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Introduction: Minimal change disease (MCD) and Focal and segmental glomerulosclerosis (FSGS) are two of the major causes of nephrotic syndrome (NS) in children and adults. According to KDIGO (Kidney Disease: Improving Global Outco...
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Introduction: Minimal change disease (MCD) and Focal and segmental glomerulosclerosis (FSGS) are two of the major causes of nephrotic syndrome (NS) in children and adults. According to KDIGO (Kidney Disease: Improving Global Outcomes) guidelines, the treatment of adult primary MCD and FSGS should be based on immunosuppressants and antiproteinuric drugs. Recently, Rituximab, a humanized monoclonal antibody (mAb) has emerged as a potential treatment for steroid or calcineurin inhibitor-dependent patients; it has however demonstrated lower efficacy in those with nephrotic syndrome that is resistant to the above indicated drugs. Area covered: Analysis of ongoing and already completed clinical trials, retrieved from clinicaltrials.gov, clinicaltrialsregister.eu and PubMed involving new therapies for nephrotic syndrome secondary to MCD and FSGS. Expert opinion: The most promising drugs under investigation for MCD and FSGS are mAbs. We are hopeful that new therapeutic options to treat multi-drug resistant MCD and FSGS will emerge from currently ongoing studies. What appears certain is the difficulty in enrolling patients affected by orphan renal diseases and the selection of valid endpoints in clinical trials, such as kidney failure.
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Eurasian deer are characterized by the extraordinary diversity of their vocal repertoires. Male sexual calls range from roars with relatively low fundamental frequency (hereafter fo) in red deer Cervus elaphus, to moans with extre...
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Eurasian deer are characterized by the extraordinary diversity of their vocal repertoires. Male sexual calls range from roars with relatively low fundamental frequency (hereafter fo) in red deer Cervus elaphus, to moans with extremely high fo in sika deer Cervus nippon, and almost infrasonic groans with exceptionally low fo in fallow deer Dama dama. Moreover, while both red and fallow males are capable of lowering their formant frequencies during their calls, sika males appear to lack this ability. Female contact calls are also characterized by relatively less pronounced, yet strong interspecific differences. The aim of this study is to examine the anatomical bases of these inter-specific and inter-sexual differences by identifying if the acoustic variation is reflected in corresponding anatomical variation. To do this, we investigated the vocal anatomy of male and female specimens of each of these three species. Across species and sexes, we find that the observed acoustic variability is indeed related to expected corresponding anatomical differences, based on the source-filter theory of vocal production. At the source level, low fo is associated with larger vocal folds, whereas high fo is associated with smaller vocal folds: sika deer have the smallest vocal folds and male fallow deer the largest. Red and sika deer vocal folds do not appear to be sexually dimorphic, while fallow deer exhibit strong sexual dimorphism (after correcting for body size differences). At the filter level, the variability in formants is related to the configuration of the vocal tract: in fallow and red deer, both sexes have evolved a permanently descended larynx (with a resting position of the larynx much lower in males than in females). Both sexes also have the potential for momentary, call-synchronous vocal tract elongation, again more pronounced in males than in females. In contrast, the resting position of the larynx is high in both sexes of sika deer and the potential for further active vocal tract elongation is virtually absent in both sexes. Anatomical evidence suggests an evolutionary reversal in larynx position within sika deer, that is, a secondary larynx ascent. Together, our observations confirm that the observed diversity of vocal behaviour in polygynous deer is supported by strong anatomical differences, highlighting the importance of anatomical specializations in shaping mammalian vocal repertoires. Sexual selection is discussed as a potential evolutionary driver of the observed vocal diversity and sexual dimorphisms. ? 2021 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.
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ABSTRACT: Dairy consumption has been studied extensively in terms of its relationship with testicular cancer (TC), yet this relationship remains unclear. In this systematic review, we aimed to answer whether TC development is asso...
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ABSTRACT: Dairy consumption has been studied extensively in terms of its relationship with testicular cancer (TC), yet this relationship remains unclear. In this systematic review, we aimed to answer whether TC development is associated with (a) high amounts of dairy product consumption, (b) the type of dairy product consumed, (c) increasing levels of dairy product consumption, and (d) dairy consumption during certain periods during the lifecourse. Following a systematic review of the literature, eight studies (all case-control studies) were included in our review. The included studies varied in terms of the dairy product(s) investigated (milk, cheese, cream, butter, and yoghurt) as well as the type of exposure to dairy consumption (e.g., high vs. low exposure, dose-response, and timing during lifecourse). We found that there was no strong evidence that high levels of dairy consumption are associated with risk of TC, conflicting evidence of a doseresponse relationship, inconsistent evidence on whether certain types of dairy are more strongly associated with TC than others, and conflicting evidence that exposure during certain life-course periods affects TC risk more than other periods. There is no consistent evidence to support the premise that dairy product consumption is associated with the risk of TC development. ?2018, ?2018 Taylor & Francis Group, LLC.
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There is an increasing awareness of the deleterious effects attributed to mycotoxins during their fate within the gut, particularly for deoxynivalenol (DON), zearalenone (ZEN), ochratoxin A (OTA), fumonisin B1 (FB1), aflatoxin B1 ...
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There is an increasing awareness of the deleterious effects attributed to mycotoxins during their fate within the gut, particularly for deoxynivalenol (DON), zearalenone (ZEN), ochratoxin A (OTA), fumonisin B1 (FB1), aflatoxin B1 (AFB1), and patulin (PAT). Evidence indicates that disruption of the epithelial barrier is well established. However, intestinal barrier function on its luminal side involves two other partners, mucus and microbiota, which have rarely been considered in the context of mycotoxin exposure. The current review aimed at providing a summary of DON, ZEN, OTA, FB1, AFB1, and PAT effects on intestinal barrier function, with special focus on mucus and microbiota. DON, ZEN, OTA, FB1, AFB1, and PAT are known to markedly affect epithelial cell integrity and functions. Regarding mucus, DON is the most documentated mycotoxin. In vivo, toxicological impact of DON generally has only been assessed through goblet cell number. Evaluation of the mycotoxins/mucus interplay considering other indicators such as composition, thickness, and penetrability of mucus, mucin O-glycosylation thus warrants further attention. With respect to microbiota, few short-term studies to date have been reported indicating deleterious effects. However, long-term exposure to mycotoxins may also produce significant changes in microbiota composition and metabolic activity, which requires further experimentation. In conclusion, mucus and microbiota are key targets for dietary mycotoxins although assessment of induced effects is preliminary. A significant research effort is now underway to determine the adverse consequences of mycotoxins on mucus and microbiota considered as individual but also as tightly connected gut players.
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Obesity and associated comorbidities are a major health burden, and novel therapeutics to help treat obesity are urgently needed. There is increasing evidence that targeting the amylin receptors (AMYRs), heterodimers of the calcit...
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Obesity and associated comorbidities are a major health burden, and novel therapeutics to help treat obesity are urgently needed. There is increasing evidence that targeting the amylin receptors (AMYRs), heterodimers of the calcitonin G protein–coupled receptor (CTR) and receptor activity-modifying proteins, improves weight control and has the potential to act additively with other treatments such as glucagon-like peptide-1 receptor agonists. Recent data indicate that AMYR agonists, which can also independently activate the CTR, may have improved efficacy for treating obesity, even though selective activation of CTRs is not efficacious. AM833 (cagrilintide) is a novel lipidated amylin analog that is undergoing clinical trials as a nonselective AMYR and CTR agonist. In the current study, we have investigated the pharmacology of AM833 across 25 endpoints and compared this peptide with AMYR selective and nonselective lipidated analogs (AM1213 and AM1784), and the clinically used peptide agonists pramlintide (AMYR selective) and salmon CT (nonselective). We also profiled human CT and rat amylin as prototypical selective agonists of CTR and AMYRs, respectively. Our results demonstrate that AM833 has a unique pharmacological profile across diverse measures of receptor binding, activation, and regulation. SIGNIFICANCE STATEMENT AM833 is a novel nonselective agonist of calcitonin family receptors that has demonstrated efficacy for the treatment of obesity in phase 2 clinical trials. This study demonstrates that AM833 has a unique pharmacological profile across diverse measures of receptor binding, activation, and regulation when compared with other selective and nonselective calcitonin receptor and amylin receptor agonists. The present data provide mechanistic insight into the actions of AM833. Copyright ? 2021 by The Author(s).
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The innate immune system serves as the first line of defense to protect the host from pathogen infection. As a first step, the pattern recognition receptors (PRRs) recognize pathogen-associated molecular patterns (PAMPs), such as ...
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The innate immune system serves as the first line of defense to protect the host from pathogen infection. As a first step, the pattern recognition receptors (PRRs) recognize pathogen-associated molecular patterns (PAMPs), such as non-self DNA derived from pathogens, and damage-associated molecular patterns (DAMPs), such as self DNA released from damaged or injured cells. Sensing of such DNAs elicits innate immune responses through the production of type I interferons (IFNs) and proinflammatory cytokines resulting from the activation of interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-κB), respectively. These cytokines are key players in interlinking innate and adaptive immune responses. However, defects in DNA sensors and their signaling cascades lead to dysregulation of immune responses, autoimmune diseases, and cancer progression. Here we provide an update on DNA signaling pathways in response to pathogen infection and cell injury, and on the roles of regulators in governing the immune system and maintaining host homeostasis. We also discuss the evasion of immunosurveillance by pathogens. ? 2018 Begell House, Inc.
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