2,905 results match your criteria Journal of Molecular Medicine [Journal]


Random gene sets in predicting survival of patients with hepatocellular carcinoma.

J Mol Med (Berl) 2019 Apr 17. Epub 2019 Apr 17.

Division of Hepatology & Division of Clinical Bioinformatics, Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.

Despite multiple publications, molecular signatures predicting the course of hepatocellular carcinoma (HCC) have not yet been integrated into clinical routine decision-making. Given the diversity of published signatures, optimal number, best combinations, and benefit of functional associations of genes in prognostic signatures remain to be defined. We investigated a vast number of randomly chosen gene sets (varying between 1 and 10,000 genes) to encompass the full range of prognostic gene sets on 242 transcriptomic profiles of patients with HCC. Read More

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http://dx.doi.org/10.1007/s00109-019-01764-2DOI Listing
April 2019
2 Reads

Benefits of a factorial design focusing on inclusion of female and male animals in one experiment.

J Mol Med (Berl) 2019 Apr 13. Epub 2019 Apr 13.

Institute of Medical Statistics and Computational Biology, Faculty of Medicine, University of Cologne, Bachemer Str. 86, 50931, Cologne, Germany.

Disease occurrence, clinical manifestations, and outcomes differ between men and women. Yet, women and men are most of the time treated similarly, which is often based on experimental data over-representing one sex. Accounting for persisting sex bias in biomedical research is the misconception that the analysis of sex-specific effects would double sample size and costs. Read More

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http://dx.doi.org/10.1007/s00109-019-01774-0DOI Listing
April 2019
1 Read

Rab5C enhances resistance to ionizing radiation in rectal cancer.

J Mol Med (Berl) 2019 Apr 9. Epub 2019 Apr 9.

International Research Center, A.C.Camargo Cancer Center, Rua Taguá, 440, Liberdade, São Paulo/SP, 01508-010, Brazil.

Rectal cancer represents one third of the colorectal cancers that are diagnosed. Neoadjuvant chemoradiation is a well-established protocol for rectal cancer treatment reducing the risk of local recurrence. However, a pathologic complete response is only achieved in 10-40% of cases and the mechanisms associated with resistance are poorly understood. Read More

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http://dx.doi.org/10.1007/s00109-019-01760-6DOI Listing
April 2019
5 Reads

Circadian rhythms: a possible new player in non-alcoholic fatty liver disease pathophysiology.

J Mol Med (Berl) 2019 Apr 5. Epub 2019 Apr 5.

Interdisciplinary Department of Medicine, University of Bari School of Medicine, Piazza G. Cesare, 11, 70124, Bari, Italy.

Over the last decades, a better knowledge of the molecular machinery supervising the regulation of circadian clocks has been achieved, and numerous findings have helped in unravelling the outstanding significance of the molecular clock for the proper regulation of our physiologic and metabolic homeostasis. Non-alcoholic fatty liver disease (NAFLD) is currently considered as one of the emerging liver pathologies in the Western countries due to the modification of eating habits and lifestyle. Although NAFLD is considered a pretty benign condition, it can progress towards non-alcoholic steatohepatitis (NASH) and eventually hepatocellular carcinoma (HCC). Read More

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http://dx.doi.org/10.1007/s00109-019-01780-2DOI Listing
April 2019
4 Reads

Metabolomic signature of type 1 diabetes-induced sensory loss and nerve damage in diabetic neuropathy.

J Mol Med (Berl) 2019 Apr 4. Epub 2019 Apr 4.

Institute of Pharmacology, Heidelberg University, Im Neuenheimer Feld 366, D-69120, Heidelberg, Germany.

Diabetic-induced peripheral neuropathy (DPN) is a highly complex and frequent diabetic late complication, which is manifested by prolonged hyperglycemia. However, the molecular mechanisms underlying the pathophysiology of nerve damage and sensory loss remain largely unclear. Recently, alteration in metabolic flux has gained attention as a basis for organ damage in diabetes; however, peripheral sensory neurons have not been adequately analyzed with respect to metabolic dysfunction. Read More

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http://dx.doi.org/10.1007/s00109-019-01781-1DOI Listing
April 2019
4 Reads

ALIX increases protein content and protective function of iPSC-derived exosomes.

J Mol Med (Berl) 2019 Apr 3. Epub 2019 Apr 3.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, 130 Dong-An Road, Building 7, Room 214, Shanghai, 200032, China.

Nature of exosome-secreting cells determines exosome content and function. ALIX, involved in exosome biogenesis, promotes cell degeneration. Here, ALIX was knocked out (iPSC-ALIX) and overexpressed (iPSC-ALIX) in induced pluripotent stem cells (iPSCs) using CRISPR-Cas9 and lentiviral transduction, respectively, and the secreted exosomes were analyzed. Read More

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http://dx.doi.org/10.1007/s00109-019-01767-zDOI Listing
April 2019
1 Read

The monocyte-dependent immune response to bacteria is suppressed in smoking-induced COPD.

J Mol Med (Berl) 2019 Mar 30. Epub 2019 Mar 30.

Medical Clinic V, Ludwig-Maximilians-University LMU, Munich, Germany.

COPD patients have an increased susceptibility to bacterial airway infections that can induce exacerbations. In response to infections, circulating monocytes become recruited to the infected tissue and secrete cytokines. We hypothesized that this cytokine response is reduced in COPD. Read More

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http://dx.doi.org/10.1007/s00109-019-01778-wDOI Listing
March 2019
1 Read

Role of adiponectin in the metabolism of skeletal muscles in collagen VI-related myopathies.

J Mol Med (Berl) 2019 Mar 29. Epub 2019 Mar 29.

Dipartimento di Scienze Biomediche, Sperimentali e Cliniche "Mario Serio", Università degli Studi di Firenze, viale Morgagni 50, 50134, Florence, Italy.

The role of adiponectin has been particularly deepened in diabetic muscles while the study of adiponectin in hereditary myopathies has been marginally investigated. Here, we report the study about adiponectin effects in Col6a1 (collagen VI-null) mice. Col6a1 mice show myophatic phenotype closer to that of patients with Bethlem myopathy, thus representing an excellent animal model for the study of this hereditary disease. Read More

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http://link.springer.com/10.1007/s00109-019-01766-0
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http://dx.doi.org/10.1007/s00109-019-01766-0DOI Listing
March 2019
4 Reads

The distinct role of CD73 in the progression of pancreatic cancer.

J Mol Med (Berl) 2019 Mar 29. Epub 2019 Mar 29.

Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, No. 3, Qingchun Road, Hangzhou, 310000, China.

Recent studies have shown that the non-enzymatic function of CD73 plays a key role in tumor progression, but this function of CD73 in pancreatic cancer cells has not been studied. Furthermore, little is known about the mechanism involved in CD73 regulation in tumors. Here, we found that CD73 expression was upregulated in pancreatic ductal adenocarcinoma (PDAC) and that its expression correlated with poor prognosis. Read More

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http://dx.doi.org/10.1007/s00109-018-01742-0DOI Listing
March 2019
3 Reads

Beraprost sodium mitigates renal interstitial fibrosis through repairing renal microvessels.

J Mol Med (Berl) 2019 Mar 28. Epub 2019 Mar 28.

Department of Internal Medicine and Diagnostics, Xuzhou Medical University, Xuzhou, 221002, China.

Beraprost sodium (BPS), as a prostacyclin analog, plays a significant role in various diseases based on its antiplatelet and vasodilation functions. However, its regulation and role in chronic kidney disease (CKD) still remain elusive. Here, we determined whether BPS could alleviate renal interstitial fibrosis, and improve the renal function and its therapeutic mechanism. Read More

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http://dx.doi.org/10.1007/s00109-019-01769-xDOI Listing

Double deletion of Panx1 and Panx3 affects skin and bone but not hearing.

J Mol Med (Berl) 2019 Mar 27. Epub 2019 Mar 27.

Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, N6A 5C1, Canada.

Pannexins (Panxs), large-pore channel forming glycoproteins, are expressed in a wide variety of tissues including the skin, bone, and cochlea. To date, the use of single knock-out mouse models of both Panx1 and Panx3 have demonstrated their roles in skin development, bone formation, and auditory phenotypes. Due to sequence homology between Panx1 and Panx3, when one Panx is ablated from germline, the other may be upregulated in a compensatory mechanism to maintain tissue homeostasis and function. Read More

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http://link.springer.com/10.1007/s00109-019-01779-9
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http://dx.doi.org/10.1007/s00109-019-01779-9DOI Listing
March 2019
4 Reads

Plasma membrane-localized TMEM16 proteins are indispensable for expression of CFTR.

J Mol Med (Berl) 2019 Mar 26. Epub 2019 Mar 26.

Physiological Institute, University of Regensburg, University Street 31, D-93053, Regensburg, Germany.

The cystic fibrosis transmembrane conductance regulator (CFTR) is the secretory chloride channel in epithelial tissues that has a central role in cystic fibrosis (CF) lung and gastrointestinal disease. A recent publication demonstrates a close association between CFTR and TMEM16A, the calcium-activated chloride channel. Thus, no CFTR chloride currents could be detected in airways and large intestine from mice lacking epithelial expression of TMEM16A. Read More

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http://dx.doi.org/10.1007/s00109-019-01770-4DOI Listing
March 2019
1 Read

PRSS21/testisin inhibits ovarian tumor metastasis and antagonizes proangiogenic angiopoietins ANG2 and ANGPTL4.

J Mol Med (Berl) 2019 Mar 25. Epub 2019 Mar 25.

Center for Vascular and Inflammatory Diseases, Department of Physiology, and the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, 800 West Baltimore Street Rm 220, Baltimore, MD, 21201, USA.

Ovarian cancer is the leading cause of death among all the gynecological cancers in the USA. Ovarian cancer employs a unique mode of metastasis, as exfoliated tumor cells disseminate within the peritoneal cavity, colonizing in several sites as well as accumulating ascites. Tumor recurrence and widespread metastasis are significant factors contributing to poor prognosis. Read More

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http://link.springer.com/10.1007/s00109-019-01763-3
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http://dx.doi.org/10.1007/s00109-019-01763-3DOI Listing
March 2019
7 Reads

Response to Yang et. al.

J Mol Med (Berl) 2019 Mar 23. Epub 2019 Mar 23.

Department of Pathology and Translational Research, Gifu University Graduate School of Medicine, Gifu, 501-1194, Japan.

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http://dx.doi.org/10.1007/s00109-019-01775-zDOI Listing

Current understanding of the immunosuppressive properties of mesenchymal stromal cells.

J Mol Med (Berl) 2019 Mar 22. Epub 2019 Mar 22.

Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.

Several studies have demonstrated the anti-inflammatory potential of mesenchymal stromal cells (MSCs) isolated from bone marrow, adipose tissue, placenta, and other sources. Nevertheless, MSCs may also induce immunosuppression when administered systemically or directly to injured environments, as shown in different preclinical disease models. MSCs express certain receptors, including toll-like receptors and the aryl-hydrocarbon receptor, that are activated by the surrounding environment, thus leading to modulation of their immunosuppressive activity. Read More

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http://dx.doi.org/10.1007/s00109-019-01776-yDOI Listing

Innate immune regulatory networks in hepatic lipid metabolism.

J Mol Med (Berl) 2019 Mar 19. Epub 2019 Mar 19.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.

Hepatic lipid metabolism is closely associated with certain diseases, such as obesity, diabetes, fatty liver, and hepatic fibrosis. Hepatic steatosis results from systemic metabolic dysfunction that occurs via multiple processes. The initial process has been characterized as hepatic lipid accumulation that may be caused by increased liver lipid uptake and de novo lipogenesis or decreased lipid oxidation and lipid export; subsequently, multiple additional factors that trigger inflammation and insulin resistance (IR) aggravate the progression of hepatic steatosis. Read More

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http://dx.doi.org/10.1007/s00109-019-01765-1DOI Listing
March 2019
3 Reads
5.107 Impact Factor

Regenerative potential of adipocytes in hypertrophic scars is mediated by myofibroblast reprogramming.

J Mol Med (Berl) 2019 Mar 19. Epub 2019 Mar 19.

Institute of Pharmaceutical Sciences, Pharmacology and Toxicology, Freie Universität Berlin, 14195, Berlin, Germany.

Abnormal scarring is a major challenge in modern medicine. The central role of myofibroblasts and TGF-β signaling in scarring is widely accepted, but effective treatment options are missing. Autologous fat grafting is a novel approach that has led to significant improvements in the functionality and appearance of scar tissue. Read More

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http://dx.doi.org/10.1007/s00109-019-01772-2DOI Listing
March 2019
10 Reads

Activation of NF-κB in B cell receptor signaling through Bruton's tyrosine kinase-dependent phosphorylation of IκB-α.

J Mol Med (Berl) 2019 Mar 19. Epub 2019 Mar 19.

Department of Clinical and Experimental Medicine, University of Catanzaro "Magna Græcia", Viale Europa, Germaneto, 88100, Catanzaro, Italy.

The antigen-mediated triggering of B cell receptor (BCR) activates the transcription factor NF-κB that regulates the expression of genes involved in B cell differentiation, proliferation, and survival. The tyrosine kinase Btk is essentially required for the activation of NF-κB in BCR signaling through the canonical pathway of IKK-dependent phosphorylation and proteasomal degradation of IκB-α, the main repressor of NF-κB. Here, we provide the evidence of an additional mechanism of NF-κB activation in BCR signaling that is Btk-dependent and IKK-independent. Read More

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http://dx.doi.org/10.1007/s00109-019-01777-xDOI Listing
March 2019
1 Read
5.107 Impact Factor

Comment on "Nuclear localization of LDL receptor-related protein 1B in mammary gland carcinogenesis".

J Mol Med (Berl) 2019 Mar 15. Epub 2019 Mar 15.

Department of Nephrology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, China.

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http://dx.doi.org/10.1007/s00109-019-01773-1DOI Listing
March 2019
5.107 Impact Factor

Mitochondrial complex I deficiency and cardiovascular diseases: current evidence and future directions.

J Mol Med (Berl) 2019 Mar 12. Epub 2019 Mar 12.

Department of Angiocardioneurology, IRCCS Neuromed, Località Camerelle, 86077, Pozzilli, IS, Italy.

Compelling evidence demonstrates the emerging role of mitochondrial complex I deficiency in the onset and development of cardiovascular diseases (CVDs). In particular, defects in single subunits of mitochondrial complex I have been associated with cardiac hypertrophy, ischemia/reperfusion injury, as well as diabetic complications and stroke in pre-clinical studies. Moreover, data obtained in humans revealed that genes coding for complex I proteins were associated with different CVDs. Read More

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http://dx.doi.org/10.1007/s00109-019-01771-3DOI Listing

Dimethylaminomicheliolide ameliorates peritoneal fibrosis through the activation of autophagy.

J Mol Med (Berl) 2019 Mar 11. Epub 2019 Mar 11.

Department of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.

Peritoneal fibrosis (PF) is a major cause of ultrafiltration failure in patients receiving long-term peritoneal dialysis (PD), and effective prevention and treatment strategies are urgently needed. The dimethylamino Michael adduct of a natural product-derived micheliolide (MCL), dimethylaminomicheliolide (DMAMCL), is a new lead compound with the advantages of high stability, low toxicity, and sustainable release of MCL. This study aimed to investigate the protective effect of DMAMCL against PD-related PF and the mechanisms involved. Read More

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http://dx.doi.org/10.1007/s00109-019-01757-1DOI Listing
March 2019
2 Reads

Repositioning of the antipsychotic drug TFP for sepsis treatment.

J Mol Med (Berl) 2019 Mar 8. Epub 2019 Mar 8.

Department of Immunology, School of Medicine, KonKuk University, 268, Chungwondaero, Chungju, 27478, South Korea.

Sepsis is a disease responsible for the death of almost all critical patients. Once infected by virus or bacteria, patients can die due to systemic inflammation within a short period of time. Cytokine storm plays an essential role in causing organ dysfunction and septic shock. Read More

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http://dx.doi.org/10.1007/s00109-019-01762-4DOI Listing
March 2019
2 Reads

Serpin B1 defect and increased apoptosis of neutrophils in Cohen syndrome neutropenia.

J Mol Med (Berl) 2019 Mar 7. Epub 2019 Mar 7.

Inserm UMR1170, Gustave Roussy Cancer Center, F-94800, Villejuif, France.

Cohen syndrome (CS) is a rare genetic disorder due to mutations in VPS13B gene. Among various clinical and biological features, CS patients suffer from inconsistent neutropenia, which is associated with recurrent but minor infections. We demonstrate here that this neutropenia results from an exaggerate rate of neutrophil apoptosis. Read More

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http://dx.doi.org/10.1007/s00109-019-01754-4DOI Listing
March 2019
3 Reads

Interleukin-26 upregulates interleukin-22 production by human CD4 T cells in tuberculous pleurisy.

J Mol Med (Berl) 2019 Mar 5. Epub 2019 Mar 5.

Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

IL-26 is a potentially important player in host defense and may be a pathogenic factor in the chronic inflammatory disorders of humans. However, the involvement of IL-26 in tuberculous pleural effusion (TPE) has not been investigated. The concentration of IL-26 was determined in pleural fluids and sera from patients with pleural effusions. Read More

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http://dx.doi.org/10.1007/s00109-018-01741-1DOI Listing
March 2019
4 Reads

Insight into the mechanism of action of dimethyl fumarate in multiple sclerosis.

J Mol Med (Berl) 2019 Apr 28;97(4):463-472. Epub 2019 Feb 28.

Department of Neurology, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA.

Dimethyl fumarate (DMF) is an oral, disease-modifying agent for the treatment of relapsing-remitting multiple sclerosis (RRMS). However, details regarding its mode of action are still emerging. It is believed that the mode of action of DMF involves both nuclear factor erythroid-derived 2-related factor (Nrf2)-dependent and independent pathways, which lead to an anti-inflammatory immune response due to type II myeloid cell and Th2 cell differentiation and neuroprotection. Read More

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http://dx.doi.org/10.1007/s00109-019-01761-5DOI Listing
April 2019
2 Reads

Improving engraftment of hepatocyte transplantation using alpha-1 antitrypsin as an immune modulator.

J Mol Med (Berl) 2019 Apr 28;97(4):563-577. Epub 2019 Feb 28.

Paediatric Liver, GI and Nutrition Centre, King's College London School of Medicine at King's College Hospital, Denmark Hill, London, UK.

For patients with non-cirrhotic liver-based metabolic disorders, hepatocyte transplantation can be an effective treatment. However, long-term function of transplanted hepatocytes following infusion has not been achieved due to insufficient numbers of hepatocytes reaching the liver cell plates caused by activation of the instant blood-mediated inflammatory reaction (IBMIR). Our aim was to determine if the natural immune modulator, alpha-1 antitrypsin (AAT), could improve engraftment of transplanted hepatocytes and investigate its mechanism of action. Read More

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http://dx.doi.org/10.1007/s00109-019-01747-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440943PMC
April 2019
1 Read

Metanephric mesenchyme-derived Foxd1 mesangial precursor cells alleviate mesangial proliferative glomerulonephritis.

J Mol Med (Berl) 2019 Apr 27;97(4):553-561. Epub 2019 Feb 27.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, 28th Fuxing Road, Beijing, 100853, China.

Mesangial proliferative glomerulonephritis (MsPGN) is a glomerular disease characterized by the proliferation of mesangial cells and the accumulation of mesangial matrix. No effective treatment is currently able to stop or reverse the disease process. Here, we isolated metanephric mesenchyme-derived Foxd1 mesangial precursor cells from E13. Read More

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http://dx.doi.org/10.1007/s00109-019-01749-1DOI Listing

Klotho recovery by genistein via promoter histone acetylation and DNA demethylation mitigates renal fibrosis in mice.

J Mol Med (Berl) 2019 Apr 26;97(4):541-552. Epub 2019 Feb 26.

Jiangsu Key Laboratory of Molecular Medicine, Nanjing University School of Medicine, 22 Hankou Road, Nanjing, 210093, China.

Renal fibrosis is a common histomorphological feature of renal aging and chronic kidney diseases of all etiologies, and its initiation and progression are substantially influenced by aberrant epigenetic modifications of fibrosis-susceptible genes, yet without effective therapy. "Epigenetic diets" exhibit tissue-protective and epigenetic-modulating properties; however, their anti-renal fibrosis functions and the underlying mechanisms are less understood. In this study, we show that genistein, a phytoestrogenic isoflavone enriched in dietary soy products, exhibits impressive anti-renal fibrosis activities by recovering epigenetic loss of Klotho, a kidney-enriched anti-aging and fibrosis-suppressing protein. Read More

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http://dx.doi.org/10.1007/s00109-019-01759-zDOI Listing

Mitochondrial quality control mechanisms as potential therapeutic targets in sepsis-induced multiple organ failure.

J Mol Med (Berl) 2019 Apr 21;97(4):451-462. Epub 2019 Feb 21.

Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China.

Sepsis is a dysregulated response to severe infection characterized by life-threatening organ failure and is the leading cause of mortality worldwide. Multiple organ failure is the central characteristic of sepsis and is associated with poor outcome of septic patients. Ultrastructural damage to the mitochondria and mitochondrial dysfunction are reported in sepsis. Read More

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http://dx.doi.org/10.1007/s00109-019-01756-2DOI Listing
April 2019
7 Reads

MOTS-c: an equal opportunity insulin sensitizer.

J Mol Med (Berl) 2019 Apr 20;97(4):487-490. Epub 2019 Feb 20.

Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, 90089-0191, USA.

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http://dx.doi.org/10.1007/s00109-019-01758-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462348PMC

Molecular modeling of LDLR aids interpretation of genomic variants.

J Mol Med (Berl) 2019 Apr 18;97(4):533-540. Epub 2019 Feb 18.

Bioinformatics Research and Development Laboratory, Genomic Sciences and Precision Medicine Center, Medical College of Wisconsin, Milwaukee, WI, 53226-0509, USA.

Genetic variants in low-density lipoprotein receptor (LDLR) are known to cause familial hypercholesterolemia (FH), occurring in up to 1 in 200 people (Youngblom E. et al. 1993 and Nordestgaard BG et al. Read More

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http://dx.doi.org/10.1007/s00109-019-01755-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440939PMC

Correction to: Trichostatin A, a histone deacetylase inhibitor, induces synergistic cytotoxicity with chemotherapy via suppression of Raf/MEK/ERK pathway in urothelial carcinoma.

J Mol Med (Berl) 2019 Mar;97(3):435-436

Department of Urology, College of Medicine, National Taiwan University, National Taiwan University Hospital, Taipei, Taiwan.

In Fig. 1b, upper part, the cell viability counts after treatment with cisplatin and TSA in T24 cells was by mistake a duplication of the image for NTUB1 on the left. In the corrected version of Fig. Read More

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http://dx.doi.org/10.1007/s00109-019-01748-2DOI Listing

Efficacy of novel selective NLRP3 inhibitors in human and murine retinal pigment epithelial cells.

J Mol Med (Berl) 2019 Apr 10;97(4):523-532. Epub 2019 Feb 10.

Department of Ophthalmology, University of Bonn, Ernst-Abbe-Str. 2, Bonn, 53127, Germany.

NLRP3 inflammasome activation in the retinal pigment epithelium (RPE) is observed in atrophic age-related macular degeneration (AMD), and pharmacological NLRP3 inhibition may provide a therapeutic strategy to halt disease progression. We tested selective NLRP3 inhibitors (IFM-514, IFM-632, and CRID3) for their efficacy in human and murine RPE cells. Inflammasome activation was induced in primary human RPE cells and ARPE-19 cells following priming with IL-1α by different stimuli, including lysosomal membrane permeabilization by leucyl-leucine methyl ester (Leu-Leu-OMe), oxidative damage induced by hydrogen peroxide, lipofuscin-mediated photooxidative damage induced by incubation with 4-hydroxynonenal-modified photoreceptor outer segments and subsequent blue light irradiation, and P2X7 receptor activation by benzoylbenzoyl-ATP. Read More

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http://dx.doi.org/10.1007/s00109-019-01753-5DOI Listing
April 2019
2 Reads

Exploring the roles of MSCs in infections: focus on bacterial diseases.

J Mol Med (Berl) 2019 Apr 7;97(4):437-450. Epub 2019 Feb 7.

Department of Experimental, Diagnostic and Specialty Medicine, Unit of Histology, Embryology and Applied Biology, University of Bologna, Via Belmeloro 8, 40126, Bologna, Italy.

Despite human healthcare advances, some microorganisms continuously react evolving new survival strategies, choosing between a commensal fitness and a pathogenic attitude. Many opportunistic microbes are becoming an increasing cause of clinically evident infections while several renowned infectious diseases sustain a considerable number of deaths. Besides the primary and extensively investigated role of immune cells, other cell types are involved in the microbe-host interaction during infection. Read More

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http://link.springer.com/10.1007/s00109-019-01752-6
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http://dx.doi.org/10.1007/s00109-019-01752-6DOI Listing
April 2019
9 Reads

FOXM1 plays a role in autophagy by transcriptionally regulating Beclin-1 and LC3 genes in human triple-negative breast cancer cells.

J Mol Med (Berl) 2019 Apr 7;97(4):491-508. Epub 2019 Feb 7.

Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Triple-negative breast cancer (TNBC) is associated with poor prognosis owing to its aggressive and heterogeneous nature, and the lack of therapeutic targets. Although Forkhead Box M1 (FOXM1) is one of the most important oncogenes contributing to tumorigenesis, progression, and drug resistance in TNBC, the underlying molecular mechanisms are not well understood. Emerging evidence indicates that autophagy plays a critical role in cell survival and protective mechanism in TNBC. Read More

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http://dx.doi.org/10.1007/s00109-019-01750-8DOI Listing
April 2019
1 Read

MicroRNA-145 targets Smad1 in endometrial stromal cells and regulates decidualization in rat.

J Mol Med (Berl) 2019 Apr 7;97(4):509-522. Epub 2019 Feb 7.

Division of Endocrinology, CSIR-Central Drug Research Institute|, Lucknow, Uttar Pradesh, 226031, India.

Decidualization of endometrial stromal cells is the pre-requisite for the embryo implantation and establishment of pregnancy. Although known to be regulated by several factors, the process of regulation of decidualization by miRNAs is largely unknown. Previous reports suggest that the upregulated expression of miR-145 is associated with repeated implantation failure. Read More

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http://dx.doi.org/10.1007/s00109-019-01744-6DOI Listing
April 2019
5 Reads

MOTS-c peptide regulates adipose homeostasis to prevent ovariectomy-induced metabolic dysfunction.

J Mol Med (Berl) 2019 Apr 6;97(4):473-485. Epub 2019 Feb 6.

State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, School of Pharmacy, Air Force Medical University, No. 169 West Chang-le Road, Xi'an, 710032, People's Republic of China.

The postmenopausal state is associated with an increased risk of metabolic disorder including reduced energy expenditure and weight gain, leading to higher cardiovascular and cancer risks among other diseases. Mitochondrial-derived peptide (MOTS-c) is a 16-amino acid peptide encoded by mitochondrial DNA. Here, we showed that MOTS-c treatment in mice prevented ovariectomy-induced obesity and insulin resistance. Read More

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http://dx.doi.org/10.1007/s00109-018-01738-wDOI Listing
April 2019
1 Read
5.107 Impact Factor

AMPK agonist AICAR ameliorates portal hypertension and liver cirrhosis via NO pathway in the BDL rat model.

J Mol Med (Berl) 2019 Mar 5;97(3):423-434. Epub 2019 Feb 5.

Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Westmead, NSW, 2145, Australia.

Recent studies have indicated that the Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathway is closely involved in liver fibrosis and other fibrotic diseases. However, whether targeting the AMPK pathway can rescue liver fibrosis and its complications, such as portal hypertension, is unknown. This study aimed to explore the therapeutic value of AICAR (5-aminoimidazole-4-carboxyamide ribonucleoside), an agonist of the AMPK pathway, on liver fibrosis and portal hypertension in bile duct ligation (BDL) rats. Read More

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http://dx.doi.org/10.1007/s00109-019-01746-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394556PMC
March 2019
9 Reads

MiR-449a-5p mediates mitochondrial dysfunction and phenotypic transition by targeting Myc in pulmonary arterial smooth muscle cells.

J Mol Med (Berl) 2019 Mar 4;97(3):409-422. Epub 2019 Feb 4.

Central Laboratory, Harbin Medical University (Daqing), Daqing, 163319, People's Republic of China.

MicroRNAs have been considered to participate in pulmonary arterial hypertension (PAH) and regulate numerous disease pathways in pulmonary vasculature. However, the molecular role in the pathologies has not yet been fully uncovered, particularly in the view of energy metabolism and vascular smooth muscle cell phenotypic regulation. Here, several altered miRNAs are founded in genome-wide miRNA sequencing analysis, in which miR-449a-5p was identified as a probable candidate in hypoxic PAH and verified such a decreasing trend. Read More

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http://dx.doi.org/10.1007/s00109-019-01751-7DOI Listing
March 2019
1 Read
5.107 Impact Factor

Role of sirtuin-1 in diabetic nephropathy.

J Mol Med (Berl) 2019 Mar 1;97(3):291-309. Epub 2019 Feb 1.

Pediatric Research Institute, Department of Pediatrics, The University of Louisville School of Medicine, Louisville, KY, 40292, USA.

Diabetic nephropathy (DN) is a research priority for scientists around the world because of its high prevalence and poor prognosis. Although several mechanisms have been shown to be involved in its pathogenesis and many useful drugs have been developed, the management of DN remains challenging. Increasing amounts of evidence show that silent information regulator 2 homolog 1 (sirtuin-1), a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase, plays a crucial role in the pathogenesis and development of DN. Read More

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http://dx.doi.org/10.1007/s00109-019-01743-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394539PMC
March 2019
2 Reads

Are glutamate transporters neuroprotective or neurodegenerative during cerebral ischemia?

J Mol Med (Berl) 2019 Mar 23;97(3):281-289. Epub 2019 Jan 23.

Department of Pathophysiology, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang, 050017, Hebei, China.

The accumulation of glutamate (Glu) in the synaptic cleft during cerebral ischemia triggers the death of neurons, causing mental or physical handicap. However, the mechanisms of the alteration in Glu homeostasis and the imbalance between the release and clearance of Glu in ischemia are not yet completely understood. Additionally, the role of Glu transporters in regulating Glu concentration in the synaptic cleft is controversial. Read More

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http://dx.doi.org/10.1007/s00109-019-01745-5DOI Listing
March 2019
1 Read

Follicular helper T cell and memory B cell immunity in CHC patients.

J Mol Med (Berl) 2019 Mar 21;97(3):397-407. Epub 2019 Jan 21.

Genetic Diagnosis Center, The First Hospital of Jilin University, Changchun, 130021, China.

Chronic hepatitis C (CHC) is associated with biological activity of T follicular helper (Tfh) cells and memory B cells (MBCs). However, the nature of Tfh cell subsets that are responsible for MBCs in CHC patients has not been evaluated. This study aimed to investigate Tfh and MBC immunity before and after direct-acting antiviral (DAA) therapy in patients with CHC. Read More

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http://dx.doi.org/10.1007/s00109-018-01735-zDOI Listing
March 2019
7 Reads

IDH-1 deficiency induces growth defects and metabolic alterations in GSPD-1-deficient Caenorhabditis elegans.

J Mol Med (Berl) 2019 Mar 19;97(3):385-396. Epub 2019 Jan 19.

Department of Medical Biotechnology and Laboratory Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.

NADPH is a reducing equivalent that maintains redox homeostasis and supports reductive biosynthesis. Lack of major NADPH-producing enzymes predisposes cells to growth retardation and demise. It was hypothesized that double deficiency of the NADPH-generating enzymes, GSPD-1 (Glucose-6-phosphate 1-dehydrogenase), a functional homolog of human glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway, and IDH-1 (isocitrate dehydrogenase-1) affect growth and development in the nematode, Caenorhabditis elegans (C. Read More

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http://dx.doi.org/10.1007/s00109-018-01740-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394583PMC
March 2019
2 Reads

Suppression of Syk activation by resveratrol inhibits MSU crystal-induced inflammation in human monocytes.

J Mol Med (Berl) 2019 Mar 12;97(3):369-383. Epub 2019 Jan 12.

Department of Biomedical Sciences, and BK21 Plus Biomedical Science Project, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea.

Monosodium urate (MSU) crystals are an endogenous sterile particulate that has been identified as a potent damage-associated molecular pattern (DAMP). In humans, the induction of IL-1β production through MSU-induced NLRP3 inflammasome activation in monocytes/macrophages is responsible for pathogenesis of gouty arthritis. It was recently reported that in a murine model of this disease, resveratrol decreases MSU-induced recurrent attacks of gouty arthritis. Read More

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http://link.springer.com/10.1007/s00109-018-01736-y
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http://dx.doi.org/10.1007/s00109-018-01736-yDOI Listing
March 2019
14 Reads

NLRP7 is increased in human idiopathic fetal growth restriction and plays a critical role in trophoblast differentiation.

J Mol Med (Berl) 2019 Mar 8;97(3):355-367. Epub 2019 Jan 8.

Institut National de la Santé et de la Recherche Médicale, Unité 1036, Grenoble, France.

Fetal growth restriction (FGR) the leading cause of perinatal mortality and morbidity is highly related to abnormal placental development, and placentas from FGR pregnancies are often characterized by increased inflammation. However, the mechanisms of FGR-associated inflammation are far from being understood. NLRP7, a member of a family of receptors involved in the innate immune responses, has been shown to be associated with gestational trophoblastic diseases. Read More

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http://dx.doi.org/10.1007/s00109-018-01737-xDOI Listing
March 2019
1 Read

Pathological role of apoptosis signal-regulating kinase 1 in human diseases and its potential as a therapeutic target for cognitive disorders.

J Mol Med (Berl) 2019 Feb 7;97(2):153-161. Epub 2019 Jan 7.

Department of Life Science, College of Science and Engineering, Kyonggi University, 154-42 Gwanggyosan-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do, 16227, Republic of Korea.

Cognitive disorders are among the leading causes of health and social issues, as well as socioeconomic burden. Cognitive dysfunction associated with diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, diabetes, and stroke can lead to dementia. Despite extensive efforts, strategies for the prevention and treatment of cognitive dysfunction are scarce. Read More

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http://dx.doi.org/10.1007/s00109-018-01739-9DOI Listing
February 2019
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Soluble and membrane-bound adenylate kinase and nucleotidases augment ATP-mediated inflammation in diabetic retinopathy eyes with vitreous hemorrhage.

J Mol Med (Berl) 2019 Mar 7;97(3):341-354. Epub 2019 Jan 7.

MediCity Research Laboratory, University of Turku, Tykistökatu 6A, 20520, Turku, Finland.

ATP and adenosine are important signaling molecules involved in vascular remodeling, retinal function, and neurovascular coupling in the eye. Current knowledge on enzymatic pathways governing the duration and magnitude of ocular purinergic signaling is incompletely understood. By employing sensitive analytical assays, this study dissected ocular purine homeostasis as a complex and coordinated network. Read More

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http://dx.doi.org/10.1007/s00109-018-01734-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394560PMC
March 2019
4 Reads

Calreticulin regulates MYCN expression to control neuronal differentiation and stemness of neuroblastoma.

J Mol Med (Berl) 2019 Mar 5;97(3):325-339. Epub 2019 Jan 5.

Department of Radiation Oncology, Chang Gung Memorial Hospital, Linkou, Taiwan.

Oncogenic N-MYC (MYCN) is widely used as a biomarker in clinics for neuroblastoma (NB) patients; nevertheless, mechanism that underlines MYCN regulation remains elusive. In the present study, we identified calreticulin (CRT) as a novel MYCN suppressor that downregulated MYCN promoter activity and protein expression to modulate neuronal differentiation and stemness. Our data showed that CRT-mediated MYCN suppression led to increased neurite length and commensurate elevation in differentiation marker GAP-43. Read More

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http://dx.doi.org/10.1007/s00109-018-1730-xDOI Listing
March 2019
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An endothelial cell line infected by Kaposi's sarcoma-associated herpes virus (KSHV) allows the investigation of Kaposi's sarcoma and the validation of novel viral inhibitors in vitro and in vivo.

J Mol Med (Berl) 2019 Mar 4;97(3):311-324. Epub 2019 Jan 4.

Model Systems for Infection and Immunity, Helmholtz Centre for Infection Research, Inhoffenstr. 7, 38124, Braunschweig, Germany.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma (KS), a tumor of endothelial origin predominantly affecting immunosuppressed individuals. Up to date, vaccines and targeted therapies are not available. Screening and identification of anti-viral compounds are compromised by the lack of scalable cell culture systems reflecting properties of virus-transformed cells in patients. Read More

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http://dx.doi.org/10.1007/s00109-018-01733-1DOI Listing
March 2019
4 Reads
5.107 Impact Factor

Nuclear localization of LDL receptor-related protein 1B in mammary gland carcinogenesis.

J Mol Med (Berl) 2019 Feb 3;97(2):257-268. Epub 2019 Jan 3.

Department of Surgical Oncology, Gifu University, Gifu University Graduate School of Medicine, Gifu, Japan.

LRP1B intracellular domain is released and transported to the nucleus; however, pathological consequences of this nuclear transport are largely unclear. We aimed to unravel the pathobiological significance of nuclear localization of LRP1B intracellular domain in mammary gland carcinogenesis. Immunohistochemical staining using antibodies for LRP1B intracellular domain was performed to determine LRP1B expression in 92 invasive ductal breast carcinomas. Read More

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http://dx.doi.org/10.1007/s00109-018-01732-2DOI Listing
February 2019
1 Read