Cationic antimicrobial peptide: LL-37 and its role in periodontitis

Background

Periodontitis i.e. inflammation of the periodontium is a multifactorial disease. Antimicrobial peptides (AMPs) which demonstrate a broad-spectrum of activity against varied number of bacteria, fungi, viruses, and parasites, and cancerous cells have been linked to periodontitis. The AMPs even possess the caliber of immunomodulation, and are significantly responsive to innate immuno-stimulation and infections. LL-37 plays a salubrious role by preventing and in treatment of chronic forms of periodontitis.

Objective

In the present work we will review the role of antimicrobial peptide LL-37 in periodontitis.

Methods

A systematic search was carried out from the beginning till August, 2016 using the Pubmed search engine. The keywords included “LL-37,” “periodontitis,” “Papillon–Lefevre syndrome,” “Morbus Kostmann,” “Haim-Munk syndrome” along with use of Boolean operator “and.”

Results

The search resulted in identifying 67 articles which included articles linking LL-37 with periodontitis, articles on Papillon–Lefevre syndrome, Morbus Kostmann, Haim-Munk syndrome, LL-37 and periodontitis and articles on pathogenicity of periodontitis.

Conclusion

The literature search concluded that LL-37 plays a pivotal role in preventing and treatment of severe form of periodontitis.

     

Crosstalk between catecholamines and erythropoiesis

Background

Erythropoiesis is regulated by a range of intrinsic and extrinsic factors, including different cytokines. Recently, the role of catecholamines has been highlighted in the development of erythroid cell lineages.

Objective

This study focuses on the biological links interconnecting erythroid development and the sympathetic nervous system. The emerging evidence that underscores the role of catecholamines in the regulation of erythropoietin and other erythropoiesis cytokines are thoroughly reviewed, in addition to elements such as iron and the leptin hormone that are involved in erythropoiesis.

Methods

Relevant English-language studies were identified and retrieved from the PubMed search engine (1981–2017) using the following keywords: “Erythropoiesis”, “Catecholamines”, “Nervous system”, and “Cytokines.”

Results

Chronic social stress alters and suppresses erythroid development. However, the physiological release of catecholamines is an additional stimulator of erythropoiesis in the setting of anemia. Therefore, the severity and timing of catecholamine secretion might distinctly regulate erythroid homeostasis.

Conclusion

Understanding the relationship of catecholamines with different elements of the erythroid islands will be essential to find the tightly regulated production of red blood cells (RBCs) in both chronic and physiological catecholamine activation.

     

Metabolomic profiling of maternal hair suggests rapid development of intrahepatic cholestasis of pregnancy

Introduction

Intrahepatic cholestasis of pregnancy (ICP) is a common maternal liver disease; development can result in devastating consequences, including sudden fetal death and stillbirth. Currently, recognition of ICP only occurs following onset of clinical symptoms.

Objective

Investigate the maternal hair metabolome for predictive biomarkers of ICP.

Methods

The maternal hair metabolome (gestational age of sampling between 17 and 41 weeks) of 38 Chinese women with ICP and 46 pregnant controls was analysed using gas chromatography–mass spectrometry.

Results

Of 105 metabolites detected in hair, none were significantly associated with ICP.

Conclusion

Hair samples represent accumulative environmental exposure over time. Samples collected at the onset of ICP did not reveal any metabolic shifts, suggesting rapid development of the disease.

     

How to manage rheumatoid arthritis according to classic biomarkers and polymorphisms?

Objectives

Single nucleotide polymorphisms (SNPs), genetic background, and epigenetics play important roles in rheumatoid arthritis (RA). These factors can be useful in RA diagnosis, prognosis, and treatment response evaluation, particularly with the growing trends in personalized medicine. Therefore, categorizing classic genes and SNPs in RA can present an appropriate guideline for RA management.

Discussion

Prognostic and diagnostic biomarkers play important roles in RA diagnosis and treatment. Categorizing SNPs is not an easy process yet, but selecting classic SNPs can be useful worldwide, according to basic similarities that exist in genomes. In this review, we compiled some of these RA-associated SNPs and biomarkers in a table, according to newly identified factors. The role of epigenetics in RA is undeniable; using epigenetic biomarkers like histone deacetylase (HDACs) can be useful in RA diagnosis and treatment. miRs such as miR-146a, miR-155, and miR-222 are useful in diagnosis and can be used in treatment by interfering with other factors’ functions. Interleukins (ILs) seem to be good prognostic and diagnostic markers and can be targeted in RA treatment.

Conclusion

Using multiple types of biomarkers, such as genes, SNPs, and epigenetic biomarkers like HDACs can be useful in RA management and treatment. PTPN22, HLA-DR polymorphisms, miRs, and HDACs are considerable in RA susceptibility; hence, they can be valuable biomarkers in future studies. This article gathered separate information from approximately 100 articles to present useful biomarkers and polymorphisms in one review.

     

Cytogenetic changes of mesenchymal stem cells in the neoplastic bone marrow niche in leukemia

Background

Bone marrow mesenchymal stromal cells (BM-MSCs) are an essential cell type in the hematopoietic microenvironment. The question of whether MSCs from patients with different leukemias have cytogenetic abnormalities is controversial. In this study, we attempted to review the cytogenetic profiles of MSCs in patients with leukemia, and verify whether these profiles were related to different ex vivo culture conditions or to chronic or acute disease states. This information could be useful in clarifying the origin of MSCs and developing clinical applications for this cell type.

Methods

A systematic literature search was performed using the PubMed search engine. Studies published over the past 15 years, i.e., between 1995 and January 2015, were considered for review. The following keywords were used: “cytogenetic,” “leukemia,” “bone marrow,” and “mesenchymal stromal cells.”

Results

Some studies demonstrated that BM-MSCs are cytogenetically normal, whereas others provided evidence of aberrations in these cells

Conclusions

Studying cytogenetic changes of MSCs in a variety of leukemias will help researchers understand the nature of these tumors and ensure the safety of human stem cells in clinical applications.

     

Assisted reproductive techniques with congenital hypogonadotropic hypogonadism patients: a systematic review and meta-analysis

Background

After hormonal replacement therapy (HRT) including androgen replacement or sequential therapy of estrogen and progesterone, The combination of human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG) and pulsatile GnRH, is not sufficient to produce sufficient gametes in some patients with Congenital hypogonadotropic hypogonadism (CHH). A Systematic review and meta-analysis was performed to determine that assisted reproductive techniques (ART) can effectively treat different causes of infertility.

Methods

To determine the effect of ART on fertility of CHH patients and investigate whether outcomes are similar to infertility due to other causes, we conducted a systematic review and meta-analysis of retrospective trials.Clinical trials were systematically searched in Medline, Embase, and the Cochrane central register of controlled trials databases. The keywords and major terms covered “hypogonadotropic hypogonadism”, “kallmann syndrome”, “assisted reproductive techniques”, “intrauterine insemination”, “intracytoplasmic sperm injection”, “testicular sperm extraction”, “in vitro fertilization”, “embryo transplantation” and “intra-Fallopian transfer”.

Results

A total of 388 pregnancies occurred among 709 CHH patients who received ART (effectiveness 46, 95% confidence interval 0.39 to 0.53) in the 20 studies we included. The I² in trials assessing overall pregnancy rate (PR) per embryo transfer (ET) cycle was 73.06%. Similar results were observed in subgroup analysis by different gender. Regression indicates pregnancy rate decreases with increasing age. Fertilization, implantation and live birth rates (72, 36 and 40%) showed no significant differences as compared to infertility due to other causes.

Conclusions

Despite CHH patients usually being difficult to generate gametes, their actual chances of fertility are similar to subjects with other non-obstructive infertility. ART is a suitable option for CHH patients who do not conceive after long-term gonadotropin treatment.

     

Neuronal activity controls the development of interneurons in the somatosensory cortex

BACKGROUND

Neuronal activity in cortical areas regulates neurodevelopment by interacting with defined genetic programs to shape the mature central nervous system. Electrical activity is conveyed to sensory cortical areas via intracortical and thalamocortical neurons, and includes oscillatory patterns that have been measured across cortical regions.

OBJECTIVE

In this work, we review the most recent findings about how electrical activity shapes the developmental assembly of functional circuitry in the somatosensory cortex, with an emphasis on interneuron maturation and integration. We include studies on the effect of various neurotransmitters and on the influence of thalamocortical afferent activity on circuit development. We additionally reviewed studies describing network activity patterns.

METHODS

We conducted an extensive literature search using both the PubMed and Google Scholar search engines. The following keywords were used in various iterations: “interneuron”, “somatosensory”, “development”, “activity”, “network patterns”, “thalamocortical”, “NMDA receptor”, “plasticity”. We additionally selected papers known to us from past reading, and those recommended to us by reviewers and members of our lab.

RESULTS

We reviewed a total of 132 articles that focused on the role of activity in interneuronal migration, maturation, and circuit development, as well as the source of electrical inputs and patterns of cortical activity in the somatosensory cortex. 79 of these papers included in this timely review were written between 2007 and 2016.

CONCLUSION

Neuronal activity shapes the developmental assembly of functional circuitry in the somatosensory cortical interneurons. This activity impacts nearly every aspect of development and acquisition of mature neuronal characteristics, and may contribute to changing phenotypes, altered transmitter expression, and plasticity in the adult. Progressively changing oscillatory network patterns contribute to this activity in the early postnatal period, although a direct requirement for specific patterns and origins of activity remains to be demonstrated.

     

Inhibition and attenuation of pathogenicity of <Emphasis Type="Italic">Porphyromonas gingivalis</Emphasis> by leupeptin: A review

Background

Porphyromonas gingivalis is a periodontal pathogen, which is considered to be a keystone pathogen for periodontitis. A diverse conglomerate of P. gingivalis virulence factors including lipopolysaccharide, fimbriae, capsular polysaccharide, haemagglutinin and cysteine proteases (Arg-gingipains and Lys-gingipain) are considered to be involved in the pathogenesis of periodontitis. Leupeptin is a cysteine protease inhibitor which is specific for Arg gingipains. The present review focuses on action of leupeptin on Arg gingipains.

Method

A search was carried out systematically from the start till September, 2016. The search was made in Medline database via PubMed. The keywords enlisted were “leupeptin”; “gingipains”; “periodontitis” using Boolean operator “and.”

Results

The result was selection of 58 articles which linked leupeptin to periodontitis and gingipains; pathogenesis of periodontitis, pathogenicity of gingipains and role of leupeptin.

Conclusion

It was concluded that leupeptin inhibits and attenuates a number of destructive activities of Arg gingipains including inhibition of platelet aggregation; inhibit degradation of LL-37, which is an antimicrobial peptide; blocking inhibition of monocyte chemoattractant protein; restoring level of interleukin-2; inhibiting degradation of collagen type I and IV to name a few.

     

Metabolomic characterization of hypertension and dyslipidemia

Background

Hypertension and dyslipidemia are two main risk factors for cardiovascular diseases (CVD). Moreover, their coexistence predisposes individuals to a considerably increased risk of CVD. However, the regulatory mechanisms involved in hypertension and dyslipidemia as well as their interactions are incompletely understood.

Objectives

The aims of our study were to identify metabolic biomarkers and pathways for hypertension and dyslipidemia, and compare the metabolic patterns between hypertension and dyslipidemia.

Methods

In this study, we performed metabolomic investigations into hypertension and dyslipidemia based on a “healthy” UK population. Metabolomic data from the Husermet project were acquired by gas chromatography–mass spectrometry and ultra-performance liquid chromatography–mass spectrometry. Both univariate and multivariate statistical methods were used to facilitate biomarker selection and pathway analysis.

Results

Serum metabolic signatures between individuals with and without hypertension or dyslipidemia exhibited considerable differences. Using rigorous selection criteria, 26 and 46 metabolites were identified as potential biomarkers of hypertension and dyslipidemia respectively. These metabolites, mainly involved in fatty acid metabolism, glycerophospholipid metabolism, alanine, aspartate and glutamate metabolism, are implicated in insulin resistance, vascular remodeling, macrophage activation and oxidised LDL formation. Remarkably, hypertension and dyslipidemia exhibit both common and distinct metabolic patterns, revealing their independent and synergetic biological implications.

Conclusion

This study identified valuable biomarkers and pathways for hypertension and dyslipidemia, and revealed common and different metabolic patterns between hypertension and dyslipidemia. The information provided in this study could shed new light on the pathologic mechanisms and offer potential intervention targets for hypertension and dyslipidemia as well as their related diseases.

     

Metabolism of pluripotent stem cells

Background

Recently, growing attention has been directed toward stem cell metabolism, with the key observation that metabolism not only fuels the proper functioning of stem cells but also regulates the fate of these cells. There seems to be a clear link between the self-renewal of pluripotent stem cells (PSCs), in which cells proliferate indefinitely without differentiation, and the activity of specific metabolic pathways. The unique metabolism in PSCs plays an important role in maintaining pluripotency by regulating signaling pathways and resetting the epigenome.

Objective

To review the most recent publications concerning the metabolism of pluripotent stem cells and the role of metabolism in PSC self-renewal and differentiation.

Methods

A systematic literature search related to the metabolism of PSCs was conducted in databases including Medline, Embase, and Web of Science. The search was performed without language restrictions on all papers published before May 2016. The following keywords were used: “metabolism” combined with either “embryonic stem cell” or “epiblast stem cell.”

Results

Hundreds of papers focusing specifically on the metabolism of pluripotent stem cells were uncovered and summarized.

Conclusion

Identifying the specific metabolic pathways involved in pluripotency maintenance is crucial for progress in the field of developmental biology and regenerative medicine. Additionally, better understanding of the metabolism in PSCs will facilitate the derivation and maintenance of authentic PSCs from species other than mouse, rat, and human.

     

Are we still keeping it “real”? Proposing a revised paradigm for recycling credits in attributional life cycle assessment

Purpose

End-of-life (EoL) recycling poses a challenge to many practitioners today due to the availability of different calculation approaches and the lack of scientific consensus, which is fueled by academic research and vested industry interests alike. One of the main challenges in EoL modeling is the credible calculation of the appropriate recycling credit in open-loop and closed-loop situations.

Methods

We believe that part of the challenge is caused by a lack of understanding of the underlying recycling paradigm, which refers to the meaning that is assigned to the recycling credit. Referred to as “system expansion through substitution” and “future displacement of primary production,” the two predominant paradigms are delineated from each other followed by a discussion of their remaining challenges.

Results and discussion

Based on these considerations, we propose a revised paradigm based on embodied burdens that is able to alleviate many of the most pressing issues associated with material recycling in attributional life cycle assessment.

Conclusions

With this discussion paper, we look forward to a productive and lively debate on the matter.

     

Analysis of the free fatty acid metabolome in the plasma of patients with systemic lupus erythematosus and fever

Introduction

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease with heterogeneous clinical manifestations mediated by immune dysregulation.

Objectives

We aimed to analyze the metabolomic differences in free fatty acids (FFAs) between patients with SLE and healthy controls (HCs).

Methods

In this study, the levels of 24 FFAs, as their tert-butyldimethylsilyl derivatives, in the plasma of 41 patients with SLE and 41 HCs, were investigated using gas chromatography with mass spectrometry in selected-ion monitoring mode.

Results

The results showed that patients with SLE and HCs had significantly different levels of 13 of the 24 FFAs. The levels of myristic, palmitoleic, oleic, and eicosenoic acids were significantly higher, whereas the levels of caproic, caprylic, linoleic, stearic, arachidonic, eicosanoic, behenic, lignoceric, and hexacosanoic acids were significantly lower in patients with SLE, than in the HCs. In the partial-correlation analysis of the FFA profiles and markers of disease activity of SLE, several metabolic markers correlated with SLE disease activity.

Conclusions

Our results provide a comprehensive understanding of the relationship between FFAs and markers of SLE disease activity. Thus, this approach has promising potential for the discovery of metabolic biomarkers of SLE.

     

The journey of gut microbiome – An introduction and its influence on metabolic disorders

Background

Metabolic disorders such as Obesity, Diabetes Type 2 (T2DM) and Inflammatory Bowel Diseases (IBD) are the most prevalent globally. Recently, there has been a surge in the evidence indicating the correlation between the intestinal microbiota and development of these metabolic conditions apart from predisposing genetic and epigenetic factors. Gut microbiome is pivotal in controlling the host metabolism and physiology. But imbalances in the microbiota patterns lead to these disorders via several pathways. Animal and human studies so far have concentrated mostly on metagenomics for the whole microbiome characterization to understand how microbiome supports health in general. However, the accurate mechanisms connecting the metabolic disorders and alterations in gut microbial composition in host and the metabolites employed by the microorganisms in regulating the metabolic disorders is still vague.

Objective

The review delineates the latest findings about the role of gut microbiome to the pathophysiology of Obesity, IBD and Diabetes Mellitus. Here, we provide a brief introduction to the gut microbiome followed by the current therapeutic interventions in restoration of the disrupted intestinal microbiota.

Methods

A methodical PubMed search was performed using keywords like “gut microbiome,” “obesity,” “diabetes,” “IBD,” and “metabolic syndromes.” All significant and latest publications up to January 2018 were accounted for the review.

Results

Out of the 93 articles cited, 63 articles focused on the gut microbiota association to these disorders. The rest 18 literature outlines the therapeutic approaches in maintaining the gut homeostasis using probiotics, prebiotics and faecal microbial transplant (FMT).

Conclusion

Metabolic disorders have intricate etiology and thus a lucid understanding of the complex host-microbiome inter-relationships will open avenues to novel therapeutics for the diagnosis, prevention and treatment of the metabolic diseases.

     

Review: life-cycle assessment,water footprinting,and carbon footprinting in Portugal

Purpose

A review of readily available quantitative environmental data was conducted in order to determine the state of sustainability reporting and identify possible future research areas in Portugal.

Methods

Internet searches of articles written in English and published between 2001 and 2015 were conducted using the keywords “life-cycle assessment,” “LCA,” “water footprint,” “carbon footprint,” and “Portugal.” Additionally, reports from the Global Reporting Initiative (2015 only) were included in the search.

Results and discussion

It was found that 79% of reports found were published in the period 2011–2015. Several reports were found for the forestry, paper and pulp, food and beverage, energy and electricity, waste management, and automotive industries, while no reports were found for the textile, footwear and clothing, and base metal and mineral industries. As such, these are industries on which future studies might focus. No reports found were published by governmental organizations, although it is thought that expanding the search to include Portuguese language results would yields more results. The majority (68%) of companies reporting to the GRI adhered to the relevant guidelines.

Conclusions

A total of 72 reports were found (41 LCAs, water- or carbon footprints, and 31 GRI reports). It is unclear if there are other reports that may be restricted to “hidden” datasets or company specific archives. The aim of this report was to highlight those that were available to a non-specialist or international audiences trying to gain a greater understanding of the LCA space in Portugal.

     

DTL reconciliation repair

Background

Maximum parsimony phylogenetic tree reconciliation is an important technique for reconstructing the evolutionary histories of hosts and parasites, genes and species, and other interdependent pairs. Since the problem of finding temporally feasible maximum parsimony reconciliations is NP-complete, current methods use either exact algorithms with exponential worst-case running time or heuristics that do not guarantee optimal solutions.

Results

We offer an efficient new approach that begins with a potentially infeasible maximum parsimony reconciliation and iteratively “repairs” it until it becomes temporally feasible.

Conclusions

In a non-trivial number of cases, this approach finds solutions that are better than those found by the widely-used Jane heuristic.

     

Identification of a microRNA (miR-663a) induced by ER stress and its target gene PLOD3 by a combined microRNome and proteome approach

Introduction

MicroRNAs (miRs) regulate gene expression to support important physiological functions. Significant evidences suggest that miRs play a crucial role in many pathological events and in the cell response to various stresses.

Methods

With the aim to identify new miRs induced by perturbation of intracellular calcium homeostasis, we analysed miR expression profiles of thapsigargin (TG)-treated cells by microarray. In order to identify miR-663a-regulated genes, we evaluated proteomic changes in miR-663a-overexpressing cells by two-dimensional differential in-gel electrophoresis coupled to mass spectrometric identification of the differentially represented proteins. Microarray and proteomic analyses were supported by biochemical validation.

Results

Results of microarray revealed 24 differentially expressed miRs; among them, miR-663a turned out to be by ER stress and under the control of the PERK pathway of the unfolded protein response. Proteomic analysis revealed that PLOD3, which is the gene encoding for collagen-modifying lysyl hydroxylase 3 (LH3), is regulated by miR-663a. Luciferase reporter assays demonstrated that miR-663a indeed reduces LH3 expression by targeting to 3′-UTR of PLOD3 mRNA. Interestingly, miR-663a inhibition of LH3 expression generates reduced extracellular accumulation of type IV collagen, thus suggesting the involvement of miR-663a in modulating collagen 4 secretion in physiological conditions and in response to ER stress.

Conclusion

The finding of the ER stress-induced PERK-miR-663a pathway may have important implications in the understanding of the molecular mechanisms underlying the function of this miR in normal and/or pathological conditions.