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41.
Sabine Schulze Christin Neuber Stephanie Mller Ute Hempel Lorenz C. Hofbauer Klaus-Dieter Schaser Jens Pietzsch Stefan Rammelt 《International journal of molecular sciences》2022,23(23)
Bone in diabetes mellitus is characterized by an altered microarchitecture caused by abnormal metabolism of bone cells. Together with diabetic neuropathy, this is associated with serious complications including impaired bone healing culminating in complicated fractures and dislocations, especially in the lower extremities, so-called Charcot neuroarthropathy (CN). The underlying mechanisms are not yet fully understood, and treatment of CN is challenging. Several in vitro and in vivo investigations have suggested positive effects on bone regeneration by modifying biomaterials with sulfated glycosaminoglycans (sGAG). Recent findings described a beneficial effect of sGAG for bone healing in diabetic animal models compared to healthy animals. We therefore aimed at studying the effects of low- and high-sulfated hyaluronan derivatives on osteoclast markers as well as gene expression patterns of osteoclasts and osteoblasts from patients with diabetic CN compared to non-diabetic patients with arthritis at the foot and ankle. Exposure to sulfated hyaluronan (sHA) derivatives reduced the exaggerated calcium phosphate resorption as well as the expression of genes associated with bone resorption in both groups, but more pronounced in patients with CN. Moreover, sHA derivatives reduced the release of pro-inflammatory cytokines in osteoclasts of patients with CN. The effects of sHA on osteoblasts differed only marginally between patients with CN and non-diabetic patients with arthritis. These results suggest balancing effects of sHA on osteoclastic bone resorption parameters in diabetes. 相似文献
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43.
Elodie Belnoue Alexis Vogelzang Natalie E. Nieuwenhuizen Magdalena A. Krzyzaniak Stephanie Darbre Mario Kreutzfeldt Ingrid Wagner Doron Merkler Paul-Henri Lambert Stefan H. E. Kaufmann Claire-Anne Siegrist Daniel D. Pinschewer 《International journal of molecular sciences》2022,23(5)
Mycobacterium tuberculosis (Mtb) represents a major burden to global health, and refined vaccines are needed. Replication-deficient lymphocytic choriomeningitis virus (rLCMV)-based vaccine vectors against cytomegalovirus have proven safe for human use and elicited robust T cell responses in a large proportion of vaccine recipients. Here, we developed an rLCMV vaccine expressing the Mtb antigens TB10.4 and Ag85B. In mice, rLCMV elicited high frequencies of polyfunctional Mtb-specific CD8 and CD4 T cell responses. CD8 but not CD4 T cells were efficiently boosted upon vector re-vaccination. High-frequency responses were also observed in neonatally vaccinated mice, and co-administration of rLCMV with Expanded Program of Immunization (EPI) vaccines did not result in substantial reciprocal interference. Importantly, rLCMV immunization significantly reduced the lung Mtb burden upon aerosol challenge, resulting in improved lung ventilation. Protection was associated with increased CD8 T cell recruitment but reduced CD4 T cell infiltration upon Mtb challenge. When combining rLCMV with BCG vaccination in a heterologous prime-boost regimen, responses to the rLCMV-encoded Mtb antigens were further augmented, but protection was not significantly different from rLCMV or BCG vaccination alone. This work suggests that rLCMV may show utility for neonatal and/or adult vaccination efforts against pulmonary tuberculosis. 相似文献
44.
Hang-Soo Park Rishi Man Chugh Melissa R. Pergande Esra Cetin Hiba Siblini Sahar Esfandyari Stephanie M. Cologna Ayman Al-Hendy 《International journal of molecular sciences》2022,23(9)
Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder in reproductive-aged women, and it typically involves elevated androgen levels. Recently, it has been reported that human bone marrow mesenchymal stem cells (hBM-MSCs) can regulate androgen synthesis pathways. However, the details of the mechanism are still unclear. hBM-MSC-derived secreted factors (the secretome) are promising sources of cell-based therapy as they consist of various types of proteins. It is thus important to know which proteins interact with disease-implicated biomolecules. This work aimed to investigate which secretome components contain the key factor that inhibits testosterone synthesis. In this study, we fractionated hBM-MSC-conditioned media into three fractions based on their molecular weights and found that, of the three fractions, one had the ability to inhibit the androgen-producing genes efficiently. We also analyzed the components of this fraction and established a protein profile of the hBM-MSC secretome, which was shown to inhibit androgen synthesis. Our study describes a set of protein components present in the hBM-MSC secretome that can be used therapeutically to treat PCOS by regulating androgen production for the first time. 相似文献
45.
Sneana Hini&#x; April Rich Nicole V. Anayannis Stephanie Cabarcas-Petroski Laura Schramm Patricio I. Meneses 《International journal of molecular sciences》2022,23(18)
High-risk human papillomaviruses (HPV) are important agents, responsible for a large percentage of the 745,000 cases of head and neck squamous cell carcinomas (HNSCC), which were identified worldwide in 2020. In addition to being virally induced, tobacco and heavy alcohol consumption are believed to cause DNA damage contributing to the high number of HNSCC cases. Gene expression and DNA methylation differ between HNSCC based on HPV status. We used publicly available gene expression and DNA methylation profiles from the Cancer Genome Atlas and compared HPV positive and HPV negative HNSCC groups. We used differential gene expression analysis, differential methylation analysis, and a combination of these two analyses to identify the differences. Differential expression analysis identified 1854 differentially expressed genes, including PCNA, TNFRSF14, TRAF1, TRAF2, BCL2, and BIRC3. SYCP2 was identified as one of the top deregulated genes in the differential methylation analysis and in the combined differential expression and methylation analyses. Additionally, pathway and ontology analyses identified the extracellular matrix and receptor interaction pathway as the most altered between HPV negative and HPV positive HNSCC groups. Combining gene expression and DNA methylation can help in elucidating the genes involved in HPV positive HNSCC tumorigenesis, such as SYCP2 and TAF7L. 相似文献
46.
Anna Kirstein Daniela Schilling Stephanie E. Combs Thomas E. Schmid 《International journal of molecular sciences》2021,22(13)
Background: Treatment resistance of glioblastoma multiforme to chemo- and radiotherapy remains a challenge yet to overcome. In particular, the O6-methylguanine-DNA-methyltransferase (MGMT) promoter unmethylated patients have only little benefit from chemotherapy treatment using temozolomide since MGMT counteracts its therapeutic efficacy. Therefore, new treatment options in radiotherapy need to be developed to inhibit MGMT and increase radiotherapy response. Methods: Lomeguatrib, a highly specific MGMT inhibitor, was used to inactivate MGMT protein in vitro. Radiosensitivity of established human glioblastoma multiforme cell lines in combination with lomeguatrib was investigated using the clonogenic survival assay. Inhibition of MGMT was analyzed using Western Blot. Cell cycle distribution and apoptosis were investigated to determine the effects of lomeguatrib alone as well as in combination with ionizing radiation. Results: Lomeguatrib significantly decreased MGMT protein and reduced radiation-induced G2/M arrest. A radiosensitizing effect of lomeguatrib was observed when administered at 1 µM and increased radioresistance at 20 µM. Conclusion: Low concentrations of lomeguatrib elicit radiosensitization, while high concentrations mediate a radioprotective effect. 相似文献
47.
48.
Stephanie Ehlers Dr. Daiane Szczerbowski Dr. Tim Harig Dr. Matthew Stell Dr. Susan Hötling Dr. Kathy Darragh Prof. Dr. Chris D. Jiggins Prof. Dr. Stefan Schulz 《Chembiochem : a European journal of chemical biology》2021,22(23):3300-3313
The butterfly Heliconius erato occurs in various mimetic morphs. The male clasper scent gland releases an anti-aphrodisiac pheromone and additionally contains a complex mixture of up to 350 components, varying between individuals. In 114 samples of five different mimicry groups and their hybrids 750 different compounds were detected by gas chromatography/mass spectrometry (GC/MS). Many unknown components occurred, which were identified using their mass spectra, gas chromatography/infrared spectroscopy (GC/IR)-analyses, derivatization, and synthesis. Key compounds proved to be various esters of 3-oxohexan-1-ol and (Z)-3-hexen-1-ol with (S)-2,3-dihydrofarnesoic acid, accompanied by a large variety of other esters with longer terpene acids, fatty acids, and various alcohols. In addition, linear terpenes with up to seven uniformly connected isoprene units occur, e. g. farnesylfarnesol. A large number of the compounds have not been reported before from nature. Discriminant analyses of principal components of the gland contents showed that the iridescent mimicry group differs strongly from the other, mostly also separated, mimicry groups. Comparison with data from other species indicated that Heliconius recruits different biosynthetic pathways in a species-specific manner for semiochemical formation. 相似文献
49.
Ramón Morales Chabrand Hyun-Jung Kim Cheng Zhang Charles E. Glatz Stephanie Jung 《Journal of the American Oil Chemists' Society》2008,85(4):383-390
Characterization and destabilization of the emulsion formed during aqueous extraction of oil from soybean flour were investigated.
This emulsion was collected as a cream layer and was subjected to various single and combined treatments, including thermal
treatments and enzymatic treatments, aimed at recovery of free oil. The soybean oil emulsion formed during the aqueous extraction
processing of full fat flour contains high molecular weight glycinin and β-conglycinin proteins and smaller oleosin proteins,
which form a multilayer interface. Heat treatment alone did not modify the free oil recovery but freeze–thaw treatment increased
the oil yield from 3 to 22%. After enzymatic treatment of the emulsion, its mean droplet size changed from 5 to 14 μm and
the oil recovery increased to 23%. This increase could be attributed to the removal (due to enzymatic hydrolysis) of large
molecular weight polypeptides from the emulsion interface, resulting in partial emulsion destabilization. When enzymatic treatment
was followed by a freeze–thaw step, the oil recovery increased to 46%. This result can be attributed to the thinner interfacial
membrane after enzymatic hydrolysis, partial coalescence during freeze–thaw, and coalescence during centrifugation. Despite
the reduction in emulsion stability achieved, additional demulsification approaches need to be pursued to obtain an acceptably
high conversion to free oil. 相似文献
50.
von Knobelsdorff-Brenkenhoff Florian Reiter Stephanie Menini Anne Janich Martin A. Schunke Tobias Ziegler Karl Scheck Roland Höfling Berthold Pilz Günter 《Magma (New York, N.Y.)》2021,34(5):757-766
Objective
Image post-processing corrects for cardiac and respiratory motion (MoCo) during cardiovascular magnetic resonance (CMR) stress perfusion. The study analyzed its influence on visual image evaluation.
Materials and methodsSixty-two patients with (suspected) coronary artery disease underwent a standard CMR stress perfusion exam during free-breathing. Image post-processing was performed without (non-MoCo) and with MoCo (image intensity normalization; motion extraction with iterative non-rigid registration; motion warping with the combined displacement field). Images were evaluated regarding the perfusion pattern (perfusion deficit, dark rim artifact, uncertain signal loss, and normal perfusion), the general image quality (non-diagnostic, imperfect, good, and excellent), and the reader’s subjective confidence to assess the images (not confident, confident, very confident).
ResultsFifty-three (non-MoCo) and 52 (MoCo) myocardial segments were rated as ‘perfusion deficit’, 113 vs. 109 as ‘dark rim artifacts’, 9 vs. 7 as ‘uncertain signal loss’, and 817 vs. 824 as ‘normal’. Agreement between non-MoCo and MoCo was high with no diagnostic difference per-patient. The image quality of MoCo was rated more often as ‘good’ or ‘excellent’ (92 vs. 63%), and the diagnostic confidence more often as “very confident” (71 vs. 45%) compared to non-MoCo.
ConclusionsThe comparison of perfusion images acquired during free-breathing and post-processed with and without motion correction demonstrated that both methods led to a consistent evaluation of the perfusion pattern, while the image quality and the reader’s subjective confidence to assess the images were rated more favorably for MoCo.
相似文献