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In general, hippocampal neurons are capable of synthesizing sex steroids de novo from cholesterol, since the brain is equipped with all the enzymes required for the synthesis of estradiol and testosterone, the end products of sex steroidogenesis. Regarding estradiol, its synthesis in hippocampal neurons is homeostatically controlled by Ca2+ transients and is regulated by GnRH. Piperlongumine Locally synthesized estradiol and testosterone maintain synaptic transmission and synaptic connectivity. Remarkably, the neurosteroid estradiol is effective in females, but not in males, and vice versa dihydrotestosterone (DHT) is effective in males, but not in females. Experimentally induced inhibition of estradiol synthesis in females and DHT synthesis in males resp. results in synapse loss, impaired LTP, and downregulation of synaptic proteins. GnRH-induced increase in estradiol synthesis appears to provide a link between the hypothalamus and the hippocampus, which may underlie estrous cyclicity of spine density in the female hippocampus. Hippocampal neurons are sex-dependently differentiated with respect to the responsiveness of hippocampal neurons to sex neurosteroids.The two voltage gated sodium channels Nav1.7 and Nav1.8 are expressed in the peripheral nervous system and involved in various pain conditions including inflammatory and neuropathic pain. Rodent models bearing deletions or mutations of the corresponding genes, Scn9a and Scn10a, were created in order to understand the role of these channels in the pathophysiological mechanism underlying pain symptoms. This review summarizes the pain behavior profiles reported in Scn9a and Scn10a rodent models. The complete loss-of-function or knockout (KO) of Scn9a or Scn10a and the conditional KO (cKO) of Scn9a in specific cell populations were shown to decrease sensitivity to various pain stimuli. link2 The Possum mutant mice bearing a dominant hypermorphic mutation in Scn10a revealed higher sensitivity to noxious stimuli. Several gain-of-function mutations were identified in patients with painful small fiber neuropathy. Future knowledge obtained from preclinical models bearing these mutations will allow understanding how these mutations affect pain. In addition, the review gives perspectives for creating models that better mimic patients' pain symptoms in view to developing novel analgesic strategies.Azure A (AA) is a cationic molecule of the class of phenothiazines that has been applied in vitro as a photosensitising agent in photodynamic antimicrobial chemotherapy. link3 It is a di-demethylated analogue of methylene blue (MB), which has been demonstrated to be intrinsically and photodynamically highly active on mitochondrial bioenergetics. However, as far as we know, there are no studies about the photodynamic effects of AA on mammalian mitochondria. Therefore, this investigation aimed to characterise the intrinsic and photodynamic acute effects of AA (0.540 μM) on isolated rat liver mitochondria, isolated hepatocytes, and isolated perfused rat liver. The effects of AA were assessed by evaluating several parameters of mitochondrial bioenergetics, oxidative stress, cell viability, and hepatic energy metabolism. The photodynamic effects of AA were assessed under simulated hypoxic conditions, a suitable way for mimicking the microenvironment of hypoxic solid tumour cells. AA interacted with the mitochondria and,ntrations. However, the fact that AA directly disrupts mitochondrial bioenergetics and affects several hepatic pathways that are linked to ATP metabolism, along with its ability to perturb cellular membranes and its little potential to reduce cell viability, could result in significant adverse effects especially in long-term treatments.The present study examines the longitudinal association between cortisol (dys)regulation - mean cortisol awakening response (CAR) and area under the curve with respect to ground (AUCg) for total daily cortisol - and autobiographical memory. 135 participants (mean age at baseline = 16.1; Females = 78.5 %) provided cortisol samples (T1). Seven months later participants retrieved autobiographical memories cued by positive and negative words (T2). Four years subsequently, participants provided cortisol samples again (T3). The retrieval of more specific memories cued by positive words, but not negative words, was associated with higher AUCg four years later, independent of sex, recent life stressors and self-reported negative self-related cognitions. There were no associations between CAR and autobiographical memory. Neither AUC nor CAR at T1 predicted subsequent autobiographical memory abilities. People who retrieve more positive specific memories may be more likely to imagine and seek out positive experiences and this may be associated with higher cortisol levels.The type and number of dependent measures assessed have varied between fear conditioning and extinction experiments and it remains unclear whether methodological differences influence results. Measuring skin conductance responses (SCRs) and between-phase subjective ratings between four conditions; Con condition had no within-phase ratings; US Exp condition included within-phase US expectancy ratings only; CS Eval condition included within-phase CS evaluations only and All Meas condition included both. All Meas condition exhibited larger SCRs compared to other conditions during acquisition, extinction, and return of differential responding at test. Differential SCRs did not extinguish in CS Eval and Con conditions, and CS Eval condition exhibited smaller CS- SCRs than other conditions throughout phases. US Exp condition revealed differential conditioning, successful extinction, and no return of differential SCRs. Between-phase ratings were not affected by within-phase ratings. Researchers should consider assessing different combinations of within-phase subjective ratings depending on the aims of their research.While emotion coherence has long been theorized to be a core feature of emotion, to date, studies examining response coherence have been conducted in laboratory settings. The present study used a combined approach of ambulatory physiology measures and ecological momentary assessment conducted over a 4-week period to examine the extent to which emotional experience and physiology show coherence in daily life within-persons; and whether individual differences in response coherence are associated with between-person differences in well-being, negative emotionality, and gender. Results revealed that, on average, individuals exhibited coherence between subjective experience and physiology of emotion, but that there was substantial between-person variation in coherence in daily life. Exploratory analyses revealed no credible link between levels of response coherence and well-being, negative emotionality, or gender. Findings contribute to the literature by demonstrating a novel methodological approach to measuring coherence in daily life and supporting the generalizability of coherence to ecologically valid contexts.

Left atrial appendage (LAA) echocardiographic assessment is difficult because of the complex shape and relatively small size of the LAA. Three-dimensional (3D) echocardiographic imaging can overcome the limitations of two-dimensional imaging. Pulsed-wave Doppler is the only currently standard LAA functional parameter. The aim of this study was to test a new approach for 3D echocardiographic volumetric analysis to obtain LAA ejection fraction (EF), its size and shape.

Transesophageal two-dimensional and 3D LAA images were prospectively obtained in 159 consecutive patients. LAA volumes were measured from 3D echocardiographic images using available software. Pulsed-wave Doppler was considered the reference value for LAA function and was used for comparison with LAA EF. Comparison with cardiac computed tomography was performed in a subgroup of 32 patients. Comparisons included linear regression and Bland-Altman analyses. Repeated measurements were performed to assess measurement variability.

Nine patients were excluded because of suboptimal image quality (94% feasibility). Three-dimensional LAA calculated EF was in good agreement with LAA pulsed-wave measurements. Three-dimensional morphologic evaluation showed that 43% of the patients had "chicken wing," 33% "cactus," 19% "windsock," and 5% cauliflower shapes. At the time of data acquisition, patients with atrial fibrillation had nonsignificantly larger LAA end-systolic and end-diastolic volumes, leading to lower calculated EFs. Three-dimensional echocardiographic LAA end-systolic volumes were in good agreement with cardiac computed tomography (r=0.75), with small biases (mean, -2.5±3.9ml). Reproducibility was better for larger LAA volumes.

A novel 3D echocardiographic approach can determine the geometry, size, and function of the LAA. A new parameter, LAA EF, provides functional quantitation.

A novel 3D echocardiographic approach can determine the geometry, size, and function of the LAA. A new parameter, LAA EF, provides functional quantitation.

Regenerative endodontics has created a desirable shift in the treatment paradigm despite current limitations of regenerative outcomes. Mesenchymal stem cells (MSCs) facilitate tissue regeneration and repair in a mild inflammatory environment. Small extracellular vesicles (sEVs) derived from MSCs play an imperative role in the paracrine modulation of regenerative responses modulated by MSCs. However, it remains unknown whether MSCs enhance dental pulp regeneration or whether this enhancement is mediated by sEVs in a mild inflammatory environment. The present study aimed to elucidate the effects of sEVs originated from lipopolysaccharide (LPS)-preconditioned human dental pulp stem cells (hDPSCs) on dental pulp regeneration.

All sEVs were isolated from hDPSCs cultured with or without LPS (ie, N-sEVs and L-sEVs, respectively). The effect of N-sEVs and L-sEVs on proliferation, migration, angiogenesis, and differentiation of rat bone marrow MSCs was identified invitro. Moreover, N-sEVs or L-sEVs were implanted into rat pulpless root canal models, and the regenerated tissue in root canals was assessed via hematoxylin-eosin staining, Masson staining, and immunohistochemistry after 30 days of transplantation.

Both N-sEVs and L-sEVs could modulate BMSC proliferation, migration, angiogenesis, and differentiation. Both kinds of sEVs enhanced the structure of the regenerated tissue closer to that of a normal dental pulp invivo. L-sEVs had a more significant effect than N-sEVs.

sEVs released by hDPSCs in a mild inflammatory microenvironment are capable of facilitating the regeneration of dental pulp through functional healing instead of scar healing, which has potential applications in regenerative endodontics.

sEVs released by hDPSCs in a mild inflammatory microenvironment are capable of facilitating the regeneration of dental pulp through functional healing instead of scar healing, which has potential applications in regenerative endodontics.

This study aimed to perform a more precise estimation of the association between tumor necrosis factor alpha (TNF-α) -308 G/A single-nucleotide polymorphism (SNP) and the risk of development of apical periodontitis (AP) and its phenotypes based on all available published studies.

The study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and is registered in PROSPERO (CRD42020176190). The literature search was conducted via Clarivate Analytics Web of Science, Scopus, PubMed, Cochrane Central Register of Controlled Trials, and China National Knowledge Infrastructure databases from inception to December 2020 with no language restrictions. Two reviewers were involved independently in the study selection, data extraction, and appraising the studies that were included. The quality of the included studies was evaluated using the Strengthening the Reporting of Genetic Association and the Grading of Recommendations Assessment, Development and Evaluation system.

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