Phosphodiesterase isoforms and cAMP compartments in the development of new therapies for obstructive pulmonary diseases.
om RS Abstract The second messenger molecule 3'5'-cyclic adenosine monophosphate (cAMP) imparts several beneficial effects in lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). While cAMP is bronchodilatory in asthma and COPD, it also displays anti-fibrotic properties that limit fibrosis. Phosphodiesterases (PDEs) metabolize cAMP and thus regulate cAMP signaling. While some existing therapies inhibit PDEs, there are only broad family specific inhibitors. The understanding of cAMP signaling compartments, some centered around lipid rafts/caveolae, has ...
Source: Current Opinion in Pharmacology - July 1, 2020 Category: Drugs & Pharmacology Authors: Schmidt M, Cattani-Cavalieri I, Nuñez FJ, Ostrom RS Tags: Curr Opin Pharmacol Source Type: research

Role of the endocannabinoid system in the regulation of the skeletal muscle response to exercise.
PC Abstract Exercise is a valuable tool in the prevention and treatment of cardiometabolic diseases like obesity and type 2 diabetes. Interestingly, endocannabinoids (eCBs), involved in a large range of physiological processes, are elevated with both obesity and acute exercise. In this review we outline this paradox overlap in the context of metabolic health and delineate the transcriptomic response of skeletal muscle to acute and chronic aerobic and resistance exercise in relation to the endocannabinoid system by utilizing a meta-analyses tool. We show that exercise modulates the expression of receptors and enzy...
Source: Current Opinion in Pharmacology - June 30, 2020 Category: Drugs & Pharmacology Authors: Schönke M, Martinez-Tellez B, Rensen PC Tags: Curr Opin Pharmacol Source Type: research

Modulation of gut microbiota to overcome resistance to immune checkpoint blockade in cancer immunotherapy.
Abstract Immune checkpoint blockade therapies that target CTLA-4 and PD-1/PD-L1 have ushered in a new era of cancer treatment. Nevertheless, a significant proportion of patients demonstrated primary or acquired resistance. Harnessing gut microbiota has been an emerging novel therapeutic strategy to overcome resistance. Here we summarized the current research status of gut microbiota in immune checkpoint blockade therapies, clinical trials, underlying mechanisms and challenges of microbiome research in checkpoint immunotherapy. Findings from preclinical models, standardized microbiome analysis and progress of multi...
Source: Current Opinion in Pharmacology - June 30, 2020 Category: Drugs & Pharmacology Authors: Huang J, Jiang Z, Wang Y, Fan X, Cai J, Yao X, Liu L, Huang J, He J, Xie C, Wu Q, Cao Y, Leung EL Tags: Curr Opin Pharmacol Source Type: research

Integrating the roles of liver X receptors in inflammation and infection: mechanisms and outcomes.
or AF Abstract Liver X receptors (LXRs) are transcription factors from the nuclear receptor family that can be pharmacologically activated by high-affinity agonists. LXR activation exerts a combination of metabolic and anti-inflammatory actions that result in the modulation of immune responses and in the amelioration of inflammatory disorders. In addition, LXR agonists modulate the metabolism of infected cells and limit the infectivity and/or growth of several pathogens. This review gives an overview of the recent advances in understanding the complexity of the mechanisms through which the LXR pathway controls inf...
Source: Current Opinion in Pharmacology - June 26, 2020 Category: Drugs & Pharmacology Authors: Glaría E, Letelier NA, Valledor AF Tags: Curr Opin Pharmacol Source Type: research

Nuclear receptors in osteoclasts.
Abstract Osteoclasts are bone-resorbing cells that play an essential role in the remodeling of bone under physiological conditions and numerous pathological conditions, such as osteoporosis, bone metastasis, and inflammatory bone erosion. Nuclear receptors are crucial to various physiological processes, including metabolism, development and inflammation, and function as transcription factors to activate target genes. Synthetic ligands of nuclear receptors are also available for the treatment of metabolic and inflammatory diseases. However, dysregulated bone phenotypes have been documented in patients who take synt...
Source: Current Opinion in Pharmacology - June 19, 2020 Category: Drugs & Pharmacology Authors: Bae S, Zeng S, Park-Min KH Tags: Curr Opin Pharmacol Source Type: research

Recent advances in the role of interleukin-6 in health and disease.
Abstract Interleukin-6 (IL-6) is a pleotropic cytokine, and in this review, we highlight recent studies focusing on the role of IL-6 in health and disease. IL-6 is known as an exercise-inducible myokine, and in rodents it was identified that a lactate-dependent increase in protease activity mediates IL-6 release from skeletal muscle, which acts in both an autocrine and paracrine roles. In humans, a series of publications observed that blocking IL-6 during exercise training prevented beneficial adaptations, such as reductions in visceral and epicardial fat mass. Independent of exercise, IL-6 impacts postprandial ph...
Source: Current Opinion in Pharmacology - June 18, 2020 Category: Drugs & Pharmacology Authors: Peppler WT, Townsend LK, Wright DC Tags: Curr Opin Pharmacol Source Type: research

Editorial overviews: Editorial matters - point of clarification.
PMID: 32506004 [PubMed - as supplied by publisher] (Source: Current Opinion in Pharmacology)
Source: Current Opinion in Pharmacology - June 4, 2020 Category: Drugs & Pharmacology Authors: Williams M Tags: Curr Opin Pharmacol Source Type: research

Mechanisms underlying N3-PUFA regulation of white adipose tissue endocrine function.
Abstract Omega-3 polyunsaturated fatty acids (N3-PUFA) are widely reported to improve obesity-associated metabolic impairments, in part, through the regulation of adipokine and cytokine secretion from white adipose tissue (WAT). However, the precise underlying molecular mechanisms by which N3-PUFA influence WAT endocrine function remain poorly described. Available evidence supports that N3-PUFA and related bioactive lipid mediators regulate several intracellular pathways that converge on two important transcription factors: PPAR-γ and NF-κB. Further, N3-PUFA signaling through GPR120 appears integral fo...
Source: Current Opinion in Pharmacology - June 3, 2020 Category: Drugs & Pharmacology Authors: Brown LH, Mutch DM Tags: Curr Opin Pharmacol Source Type: research

Genetic variation, adipokines, and cardiometabolic disease.
TO Abstract Adipokines are adipocyte-secreted cell signalling proteins that travel to distant target organs and tissues, where they regulate a variety of biological actions implicated in cardiometabolic health. In the past decade, genome-wide association studies have identified multiple genetic variants associated with circulating levels of adipokines, providing new instruments for examining the role of adipokines in cardiometabolic pathologies. Currently, there is limited genetic evidence of causal relationships between adipokines and cardiometabolic disease, which is consistent with findings from randomized cli...
Source: Current Opinion in Pharmacology - May 29, 2020 Category: Drugs & Pharmacology Authors: Metz S, Huang LO, Kilpeläinen TO Tags: Curr Opin Pharmacol Source Type: research

Role of CD38/cADPR signaling in obstructive pulmonary diseases.
Abstract The worldwide socioeconomical burden associated with chronic respiratory diseases is substantial. Enzymes involved in the metabolism of nicotinamide adenine dinucleotide (NAD) are increasingly being implicated in chronic airway diseases. One such enzyme, CD38, utilizes NAD to produce several metabolites, including cyclic ADP ribose (cADPR), which is involved in calcium signaling in airway smooth muscle (ASM). Upregulation of CD38 in ASM caused by exposure to cytokines or allergens leads to enhanced calcium mobilization by agonists and the development of airway hyperresponsiveness (AHR) to contractile agon...
Source: Current Opinion in Pharmacology - May 29, 2020 Category: Drugs & Pharmacology Authors: Guedes AG, Dileepan M, Jude JA, Deshpande DA, Walseth TF, Kannan MS Tags: Curr Opin Pharmacol Source Type: research

Bile acid-activated receptors and the regulation of macrophages function in metabolic disorders.
Abstract Bile acids are produced in the liver by the cholesterol breakdown and further metabolized by the intestinal microbiota to generate a group of chemically heterogeneous steroids that bind and activate a family of cells surface and nuclear receptors, collectively known as the bile acid-activated receptors (BARs). The two best characterized members of this family are the farnesoid-x-receptor (FXR) and G protein Bile Acid Receptor (GPBAR1). Both receptors are expressed by cells of innate immunity including liver-resident and intestinal-resident macrophages and monocytes-derived macrophages. Because FXR and GPB...
Source: Current Opinion in Pharmacology - May 29, 2020 Category: Drugs & Pharmacology Authors: Fiorucci S, Baldoni M, Ricci P, Zampella A, Distrutti E, Biagioli M Tags: Curr Opin Pharmacol Source Type: research

Exercise and browning of white adipose tissue - a translational perspective.
en BK Abstract Browning of white adipose tissue is a cold-induced phenomenon in rodents, constituted by the differentiation of a subset of thermogenic adipocytes among existing white adipocytes. Emerging evidence in the literature points at additional factors and environmental conditions stimulating browning in rodents, including physical exercise training. Exercise engages sympathetic activation which during cold activation promotes proliferation and differentiation of brown preadipocytes. Exercise also stimulates the release of multiple growth factors and cytokines. Importantly, there are clear discrepancies bet...
Source: Current Opinion in Pharmacology - May 28, 2020 Category: Drugs & Pharmacology Authors: Severinsen MCK, Schéele C, Pedersen BK Tags: Curr Opin Pharmacol Source Type: research

Regulation of adipose tissue and skeletal muscle substrate metabolism by the stomach-derived hormone, ghrelin.
Abstract Ghrelin is a stomach-derived hormone and a potent appetite stimulant. Ghrelin has recently harbored interest as a potential regulator of carbohydrate and lipid metabolism in skeletal muscle and adipose tissue; however, in vivo ghrelin administration is confounded by secondary effects. The assessment of the direct metabolic effects of acylated (AG) and unacylated (UnAG) ghrelin is a relatively new area of research. In isolated adipocytes and muscle, ghrelin has demonstrated antilipolytic effects. In muscle, ghrelin has been shown to acutely stimulate fat oxidation, which may protect the muscle from the ins...
Source: Current Opinion in Pharmacology - May 28, 2020 Category: Drugs & Pharmacology Authors: Cervone DT, Lovell AJ, Dyck DJ Tags: Curr Opin Pharmacol Source Type: research

Anti-inflammatory glucocorticoid action: genomic insights and emerging concepts.
Abstract Glucocorticoids (GCs) are widely used immunomodulators. They regulate gene expression by binding and activating the Glucocorticoid Receptor (GR), but underlying transcriptional mechanisms remain enigmatic. This review summarizes recent findings identifyingspecific GR-bound DNA sequences whose configuration may affect transcriptional output. Additional factors affecting GR's anti-inflammatory actions, including different chromatin states such as DNAse hypersensitive regions and histone marks will be discussed, together with the relevant transcriptional co-regulators and promoter/enhancer features. Furtherm...
Source: Current Opinion in Pharmacology - May 13, 2020 Category: Drugs & Pharmacology Authors: Syed AP, Greulich F, Ansari SA, Uhlenhaut NH Tags: Curr Opin Pharmacol Source Type: research

Molecular control of tissue-resident macrophage identity by nuclear receptors.
P, Ricote M Abstract Macrophages are key immune cells that reside in almost all tissues of the body, where they exert pleiotropic functions in homeostasis and disease. Development and identity of macrophages in each organ are governed by tissue-dependent signaling pathways and transcription factors that ultimately define specific tissue-resident macrophage phenotypes and functions. In recent years, nuclear receptors, a class of ligand-activated transcription factors, have been found to play important roles in macrophage specification in several tissues. Nuclear receptors are thus important targets for therapies ai...
Source: Current Opinion in Pharmacology - May 8, 2020 Category: Drugs & Pharmacology Authors: Porcuna J, Menéndez-Gutiérrez MP, Ricote M Tags: Curr Opin Pharmacol Source Type: research

Gut microbiota and regulation of myokine-adipokine function.
Abstract Both skeletal muscle and adipose tissue are considered as endocrine organs due to their ability to produce and secrete several bioactive peptides (e.g. myokines and adipokines). Those bioactive molecules are well known for their capacity to influence whole-body homeostasis and alterations in their production/secretion are contributing to the development of various metabolic disorders. While it is well accepted that changes in the composition and functionality of the gut microbiota are associated with the onset of several pathological disorders (e.g. obesity, diabetes, and cancer), its contribution to the ...
Source: Current Opinion in Pharmacology - May 7, 2020 Category: Drugs & Pharmacology Authors: Suriano F, Van Hul M, Cani PD Tags: Curr Opin Pharmacol Source Type: research

Adipose tissue depot differences in adipokines and effects on skeletal and cardiac muscle.
Frühbeck G Abstract White (WAT) and brown (BAT) adipose tissue communicate with skeletal muscle and heart through the secretion of adipokines (adiponectin, leptin, omentin, osteopontin or cardiotrophin-1) and batokines (BMP8b, FGF-21, endothelin-1 or IL-6), respectively. Furthermore, several bioactive lipids termed lipokines [palmitoleate (C16:1n7) or 12,13-diHOME] and microRNAs capsuled in exosomes (miR-27a, miR122, miR-130b, miR-155, miR-200a or miR-320d) secreted from white and brown adipocytes also influence the skeletal and cardiac muscle function. The review focuses on the depot-related differences in a...
Source: Current Opinion in Pharmacology - May 5, 2020 Category: Drugs & Pharmacology Authors: Rodríguez A, Becerril S, Hernández-Pardos AW, Frühbeck G Tags: Curr Opin Pharmacol Source Type: research

Class C GPCRs in the airway.
Abstract Understanding and targeting of GPCRs remain a critical aspect of airway pharmacology and therapeutics for diseases such as asthma or COPD. Most attention has been on the large Class A GPCRs towards improved bronchodilation and blunting of remodeling. Better known in the central or peripheral nervous system, there is increasing evidence that Class C GPCRs which include metabotropic glutamate and GABA receptors, the calcium sensing receptor, sweet/umami taste receptors and a number of orphan receptors, can contribute to airway structure and function. In this review, we will summarize current state of knowle...
Source: Current Opinion in Pharmacology - May 3, 2020 Category: Drugs & Pharmacology Authors: Patel BS, Ravix J, Pabelick C, Prakash YS Tags: Curr Opin Pharmacol Source Type: research

Kinase inhibitors in the treatment of obstructive pulmonary diseases.
Abstract Chronic pulmonary diseases, including chronic obstructive pulmonary disease (COPD) and asthma, are major causes of death and reduced quality of life. Characteristic of chronic pulmonary disease is excessive lung inflammation that occurs in response to exposure to inhaled irritants, chemicals, and allergens. Chronic inflammation leads to remodeling of the airways that includes excess mucus secretion, proliferation of smooth muscle cells, increased deposition of extracellular matrix proteins and fibrosis. Protein kinases have been implicated in mediating inflammatory signals and airway remodeling associated...
Source: Current Opinion in Pharmacology - April 30, 2020 Category: Drugs & Pharmacology Authors: Defnet AE, Hasday JD, Shapiro P Tags: Curr Opin Pharmacol Source Type: research

The proton-sensing receptor ovarian cancer G-protein coupled receptor 1 (OGR1) in airway physiology and disease.
Abstract Numerous G protein-coupled receptors (GPCRs) regulate multiple airway functions and play fundamental roles in normal and aberrant airway and lung physiology. Thus, GPCRs are prime candidates of targeting by disease therapeutics. The intriguing proton-sensing GPCR Ovarian cancer G-protein coupled receptor 1 (OGR1; aka GPR68) has recently been shown capable of regulating airway smooth muscle (ASM) contraction and proliferation. Although the study of OGR1 has been confounded by the fact that the proton is the presumed cognate ligand of OGR1, recent studies have begun to identify novel ligands and modulators ...
Source: Current Opinion in Pharmacology - April 29, 2020 Category: Drugs & Pharmacology Authors: Nayak AP, Penn RB Tags: Curr Opin Pharmacol Source Type: research

Lipid metabolism as a mechanism of immunomodulation in macrophages: the role of liver X receptors.
Abstract Macrophages are immune myeloid cells with an extreme ability to modulate their phenotype in response to insults and/or pathogens. The immunomodulatory capacity of macrophages is also patent during development as they adapt their phenotype to the host tissue environment establishing the heterogeneous populations of tissue-resident macrophages. An important mechanism of immunomodulation in macrophages occurs through the regulation of transcriptional activity. Numerous transcription factors are associated with macrophage plasticity, among them, several nuclear receptors. The nuclear receptors Liver X Recepto...
Source: Current Opinion in Pharmacology - April 28, 2020 Category: Drugs & Pharmacology Authors: Leussink S, Aranda-Pardos I, A-Gonzalez N Tags: Curr Opin Pharmacol Source Type: research

Enteric Nervous System: lessons from neurogenesis for reverse engineering and disease modelling and treatment.
Abstract Normal activity and functional integration of the enteric nervous system (ENS) into the gut tissue circuitry and the luminal ecosystem are essential for digestive physiology and human health. A range of debilitating gastrointestinal disorders are linked to ENS dysfunction, caused either by developmental deficits, such as congenital megacolon (Hirschsprung's disease-HSCR) or a host of acquired intestinal neuropathies with unclear molecular or cellular pathogenesis. Recent advances in cell engineering underscore the potential use of cell replacement technologies for the treatment of ENS disorders. This revi...
Source: Current Opinion in Pharmacology - March 30, 2020 Category: Drugs & Pharmacology Authors: Chng SH, Pachnis V Tags: Curr Opin Pharmacol Source Type: research

Editorial overview: Modulation of neurogenesis.
PMID: 32179439 [PubMed - as supplied by publisher] (Source: Current Opinion in Pharmacology)
Source: Current Opinion in Pharmacology - March 12, 2020 Category: Drugs & Pharmacology Authors: Buffo A, Ceruti S Tags: Curr Opin Pharmacol Source Type: research

Adult hippocampal neurogenesis and antidepressants effects.
Abstract The hippocampus is particularly involved in cognitive processes and is a key regulator of stress responses and emotions. Therefore, the role of adult-born neurons in this region has become a crucial field of research in order to understand mood and stress disorders, such as major depression. Many studies have characterized the role of these neurons in cognition, mood regulation and antidepressant actions. Nevertheless, the precise mechanisms underpinning these antidepressant effects remain unclear. In this review, we first discuss the effects of stress and antidepressant treatments on adult-born neurons, ...
Source: Current Opinion in Pharmacology - January 30, 2020 Category: Drugs & Pharmacology Authors: Planchez B, Surget A, Belzung C Tags: Curr Opin Pharmacol Source Type: research

Potential of glucocorticoids to treat intestinal inflammation during sepsis.
Abstract Glucocorticoids (GCs) are steroid hormones characterized by their anti-inflammatory and immunosuppressive nature. Although GCs are very commonly prescribed, in several diseases, including sepsis, their clinical treatment is hampered by side effects and by the occurrence of glucocorticoid resistance (GCR). Sepsis is defined as a life-threatening organ dysfunction, initiated by a dysregulated systemic host response to infections. With at least 19 million cases per year and a lethality rate of about 25%, sepsis is one of the most urgent unmet medical needs. The gut is critically affected during sepsis and is...
Source: Current Opinion in Pharmacology - January 25, 2020 Category: Drugs & Pharmacology Authors: Van Looveren K, Wallaeys C, Libert C Tags: Curr Opin Pharmacol Source Type: research

Next-generation drug repurposing using human genetics and network biology.
Abstract Drug repurposing has attracted increased attention, especially in the context of drug discovery rates that remain too low despite a recent wave of approvals for biological therapeutics (e.g. gene therapy). These new biological entities-based treatments have high costs that are difficult to justify for small markets that include rare diseases. Drug repurposing, involving the identification of single or combinations of existing drugs based on human genetics data and network biology approaches represents a next-generation approach that has the potential to increase the speed of drug discovery at a lower cost...
Source: Current Opinion in Pharmacology - January 22, 2020 Category: Drugs & Pharmacology Authors: Nabirotchkin S, Peluffo AE, Rinaudo P, Yu J, Hajj R, Cohen D Tags: Curr Opin Pharmacol Source Type: research

Null hypothesis significance testing and effect sizes: can we 'effect' everything … or … anything?
Null hypothesis significance testing and effect sizes: can we 'effect' everything … or … anything? Curr Opin Pharmacol. 2020 Jan 13;: Authors: Lovell DP Abstract The Null Hypothesis Significance Testing (NHST) paradigm is increasingly criticized. Estimation approaches such as point estimates and confidence intervals, while having limitations, provide better descriptions of results than P-values and statements about significance levels. Their use is supported by many statisticians. The effect size approach is an important part of power and sample size calculations at the experimental desi...
Source: Current Opinion in Pharmacology - January 13, 2020 Category: Drugs & Pharmacology Authors: Lovell DP Tags: Curr Opin Pharmacol Source Type: research

Histone deacetylases 1, 2 and 3 in nervous system development.
Abstract Although histone acetylases (HDACS) were initially believed to render chromatin in a transcriptionally repressed state by deacetylating histones, it is now known that they both repress and activate transcription. Moreover, HDACs regulate the activity and/or function of a large number of other cellular proteins localized in the nucleus and cytoplasm. Accumulating evidence indicates that HDACs also play a key role in the development of the nervous system. This review focuses on three classical HDACS - HDACs 1, 2 and 3. Although much evidence on the involvement of HDACs in neurodevelopment has come from the ...
Source: Current Opinion in Pharmacology - January 2, 2020 Category: Drugs & Pharmacology Authors: D'Mello SR Tags: Curr Opin Pharmacol Source Type: research

Untangling human neurogenesis to understand and counteract brain disorders.
Abstract Neurogenesis in the human postnatal brain occurs in two regions, the subventricular zone of the later ventricle and the dentate gyrus of the hippocampus. While it is well accepted that SVZ and hippocampal neurogenesis are active during juvenile stages in human, their contribution during adulthood and ageing as well as pathological states is recently animating the neural stem cell research field. In this review we will discuss recent evidence about the organization of SVZ and hippocampal neurogenic niches, and will report on how human adult neurogenesis may contribute to disease and appears to respond to n...
Source: Current Opinion in Pharmacology - December 31, 2019 Category: Drugs & Pharmacology Authors: Beckervordersandforth R, Rolando C Tags: Curr Opin Pharmacol Source Type: research

Ependymal cells in the spinal cord as neuronal progenitors.
Abstract Ependymal cells are neural progenitors and form part of the central canal of the spinal cord. Therefore, ependymal cells could serve as a potential source of neural progenitors for regenerative medicine applications. Such applications consist of endogenous activation or exogenous transplantation, alone or in combination with pharmacological treatments, to repair spinal cord injuries. This mini review describes the main phenotypical characteristics of ependymal cells from spinal cord and the opportunities offered for spinal cord injury therapeutic application. PMID: 31901616 [PubMed - as supplied by p...
Source: Current Opinion in Pharmacology - December 31, 2019 Category: Drugs & Pharmacology Authors: Moreno-Manzano V Tags: Curr Opin Pharmacol Source Type: research

Understanding the effects of air pollution on neurogenesis and gliogenesis in the growing and adult brain.
Abstract Exposure to air pollution - and particularly to particulate matter (PM) - is strongly associated with higher risk of neurodevelopmental disorders, poor mental health and cognitive defects. In animal models, disruption of CNS development and disturbances of adult neurogenesis contribute to PM neurotoxicity. Recent studies show that gestational PM exposure not only affects embryonic neurodevelopment, but also disturbs postnatal brain growth and maturation, by interfering with neurogenic/gliogenic events, myelination and synaptogenesis. Similarly, adult neurogenesis is affected at many levels, from neural st...
Source: Current Opinion in Pharmacology - December 30, 2019 Category: Drugs & Pharmacology Authors: Boda E, Rigamonti AE, Bollati V Tags: Curr Opin Pharmacol Source Type: research

NG2 cells and their neurogenic potential.
Abstract NG2 cells, which comprise a cycling population of glial cells, appear in the early phases of development and are present in the adult central nervous system. When a specific subpopulation of NG2 cells give rise to myelinating oligodendrocytes, they are also termed as oligodendrocyte precursor cells. Considering their capacity to proliferate and differentiate into other cellular types, their fate has been extensively investigated in several genetically modified mice. It is generally accepted that NG2 cells are restricted to the oligodendrocyte lineage, but numerous reports describe their differentiation in...
Source: Current Opinion in Pharmacology - December 23, 2019 Category: Drugs & Pharmacology Authors: Kirdajova D, Anderova M Tags: Curr Opin Pharmacol Source Type: research

Nutrients and neurogenesis: the emerging role of autophagy and gut microbiota.
Abstract Adult neurogenesis, the generation of mature functional neurons from neural stem cells in specific regions of the adult mammalian brain, is implicated in brain physiology, neurodegeneration and mood disorders. Among the many intrinsic and extrinsic factors that modulate neurogenic activity, the role of nutrients, energy metabolism, and gut microbiota has recently emerged. It is increasingly evident that excessive calorie intake accelerates the age-dependent decline of neurogenesis, while calorie restriction and physical exercise have the opposite effect. Mechanistically, nutrient availability could affect...
Source: Current Opinion in Pharmacology - December 20, 2019 Category: Drugs & Pharmacology Authors: Cavallucci V, Fidaleo M, Pani G Tags: Curr Opin Pharmacol Source Type: research

New insights into the regulatory roles of microRNAs in adult neurogenesis.
Abstract Adult neurogenesis, the process of generation of new functional neurons from neural stem cells, occurs in the subventricular zone and the subgranular zone neurogenic niches. This neurogenic process is tightly controlled by several intrinsic factors, including microRNAs (miRNAs), a class of small non-coding RNAs, which control protein translation. MiRNAs have emerged as important regulators of both embryonic and adult neural stem cells self-renewal and proliferation, neuronal differentiation, migration, maturation and integration into the complex neuronal circuitry. Herein, we will provide a review of the ...
Source: Current Opinion in Pharmacology - December 19, 2019 Category: Drugs & Pharmacology Authors: Esteves M, Serra-Almeida C, Saraiva C, Bernardino L Tags: Curr Opin Pharmacol Source Type: research

Endocannabinoid system and adult neurogenesis: a focused review.
Abstract The endocannabinoid system (eCB) is a ubiquitous lipid signaling system composed of at least two receptors, their endogenous ligands, and the enzymes responsible for their synthesis and degradation. Within the brain, the eCB system is highly expressed in the hippocampus and controls basic biological processes, including neuronal proliferation, migration and differentiation, which are intimately linked with embryonal neurogenesis. Accumulated preclinical evidence has indicated that eCBs play a major role also in regulating adult neurogenesis. Increased cannabinoid receptor activity, either by increased eCB...
Source: Current Opinion in Pharmacology - December 18, 2019 Category: Drugs & Pharmacology Authors: Oddi S, Scipioni L, Maccarrone M Tags: Curr Opin Pharmacol Source Type: research

Impact of gut microbiota on neurogenesis and neurological diseases during infancy.
E, Campoy C Abstract The first years of life constitute a crucial period for neurodevelopment and a window of opportunity to develop new strategies to prevent neurological and mental diseases. Different studies have shown the influence of gut bacteria in neurogenesis and a functional relationship between gut microbiota and the brain, known as 'gut-brain axis', in which the intestinal microbiota is proposed to play a key role in neurophysiological processes. It has been observed that certain microbiome metabolites could be related to the development of neurological disorders through mechanisms still unknown. Then, ...
Source: Current Opinion in Pharmacology - December 18, 2019 Category: Drugs & Pharmacology Authors: Cerdó T, Diéguez E, Campoy C Tags: Curr Opin Pharmacol Source Type: research

Editorial.
PMID: 31836467 [PubMed - as supplied by publisher] (Source: Current Opinion in Pharmacology)
Source: Current Opinion in Pharmacology - December 10, 2019 Category: Drugs & Pharmacology Authors: Williams M, Trist D Tags: Curr Opin Pharmacol Source Type: research

Adult hippocampal neurogenesis and antidepressants effects.
Abstract The hippocampus is particularly involved in cognitive processes and is a key regulator of stress responses and emotions. Therefore, the role of adult-born neurons in this region has become a crucial field of research in order to understand mood and stress disorders, such as major depression. Many studies have characterized the role of these neurons in cognition, mood regulation and antidepressant actions. Nevertheless, the precise mechanisms underpinning their antidepressant effects remain unclear. In this review, we first discuss the effects of stress and antidepressant treatments on adult neurogenesis, ...
Source: Current Opinion in Pharmacology - November 27, 2019 Category: Drugs & Pharmacology Authors: Planchez B, Surget A, Belzung C Tags: Curr Opin Pharmacol Source Type: research

Neuroimmune and epigenetic mechanisms underlying persistent loss of hippocampal neurogenesis following adolescent intermittent ethanol exposure.
Abstract Alcohol abuse and binge drinking are common during adolescence - a maturational period characterized by heightened hippocampal neuroplasticity and neurogenesis. Preclinical rodent models of adolescent binge drinking (i.e., adolescent intermittent ethanol [AIE]) find unique vulnerability of adolescent hippocampal neurogenesis with reductions persisting into adulthood after ethanol cessation. Recent discoveries implicate increased neuroimmune signaling and decreased neurotrophic support through epigenetic mechanisms in the persistent AIE-induced loss of neurogenesis. Importantly, interventions aimed at rect...
Source: Current Opinion in Pharmacology - November 25, 2019 Category: Drugs & Pharmacology Authors: Macht V, Crews FT, Vetreno RP Tags: Curr Opin Pharmacol Source Type: research

Recent advances in the non-invasive assessment of fibrosis using biomarkers.
Abstract Fibrosis can occur in most organs and is characterised by excessive and progressive extracellular matrix deposition and destruction of normal tissue architecture and function. In many cases treatment options are limited. Fibrotic diseases are therefore associated with high morbidity and mortality. Tissue biopsies remain a key part of diagnosing fibrosis; however, due to their invasive nature, tissue biopsies are unsuitable for monitoring disease progression. In some cases, tissue biopsies carry an unacceptable risk of mortality to the patient. Furthermore, assessing fibrosis via tissue biopsy is severely ...
Source: Current Opinion in Pharmacology - November 19, 2019 Category: Drugs & Pharmacology Authors: Tatler AL Tags: Curr Opin Pharmacol Source Type: research

Rejuvenating subventricular zone neurogenesis in the aging brain.
Abstract Neural stem cells exist in specialized regions of the brain and have the capacity to give rise to neurons and glia over the lifespan. The process of giving rise to new neurons, also known as neurogenesis, is thought to be important in cognition and certain types of brain repair. However, during aging, neural stem cell number and function is reduced resulting in fewer new neurons and declines in learning, memory and repair. Recently, research has approached this problem through the lens of rejuvenation that now has produced several strategies, from dietary to pharmacological interventions, to restore funct...
Source: Current Opinion in Pharmacology - November 19, 2019 Category: Drugs & Pharmacology Authors: Cutler RR, Kokovay E Tags: Curr Opin Pharmacol Source Type: research

Advances in the epigenetics of fibroblast biology and fibrotic diseases.
Abstract Fibroblasts have a central role in tissue fibrosis and fibrotic diseases. Fibroblast activation is regulated by several mechanisms including epigenetic modifications; histone modifications, DNA methylation and non-coding RNAs. Although research has significantly contributed to our basic understanding of fibrotic diseases over the last decade, cooperative activity of epigenetic mechanisms demonstrates the complexity of fibrogenesis. This review will summarise the latest epigenetic advances in fibroproliferative diseases. Current studies investigating biological implications of epigenetic modifiers, inhibit...
Source: Current Opinion in Pharmacology - November 12, 2019 Category: Drugs & Pharmacology Authors: Ulukan B, Sila Ozkaya Y, Zeybel M Tags: Curr Opin Pharmacol Source Type: research

Implementation of pre-clinical methodologies to study fibrosis and test anti-fibrotic therapy.
Abstract Diseases where fibrosis plays a major role accounts for enormous morbidity and mortality and yet we have very little in our therapeutic arsenal despite decades of research and clinical trials. Our understanding of fibrosis biology is primarily built on data generated in conventional mono-culture or co-culture systems and in vivo model systems. While these approaches have undoubtedly enhanced our understanding of basic mechanisms, they have repeatedly failed to translate to clinical benefit. Recently, there had been a push to generate more physiologically relevant platforms to study fibrosis and identify n...
Source: Current Opinion in Pharmacology - November 11, 2019 Category: Drugs & Pharmacology Authors: Oakley F, Gee LM, Sheerin NS, Borthwick LA Tags: Curr Opin Pharmacol Source Type: research

Adult hippocampal neurogenesis as a target for cocaine addiction: a review of recent developments.
;n LJ Abstract Basic research in rodents has shown that adult hippocampal neurogenesis (AHN) plays a key role in neuropsychiatric disorders that compromise hippocampal functioning. The discovery that dependence-inducing drugs regulate AHN has led to escalating interest in the potential involvement of AHN in drug addiction over the last decade, with cocaine being one of the most frequently investigated drugs. This review argues that, unlike other drugs of abuse, preclinical studies do not, overall, support that cocaine induces a marked or persistent impairment in AHN. Nevertheless, experimental reduction of AHN con...
Source: Current Opinion in Pharmacology - November 7, 2019 Category: Drugs & Pharmacology Authors: Castilla-Ortega E, Santín LJ Tags: Curr Opin Pharmacol Source Type: research

Editorial overview: Fibrosis.
PMID: 31699602 [PubMed - as supplied by publisher] (Source: Current Opinion in Pharmacology)
Source: Current Opinion in Pharmacology - November 4, 2019 Category: Drugs & Pharmacology Authors: Borthwick L, Oakley F Tags: Curr Opin Pharmacol Source Type: research

Resolving intestinal fibrosis through regenerative medicine.
Abstract Crohn's Disease and Ulcerative Colitis, known collectively as Inflammatory Bowel Disease (IBD), are lifelong gastrointestinal disorders that commonly present at a young age and are increasing in incidence and prevalence. Fibrosis is a common and incurable complication of IBD. When fibrotic complications occur, patients often have to undergo disfiguring surgery. Thus, research has focused on regenerative therapies as a means to prevent and treat established fibrosis. Both cell and non-cell therapies (exosomes) have anti-fibrotic and anti-inflammatory properties. This review discusses these emerging therape...
Source: Current Opinion in Pharmacology - November 1, 2019 Category: Drugs & Pharmacology Authors: Schwab R, Lim R, Goldberg R Tags: Curr Opin Pharmacol Source Type: research

Pathology and natural history of organ fibrosis.
Abstract Histopathological assessment of fibrosis focusing on morphological patterns provides important information for the management of patients with chronic diseases of the kidney, liver and the lung. This review summarizes key histopathological features of pulmonary, renal and hepatic fibrosis and discusses advances in the understanding of the pathogenesis of pulmonary fibrosis and pathogenetic insights with translational implications for renal fibrosis. The review also tackles new staging approaches based on liver fibrosis dynamics and evaluation of fibrosis regression, digital pathology and second harmonic g...
Source: Current Opinion in Pharmacology - October 28, 2019 Category: Drugs & Pharmacology Authors: Majo J, Klinkhammer BM, Boor P, Tiniakos D Tags: Curr Opin Pharmacol Source Type: research

Unravelling fibrosis using single-cell transcriptomics.
Abstract Fibrosis, the excessive accumulation of extracellular matrix, is a major global healthcare burden. Despite major advances in our understanding of the mechanisms regulating fibrosis, treatment options for patients with fibrosis remain very limited. However, recent developments in the rapidly evolving field of single-cell transcriptomics are enabling the interrogation of individual pathogenic cell populations in the context of fibrosis at unprecedented resolution. In this review, we will discuss how single-cell transcriptomics is driving this step change in our understanding of fibrotic disease pathogenesis...
Source: Current Opinion in Pharmacology - October 25, 2019 Category: Drugs & Pharmacology Authors: Dobie R, Henderson NC Tags: Curr Opin Pharmacol Source Type: research

Fibrosis and the intestinal microbiome; a focus on chronic liver disease.
Abstract The role of the microbiome in progression of liver disease is an exciting area of research that is advancing rapidly supported by the development of next-generation sequencing and bioinformatics tools that simultaneously identify the composition and function of the microbiome. Changes in the microbiome are associated with pathogenesis of chronic liver disease; specifically, changes in microbiome composition predict disease severity and specific microbial signatures can be used to distinguish between mild disease, advanced fibrosis and cirrhosis. Future work combining functional metagenomic analysis with p...
Source: Current Opinion in Pharmacology - October 25, 2019 Category: Drugs & Pharmacology Authors: Beraza N Tags: Curr Opin Pharmacol Source Type: research

Microfluidics for personalized drug screening of cancer.
Abstract Resistance to targeted therapies is a major clinical challenge in cancer treatment. Despite technological advances, robust biomarkers or platforms predictive of treatment response are lacking owing to the inherent nature of complex genomic landscape of carcinoma. Nevertheless, recent efforts centred on performing direct drug screening on patient-derived cells through their ex vivo expansion and maintenance have enabled personalized stratification of treatment modalities. Microfluidics is one such technology that allows high-throughput drug screening through parallelization and automation using small-volum...
Source: Current Opinion in Pharmacology - October 18, 2019 Category: Drugs & Pharmacology Authors: Venugopal Menon N, Lim SB, Lim CT Tags: Curr Opin Pharmacol Source Type: research