on the prevention of relapses and slowing of disease progression. Fibroblast growth factors (FGFs) and FGF receptors (FGFRs) are known to play a key role in the pathology of MS and its model EAE. To investigate the effects of short-term treatment with s.c. IFNβ-1a versus the combined application of s.c. IFNβ-1a and oligodendrocyte-specific deletion of FGFR1 (Fgfr1\(^{ind−/−}\) mice) in MOG\(_{35-55}\)-induced EAE. IFNβ-1a (30 mg/kg) was applied s.c. from days 0–7 p.i. of EAE in controls and Fgfr1\(^{ind−/−}\) mice. FGFR signaling proteins associated with inflammation/degeneration in MS/EAE were analyzed by western blot in the spinal cord. Further, FGFR1 in Oli-neu oligodendrocytes were inhibited by PD166866 and treated with IFNβ-1a (400 ng/mL). Application of IFNβ-1a over 8 days resulted in less symptoms only at the peak of disease (days 9–11) compared to controls. Application of IFNβ-1a in Fgfr1\(^{ind−/−}\) mice resulted in less symptoms primarily in the chronic phase of EAE. Fgfr1\(^{ind−/−}\) mice treated with IFNβ-1a showed increased expression of pERK and BDNF. In Oli-neu oligodendrocytes, treatment with PD166866 and IFNβ-1a also showed an increased expression of pERK and BDNF/TrkB. These data suggest that the beneficial effects in the chronic phase of EAE and on signaling molecules associated with ERK and BDNF expression are caused by the modulation of FGFR1 and not by interferon beta-1a. FGFR may be a potential target for therapy in MS.
KW  - FGFR1
KW  - interferon beta-1a
KW  - oligodendrocytes
KW  - EAE
KW  - multiple sclerosis
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-290401
SN  - 1422-0067
VL  - 23
IS  - 20
ER  - 
TY  - JOUR
A1  - Reschke, Moritz
A1  - Salvador, Ellaine
A1  - Schlegel, Nicolas
A1  - Burek, Malgorzata
A1  - Karnati, Srikanth
A1  - Wunder, Christian
A1  - Förster, Carola Y.
T1  - Isosteviol sodium (STVNA) reduces pro-inflammatory cytokine IL-6 and GM-CSF in an in vitro murine stroke model of the blood–brain barrier (BBB)
JF  - Pharmaceutics
N2  - Early treatment with glucocorticoids could help reduce both cytotoxic and vasogenic edema, leading to improved clinical outcome after stroke. In our previous study, isosteviol sodium (STVNA) demonstrated neuroprotective effects in an in vitro stroke model, which utilizes oxygen-glucose deprivation (OGD). Herein, we tested the hypothesis that STVNA can activate glucocorticoid receptor (GR) transcriptional activity in brain microvascular endothelial cells (BMECs) as previously published for T cells. STVNA exhibited no effects on transcriptional activation of the glucocorticoid receptor, contrary to previous reports in Jurkat cells. However, similar to dexamethasone, STVNA inhibited inflammatory marker IL-6 as well as granulocyte-macrophage colony-stimulating factor (GM-CSF) secretion. Based on these results, STVNA proves to be beneficial as a possible prevention and treatment modality for brain ischemia-reperfusion injury-induced blood–brain barrier (BBB) dysfunction.
KW  - IL-6
KW  - ischemia
KW  - isosteviol sodium (STVNA)
KW  - dexamethasone
KW  - glucocorticoid receptor
KW  - cerebEND
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-286275
SN  - 1999-4923
VL  - 14
IS  - 9
ER  -