Sensing acidosis: nociception or sngception?

Background

Sensing tissue acidosis is an important function of the somatosensory nervous system to response to noxious stimuli.

Main body

In the pain clinic, acid or soreness sensation is a characteristic sensory phenotype of various acute and chronic pain syndromes, such as delayed onset muscle soreness, fibromyalgia, and radicular pain. However, soreness sensation is a sign of successful analgesia for acupuncture and noxipoint therapy. Thus, the nature of acid or soreness sensation is not always nociceptive (or painful) and could be anti-nociceptive. To facilitate the investigation of the molecular and neurobiological mechanisms of soreness sensation, we propose a concept called “sngception (sng- ception)” to describe the response of the somatosensory nervous system to sense tissue acidosis and to distinguish it from nociception. “Sng” is a Taiwanese word that represents the state of soreness while at the same time imitates the natural vocalization of humans feeling sore.

Conclusion

Here we propose sngception as a specific somatosensory function that transmits the acid sensation from the peripheral to the central nervous system. Sngception could partially overlap with nociception, but it could also transmit antinociception, proprioception, and pruriception.

     

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.

     

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.

     

ReToAd: simple method for the rapid replacement of promoters to improve protein production

Objective

To develop a method for fast replacement of promoters to improve protein production.

Results

A method (entitled retreat to advance or “ReToAd”), which includes a deleting PCR and a touchdown PCR, was validated by replacing seven IPTG-inducible promoters with enhanced green fluorescent protein (eGFP). The seven promoters were fully recovered by sequencing only 30 clones. The activity of E. coli harboring ω-transaminase (ω-TA) was increased from 112 U/mg cells (T7 promoter) to 147 U/mg cells (Trc promoter) by combining ReToAd and screening experiments. After screening a library comprising glutamate dehydrogenase (GDH) expressed by different promoters, the activity of E. coli cell harboring Trc-promoter-expressed GDH was ~31-fold higher than that of T7-promoter-expressed GDH.

Conclusions

The “ReToAd” for in situ rapid replacement of promoters was developed and optimized, and one round of “ReToAd” can be completed within 3 days.

     

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.

     

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.

     

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.

     

Neuroprotective strategies for NMDAR-mediated excitotoxicity in Huntington’s Disease

BACKGROUND

Huntington’s Disease (HD) is an autosomal dominant neurodegenerative disease causing severe neurodegeneration of the striatum as well as marked cognitive and motor disabilities. Excitotoxicity, caused by overstimulation of NMDA receptors (NMDARs) has been shown to have a key role in the neuropathogenesis of HD, suggesting that targeting NMDAR-dependent signaling may be an effective clinical approach for HD. However, broad NMDAR antagonists are generally poor therapeutics in clinical practice. It has been suggested that GluN2A-containing, synaptically located NMDARs activate cell survival signaling pathways, while GluN2B-containing, primarily extrasynaptic NMDARs trigger cell death signaling. A better approach to development of effective therapeutics for HD may be to target, specifically, the cell-death specific pathways associated with extrasynaptic GluN2B NMDAR activation, while maintaining or potentiating the cellsurvival activity of GluN2A-NMDARs.

OBJECTIVE

This review outlines the role of NMDAR-mediated excitotoxicity in HD and overviews current efforts to develop better therapeutics for HD where NMDAR excitotoxicity is the target.

METHODS

A systematic review process was conducted using the PubMed search engine focusing on research conducted in the past 5-10 years. 235 articles were consulted for the review, with key search terms including “Huntington’s Disease,” “excitotoxicity,” “NMDAR” and “therapeutics.”

RESULTS

A wide range of NMDAR excitotoxicity-based targets for HD were identified and reviewed, including targeting NMDARs directly by blocking GluN2B, extrasynaptic NMDARs and/or potentiating GluN2A, synaptic NMDARs, targeting glutamate release or uptake, or targeting specific downstream cell-death signaling of NMDARs.

CONCLUSION

The current review identifies NMDAR-mediated excitotoxicity as a key player in HD pathogenesis and points to various excitotoxicity-focused targets as potential future preventative therapeutics for HD.

     

Threatening biomarkers in lupus pregnancy: Biochemistry and genetic challenges

Objective

Using genetic markers and miRs work strongly beside other sensitive biomarkers in lupus management during sensitive period of pregnancy.

Methods

PubMed and Google Scholar databases were searched from 2000 to 2017 using the terms “lupus,” “lupus pregnancy,” “biomarkers,” “micro-RNA,” “polymorphisms,” “anti-phospholipid antibodies,” and “cluster differentiation markers.”

Discussion

Complement is a valuable biomarker in lupus pregnancy. However, the complement profile has ambiguous meaning because decreased levels of C3 and C4 reflect inflammation and because they are also prognostic biomarkers for abortion. Furthermore, increased C3 and C4 levels indicate hepatic protein synthesis in hepatocytes. Anti-phospholipid (APL) antibodies are present in 25% to 50% of lupus patients, and can lead to thrombotic and obstetric complications in some pregnancies and increase the risk of abortion, especially in a pregnant woman in the active phase of lupus. Several studies have associated APL with HELLP syndrome. However, other pregnancy complications have not been associated with APL. Autoantibodies against the major vault protein and anti-double strand DNA antibodies are valuable biomarkers in evaluating lupus activity. The expression pattern of micro-RNAs (miRs) differs in various diseases. Current studies have demonstrated the potential of miRs as diagnostic and prognostic biomarkers in various diseases; for example, the level of miR-126 is higher in lupus.

Conclusion

Mir-223-3p and miR-451 are informative biomarkers in estimating disease activity. TWEAK, BAFF, and APOL1 genes, and their polymorphisms are informative in estimating disease activity, especially renal effects, and in monitoring higher-risk pregnant women. Further studies of these genes and their relevant polymorphisms are needed.

     

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.

     

Relationships between catastrophic thought,bodily sensations and physical symptoms

Background

Researchers have recently begun to seek cognitive explanations for physical symptoms with no obvious biological cause. Concepts such as somatization, somatosensory amplification, and somatosensory catastrophizing have been invoked to explain these phenomena. Somatosensory amplification occurs when these bodily sensations become stronger and more painful. Somatosensory catastrophizing is the tendency to attribute these bodily sensations to unbearable functional modulation or as signs of serious illness. This causes the sufferer to pay excessive attention to these physical sensations. However, there is no scale for evaluating somatosensory catastrophizing, and there are no standard diagnostic criteria. There were two objectives for this study: to develop a scale for evaluating somatosensory catastrophizing and to investigate relationships between somatosensory amplification, somatosensory catastrophizing, and physical symptoms.

Methods

In the first part of this study, in which we developed the scale, there were 231 student participants with an average age of 20.1 years. Of these, 57% of the participants were female. In the second part of the study, there were two groups of participants. The first group consisted of 158 non-patient subjects, 56% of whom were female, with an average age of 20.2 years. There were 33 outpatients receiving treatment for somatoform disorders in the second group. The average age of these participants, of whom 67% were female, was 48.8 years. The second part of the study was conducted using standardized self-rating questionnaires to assess somatosensory amplification and catastrophizing.

Results

We developed a 27-item scale, which we have called the Somatosensory catastrophizing scale (SSCS). The SSCS assesses five key areas, and our analysis confirmed it to be valid and highly reliable. The scale identified that the patient group from the second part of the study scored more highly than the control group for both somatosensory amplification and catastrophizing. Additionally, the results of covariance structure analyses revealed a significant causal relationship of the form “somatosensory amplifcation” via “somatosensory catastrophizing” to “physical symptoms”. This relationship held in both groups of participants. The key difference between the patient and non-patient groups was that somatosensory catastrophizing had a greater impact on the physical symptoms of the participants in the patient group.

Conclusions

In this study, we developed the SSCS, which enables us to measure somatosensory catastrophizing empirically. We then clarified the relationship between somatosensory amplification, somatosensory catastrophizing, and physical symptoms. In the future, we expect to be able to apply our new understanding to developing intervention techniques to mitigate the physical symptoms caused by somatosensory catastrophizing.

     

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.

     

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.

     

To be or not to be [fertile], that is the question

Background

According to our literature analysis, there are no data focused on spermatozoa emotional representations in childless men and data on the emotional repercussions of a diagnosis of infertility on men are still scarce. Thus, in this work, we investigated what the presence or absence of spermatozoa in the semen symbolize for men.

Material and methods

To answer this question, 441 childless heterosexual men participated in an anonymous, prospective, Internet-based survey.

Results

In response to the question “What would having a high or normal sperm count symbolize for you?” the most frequent answer was “ability to father a child”. Men living with a partner were significantly more likely than single men to answer “ability to father a child” (p?<?0.05) and less likely to answer “virility” and/or “ability to have an erection/ejaculation” (p?=?0.001). In response to the question “If you found out that you had a low sperm count or no spermatozoa at all, how would you feel?”, most of the men stated that they would be disappointed. Men living with a partner were more likely to state that they would feel ashamed (p?<?0.05) or guilty with regard to their partner (p?<?0.0001).

Conclusions

These preliminary results should help us to improve (i) the way that male infertility is announced (it is easier to find the right words if one understands the possible importance of having a high sperm count) and (ii) the psychological, marital and sexual counselling provided to men with a diagnosis of infertility.