The effect of fornix deep brain stimulation in brain diseases.
Abstract Deep brain stimulation is used to alleviate symptoms of neurological and psychiatric disorders including Parkinson's disease, epilepsy, and obsessive-compulsive-disorder. Electrically stimulating limbic structures has been of great interest, and in particular, the region of the fornix. We conducted a systematic search for studies that reported clinical and preclinical outcomes of deep brain stimulation within the fornix up to July 2019. We identified 13 studies (7 clinical, 6 preclinical) that examined the effects of fornix stimulation in Alzheimer's disease (n = 9), traumatic brain injury (...
Source: Cellular and Molecular Life Sciences : CMLS - January 23, 2020 Category: Cytology Authors: Liu H, Temel Y, Boonstra J, Hescham S Tags: Cell Mol Life Sci Source Type: research

The lung microbiota: role in maintaining pulmonary immune homeostasis and its implications in cancer development and therapy.
Abstract Like other body districts, lungs present a complex bacteria community. An emerging function of lung microbiota is to promote and maintain a state of immune tolerance, to prevent uncontrolled and not desirable inflammatory response caused by inhalation of harmless environmental stimuli. This effect is mediated by a continuous dialog between commensal bacteria and immune cells resident in lungs, which express a repertoire of sensors able to detect microorganisms. The same receptors are also involved in the recognition of pathogens and in mounting a proper immune response. Due to its important role in preser...
Source: Cellular and Molecular Life Sciences : CMLS - January 23, 2020 Category: Cytology Authors: Sommariva M, Le Noci V, Bianchi F, Camelliti S, Balsari A, Tagliabue E, Sfondrini L Tags: Cell Mol Life Sci Source Type: research

The mechanisms of pathological extramedullary hematopoiesis in diseases.
This article reviews the recent progress of research on the cellular and molecular mechanisms of pathological EMH in specific diseases. PMID: 31974657 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - January 23, 2020 Category: Cytology Authors: Yang X, Chen D, Long H, Zhu B Tags: Cell Mol Life Sci Source Type: research

Biomedical applications of electrical stimulation.
Abstract This review provides a comprehensive overview on the biomedical applications of electrical stimulation (EStim). EStim has a wide range of direct effects on both biomolecules and cells. These effects have been exploited to facilitate proliferation and functional development of engineered tissue constructs for regenerative medicine applications. They have also been tested or used in clinics for pain mitigation, muscle rehabilitation, the treatment of motor/consciousness disorders, wound healing, and drug delivery. However, the research on fundamental mechanism of cellular response to EStim has fell behind i...
Source: Cellular and Molecular Life Sciences : CMLS - January 23, 2020 Category: Cytology Authors: Zhao S, Mehta AS, Zhao M Tags: Cell Mol Life Sci Source Type: research

Melatonin inhibits Warburg-dependent cancer by redirecting glucose oxidation to the mitochondria: a mechanistic hypothesis.
Abstract Melatonin has the ability to intervene in the initiation, progression and metastasis of some experimental cancers. A large variety of potential mechanisms have been advanced to describe the metabolic and molecular events associated with melatonin's interactions with cancer cells. There is one metabolic perturbation that is common to a large number of solid tumors and accounts for the ability of cancer cells to actively proliferate, avoid apoptosis, and readily metastasize, i.e., they use cytosolic aerobic glycolysis (the Warburg effect) to rapidly generate the necessary ATP required for the high metabolic...
Source: Cellular and Molecular Life Sciences : CMLS - January 22, 2020 Category: Cytology Authors: Reiter RJ, Sharma R, Ma Q, Rorsales-Corral S, de Almeida Chuffa LG Tags: Cell Mol Life Sci Source Type: research

Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy.
Abstract Mesenchymal stem cells (MSCs) have been extensively investigated for the treatment of various diseases. The therapeutic potential of MSCs is attributed to complex cellular and molecular mechanisms of action including differentiation into multiple cell lineages and regulation of immune responses via immunomodulation. The plasticity of MSCs in immunomodulation allow these cells to exert different immune effects depending on different diseases. Understanding the biology of MSCs and their role in treatment is critical to determine their potential for various therapeutic applications and for the development of...
Source: Cellular and Molecular Life Sciences : CMLS - January 21, 2020 Category: Cytology Authors: Fan XL, Zhang Y, Li X, Fu QL Tags: Cell Mol Life Sci Source Type: research

Deciphering the neuroprotective and neurogenic potential of soluble amyloid precursor protein alpha (sAPP α).
Deciphering the neuroprotective and neurogenic potential of soluble amyloid precursor protein alpha (sAPPα). Cell Mol Life Sci. 2020 Jan 20;: Authors: Dar NJ, Glazner GW Abstract Amyloid precursor protein (APP) is a transmembrane protein expressed largely within the central nervous system. Upon cleavage, it does not produce the toxic amyloid peptide (Aβ) only, which is involved in neurodegenerative progressions but via a non-amyloidogenic pathway it is metabolized to produce a soluble fragment (sAPPα) through α-secretase. While a lot of studies are focusing on the role played by...
Source: Cellular and Molecular Life Sciences : CMLS - January 20, 2020 Category: Cytology Authors: Dar NJ, Glazner GW Tags: Cell Mol Life Sci Source Type: research

Loss of function in the Drosophila clock gene period results in altered intermediary lipid metabolism and increased susceptibility to starvation.
ekete A Abstract The fruit fly Drosophila is a prime model in circadian research, but still little is known about its circadian regulation of metabolism. Daily rhythmicity in levels of several metabolites has been found, but knowledge about hydrophobic metabolites is limited. We here compared metabolite levels including lipids between period01 (per01) clock mutants and Canton-S wildtype (WTCS) flies in an isogenic and non-isogenic background using LC-MS. In the non-isogenic background, metabolites with differing levels comprised essential amino acids, kynurenines, pterinates, glycero(phospho)lipids, and fatty acid...
Source: Cellular and Molecular Life Sciences : CMLS - January 20, 2020 Category: Cytology Authors: Schäbler S, Amatobi KM, Horn M, Rieger D, Helfrich-Förster C, Mueller MJ, Wegener C, Fekete A Tags: Cell Mol Life Sci Source Type: research

PEBP1/RKIP behavior: a mirror of actin-membrane organization.
Abstract Phosphatidylethanolamine-binding protein 1 (PEBP1), a small 21 kDa protein, is implicated in several key processes of the living cell. The deregulation of PEBP1, especially its downregulation, leads to major diseases such as cancer and Alzheimer's disease. PEBP1 was found to interact with numerous proteins, especially kinases and GTPases, generally inhibiting their activity. To understand the basic functionality of this amazing small protein, we have considered several known processes that it modulates and we have discussed the role of each molecular target in these processes. Here, we propose that c...
Source: Cellular and Molecular Life Sciences : CMLS - January 20, 2020 Category: Cytology Authors: Schoentgen F, Jonic S Tags: Cell Mol Life Sci Source Type: research

Regulation of spermatogenesis and reproductive capacity by Igf3 in tilapia.
Abstract A novel insulin-like growth factor (igf3), which is exclusively expressed in the gonads, has been widely identified in fish species. Recent studies have indicated that Igf3 regulates spermatogonia proliferation and differentiation in zebrafish; however, detailed information on the role of this Igf needs further in vivo investigation. Here, using Nile tilapia (Oreochromis niloticus) as an animal model, we report that igf3 is required for spermatogenesis and reproduction. Knockout of igf3 by CRISPR/Cas9 severely inhibited spermatogonial proliferation and differentiation at 90 days after hatching, the t...
Source: Cellular and Molecular Life Sciences : CMLS - January 18, 2020 Category: Cytology Authors: Li M, Liu X, Dai S, Xiao H, Qi S, Li Y, Zheng Q, Jie M, Cheng CHK, Wang D Tags: Cell Mol Life Sci Source Type: research

Epigenetic histone modulation contributes to improvements in inflammatory bowel disease via EBI3.
In conclusion, our results reveal that under inflammatory conditions, EBI3 is upregulated by the epigenetic mechanism of histone acetylation. The in vivo data show that the deficiency of EBI3 plays a key role in colitis manifestation. Concordantly, our data suggest that conditions promoting histone acetylation, such as upon HDACi application, improve colitis by a mechanism involving the local formation of the anti-inflammatory cytokine IL-35. PMID: 31955243 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - January 18, 2020 Category: Cytology Authors: Wetzel A, Scholtka B, Gerecke C, Kleuser B Tags: Cell Mol Life Sci Source Type: research

DNA-PK: gatekeeper for IKK γ/NEMO nucleocytoplasmic shuttling in genotoxic stress-induced NF-kappaB activation.
DNA-PK: gatekeeper for IKKγ/NEMO nucleocytoplasmic shuttling in genotoxic stress-induced NF-kappaB activation. Cell Mol Life Sci. 2020 Jan 13;: Authors: Medunjanin S, Putzier M, Nöthen T, Weinert S, Kähne T, Luani B, Zuschratter W, Braun-Dullaeus RC Abstract The transcription factors of the nuclear factor κB (NF-κB) family play a pivotal role in the cellular response to DNA damage. Genotoxic stress-induced activation of NF-κB differs from the classical canonical pathway by shuttling of the NF-κB Essential Modifier (IKKγ/NEMO) subunit through the nucleus. H...
Source: Cellular and Molecular Life Sciences : CMLS - January 13, 2020 Category: Cytology Authors: Medunjanin S, Putzier M, Nöthen T, Weinert S, Kähne T, Luani B, Zuschratter W, Braun-Dullaeus RC Tags: Cell Mol Life Sci Source Type: research

Systems biology: current status and challenges.
Abstract We put together a special issue on current approaches in systems biology with a focus on mathematical modeling of metabolic networks. Mathematical models have increasingly been used to unravel molecular mechanisms of complex dynamic biological processes. We here provide a short introduction into the topics covered in this special issue, highlighting current developments and challenges. PMID: 31932855 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - January 13, 2020 Category: Cytology Authors: Zupanic A, Bernstein HC, Heiland I Tags: Cell Mol Life Sci Source Type: research

GRK2 levels in myeloid cells modulate adipose-liver crosstalk in high fat diet-induced obesity.
Kavelaars A, Mayor F, Murga C Abstract Macrophages are key effector cells in obesity-associated inflammation. G protein-coupled receptor kinase 2 (GRK2) is highly expressed in different immune cell types. Using LysM-GRK2+/- mice, we uncover that a reduction of GRK2 levels in myeloid cells prevents the development of glucose intolerance and hyperglycemia after a high fat diet (HFD) through modulation of the macrophage pro-inflammatory profile. Low levels of myeloid GRK2 confer protection against hepatic insulin resistance, steatosis and inflammation. In adipose tissue, pro-inflammatory cytokines are reduced and ins...
Source: Cellular and Molecular Life Sciences : CMLS - January 11, 2020 Category: Cytology Authors: Vila-Bedmar R, Cruces-Sande M, Arcones AC, Willemen HLDM, Prieto P, Moreno-Indias I, Díaz-Rodríguez D, Francisco S, Jaén RI, Gutiérrez-Repiso C, Heijnen CJ, Boscá L, Fresno M, Kavelaars A, Mayor F, Murga C Tags: Cell Mol Life Sci Source Type: research

The cannabinoid ligands SR141716A and AM251 enhance human and mouse islet function via GPR55-independent signalling.
CONCLUSION: These observations may be useful in directing development of peripherally restricted novel therapeutics that are structurally related to SR141716A and AM251, and which potentiate glucose-induced insulin secretion and stimulate β-cell proliferation. PMID: 31925452 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - January 10, 2020 Category: Cytology Authors: Ruz-Maldonado I, Liu B, Atanes P, Pingitore A, Huang GC, Choudhary P, Persaud SJ Tags: Cell Mol Life Sci Source Type: research

Biased agonists at the human Y1 receptor lead to prolonged membrane residency and extended receptor G protein interaction.
Abstract Functionally selective ligands to address specific cellular responses downstream of G protein-coupled receptors (GPCR) open up new possibilities for therapeutics. We designed and characterized novel subtype- and pathway-selective ligands. Substitution of position Q34 of neuropeptide Y to glycine (G34-NPY) results in unprecedented selectivity over all other YR subtypes. Moreover, this ligand displays a significant bias towards activation of the Gi/o pathway over recruitment of arrestin-3. Notably, no bias is observed for an established Y1R versus Y2R selective ligand carrying a proline at position 34 (F7,P34...
Source: Cellular and Molecular Life Sciences : CMLS - January 9, 2020 Category: Cytology Authors: Kaiser A, Wanka L, Ziffert I, Beck-Sickinger AG Tags: Cell Mol Life Sci Source Type: research

Correction to: Molecular mechanism of olesoxime-mediated neuroprotection through targeting α-synuclein interaction with mitochondrial VDAC.
Correction to: Molecular mechanism of olesoxime-mediated neuroprotection through targeting α-synuclein interaction with mitochondrial VDAC. Cell Mol Life Sci. 2020 Jan 09;: Authors: Rovini A, Gurnev PA, Beilina A, Queralt-Martín M, Rosencrans W, Cookson MR, Bezrukov SM, Rostovtseva TK Abstract In the published article, an error was noticed and this has been corrected with this erratum publication. PMID: 31919572 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - January 9, 2020 Category: Cytology Authors: Rovini A, Gurnev PA, Beilina A, Queralt-Martín M, Rosencrans W, Cookson MR, Bezrukov SM, Rostovtseva TK Tags: Cell Mol Life Sci Source Type: research

Retraction Note to: cGMP-phosphodiesterase 6, transducin and Wnt5a/Frizzled-2-signaling control cGMP and Ca2+ homeostasis in melanoma cells.
SB Abstract The Editor-in-Chief has retracted this article [1] due to errors in Figs. 1b, c and 4. PMID: 31919573 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - January 9, 2020 Category: Cytology Authors: Bazhin AV, Tambor V, Dikov B, Philippov PP, Schadendorf D, Eichmüller SB Tags: Cell Mol Life Sci Source Type: research

Correction to: Tet3 regulates cellular identity and DNA methylation in neural progenitor cells.
Abstract The article Tet3 regulates cellular identity and DNA methylation in neural progenitor cells, written by Miguel R. Branco and C. Joana Marques, was originally published electronically on the publisher's internet portal. PMID: 31919574 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - January 9, 2020 Category: Cytology Authors: Santiago M, Antunes C, Guedes M, Iacovino M, Kyba M, Reik W, Sousa N, Pinto L, Branco MR, Marques CJ Tags: Cell Mol Life Sci Source Type: research

Human pluripotent stem cell-derived chondroprogenitors for cartilage tissue engineering.
Abstract The cartilage of joints, such as meniscus and articular cartilage, is normally long lasting (i.e., permanent). However, once damaged, especially in large animals and humans, joint cartilage is not spontaneously repaired. Compensating the lack of repair activity by supplying cartilage-(re)forming cells, such as chondrocytes or mesenchymal stromal cells, or by transplanting a piece of normal cartilage, has been the basis of therapy for biological restoration of damaged joint cartilage. Unfortunately, current biological therapies face problems on a number of fronts. The joint cartilage is generated de novo f...
Source: Cellular and Molecular Life Sciences : CMLS - January 8, 2020 Category: Cytology Authors: Nakayama N, Pothiawala A, Lee JY, Matthias N, Umeda K, Ang BK, Huard J, Huang Y, Sun D Tags: Cell Mol Life Sci Source Type: research

Metabolic regulation of neurodifferentiation in the adult brain.
Abstract Understanding the mechanisms behind neurodifferentiation in adults will be an important milestone in our quest to identify treatment strategies for cognitive disorders observed during our natural ageing or disease. It is now clear that the maturation of neural stem cells to neurones, fully integrated into neuronal circuits requires a complete remodelling of cellular metabolism, including switching the cellular energy source. Mitochondria are central for this transition and are increasingly seen as the regulatory hub in defining neural stem cell fate and neurodevelopment. This review explores our current k...
Source: Cellular and Molecular Life Sciences : CMLS - January 7, 2020 Category: Cytology Authors: Maffezzini C, Calvo-Garrido J, Wredenberg A, Freyer C Tags: Cell Mol Life Sci Source Type: research

An intact keratin network is crucial for mechanical integrity and barrier function in keratinocyte cell sheets.
In this study, the role and significance of the keratin network for mechanical integrity, force transmission, and barrier formation were analyzed in murine keratinocytes. Following the time-course of single-cell wound closure, wild-type (WT) cells slowly closed the gap in a collective fashion involving tightly connected neighboring cells. In contrast, the mechanical response of neighboring cells was compromised in keratin-deficient cells, causing an increased wound area initially and an inefficient overall wound closure. Furthermore, the loss of the keratin network led to impaired, fragmented cell-cell junctions, and ...
Source: Cellular and Molecular Life Sciences : CMLS - January 7, 2020 Category: Cytology Authors: Karsch S, Büchau F, Magin TM, Janshoff A Tags: Cell Mol Life Sci Source Type: research

Dynein-mediated nuclear translocation of yes-associated protein through microtubule acetylation controls fibroblast activation.
Abstract Myofibroblasts are the major cell type that is responsible for increase in the mechanical stiffness in fibrotic tissues. It has well documented that the TGF-β/Smad axis is required for myofibroblast differentiation under the rigid substrate condition. However, the mechanism driving myofibroblast differentiation in soft substrates remains unknown. In this research, we demonstrated that interaction of yes-associated protein (YAP) and acetylated microtubule via dynein, a microtubule motor protein drives nuclear localization of YAP in the soft matrix, which in turn increased TGF-β1-induced transcrip...
Source: Cellular and Molecular Life Sciences : CMLS - January 7, 2020 Category: Cytology Authors: You E, Ko P, Jeong J, Keum S, Kim JW, Seo YJ, Song WK, Rhee S Tags: Cell Mol Life Sci Source Type: research

Hypoxia: a barricade to conquer the pancreatic cancer.
Abstract Pancreatic cancer (PC) remains one of the most extremely lethal malignancies worldwide due to late diagnosis and early metastasis, with a 1-year overall survival rate of approximately 20%. The hypoxic microenvironment, induced by intratumoral hypoxia, promotes tumor invasion and progression, leading to chemotherapy or radiotherapy resistance and eventual mortality after treatment of PC. However, the role of the hypoxic microenvironment in PC is complicated and requires further investigation. In this article, we review recent advances regarding the regulation of malignant behaviors in PC, which provide ins...
Source: Cellular and Molecular Life Sciences : CMLS - January 6, 2020 Category: Cytology Authors: Tan Z, Xu J, Zhang B, Shi S, Yu X, Liang C Tags: Cell Mol Life Sci Source Type: research

The role of lipocalin-2 in age-related macular degeneration (AMD).
Abstract Lipocalins are a family of secreted adipokines which play important roles in various biological processes. Lipocalin-2 (LCN-2) has been shown to be involved in acute and chronic inflammation. This particular protein is critical in the pathogenesis of several diseases including cancer, diabetes, obesity, and multiple sclerosis. Herein, we discuss the general molecular basis for the involvement of LCN-2 in acute infections and chronic disease progression and also ascertain the probable role of LCN-2 in ocular diseases, particularly in age-related macular degeneration (AMD). We elaborate on the signaling cas...
Source: Cellular and Molecular Life Sciences : CMLS - January 4, 2020 Category: Cytology Authors: Ghosh S, Stepicheva N, Yazdankhah M, Shang P, Watson AM, Hose S, Liu H, Weiss J, Zigler JS, Valapala M, Watkins SC, Sinha D Tags: Cell Mol Life Sci Source Type: research

GPR50-Ctail cleavage and nuclear translocation: a new signal transduction mode for G protein-coupled receptors.
ers R Abstract Transmission of extracellular signals by G protein-coupled receptors typically relies on a cascade of intracellular events initiated by the activation of heterotrimeric G proteins or β-arrestins followed by effector activation/inhibition. Here, we report an alternative signal transduction mode used by the orphan GPR50 that relies on the nuclear translocation of its carboxyl-terminal domain (CTD). Activation of the calcium-dependent calpain protease cleaves off the CTD from the transmembrane-bound GPR50 core domain between Phe-408 and Ser-409 as determined by MALDI-TOF-mass spectrometry. The cyt...
Source: Cellular and Molecular Life Sciences : CMLS - January 3, 2020 Category: Cytology Authors: Ahmad R, Lahuna O, Sidibe A, Daulat A, Zhang Q, Luka M, Guillaume JL, Gallet S, Guillonneau F, Hamroune J, Polo S, Prévot V, Delagrange P, Dam J, Jockers R Tags: Cell Mol Life Sci Source Type: research

Frizzled 1 and Wnt1 as new potential therapeutic targets in the traumatically injured spinal cord.
enberg M, Rodríguez FJ Abstract Despite the experimental evidence pointing to a significant role of the Wnt family of proteins in physiological and pathological rodent spinal cord functioning, its potential relevance in the healthy and traumatically injured human spinal cord as well as its therapeutic potential in spinal cord injury (SCI) are still poorly understood. To get further insight into these interesting issues, we first demonstrated by quantitative Real-Time PCR and simple immunohistochemistry that detectable mRNA expression of most Wnt components, as well as protein expression of all known Wnt rec...
Source: Cellular and Molecular Life Sciences : CMLS - January 3, 2020 Category: Cytology Authors: González P, González-Fernández C, Campos-Martín Y, Mollejo M, Carballosa-Gautam M, Marcillo A, Norenberg M, Rodríguez FJ Tags: Cell Mol Life Sci Source Type: research

Curse of the devil: molecular insights into the emergence of transmissible cancers in the Tasmanian devil (Sarcophilus harrisii).
Abstract The Tasmanian devil (Sarcophilus harrisii) is the only mammalian species known to be affected by multiple transmissible cancers. Devil facial tumours 1 and 2 (DFT1 and DFT2) are independent neoplastic cell lineages that produce large, disfiguring cancers known as devil facial tumour disease (DFTD). The long-term persistence of wild Tasmanian devils is threatened due to the ability of DFTD cells to propagate as contagious allografts and the high mortality rate of DFTD. Recent studies have demonstrated that both DFT1 and DFT2 cancers originated from founder cells of the Schwann cell lineage, an uncommon ori...
Source: Cellular and Molecular Life Sciences : CMLS - January 3, 2020 Category: Cytology Authors: Patchett AL, Flies AS, Lyons AB, Woods GM Tags: Cell Mol Life Sci Source Type: research

Introduction to the multi-author review on macular degeneration.
Abstract Prolonged life expectancies contribute to the increasing prevalence of age-related macular degeneration (AMD) that is already the leading cause of severe vision loss among the elderly in developed countries. In dry AMD, the disease culminates into vast retinal atrophy, whereas the wet form is characterized by retinal edema and sudden vision loss due to neovascularization originating from the choroid beneath the Bruch's membrane. There is no treatment for dry AMD and despite intravitreal injections of anti-vascular endothelial growth factor (VEGF) that suppress the neovessel formation, also wet AMD needs n...
Source: Cellular and Molecular Life Sciences : CMLS - January 2, 2020 Category: Cytology Authors: Kauppinen A Tags: Cell Mol Life Sci Source Type: research

The role of lymphocytes and phagocytes in age-related macular degeneration (AMD).
Abstract Age-related macular degeneration (AMD) is a leading cause of visual impairment of the elderly population. Since AMD is a multifactorial age-related disease with various genetic risk factors, the understanding of its complex pathophysiology is still limited. However, animal experiments, genome-wide association data and the molecular profiling of AMD patient samples have highlighted a key role of systemic and local immune processes that contribute to this chronic eye disease. In this overview article, we concentrate on the role of lymphocytes and mononuclear phagocytes and their interplay in triggering a pe...
Source: Cellular and Molecular Life Sciences : CMLS - January 2, 2020 Category: Cytology Authors: Behnke V, Wolf A, Langmann T Tags: Cell Mol Life Sci Source Type: research

Epigenetics in age-related macular degeneration: new discoveries and future perspectives.
Abstract The study of epigenetics has explained some of the 'missing heritability' of age-related macular degeneration (AMD). The epigenome also provides a substantial contribution to the organisation of the functional retina. There is emerging evidence of specific epigenetic mechanisms associated with AMD. This 'AMD epigenome' may offer the chance to develop novel AMD treatments. PMID: 31897542 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - January 2, 2020 Category: Cytology Authors: Gemenetzi M, Lotery AJ Tags: Cell Mol Life Sci Source Type: research

Senescence in the pathogenesis of age-related macular degeneration.
Abstract Age-related macular degeneration (AMD) is a complex eye disease underlined by the death of photoreceptors and degeneration of retinal pigment epithelium (RPE) and choriocapillaris (CC). The mechanism(s) responsible for massive and progressive retinal degeneration is not completely known. Senescence, a state of permanent inhibition of cell growth, may be induced by many factors important for AMD pathogenesis and results in senescence-associated secretory phenotype (SASP) that releases growth factors, cytokines, chemokines, proteases and other molecules inducing inflammation and other AMD-related effects. T...
Source: Cellular and Molecular Life Sciences : CMLS - January 2, 2020 Category: Cytology Authors: Blasiak J Tags: Cell Mol Life Sci Source Type: research

The dark side of Alzheimer's disease: unstructured biology of proteins from the amyloid cascade signaling pathway.
Abstract Alzheimer's disease (AD) is a leading cause of age-related dementia worldwide. Despite more than a century of intensive research, we are not anywhere near the discovery of a cure for this disease or a way to prevent its progression. Among the various molecular mechanisms proposed for the description of the pathogenesis and progression of AD, the amyloid cascade hypothesis, according to which accumulation of a product of amyloid precursor protein (APP) cleavage, amyloid β (Aβ) peptide, induces pathological changes in the brain observed in AD, occupies a unique niche. Although multiple proteins ha...
Source: Cellular and Molecular Life Sciences : CMLS - January 2, 2020 Category: Cytology Authors: Gadhave K, Gehi BR, Kumar P, Xue B, Uversky VN, Giri R Tags: Cell Mol Life Sci Source Type: research

hnRNPA2B1 inhibits the exosomal export of miR-503 in endothelial cells.
man I Abstract The chemotherapeutic drug epirubicin increases the exosomal export of miR-503 in endothelial cells. To understand the mechanisms behind this process, we transfected endothelial cells with miR-503 carrying a biotin tag. Then, we pulled-down the proteins interacting with miR-503 and studied their role in microRNA exosomal export. A total of four different binding partners were identified by mass spectrometry and validated by western blotting and negative controls, among them ANXA2 and hnRNPA2B1. Using knock-down systems combined with pull-down analysis, we determined that epirubicin mediates the expor...
Source: Cellular and Molecular Life Sciences : CMLS - January 2, 2020 Category: Cytology Authors: Pérez-Boza J, Boeckx A, Lion M, Dequiedt F, Struman I Tags: Cell Mol Life Sci Source Type: research

Highly photostable fluorescent labeling of proteins in live cells using exchangeable coiled coils heterodimerization.
In conclusion, KECs can be used to visualize various target proteins which are directly exposed to the cytosol, thereby enabling their advanced characterization in time and space. PMID: 31894363 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - January 2, 2020 Category: Cytology Authors: Perfilov MM, Gurskaya NG, Serebrovskaya EO, Melnikov PA, Kharitonov SL, Lewis TR, Arshavsky VY, Baklaushev VP, Mishin AS, Lukyanov KA Tags: Cell Mol Life Sci Source Type: research

The versatile Kv channels in the nervous system: actions beyond action potentials.
Abstract Voltage-gated K+ (Kv) channel opening repolarizes excitable cells by allowing K+ efflux. Over the last two decades, multiple Kv functions in the nervous system have been found to be unrelated to or beyond the immediate control of excitability, such as shaping action potential contours or regulation of inter-spike frequency. These functions include neuronal exocytosis and neurite formation, neuronal cell death, regulation of astrocyte Ca2+, glial cell and glioma proliferation. Some of these functions have been shown to be independent of K+ conduction, that is, they suggest the non-canonical functions of Kv...
Source: Cellular and Molecular Life Sciences : CMLS - January 1, 2020 Category: Cytology Authors: Chow LWC, Leung YM Tags: Cell Mol Life Sci Source Type: research

Communication between human macrophages and epithelial cancer cell lines dictates lipid mediator biosynthesis.
Abstract In tumors, cancer cells coexist and communicate with macrophages that can promote tumorigenesis via pro-inflammatory signals. Lipid mediators (LMs), produced mainly by cyclooxygenases (COXs) or lipoxygenases (LOs), display a variety of biological functions with advantageous or deleterious consequences for tumors. Here, we investigated how the communication between human monocyte-derived M2-like macrophages (MDM) and cancer cells affects LM biosynthesis using LM metabololipidomics. Coculture of human MDM with human A549 epithelial lung carcinoma cells, separated by a semipermeable membrane, increased LM fo...
Source: Cellular and Molecular Life Sciences : CMLS - January 1, 2020 Category: Cytology Authors: Werner M, Pace S, Czapka A, Jordan PM, Gerstmeier J, Koeberle A, Werz O Tags: Cell Mol Life Sci Source Type: research

Pharmacological inhibition of androgen receptor expression induces cell death in prostate cancer cells.
In this study, we determined the anticancer effect of a newly found natural compound, sakurasosaponin (S-saponin), using androgen-dependent and castration-resistant PCa cell lines. S-saponin induces mitochondrial-mediated cell death in both androgen-dependent (LNCaP) and castration-resistant (22Rv1 and C4-2) PCa cells, via AR expression. S-saponin treatment induces a decrease in AR expression in a time- and dose-dependent manner and a potent decrease in the expression of its target genes, including prostate-specific antigen (PSA), transmembrane protease, serin 2 (TMPRSS2), and NK3 homeobox 1 (NKX3.1). Furthermore, S-saponi...
Source: Cellular and Molecular Life Sciences : CMLS - January 1, 2020 Category: Cytology Authors: Song IS, Jeong YJ, Kim J, Seo KH, Baek NI, Kim Y, Kim CS, Jang SW Tags: Cell Mol Life Sci Source Type: research

Integrative genomics reveal a role for MCPIP1 in adipogenesis and adipocyte metabolism.
Abstract Obesity is considered a serious chronic disease, associated with an increased risk of developing cardiovascular diseases, non-alcoholic fatty liver disease and type 2 diabetes. Monocyte chemoattractant protein-1-induced protein-1 (MCPIP1) is an RNase decreasing stability of transcripts coding for inflammation-related proteins. In addition, MCPIP1 plays an important role in the regulation of adipogenesis in vitro by reducing the expression of key transcription factors, including C/EBPβ. To elucidate the role of MCPIP1 in adipocyte biology, we performed RNA-Seq and proteome analysis in 3T3-L1 adipocyte...
Source: Cellular and Molecular Life Sciences : CMLS - December 31, 2019 Category: Cytology Authors: Losko M, Dolicka D, Pydyn N, Jankowska U, Kedracka-Krok S, Kulecka M, Paziewska A, Mikula M, Major P, Winiarski M, Budzynski A, Jura J Tags: Cell Mol Life Sci Source Type: research

Eph receptors: the bridge linking host and virus.
Abstract Eph (erythropoietin-producing hepatoma) receptors and Ephrin ligands constitute the largest subfamily of receptor tyrosine kinase (RTK), which were first discovered in tumors. Heretofore, Eph protein has been shown to be involved in various tumor biological behaviors including proliferation and progression. The occurrence of specific types of tumor is closely related to the virus infection. Virus entry is a complex process characterized by a series of events. The entry into target cells is an essential step for virus to cause diseases, which requires the fusion of the viral envelope and host cellular memb...
Source: Cellular and Molecular Life Sciences : CMLS - December 31, 2019 Category: Cytology Authors: Wang J, Zheng X, Peng Q, Zhang X, Qin Z Tags: Cell Mol Life Sci Source Type: research

The role of hypoxia-inducible factors in neovascular age-related macular degeneration: a gene therapy perspective.
te; H Abstract Understanding the mechanisms that underlie age-related macular degeneration (AMD) has led to the identification of key molecules. Hypoxia-inducible transcription factors (HIFs) have been associated with choroidal neovascularization and the progression of AMD into the neovascular clinical phenotype (nAMD). HIFs regulate the expression of multiple growth factors and cytokines involved in angiogenesis and inflammation, hallmarks of nAMD. This knowledge has propelled the development of a new group of therapeutic strategies focused on gene therapy. The present review provides an update on current gene th...
Source: Cellular and Molecular Life Sciences : CMLS - December 31, 2019 Category: Cytology Authors: Mammadzada P, Corredoira PM, André H Tags: Cell Mol Life Sci Source Type: research

Behind the pathology of macrophage-associated demyelination in inflammatory neuropathies: demyelinating Schwann cells.
Abstract In inflammatory peripheral demyelinating disorders, demyelination represents segmental demyelination in which the myelin sheath of a myelinating Schwann cell (SC) is completely removed by macrophages or a partial myelin degeneration in the paranode occurring due to autoantibodies attacking the node/paranode. For the segmental demyelination from living myelin-forming SCs, macrophages infiltrate within the endoneurium and insinuate between myelin lamellae and the cytoplasm of SCs, and the myelin is then removed via phagocytosis. During the macrophage invasion into the SC cytoplasm from the node of Ranvier a...
Source: Cellular and Molecular Life Sciences : CMLS - December 28, 2019 Category: Cytology Authors: Park HT, Kim YH, Lee KE, Kim JK Tags: Cell Mol Life Sci Source Type: research

Molecular crosstalk between cancer and neurodegenerative diseases.
Abstract The progression of cancers and neurodegenerative disorders is largely defined by a set of molecular determinants that are either complementarily deregulated, or share remarkably overlapping functional pathways. A large number of such molecules have been demonstrated to be involved in the progression of both diseases. In this review, we particularly discuss our current knowledge on p53, cyclin D, cyclin E, cyclin F, Pin1 and protein phosphatase 2A, and their implications in the shared or distinct pathways that lead to cancers or neurodegenerative diseases. In addition, we focus on the inter-dependent regul...
Source: Cellular and Molecular Life Sciences : CMLS - December 28, 2019 Category: Cytology Authors: Seo J, Park M Tags: Cell Mol Life Sci Source Type: research

Extracellular signal-regulated kinase 1/2 regulates NAD metabolism during acute kidney injury through microRNA-34a-mediated NAMPT expression.
In this study, ERK1/2 regulation of cellular nicotinamide adenine dinucleotide (NAD) and PGC-1α were explored. Inhibition of ERK1/2 activation during AKI in mice using the MEK1/2 inhibitor, trametinib, attenuated renal cortical oxidized NAD (NAD+) depletion. The rate-limiting NAD biosynthesis salvage enzyme, NAMPT, decreased following AKI, and this decrease was prevented by ERK1/2 inhibition. The microRNA miR34a decreased with the inhibition of ERK1/2, leading to increased NAMPT protein. Mice treated with a miR34a mimic prevented increases in NAMPT protein in the renal cortex in the presence of ERK1/2 inhibition. In ...
Source: Cellular and Molecular Life Sciences : CMLS - December 23, 2019 Category: Cytology Authors: Collier JB, Schnellmann RG Tags: Cell Mol Life Sci Source Type: research

Cas12a mediates efficient and precise endogenous gene tagging via MITI: microhomology-dependent targeted integrations.
Abstract Efficient exogenous DNA integration can be mediated by Cas9 through the non-homology end-joining pathway. However, such integrations are often imprecise and contain a variety of mutations at the junctions between the external DNA and the genomic loci. Here we describe a microhomology-dependent targeted integration method, designated MITI, for precise site-specific gene insertions. We found that the MITI strategy yielded higher knock-in accuracy than Cas9 HITI for the insertion of external DNA and tagging endogenous genes. Furthermore, in combination with negative selection and four different CrRNAs target...
Source: Cellular and Molecular Life Sciences : CMLS - December 17, 2019 Category: Cytology Authors: Li P, Zhang L, Li Z, Xu C, Du X, Wu S Tags: Cell Mol Life Sci Source Type: research

Modulation of SRSF2 expression reverses the exhaustion of TILs via the epigenetic regulation of immune checkpoint molecules.
Abstract The elevated expression of immune checkpoints by the tumor microenvironment is associated with poor prognosis in several cancers due to the exhaustion of tumor-infiltrating lymphocytes (TILs), and the effective suppression of the expression of these genes is key to reversing the exhaustion of TILs. Herein, we determined that serine/arginine-rich splicing factor 2 (SRSF2) is a target for blocking the tumor microenvironment-associated immunosuppressive effects. We found that the expression of SRSF2 was increased in exhausted T cells and that SRSF2 was involved in multiple immune checkpoint molecules mediati...
Source: Cellular and Molecular Life Sciences : CMLS - December 14, 2019 Category: Cytology Authors: Wang Z, Li K, Chen W, Wang X, Huang Y, Wang W, Wu W, Cai Z, Huang W Tags: Cell Mol Life Sci Source Type: research

Astrocyte-specific NDRG2 gene: functions in the brain and neurological diseases.
Abstract In recent years, the roles of astrocytes of the central nervous system in brain function and neurological disease have drawn increasing attention. As a member of the N-myc downstream-regulated gene (NDRG) family, NDRG2 is principally expressed in astrocytes of the central nervous system. NDRG2, which is involved in cell proliferation and differentiation, is commonly regarded as a tumor suppressor. In astrocytes, NDRG2 affects the regulation of apoptosis, astrogliosis, blood-brain barrier integrity, and glutamate clearance. Several preclinical studies have revealed that NDRG2 is implicated in the pathogene...
Source: Cellular and Molecular Life Sciences : CMLS - December 13, 2019 Category: Cytology Authors: Li X, Wu X, Luo P, Xiong L Tags: Cell Mol Life Sci Source Type: research

TGF β-induced metabolic reprogramming during epithelial-to-mesenchymal transition in cancer.
We describe TGFβ signaling is involved in stimulating both glycolysis and mitochondrial respiration. Interestingly, the subsequent metabolic consequences for the redox state and lipid metabolism in cancer cells are found to be in favor of EMT as well. Combined we illustrate that a better understanding of the mechanistic links between TGFβ signaling, cancer metabolism and EMT holds promising strategies for cancer therapy, some of which are already actively being explored in the clinic. PMID: 31822964 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - December 10, 2019 Category: Cytology Authors: Hua W, Ten Dijke P, Kostidis S, Giera M, Hornsveld M Tags: Cell Mol Life Sci Source Type: research

Vsx1 and Chx10 paralogs sequentially secure V2 interneuron identity during spinal cord development.
Abstract Paralog factors are usually described as consolidating biological systems by displaying redundant functionality in the same cells. Here, we report that paralogs can also cooperate in distinct cell populations at successive stages of differentiation. In mouse embryonic spinal cord, motor neurons and V2 interneurons differentiate from adjacent progenitor domains that share identical developmental determinants. Therefore, additional strategies secure respective cell fate. In particular, Hb9 promotes motor neuron identity while inhibiting V2 differentiation, whereas Chx10 stimulates V2a differentiation while ...
Source: Cellular and Molecular Life Sciences : CMLS - December 10, 2019 Category: Cytology Authors: Debrulle S, Baudouin C, Hidalgo-Figueroa M, Pelosi B, Francius C, Rucchin V, Ronellenfitch K, Chow RL, Tissir F, Lee SK, Clotman F Tags: Cell Mol Life Sci Source Type: research

HAS3-induced extracellular vesicles from melanoma cells stimulate IHH mediated c-Myc upregulation via the hedgehog signaling pathway in target cells.
This study shows for the first time that EVs originating from HAS3 overexpressing cells carry mitogenic signals that induce proliferation and epithelial-to-mesenchymal transition in target cells. The study also identifies a novel feedback regulation between the hedgehog signaling pathway and HA metabolism in melanoma, mediated by EVs carrying HA and IHH. PMID: 31820036 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - December 9, 2019 Category: Cytology Authors: Arasu UT, Deen AJ, Pasonen-Seppänen S, Heikkinen S, Lalowski M, Kärnä R, Härkönen K, Mäkinen P, Lázaro-Ibáñez E, Siljander PR, Oikari S, Levonen AL, Rilla K Tags: Cell Mol Life Sci Source Type: research