Neisseria gonorrhoeae is a strict human pathogen responsible for more than 100 million new sexually transmitted infections worldwide each year. Due to the global emergence of antibiotic resistance, the CDC recently listed N. gonorrhoeae as an urgent threat to public health. No vaccine is available in spite of the huge disease burden and the possibility of untreatable gonorrhea. The aim of this study is to investigate the immunogenicity of a novel whole-cell based inactivated gonococcal microparticle vaccine formulation loaded in dissolvable microneedles for transdermal administration. The nanotechnology-based vaccine formulation consists of inactivated whole-cell gonococci strain CDC-F62, spray dried and encapsulated into biodegradable cross-linked albumin matrix with sustained slow antigen release. The dry vaccine nanoparticles were then loaded in a dissolvable microneedle skin patch for transdermal delivery. The efficacy of the whole-cell microparticles vaccine formulation loaded in microneedles was assessed in vitro using dendritic ,cells and macrophages as well as in vivo mouse model. Antibody titers were measured using an ELISA and antigen-specific T lymphocytes were assessed in spleens and lymph nodes. Here we report that whole-cell based gonococcal microparticle vaccine loaded in dissolvable microneedles for transdermal administration induced significant increase in antigen-specific IgG antibody titers and antigen-specific CD4 and CD8 T lymphocytes in mice compared to gonococcal antigens in solution or empty microneedles. Significant increase in antigen-specific IgG antibody levels was observed at end of week 2 in groups that received the vaccine compared to the group receiving empty nanoparticles. The advantages of using formalin-fixed whole-cell gonococci that all immunogenic epitopes are covered and preserved from degradation. The spherical shaped micro and nanoparticles are biological mimics of gonococci, therefore present to the immune system as invaders but without the ability to suppress adaptive immunity. In conclusion, the transdermal delivery of microparticles vaccine via a microneedle patch was shown to be an effective system for vaccine delivery. The novel gonorrhea nanovaccine is cheap to produce in a stable dry powder and can be delivered in microneedle skin patch obviating the need for needle use or the cold chain.

Humans have extremely variable skin pigmentation and melanin production influenced by genetics, UV exposure, and some medications. A significant number of skin illnesses that result in pigmentary abnormalities have an impact on patients’ physical appearance as well as their psychological and social well-being. Skin pigmentation can be divided into two basic categories: hyperpigmentation, where pigment appears to overflow, and hypopigmentation, where pigment is reduced. Albinism, melasma, vitiligo, Addison's disease, and post-inflammatory hyperpigmentation, which can be brought on by eczema, acne vulgaris, and drug interactions, are the most common skin pigmentation disorders in clinical practice. Anti-inflammatory medications, antioxidants, and medications that inhibit tyrosine, which prevents the production of melanin, are all possible treatments for pigmentation problems. Skin pigmentation can be treated orally and topically with medications, herbal remedies, and cosmetic products, but a doctor should always be consulted before beginning any new medicine or treatment plan. This review article explores the numerous types of pigmentation problems, their causes, and treatments, as well as the 25 plants, four marine species, and 17 topical and oral medications now on the market that have been clinically tested to treat skin diseases.

The biology of aging is focused on the identification of novel pathways that regulate the underlying processes of aging to develop interventions aimed at delaying the onset and progression of chronic diseases to extend lifespan. However, the research on the aging field has been conducted mainly in animal models, yeast, Caenorhabditis elegans and cell culture. Thus, it is unclear to what extent this knowledge is transferable to humans since they might not reflect the complexity of aging in people. Organoid culture is an in vitro 3D cell-culture technology that reproduces the physiological and cellular composition of the tissues and/or organs. This technology is being used in the cancer field to predict the response of a patient-derived tumor to a certain drug or treatment serving as patient stratification and drug-guidance approaches. Modeling aging with patient-derived organoids has a tremendous potential as a preclinical model tool to discover new biomarkers of aging, to predict adverse outcomes during aging and to design personalized approaches for prevention and treatment of aging-related diseases and geriatric syndromes. This could represent a novel approach to study chronological and/or biological aging paving the way to personalized interventions targeting the biology of aging.

The last decade has seen remarkable progress in the characterization of methylation clocks that track biological age in humans and many other mammalian species. While the biological processes of aging that underlie these clocks have remained unclear, several clues have pointed to a link to developmental mechanisms. These include the presence in the vicinity of clock CpG sites of genes that specify development, including those of the Hox (homeobox) and polycomb classes. Here we discuss how recent advances in programmatic theories of aging provide a framework within which methylation clocks can be understood as part of a developmental process of aging. This includes how such clocks evolve, how developmental mechanisms cause aging, and how they give rise to late-life disease. The combination of ideas from evolutionary biology, biogerontology and developmental biology open a path to a new discipline, that of developmental gerontology (devo-gero). Drawing on the properties of methylation clocks, we offer several new hypotheses that exemplify devo-gero thinking. We suggest that polycomb controls a trade-off between earlier developmental fidelity and later developmental plasticity. We also propose the existence of an evolutionarily-conserved developmental sequence spanning ontogenesis, adult development and aging, that both constrains and determines the evolution of aging.

The pomegranate, an ancient plant native to Central Asia, cultivated in different geographical areas including the Mediterranean basin and California, consists of flowers, roots, fruits and leaves. Presently, it is utilized not only for the exterior appearance of its fruit but above all, for the nutritional and health characteristics of the various parts composing this last one (carpellary membranes, arils, seeds and bark). The fruit, the pomegranate, is rich in numerous chemical compounds (flavonoids, ellagitannins, proanthocyanidins, mineral salts, vitamins, lipids, organic acids) of high biological and nutraceutical value that make it the object of study for many research groups, particularly in the pharmaceutical sector. Its interest is mainly addressed to the knowledge of its biological and functional properties and the research of new formulations to apply it in a wide range of diseases such as neoplastic, cardiovascular, viral, inflammatory, metabolic, microbial, intestinal, reproductive and skin diseases. In this review we highlight the health-promoting properties of pomegranate and its bioactive compounds against human diseases.

Electromagnetic sensors have been used for inspecting small surface defects of metals. Based on the eddy-current thin-skin regime, a revised algorithm is proposed for a triple-coil drive-pickup eddy-current sensor scanning over long surface crack slots (10 mm) with different rotary angles. The method is validated by the voltage measurement of the designed EC sensor scanning over a benchmark (ferromagnetic) steel with surface defects of different depths and rotary angles. With an additional sensing coil for the designed EC sensor, the defect angle (or orientation) can be measured without spatially and coaxially rotating the excitation coil. By referring to the voltage change (due to the defect) diagram (voltage sum versus voltage different) of two sensing pairs, the rotary angle of the surface crack is retrieved with a maximum residual deviation of 3.5 %.

Liquid metal alloy, incorporated with microfluidic manipulation, has become a promising candidate for flexible resistive sensor array (RSA) that can imitate the functions of human skin. One advantage of RSA with shared rows and shared columns is to reduce the number of wires from M × N to M + N (rows: M and columns: N) and hence to greatly lessen the complexity and burden on the electrical system. The associated drawback is the crosstalk effect between adjacent elements during measurement. Although many literatures have reported several methods to resolve this limitation, almost all of them focus only on the high resistance value (≥100 Ω) RSA. There is a lack of detailed experimental data that addresses low resistance RSA with sensing elements below 100 Ω. Here, we aim to fill the gap of this field. We established two common RSA readout systems, i.e. zero potential methods (ZPM) (setting non-scanned-sampling-electrode zero potential (S-NSSE-ZP) and setting non-scanned-sampling-electrode zero potential with amplifier (S-NSSE-ZP-A)) and to compare their performances in low resistance value (≤100 Ω) RSA. For ideal resistor RSA, the measurement results show that S-NSSE-ZP has at least one time higher error than S-NSSE-ZP-A.

Traditional edible barbecue products use with lemon juice not only make the barbecue more delicious but also reduce the risk of PAHs in the barbecue products. One of the major economics crops in Taiwan, the waste from citrus fruits was very tremendous mass. However, the peelings of citrus fruits are rich in essential oil, especially, the limonene is the major. Whether the anti-carcinogenesis activities of terpene, such as limonene, in citrus fruits essential oil extraction. This study to demonstrate the PAHs content in fish skin increased markedly after being roasted at 210℃ for 20 minutes and greater mutagenicity risk of roasted fish skin was observed by Ame's test. The reduction of mutagenicity risk of roasted fish skin, which the antimutagenic abilities of substances in descending order were limonene > cold pressure oil > lemon >grapefruit. The antimutagenicity rate and ability of the three extracts were limonene: 18–23%; cold-pressed lemon oil: 18–22%; and steam distilled lemon essential oil: 8–16%. The obvious anti- mutagenicity effects against the PAHs mutagenicity of roasted fish skins can be found in citrus fruits essential oil extraction.

Atopic dermatitis (AD) is a chronic inflammatory skin disease, which can cause skin barrier function damaged. Although co-incubation with docosahexaenoic acid (DHA) exerts a positive effect in deficient skin model, there is no study to investigate the effects of topical treatment with DHA in inflammatory reconstructed human epidermis (RHE) model. The effects of DHA on monolayer normal human epidermal keratinocyte (NHEK) cells were evaluated via CCK-8, qPCR and ELISA. The skin related barrier function was assessed by hematoxylin-eosin (HE) staining, western blot (WB), Immunohistofluorescence (IF) and ELISA in normal and inflammatory RHE models. DHA upregulated filaggrin and loricrin expression at mRNA levels in addition to suppress overexpression of TNF-α，IL-1α and IL-6 stimulated by poly I:C plus LPS (stimulation cocktail) in cultured NHEK cells. After topical treatment with DHA, cocktail induced inflammatory characteristics of skin diseases including barrier morphological, differentiation proteins and TSLP secretion, which were alleviated in RHE models. Supplementation with DHA can improved related barrier function and have anti-inflammation effects in monolayer keratinocytes and RHE models, which indicated that DHA may have a potential value for the treatment of inflammation-associate skin diseases.

Background: Periodontitis is a disease that leads to serious functional and aesthetic dysfunctions resulting in impairment of life quality; it exists in different forms and its etiology is related with multiple component causes. Angiogenesis, together with inflammatory infiltrate, are two key processes in the evolution of inflammatory processes involving gingival tissues. The aim of this study was to evaluate their alterations in relation to some important periodontal diseases-associated factors (i.e. smoke, sex, age, plaque, pus, probing pocket depth) in patients with diagnosis of Generalized Aggressive Periodontitis (GAP). Methods: Eighteen subjects with GAP were enrolled for this study. Percentage of inflammatory cells and vascular area were measured and evaluated in relation with each periodontal diseases-associated factor. Results: The results showed a significant decrease of the percentage of vascular area in association with almost all the periodontal diseases-related factors (smoke, age, PPD, plaque) and not significant differences in the percentage of inflammatory cells. Conclusions: Data suggest that, even if these factors are often commonly related to worsening of periodontal status, they did not affect inflammatory and vascular pattern, as we can assume. For the future, additional studies, aimed to evaluated each singular factor in a wider sample size, should be planned.

A catastrophic loss of microbial biodiversity on the skin has led to alarming increase in the prevalence of allergies and long-term damage to the skin, which could also have damaging knock on effects to overall health. This study uses 50 human participants, to obtain an average (benchmark) value for the biodiversity of ‘healthy’ western skin, which is crucial in updating our 2017 skin health measuring mechanism to use standardised methodology. Previous work with a larger sample size was unsatisfactory for use as a benchmark due to its use of different and outdated diversity indices. We also investigated the effect of age and sex, two known skin microbiome affecting factors. Although no statistical significance is seen for age- and sex- related changes in diversity, there appear to be changes related to age which elaborates on previous work which used larger, more general age ranges. Our study indicates adults age 28-37 have highest diversity, and age 48-57 the lowest. Crucially, because of this study we are now able to update the skin health measuring mechanism from our 2017 work. This will aid diagnostic assessment of susceptibility to cutaneous conditions or diseases, and treatment. Testing any human subject will be rapidly improved by obtaining future benchmark diversity values for any age, sex, body site and area of residence, to which they can be compared. This improvement means we can also more accurately investigate the ultimate question: What factors in the western world are a main cause of the skin allergy epidemic? This could lead to future restriction of certain synthetic chemicals or products found to be particularly harmful to the skin.

The effect of retrogression re-aging treatment (RRA) on corrosion behavior of 7055 Al-Zn-Mg alloy were studied. Results provides the corrosion resistance could be greatly improved by RRA. After the RRA treatment, the isolated precipitates occurred on grain boundaries (GBs) and the low angle grain boundaries (LAGBs) presented a larger fraction compared to the single-stage peaking aging. The samples after RRA treatment also show better corrosion resistance than the single-stage peak aging. The results of electrochemical impedance spectroscopy (EIS) show that impedance spectrum is consisted of semi-infinite layer diffusion impedance and stagnant Weber impedance. The semi-infinite layer diffusion impedance corresponded a limited retention layer on the electrode surface. In corrosion process, Weber impedance corresponded to stagnant layer of corrosion products generated by the anode branches. The RRA sample has the high Rf and low Cf, Cp values, and the corrosion current density of the RRA samples is ten times less than the single-stage peak aging samples with the 10% hardness losing.

Skin and proximity effects have a considerable impact on current distribution in multi-strand cable lines. Under unfavorable heat exchange conditions some strands may be subject to excessive overheating, what may lead to serious malfunctions or even fires of the installation. The paper proposes a new criterion for a quick choice of spatial configurations, for which the effect might be minimized. A comprehensive analysis of literature cases is provided, including the recommendations of the U.S. National Code and the Canadian standard.

Description of a novel bovine antimicrobial peptide and its antimicrobial spectrum. RNA isolation and RT-PCR were done from various tissues. DCD peptide was synthesized, and antimicrobial activity was analyzed. Bovine dermcidin gene contains five exons intermittent by 4 introns. Bovine DCD-mRNA was 398 bp with ORF 336 bp. Bovine DCD was expressed in skin and blood. Analysis of the amino acid compositions revealed that cysteine was repeated 6 times indicating the presence of 3 disulfide bonds that play role in the peptide stability. Staphylococcus epidermidis, Streptococcus bovis, and Enterococcus faecalis were affected by Bovine DCD peptide. Highest antimicrobial effect was at 50 and 100 µg/ml. The effect on Escherichia coli and Candida albicans was slightly low. In all bacteria, Bovine DCD peptide activity did not affect by varying pH values, but in Staphylococcus aureus, the activity was affected greatly at pH 4.5 and 5.5. The optimum salt concentrations were 100 and 50 mM NaCl with all bacterial strains and E. coli, respectively. In case of C. albicans, the antimicrobial activity of Bovine DCD peptide decreased with increasing the pH value regardless the NaCl concentration. The pH 6.5 of the sweat buffer was the optimum for the Bovine DCD peptide activity.

The workforce crisis of primary care is reflected in the increasing number of general medical practices (GMP) with vacant general practitioner (GP) position, and the GPs’ ageing. Our study aimed to describe the association between this crisis and premature mortality. Age-sex-standardized mortality for 18-64 years old adults were calculated for all Hungarian GMPs annually in the period from 2006 to 2014. The relationship of premature mortality with GPs’ age and vacant GP position were evaluated by standardized linear regression controlled for list size, urbanization, geographical location, clients’ education, and type of the GMP. The clients’ education was the strongest protective factor (beta=-0175; p<0.001), followed by urban residence (beta=-0.149; p<0.001), and the bigger list size (beta1601-2000=-0.054; p<0.001; beta2001-X=-0.096; p<0.001). The geographical localization influenced significantly also the risk. Although, GMP with a GP aged older than 65 years (beta=0; p=0.995) did not affected the risk, GP vacancy was associated with higher risk (beta=0.010; p=0.033), but the corresponding number of attributable cases was 23.54 for 9 years. The vacant GP position is associated with significant but hardly detectable increased risk of premature mortality without considerable public health importance. Nevertheless, employment of GPs aged more than 65 does not impose premature mortality risk elevation.

Skin cancer is an uncommon but serious malignancy. Dermoscopic images examination and biopsy are required for cancer detection. Deep learning (DL) is extremely effective in learning characteristics and predicting malignancies. However, DL requires a large number of images to train. Image augmentation and transferring learning were employed to overcome the lack of images issue. In this study we divided images into two categories: benign and malignant. To train and test our models, we used the public ISIC 2020 database. Melanoma is classified as malignant in the ISIC 2020 dataset. Along with categorization, the dataset was studied to demonstrate variation. The performance of three top pretrained models was then benchmarked in terms of training and validation accuracy. Three optimizers were employed to optimize the loss: RMSProp, SGD, and ADAM. Using ResNet, VGG16, and MobileNetV2, we obtained training accuracy of 98.73%, 99.12%, and 99.76%, respectively. Using these three pretrained models, we attained a validation accuracy of 98.39%.

Treating infections caused by Pseudomonas aeruginosa is increasingly difficult due to high antimicrobial resistance, materialized through the presence of multiple resistance strains, as well as due to rapid development of resistance throughout treatment. The present survey was conducted to investigate the antibiotic susceptibility profile of Pseudomonas aeruginosa pathogens, in two University Veterinary hospitals from different geographical regions of Romania (i.e., south-west - Timisoara county and north-east – Iasi county) involved in canine superficial infections. A total of 142 swab specimens were collected from dogs with superficial infections (superficial skin infections, otitis externa, perianal abscess), with the aim of assessing the presence of Pseudomonas aeruginosa, based on phenotypic and molecular characterization. Fifty-eight samples (40.84%; 58/142) were positive for Pseudomonas aeruginosa (according to their confirmed morphological and molecular features). Susceptibility to usual antibiotics used in the treatment of canine skin conditions was tested for all Pseudomonas strains that were isolated from canine superficial infections, using the Kirby Bauer disc diffusion method. Drug resistance was observed in the case of all tested antibiotics. The susceptibility rate of P. aeruginosa strains that were tested in this study was in the following order: ampicillin sulbactam (55.17%; 32/58), followed by ceftazidime (53.44%; 31/58), aztreonam (51.72%; 30/58), amikacin (44.82%; 26/58), azithromycin (41.37%; 24/58), gentamycin (37.93%; 22/58), cefepime (36.20%; 21/58) meropenem (25.86%; 13/58), piperacillin-tazobactam (25.86%; 13/58) imipenem (22.41%; 13/158), ciprofloxacin (17.24%; 10/58) tobramycin (8.62; 5/58), and polymyxin B (1.72; 1/58) respectively. The results highlight the importance of antibiotic susceptibility testing in Pseudomonas aeruginosa isolates from dogs with superficial infections, in order to use an adequate treatment plan for the management of the skin condition, and other pathology (otitis externa and perianal abscesses).

Calorie restriction (CR) has been shown to prolong the lifespan of humans, but enforcing long-term CR is difficult. Therefore, a compound that reproduces the effect of CR without CR is needed. In this review, we summarize the current knowledge on compounds with CR mimetic (CRM) effects. More than 10 compounds have been listed as CRMs, some of which are conventionally categorized as upstream-type CRMs showing glycolytic inhibition while the others are categorized as downstream-type CRMs that regulate or genetically modulate intracellular signaling proteins. Among these, we focus on upstream-type CRMs and propose their classification as compounds with energy metabolism inhibition effects, particularly glucose metabolism modulation effects. The upstream-type CRMs reviewed include chitosan, acarbose, sodium-glucose cotransporter 2 inhibitors, and hexose analogs such as 2-deoxy-D-glucose, D-glucosamine, and D-allulose, which show anti-aging and longevity effects. Finally, we discuss the molecular definition of upstream-type CRMs.

Cutaneous lymphocytosis (CL) is an uncommon and controversial lymphoproliferative disorder described in dogs and cats. CL is generally characterized by a heterogeneous clinical presentation and histological features that may overlap with epitheliotropic lymphoma. Therefore, its neoplastic or reactive nature is still debated. Here, we describe clinicopathological, immunohistochemical and clonality features of a retrospective case series of 19 cats and 10 dogs with lesions histologically compatible with CL. In both species, alopecia, erythema and scales were the most frequent clinical signs. Histologically, a dermal infiltrate of small to medium-sized lymphocytes, occasionally extending to the subcutis, was always identified. Conversely, when present, epitheliotropism was generally mild. In cats, the infiltrate was consistently CD3+; in dogs, a mixture of CD3+ and CD20+ lymphocytes was observed only in 4 cases. The infiltrate was polyclonal in all cats, while BCR and TCR clonal rearrangements were identified in dogs. Overall, cats had a long-term survival (median overall survival=1080 days) regardless of the treatment received, while dogs showed a shorter and variable clinical course, with no evident associations with clinicopathological features. In conclusion, our results support a reactive nature of the disease in cats, associated with prolonged survival; despite a similar histological picture, canine CL was associated with a more heterogeneous lymphocytic infiltrate, clonality results, and response to treatment.

The study’s objective was to evaluate the influence of thinning on the quality and regularity of yield of 'Regina' cherries grown on a dwarf Gisela 5 rootstock. The experiments were conducted in the years 2009-2012 in Western Poland. Trees were thinned using a chemical agent, ammonium thiosulphate (ATS) at doses of 20g ATS × L-1, 30g ATS × L-1 and 40g ATS × L-1, and by hand, and the results of chemical and hand thinning were compared with those obtained for unthinned trees. The course of weather conditions in winter and during flowering had a significant impact on yield. Chemical thinning is known to be an effective method to regulate fruiting of pome trees, but it can also be successful if applied to cherry trees, as reflected by the alternate bearing index, which was the lowest after applying ATS at a dose of 40g. ATS treatment improved fruit quality in full crop years. Thinning resulted in, among other things, larger and darker fruit and higher content of total soluble solids and titratable acidity. Treatment with 40g ATS × L-1 significantly stimulated the vegetative growth of trees.

Lipofuscin is indigestible garbage that accumulates in the autophagic vesicles and cytosol of post-mitotic cells with age. Drs. Brunk and Terman postulated that lipofuscin accumulation is the main or at least a major driving factor in aging. They even posited that the evolution of memory is the reason why we get lipofuscin at all, as stable synaptic connections must be maintained over time, meaning that the somas of neurons must also remain in the same locale. In other words, they cannot dilute out their garbage over time through cell division. Mechanistically, their position certainly makes sense given that rendering a large percentage of a post-mitotic cell’s lysosomes useless must almost certainly negatively affect that cell and the surrounding microenvironment. It may be the case that lipofuscin accumulation is the main issue with regard to current age-related disease. Degradation in situ may be an insurmountable task currently. However, a method of systemic lipofuscin removal is discussed herein.

Although the signaling function of Na/K ATPase is been studied for decades, the chasm between the pumping function and the signaling function of Na/K – ATPase is still an open issue. This article explores the relationship between ion pumping and signaling with attention to the amplification of oxidants through this signaling function. Starting with some experimental observations published by our laboratories and others, we develop some predictions regarding cellular oxidant stress.

There is a general lack of research involving older lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ) people. This systematic review aimed to synthesize Japanese and Swedish qualitative research on LGBTQ people aged 60 years or older. PRISMA guidelines were followed. Japanese and Swedish articles, published in English-language journals, were searched across PsychINFO, Medline, CINAHL, and Sociological Abstracts databases. Additional searches were carried out to include studies written in Japanese or Swedish. There were no papers from Japan, and five from Sweden were reviewed. Four articles were included, including 48 participants aged 60–94 years. We summarized the findings using a deductive thematic synthesis. Two major themes emerged: (a) quality of life, minority joy, and resilience (positive aspects), and (b) experiences of discrimination, stigmatization, and minority stress (negative aspects). The participants described a wish to be acknowledged for their own assets and unique life histories, and to be treated as everyone else. They emphasized the importance of knowledge of LGBTQ issues among nursing staff, so that older LGBTQ people are treated in a competent and affirmative way. The study revealed several important topics for understanding older LGBTQ people’s life circumstances and the severe lack of qualitative studies in Japan and Sweden.

Small RNAs are essential for the coordination of many cellular processes, including the regulation of gene expression patterns, the prevention of genomic instability, and the suppression of mutagenic transposon activity. These processes determine aging, longevity, and sensitivity of cells and an organism to stress factors (particularly, ionizing radiation). The biogenesis and activity of small RNAs are provided by proteins of the Argonaute family. These proteins participate in the processing of small RNA precursors and the formation of an RNA-induced silencing complex. However, the role of Argonaute proteins in the regulation of lifespan and radioresistance remains poorly explored. We studied the effect of knockdown of Argonaute genes (AGO1, AGO2, AGO3, piwi) in various tissues on the Drosophila melanogaster lifespan and survival after the γ-irradiation at a dose of 700 Gy. In most cases, these parameters were reduced or did not change significantly in flies with tissue-specific RNA interference. Surprisingly, piwi knockdown in both the fat body and the nervous system caused a lifespan increase. But changes in radioresistance depended on the tissue in which the gene was knocked out. In addition, analysis of changes in retrotransposon levels and expression of stress response genes allowed us to determine associated molecular mechanisms.

As the novel COVID-19 disease spreads around the world, the most affected population are those who suffer from the most common chronic diseases, such as obesity, hypertension, and type 2 diabetes, which are quite associated with the so-called age-related diseases. On the other hand, since the Spanish influenza outbreak, humanity has not experienced an infectious disease that synergizes so quickly with chronic diseases, making it mortal for those individuals with comorbidities. In this context, COVID-19 is challenging for health systems all around the world due to the high prevalence of chronic diseases. Nowadays, we are facing the beginning of a new era in which health infectious and chronic diseases meet. Therefore, epidemiologic and biomedical researchers must work together to solve further contingencies, and politicians should direct science-centered decisions on public health. In the present paper, we make an urgent call to learn from the COVID-19 lessons in order to mitigate the chronic diseases prevalence and to address the influence of the infectious diseases on the aging process; since we are about to begin the Decade of Healthy Aging.

Stress plays a central role in functioning for all life forms. As humans, we experience stress in a multitude of ways through various types of stimuli. Due to the constancy of stressors in our lives, the nervous system has learned to allosterically adapt to the stimuli, but when the body cannot adapt, chronic stress can have morphological and degenerative impacts on neuroanatomy and cognitive function that may or may not be reversible. This literature review aimed to identify the specific neuroanatomical structures impacted most by the long-term effects of chronic stress and the subsequent relationship the morphological changes had on cognitive function in rodent models. We examined articles published from PubMed, Google Scholar, and Science Direct, while focusing the search on anatomical and neurodegenerative effects associated with chronic stress stimuli. The degenerative effects of various types simulated physiological chronic stress showed the most impact on neurogenesis and neuronal development, brain plasticity, and spatial learning and memory with association to the hippocampus. The hippocampus, amygdala, prefrontal cortex, and hypothalamic-pituitary-adrenal axis (HPA) all had reversible and non-reversible morphological alterations, which also had a direct impact on the brain’s cognitive abilities. While studies regarding chronic stress are still being conducted, future research may be able to further highlight why stressful stimuli can particularly impact these structures and the tangential impacts that it may have on related or adjacent structures.

Prefrontal cortex (PFC) is one of the brain regions with more prominent changes in human aging. The molecular processes related to the aging cognitive decline and mood changes are not completely understood. In order to improve our knowledge, we integrated transcriptomic data of four studies of human PFC from old people -58-80 years old- compared with young people -20-40 years old- using a meta-analytic approximation combined with molecular signature analysis. We identified 1816 differentially expressed genes -561 up-regulated and 1256 down-regulated. Pathway analysis revealed down-regulation of synaptic genes with conservation of gene expression of other neuronal regions. Additionally, we identified up-regulation of markers of astrogliosis with transcriptomic signature compatible with A1 neurotoxic astrocytes and A2 neuroprotective astrocytes. Response to interferon is related to A1 astrocytes and the A2 phenotype is mediated in aging by activation of SHH pathway and up-regulation of metallothioneins I and genes of the family EZR -ezrin, radixin, and moesin-. The main conclusions of our study are the confirmation that in aged PFC there is a global dysfunction of the synapses and we reported for the first time opposite phenotypes of astrogliosis because of brain aging.

The main focus of this work is to extend the knowledge about the complexity of issues of oxidative stress. Natural compounds play a serious role in multiple aspects of both human, leading to clear health-promoting effects. This work is focused on the potential application cosmetic formulations containing including but not limited to of clove water and isolated clove oils on their aid in the control of the diseases. The aim of our work was to prepare to evaluate cosmetic formulations containing clove oil, eugenol or new eugenol ester derivative (eugenyl dichloroacetate - EDChA) but also cosmetic formulations containing the aqueous phase obtained after separation of essential oil following the clove buds steam distillation. To evaluate the antioxidants transdermal delivery system, in vitro permeation experiments in a Franz diffusion cell were performed using pig skin. The antioxidative capacity of the cosmetic formulations obtained was determined by the DPPH free radical reduction method. In the next stage, the antioxidant activity (DPPH, ABTS, and Folin–Ciocalteu methods) of the fluid that penetrated through pig skin and of the fluid obtained after skin extraction, were also evaluated. For comparison, studies of cosmetic formulation containing alone dichloroacetic acid (DChAA) were as well carried out. The obtained cosmetic formulations were characterized by of antioxidant activity estimated after 24 hours of conducting the experiment, which indicates long-term protection against reactive oxygen species (ROS) in the deeper layers of the skin. The results of this work contribute to the development of cosmetic formulations with antioxidant potential, emphasizing that the water phases are waste from the process of cloves steam distillation and are not used to prepare cosmetic formulations. The use of waste water from the clove buds steam distillation process is environmentally friendly and not allows us to waste, containing however valuable biologically active compounds (furfural, methyl salicylate, 4-allilofenol, eugenol, α- and β-caryophyllene, eugenyl acetate, β-caryophyllene oxide). Together, these results suggest that cosmetic formulations may be potential drug candidates for chemopreventive, antineoplastic and antimutagenic therapy.

SIRT6 is a NAD+ dependent enzyme and stress response protein that has sparked the curiosity of a plethora of researchers in different branches of the biomedical sciences. A unique member of the known Sirtuin family, SIRT6 has several different functions in several different molecular pathways related to DNA repair, glycolysis, gluconeogenesis, tumorigenesis, neurodegeneration, cardiac hypertrophic responses and so on. Only in recent times however did the potential usefulness of SIRT6 come to light as we learned more about its biochemical activity, regulation, biological roles and structure [1]. Even until very recently, SIRT6 was known more for chromatin signaling but being a nascent topic of study, more information has been ascertained and its potential involvement in major human diseases namely, diabetes, cancer, neurodegenerative diseases and heart disease has been demonstrated. It is pivotal to explore the mechanistic workings of SIRT6 since future research may hold the key to engendering strategies, involving SIRT6, that may have significant implications for human health and expand upon possible treatment options. In this review, we are primarily concerned with exploring the latest understanding of SIRT6 and how it can alter the course of several life-threatening diseases that cripple today’s society such as processes related to aging, cancer, neurodegenerative diseases, heart disease and diabetes. In addition, SIRT6 has shown to be involved in liver disease, inflammation and bone related issues but more emphasis is given to the former. Lastly, any recent promising pharmacological investigations and study of potential therapeutic targets are also delineated in this review.

Alzheimer’s disease (AD) is characterized by cognitive impairment and different non-cognitive deficits called “Behavioural and psychological symptoms of dementia” (BPSD) related to neurotrophin alterations, which differ from those presented in normal aging. Mouse models, both transgenics and inbreed mice models of AD, are a useful tool in understanding the underlying mechanisms of the disease. The SAMP8 (senescence-accelerated mouse prone 8) mice line was generated from AKR/J strain by Professor Toshio Takeda at the University of Kyoto. This strain exhibited a particular early-onset and accelerated aging phenotype. The present study characterizes and provides information regarding the non-cognitive and cognitive states as well as molecular alterations and their relationship, demonstrating the AD-like symptoms presented in older SAMP8 males. The cognitive impairment presented was accompanied by a reduction in sociability and an increase in aggressive as well as anxiety behaviours. Furthermore, changes in three of the most important neurotrophins, such as NT3, BDNF, and NGF as well as their receptors TrkA and TrkB, were found. Thus, the present results reveal new insights in this useful inbred mouse model of neurodegeneration and AD, demonstrating the potential relationship between neurotrophin alterations, cognitive impairment and neuropsychiatric disorders (ND).

This review summarizes current understanding of the interaction between circadian rhythms of gene expression and epigenetic clocks characterized by the specific profile of DNA methylation in CpG-islands which mirror the chronological age of individual cells and the entire organism. Basic mechanisms of regulation for circadian genes CLOCK- BMAL1 as well as downstream clock-controlled genes (ССG) are also discussed here. It has been shown that circadian rhythms operate by finely tuned regulation of transcription and rely on various epigenetic mechanisms including activation of enhancers / suppressors, acetylation / deacetylation of histones and other proteins as well as DNA methylation. Overall, up to 20% of all genes expressed by the cell are subject to expression oscillations associated with circadian rhythms. Also included in the review is a brief list of genes involved in the regulation of circadian rhythms, along with genes important for metabolic control, aging, and oncogenesis. Knocking out some of them (for example, Sirt1) accelerates the aging process, while overexpression of Sirt1, on the contrary, protects against age-related changes. Circadian regulators control a number of genes that activate the cell cycle (Wee1, c-Myc, p20, p21, and Cyclin D1) and regulate histone modification and DNA methylation. Approaches for determining the epigenetic age from methylation profiles across CpG islands in individual cells are described. DNA methylation, which characterizes the function of the epigenetic clock, appears to link together such key biological processes as regeneration and functioning of stem cells, aging and malignant transformation. Finally, main features of adult stem cell aging in stem cell niches and current possibilities for modulating the epigenetic clock as part of antiaging therapy are discussed.

Polyamines are nitrogen-rich polycationic ubiquitous bioactive molecules with diverse evolutionary-conserved functions. Their activity interferes with numerous genes' expression resulting in cell proliferation and signaling modulation. The intracellular levels of polyamines are precisely controlled by evolutionary-conserved machinery. Their transient synthesis is induced by heat stress, radiation, and other traumatic stimuli in a process termed the polyamine stress response (PSR). Notably, polyamine levels decline gradually with age; and external supplementation improves lifespan in model organisms. This corresponds to cytoprotective and reactive oxygen species scavenging properties of polyamines. Paradoxically, age-associated neurodegenerative disorders are characterized by an upsurge in polyamine levels, indicating polyamine pleiotropic, adaptive, and pathogenic roles. Specifically, arginase overactivation and arginine brain deprivation have been shown to play an important role in Alzheimer’s disease (AD) pathogenesis. Here, we assert that a universal short-term PSR associated with acute stimuli is beneficial for survival. However, it becomes detrimental and maladaptive following chronic noxious stimuli, especially in an aging organism. Furthermore, we regard cellular senescence as an adaptive response to stress and suggest that PSR plays a central role in age-related neurodegenerative diseases' pathogenesis. Our perspective on AD proposes an inclusive reassessment of the causal relationships between the classical hallmarks and clinical manifestation. Consequently, we offer a novel treatment strategy predicated upon this view and suggest fine-tuning of arginase activity with natural inhibitors to preclude or halt the development of AD-related dementia.

Nanostructured carriers have been widely used in pharmaceutical formulations for dermatological treatment. They offer targeted drug delivery, sustained release, improved biostability, and low toxicity, usually presenting advantages over conventional formulations. Due to its large surface area, small size and photothermal properties, graphene oxide (GO) has the potential to be used for such applications. Nanographene oxide (GOn) presented average sizes of 197.6 ± 11.8 nm, and a surface charge of -39.4 ± 1.8 mV, being stable in water for over 6 months. 55.5 % of the mass of GOn dispersion (at a concentration of 1 mg mL-1) permeated the skin after 6 h of exposure. GOn dispersions have been shown to absorb near-infrared radiation, reaching temperatures up to 45.7 °C, within mild photothermal therapy temperature range. Furthermore, GOn in amounts superior to those which could permeate the skin were shown not to affect human skin fibroblasts (HFF-1) morphology or viability, after 24 h of incubation. Due to its large size, no skin permeation was observed for graphite particles in aqueous dispersions stabilized with Pluronic P-123 (Gt-P-123). Altogether, for the first time, GOn potential as a topic administration agent and for delivery of photothermal therapy has been demonstrated.

A combination of physical-chemical analysis has been used to monitor the aging of red wines from D.O. Toro (Spain). The changes in the chemical composition of wines that occur along aging time can be permitted to discriminate wine samples collected after one, four, seven and ten months of aging. Different computational models were used to develop a good authenticity tool to certificate wines. In this research different models have developed: Artificial Neural Network models (ANNs), Support Vector Machine (SVM) and Random Forest (RF) models. The results obtained for the ANN model developed with sigmoidal function in the output neuron and the RF model permit to determine the aging time, with an average absolute percentage deviation below 1% and it can conclude that these two models have demonstrated its capacity as a valid tool to predict the wine age.

In contemporary design practices, there is a disconnect between the design techniques used for early-stage design experimentation and performance analysis, and those used for the manufacture and construction. This study addresses the problems in developing an integrated digital design workflow and provides a research framework for integrating environmental performance requirements with robotic manufacturing processes on a construction site. The proposed method enables the user to import a design surface, identify design parameters, set several environmental performance goals, and thereafter simulate and select a robotic building strategy. Based on these inputs, design alternatives are developed and evaluated, considering their robotically simulated constructibility, in terms of their performance criteria. To validate the proposed method, the design is evaluated in an experiment wherein a double-skin facade perforation is generated using the proposed methodology. Initial results suggest a heuristic feature to improve the simulated robotic constructibility. Moreover, the functionality of the prototype is demonstrated.

Background: While intimate feminine hygiene products are widely used by women as part of daily cleansing routines, little is known about how these products impact the vulvovaginal area and its microbiome stability. A novel gel wash containing lactic acid (pH 4.2) for external daily use was formulated to provide gentle cleansing, freshness, and antimicrobial protection to maintain a healthy balance of the vulvar skin area. This 4-week clinical study assessed tolerance of the gel wash when used on the external genital area and its effects on skin hydration, vulvar skin pH, and the vulvar microbiome. After a 7-day pre-study conditioning period, 36 healthy females in 3 balanced age groups (18-29, 30-44, and 45-55 years) used the gel wash to cleanse their external genital area (mons pubis and vulva) and entire body at least once per day for 28 days. The primary endpoint wasSkin tolerance of the gel wash was assessed by the gynecologist. Effects of the gel wash on vulvar skin microbiota were studied by performing bacterial 16S rRNA and fungal ITS microbial richness and diversity analysis. Results: Based on gynecologic assessment after 28 days of use, the gel wash showed acceptable tolerance, with no signs of increased dryness, redness, edema, itching, stinging, or burning. Use of the gel wash was associated with a significant increase in both short-term (single application) and longer-term (daily use for 28 days) skin moisturization. There was no significant change in vulvar skin pH over time with daily product use, and the gel wash did not significantly affect the natural vulvar microbiome species richness or diversity for bacteria or fungi. Conclusions: Results of the study showed that this new gel wash is a mild, moisturizing cleanser that does not harm and instead maintains the natural pH and microbial diversity of vulvar skin. To our knowledge, this was the first study to assess the effect of an antimicrobial feminine gel wash on the natural pH and vulvar microbiome habitat of the skin using bacterial 16S rRNA and fungal ITS genetic sequencing techniques, thereby providing a better understanding of the bacterial and fungal communities that inhabit the external vulvar area in healthy women.

Mesenchymal stem cells (MSCs) showed in vitro mesoderm-lineage differentiation and self-renew capacity. However, no comparative study was reported on the biological characteristics of stem cells derived from skeletal muscle (SM-MSCs), dermal skin (DS-MSCs), and adipose tissues (A-MSCs) from a single donor in camels. The present study aimed to evaluate the influence of MSCs source on stem cell characteristics. We evaluated proliferation capacity and mesoderm-lineage differentiation potential from SM-MSCs, DS-MSCs, and A-MSCs. They showed spindle-like morphology after homogenization. The proliferation ability was no significant difference in all groups. Furthermore, the portion of the cell cycle and expression of pluripotent markers (Oct4, Sox2, and Nanog) were similar in all cell lines at passage 3. The differentiation capacity of A-MSCs into adipocytes was significantly higher than that of SM-MSCs and DS-MSCs. However, the osteoblast differentiation capacity of A-MSCs was significantly lower than that of SM-MSCs and DS-MSCs. Additionally, after osteoblast differentiation, the ALP activity and calcium content was significantly decreased in A-MSCs as compared to SM-MSCs and DS-MSCs. To the best of our knowledge, we primally established MSCs from the single camel and demonstrated their comparative characteristics including expression of pluripotent factors and proliferation, and in vitro differentiation capacity into adipocytes and osteoblasts.

In contemporary design practices, there is a disconnect between the design techniques used for early-stage design experimentation and performance analysis, and those used for the manufacture and construction. This study addresses the problems in developing an integrated digital design workflow and provides a research framework for integrating environmental performance requirements with robotic manufacturing processes on a construction site. The proposed method enables the user to import a design surface, identify design parameters, set several environmental performance goals, and thereafter simulate and select a robotic building strategy. Based on these inputs, design alternatives are developed and evaluated, considering their robotically simulated constructibility, in terms of their performance criteria. To validate the proposed method, the design is evaluated in an experiment wherein a double-skin facade perforation is generated using the proposed methodology. The results suggest a heuristic feature to improve the simulated robotic constructibility. Moreover, the functionality of the prototype is demonstrated.

Functional mobility assessments (i.e., Timed Up and Go) are commonly used clinical tools for mobility and fall risk screening in the aging population. In this work, we proposed a new Mixed Reality (MR)-based assessment that utilized a Microsoft HoloLens^TM headset to automatically lead and track the performance of functional mobility tests, and subsequently evaluated its validity in comparison with reference inertial sensors. Twenty-two healthy adults (10 older, 12 young) participated in this study. An automated functional mobility assessment app was developed based on the HoloLens platform. Mobility performance was recorded with the headset built-in sensor and validated with reference inertial sensor (Opal, APDM) taped on the headset and lower back. Results indicate vertical kinematic measures by HoloLens was in good agreement with the reference sensor (Normalized RMSE ~ 10%). Additionally, the HoloLens-based test completion time was in perfect agreement with clinical standard stopwatch measure. Overall, our preliminary investigation indicates that it is possible to use an MR headset to automatically guide users to complete common mobility tests with good measurement accuracy, thus it has great potential to provide objective and efficient sensor-based mobility assessment.

Dermal water content is an important biophysical parameter in preserving skin integrity and preventing skin damage. Traditional electrical-based and open-chamber evaporimeters have several well-known limitations. In particular, such devices are costly, sizeable, and only provide arbitrary outputs. They also do not permit continuous and non-invasive monitoring of dermal water content, which can be beneficial for various consumer, clinical and cosmetic purposes. We report here on the design and development of a digital multi-wavelength optical sensor that performs continuous and non-invasive measurement of dermal water content. In-silico investigation on porcine skin was carried out using the Monte Carlo modelling strategy to evaluate the feasibility and characterise the sensor. Subsequently, an in-vitro experiment was carried out to evaluate the performance of the sensor and benchmark its accuracy against a high-end, broad band spectrophotometer. Reference measurements were made against gravimetric analysis. The results demonstrate that the developed sensor can deliver accurate, continuous, and non-invasive measurement of skin hydration through measurement of dermal water content. Remarkably, the novel design of the sensor exceeded the performance of the high-end spectrophotometer due to the important denoising effects of temporal averaging. The authors believe, in addition to wellbeing and skin health monitoring, the designed sensor can particularly facilitate disease management in patients presenting diabetes mellitus, hypothyroidism, malnutrition, and atopic dermatitis.

Motor functions are deteriorated by aging. Some conditions may magnify this deterioration. To examine whether hemodialysis (HD) process would negatively impact gait and balance beyond diabetes condition among mid-age adults (48-64 years) and older adults (65+ years). One hundred and ninety-six subjects (age=66.2±9.1 years, body-mass-index=30.1±6.4 kg/m², female=56%) in 5 groups were recruited: mid-age adults with diabetes undergoing HD (Mid-age HD+, n=38) and without HD (Mid-age HD-, n=40); older adults with diabetes undergoing HD (Older HD+, n=36) and without HD (Older HD-, n=37); and non-diabetic older adults (Older DM-, n=45). Gait parameters (stride velocity, stride length, gait cycle time, and double support) and balance parameters (ankle, hip, and center of mass sways) were quantified using validated wearable platforms. Groups with diabetes had overall poorer gait and balance compared to the non-diabetic group (p<0.050). Among people with diabetes, the HD+ had significantly worsened gait and balance when comparing to the HD- (Cohen’s effect size d=0.63-2.32, p<0.050). Between-group difference was more pronounced among older adults with the largest effect size observed for stride length (d=2.32, p<0.001). Results suggested that deterioration in gait speed among the HD+ was correlated with age (r=-0.440, p<0.001), while this correlation was diminished among the HD-. Interestingly, results also suggested that poor gait in the Older HD- related to poor balance, while no correlation was observed between poor balance and poor gait among the Older HD+. Using objective assessments, results confirmed that the presence of diabetes can deteriorate gait and balance, and this deterioration can be magnified by HD process. Among non-HD people with diabetes, poor static balance described poor gait. However, among people with diabetes undergoing HD, age was a dominate factor describing poor gait irrespective of static balance. Results also suggested feasibility of using wearable platforms to quantify motor performance during routine dialysis clinic visits. These objective assessments may assist in identifying early deterioration in motor function, which in turn may promote timely intervention.

Silybum marianum (L.) Gaertn. (aka milk thistle) constitute the almost exclusive source of silymarin, a mixture of different flavonolignans, and is thus considered as a unique model for their extraction. The present research deals with ultrasound-assisted extraction (UAE) of S. marianum flavonolignans and their quantification using LC system. The optimal conditions for UAE were: aqueous EtOH 54.5% (v/v) as solvent, applying an ultrasound frequency of 36.6 kHz during an extraction time of 60 min at 45°C with a liquid to solid ratio of 25:1 ml/g DW. Following optimization, the extraction method was validated according to international standards of the association of analytical communities (AOAC) in order to ensure its precision and accuracy for the quantitation of the individual silymarin components. The efficiency of UAE was compared with maceration protocol of the same duration. The optimized and validated conditions allowed highest extraction yields of flavonolignans in comparison to maceration. The antioxidant capacity of the extracts was confirmed by the CUPRAC assays and inhibition of advanced glycation end products. The skin anti-aging action was also confirmed toward the strong in vitro inhibition capacity of the obtained extract against collagenase and elastase enzymes. The procedure presented here allows a green efficient extraction and quantification of the main flavonolignans from the fruits of S. marianum with attractive antioxidant and anti-aging activities for future cosmetic applications.

In today's world it is very much important to maintain the security of information and its risks. The biometric-based techniques are very much useful in these problems. Among the several kinds of biometric-based technique, face detection is much complex and much more important. Due to the age and several other problems, a human face structure changes over time, again a human has lots of expressions. Sometimes due to the lighting condition or the variation of the angle of an input device, the pattern of a human face structure also changed. As a result, the face cannot be detected properly. In this paper, a method is proposed that can detect the human faces both automatically and manually very efficiently. In manual mode, a user can select the input faces referred by the system according to their choice. In automated mode, the system detected all possible face areas using the Kohonen Self-Organizing Feature Map technique. This method reduced the complex color image into a vector quantized image with desired colors. Then a color segmentation technique is used to detect the possible face skin areas from the vector quantized image. Then the Histogram Oriented Gradient technique used to detect the feature from the faces and K-Nearest Neighbour Classifier is used to compare both face images detected by the two modes. The automated method prosed better accuracy than the manual method.

Background: Aging is commonly accepted as a time period of declining heath. Aims: This review aimed to examine the research base concerning the use of term ‘successful aging’, a process and outcome deemed desirable, but challenging to attain. A second was to provide related information to demonstrate how health professionals as well as individuals can aim for a ‘successful aging’ process and outcome, despite the presence of disabling osteoarthritis. Methods: Information specifically focusing on ‘successful aging’ and the concept of improving opportunities for advancing ‘successful aging’ despite osteoarthritis was sought. Results: Among the many articles on ‘successful aging’, several authors highlight the need to include, a broader array of older adults into the conceptual framework. Moreover, conditions such as osteoarthritis should not necessarily preclude the individual from attaining a personally valued successful aging outcome. Conclusion: Pursuing more inclusive research and research designs, and not neglecting to include people with chronic osteoarthritis can potentially heighten the life quality of all aging individuals, while reducing pain and depression, among other adverse aging and disability correlates among those with osteoarthritis

Mental stress represents a pivotal factor in cardiovascular diseases. The mechanism by which stress produces its deleterious effects is still under study but one of the most explored pathway is cell senescence. In this scenario, circulating microRNAs appear to be mobile regulatory elements of the telomerase activity and alternative splicing within the ”senectome” network. Anti-stress techniques seem to be able to slow-down aging process. As we have recently verified how the practice of Relaxation Response (RR), counteracting psychological stress, determines favorable changes of some inflammatory genes expression, of some neurotransmitters, hormones, cytokines and inflammatory circulating microRNAs, we aimed to verify a possible change even in serum levels of 4 senectome micro-RNAs (SE-miRNAs -20, -30, -410, -515), testing the activity of telomerase in peripheral blood mononuclear cells-PBMCs. We analyzed also alternative splicing microRNAs 134 and 183. According to our data, miRNA-20 and -30 levels and PBMCs-telomerase activity increase during the RR while -410 and -515 levels decrease. Moreover, during the RR sessions both miRNA-134 and -183 decrease. The mediators considered in this work seem to vary rapidly according to a (stress)-relaxation condition showing that psychic activity should be part of the study of aging factors.

This article discuss the effects of heat treatment and lubrication modes on the machinability of an A356 alloy (Al-Si-Mg); the alloy is studied as-received, with solution heat-treated alloy (SHT) as well as with an alloy that is solution heat-treated and then aged at 155, 180 and 220 °C. In the course of machinability evaluation, several criteria including cutting force, surface roughness, tool wears and burr analysis (chip) were studied. The results and analysis in this work indicated that the selected machinability criteria are important and necessary to effectively evaluate the machinability of A356 alloys. The machinability of both materials and tools were estimated in terms of cutting force, chip thickness ratio and burr formation, flank wear and roughness. The effects of different cutting parameters (cutting speed and feed rate) and lubrication modes (dry, mist and wet) on the machinability of the A356 cast alloy were also examined. The influence of heat treatments on the burr formation and surface quality was clearly revealed by the experimental results. Experimental work revealed that cutting forces were influenced significantly by aging and cutting speed. However, the different aging at 155, 180, and 220 °C and the cutting speed significantly affected the machinability of the A356 cast alloy. The results obtained show that a better drilling performance in terms of surface quality occurs at a high feed rate, with dry drilling and artificial aging at T6.

Currently, skin cancer is the most commonly diagnosed form of cancer in humans and is one of the leading causes of death in patients with cancer. Biopsy methods are an invasive research method and are not always available for primary diagnosis. Imaging methods have low accuracy and depend on the experience of the dermatologist. Artificial intelligence technologies can match and surpass visual analysis methods in accuracy, but they have the risk of a false negative response when a malignant pigmented lesion can be recognized as benign. One possible way to improve accuracy and reduce the risk of false negatives is to analyze heterogeneous data, combine different preprocessing methods, and use modified loss functions to eliminate the negative impact of unbalanced dermatological data. The paper proposes a multimodal neural network system with a modified cross-entropy loss function that is sensitive to unbalanced heterogeneous dermatological data. The accuracy of recognition in 10 diagnostically significant categories for the proposed system was 85.19%. The novelty of the proposed system lies in the use of cross-entropy loss when training the modified function with the help of weight coefficients. The introduction of weighting factors has reduced the number of false negative forecasts, as well as improved accuracy by 1.02-4.03 percentage points compared to the original multimodal systems. The introduction of the proposed multimodal system as an auxiliary diagnostic tool can reduce the consumption of financial and labor resources involved in the medical industry, as well as increase the chance of early detection of skin cancer.

The ageing transformation of digital health services faces issues of how to distinguish influencing factors, redesign services, and effectively promote measures and policies. In this study, in-depth interviews are conducted and grounded theory applied to open coding, main axis coding, and selective coding to form concepts and categories. Trajectory equifinality modeling clarified the evolution logic of digital transformation. Based on the theory of service ecology, a digital health service ageing model is constructed from the "macro-medium-micro" stages and includes governance, service, and technology transformation paths. The macro stage relies on organizational elements to promote the institutionalization of management and guide the transformation of governance for value realization, including the construction of three categories: mechanism, indemnification, and decision-making. The meso stage relies on service elements to promote service design and realize service transformation suitable for aging design, including the construction of three categories: organization, resources, and processes. The micro stage relies on technical elements to practice experiencing humanization, including the construction of three categories: target, methods, and evaluation. These results deepen the understanding of the main behaviors and roles of macro-organizational, meso-service, and micro-technical elements in digital transformation practice and have positive significance for health administrative agencies to implement action strategies.

Evolutionary medicine argues that disease can arise because modern conditions do not match those in which we evolved. For example, a decline in exposure to commensal microbes and gastrointestinal helminths in developed countries has been linked to increased prevalence of allergic and autoimmune inflammatory disorders (the hygiene hypothesis). Accordingly, microbial and helminthic probiotic therapies have been explored as Darwinian treatments for these disorders. A further possibility is that loss of old friend commensals also increases the sterile, aging-associated inflammation known as inflammaging, that contributes to a range of age-related diseases, including cardiovascular disease, dementia and cancer. Interestingly, Crowe et al. (2020) recently reported that treatment with a secreted glycoprotein from a parasitic nematode can protect against murine aging by induction of anti-inflammatory mechanisms. Here, we explore the hypothesis that restorative helminth therapy would have anti-inflammaging effects. Could worm infections provide broad-spectrum protection against age-related disease?

Structural and morphological properties of the hydronium-potassium jarosite microstructures were investigated in this work, and their electrical properties were evaluated. All microstructures were synthesized at a reasonable temperature of 343 K with a reduced reaction time of 3 hours. Increase in the pH from 0.8 to 2.1 decreased the particle sized from 3 µm to 200 nm and increasing the aging time from 0, 3 to 7 days resulted in semispherical, spherical and euhedreal jarosite structures, respectively. A Rietveld analysis also was done, finding that increasing pH, the amount of hydronium substitution by potassium in the cationic site also increases, having a 77.72 % of hydronium jarosite (JH) plus 22.29 % potassium jarosite (JK) at pH 0.8; 82.44 % (JH) and 17.56 % (JK) at pH 1.1, and 89.98 % (JH) plus 10.02 % (JK) at pH 2.1. The results obtained in this work show that the obtained hydronium potassium jarosite microstructures with reduced particle size and euhedreal morphology can be used as anode materials for improving the life time of lithium ion batteries, due that during the analysis of the voltage obtained using electrodes made with this particles and graphite, this ranged from 0.89 to 1.36 V.

Physical frailty and sarcopenia (PF&S) are hallmarks of aging that share a common pathogenic background. Perturbations in protein/amino acid metabolism may play a role in the development of PF&S. In this preliminary study, 68 community-dwellers aged 70 years and older, 38 with PF&S and 30 non-sarcopenic, non-frail controls (nonPF&S), were enrolled. A panel of 37 serum amino acids and derivatives was assayed by UPLC-MS. Partial Least Squares Discriminant Analysis (PLS-DA) was used to characterize the amino acid profile of PF&S. The optimal complexity of the PLS-DA model was found to be three latent variables. The proportion of correct classification was 76.6 ± 3.9% (75.1 ± 4.6% for enrollees with PF&S; 78.5 ± 6.0% for controls). Older adults with PF&S were characterized by higher levels of asparagine, aspartic acid, citrulline, ethanolamine, glutamic acid, sarcosine, and taurine. The profile of nonPF&S individuals was defined by higher levels of α-aminobutyric acid and methionine. Distinct profiles of circulating amino acids and derivatives characterize older individuals with PF&S. The dissection of these patterns may provide novel insights into the role played by protein/amino acid perturbations in the disabling cascade and possible new targets for interventions.

Age-related hearing loss (ARHL) is the most common sensory disorder in the elderly. It is associated with aging and hair cell death due to oxidative stress-induced mitochondrial dysfunction. Although transgenic mice and long-term cultures for induction of aging have been used to study ARHL, there are presently no ARHL animal models stimulated by intermittent environmental change for aging. In this study, an ARHL animal model was established by inducing continuous oxidative stress to promote short-term aging of cells, determined based on the expression of the hearing loss-induced phenotype and aging related factors in the short term. The incidence of hearing loss was significantly different among the groups subjected to intermittent hypoxic environment, high-fat diet (HFD), and injection with D-galactose. Continuous oxidative stress and HFD were factors that accelerated cellular aging. Increase in UCP2 affected oxidative stress and mitochondrial dysfunction. CDH23, SLC26A4, KCNQ4, Myo7a, and Myo6, which are ARHL-related factors, were modified by oxidative stress in cells of the hearing organ. We found that intermittent hypoxic, HFD, and galactose injection accelerated cellular aging in the short term. Thus, we anticipate that the development of this hearing loss animal model, which reflects intermittent environmental changes, will benefit future research on ARHL.

Alzheimer’s disease (AD) is characterized by cognitive impairment and different non-cognitive deficits called “Behavioural and psychological symptoms of dementia” (BPSD) related to neurotrophin alterations, which differ from those presented in normal aging. Mouse models, both transgenics and inbreed mice models of AD, are a useful tool in understanding the underlying mechanisms of the disease. The SAMP8 (senescence-accelerated mouse prone 8) mice line was generated from AKR/J strain by Professor Toshio Takeda at the University of Kyoto. This strain exhibited a particular early-onset and accelerated aging phenotype. The present study characterizes and provides information regarding the non-cognitive, cognitive and neurotrophin alterations and their correlation, demonstrating the AD-like symptoms presented in older males SAMP8. The cognitive impairment presented was accompanied by a reduction in sociability and an increase in aggressive as well as anxiety behaviours. Furthermore, changes in two of the most important neurotrophins, such as brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) were found. Thus, the present results reveal new insights in this useful inbred mouse model of neurodegeneration and AD, demonstrating the potential relationship between neurotrophin modifications, cognitive impairment and neuropsychiatric disorders (ND).

Background & aims It is documented that low protein and amino-acid dietary intake is related to poorer cognitive health and increased risk of dementia. Degradation of the neuromodulatory pathways, (comprising the cholinergic, dopaminergic, serotoninergic and noradrenergic systems) is observed in neurodegenerative diseases and impairs the proper biosynthesis of key neuromodulators from micro-nutrients and amino acids. How these micro-nutrients are linked to neuromodulatory pathways in healthy adults is less studied. The Locus Coeruleus–Noradrenergic System (LC-NA) is the earliest subcortical structure affected in Alzheimer’s disease, showing marked neurodegeneration, but is also sensitive for age-related changes. The LC-NA system is critical for supporting attention and cognitive control, functions that are enhanced both by tyrosine administration and chronic tyrosine intake. The purpose of this study was to 1) investigate whether the dietary intake of tyrosine, the key precursor for noradrenaline (NA), is related to LC integrity 2) whether LC integrity mediates the reported association between tyrosine intake and higher cognitive performance (measured with Trail Making Test – TMT), and 3) whether LC integrity relates to an objective measure of brain maintenance (BrainPAD). Methods The analyses included 398 3T MRIs of healthy participants from the Berlin Aging Study II to investigate the relationship between LC integrity and habitual dietary tyrosine intake-daily average (HD-Tyr-IDA). As a control procedure, the same analyses were repeated on other main seeds of the neuromdulatory subcortical system (Dorsal and Medial Raphe, Ventral Tegmental Area and Nucleus Basalis of Meynert). In the same way, the relationships between the five nuclei and BrainPAD were tested. Results Results show that HD-Tyr-IDA is positively associated with LC integrity. Similarly, LC integrity disproportionally relates to better brain maintenance (BrainPAD). Mediation analyses reveal that only LC, relative to the other nuclei tested, mediates the relationship between HD-Tyr-IDA I and performance in the TMT and between HD-Tyr-IDA and BrainPAD. Conclusions These findings provide the first evidence linking tyrosine intake with LC-NA system integrity and its correlation with neuropsychological performance. This study strengthens the role of diet for maintaining brain and cognitive health and supports the noradrenergic theory of cognitive reserve. Within this framework, adequate tyrosine intake might increase the resilience of LC-NA system functioning, by preventing degeneration and supporting noradrenergic metabolism required for LC function and neuropsychological performance.

Collagen is the most abundant protein in the animal kingdom. Industrial collagen is mainly bovine and porcine origin. However, due to religious beliefs, allergic issues, and infectious diseases, alternative sources of collagen as marine are gaining increasing interest. In this work, the acid-soluble collagen (ASC) were extracted from salt-cured Atlantic cod (Gadus morhua) skin and characterized. The extraction yield was about 2.0%, equivalent to the extraction yield reported for other fish skins. The electrophoretic pattern showed the typical type I structure (α, β and γ chains). UV-VIS and FTIR absorbance spectra suggested a very pure ASC with an intact triple helical structure. The integrity and the adequate porosity required for different applications were then confirmed by electron micrograph. Our findings allow us to say that, for the first time, we extracted acid-soluble type I collagen from salt-cured Atlantic cod skin, with characteristics suitable for application in various fields, such as biomedical.

Human Face and facial parts are the most significant parts as it reveals a person’s true identity. It plays an important role in various biometric applications like crowd analysis, human tracking, photography, cosmetic surgery, etc. There are many techniques are available to detect a facial image. Among them, skin detection is the most popular one. The aim of this paper is to detect first the person's identity from facial image and finally check any spot present the the detected person. The first step is to detect the maximum skin region based on a combination method of RGB and HSV color space model. Next it is to verify the skin areas of human through machine learning approach. The Aggregated Channel Features (ACF) detector is used to identify the different facial parts like eye pairs, nose, and mouth. Bootstrap aggregation decision tree classifier is applied to classify the person’s identity based on Histogram Oriented Gradient (HOG) features value. The experimental results show that the proposed method gives the average 97% accuracy.

The activity of the mitochondrial Permeability Transition Pore, mPTP, a highly regulated multi-component mega-channel, is enhanced in aging and in aging-driven degenerative diseases. mPTP activity accelerates aging by releasing large amounts of cell-damaging Reactive Oxygen Species, Ca2+ and NAD+. The various pathways that control the channel activity, directly or indirectly, can therefore either, inhibit, or accelerate aging, retards, or enhance the progression of aging-driven degenerative diseases, and determine lifespan and healthspan. Autophagy, a catabolic process that removes and digests damaged proteins and organelles protects the cell against aging and disease. However, the protective effect of autophagy depends on mTORC2/SKG1 inhibition of mPTP. Autophagy is inhibited in aging cells. Mitophagy, a specialized form of autophagy, which retards aging by removing mitochondrial fragments with activated mPTP, is also inhibited in aging cells, and this inhibition leads to increased mPTP activation, which is a major contributor to neurodegenerative diseases, such as Alzheimer’s and Parkinson’s Diseases. The Increased activity of mPTP in aging turns autophagy/mitophagy into a destructive process leading to cell aging and death. Several drugs and lifestyle modifications that enhance healthspan and lifespan enhance autophagy and inhibit the activation of mPTP. Therefore, elucidating the intricate connections between pathways that activate and inhibit mPTP, in the context of aging and degenerative diseases, could enhance the discovery of new drugs and lifestyle modifications that slow aging and degenerative disease.

The Lewy Body Dementia Association (LBDA) held a virtual event, the LBDA Biofluid/Tissue Biomarker Symposium, on January 25, 2021, to present advances in biomarkers for Lewy Body Dementia (LBD), which includes Dementia with Lewy Bodies (DLB) and Parkinson's Disease Dementia (PDD). The meeting featured eight internationally known scientists from Europe and the United States and attracted over 200 scientists and physicians from academic centers, the National Institutes of Health and the pharmaceutical industry. Methods for confirming and quantifying the presence of Lewy body and Alzheimer pathology as well as novel biomarkers were discussed.

The prediction of capacity degradation, and more generally of the behaviors related to battery aging, is useful in the design and use phases of a battery to help improve the efficiency and reliability of energy systems. In this paper, a stochastic model for the prediction of battery cell degradation is presented. The proposed model takes its cue from an approach based on Markov chains, although it is not comparable to a Markov process, as the transition probabilities vary as the number of cycles that the cell has performed varies. The proposed model can reproduce the abrupt decrease in the capacity that occurs near the end of life condition (80% of the nominal value of the capacity) for the cells analyzed. Furthermore, we illustrate the ability of this model to predict the capacity trend for a lithium-ion cell with nickel-manganese-cobalt (NMC) at the cathode and graphite at the anode subjected to a life cycle in which there are different aging factors, using the results obtained for cells subjected to single aging factors.

Cognitive impairment and sarcopenia may share common risk factors and pathophysiological pathways. This study was performed to examine the association between impairments in specific cognitive domains and sarcopenia (and its defining components) in a large group of community-dwelling older adults. Cross-sectional analysis was performed on the baseline data of 3,014 adults aged 70–84 years enrolled in the Korean Frailty and Aging Cohort Study (KFACS). The final analysis included 1,887 adults underwent dual-energy X-ray absorptiometry and cognitive function assessments. Those with disability in activities of daily living, dementia, severe cognitive impairment, Parkinson’s disease, musculoskeletal complaints, neurological disorders, or who were illiterate were excluded. Cognitive function was assessed using the Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease Assessment Packet, the Frontal Assessment Battery. For sarcopenia, we used the diagnostic criteria of the Asian Working Group for Sarcopenia. The prevalence of sarcopenia was 9.6% for men and 7.6% for women. Sarcopenia (odds ratio [OR] 1.76, 95% confidence interval [CI] 1.04–2.99) and slow gait speed (OR 2.58, 95% CI 1.34–4.99) were associated with cognitive impairment in men. Only slow gait speed (OR 1.88, 95% CI 1.05–3.36) was associated with cognitive impairment in women. Sarcopenia is associated with cognitive impairment mainly due to slow gait speed. Our results suggested that cognitive impairment domains, such as processing speed and executive function, are associated with sarcopenia-related slow gait speed.

Mechanisms for somatic chromosomal mosaicism (SCM) and chromosomal instability (CIN) are incompletely understood. During SNP-array molecular karyotyping and bioinformatic analyses of children with neurodevelopmental disorders and congenital malformations (n=612), we observed colocalizaion of regular chromosomal imbalances or copy number variations (CNV) with mosaic ones (n=47 or 7.7%). Analyzing molecular karyotyping data and pathways affected by CNV burdens, we proposed a mechanism for SCM/CIN, which had been designated as “chromohelkosis” (from the Greek chromosome ulceration/open wound). Briefly, structural chromosomal imbalances are likely to cause local instability (“wreckage”) at the breakpoints, which results either to partial/whole chromosome loss (e.g. aneuploidy) or elongation of duplicated regions. Accordingly, a function for classical/alpha satellite DNA (protection from the wreckage towards the centromere) has been hypothesized. Since SCM and CIN are ubiquitously involved in development, homeostasis and disease (e.g. prenatal development, cancer, brain diseases, aging), we have metaphorically (ironically) designate the system explaining chromohelkosis contribution to SCM/CIN as the cytogenomic “theory of everything” like the homonymous theory in physics inasmuch as it might explain numerous phenomena in chromosome biology. Recognizing possible empirical and theoretical weaknesses of this “theory”, we nevertheless believe that studies of chromohelkosis-like processes are required to understand structural variability and flexibility of the genome.

This paper is a review of the current state of IoT-based technologies in the healthcare field for the elderly population. The increasing population of elderly people has led to a greater demand for healthcare services to meet their unique needs. IoT-based technologies have emerged as a promising solution to address this demand. The paper analyses the current trends, challenges, and future opportunities for research in this area. It highlights how IoT-based technologies can be utilized to improve healthcare for older adults, from remote monitoring and telemedicine to fall detection and medication management. The paper also acknowledges that there are still challenges to be addressed, such as data privacy and security, but the potential benefits for older adults outweigh the challenges. The paper also examines the impact of the industrial revolution on the aging population and the corresponding increase in demand for geriatric healthcare. In summary, this paper delves into the current status of IoT-based technologies in geriatric healthcare and its future prospects, with a focus on addressing the needs of the aging population and improving their quality of life.

The extrinsic and intrinsic factors are essential in glioma initiation. Many extrinsic factors (UV, radiation, food, etc.) and intrinsic factors (proteins, hormones, ageing, DNA and RNA damages, etc.) was reported to being responsible for glioma initiation and progression. However, the cell responsible for glioma origin is still unknown. Many research papers have reported that glioma stem cells, senescent cells, injured cells, and death neurons are the cells of glioma origin. However, gene mutation and oncogene protein overexpression doesn’t occur only in cancer but during life evolution. The source of genetic mutations has become a fundamental issue in understanding its role in the initiation of glioma. The glioma is the precise coordination of several distant factors that work together in the initiation and development of glioma. However, the role and effects of the genes (GDNF and SOX1) on cancer cells are well known, but their gene mutation origin is controversial. Several models and theories have been proposed to explain the origins of GDNF and SOX1 genetic mutations and epigenetic modification related to cancer. Our aim in this review is to clear that incertitude about glioma origin (gene mutation and epigenetic modifications) and those factors involved in glioma initiation and recurrence.

A growing body of evidence indicates that aging of the brain is strictly related to the decline of energy metabolism. In particular, in older adults, the neuronal metabolism of glucose declines steadily resulting in a growing deficit of ATP production. The decline is evoked by deficient NAD recovery in the salvage pathway and subsequent impairment of the Krebs cycle. NAD deficit impairs also the activity of NAD-dependent enzymes. All these open vicious circles of neurodegeneration and neuronal death. Some brain structures are particularly prone to aging and neurodegeneration. These are pathological foci of neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. This review article summarizes the impacts and mutual relationships between metabolic processes both on neuronal and brain levels. It also provides directions on how to reduce the risk of neurodegeneration and protect the elderly against neurodegenerative diseases.

The angiotensin-converting enzyme (ACE) is a peptidase that is involved in the synthesis of Angiotensin II, the bioactive component of the renin-angiotensin system. A growing body of literature argues for a beneficial impact of ACE inhibitors (ACEi) on age-associated metabolic disorders, mediated by cellular changes in reactive oxygen species (ROS) that improve mitochondrial function. Yet, our understanding of the relationship between ACEi therapy and metabolic parameters is limited. Here, we used three genetically diverse strains of Drosophila melanogaster to show that Lisinopril treatment reduces thoracic ROS levels and mitochondrial respiration in young flies, and increases mitochondrial content in middle-aged flies. Using untargeted metabolomics analysis, we also showed that Lisinopril perturbs the thoracic metabolic network structure by affecting metabolic pathways involved in glycogen degradation, glycolysis, and mevalonate metabolism. The Lisinopril-induced effects on mitochondrial and metabolic parameters, however, are genotype-specific and likely reflect the drug’s impact on nutrient-dependent fitness traits. Accordingly, we found that Lisinopril negatively affects survival under nutrient starvation, an effect that can be blunted by genotype and age in a manner that partially mirrors the drug-induced changes in mitochondrial respiration. In conclusion, our results provide novel and important insights into the role of ACEi in cellular metabolism.

Elite camels often suffer from massive injuries. Thus, there is a pivotal need for a cheap and readily available regenerative medicine source. We isolated novel stem-like cells from camel skin and investigated their multipotency and resistance against various stresses. Skin samples were isolated from ears of five camels. Fibroblasts, keratinocytes, and spheroid progenitors were extracted. After separation of different cell lines by trypsinization, all cell lines were exposed to heat shock. Then, fibroblasts and dermal cyst-forming cells were examined under cryopreservation. Dermal cyst-forming cells were evaluated for resistance against osmotic pressure. The results revealed that resistance periods against trypsin were 1.5, 4, and 7 minutes for fibroblasts, keratinocytes, and spheroid progenitors, respectively. Furthermore, complete recovery of different cell lines after heat shock along with the differentiation of spheroid progenitors into neurons was observed. Fibroblasts and spheroid progenitors retained cell proliferation after cryopreservation. Dermal cyst-forming cells regained their normal structure after collapsing by osmotic pressure. The spheroid progenitors incubated in the adipogenic, osteogenic, and neurogenic media differentiated into the adipocytes, osteoblasts, and neurons, respectively. To the best of our knowledge, we isolated different unique cellular differons and stem-like cells from the camel skin and examined their multipotency for the first time.

RNA epigenetics is perhaps the most recent aspect of interest for translational epigeneticists. RNA modifications create such an extensive network of epigenetically driven combination whose role in physiology and pathophysiology is still far from being elucidated. Not surprisingly, some of the players determining changes into RNA structure are in common with those involved in DNA and chromatin structure regulation, while other molecules seem very specific to RNA. It is envisaged, then, that new small molecules, acting selectively on RNA epigenetic changes, will be reported soon, opening new therapeutic interventions based on the correction of the RNA epigenetic landscape. In this review, we shall summarize some aspects of RNA epigenetics limited to those in which the potential clinical translatability to cardiovascular disease is emerging.

Cardiovascular disease (CVD) places a heavy burden on older patients and the global healthcare system. A large body of evidence suggests that exercise training is essential in preventing and treating cardiovascular disease, but the underlying mechanisms are not well understood. Here, we used the Drosophila melanogaster animal model to study the effects of early-life exercise training (ELET) on the aging heart and lifespan. We found in flies that age-induced arrhythmias are conserved across different genetic backgrounds. The fat body is the primary source of circulating lipoproteins in flies. Inhibition of fat body apoLpp (the flies apoB homolog) demonstrated that low expression of apoLpp reduced the development of arrhythmias in aged flies but did not affect average lifespan. At the same time, ELET can also reduce the expression of apoLpp mRNA in aged flies and have a protective effect on the heart, which is similar to the inhibition of apoLpp mRNA. Although treatment of apoLppRNAi and ELET alone had no significant effect on lifespan, the combination of apoLppRNAi and ELET extended the average lifespan of flies. Therefore, we conclude that apoLppRNAi and ELET are sufficient to resist age-induced arrhythmias, which may be related to the decreased expression of apoLpp mRNA, and that apoLppRNAi and ELET have a combined effect on prolonging the average lifespan.

Atopic dermatitis (AD) is a chronic eczematous inflammatory disease that may arise from environmental, genetic and immunological factors. Despite the efficacy of current treatment options like corticosteroids, such approaches are mainly focused on symptoms relief, and may present certain undesirable side effects. In recent years, investigation regarding isolated natural compounds, oils, mixtures and/or extracts, have gained scientific attention because of their high efficiency and moderate to low toxicity. Despite their promising therapeutic effects, the applicability of such natural health care solutions is somehow limited by their instability, poor solubility, and low bioavailability. Therefore, novel nanoformulation-based systems have been designed to overpass these limitations, thus enhancing the therapeutic potential, by promoting the capacity of these natural drugs to properly exert their action in AD-like skin lesions. For the best of our knowledge, this is the first literature review that focused on summarizing the last nanoformulation-based solutions loaded with natural ingredients, and specifically for the management of AD. We suggest that future studies should focus on robust clinical trials that may confirm the security and effectiveness of such natural-based nanosystems, thus paving the way for more reliable AD treatments.

During the last decade, essential polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) derived from marine sources have been investigated as nonpharmacological dietary supplements to improve different pathological conditions, as well as aging. The aim of this study was to determine the effects of dietary n-3 PUFA monoacylglycerides (MAG, both EPA and DHA) on the mitochondrial metabolism and oxidative stress of a short-lifespan model, Drosophila melanogaster, sampled at five different ages. Our results showed that diets supplemented with MAG-EPA and MAG-DHA increased median lifespan by 14.6% and decreased mitochondrial proton leak resulting in an increase of mitochondrial coupling. The flies fed on MAG-EPA also had higher electron transport system capacity and mitochondrial oxidative capacities. Moreover, both n-3 PUFAs delayed the occurrence of lipid peroxidation, but only flies fed the MAG-EPA diet showed maintenance of superoxide dismutase activity during aging. Our study therefore highlights the potential of n-3 PUFA monoacylglycerides as nutraceutical compounds to delay the onset of senescence by acting directly or indirectly on the mitochondrial metabolism, and suggests that Drosophila could be a relevant model for the study of the fundamental mechanisms linking the effects of n-3 PUFAs to aging.

Atopic dermatitis (AD) is a chronic and allergic skin disease, however, there is no cure for the disease. Many studies have shown anti-AD potentials of red ginseng, while red ginseng marc (RGM) remained after the ginseng extraction is discarded as industrial waste. However, it is recently reported that RGM, particularly fermented RGM (fRGM), still contains the bioactive properties. Thus, anti-allergic effects of fRGM were examined in 2,4-dinitrochlorobenzene-induced AD-like mice model. The model was topically treated with distilled water (control), dexamethasone, or fRGM for six weeks. The treatments of fRGM alleviated the skin lesions and reduced serum IgE levels, compared with the control. The fRGM also reduced skin levels of lipid peroxidation and superoxide anion, however, increased glutathione contents, with down-regulated gene expressions for inflammatory mediators. The histopathological analyses demonstrated that fRGM suppressed the epidermal thickening, collagen deposition, and inflammatory cell and mast cell infiltration, which involved the anti-inflammatory, anti-oxidant, and anti-apoptotic effects. Further, fRGM suppressed hypertrophic changes and inflammatory responses in the spleen and lymph node. The beneficial effects were observed in the dexamethasone and fRGM groups, however, the antioxidant effects were evident only in the fRGM treatments. These provide useful information for developing fRGM as therapeutic sources for AD.

Prior research shows that individuals who have exhibited antisocial behavior are in poorer health than their same-aged peers. A major driver of poor health is aging itself, yet research has not investigated relationships between offending trajectories and biological aging. We tested the hypothesis that individuals following a life-course persistent (LCP) antisocial trajectory show accelerated aging in midlife. Trajectories of antisocial behavior from age 7 to 26 years were studied in the Dunedin Multidisciplinary Health and Development Study, a population-representative birth cohort (N=1037). Signs of aging were assessed at age 45 years using previously validated measures including biomarkers, clinical tests, and self-reports. First, we tested whether the association between antisocial behavior trajectories and midlife signs of faster aging represented a decline from initial childhood health. We then tested whether decline was attributable to tobacco smoking, antipsychotic medication use, debilitating illnesses in adulthood, adverse exposures in childhood (maltreatment, socioeconomic disadvantage) and adulthood (incarceration), and to childhood self-control difficulties. Study members with a history of antisocial behavior had a significantly faster pace of biological aging by midlife, and this was most evident among individuals following the LCP trajectory (β, .22, 95%CI, .14, .28, p.001). This amounted to 4.3 extra years of biological aging between ages 25-45 years for Study members following the LCP trajectory compared to low-antisocial trajectory individuals. LCP offenders also experienced more midlife difficulties with hearing (β, -.14, 95%CI, -.21, -.08, p.001), balance (β, -.13, 95%CI, -.18, -.06, p.001), gait speed (β, -.18, 95%CI, -.24, -.10, p.001), and cognitive functioning (β, -.25, 95%CI, -.31, -.18, p.001). Associations represented a decline from childhood health. Associations persisted after controlling individually for tobacco smoking, antipsychotic medication use, midlife illnesses, maltreatment, socioeconomic status, incarceration, and childhood self-control difficulties. However, the cumulative effect of these lifestyle characteristics together explained why LCP offenders have a faster Pace of Aging than their peers. While older adults typically age-out of crime, LCP offenders will likely age-into the healthcare system earlier than their chronologically same-aged peers. Preventing young people from offending is likely to have substantial benefits for health, and people engaging in a LCP trajectory of antisocial behaviors might be the most in need of health promotion programs. We offer prevention and intervention strategies to reduce the financial burden of offenders on health care systems and improve their wellbeing.

The noradrenergic theory of Cognitive Reserve (Robertson, 2013-2014) postulates that the upregulation of the Locus Coeruleus - Noradrenergic System (LC-NA) originating in the Brainstem might facilitate cortical networks involved in attention, and protracted activation of this system throughout the lifespan may enhance cognitive stimulation contributing to Reserve. To test the above-mentioned theory, a study was conducted on a sample of 686 participants (395 controls, 156 Mild Cognitive Impairment, 135 Alzheimer’s Disease) investigating the relationship between LC volume, attentional performance and a biological index of brain maintenance (BrainPAD – an objective measure which compares an individual’s structural brain health, reflected by their voxel-wise grey matter density, to the state typically expected at that individual’s age). Further analyses were carried out on Reserve indices including education and occupational attainment. Volumetric variation across groups was also explored along with gender differences. Control analyses on the Serotoninergic (5-HT), Dopaminergic (DA) and Cholinergic (Ach) systems were contrasted with the Noradrenergic (NA) hypothesis. The antithetic relationships were also tested across the neuromodulatory subcortical systems.Results supported by bayesian modelling showed that LC volume disproportionately predicted higher attentional performance as well as biological brain maintenance across the three groups. These findings lend support to the role of the noradrenergic system as a key mediator underpinning the neuropsychology of Reserve, and they suggest that early prevention strategies focused on the noradrenergic system (e.g. cognitive-attentive training, physical exercise, pharmacological and dietary interventions) may yield important clinical benefits to mitigate cognitive impairment with age and disease.

Across different cultures around the globe, human beings have historically depended largely on medicinal plants for managing diseases that have hitherto threatened their optimal health, survival, and longevity. Evidently, the health-derived benefits of medicinal plants can be strongly attributed to the presence of secondary metabolites, particularly polyphenols. The health-promoting effects of Sorghum bicolor supplement Jobelyn® (SBSJ) —a unique supplement derived from the leaf sheaths of a West African variety of Sorghum bicolor (L.) Moench—have also been ascribed to its high levels of polyphenols. This review seeks to gather and synthesize findings from various experimental and clinical studies on the health benefits of SBSJ in arthritis, cancer, chronic viral infections, stroke, anaemia, and aging. SBSJ has been reported to contain potent bioactive polyphenolic compounds with polyvalent biological activities, including antioxidant, anti-inflammatory, immunomodulatory, chemopreventive, and neuroprotective activities. Moreover, the probable benefits of SBSJ in chronic viral infections (e.g., HIV/AIDS and COVID-19) have been attributed to its potent anti-inflammatory and immunomodulatory activities. As this supplement is increasingly becoming one of the fastest-selling herbal medicines in Nigeria, there is a need for more robust studies (including clinical trials) in order to replicate and validate the prior insights gleaned from experimental studies.

Medical imaging is an active field of research that fosters the necessity for novel multimodal imaging probes. In this line, nanoparticle-based contrast agents are of special interest, since those can host functional entities either within their interior, reducing potential toxic effects of the imaging tracers, and on their surface, providing high payloads of probes, due to their large surface-to-volume ratio. The long-term stability of the particles in solution is an aspect usually under-tackled during probe design in research laboratories, since their performance is generally tested briefly after synthesis. This may jeopardize a later translation into practical medical devices, due to stability reasons. To dig into the effects of nanoparticle aging in solution, respect to their behavior in vivo, iron oxide stealth nanoparticles were used at two stages (3 weeks vs. 9 months in solution), analyzing their biodistribution in mice. Both sets of nanoprobes showed similar sizes, zeta potentials and morphology, as observed by DLS and TEM but, fresh nanoparticles accumulated in the kidneys after systemic administration, while aged ones accumulated in liver and spleen, confirming an enormous effect of particle aging on their in vivo behavior, despite barely noticeable changes perceived on a simple inspection of their structural integrity.

Collagen type I production decreases with aging, leading to wrinkles and impaired skin function. Prostaglandin E2 (PGE2), a lipid-derived signaling molecule produced from arachidonic acid by cyclo-oxygenase, inhibits collagen production and induces matrix metallopeptidase 1 (MMP1) expression by fibroblasts in vitro. PGE2-induced collagen expression inhibition and MMP1 promotion are aging mechanisms. This study investigated the role of E-prostanoid 1 (EP1) in PGE2 signaling in normal human dermal fibroblasts (NHDFs). When EP1 expression was inhibited by EP1 small interfering RNA (siRNA), there were no significant changes in messenger RNA (mRNA) levels of collagen, type I, alpha 1 (COL1A1)/MMP1 between siRNA-transfected NHDFs and siRNA-transfected NHDFs with PGE2. This result showed that EP1 is a PGE2 receptor. Extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation after PGE2 treatment significantly increased by ~2.5 times. In addition, PGE2 treatment increased the intracellular Ca²⁺ concentration in NHDFs. These results indicated that PGE2 is directly associated with EP1 pathway–regulated ERK1/2 and inositol trisphosphate (IP₃) signaling in NHDFs.

Ulmus species have been widely used in Korean folk medicine because of their anti-inflammatory and antimicrobial properties. We intended to investigate the wound healing effect of the powder of Ulmus parvifolia (UP) root bark in a mouse wound healing model. We also determined the mechanisms of effects of Ulmus parvifolia (UP) in skin and skin wound healing effect using keratinocyte model. in vivo experiments showed that the wound lesions in the mice decreased by U. parvifolia with 200 mesh size of root bark powder and significantly reduced by treatment with UP, compared with those treated with U. macrocarpa (UM). Results from in vitro experiments also revealed that UP extract promoted the migration of human skin keratinocytes. UP powder treatment upregulated the expression of the matrix metalloproteinase-2 and -9 protein and significantly increased transforming growth factor (TGF)-β levels. We confirmed that topical administration of the bark powder of exerted a significant effect on skin wound healing by upregulating the expression of MMP and transforming growth factor-β. TGF-β In, Our study suggests that U. parvifolia may be a potential candidate for skin wound healing including epidermal skin rejuvernation.

Eye movements support memory encoding by binding distinct elements of the visual world into coherent representations. However, the role of eye movements in memory retrieval is less clear. We propose that eye movements play a functional role in retrieval by reinstating the encoding context. By overtly shifting attention in a manner that broadly recapitulates the spatial locations and temporal order of encoded content, eye movements facilitate access to, and reactivation of, associated details. Such mnemonic gaze reinstatement may be obligatorily recruited when task demands exceed cognitive resources, as is often observed in older adults. We review research linking gaze reinstatement to retrieval, describe the neural integration between the oculomotor and memory systems, and discuss implications for models of oculomotor control, memory, and aging.

Multidrug resistance protein 4 (MRP4) is an energy-dependent membrane transporter that is responsible for cellular efflux of a broad range of xenobiotics and physiological substrates. In this trial, we aimed to investigate the co-effects of aging and MRP4 deficiency using gene expression microarray and morphological and electrophysiological analyses of the mouse retina. Mrp4-knockout (null) mice and wild-type (WT) mice were reared in the same condition to 8–12 wk (young) or 45–55 wk (aged). Microarray analysis identified 186 differently expressed genes from the retinas of aged Mrp4-null mice as compared to that from aged WT mice, and subsequence gene ontology and KEGG pathway analyses showed that differently expressed genes were related to lens, eye development, vision, and transcellular barrier function that are involved in metabolic pathways or viral infection pathways. No significant change in thickness was observed for each retinal layer among young/aged WT mice and young/aged Mrp4-null mice. Moreover, immunohistochemical analyses of retinal cell type did not exhibit an overt change in the cellular morphology or distribution among the 4 age/genotype groups, and the electroretinogram responses showed no significant differences in the amplitude or the latency between aged WT mice and aged Mrp4-null mice. Aging would be an insufficient stress to cause some damage to the retina in the presence of MRP4 deficiency.

Environmental factors as maternal high-fat diet (HFD) intake can increase the risk of age-related cognitive decline in adult offspring. The epigenetic mechanisms are a possible link between diet effect and neurodegeneration across generations. Here, we found a significant decrease in triglyceride levels in a high-fat diet with resveratrol HFD+RV group and the offspring. Firstly, we obtained better cognitive performance in HFD+RV groups and their offspring. Molecularly, a significant increase in 5-mC levels, as well as increased gene expression of Dnmt1 and Dnmt3a in HFD+RV F1 group, were found. Furthermore, a significantly increased of m6A levels in HFD+RV F1 were found, and there were changes in gene expression of its enzymes (Mettl3 and Fto). Moreover, we found a decrease in gene expression levels of pro-inflammatory markers such as Il1-β, Il-6, Tnf-α, Cxcl-10, Mcp-1 and Tgf-β1 in HFD+RV and HFD+RV F1 groups. Moreover, there was increased gene expression of neurotrophins such as Ngf and Nt3 and its receptors TrkA and TrkB. Likewise, an increase in protein levels of BDNF and p-Akt in HFD+RV F1 was found. These results suggest that maternal RV supplementation under HFD intake prevents cognitive decline in SAMP8 adult offspring, promoting a reduction in triglycerides and leptin plasma levels, changes in the pro-inflammatory profile, restoring the epigenetic landscape as well as synaptic plasticity.

Dietary guidelines emphasizes the importance of a varied diet to provide an adequate nutrient intake. However, the aging is often associated with consumption of monotonous diets that can be nutritionally inadequate, increasing the risk for the development or progression of diet-related chronic diseases such as the metabolic syndrome (MetS). To assess the relationship between dietary diversity (DD) and nutrient adequacy and to identify associated demographic variables related with DD. We analysed cross-sectional baseline data from the PREDIMED-Plus study: 6587 Spanish adults, aged 55–75 years, with overweight/obesity and MetS. Using a 143-item validated semi-quantitative food frequency questionnaire (FFQ), we calculated an energy-adjusted score of DD (DDS). Nutrient inadequacy was defined as an intake below 2/3 of the recommended dietary intake at least of ≥4 of 17 nutrients. Logistic regression models were used to evaluate the relationship between nutritional inadequate intakes and DDS. In the higher DDS quartile there were more women and less current smokers. Compared with subjects in the highest DDS quartile, those in the lowest DDS quartile had a higher risk of inadequate nutrient intake OR=28.56 (95% C.I. 20.80-39.21). When we estimated diversity for each one of the food groups, participants in the first quartile of diversity had a higher risk of nutrient deficiency: for vegetables, OR= 14.03 (IC 95% 10.55-18.65), fruits OR=11.62 (IC 95% 6.81-19.81), dairy products OR= 6.54 (IC 95% 4.64-9.22) and protein foods OR=6.60 (IC 95% 1.96-22.24). As DDS decreases, the risk of inadequate nutrients intake rises. Given the impact of nutrient intake adequacy on the prevention of non-communicable diseases, health policies should focus on the promotion of a healthy varied diet, specifically promoting the intake of vegetables and fruit among population groups with lower DDS such as men, smokers or widow people.

The aim of the study is to investigate the effects of artificial aging by thermocycling and mechanical loading on force/torque delivery by thermoplastic orthodontic aligners. Ten thermoformed aligners made of Zendura™ thermoplastic polyurethane sheets were aged over two weeks in deionized water by thermocycling alone (n=5) and by both thermocycling and mechanical loading (n=5). The force/torque generated on upper second premolar (Tooth 25) of a plastic model was measured before aging (as control), and after 2, 4, 6, 10, and 14 days of aging, using a biomechanical set-up. Before aging, the extrusion-intrusion forces were in the range of 2.4 to 3.0 N, the oro-vestibular forces were 1.8 to 2.0 N, and the torques on mesio-distal rotation were 13.6 to 40.0 Nmm. Pure thermocycling had no significant effect on the force decay of the aligners. However, there was a significant decrease in force/torque after 2 days of aging for both thermocycling and mechanical loading aging group, which is no longer significant over 14 days of aging. In conclusion, artificial aging of aligners in deionized water with thermocycling and mechanical loading results in a significant decrease in force/torque generation. However, the mechanical loading of aligners has a greater impact than thermocycling alone.

G protein-coupled receptors (GPCRs) serve prominent roles in melanocyte lineage physiology, with an impact at all stages of development, as well as on mature melanocyte functions. GPCR ligands are present in the skin and regulate melanocyte homeostasis, including pigmentation. The role of GPCRs in the regulation of pigmentation and, consequently, protection against external aggression, such as ultraviolet radiation, has long been established. However, evidence of new functions of GPCRs directly in melanomagenesis has been highlighted in recent years. GPCRs are coupled, through their intracellular domains, to heterotrimeric G proteins, which induce cellular signaling through various pathways. Such signaling modulates essential cellular processes of melanomagenesis, such as proliferation and migration. GPCR-associated signaling in melanoma can be activated by the binding of paracrine factors to their receptors or directly by activating mutations. In this review, we present melanoma-associated alterations of GPCRs and their downstream signaling and discuss the various preclinical models used to evaluate new therapeutic approaches against GPCR activity in melanoma. Recent striking advances in our understanding of the structure, function, and regulation of GPCRs will undoubtedly broaden treatment options in melanoma in the future.

In the past decades, regenerative medicine applied on skin lesions has been a field of constant improvement for both human and veterinary medicine. The process of healing cutaneous wound injuries implicates a well-organized cascade of molecular and biological processes. However, sometimes the normal process fails and can result in a chronic lesion. In addition, wounds are considered an increasing clinical impairment, due to the progressive ageing of the population, as well as the prevalence of concomitant diseases, such as diabetes and obesity, that represent risk aggravating factors for the development of chronic skin lesions. Stem cells regenerative potential has been recognized worldwide, including towards skin lesion repair, Tissue engineering techniques have long been successfully associated with stem cell therapies, namely the application of 3D bioprinted scaffolds. With this review we intend to explore several stem cell sources with promising aptitude towards skin regeneration, as well as different techniques used to deliver those cells and provide a supporting extracellular matrix environment, with effective outcomes. Furthermore, different studies are discussed, both in vitro and in vivo, towards their relevance in the skin regeneration field.

The results of this study offer a potential to gain a better understanding of the mechanisms underlying the falls in the elderly. The results were recorded for a group of 27 women in a control group (CON) and 16 women in an experimental group (EXP), aged 60-70. Participants took part in the six-weeks Elderly Recreation Movement Program (ERMP) with the difference, that the EXP group practiced twice as often as the CON group. The measurement of variations in the index called limits of stability (LOS) was performed by application of Kistler force plate and the coactivation index (CI) was registered by means of sEMG. The results demonstrate the existence of statistically significant differences in terms of the principal outcome of the exercise time in the measurements of LOS (F (1.42) = 10.0, p = 0.003), and CI (F (1.42) = 10.5, p = 0.002). The effect of the program was associated with an increase the level of the maximum LOS, and a decrease of the CI level, especially in the experimental group. Hence, the implementation of an innovative ERMP exercise program results in the improvement of the physical capabilities of senior subjects and a reduction of the risk of falls.

Extracts of Cordyceps militaris which possess the bioactive capacity such as antimicrobial activity and DPPH-free radical scavenging capacity, are applied to the serum product. This finished serum product has been evaluated the in vitro bioactivity and the stability with expect to find out a good extract with a suitable percentage used for serum product as natural materials on preservatives and antioxidation.

Diffusion bonding is often used on pre-machined parts to generate internal cavities, e.g. for cooling injection molding tools close to the mold cavity. Only then, the workpieces are finished to their final dimensions. In the case of micro-process devices, however, it is essential to precisely control the deformation, as otherwise uncontrollable pressure losses will occur with channel cross-sections in the sub-millimeter range. Post-processing is not possible. The most important process parameters for diffusion bonding are temperature, dwell time and contact pressure, with the bonding temperature and contact pressure acting in opposite directions and showing a strong non-linear dependence on deformation. In addition, the deformation is influenced by a number of other factors such as the absolute size of the cross-section and the aspect ratio of the parts, the dimensions and distribution of the internal cross sections and the overall percentage of the cross-section to be bonded. In micro process engineering, small material cross-sections in the range of the materials microstructure can facilitate additional deformation mechanisms such as grain boundary sliding, which are not relevant at all for larger structures. For parts consisting of multiple layers, tolerances in thickness and roughness of multiple surfaces must be levelled, contributing to the percentaged deformation. This makes it difficult, especially in micro process engineering and in single or small series production, to determine suitable joining parameters in advance, which on the one hand do not cause unforeseen large deformations, but on the other hand reliably produce highly vacuum-tight components. Hence, a definition of a fixed percentaged deformation does not work for all kinds of components. This makes it difficult to specify parameters for surely obtain high-vacuum tight parts. For successful diffusion bonding, atoms must diffuse over the bonding planes, forming a monolithic part in which the original layers are no longer visible. Only then, mechanical properties identical to those of the base material, which has been subjected to identical heat treatment, can be achieved. In this paper, the impacts of different material cross section widths as well as of the aspect ratio on deformation were investigated. By accident, it was found that also accuracy of the temperature measurement may have a serious impact in terms of deformation.

Advanced paternal age at fertilization is a risk factor for multiple disorders in offspring and may be linked with age-related epigenetic changes in fathers sperm. Understanding of aging-related epigenetic changes in sperm and environmental factors that modify such changes is needed. Here we characterize changes in sperm sncRNA between young pubertal and mature rats. We also analyze modification of these changes by exposure to environmental xenobiotic 2,2’,4,4’-tetrabromodiphenyl ether (BDE-47). SncRNA libraries prepared from epididymal spermatozoa were sequenced and analyzed using DESeq 2. Distribution of small RNA fractions changed with age, with fractions mapping to rRNA and lncRNA decreasing and fractions mapping to tRNA and miRNA increasing. 249 miRNA, 908 piRNA and 227 tRNA-derived RNA were differentially expressed (2-fold change, FDR p ≤ 0.05) between age groups in control animals. Differentially expressed miRNA and piRNA were enriched for protein-coding targets involved in development and metabolism, piRNA were enriched for LTR targets. BDE-47 accelerated age dependent changes in sncRNA in younger animals, decelerated these changes in older animals and increased the variance in expression of all sncRNA. Our results indicate that the natural aging process has profound effects on sperm sncRNA profiles and this effect may be modified by environmental exposures.

Rosacea is a chronic inflammatory skin disease characterized by recurrent erythema, flushing, telangiectasia, papules, pustules, and phymatous changes in the central area of the face. Patients with this condition often experience a significant negative impact on their quality of life, self-esteem, and overall well-being. Despite its prevalence, the pathogenesis of rosacea is not yet fully understood. Recent research advances are reshaping our understanding of the underlying mechanisms of rosacea, and treatment options based on the pathophysiological perspective hold promise to improve patient outcomes and reduce incidence. In this comprehensive review, we investigate the pathogenesis of rosacea in-depth, with a focus on emerging and novel mechanisms, and provide an up-to-date overview of therapeutic strategies that target the diverse pathogenic mechanisms of rosacea. Lastly, we discuss potential future research directions aimed at enhancing our understanding of the condition and developing effective treatments.

Aging is accompanied by frontal lobe and non-dominant hemisphere recruitment that supports executive functioning, such as inhibitory control, which is crucial to all cognitive functions. Yet, the spatio-temporal sequence of processing underlying successful inhibition and how it changes with age is understudied. Thus, we assessed N200 (conflict monitoring) and P300 (response inhibition, performance evaluation) event-related potentials (ERPs) in young and healthy older adults during comparably performed successful stop-signal inhibition. We additionally interrogated the continuous spatio-temporal dynamics of N200- and P300-related activation within each group. Young adults had left hemisphere dominant N200, while older adults had overall larger amplitudes and right hemisphere dominance. N200 activation was biphasic in both groups but differed in scalp topography. P300 also differed, with larger right amplitudes in young, but bilateral amplitudes in old, with old larger than young in the left hemisphere. P300 was characterized by an early parieto-occipital peak in both groups, followed by a parietal slow wave only in older adults. A temporally similar but topographically different final wave followed in both groups that showed anterior recruitment in older adults. These findings illuminate differential age-related spatio-temporal recruitment patterns for conflict monitoring and response inhibition that are critically important for understanding age-related compensatory activation.

Abstract: Ultraviolet (UV) induces skin photoaging, which is characterized by thickening, wrinkling, pigmentation, and dryness. Astaxanthin, a ketocarotenoid from Haematococcus pluvialis, has been extensively studied with respect to its possible effect on skin health as well as UV protection. In addition, astaxanthin attenuates increases in the generation of reactive oxygen species (ROS) and capillary regression of skeletal muscle. In the present study, we investigated whether astaxanthin would protect UV-induced photoaging and capillary regression in the skin of HR-1 hairless mice. UV induces wrinkle formation, thickness and capillary regression in dermis of hairless mice and the administration of astaxanthin decreased the UV-induced wrinkle formation, skin thickness, and increase in collagen fibers in skin. Astaxanthin supplementation also inhibited the levels of ROS generation and attenuated the decreases in wrinkle formation, thickness and capillary number in the skin. We also found an inverse correlation between wrinkling and capillary number, and the photoaging associated with capillary regression in skin. These results suggest that astaxanthin can protect against photoaging caused by ultraviolet irradiation and the effects of astaxanthin in photoaging inhibition may be associated with the protection of capillary regression in skin.

Atopic dermatitis (AD) is a common chronic inflammatory skin disease with high prevalence worldwide, including countries from Asia, Africa and Latin America, and in different ethnic groups. In recent years, more attention on AD heterogeneity associated on multiple factors, including patient’s ethnic background, has been posed, resulting in an increasing body of clinical, genetic, epidemiologic, and immune-phenotypic evidence that delineate differences among racial groups with AD. Filaggrin (FLG) mutations, the strongest genetic risk factor for the development of AD, are detected in up to 50% of European and 27% of Asian AD patients, while very rarely in Africans. The Th2 activation is a common attribute of all ethnic groups, though the Asian endotype of AD is also characterized by an increased Th17-mediated signal whereas African Americans own a strong Th2/Th22 signature and the absence of Th1/Th17 skewing. In addition, the ethnic heterogeneity may own important therapeutic implications as the genetic predisposition may affect treatment response and, thereby, a tailored strategy that better targets the dominant immunologic pathways in each ethnic subgroup may be envisaged. Nevertheless, white patients with AD represent the largest ethnicity enrolled and tested in clinical trials and the most treated in a real-world setting, limiting the investigation about safety and efficacy across different ethnicities. The purpose of this review is to describe the heterogeneity of pathophysiology across ethnicities and its potential therapeutic implications.

Herbal cosmetics are cosmetics derived from plants. One example is bakuchiol. Bakuchiol is a meroterpene phenol from the seeds of the Psoralea corylifolia plant. Bakuchiol can be derived from Psoralea grandulosa, Pimelea drupaceae, Ulmus davidiana, Otholobium pubescens, and Piper longum. Bakuchiol has antioxidant, anti-inflammatory, and anti-aging activities such as retinol. Bakuchiol will replace retinol with much better safety. Bakuchiol and retinoids share similar cellular pathways, such as the regulation of retinoic acid, the expression of collagen, and extracellular matrix synthesis enzymes. Bakuchiol has many benefits for the skin, so cosmetics and skin therapy can use bakuchiol. This review aims to provide information about the activity of bakuchiol, which has benefits for facial skin, so that this review can be a reference in making cosmetics containing bakuchiol. Bakuchiol has many benefits for skincare such as anti-aging, anti-hyperpigmentation, anti-oxidant, anti-inflammatory, anti-acne, and anti-melanogenesis. Products containing bakuchiol on the market are cleansers, serum, nanoemulsion, and cream.

Skin aging is one of the most common problems facing humanity. It occurs because of altering the balance between free radicals and antioxidants and increasing the amount of the reactive oxygen species (ROS) in skin cells, which leads to oxidative stress especially when exposed to UV radiation. Antioxidants can neutralize the harmful effects of ROS, and secondary plant metabolites can help protect against UV radiation. In this study, punicalagin was extracted from pomegranate and concentrations of total polyphenolics and flavonoids were determined and antioxidant activities measured. Punicalagin was loaded onto niosomes and its morphology and release were studied. An in vitro study was performed on human fibroblast cell line HFB4 cells with aging induced by H2O2 and UV radiation. Cell cycle arrest was studied and different genes (MMP3, Col1A1, Timp3, and TERT) involved in the skin aging process were selected to measure punicalagin's effect. Punicalagin succeeded in reducing the growth arrest of HFB4 cells, activated production of the Col1A1 and Timp3 genes, maintained collagen level, and lowered of MMP3. Punicalagin increased human TERT concentration in skin cells. Punicalagin is promising as a natural antioxidant to protect human skin from aging.

Abstract: Since ancient times aging has also been regarded as a disease, and humankind has always strived to extend the natural lifespan. Analyzing the genes involved in aging and disease allows for finding important indicators and biological markers for pathologies and possible therapeutic targets. An example of the use of omics technologies is the research regarding aging and the rare and fatal premature aging syndrome progeria (Hutchinson-Gilford progeria syndrome, HGPS). In our study, we focused on the in silico analysis of differentially expressed genes (DEGs) in progeria and aging, using a publicly available RNA Seq dataset (GEO dataset GSE113957) and a variety of bioinformatics tools. We identified several genes that appear to be involved both in natural aging and progeria (KRT8, KRT18, ACKR4, CCL2, UCP2, ADAMTS15, ACTN4P1, WNT16, IGFBP2). Further analyzing these genes and the pathways involved confirmed their possible roles in aging, suggesting the need for further in vitro and in vivo research. The graphical abstract illustrates the analysis workflow we used and will introduce in the following as an example to demonstrate the power of omics and bioinformatics.

Stress mechanisms have long been associated with neuronal loss and neurodegenerative diseases. The origin of cell stress and neuronal loss likely stems from multiple pathways. These include (but are not limited to) bioenergetic failure, neuroinflammation, and loss of proteostasis. Cells have adapted compensatory mechanisms to overcome stress and circumvent death. One mechanism is mitophagy. Recent studies have implicated mitophagy in several neurodegenerative diseases and clinical trials are underway which target mitophagy pathways. Here, we review mitophagy pathways, the role of mitophagy in neurodegeneration, potential therapeutics, and the need for further study.

Mitochondrial malfunction is supposed to be involved in the etiology and pathology of major depressive disorder (MDD). Here, we aimed to identify and characterize the molecular pathomechanisms related to mitochondrial disfunction in adult human skin fibroblasts which were derived from MDD patients or non-depressive control subjects. We found that MDD fibroblasts showed significantly impaired mitochondrial functioning: basal and maximal respiration, spare respiratory capacity, non-mitochondrial respiration and ATP-related oxygen consumption was lower. Moreover, MDD fibroblasts harbor lower ATP levels and showed hyperpolarized mitochondrial membrane potential. To investigate cellular resilience, we challenged both groups of fibroblasts with hormonal (dexamethasone) or metabolic (galactose) stress for one week, and found that both stressors increased oxygen consumption but lowered ATP content in MDD as well as in non-depressive control fibroblasts. Interestingly, the bioenergetic differences between fibroblasts from MDD or non-depressed subjects, which were observed under non-treated conditions, could not be detected after stress. Our findings support the hypothesis that altered mitochondrial function causes a bioenergetic imbalance which is associated with the molecular pathophysiology of MDD. The observed alterations in OXPHOS and other mitochondria-related properties represent a basis for further investigations of pathophysiological mechanisms and might open new ways to gain insight into antidepressant signaling pathways.

The aging of the global population has increased the prevalence of neurodegenerative conditions. Bacopa monnieri (BM), an herb with active compounds, such as bacosides A and B, betulinic acid, loliolide, asiatic acid, and quercetin, demonstrates the potential for brain health. Limited research has been conducted on the therapeutic applications of BM in neurodegenerative conditions. This systematic review aims to project BM's beneficial role in brain disorders. BM has anti-apoptotic and antioxidant actions and can repair damaged neurons, stimulate kinase activity, restore synaptic function, improve nerve transmission, and increase neuroprotection. The included twenty-two clinical trials demonstrated that BM can reduce Nuclear Factor-κB phosphorylation, improve emotional function, cognitive functions, anhedonia, hyperactivity, sleep routine, depression, attention deficit, learning problems, memory retention, impulsivity, and psychiatric problems. Moreover, BM can reduce the levels of pro-inflammatory biomarkers and oxidative stress. Here, we highlight that BM provides notable therapeutic benefits and can serve as a complementary approach for the care of patients with neurodegenerative conditions associated with brain disorders. This review adds to the growing interest in natural products and their potential therapeutic applications by improving our understanding of the mechanisms underlying cognitive function and neurodegeneration and informing the development of new therapeutic strategies for neurodegenerative diseases.

Neuronal lesion or injury is a traditional approach to investigate neural circuit. Is any new neural pathway or new neurodegeneration related central nerve system injury? Spinal disc herniation can cause the spinal cord injury. However, the histological examination is still lack. It happened that a case of spinal disc herniation of a 10-year old dog was examined with NADPH diaphorase (N-d) histology. We did not find the N-d neurodegenerative aberrant in the tissue of the mid-rostral lumber segment besides the metamorphoses by the compression of the disc herniation. However, the severe neuropathological changes majorly occurred in the lumbosacral spinal cord. We found more diverse neurodegenerative alterations: the aging-related N-d body (ANB), megaloneurite and N-d homogeneous formazan globule in the lumbosacral spinal cord. We also found that a new circuit pathway (intermedial collateral pathway) showed by a megaloneurite between the lateral collateral pathway and the medial collateral pathway. The enormous notch caused by spinal disc herniation located at the mid-rostral lumber segments. The aging-related neurodegeneration occurred the specific lumbosacral segments. The homogeneous formazan globule was round or oval homogeneous N-d positivity which distributed in the gray matter and dorsal column. In the medulla oblongata, ANBs were revealed in the gracile nucleus, nucleus reticularis lateralis (ventrolateral spinal trigeminal nucleus) and middle of the spinal trigeminal nucleus.

Mast cells (MCs) are best known as key effector cells of immediate type allergic reactions that may even culminate in life-threatening anaphylactic shock syndromes. However, strategically positioned at host-environment interfaces and equipped with a plethora of receptors, MCs also play an important role in the first line defense against pathogens. Their main characteristic, the huge amount of preformed pro-inflammatory mediators embedded in secretory granules, allow for a rapid response and initiation of further immune effector cell recruitment. The same mechanism, however, may account for detrimental overshooting responses. MCs are not only detrimental in MC-driven diseases, but also responsible for disease exacerbation in other inflammatory disorders. Focusing on the skin as the largest immune organ, we herein review both beneficial and detrimental functions of skin MCs all the way from skin barrier integrity via host defense mechanisms to MC-driven inflammatory skin disorders. Moreover, we emphasize the importance of IgE-independent pathways of MC activation and their role in sustained chronic skin inflammation and disease exacerbation.