Lupus nephritis (LN) is a kidney inflammatory disease caused by systemic lupus erythematosus (SLE). NLRP3 inflammasome activation is implicated in LN pathogenesis, suggesting its potential targets ...for LN treatment. Melatonin, an endogenous indoleamine, is considered an important multitasking molecule that has been reported to have anti-inflammatory effects by inhibiting nuclear factor-kappa B (NF-κB)-mediated inflammatory responses in vivo. This molecule has also protective effects against the activation of the inflammasomes and, in particular, the NLRP3 inflammasome. Thus, this work evaluated the effect of melatonin on morphological alteration and NLRP3 inflammasome activation in LN pristane mouse models. To evaluate the melatonin effects in these mice, we studied the renal cytoarchitecture by means of morphological analyses and immunohistochemical expression of specific markers related to oxidative stress, inflammation and inflammasome activation. Our results showed that melatonin attenuates pristane-induced LN through restoring of morphology and attenuation of oxidative stress and inflammation through a pathway that inhibited activation of NLRP3 inflammasome signaling. Our data clearly demonstrate that melatonin has protective activity on lupus nephritis in these mice that is highly associated with its effect on enhancing the Nrf2 antioxidant signaling pathway and decreasing renal NLRP3 inflammasome activation.
The intestinal epithelium plays a key role in managing the relationship with the environment, the internal and external inputs, and their changes. One percent of the gut epithelium is represented by ...the enteroendocrine cells. Among the enteroendocrine cells, a group of specific cells characterized by the presence of yellow granules, the enterochromaffin cells, has been identified. These granules contain many secretion products. Studies showed that these cells are involved in gastrointestinal inflammatory conditions and hyperalgesia; their number increases in these conditions both in affected and not-affected zones of the gut. Moreover, they are involved in the preservation and modulation of the intestinal function and motility, and they sense metabolic-nutritional alterations. Sometimes, they are confused or mixed with other enteroendocrine cells, and it is difficult to define their activity. However, it is known that they change their functions during diseases; they increased in number, but their involvement is related mainly to some secretion products (serotonin, melatonin, substance P). The mechanisms linked to these alterations are not well investigated. Herein, we provide an up-to-date highlight of the main findings about these cells, from their discovery to today. We emphasized their origin, morphology, and their link with diet to better evaluate their role for preventing or treating metabolic disorders considering that these diseases are currently a public health burden.
For years the thymus gland (TG) and the pineal gland (PG) have been subject of increasingly in-depth studies, but only recently a link that can associate the activities of the two organs has been ...identified. Considering, on the one hand, the well-known immune activity of thymus and, on the other, the increasingly emerging immunological roles of circadian oscillators and the rhythmically secreted main pineal product, melatonin, many studies aimed to analyse the possible existence of an interaction between these two systems. Moreover, data confirmed that the immune system is functionally associated with the nervous and endocrine systems determining an integrated dynamic network. In addition, recent researches showed a similar, characteristic involution process both in TG and PG. Since the second half of the 20th century, evidence led to the definition of an effectively interacting thymus-pineal axis (TG-PG axis), but much has to be done. In this sense, the aim of this review is to summarize what is actually known about this topic, focusing on the impact of the TG-PG axis on human life and ageing. We would like to give more emphasis to the implications of this dynamical interaction in a possible therapeutic strategy for human health. Moreover, we focused on all the products of TG and PG in order to collect what is known about the role of peptides other than melatonin. The results available today are often unclear and not linear. These peptides have not been well studied and defined over the years. In this review we hope to awake the interest of the scientific community in them and in their future pharmacological applications.
Interactive relationships among metabolism, mitochondrial dysfunction and inflammation at skeletal muscle level play a key role in the pathogenesis of disorders related to oxidative stress. ...Mitochondrial dysfunction and oxidative stress result in cellular energy deficiency, inflammation and cell death inducing a vicious cycle that promotes muscle wasting. The histidine-containing dipeptides, carnosine and anserine, are carbonyl scavengers whose cytoprotective contributions extend beyond the antioxidant defence, but the physiological meaning of these capacities is actually limited. In the present study, we compared and investigated the potential protective effects of three different histidine-containing dipeptides: carnosine, anserine and carnosinol, a carnosine-mimetic new compound, against oxidative stress induction in rat L6 skeletal muscle cells. The hydrogen peroxide induced-oxidative stress significantly altered cell morphology, induced apoptosis, oxidative stress and inflammation, decreased mitochondrial peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α)/sirtuin3 pathway and the antioxidant system. Notably, all three investigated dipeptides in the present study, with a different extent and in a concentration-dependent manner, reduced myotube oxidative stress, apoptosis and inflammation. The present study underlined that carnosinol, maintaining the safety condition of carnosine and anserine, was the more efficient studied dipeptide in the preservation of mitochondrial environment mediated by PGC-1α and sirtuin3 expression and thereby in the reduction of oxidative stress-related alterations in this in vitro skeletal muscle model. Furthermore, we observed that carnosinol's antioxidant effects are not blocked inhibiting sirtuin3, but are maintained with almost the same extend, indicating its multiple capacities of reactive carbonyl species-scavenging and of mitochondrial modulation through PGC-1α. In conclusion, carnosinol retained and surpassed the efficacy of the well-known investigated histidine-containing dipeptides improving oxidative stress, inflammation and also cell metabolism and so becoming a greatly promising therapeutic carnosine derivate.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Melatonin displays antitumor activity in several types of malignancies; however, the best delivery route and the underlying mechanisms are still unclear. Alternative non-invasive delivery route based ...on transdermal administration of melatonin by cryopass-laser treatment demonstrated efficiency in reducing the progression of LNCaP prostate tumor cells xenografted into nude mice by impairing the biochemical pathways affecting redox balance. Here, we investigated the impact of transdermal melatonin on the tumor dimension, microenvironment structure, and SIRT1-modulated pathways. Two groups (vehicle cryopass-laser and melatonin cryopass-laser) were treated for 6 weeks (3 treatments per week), and the tumors collected were analyzed for hematoxylin eosin staining, sirius red, and SIRT1 modulated proteins such as PGC-1α, PPARγ, and NFkB. Melatonin in addition to simple laser treatment was able to boost the antitumor cancer activity impairing the tumor microenvironment, increasing the collagen structure around the tumor, and modulating the altered SIRT1 pathways. Transdermal application is effective, safe, and feasible in humans as well, and the significance of these findings necessitates further studies on the antitumor mechanisms exerted by melatonin.
The role of the microbiome in hair follicle (HF) growth represents a growing field of research. Here, we studied the bacterial population in the scalp hair follicles of subjects with alopecia areata ...(AA). Two Healthy and two AA subjects, respectively (20−60 years old), were enrolled and studied regarding the microbial community in the subepidermal scalp compartments by means of a 4-mm biopsy punch. Samples were examined by 16S sequencing, histochemical staining (Gram’s method), and transmission electron microscopy (TEM). Bacterial foci were observed in the AA subjects’ follicles with both the two adopted complementary approaches (electron microscopy and Gram staining). Significant (p < 0.05) differences were also found in the three-layer biopsy samples (p < 0.05) regarding the bacterial population. In particular, in the deep epidermis and dermis levels, a significant (p < 0.05) lower abundance of Firmicutes and a higher abundance of Proteobacteria were found in AA samples compared to the healthy control. Firmicutes also showed a significant (p < 0.05) lower abundance in hypodermis in AA subjects. In addition, Enterobacteriaceae and the genera Streptococcus, Gemella, Porphyromonas, and Granulicatella were relatively more abundant in AA groups at the deep epidermis level. The Staphylococcus and Flavobacterium genera were significantly less abundant in AA samples than in controls in all three-layer biopsy samples (p < 0.05). In contrast, Veillonella and Neisseriaceae were relatively more abundant in the healthy control group compared to the AA sample. Therefore, higher alpha diversity was observed in all three-layer biopsy samples of AA patients compared to the control. In conclusion, our data suggest that tAA could be defined as a “hair disease associated with dysregulated microbiome-immunity axis of hair follicles”.
•Atherosclerosis is a chronic vascular disease in which oxidative stress is a major causative factor.•Possible identification of molecular targets for prevention and therapy against ...atherogenesis.•Melatonin can be beneficial against atherosclerosis.
Atherosclerosis is a chronic vascular disease in which oxidative stress and inflammation are commonly implicated as major causative factors. Identification of novel strategies that contribute to plaque stabilization or inhibition represents a continuing challenge for the medical community.
The evidence from the last decade highlights that melatonin influences the cardiovascular system, but its mechanisms of action have not been definitively clarified. Melatonin has atheroprotective effects by acting on different pathogenic signaling processes; these result from its direct free radical scavenger activity, its indirect antioxidant properties and its anti-inflammatory actions.
In this review, we summarize the many pieces of the puzzle which identified molecular targets for prevention and therapy against the atherosclerotic pathogenic processes and we evaluate the data documenting that melatonin treatment has important actions that protect against atherosclerosis and atherosclerosis-related cardiovascular diseases.
A rare branching pattern of the aortic arch in a female cadaver is reported. An aberrant right subclavian artery originated from the distal part of the aortic arch and following a retroesophageal ...course was recognized. Next to it, from the left to the right, the left subclavian artery and a short bicarotid trunk originating the left and the right common carotid artery were recognized. An unusual origin of the vertebral arteries was also identified. The left vertebral artery originated directly from the aortic arch, whereas the right vertebral artery originated directly from the right common carotid artery. Retroesophageal right subclavian artery associated with a bicarotid trunk and ectopic origin of vertebral arteries represents an exceptional and noteworthy case.
Obesity is a worldwide epidemic disease that induces important structural and functional changes to the heart and predisposes a patient to devastating cardiac complications. Sirtuin1 (SIRT1) has been ...found to have roles in regulating cardiac function, but whether it can help in cardioprotection is not clear. The aim of the present study was to determine whether melatonin, by modulating SIRT1 and in turn mitochondria signaling, may alleviate obesity-induced cardiac injuries. We investigated 10 lean control mice and 10 leptin-deficient obese mice (
) orally supplemented with melatonin for 8 weeks, as well as equal numbers of age-matched lean and
mice that did not receive melatonin. Hearts were evaluated using multiple parameters, including biometric values, morphology, SIRT1 activity and expression of markers of mitochondria biogenesis, oxidative stress, and inflammation. We observed that
mice experienced significant heart hypertrophy, infiltration by inflammatory cells, reduced SIRT1 activity, altered mitochondrial signaling and oxidative balance, and overexpression of inflammatory markers. Notably, melatonin supplementation in
mice reverted these obesogenic heart alterations. Melatonin prevented heart remodeling caused by obesity through SIRT1 activation, which, together with mitochondrial pathways, reduced oxidative stress and inflammation.
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