scholarly journals Cellular Senescence in the Kidney

2019 ◽  
Vol 30 (5) ◽  
pp. 726-736 ◽  
Author(s):  
Marie-Helena Docherty ◽  
Eoin D. O’Sullivan ◽  
Joseph V. Bonventre ◽  
David A. Ferenbach

Senescent cells have undergone permanent growth arrest, adopt an altered secretory phenotype, and accumulate in the kidney and other organs with ageing and injury. Senescence has diverse physiologic roles and experimental studies support its importance in nephrogenesis, successful tissue repair, and in opposing malignant transformation. However, recent murine studies have shown that depletion of chronically senescent cells extends healthy lifespan and delays age-associated disease—implicating senescence and the senescence-associated secretory phenotype as drivers of organ dysfunction. Great interest is therefore focused on the manipulation of senescence as a novel therapeutic target in kidney disease. In this review, we examine current knowledge and areas of ongoing uncertainty regarding senescence in the human kidney and experimental models. We summarize evidence supporting the role of senescence in normal kidney development and homeostasis but also senescence-induced maladaptive repair, renal fibrosis, and transplant failure. Recent studies using senescent cell manipulation and depletion as novel therapies to treat renal disease are discussed, and we explore unanswered questions for future research.

2019 ◽  
Vol 20 (5) ◽  
pp. 376-389 ◽  
Author(s):  
Sonali Mishra ◽  
Nupur Srivastava ◽  
Velusamy Sundaresan ◽  
Karuna Shanker

Background: Decalepis arayalpathra (J. Joseph and V. Chandras.) Venter is used primarily for nutrition besides its therapeutic values. Traditional preparations/formulations from its tuber are used as a vitalizer and blood purifier drink. The folklore medicinal uses cover inflammation, cough, wound healing, antipyretic, and digestive system management. A comprehensive review of the current understanding of the plant is required due to emerging concerns over its safety and efficacy. Objective: The systematic collection of the authentic information from different sources with the critical discussion is summarised in order to address various issues related to botanical identity, therapeutic medicine, nutritional usage, phytochemical, and pharmacological potentials of the D. arayalpathra. Current use of traditional systems of medicine can be used to expand future research opportunities. Materials and Methods: Available scripted information was collected manually, from peered review research papers and international databases viz. Science Direct, Google Scholar, SciFinder, Scopus, etc. The unpublished resources which were not available in database were collected through the classical books of ‘Ayurveda’ and ‘Siddha’ published in regional languages. The information from books, Ph.D. and MSc dissertations, conference papers and government reports were also collected. We thoroughly screened the scripted information of classical books, titles, abstracts, reports, and full-texts of the journals to establish the reliability of the content. Results: Tuber bearing vanilla like signature flavor is due to the presence of 2-hydroxy-4-methoxybenzaldehyde (HMB). Among five other species, Decalepis arayalpathra (DA) has come under the ‘critically endangered’ category, due to over-exploitation for traditional, therapeutic and cool drink use. The experimental studies proved that it possesses gastro-protective, anti-tumor, and antiinflammatory activities. Some efforts were also made to develop better therapeutics by logical modifications in 2-Hydroxy-4-methoxy-benzaldehyde, which is a major secondary metabolite of D. arayalpathra. ‘Amruthapala’ offers the enormous opportunity to develop herbal drink with health benefits like gastro-protective, anti-oxidant and anti-inflammatory actions. Results: The plant has the potential to generate the investigational new lead (IND) based on its major secondary metabolite i.e. 2-Hydroxy-4-methoxy-benzaldehyde. The present mini-review summarizes the current knowledge on Decalepis arayalpathra, covering its phytochemical diversity, biological potentials, strategies for its conservation, and intellectual property rights (IPR) status. Chemical Compounds: 2-hydroxy-4-methoxybenzaldehyde (Pubchem CID: 69600), α-amyrin acetate (Pubchem CID: 293754), Magnificol (Pubchem CID: 44575983), β-sitosterol (Pubchem CID: 222284), 3-hydroxy-p-anisaldehyde (Pubchem CID: 12127), Naringenin (Pubchem CID: 932), Kaempferol (Pubchem CID: 5280863), Aromadendrin (Pubchem CID: 122850), 3-methoxy-1,2-cyclopentanedione (Pubchem CID: 61209), p-anisaldehyde (Pubchem CID: 31244), Menthyl acetate (Pubchem CID: 27867), Benzaldehyde (Pubchem CID: 240), p-cymene (Pubchem CID: 7463), Salicylaldehyde (Pubchem CID: 6998), 10-epi-γ-eudesmol (Pubchem CID: 6430754), α -amyrin (Pubchem CID: 225688), 3-hydroxy-4-methoxy benzaldehyde (Pubchem CID: 12127).


Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 723
Author(s):  
Hafid Ait-Oufella ◽  
Jean-Rémi Lavillegrand ◽  
Alain Tedgui

Experimental studies have provided strong evidence that chronic inflammation triggered by the sub-endothelial accumulation of cholesterol-rich lipoproteins in arteries is essential in the initiation and progression of atherosclerosis. Recent clinical trials highlighting the efficacy of anti-inflammatory therapies in coronary patients have confirmed that this is also true in humans Monocytes/macrophages are central cells in the atherosclerotic process, but adaptive immunity, through B and T lymphocytes, as well as dendritic cells, also modulates the progression of the disease. Analysis of the role of different T cell subpopulations in murine models of atherosclerosis identified effector Th1 cells as proatherogenic, whereas regulatory T cells (Tregs) have been shown to protect against atherosclerosis. For these reasons, better understanding of how Tregs influence the atherosclerotic process is believed to provide novel Treg-targeted therapies to combat atherosclerosis. This review article summarizes current knowledge about the role of Tregs in atherosclerosis and discusses ways to enhance their function as novel immunomodulatory therapeutic approaches against cardiovascular disease.


Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 759
Author(s):  
Gaku Yamanaka ◽  
Fuyuko Takata ◽  
Yasufumi Kataoka ◽  
Kanako Kanou ◽  
Shinichiro Morichi ◽  
...  

Pericytes are a component of the blood–brain barrier (BBB) neurovascular unit, in which they play a crucial role in BBB integrity and are also implicated in neuroinflammation. The association between pericytes, BBB dysfunction, and the pathophysiology of epilepsy has been investigated, and links between epilepsy and pericytes have been identified. Here, we review current knowledge about the role of pericytes in epilepsy. Clinical evidence has shown an accumulation of pericytes with altered morphology in the cerebral vascular territories of patients with intractable epilepsy. In vitro, proinflammatory cytokines, including IL-1β, TNFα, and IL-6, cause morphological changes in human-derived pericytes, where IL-6 leads to cell damage. Experimental studies using epileptic animal models have shown that cerebrovascular pericytes undergo redistribution and remodeling, potentially contributing to BBB permeability. These series of pericyte-related modifications are promoted by proinflammatory cytokines, of which the most pronounced alterations are caused by IL-1β, a cytokine involved in the pathogenesis of epilepsy. Furthermore, the pericyte-glial scarring process in leaky capillaries was detected in the hippocampus during seizure progression. In addition, pericytes respond more sensitively to proinflammatory cytokines than microglia and can also activate microglia. Thus, pericytes may function as sensors of the inflammatory response. Finally, both in vitro and in vivo studies have highlighted the potential of pericytes as a therapeutic target for seizure disorders.


2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Maja Dorota Wojciechowska

Purpose The purpose of the paper is to present the latest scholarly trends in the field of social capital in libraries, to review research concepts published by LIS professionals and to suggest further research possibilities in this area. Design/methodology/approach This paper presents a review and critical analysis of literature associated with research on social capital in libraries to highlight its importance for the development of LIS and its impact on the functioning of environments linked with various types of libraries. The goal of literature analysis was to determine the current condition of research on social capital in libraries. The main trends were identified and the need for further qualitative analyses, which are missing at the moment, was confirmed. Findings It was determined that, so far, LIS professionals have focussed mainly on the role of municipal libraries in developing social capital, the problem of building trust, especially in immigrant circles and the impact of libraries on promoting a civil society. Academic libraries, rural libraries, organisational capital in libraries and individual social capital of librarians were a much less frequent subject of research. The role of libraries in developing social capital in educational (primary and secondary education) and professional (non-university professionals) circles is practically non-existent in research, and it will require in-depth studies and analyses in the coming years. Originality/value This paper constitutes a synthetic review of the latest research concepts concerning social capital in libraries. It identifies the most important research trends and areas that so far have not been explored and suggests research methods to help LIS professionals design future research in this area more effectively.


2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Manita Kusi ◽  
Fuqiang Zhao ◽  
Dinesh Sukamani

PurposeThe study aims to scrutinize the concomitant associations between corporate social responsibility (CSR), perceived organizational support (POS), green transformational leadership (GTL) and organizational performance (OP). This paper aims to explore the role of intervening variable to measure the strength on the relationship between CSR and OP.Design/methodology/approachThis research administered a survey through self-administered questionnaire among the staff-level employees of construction companies of Nepal. Fully filled 305 responses from the participants were analyzed using a structural equation model. The study used self-structured questionnaire as research tool and face-to-face meetings as data collection technique.FindingsThe research indicates that POS showed competitive partial mediation relation between CSR and OP. Besides, a novel exploration of the moderation effect of GTL displays a supportive role in harmonizing the CSR with organizational support to achieve better OP. This study enriches empirical evidence to understand the linkage between CSR and POS in staff-level employees in the construction area. Moreover, the research shed a light on GTL 's moderating influence on the mediated model of CSR, POS and OP.Research limitations/implicationsAlthough the results of the study add to the current knowledge base, several limitations highlight avenues for future research. Future studies can explore the relationship in other study areas with added evidence on a similar result with different analysis patterns and study sample. The research model studied in the context of Nepal creating evidence as a representation for the developing countries.Originality/valueThe intervening role of POS and GTL gives new insight for the research-based organization based social behavior and performance


2019 ◽  
Vol 141 (6) ◽  
Author(s):  
Nicole Damen ◽  
Christine Toh

Although trust can have a positively mediating effect on information technology adoption and usage, the concept has not been extensively investigated in the home automation field. Therefore, this work is aimed at exploring the role of agent location and the gender of the agent's voice on users' perception of trust toward automation through two experimental studies (N = 8 and N = 20) and a web-based smart lock simulation. Explicit trust behavior was captured using directly observable behaviors and decisions, while implicit trust behavior was captured using detailed click-level user behaviors with the smart lock simulation as a proxy for reaction time. The results show that users displayed more explicit trusting behavior toward the system when it displayed design characteristics that were stereotype congruent (female-home and male-office) compared to stereotype incongruent systems (male-home and female-office). These results show that users carry over the social expectations and roles encountered in human-to-human relationships to interactions with simulated automated agents. These findings empirically demonstrate the influence of design characteristics on the formation of trust relationships between users and automated devices and provide a foundation for future research geared at critically examining our evolving relationship with technology.


ExRNA ◽  
2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Fangfang Jin ◽  
Zhigang Guo

Abstract The discovery of small non-coding RNAs, such as miRNA and piRNA, has dramatically changed our understanding of the role RNA plays in organisms. Recent studies show that a novel small non-coding RNA generated from cleavage of tRNA or pre-tRNA, called tRNA-derived small RNA (tsRNA), serves as a new regulator of gene expression. tsRNA has been determined participate in regulating some specific physiological and pathological processes. Although knowledge regarding the biological roles of miRNA and piRNA is expanding, whether tsRNAs play similar roles remains poorly understood. Here, we review the current knowledge regarding the mechanisms of action and biological functions of tsRNAs in intracellular, extracellular and intergenerational inheritance, and highlight the potential application of tsRNAs in human diseases, and present the current problems and future research directions.


2021 ◽  
Vol 2 ◽  
Author(s):  
Siti Farah Rahmawati ◽  
Maurice te Velde ◽  
Huib A. M. Kerstjens ◽  
Alexander S. S. Dömling ◽  
Matthew Robert Groves ◽  
...  

Asthma is a respiratory disease that currently affects around 300 million people worldwide and is defined by coughing, shortness of breath, wheezing, mucus overproduction, chest tightness, and expiratory airflow limitation. Increased levels of interleukin 17 (IL-17) have been observed in sputum, nasal and bronchial biopsies, and serum of patients with asthma compared to healthy controls. Patients with higher levels of IL-17 have a more severe asthma phenotype. Biologics are available for T helper 2 (Th2)-high asthmatics, but the Th17-high subpopulation has a relatively low response to these treatments, rendering it a rather severe asthma phenotype to treat. Several experimental models suggest that targeting the IL-17 pathway may be beneficial in asthma. Moreover, as increased activation of the Th17/IL-17 axis is correlated with reduced inhaled corticosteroids (ICS) sensitivity, targeting the IL-17 pathway might reverse ICS unresponsiveness. In this review, we present and discuss the current knowledge on the role of IL-17 in asthma and its interaction with the Th2 pathway, focusing on the rationale for therapeutic targeting of the IL-17 pathway.


Reproduction ◽  
2021 ◽  
Vol 161 (1) ◽  
pp. F1-F17
Author(s):  
Rocío Martínez-Aguilar ◽  
Lucy E Kershaw ◽  
Jane J Reavey ◽  
Hilary O D Critchley ◽  
Jacqueline A Maybin

The endometrium is a multicellular tissue that is exquisitely responsive to the ovarian hormones. The local mechanisms of endometrial regulation to ensure optimal function are less well characterised. Transient physiological hypoxia has been proposed as a critical regulator of endometrial function. Herein, we review the literature on hypoxia in the non-pregnant endometrium. We discuss the pros and cons of animal models, human laboratory studies and novel in vivo imaging for the study of endometrial hypoxia. These research tools provide mounting evidence of a transient hypoxic episode in the menstrual endometrium and suggest that endometrial hypoxia may be present at the time of implantation. This local hypoxia may modify the inflammatory environment, influence vascular remodelling and modulate endometrial proliferation to optimise endometrial function. Finally, we review current knowledge of the impact of this hypoxia on endometrial pathologies, with a focus on abnormal uterine bleeding. Throughout the manuscript areas for future research are highlighted with the aim of concentrating research efforts to maximise future benefits for women and society.


2018 ◽  
Vol 44 (08) ◽  
pp. 765-779 ◽  
Author(s):  
Sigrid Brækkan ◽  
John-Bjarne Hansen ◽  
Line Evensen

AbstractVenous thromboembolism (VTE) is a complex multifactorial disease that represents a growing public health concern. Identification of modifiable risk factors at the population level may provide a measure to reduce the burden of VTE. In this review, we summarize current knowledge of the role of physical activity on the risk of VTE and VTE-related complications. We also discuss methodological challenges related to research on physical activity, and put forward plausible mechanisms for an association between physical activity and VTE. Up to now, published studies have reported diverging results on the relationship between physical activity and VTE, and a complex picture has emerged. However, the available evidence appears to be balanced toward a small beneficial effect of physical activity on the risk of incident VTE, but not in a dose-dependent manner. Still, the lack of an operational definition and standardized assessment method for physical activity, as well as several sources of bias, impairs the interpretation of the available literature. Additional work is necessary to understand the role and how to apply physical activity in the VTE setting. Future research should utilize objective assessment strategies of physical activity and physical fitness, account for the fluctuating nature in habitual activity levels, and explore the role of physical activity in the areas of secondary prevention and VTE-related complications.


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