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Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"

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https://www.readbyqxmd.com/read/30406363/identification-of-molecular-signatures-involved-in-radiation-induced-lung-fibrosis
#1
Hee Jin, Ga-Young Kang, Seulgi Jeon, Jin-Mo Kim, You Na Park, Jaeho Cho, Yun-Sil Lee
In radiotherapy, radiation (IR)-induced lung fibrosis has severe and dose-limiting side effects. To elucidate the molecular effects of IR fibrosis, we examined the fibrosis process in irradiated mouse lung tissues. High focal IR (90 Gy) was exposed to a 3-mm volume of the left lung in C57BL6 mice. In the diffused irradiation, 20 Gy dose delivered with a 7-mm collimator almost covered the entire left lung. Histological examination for lung tissues of both irradiated and neighboring regions was done for 4 weeks after irradiation...
November 7, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30397790/propionibacterium-acnes-induces-discogenic-low-back-pain-via-stimulating-nucleus-pulposus-cells-to-secrete-pro-algesic-factor-of-il-8-cinc-1-through-tlr2-nf-%C3%AE%C2%BAb-p65-pathway
#2
Yucheng Jiao, Ye Yuan, Yazhou Lin, Zezhu Zhou, Yuehuan Zheng, Wenjian Wu, Guoqing Tang, Yong Chen, Jiaqi Xiao, Changwei Li, Zhe Chen, Peng Cao
Latent infection of Propionibacterium acnes was considered as a new pathogeny for low back pain (LBP); however, there is no credible animal evidence or mechanism hypothesis. This study proved that P. acnes is a causative pathogen of bacteria-induced LBP and investigated its underlying mechanism. For this, P. acnes was firstly identified in patients' degenerated intervertebral disc (IVDs) samples. The results of patients' Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ), Japanese Orthopaedic Association (JOA), and Oswestry Disability Index (ODI) scores indicated that P...
November 6, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30386909/hypoxia-inducible-factor-1%C3%AE-regulation-of-myeloid-cells
#3
REVIEW
C L Stothers, L Luan, B A Fensterheim, J K Bohannon
Hematopoietic myeloblasts give rise to macrophages, dendritic cells, and neutrophils. Circulating myeloid cells detect invading microbes using pattern recognition receptors and subsequently orchestrate an innate immune response to contain and kill the pathogens. This innate immune response establishes an inflammatory niche characterized by hypoxia due to host and pathogen factors. Hypoxia-inducible factor (HIF) transcription factors are the primary regulators of the myeloid response to hypoxia. In particular, HIF-1α is a critical hub that integrates hypoxic and immunogenic signals during infection or inflammation...
November 1, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30386908/antigen-presenting-cell-diversity-for-t-cell-reactivation-in-central-nervous-system-autoimmunity
#4
REVIEW
Ari Waisman, Lisa Johann
Autoreactive T cells are considered the major culprits in the pathogenesis of many autoimmune diseases like multiple sclerosis (MS). Upon activation in the lymphoid organs, autoreactive T cells migrate towards the central nervous system (CNS) and target the myelin sheath-forming oligodendrocytes, resulting in detrimental neurological symptoms. Despite the availability of extensively studied systems like the experimental autoimmune encephalomyelitis (EAE) model, our understanding of this disease and the underlying pathogenesis is still elusive...
November 1, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30374682/pre-treatment-with-angiotensin-1-7-inhibits-tumor-growth-via-autophagy-by-downregulating-pi3k-akt-mtor-signaling-in-human-nasopharyngeal-carcinoma-xenografts
#5
Yu-Tsai Lin, Hung-Chen Wang, Hui-Ching Chuang, Yi-Chiang Hsu, Ming-Yu Yang, Chih-Yen Chien
The highest incidence of nasopharyngeal carcinoma (NPC) is in southeast China, including Taiwan. Many side effects have been observed following radiation therapy with chemotherapy; hence, exploring new treatment modalities for NPC is an important future direction. Angiotensin-(1-7) [Ang-(1-7)] is an endogenous heptapeptide hormone and important component of the renin-angiotensin system that acts through both the Mas receptor and AT2 receptor, exhibiting anti-proliferative and anti-angiogenic properties in cancer cells...
October 29, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30361814/hypoxia-inducible-factor-1%C3%AE-protects-peripheral-sensory-neurons-from-diabetic-peripheral-neuropathy-by-suppressing-accumulation-of-reactive-oxygen-species
#6
Daniel Rangel Rojas, Irmgard Tegeder, Rohini Kuner, Nitin Agarwal
Diabetic peripheral neuropathy (DPN) is one of the most common diabetic complications. Mechanisms underlying nerve damage and sensory loss following metabolic dysfunction remain largely unclear. Recently, hyperglycemia-induced mitochondrial dysfunction and the generation of reactive oxygen species (ROS) have gained attention as possible mechanisms of organ damage in diabetes. Hypoxia-inducible factor 1 (HIF1α) is a key transcription factor activated by hypoxia, hyperglycemia, nitric oxide as well as ROS, suggesting a fundamental role in DPN susceptibility...
October 25, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30357435/thymus-derived-foxp3-regulatory-t-cells-upregulate-ror%C3%AE-t-expression-under-inflammatory-conditions
#7
Juhao Yang, Mangge Zou, Joern Pezoldt, Xuyu Zhou, Jochen Huehn
Foxp3+ regulatory T cells (Tregs) co-expressing the Th17-lineage specification factor RORγt represent a unique Treg subpopulation that has been reported to be induced upon response to gut microbiota within the intestinal immune system. Hence, RORγt+ Tregs are considered to solely consist of peripherally induced Foxp3+ Tregs (pTregs), and the possibility that also thymus-derived Treg (tTregs) can upregulate RORγt expression and contribute to the pool of RORγt+ Tregs was largely ignored. Here, we expand our knowledge on the origin of RORγt+ Tregs by demonstrating that also tTregs can attain RORγt expression...
October 24, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30353303/genomics-and-response-to-long-term-oxygen-therapy-in-chronic-obstructive-pulmonary-disease
#8
Minseok Seo, Weiliang Qiu, William Bailey, Gerard J Criner, Mark T Dransfield, Anne L Fuhlbrigge, John J Reilly, Mary Beth Scholand, Peter Castaldi, Robert Chase, Margaret Parker, Aabida Saferali, Jeong H Yun, James D Crapo, Michael H Cho, Terri H Beaty, Edwin K Silverman, Craig P Hersh
Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide, and long-term oxygen therapy has been shown to reduce mortality in COPD patients with severe hypoxemia. However, the Long-term Oxygen Treatment Trial (LOTT), a large randomized trial, found no benefit of oxygen therapy in COPD patients with moderate hypoxemia. We hypothesized that there may be differences in response to oxygen which depend on genotype or gene expression. In a genome-wide time-to-event analysis of the primary outcome of death or hospitalization in 331 subjects, 97 single nucleotide polymorphisms (SNPs) showed evidence of interaction with oxygen therapy at P < 1e-5, including 7 SNPs near arylsulfatase B (ARSB; P = 6e-6)...
October 23, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30341570/progranulin-associates-with-hexosaminidase-a-and-ameliorates-gm2-ganglioside-accumulation-and-lysosomal-storage-in-tay-sachs-disease
#9
Yuehong Chen, Jinlong Jian, Aubryanna Hettinghouse, Xueheng Zhao, Kenneth D R Setchell, Ying Sun, Chuan-Ju Liu
Tay-Sachs disease (TSD) is a lethal lysosomal storage disease (LSD) caused by mutations in the HexA gene, which can lead to deficiency of β-hexosaminidase A (HexA) activity and consequent accumulation of its substrate, GM2 ganglioside. Recent reports that progranulin (PGRN) functions as a chaperone of lysosomal enzymes and its deficiency is associated with LSDs, including Gaucher disease and neuronal ceroid lipofuscinosis, prompted us to screen the effects of recombinant PGRN on lysosomal storage in fibroblasts from 11 patients affected by various LSDs, which led to the isolation of TSD in which PGRN demonstrated the best effects in reducing lysosomal storage...
October 20, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30341569/adiporon-an-adiponectin-receptor-agonist-attenuates-cardiac-remodeling-induced-by-pressure-overload
#10
Ning Zhang, Wen-Ying Wei, Hai-Han Liao, Zheng Yang, Can Hu, Sha-Sha Wang, Wei Deng, Qi-Zhu Tang
AdipoRon, a small-molecule adiponectin receptor (AdipoR) agonist, has been reported to be implicated in cardiovascular diseases. However, its role in pressure-overload-induced cardiac remodeling is still elusive. To elucidate the role of AdipoRon in the pathogenesis of cardiac remodeling in vivo and vitro, in the left ventricle of human end-stage heart failure, the expression of AdipoR2 is upregulated. Meanwhile, increased expression of AdipoR2 was also observed in mice failing hearts. Oral administration of AdipoRon alleviated cardiac hypertrophy and fibrosis induced by pressure overload, as evidenced by the beneficial change of cross-sectional area of cardiomyocytes, heart weight-to-body weight ratio, gene expression of hypertrophic markers, ventricle collagen ratio, and cardiac function...
October 19, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30341568/plasminogen-thrombomodulin-signaling-enhances-vegf-expression-to-promote-cutaneous-wound-healing
#11
Tsung-Lin Cheng, Po-Ku Chen, Wei-Kai Huang, Cheng-Hsiang Kuo, Chia-Fong Cho, Kuan-Chieh Wang, Guey-Yueh Shi, Hua-Lin Wu, Chao-Han Lai
Plasminogen (Plg) and thrombomodulin (TM) are glycoproteins well known for fibrinolytic and anticoagulant functions, respectively. Both Plg and TM are essential for wound healing. However, their significance during the reparative process was separately demonstrated in previous studies. Here, we investigate the interaction between Plg and epithelial TM and its effect on wound healing. Characterization of the wound margin revealed that Plg and TM were simultaneously upregulated at the early stage of wound healing and the two molecules were bound together...
October 19, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30315331/pentraxin-3-promotes-long-term-cerebral-blood-flow-recovery-angiogenesis-and-neuronal-survival-after-stroke
#12
Ivana Rajkovic, Raymond Wong, Eloise Lemarchand, Jack Rivers-Auty, Olivera Rajkovic, Cecilia Garlanda, Stuart M Allan, Emmanuel Pinteaux
Restoration of cerebral blood flow (CBF) and upregulation of angiogenesis are crucial for brain repair and functional recovery after cerebral ischaemia. Pentraxin 3 (PTX3) is a key regulator of angiogenesis and is emerging as a promising target for cerebrovascular repair after stroke. Here, we investigated for the first time the role of PTX3 in long-term CBF, angiogenesis, and neuronal viability after ischaemic stroke induced by transient middle cerebral artery occlusion (MCAo). Lack of PTX3 had no effect on early brain damage, but significantly impaired restoration of CBF, 14 and 28 days after MCAo, compared to wild-type (WT) mice...
October 13, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30288546/trichostatin-a-a-histone-deacetylase-inhibitor-induces-synergistic-cytotoxicity-with-chemotherapy-via-suppression-of-raf-mek-erk-pathway-in-urothelial-carcinoma
#13
Wei-Chou Lin, Fu-Shun Hsu, Kuan-Lin Kuo, Shing-Hwa Liu, Chia-Tung Shun, Chung-Sheng Shi, Hong-Chiang Chang, Yu-Chieh Tsai, Ming-Chieh Lin, June-Tai Wu, Yu Kuo, Po-Ming Chow, Shih-Ming Liao, Shao-Ping Yang, Jo-Yu Hong, Kuo-How Huang
In this study, we aimed to investigate the antitumor effects of trichostatin A (TSA), an antifungal antibiotic that inhibits histone deacetylase (HDAC) family of enzymes, alone or in combination with anyone of the three chemotherapeutic agents (cisplatin, gemcitabine, and doxorubicin) for the treatment of human urothelial carcinoma (UC). Two high-grade human UC cell lines (T24 and NTUB1) were used. Cytotoxicity and apoptosis were assessed by MTT assay and flow cytometry, respectively. The expression of phospho-c-Raf, phospho-MEK1/2, and phospho-ERK1/2 was measured by western blotting...
October 4, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30324339/trib2-regulates-the-differentiation-of-mll-tet1-transduced-myeloid-progenitor-cells
#14
Hyeng-Soo Kim, Seung Hwan Oh, Ju-Heon Kim, Wern-Joo Sohn, Jae-Young Kim, Do-Hyung Kim, Sang-Un Choi, Kwon Moo Park, Zae Young Ryoo, Tae Sung Park, Sanggyu Lee
The function and mechanism of action of MLL-TET1 (MT1) fusion protein in hematological cells are unclear and require further investigation. In the present study, we found that the MT1 fusion protein attenuated the expression of Cebpa, Csf1r, and Cd11b and inhibited the differentiation of myeloid progenitor cells. Increased binding of the MT1 fusion protein to the Trib2 promoter upregulated Trib2 mRNA and protein expression and downregulated Cebpa expression. Trib2 knockdown relieved the inhibition of myeloid cell differentiation induced by the MT1 fusion protein...
November 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30298385/the-combination-of-everolimus-and-terameprocol-exerts-synergistic-antiproliferative-effects-in-endometrial-cancer-molecular-role-of-insulin-like-growth-factor-binding-protein-2
#15
Angel Chao, Chiao-Yun Lin, Ren-Chin Wu, Yun-Shien Lee, Li-Yu Lee, Chia-Lung Tsai, Lan-Yan Yang, Hsuan Liu, Shu-Jen Chen, Tzu-Hao Wang, Chyong-Huey Lai
Oncogenic PIK3CA mutations are common in endometrial cancers, and the PI3K/AKT/mTOR pathway is targetable by drugs. We sought to investigate whether the combination of an mTOR inhibitor, everolimus (RAD001), and an AKT inhibitor, terameprocol (M4N), exerts better antiproliferative effects in endometrial cancer. The molecular mechanisms underlying their pharmacological action were also examined. The combination of RAD001 and M4N exerted in vitro synergistic effects on cell viability, apoptosis, and expression of IGFBP2 in endometrial cancer cells...
November 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30293136/nuclear-calcineurin-is-a-sensor-for-detecting-ca-2-release-from-the-nuclear-envelope-via-ip-3-r
#16
Silvana Olivares-Florez, Martin Czolbe, Fabian Riediger, Lea Seidlmayer, Tatjana Williams, Peter Nordbeck, Jörn Strasen, Cristina Glocker, Monique Jänsch, Petra Eder-Negrin, Paula Arias-Loza, Melanie Mühlfelder, Jelena Plačkić, Katrin G Heinze, Jeffery D Molkentin, Stefan Engelhardt, Jens Kockskämper, Oliver Ritter
In continuously beating cells like cardiac myocytes, there are rapid alterations of cytosolic Ca2+ levels. We therefore hypothesize that decoding Ca2+ signals for hypertrophic signaling requires intracellular Ca2+ microdomains that are partly independent from cytosolic Ca2+ . Furthermore, there is a need for a Ca2+ sensor within these microdomains that translates Ca2+ signals into hypertrophic signaling. Recent evidence suggested that the nucleus of cardiac myocytes might be a Ca2+ microdomain and that calcineurin, once translocated into the nucleus, could act as a nuclear Ca2+ sensor...
November 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30280293/ripor2-is-involved-in-auditory-hair-cell-stereociliary-bundle-structure-and-orientation
#17
Oscar Diaz-Horta, Clemer Abad, Filiz Basak Cengiz, Guney Bademci, Pat Blackwelder, Katherina Walz, Mustafa Tekin
RIPOR2 (previously known as FAM65B) localizes to stereocilia of auditory hair cells and causes deafness when its function is disturbed by mutations. Here, we demonstrate that during the morphogenesis of the hair cell bundle, absence of Ripor2 affects the orientation of this key subcellular structure. We show that Ripor2 interacts with Myh9, a protein encoded by a known deafness gene. Absence of Ripor2 is associated with low Myh9 abundance in the mouse cochlea despite increased amount of Myh9 transcripts. While Myh9 is mainly expressed in stereocilia, a phosphorylated form of Myh9 is particularly enriched in the kinocilium...
November 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30276549/low-dose-aspirin-treatment-enhances-the-adhesion-of-preeclamptic-decidual-mesenchymal-stem-stromal-cells-and-reduces-their-production-of-pro-inflammatory-cytokines
#18
Ramin Khanabdali, Aida Shakouri-Motlagh, Sarah Wilkinson, Padma Murthi, Harry M Georgiou, Shaun P Brennecke, Bill Kalionis
Preeclampsia (PE) is a hypertensive disorder of human pregnancy. Low-dose aspirin (acetylsalicylic acid) (60-150 mg/day) is used to prevent PE when taken early in pregnancy. The effect of aspirin on term PE remains uncertain. Abnormal placentation is a hallmark of PE and leads to increased placental oxidative stress, which triggers the release of anti-angiogenic factors that cause local damage to the decidual vasculature. The damage subsequently spreads systemically and culminates in maternal clinical symptoms...
November 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30232504/transfer-rna-derived-fragments-and-trna-halves-biogenesis-biological-functions-and-their-roles-in-diseases
#19
REVIEW
Yijing Shen, Xiuchong Yu, Linwen Zhu, Tianwen Li, Zhilong Yan, Junming Guo
The number of studies on non-coding RNAs has increased substantially in recent years owing to their importance in gene regulation. However, the biological functions of small RNAs from abundant species of housekeeping non-coding RNAs (rRNA, tRNA, etc.) remain a highly studied topic. tRNA-derived small RNAs (tsRNAs) refer to the specific cleavage of tRNAs by specific nucleases [e.g., Dicer and angiogenin (ANG)] in particular cells or tissues or under certain conditions such as stress and hypoxia. tsRNAs are a type of non-coding small RNA that are widely found in the prokaryotic and eukaryotic transcriptomes and are generated from mature tRNAs or precursor tRNAs at different sites...
November 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30229272/targeting-senescence-to-delay-progression-of-multiple-sclerosis
#20
REVIEW
Wendy Oost, Nynke Talma, Jan F Meilof, Jon D Laman
Multiple sclerosis (MS) is a chronic and often progressive, demyelinating disease of the central nervous system (CNS) white and gray matter and the single most common cause of disability in young adults. Age is one of the factors most strongly influencing the course of progression in MS. One of the hallmarks of aging is cellular senescence. The elimination of senescent cells with senolytics has very recently been shown to delay age-related dysfunction in animal models for other neurological diseases. In this review, the possible link between cellular senescence and the progression of MS is discussed, and the potential use of senolytics as a treatment for progressive MS is explored...
November 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
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