Abstract: Background: Cancer and cancer treatments may affect aging processes, altering the trajectory of cognitive aging, but extant studies are limited in interval of assessment (2-5 years). We studied cognitive performance in a cohort of survivors and controls utilizing cross-sectional cognitive performance data from age 60 to 89 years as an indicator of potential aging trajectories and contrasted these trends with longitudinal data collected over two years. Methods: Female breast cancer survivors who had been diagnosed and treated at age 60 or older and were 5– to 15-year survivors (N=328) and non-cancer controls (N=158) were assessed at enrollment and at 8, 16 and 24 months with standard neuropsychological tests and comprehensive geriatric as-sessment. Results: Cross-sectional baseline analysis found the expected inverse association of age with cognition in both groups, with survivors performing lower than controls in learning and memory (LM) but not in attention, processing speed and executive function (APE). Younger survivors, i.e., those under 75 years of age, exhibited early decline in performance in both LM and APE compared to controls, with no differences between older survivors and controls, which tracked with deficit accumulation trends. Conclusion: Differences between survivors and controls were prominent in younger survivors, as was deficit accumulation, suggesting a mediating effect on cognition. Deficit accumulation may represent a modifiable risk factor in cancer survivorship that may be targeted for prevention and intervention.

Norepinephrine plays an important role in modulating memory consolidation and evocation through its beta-adrenergic receptors (Adrβ: β1, β2 and β3), which are expressed in the hippocampus (HC) and amygdala (AMY). Here we hypothesized that multisensory stimulation would reverse the memory impairment caused by the inactivation of the Adrβ3 with consequent inhibition of sustained glial-mediated inflammation and glutamatergic depuration. To test this, 21- and 86-day-old Adrβ3KO mice and respective controls underwent to (i) gustative and olfactive stimuli of positive and negative valence associated with (ii) intellectual challenges to reach the food in addition to (iii) objects in hidden places (iv) foraging for 8 weeks followed by (v) analysis of GFAP, Iba-1 and EAAT2 protein expression in the HC and AMY. While this protocol restored the memory impairment when applied to Adrβ3KO animals immediately after weaning, it had no effect when applied to adult animals. In fact, we observed that aging worsens the memory of Adrβ3KO mice. Although no significant expression of GFAP and Iba1 were observed in HC of young and old mice, Adrβ3KO increased EAAT2 expression HC of old mice, while MS didn’t change EAAT2 in young mice but enhanced it expression in older. Relative to AMY of old mice Adrβ3KO increased GFAP expression compared whit WT mice and MS sustained the GFAP expression and increased the EAAT2 expression compared with WT group. These results suggest that a richer and more diverse environment helps to correct memory impairment when applied right after weaning Adrβ3KO animals, also show that the changes in GFAP, Iba1 and EAAT2 expression levels in young and old mice indicate a functional significance in the process of learning and memory and that the control of neuroinflammation in limbic areas mediates this response. They also reinforce the idea that disruption of noradrenergic signaling could be involved in the cognitive impairment observed later in life.

There is increasing evidence that many molecular processes exhibit differences with age 1 and sex. Such differences produces also differences in the insurgence and progression of many 2 complex diseases. For instances, demographic data on insurgence of comorbidities of mellitus 3 diabetes, on lethality of COVID-19, and on some cancers, shows differences between sex and age 4 groups. Therefore, the growing interest on such area requires the management of related data as 5 well as the development of algorithms and tool for the analysis. The availability of omics data 6 annotated with metadata related to age and sex is mandatory for building pipeline of the analysis. 7 The number of databases containing data related to age and sex is hencefort growing. We here show 8 some databases and tools storing such data. Finally, future research direction are highlighte

The transcriptional coactivators YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif) are the main downstream effectors of the evolutionary conserved Hippo signaling pathway. YAP/TAZ is implicated in the transcriptional regulation of target genes that are involved in a wide range of key biological processes affecting tissue homeostasis and play dual roles in the aging process depending on cellular and tissue context. The aim of the present study was to investigate whether pharmacological inhibitors of Yap/Taz may increase the lifespan of Drosophila melanogaster. qRT-PCR was performed to measure the changes in the expression level of Yki (Yorkie, the Drosophila homolog of YAP/TAZ) target genes. We have revealed a lifespan increasing effect of YAP/TAZ inhibitors that was mostly associated with decreased expression level of wg and E2f1 genes. However further analysis is required to understand how YAP/TAZ pathway is linked with aging.

We have previously demonstrated that the acute ingestion of essential amino acids may augment net protein balance in the elderly. Using a double blind, randomized controlled trial, our objective was to compare an experimental meal replacement enriched with essential amino acids (EMR) compared to a commercial meal replacement (Optifast®) provided once/day (q.d.) for four weeks on body composition and physical function in older, obese participants. Twenty-seven individuals (69±5 yrs; body mass index of 32±4 kg/m2) were randomly assigned to EMR (n=13) or Optifast® (n=15) supplementation. Measurements of body composition, skeletal muscle cross-sectional area (CSA), intrahepatic lipid and physical function were completed pre- and post-supplementation. Body mass, fat mass, and visceral fat mass were reduced with EMR but not altered with Optifast®. Thigh muscle CSA increased ( 4.1 ± 1.9 cm2, P = 0.03) with EMR but not Optifast®. There was a significant increase in the distance covered during the six-minute walk test with EMR ( 21±26 m) but no change in Optifast® ( 22±54 m). Improvements in body composition and physical function support the efficacious use of EMR-based meal replacements in the obese elderly.

Fenugreek seeds are widely used in Asia and other places of the world for their nutritive and medicinal properties. In Asia, Fenugreek seeds are also widely recommended for the geriatric populations. Here, we evaluated for the first time the effect of fenugreek seed feed supplementation on the liver antioxidant defense systems in aging mice. The study was conducted on 12 months aged mice which were given fenugreek seed dietary supplement. We have evaluated the activities of various antioxidant defense enzymes like superoxide dismutase (SOD), glutathione reductase (GR), and glutathione peroxidase (GPx), and estimated the phenolics and free radical scavenging properties in mice liver upon fenugreek supplementation. The estimation of SOD, GPx and GR activities in aged mice liver revealed a significant (P<0.01) difference among all the liver enzymes. Overall, this study reveals that fenugreek seed dietary supplementation has a positive effect in on the activities of the hepatic antioxidant defense enzymes in the aged mice.

Background: Melatonin is a potent mitochondrial, cytoprotective and antioxidant molecule with potentially strong anti-aging properties. Topical melatonin has shown to improve the clinical signs of skin aging. Melatosphere™ is a new lipid-based delivery system able to improve stability and skin penetration of melatonin when used in topical formulations. No clinical studies, using objective instrumental data, are available so far regarding the positive effect of Melatosphere™ in improving wrinkles in women with mild-to-moderate skin aging. Study Aim: We evaluate, in an open prospective, evaluator-blinded trial, the effects on skin texture of 2 months treatment with a Melatosphere™ based cream. Subjects and Methods: 15 women aged >45 years with mild to moderate facial skin aging (Glogau score ≥2) participated in the trial, after their informed consent. An ANTERA 3D computer-assisted skin analysis evaluation for the assessment of coarse and fine wrinkles of the periorbital area and melanin content was performed at baseline and after two months of treatment. An evaluator-blinded Investigator Global assessment of skin elastosis, roughness, level of dyscromia, skin dryness and presence of actinic damage was also performed at the same time points using a 4-grade score from 0 (no sign) to 3 (severe sign). Results: At baseline the mean (SD) IGA score was 8.2(1.0). After 2 months the IGA score significantly decrease to 4.2(1.4) (49% reduction) (P=0.0007). ANTERA 3D evaluations showed a significant reduction in skin coarse and fine wrinkles volume in the target area of -31% and -18%, respectively. Melanin content was reduced significantly by -17%. Conclusion: Topical melatonin carried in Melatosphere improves in the short-term signs of skin aging evaluated clinically and by ANTERA 3D device in women with mild to moderate skin aging.

Immune-mediated necrotizing myopathy (IMNM) is a rare and severe disease that corresponds to a specific entity of idiopathic inflammatory myopathy. Patients with IMNM suffer from proximal muscle weakness, and present high levels of creatine kinase and necrotic myofibers. Anti-Signal Recognition Particle (SRP) and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase autoantibodies (HMGCR) have recently been identified in two thirds of patients with IMNM and are used as a hallmark of the disease. In this review, we provide a detailed description of these antibodies and the tests used to detect them in the serum of patients. Based on in vitro studies and mouse models of IMNM, we will discuss the role of autoantibodies in the pathogenesis of the disease. Finally, in the light of the latest knowledge, we will conclude with a review of recent therapeutic approaches.

Three new polyketides (penidihydrocitrinins A–C, 1–3) and 14 known compounds (4–17) were isolated from the deep-sea-derived Penicillium citrinum W17. Their structures were elucidated by comprehensive analyses of 1D and 2D NMR, HRESIMS, and ECD calculations. Compounds 1–17 were evaluated for their anti-inflammatory and anti-osteoporotic bioactivities. All isolates exhibited significant inhibitory effects on microglial activation in LPS-stimulated BV-2 cells in a dose-response manner. Notably, compound 14 displayed the strongest effect with the IC50 value of 4.7 µM. Moreover, compounds 6, 7, and 8 not only suppressed osteoclastogenesis, but also promoted osteoblast mineralization.

Green products have excellent potential for discovering and producing new medicinal products. In recent years, there is a growing interest towards the green synthesis of metal nanoparticles, particularly from plants sources. This eco-friendly approach was used in the recent research to biosynthesize zinc oxide nanoparticles (ZnO NPs) from Cissus antractica plant. The present study aims to examine the cell cytotoxicity, cell death, and pathways of apoptosis in lung cancer cells (A549) and inflammation properties treated with biosynthesized ZnO NPs. Additionally, synthe-sized ZnO nanoparticles were characterized using UV–vis spectroscopy, X-ray diffraction (XRD), Transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FT-IR), and Energy-dispersive X-ray spectroscopy (EDS). The XRD and TEM analyses exhibited 31 nm as the size of synthesized nanoparticles, the pure crystal form of ZnO NPs, and the shape of the NPs as nearly spherical and hexagonal quartzite. The MTT assay used for cytotoxicity evaluation de-picted the significant toxic effect of CA-ZnONPs against the A549 lung cancer cells at concentra-tions up to 20 µg/mL than non-cancerous cells. Furthermore, we observed an elevated ROS level in cancer cells. These NPs also demonstrated dose-dependent ability to suppress colony for-mation and cell migration, which increases their potential as a lung cancer treatment. Further-more, The NPs formulation's ability to induce apoptosis in cancer cells was further supported by Hoechst and propidium iodide dye. Further, CA ZnO NPs increased the gene expression of BAX, Cyto-c, Caspase 3 and 9, but decreased the expression of Bcl-2, indicating that the nanoformulation triggered mitochondrial-mediated apoptosis. Besides, this study showed that NPs suppressed in-flammatory responses by subsequently decreasing reactive oxygen species (ROS) generation, downregulating the expression of the pro-inflammatory cytokines TNF-α, iNOS, COX-2, IL-6, IL-8, and NO. Moreover, the study's findings imply that Cissus antractica are a potential source with biosynthesize nanoparticles that can might be further investigated for the progress of an-ti-inflammatory and anti-cancer drugs with further study.

Acemella oleracea is known as toothache plant belongs to the family of Asteraceae. It is treated as a medicinal remedy like tuberculosis, illness, cough, rheumatism, and illness. This study was concentrated on the antioxidant, cytotoxic, antimicrobial & thrombolytic activities of methanol extract of Acmella oleracea leaves using in vitro model. The antioxidant activity was estimated as trolox equivalent antioxidant capacity utilizing the DPPH and reducing power tests. The plant extract was tested for its cytotoxic action using a brine shrimp lethality bioassay, thrombolytic activity using clot disruption, and antibacterial activity using a disc diffusion assay technique against four distinct gram-positive and gram-negative bacteria. IC₅₀ value of standard ascorbic acid for DPPH was 7.8µg/ml and the IC50 of the methanol extract of Acmella oleracea leaves was 198.34µg/ml that was moderate effect at all compare with ascorbic acid. Thrombolytic assay of Streptokinase as a positive control showed 88.49% where the extract shows 18.69% lytic activity shows the assay. In this study, the sample of LC₅₀ results of cytotoxicity assay was 1.431 µg/mL which can be treated as less activity. Moreover, the extracts showed low to moderate antibacterial activity against both gram-negative and gram-positive bacterial stains (zone of inhibition-10-26 mm). Vibrio Mimicus bacteria stains exhibited the highest level of activity, with a range of 23 for the diameter of the growth inhibition zone. The current review shows leaf extracts of Acmella oleracea may be used as a source of antioxidant and thrombolytic activity, as well as a significant source of antibacterial and anticancer substances. Further research is required to evaluate in-vivo the pharmacological activity of Acmella oleracea leaves in order to identify the essential metabolites and potential mechanisms.

Methotrexate (MTX) is a potent drug for the treatment of various diseases globally amidst being a chemotherapeutic and immunosuppressant agent. However, hepatotoxicity induced by MTX could be life-threatening if left untreated. Folate supplementation is concurrently applied to reduce the adverse effects of MTX, albeit efficacy compromise. Therefore, there is the need to understand the process for the prevention and treatment strategies for MTX induced hepatotoxicity (MIH). In recent times, preliminary preclinical and clinical findings indicate the potential of natural phytobioactive compounds for MIH prevention and treatment. This mini review therefore summarizes proposed mechanisms of MIH and recent advances in the prevention and treatment prospects of natural phytobioactive compounds on MIH.

The use of plant extracts in the synthesis of metal nanoparticles is a very attractive approach in the field of green synthesis. To benefit from the potential synergy between the biological activities of the Moringa oleifera leaves extract and metallic bismuth, our study aimed at synthesizing bismuth nanoparticles using a hydroalcoholic extract of M. oleifera leaves as a means of green synthesis that yields nontoxic products and reduces the production of wasteful material. To this end, the M. oleifera leaves extract was treated with a bismuth nitrate pentahydrate solution. A color change from light brown to dark brown indicates the synthesis of bismuth nanoparticles. The total phenolic content in the M. oleifera leaves extract used was 23.0 ± 0.3 mg gallic acid equivalent/g of dried M. oleifera leaves powder. Antioxidant property of MO synthesised bismuth Nanoparticles was evaluated and in line with the extract used in the synthesis of NPs. The physical properties of the synthesized bismuth nanoparticles were characterized using UV-Vis spectrophotometer, FT-IR spectrometer, TEM, SEM, and XRD. The synthesized bismuth nanoparticles have a size in the range of 40.4-57.8 nm with amorphous morphology. Using DPPH and phosphomolybdate assays, our findings revealed that the M. oleifera leaves extract and the synthesized bismuth nanoparticles possess antioxidant properties. Using resazurin microtiter assay, we also demonstrate that the M. oleifera leaves extract and the synthesized bismuth nanoparticles exert potent anti-bacterial activity against Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus and Enterococcus faecalis, similarly to the inhibition exerted by Moringa extract, especially against Enterococcus faecalis (MIC values for the extract: 500, 250, 250, and 250 µg/mL; MIC values for the bismuth nanoparticles: 500, 500, 500, and 250 µg/mL, respectively). Similarly, the M. oleifera leaves extract and the synthesized bismuth nanoparticles display relatively stronger anti-fungal activity against Aspergillus niger, Aspergillus flavus, Candida albicans, and Candida glabrata (MIC values for the extract: 62.5, 62.5, 125, and 250 µg/mL; MIC values for the bismuth nanoparticles: 250, 250, 62.5, and 62.5 µg/mL, respectively). Thus, the hydroalcoholic extract of M. oleifera leaves was successfully used in the synthesis of bismuth nanoparticles, showing a positive antioxidant, anti-bacterial, and anti-fungal activity. Therefore, the synthesized bismuth nanoparticles can potentially be employed in the alleviation of symptoms associated with oxidative stress and in the topic treatment of Candida infections.

The synthesis of metal nanoparticles using plant extracts is a very promising method in green synthesis. The medicinal value of Moringa oleifera leaves and the anti-microbial activity of metallic copper were combined in the present study to synthesize copper nanoparticles having a desirable added-value inorganic material. The use of a hydroalcoholic extract of M. oleifera leaves for the green synthesis of copper nanoparticles is an attractive method as it leads to the production of harmless chemicals and reduces waste. The total phenolic content in the M. oleifera leaves extract was 23.0 ± 0.3 mg gallic acid equivalent/g of dried M. oleifera leaves powder. The M. oleifera leaves extract was treated with a copper sulphate solution. A color change from brown to black indicates the formation of copper nanoparticles. Characterization of the synthesized copper nanoparticles was performed using UV-Vis spectrophotometer, FT-IR spectrometer, TEM, SEM, and XRD. The synthesized copper nanoparticles have an amorphous nature and particle size of 35.8-49.2 nm. We demonstrate that the M. oleifera leaves extract and the synthesized copper nanoparticles display considerable antioxidant activity. Moreover, the M. oleifera leaves extract and the synthesized copper nanoparticles exert potent anti-bacterial activity against Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, and Enterococcus faecalis (MIC values for the extract: 500, 250, 250, and 250 μg/mL; MIC values for the cooper nanoparticles: 500, 500, 500, and 250 μg/mL, respectively). Similarly, the M. oleifera leaves extract and the synthesized copper nanoparticles exert relatively more potent anti-fungal activity against Aspergillus niger, Aspergillus flavus, Candida albicans, and Candida glabrata (MIC values for the extract: 62.5, 62.5, 125, and 250 μg/mL; MIC values for the cooper nanoparticles: 125, 125, 62.5, and 31.2 μg/mL, respectively). Our study reveals that the green synthesis of copper nanoparticles using a hydroalcoholic extract of M. oleifera leaves was successful. In addition, the synthesized copper nanoparticles can be potentially employed in the treatment of various microbial infections due to their potent antioxidant, anti-bacterial, and anti-fungal activities.

The anti-money laundering (AML) process has failed both in identifying suspicious cases in due time as in assisting the AML analysts in decision making. Starting from a new generic anti-fraud approach, this article presents the main aspects related to the development of a multi-agent system that goes beyond the capture of suspicious transactions, seeking to assist the human expert in the analysis of suspicious behaviour. First, a transactional behavioural profile of clients is obtained in a data mining process. A set of rules, obtained through data mining over a real database, in conjunction with specific rules based on legal aspects and in the expertise of the AML analysts make up the agents' knowledge base. The cases for which the system was unable to suggest a decision are flagged as requiring more detailed analysis. The system analysed 6 months of real transactions and indicated several suspicious profiles, a set of these suspects was investigated by the AML analysts who proved the suspicion of several cases, including some that had not been identified by the systems in execution.

Several vaccines against COVID -19 have been developed and licenced to enhance the immune response against SARS-CoV-2. Similarly, infection with SARS-CoV-2 before vaccination has been shown to provide significant protection against severe infection and hospitalisation. The aim of this study was to investigate the effect of three doses of Sinopharm vaccine and SARS-CoV-2 infection on the specific immune response in 103 volunteers, measuring neutralizing antibodies, anti-S1 IgG, anti-RBD IgM, anti-N IgM, anti-N IgG antibodies and interferon γ. Our results showed that the presence of cardiovascular diseases increased the level of anti-N-IgG antibodies, while endocrinological diseases decreased the level of neutralizing antibodies and anti-N-IgG antibodies, suggesting that these diseases alter the effect of vaccine immunity. In addition, there was a significant decrease in anti-S1 IgG levels 6 months and in anti-N IgG levels 18 months post-infection, while neutralizing antibody and interferon γ levels were constant at 3, 6 and 18 months post-infection. Therefore, our results confirm the importance of hybrid immunity as the strongest and most durable compared to exclusively natural or vaccine-induced immunity. Significant positive correlations were found between humoral and cellular immunity markers: neutralizing antibodies, anti-S1 IgG, anti-N IgG and interferon γ, indicating a unique coordinated response specific to COVID-19.

The process of senescence (aging) is largely determined by the action of wild-type genes. For most organisms, this does not reflect any adaptive function of senescence, but rather evolutionary effects of declining selection against genes with deleterious effects later in life. To understand aging requires an account of how evolutionary mechanisms give rise to pathogenic gene action and late-life disease, that integrates evolutionary (ultimate) and mechanistic (proximate) causes into a single explanation. A well-supported evolutionary explanation by G.C. Williams argues that senescence can evolve due to pleiotropic effects of alleles with antagonistic effects on fitness and late-life health (antagonistic pleiotropy, AP). What has remained unclear is how gene action gives rise to late-life disease pathophysiology. One ultimate-proximate account is T.B.L. Kirkwood’s disposable soma theory. Based on the hypothesis that stochastic molecular damage causes senescence, this reasons that aging is coupled to reproductive fitness due to preferential investment of resources into reproduction, rather than somatic maintenance. An alternative and more recent ultimate-proximate theory argues that aging is largely caused by programmatic, developmental-type mechanisms. Here ideas about AP and programmatic aging are reviewed, particularly those of M.V. Blagosklonny (the hyperfunction theory) and J.P. de Magalhães (the developmental theory), and their capacity to make sense of diverse experimental findings is described.

The extraocular muscles (EOMs) possess unique characteristics that set them apart from other skeletal muscles. These muscles, responsible for eye movements, exhibit remarkable resistance to various muscular dystrophies and aging, presenting a significant contrast to the vulnerability of skeletal muscles to these conditions. In this review, we delve into the cellular and molecular underpinnings of the distinct properties of EOMs. We explore their structural complexity, highlighting differences in fiber types, innervation patterns, and developmental origins. Notably, EOM fibers express a diverse array of myosin heavy chain isoforms, retaining embryonic forms into adulthood. Moreover, their motor innervation is characterized by a high ratio of nerve fibers to muscle fibers and the presence of unique neuromuscular junctions. These features contribute to the specialized functions of EOMs, including rapid and precise eye movements. Understanding the mechanisms behind the resilience of EOMs to disease and aging may offer insights into potential therapeutic strategies for treating muscular dystrophies and myopathies affecting other skeletal muscles.

Sensory processing is a crucial function of the nervous system that significantly affects a large portion of the population, particularly older individuals who may be dealing with different forms of dementia. The global population of people aged 65 or older has reached a substantial count of around 703 million, representing approximately 9% of the total global population. Within this demographic, an estimated 5-8% of those aged 60, highlighting the growing need to address sensory modulation challenges for healthy aging. Sensory diet, derived from sensory integration theory, provide a tailored approach to modulating sensory experiences and triggering neuroplastic changes in the brain. Recent neuroimaging studies have revealed intricate structural and functional alterations in the brain associated with the implementation of sensory diets. Furthermore, the integration of the Metaverse, augmented reality, and virtual reality has opened up personalized experiences, fostering cognitive stimulation and emotional well-being for individuals during aging. This article offers a comprehensive exploration of the effectiveness of sensory diets in enhancing attentional control, self-regulation, and alleviating sensory-related distress among the healthy aging and dementia population. By employing precise quantitative evaluations such as sensory processing scales and advanced neuroimaging methodologies, it presents solid evidence of the tangible impact of these interventions. Emphasizing the importance of interdisciplinary cooperation and leveraging technological advancements, the article underscores the crucial need for customized sensory diets to optimize sensory processing and improve the overall well-being of older individuals contending with sensory modulation challenges and dementia.

Human longevity is an important but difficult goal due to the extreme complication of human body. If people could repeatedly transfer their consciousness from old bodies to new ones, their lifespan might be prolonged extremely. However, there are several difficulties which prevent the achievement of such a technique. In this paper, we propose an approach that can transfer human consciousness indirectly, and avoid or significantly relieve those difficulties. The strategy of our approach is to integrate the consciousnesses of two bodies (old and new) into a unique consciousness. By doing so, the consciousness is extended to the new body. After that, the consciousness shrinks and remains in the new body when the old body dies. This may also apply to integrating more than two bodies of human, or animal, or even across different species. After investigating thousands of literatures, we find quite strong evidence (related discoveries and technologies) that can support the proposed approach and its advantages. Beside prolonging human lifespan, the approach could also have other meaningful applications.

Abstract: Down Syndrome (DS) is a common genetic disorder characterized by an extra copy of chromosome 21, leading to dysregulation of various metabolic pathways. Oxidative stress in DS is associated with neurodevelopmental defects, neuronal dysfunction, and the onset of dementia re-sembling Alzheimer's disease. Additionally, chronic oxidative stress contributes to cardiovascular diseases and certain cancers prevalent in DS individuals. This study investigates the impact of ageing on oxidative stress and liver fibrosis using a DS murine model (Ts2Cje mice). The liver in DS mice shows increased oxidative stress and impaired antioxidant defenses, as evidenced by reduced glutathione levels and increased lipid peroxidation. Furthermore, DS liver exhibits an altered in-flammatory response as measured by the expression of cytokines and heat shock proteins. DS liver also displays dysregulated lipid metabolism, indicated by altered expression of peroxisome prolif-erator-activated receptors and fatty acid transport proteins. Consistently, these changes might contribute to non-alcoholic fatty liver disease development, a condition characterized by liver fat accumulation. Finally, histological analysis of DS liver reveals increased fibrosis and steatosis, in-dicative of potential progression to liver cirrhosis. This finding highlights the increased risk of liver pathologies in DS individuals, particularly when combined with the higher prevalence of obesity and metabolic dysfunctions in DS patients. These results shed light on the liver's role in DS-associated pathologies and suggest potential therapeutic strategies targeting oxidative stress and lipid metabolism to prevent or mitigate liver-related complications in DS individuals.

The second external cause of death from unintentional injuries is falls in people over 60, a worldwide public health problem. Associated factors are identified early in Primary Health Care. Thus, we analyze professional narratives about older adults/old age and the organization of services in the presence of fall-inducing frailty. A structured narrative was applied under the following stages: understanding the context; setting/plot/character analysis; and interpretive synthesis. Data were collected from August to November 2022, distributing 21 health professionals in three Narrative Focus Groups. In the analyses, the collective conceptions dialogued with Bourdieu’s Epistemology of field, habitus, and capital. Among the results, technical and common sense representations of older adults were simultaneously observed, along with the belief of old age as a problematic life stage. Care is centered on the installed disease/ailment. Encouraging autonomy and self-care emerges in integrative health practices, which older adults underestimate. Professionals access the lives of older adults according to their habitus, which, in turn, is structured (structuring) in the disputes for installed capital. Thus, the care provided disregards subjectivities and symbolic systems associated with falls.

The effects of 0.4wt.% Sc addition on a typical Al-Si10-Mg alloy were systematically investigated in the present research. Samples with and without Sc produced refined dendritic arranged microstructures with sensitivity to the aging treatment after solidification, particularly in the case of the alloy without Sc. After being exposed to 300°C for 90 minutes, the dendritic spacing nearly doubled in the Al-10wt.%Si-0.45wt.%Mg samples. The rapidly solidified microstructures were constituted by the -Al dendritic phase surrounded by eutectic phases/intermetallics such as Si, Mg2Si and Al3Sc (in the case of the alloy containing Sc). 255°C and 300°C were deemed most appropriate temperatures for aging treatments, with four exposure times of up to 120 minutes tested for each alloy. The heat treatments allowed the Vickers hardness profiles to be plotted and compared. Moreover, in order to detect both Sc- and Mg- precipitates after aging, specific samples have been prepared for either SEM or TEM analyses. At first, the results pointed to a strong precipitate-related hardening effect formed as a result of the Sc addition to the alloy. All samples containing Sc showed a higher hardness value when compared to their respective treated samples without Sc. Secondly, when comparing the Al-10Si-Mg-Sc alloy samples among themselves after being treated at different conditions, high temperatures and excessive treatment times can become detrimental to the hardness. This was due to the growth of larger Sc-bearing precipitates of approximately 1 µm in size under such conditions, having less pronounced hardening effect. The best condition (255°C for 60 min) for as centrifuged samples in Cu-mold produced very fine dispersion of Mg- and Sc- intermetallics (~200 nm in size) with a peak hardness of 110 HV.

Aging is a complex biological process, with gradual and progressive decline in structure and function in many organ systems. Our objective is to determine if structural changes produced by aging, vary with sex, in a stressful situation such as dehydration. The expression of Slc12a3 mRNA in renal cortex, α-smooth muscle actin (α-SMA) and fibronectin, was evaluated in male and female rats aged 3 and 18 months submitted or not to water deprivation (WD) for 48 hours. When comparing ages, 18-month-old males showed lower expression of Slc12a3 mRNA than 3-month-old males, and control and WD 18-moth-old male and female rats exhibited higher expression of α-SMA than respective 3-month-old rats. Fibronectin was higher in both control and WD 18-month-old males than respective 3-month-old males. In females, only control 18-month-old rats showed higher fibronectin than control 3-month-old rats. When we compared sex, control and WD 3-month-old female rats had lower expression of Slc12a3 mRNA than re-spective males. WD 18-month-old male rats presented higher expression of fibronectin and α-SMA than WD 18-month-old female rats. When we compared hydric condition, WD 18-month-old males displayed lower relative expression of Slc12a3 mRNA and higher α-SMA expression than control 18-month-old males. Aging, sex, and dehydration lead to alteration in kidney structure.

We have developed a self-consistent model for predicting velocity of 1/2[111] screw dislocation in binary iron--carbon alloys gliding by a high-temperature Peierls mechanism. The methodology of modelling includes: (i) Kinetic Monte-Carlo (kMC) simulation of carbon segregation in dislocation core and determination the total carbon occupancy of the core binding sites; (ii) Determination of kink-pair formation enthalpy of a screw dislocation in iron---carbon alloy; (iii) KMC simulation of carbon drag and determination of maximal dislocation velocity at which the atmosphere of carbon atoms can follow a moving screw dislocation; (iv) Self consistent calculation of average velocity of screw dislocation in binary iron--carbon alloys gliding by a high-temperature kink-pair mechanism under constant strain rate. We conduct a quantitative analysis of the conditions of stress and temperature at which screw dislocation glide in iron--carbon alloy is accomplished by a high-temperature kink-pair mechanism. We estimate the dislocation's velocity at which screw dislocation brakes away from the carbon cloud and thermally-activated smooth dislocation propagation is interrupted by sporadic bursts controlled by athermal dislocation activity.

PSD-95 (Dlg4) is an ionotropic glutamate receptor scaffolding protein essential in synapse stability and neurotransmission. PSD-95 levels are reduced during aging and in neurodegenerative diseases like Huntington’s disease (HD), and it is believed to contribute to synaptic dysfunction and behavioral deficits. However, the mechanism responsible for PSD-95 dysregulation under these conditions is unknown. The Heat Shock transcription Factor 1 (HSF1), canonically known for its role in protein homeostasis, is also depleted in both aging and HD. Synaptic protein levels, including PSD-95, are influenced by alterations in HSF1 levels and activity, but the direct regulatory relationship between PSD-95 and HSF1 has yet to be determined. Here, we showed that HSF1 chronic or acute depletion in cell lines and mice decreased PSD-95 expression. Furthermore, HSF1(+/-) mice had reduced PSD-95 synaptic puncta that paralleled a loss in thalamo-striatal excitatory synapses, an important circuit disrupted early in HD. We demonstrated that HSF1 binds to regulatory elements present in the PSD-95 gene and directly regulates PSD-95 expression. HSF1 DNA-binding on the PSD-95 gene was disrupted in an age-dependent manner in WT mice and worsened in HD cells and mice, leading to reduced PSD-95 levels. These results demonstrate a direct role of HSF1 in synaptic gene regulation that has important implications in synapse maintenance in basal and pathological conditions.

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.

With the goal of representing common denominators of aging in different organisms López-Otín et al. in 2013 described nine hallmarks of aging. Since then, this representation has become a major reference point for the biogerontology field. The template for the hallmarks of aging account originated from landmark papers by Hanahan and Weinberg (2000, 2011) defining first six and later ten hallmarks of cancer. Here we assess the strengths and weaknesses of the hallmarks of aging account. As a checklist of diverse major foci of current aging research, it has provided a useful shared overview for biogerontology during a time of transition in the field. It also seems useful in applied biogerontology, to identify interventions (e.g. drugs) that impact multiple symptomatic features of aging. However, while the hallmarks of cancer provide a paradigmatic account of the causes of cancer with profound explanatory power, the hallmarks of aging do not. A worry is that as a non-paradigm the hallmarks of aging have obscured the urgent need to define a genuine paradigm, one that can provide a useful basis for understanding the mechanistic causes of the diverse aging pathologies. We argue that biogerontology must look and move beyond the hallmarks to understand the process of aging.

Background and Objectives: Blood flow restriction (BFR) has been investigated as an alternative method combined with resistance training or AT to promote different health benefits for older people. Nevertheless, no study analyzed chronic effects of BFR on muscle activation in this population, and in some investigations, the application of BFR has been employed arbitrary pressures, which can be a serious methodological error, both from the results and of the risk to the health of the older. Thus, this study analyzed the effect of 24 weeks of walking with BFR on activation and muscle strength in elderly women with osteoporosis. Materials and Methods: Thirty older women (66.0±4.6 years) performed randomly to one of three training groups: WALK (moderate-intensity walking), WALK+BFR (low-intensity walking with BFR), or BFR (BFR alone). Muscle activation (sEMG) and strength of knee flexors and extensors were measured pre-intervention and after 12 and 24 weeks. Results: Only a trivial effect size (ES) for the WALK+BFR (ES= 0.16) was observed in sEMG of the knee flexors compared to WALK. A moderate effect was observed in sEMG of the knee extensors (ES= 0.65) for the WALK+BFR compared to the WALK. However, adverse effects were found in the strength of the knee flexors for the BFR (ES= −0.86) and WALK+BFR (ES= −0.69) compared to WALK. Adverse and null effects, respectively for the BFR (ES= −0.16) and WALK+BFR (ES= 0.06) groups, were also observed on the strength gain of the knee extensors. Conclusions: Low-intensity walk combined with BFR does not provide relevant chronic effects on strength gain or even limit muscle strength gain, however, due to greater activation of knee extensors over 24 weeks, it is possible to benefit from the use of similar strategies to obtain neuromuscular gains in the long‐term for elderly women with osteopenia and osteoporosis.

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).

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.

Dual energy X-ray absorptiometry (DEXA) measuring tool is a reliable and accurate technology to measure bone density and bone mineral composition. This research examined the composition and bone density (bone mineral composition and bone mineral density) of the whole body and representative body parts using DEXA. The participants were 240 healthy adult men and women who were divided into three groups based on age. The total bone mineral density (BMD) of women amounted to an average of 1.14 g/㎠ in Group A, 1.14 g/㎠ in Group B, and 0.98 g/㎠ in Group C. For men, the average BMD was 1.25 g/㎠ in Group A, 1.20 g/㎠ in Group B, and 1.17 g/㎠ in Group C. As a result, the reduction of age-specific BMD was shown to have a correlation with aging and body mass index(BMI), and it is determined that exercising on a regular basis can prevent reduction in BMD by maintaining appropriate muscle mass.

Osteosarcopenic obesity (OSO) is described by the simultaneous presence of osteopenia/osteoporosis, sarcopenia, and increased adiposity. Over time, older adults with OSO syndrome might be at greater risk for loss of physical function and bone fractures. Furthermore, a sedentary lifestyle, inadequate nutrition, pharmaceutical drugs and chronic conditions encompass the multifactorial nature of OSO syndrome. Physical activity and a healthy diet play a crucial role in management and treatment of OSO syndrome. Research has shown that even low-intensity physical activity or daily habitual activity can maintain bone mineral density, muscle strength and improve muscle quality, and reduce adiposity. However, older adults with high risk of fall and injuries require tailored exercise intensity. Also, balanced daily intake of vitamin D, calcium and protein is important in prevention and treatment of OSO syndrome in postmenopausal women. Effective measurement of bone mass, muscle mass and strength is required when detecting OSO syndrome and to evaluate the balance, strength and endurance of elder individuals and severity of the condition.

The increase in the average lifespan and the consequent proportional growth of the elderly segment of society has furthered the interest in studying ageing processes. Ageing may be considered a multifactorial process derived from the interaction between genetic and environmental factors including lifestyle. There is ample evidence in many species that the maximum age attainable (maximum lifespan potential, MLSP) is genetically determined and several mitochondrial DNA polymorphisms are associated with longevity. Many studies have shown that most of the phenotypic characteristics observed in the aging process are the result of the occurrence, with age, of a low grade chronic pro-inflammatory status called "inflammaging", partially under genetic control. The term indicate that aging is accompanied by a low degree of chronic inflammatory, an up-regulation of inflammatory response and that inflammatory changes are common to many age-related diseases. Therefore, the theory of oxidation-inflammation was proposed as the main cause of aging. Accordingly, the chronic oxidative stress, that appears with age, affects all cells and especially those of the regulatory systems, such as the nervous, endocrine, and immune systems and the communication between them. This prevents an adequate homeostasis and, therefore, the preservation of health. It was also proposed that the immune system plays a key role in the aging process, specifically in the rate of aging, since there is a relationship between the redox state and functional capacity of immune cells and longevity of individuals. Moreover, the role of the immune system in senescence could be of universal application. A confirmation of the central role of the immune system in oxi-inflamm-aging is that the administrationintake? of adequate amounts of antioxidants in the diet improves immune function, decreases their oxidative stress, and consequently increases longevity. The promotion of healthy lifestyles is one of the major goals of governments and international agencies all over the world. Human molecular processes are influenced by both physiological pathways and exogenous factors which include, for instance, those originating from diet. Dietary intake has substantive effects on molecular processes of metabolic health. Nutrients can directly regulate physiological changes in human body. In fact, in addition to have an energetic and structural value, nutritional intake provides bioactive molecules which are selectively able to modulate specific metabolic pathways, noticeably affecting cardiovascular and neoplastic diseases development or progress. Numerous bioactive nutrients are being progressively identified and their chemopreventive effects are being described at clinical and molecular mechanism levels. Systematic analyses comprise all “omics” technologies (such as transcriptomics, proteomics and metabolomics) and the goal is to investigate bioactive molecules effects derived from the diet. Nutrigenomic knowledge on physiologic status and disease risk will provide both developments of better diagnostic procedures and of new therapeutic strategies specifically targeted on nutritionally relevant processes. The present review was aimed to understand the molecular mechanisms underlying beneficial effects of bioactive nutrients and nutrigenomics on age-related diseases.

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.

Hydrogenated water has emerged as a novel approach in the field of health and wellness. It is be-lieved to have potent antioxidant properties that can neutralize harmful free radicals in the hu-man body. It has also been shown to be beneficial in mitigating oxidative stress-induced damage through its anti-inflammatory and anti-apoptotic pathways. We aim to conduct a systematic re-view to evaluate the potential benefits of hydrogenated water. The review protocol was uploaded on PROSPERO. After the initial search criteria, the articles were reviewed by two blinded inves-tigators, and a total of 25 articles were included in the systematic review. The potential benefits of hydrogenated water on various aspects of health, including exercise capacity, physical endurance, liver function, cardiovascular disease, mental health, COVID-19, oxidative stress, and anti-aging research, are a subject of growing interest and ongoing research. Although preliminary results in clinical trials and studies are encouraging, further research with larger sample sizes and rigor-ous methodologies is needed to substantiate these findings. Current research needs to fully ex-plain the mechanisms behind the potential benefits of hydrogenated water. Continued scientific exploration will provide valuable insights into the potential of hydrogenated water as an adjunc-tive therapeutic approach in the future.

A healthy cornea is a nonvascularized, transparent tissue. It is nourished by diffusion through the tear film, aqueous fluid and neurotrophins supplied by the corneal innervation. The cornea is devoid of both blood and lymphatic vessels, which makes it an immunologi-cally privileged tissue. Corneal neovascularization develops due to an imbalance between angiogenic and anti-angiogenic factors and can lead to a significant decrease in visual acui-ty. It may cause scarring, lipid keratopathy, and corneal edema. The resulting pathological vascularization of the cornea reduces its immune privilege and significantly worsens the prognosis after subsequent penetrating keratoplasty, increasing the risk of rejection of the transplanted flap. Neovascularization is favored by many disease processes, including auto-immune diseases, viral inflammations, mainly herpes and varicella-zoster, and blepharitis [1]. There are several options to treat corneal neovascularization, both pharmacological and surgical. Angiostatic treatment involves inhibiting the growth of new vessels by suppressing inflammatory responses. VEGF inhibitors, steroids, cyclosporine A, and amniotic membrane grafts secured to the cornea work this way. VEGF inhibitors are the agents with the direct and most potent angiostatic effect. Angioregressive treatment, on the other hand, results in the regression of already existing pathological vessels. This therapy is also based on VEGF inhibitors, which, however, have the most potent effect on newly formed and small vessels but are less effective in reducing large-caliber and mature vessels. A more effective method for such vessels is ablation, which involves surgical closure. The most commonly used an-gio-occlusive method is needle diathermy and argon or yellow laser therapy. In advanced corneal neovascularization, corneal transplant surgery may be necessary. It is best performed after pretreatment with anti-VEGF preparations, often continued after corneal transplanta-tion to reduce the risk of transplant rejection [2]. This paper discusses the pathogenesis of corneal neovascularization and the current and future trends in its treatment.

Quinoa, known as the "golden grain" for its high nutritional value, is a significant source of essential nutrients, including proteins, minerals, vitamins, polyphenols, phytosterols, and flavonoids. However, the biological functions of quinoa polysaccharides remain understudied. In this research, two crude quinoa polysaccharides extracts (Q-40 and Q-60) were obtained extracting by 40% and 60% alcohol. The purity of Q-40 and Q-60 was 58.29% and 62.15%, with protein contents of 8.27% and 9.60%, respectively. Monosaccharide analysis revealed that Q-40 contained glucose (Glc), galacturonic acid (GalA), and arabinose (Ara) in a molar ratio of 0.967:0.027:0.006. Q-60 was composed of xylose (xyl), arabinose (Ara), galactose, and galacturonic acid (GalA) with a molar ratio of 0.889:0.036:0.034:0.020. The average molecular weight of Q-40 ranged from 47484 to 626488 Da, while Q-60 showed a range of 10025 to 47990 Da. Rheological experiments showed that Q-40 exhibited higher viscosity, while Q-60 demonstrated more elastic properties. Remarkably, Q-60 showed potent antioxidant abilities, with scavenging rates of 98.49% for DPPH and 57.5% for ABTS. Antibacterial experiments using the microdilution method revealed that Q-40 inhibited the growth of Methicillin-resistant Staphylococcus aureus (MRSA) and E. coli, while Q-60 specifically inhibited MRSA. At lower concentrations, both polysaccharides inhibited MDA cell proliferation, but at higher concentrations, they promoted proliferation. Similar proliferation-promoting effects were observed in HepG2 cells. The research provides important information in application of quinoa in food and functional food industries.

Rhizophora mangle L. is a well-known medicinal plant found in mangroves worldwide used to treatment diabetes. This study evaluated the chemical composition of the acetonic extract from Rhizophora mangle barks (AERM), by HPLC-PDA and FIA-ESI-IT-MS/MS and the effects on high-fat diet induced obesity in mice and its mechanism of action by gene expression of inflammatory markers (Pparg, Ppara, Srebf1, Cd36, Tnf, Ccl2, Lep, Il10, Il6, Fasn, 18s). High-fat diet fed mice during 12 weeks was used as model of obesity and associated alterations. The results were very satisfactory, the extract, rich in polyphenolic compounds, flavonoids and phenolic acids, displayed intense antioxidant activity in vitro (608 µmol Trolox/g), and showed excellent activity against non-alcoholic fatty liver disease (NAFLD) and reverse insulin resistance in a model of diet-induced obesity. We can registered a modulatory effect of AERM in liver PPAR-γ mRNA expression associated to an important inhibition of CD36 mRNA expression suggesting that AERM induces the down regulation of CD36 mRNA via PPAR-gamma inhibition. These results support the traditional knowledge about the use of R. mangle for the treatment of type 2 diabetes and reveal the potential of AERM for the treatment of NAFLD and management of obesity and comorbidities.

To investigate factors associated with the success of switching to faricimab for type 1 macular neovascularization (MNV) refractory to intravitreal aflibercept (IVA). This retrospective cohort study included patients with type 1 MNV who were switched to faricimab because they were refractory to IVA at two centers. The main outcome was an extension of the treatment interval after 6 months, and factors related to the success or failure of the extension and visual and anatomical outcomes were assessed. The analysis included 43 eyes of 43 patients. Extended dosing intervals of more than 2 weeks were identified in 14 eyes (32.6%). A short dosing interval before the switch, the absence of polypoidal lesions, and a thin central choroidal thickness before the switch were identified as factors involved in successful extension. For patients with refractory type 1 MNV, switching to faricimab is a safe and potential option to extend from existing dosing intervals.

Our report presents the findings from a treatment program that involved plant-based diets (PBDs) and supplements for 1,750 elderly cardiology patients diagnosed with COVID-19 between April 2020 and June 2023. At the start of the program, there was no published data supporting the use of PBDs for COVID-19 patients. However, after 18 months, studies were released that indicated the effectiveness of PBDs in decreasing the incidence and severity of COVID-19. Our treatment protocol differed from these studies in several ways. We carefully controlled the quality, quantity, and processing method of the foods we provided, opting for raw instead of cooked vegetables. Additionally, we incorporated supplementation that complemented the nutrients lacking in a PBD and enhanced the anti-viral, anti-inflammatory, antioxidant, antithrombotic, and immunomodulatory properties of a PBD. Our patients recovered faster (12±1.4 days vs. 20.9±4.3 days), with lower severity (2% vs. 10-20%), hospitalizations (0 vs. 5-10%), and deaths (0 vs. 15-17%) compared to the general population. These favorable outcomes are particularly noteworthy given Indonesia's high COVID-19 morbidity and mortality rates, among the highest in Asia. The findings of this report provide valuable insights for practitioners in managing high-risk elderly COVID-19 patients, particularly in avoiding severity and mortality.

The goal of this study was to develop a rapid diagnostic kit for rheumatic disease and systemic lupus erythematosus (SLE) screening. A novel rapid vertical flow assay (VFA) was engineered and used to assay anti-nuclear (ANA) and anti-dsDNA (αDNA) autoantibodies from systemic lupus erythematosus (SLE) patients and healthy controls (HC). Observer scores and absolute signal intensities from the VFA were validated by ELISA. The rapid ten minute point of care VFA test engineered demonstrated a limit of detection of 0.5 IU/ml for ANA and αDNA autoantibodies in human plasma with inter-operator CV of 19% for ANA and 12% for αDNA. Storage stability was verified over a three-month period. When testing anti-dsDNA and ANA levels in 22 SLE and 18 HC serum samples, the duplex VFA revealed 95% sensitivity, 72% specificity and 84% accuracy in discriminating disease groups, comparable to the gold standard, ELISA. The rapid αDNA/ANA duplex VFA can potentially be used in primary care clinics for evaluating patients or at-risk subjects for rheumatic diseases and for planning follow-up testing. Given its low cost, ease and rapid turnaround, it can also be used to assess SLE prevalence estimates.

Neuromyelitis Optica Spectrum Disorder (NMOSD) is a rare immune-mediated relapsing-remitting disease of the central nervous system. The usage of rituximab, to prevent NMOSD relapses, is common in Sweden, but the knowledge on long-term efficacy and risk for severe infections are limited. We performed a retrospective cohort study with medical chart review of rituximab-treated NMOSD patients at the Karolinska University Hospital, Sweden, to assess the occurrence of relapses and severe infectious events (SIE). Furthermore, we collected data on CD19+ lymphocyte, and IgG levels during therapy. A total of 42 NMOSD patients; 24 with aquaporin -4 antibodies (AQP4+), eight with myelin oligodendrocyte glycoprotein antibodies (MOG+) and 10 with absence of antibodies (double-seronegative) were included. During a mean treatment time of 4.4 years, 37% AQP4+, 75% MOG+, and 60% double-seronegative patients experienced 1 relapse. SIEs were common with 46% of AQP4+, 25% of MOG+, and 40% of double-seronegative patients affected. Incomplete CD19+ lymphocyte suppression did not predict a relapse and there was no correlation between IgG levels and SIEs. In conclusion, our data demonstrated a high risk for both relapses and SIEs in rituximab-treated NMOSD patients highlighting the need for close clinical vigilance of disease activity and infections during treatment.

More than 15,000 prescriptions and over the counter drugs are available according to the US Food and Drug Administration website. Moreover, several herbal medicines and dietary supplements are readily available to add to the list of possible drugs, which can potentially cause adverse drug interactions. These are a pressing concern for all as they can interfere with many dental procedures. Additionally, the number of geriatric patients seen in routine dental practice has increased over time. This implies that there are more patients with multiple diseases and health conditions like hypertension, diabetes, problems associated with the cardiovascular, renal and gastrointestinal systems, arthritis, osteoporosis, etc. All these require patients to be on certain medications. Furthermore, advancement in the dental field has led to more complex dental procedures (implants, grafts) being carried out in a general dental practice. These advanced and slightly more invasive treatments require the use of certain drugs before, during and after the treatment like local anesthetics, vasoconstrictors, anxiolytics, analgesics and antibiotics. All of these can possibly interact with medications a patient is already taking and can also interfere with the current dental treatment and create complications. This article aims to provide necessary information about commonly encountered systemic diseases and associated treating medications, their mechanism of action, possible complications and their management. The classes of drugs discussed include anti-platelet agents, vitamin K antagonists, novel oral anticoagulants, bisphosphonates, disease-modifying anti-rheumatic drugs and oral contraceptives.

Abstract: This study reviewed aspects of the biology of two members of the glucosinolate family, namely sinigrin and glucoraphanin and their anti-tumour and anti-microbial properties. Sinigrin and glucoraphanin are converted by the β-sulphoglucosidase myrosinase or the gut microbiota into their bioactive forms, allyl isothiocyanate (AITC) and sulphoraphanin (SFN) which constitute part of a sophisticated defence system plants developed over several hundred million years of evolution to protect them from parasitic attack from aphids, ticks, bacteria or nematodes. Delivery of these components from consumption of cruciferous vegetables rich in the glucosinolates also delivers many other members of the glucosinolate family so the dietary AITCs and SFN do not act in isolation. In-vitro experiments with purified AITC and SFN have demonstrated their therapeutic utility as antimicrobials against a range of clinically important bacteria and fungi. AITC and SFN are as potent as Vancomycin in the treatment of bacteria listed by the World Health Organisation as antibiotic-resistant "priority pathogens" and also act as anti- cancer agents through the induction of phase II antioxidant enzymes which inactivate potential carcinogens. Glucosinolates may be useful in the treatment of biofilms formed on medical implants and catheters by problematic pathogenic bacteria such as Pseudomonas aeruginosa and Staphylococcus aureus and are potent antimicrobials against a range of clinically important bacteria and fungi. The glucosinolates have also been applied in the prevention of bacterial and fungal spoilage of food products in advanced atmospheric packaging technology which improves the shelf-life of these products.

Sleep is an essential component of a healthy lifespan, influencing both physical and mental well-being along with good quality of life. Adequate sleep quality and quantity are associated with a host of health advantages, including enhanced immune function, learning and memory, emotional well-being, and cardiovascular health. Chronic sleep deprivation, or poor sleep quality, is associated with a variety of negative health outcomes, including an increased risk of obesity, diabetes, hypertension, depression, cancer, and even premature death. One compelling argument in favor of sleep as a predictor of a healthy lifespan is its effect on cellular repair and regeneration. During sleep, the body goes through important activities such as tissue repair, muscular growth, and memory consolidation. Sleep also helps the brain eliminate toxins and metabolic waste, which contributes to its optimal functioning. Without adequate sleep, these important processes are jeopardized, resulting in accelerated aging and greater susceptibility to chronic illnesses. Furthermore, sleep is essential for maintaining hormone balance, particularly those involved in appetite regulation and metabolism. Sleep disturbances can disrupt the regulation of these hormones, resulting in weight gain, metabolic diseases, and, ultimately, a shorter life span. Finally, prioritizing optimal sleep is pivotal for increasing longevity and general health. Emphasizing the importance of sleep hygiene and treating sleep-related dysfunctions should be part of the modern approach to extending healthy life.

Brain aging causes a wide variety of changes at molecular and cellular levels, leading to the decline of cognitive functions and increased vulnerability to neurodegenerative disorders. The research aimed at understanding the aging of the brain has made much progress in recent decades. Technological innovations such as single-cell RNA-sequencing (scRNA-seq), proteomic analyses, and spatial transcriptomic analyses have facilitated the research on the dynamic changes occurring within neurons, glia, and other cells along with their impacts on intercellular communication during aging. In this review, we introduce recent trends of how neurons and glia change during aging and discuss the impact of the brain microenvironment such as the blood-brain barrier (BBB).

Pregnancy at advanced maternal age (AMA) is a condition of potential risk for the development of maternal-fetal complications with possible repercussions even in the long-term. Here, we analyzed the changes of plasma redox balance and the effects of plasma on human umbilical cord mesenchymal cells (hUMSCs) in AMA pregnant women (patients) at various timing of pregnancy. One hundred patients and twenty pregnant women younger than 40 years (controls) were recruited, and evaluated at various timings during pregnancy until after delivery. Plasma samples were used to measure the thiobarbituric acid reactive substances (TBARS), glutathione and nitric oxide (NO). In addition, plasma was used to stimulate the hUMSCs, which were tested for cell viability, reactive oxygen species (ROS) and NO release. The obtained results showed that throughout pregnancy until after delivery in patients the levels of plasma glutathione and NO were lower than those of controls, while those of TBARS were higher. Moreover, plasma of patients reduced cell viability and NO release, and increased ROS release in hUMSCs. Our results highlighted alterations in the redox balance and the presence of potentially harmful circulating factors in plasma of patients They could have clinical relevance for the prevention of complications related to AMA pregnancy.

The operation of transformers suffers from natural or man-made disasters, subjecting the equipment to prolonged exposure to temperature, lightning strikes, transient over-voltages, and over-current, gradually producing insulation aging phenomenon, which results in partial discharges within the transformer. Without dealing with it beforehand properly, it may lead to insulation breakdown. Nowadays, with the mature development of microchip control technology and wireless communication technology, which is helpful for realizing the research for online real-time and long-term monitoring capabilities for power equipment. A transformer operating condition monitoring and diagnostic system that can rapidly and effectively prevent the breakdown of transformer insulation, which can impact the overall power supply system is developed in this paper. The system is divided into two parts based on its function. The first part is the operating condition monitoring and real-time alert unit for the transformer, primarily composed of an embedded computing module, a sensor module, and a transmission module. Its work content is to capture real-time online partial discharge ultrasonic signals and high frequency current comparator pulse signals, and analyze and determine the condition of the internal insulation and operational status whether it is fault or not. The second part is the central control unit, consisting mainly of an industrial computer and a transmission module. Its work content is to store the ultrasonic and high frequency current comparator pulse signals from the transformer operation monitoring and real-time alert unit. It uses the software to eliminate signal noise and interference, and then utilizes artificial neural networks to identify the type of fault. In this paper, the research for the phenomenon of insulation degradation in transformer equipment aims to establish aging trend profiles through the dual malfunctioning alert and aging process analysis, as well as the long-term measurement of ultrasonic signals from partial discharges and high-frequency current comparator pulse signals. This approach provides crucial reference data and a foundation for disposable on-site measurement, assessing the phenomenon of insulation aging stages, defects and damage of the transformers effectively. It allows for timely replacement or maintenance in advance, achieving the prevention of malfunctioning and predictive diagnosis of aging.

We conducted a hybrid-design study on a historical cohort of 359 adult recipients of a liver graft who received transplants between 1996 and 2002. The study aimed to identify predictors of survival and investigate the prevalence of co-morbidities among long-term survivors. The actuarial (95% CI) patient survival of the overall study cohort was 96% (94.6%-98.3%), 69% (64.2%-73.6%), 55% (49.8%-59.9%), 42.8% (37.6%-47.8%), and 34% (29.2%-38.9%) at 1, 5, 10, 15, and 20 years, respectively. The actuarial (95% CI) graft survival was 93.8% (91.6%-97.2%), 67.6% (62.2%-71.5%), 54.3% (49.6%-59.3%), 42.1% (37.3%-47.4%), and 33.8% (29.0%-38.4%) at 1, 5, 10, 15, and 20 years, respectively. The leading cause of death was hepatitis C virus recurrence (24.6%), followed by extrahepatic malignancies (16.9%), infection (14.4%), and hepatocellular carcinoma recurrence (14.4%). The Cox proportional hazards analysis revealed that several independent factors were associated with the survival probability. These factors include younger donor and recipient ages (p=0.001 and 0.004, respectively), female recipient sex (p<0.001), absence of HCV (p<0.01), absence of HCC (p=0.001), and absence of diabetes mellitus at one year (p<0.01). At the latest follow-up, the leading comorbidities in the long-term survivors were hypertension (53.6%), obesity (18.7%), diabetes mellitus (17.1%), hyperlipidemia (14.7%), chronic kidney dysfunction (14.7%), and extrahepatic malignancies (13.8%), with 73.9% of patients having more than one complication. The Kaplan-Meier probability (95% CI) of complication-free survival was 65.4% (60.2%-70.3%), 38.4% (33.4%-43.7%), 17.8% (14.1%-22.2%), 7.2% (4.8%-10.5%), and 1.94% (0.85%-4.15%) at 1, 5, 10, 15, and 20 years, respectively. Aging with a liver graft is associated with an increased risk of complications and requires ongoing care to reduce the long-term attrition rate resulting from chronic immunosuppression.

As global life expectancy continues to rise, we are challenged with maintaining health into old age, and research has thus concentrated on various strategies aimed at mitigating the effects of skin aging. Aromatic plants stand out as potential sources of anti-aging compounds due to their secondary metabolites, particularly essential oils (EO). The aim of this study was to ascribe to Ferulago lutea EO several biological activities that could be useful in the context of skin aging. The EO was obtained using hydrodistillation and characterized by gas chromatography-mass spectrometry (GC/MS). The anti-inflammatory potential was assessed using lipopolysaccharide (LPS)-stimulated macrophages. The effect on cell migration was disclosed using scratch wound assay. Lipogenesis was induced using T0901317, hyperpigmentation with 3-isobutyl-1-methylxantine (IBMX) and senescence with Etoposide. Our results show that the EO was characterized mainly by α-pinene and limonene. The EO was able to decrease nitric oxide (NO) release as well as iNOS and pro-IL-1β protein levels. The EO promoted wound healing while decreasing lipogenesis and having depigmenting effects. The EO also reduced senescence associated β-galactosidase and p21/p53 protein levels and nuclear accumulation of γH2AX. Overall, our study highlights the properties of F. lutea EO that make it a compelling candidate for dermocosmetics applications.

The association between depressive symptomatology and cognitive decline has been examined using the Centre for Epidemiologic Studies-Depression Scale (CES-D), however, concerns have been raised about this self-report measure. Here, we examined how the CES-D total score from the 14- and 10-item versions compared to the 20-item version in predicting progression to cognitive decline from a cognitively unimpaired baseline. Data from 1,054 participants were analysed using ordinal logistic regression, alongside moderator and receiver-operating characteristics curve analyses. All baseline total scores significantly predicted progression to cognitive decline. The 14-item version was better than the 20-item version in predicting consensus diagnosis, as shown by their AICs, while also showing the highest accuracy when discriminating between participants by diagnosis at last visit. We did not find sex to moderate the relationship between CES-D score and cognitive decline. Current findings suggest the 10- and 14-item versions of the CES-D are comparable to the 20-item version, and that the 14-item version may be better at predicting longitudinal consensus diagnosis compared to the 20-item version.

Programmed aging refers to the idea that mammals (and some other multiparous sexually reproducing organisms) evolved complex biological mechanisms that cause gradually increasing fitness deterioration and internally limit individual organism lifetimes. The rationale is that this process enhances the survival (non-extinction) of a species population. Evolvability theories propose that mammals have evolved design characteristics that aid their ability to evolve, that is, reduce the time required for a particular increment of evolutionary adaptation and/or increase the precision with which the adaptation can be performed. Because an increase in evolvability aids a population in escaping extinction, evolution selects the associated design characteristics. Both of these concepts conflict with traditional (Darwinian) theory regarding the nature of evolution. However, more recent genetics discoveries have exposed rich detail regarding the nature of the evolution process including the fact that biological inheritance involves the transmission of organism design information from parent to descendant in digital form. These discoveries have acted to support both programmed aging and evolvability theories. Acquisition traits are those that depend for their evolutionary (fitness) value on the acquisition of something that gradually accumulates during an organism’s life but is not transmitted genetically to descendants. This situation causes these traits including language, immunity, intelligence, and social status to represent a special need for evolvability and programmed aging.

The origin of cancer remains one of the most important enigmas in modern biology. This paper presents a hypothesis for the origin of carcinomas in which cellular aging and inflammation enable the recovery of cellular plasticity that may ultimately result in cancer. The process is described as the result of dedifferentiation undergone by epithelial cells in hyperplasia due to replicative senescence towards a mesenchymal cell state with potential cancerous behavior. In support of the hypothesis, the molecular, cellular, and histopathological evidence was critically reviewed and reinterpreted when necessary to postulate a plausible generic model for the origin and progression of carcinomas. In addition, the implications of this theoretical framework for the current strategies of cancer treatment are discussed against recent evidence of the molecular events underlying the epigenetic switches involved in the resistance of breast carcinomas. Subsequently, is proposed an epigenetic landscape for their progression and a potential mechanism to restrain the degree of dedifferentiation and malignant behavior. Finally, is suggested a novel understanding of the involution and carcinogenesis of tissues associated with aging as a perspective that might inspire integrative approaches in the study and management of chronic diseases.

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.

Background: Assessment and management of pain in elderly people with cognitive impairment is particularly challenging. Physiological changes due to aging as well as comorbidities and polypharmacy are responsible for a complex clinical approach. Concomitantly, in cognitive impairment, including advanced dementia, changes in central nervous system along with changes in the peripheral nervous system due to aging have a significant impact in pain perception. Often clinicians decide to prescribe opioids in order to relief pain, also without a clear indication. Aim: This review aims to investigate the effect of opioids in elderly patients with cognitive impairment. Methods: A literature search of PubMed/Medline, Scopus, and Cochrane databases was conducted using keyword searches to generate lists of articles which were screened for relevance by title and abstract to give a final list of articles for full-text review. Further articles were identified by snowballing from the reference lists of the full-text articles. Results: This review discuss the complex physiological and pharmacological changes in elderly as well as the neurological changes that affect pain perception in this population. Additionally, it focuses on cognitive impairment and pain in Alzheimer’s disease and other dementias, the pain assessment in the elderly with cognitive impairment as well as the safety of opioid use in elderly. Information regarding opioid prescription in nursing homes as well as recorded indications for opioids use, type and dosing of opioid and compliance of treatment in advanced dementia are also provided. Conclusions: Opioid prescription in elderly population with cognitive impairment is particularly complex. All healthcare professionals involved in the care of such patients, need to be aware of the challenges and strive to ensure analgesic use is guided by appropriate and accurate pain assessment.

This study aimed to characterize the risk of falling in low, moderate and high risk participants from two different geographical locations using a portable force-plate. A sample of 390 older adults from South and North America were matched for age, sex, height and weight. All participants performed a standardized balance assessment using a force plate. Participants were classified in low, moderate and high risk of falling. No differences were observed between South and North American men, nor comparing North American men and women. South American women showed the significantly shorter center of pressure path length compared to other groups. The majority of the sample was categorized as having low risk of falling (male: 65.69 % and female: 61.87 %), with no differences between men and women. Also, no differences were found between North vs. South Americans, nor for falls risk levels when male and female groups were compared separately. In conclusion, South American women had better balance compatible with the status of the 50-59 years’ normative age-range. The prevalence of low falls risk was ~ 61-65 % and the prevalence of moderate to high risk was ~ 16-19 %. The frequency of fall risk did not differ significantly between North and South Americans, nor between males and females.

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.

Inhibition of mTORC1 (mechanistic Target Of Rapamycin Complex 1) signaling promotes health and longevity in diverse model organisms. Over the past decade, excitement has built over the possibility that treatment with the mTORC1 inhibitor rapamycin can be utilized to treat or prevent age-related disease in humans. However, concerns over the side effects of rapamycin on immunity and metabolism have precluded the routine use of rapamycin as a geroprotective therapy. Here, we discuss the evidence that these negative side effects of rapamycin are largely mediated by off-target inhibition of a second mTOR Complex (mTORC2). Further, we discuss how intermittent treatment with rapamycin, specific dietary regimens, and new molecules may provide routes to the safer and more selective inhibition of mTORC1. We conclude that the time is ripe for the development of therapies based on the safe and selective inhibition of mTORC1 for the treatment or prevention of diseases of aging.

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).

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.

Despite increasing research efforts, there is a lack of consensus on defining aging or health. To understand the underlying processes, and to foster the development of targeted interventions towards increasing one’s health, there is an urgent need: (1) to find a broadly acceptable and useful definition of health, based on a list of features (which may or may not be molecular); (2) to operationalize features of health so that it can be measured; (3) to identify predictive biomarkers and (molecular) pathways of health, and (4) to suggest interventions, such as nutrition and exercise, targeted at putative causal pathways and processes. Based on a survey of the literature, we propose to define health as a state of an individual characterized by the core features of (a) physiological function, (b) cognitive function and (c) physical function, amended, specifically in case of humans, by (d) lack of disease, and by (e) reproductive function. Often used concepts such as lack of frailty, allostatic load, or self-reported health (in case of human), and indices such as the Healthy Aging Index can be viewed as projections or surrogates of our definition. We further define aging as the set of all processes in an individual that reduce its “wellbeing”, that is, its health or survival or both. We define biomarkers of health by their attribute of predicting future health better than chronological age. We define healthspan pathways as molecular features of health that relate to each other, specifically by belonging to the same molecular pathway. Our conceptual framework may integrate diverse operationalizations of health and guide precision prevention efforts that are a key to reducing the need for medical and nursing care.

Irisin, a skeletal muscle-secreted myokine, produced in response to physical exercise, has protective functions in both the central and the peripheral nervous systems, including the regulation of brain-derived neurotrophic factors and modification of telomere length. Such beneficial effects may inhibit or delay the emergence of neurodegenerative diseases, including Alzheimer’s disease (AD). This review is based on the hypothesis that irisin produced by physical exercise helps control AD progression. Herein, we describe the physiology of irisin and its potential role in delaying or preventing AD. Although current and ongoing studies on irisin show promising results, further research is required to clarify its potential as a meaningful therapeutic target for treating human diseases.

: Since the COVID-19 pandemic, people have become aware that materials (products) can transmit infection and have begun to focus on questions such as how bacteria and germs, the sources of in-fection, maintain their infectivity on material surfaces, and the extent to which materials can or cannot prevent this. and to what extent materials can and cannot prevent it. The SIAA, a non-profit organization of many Japanese companies, had created an entirely separate interna-tional standard for materials' antibacterial, antiviral, and antibiofilm properties (products). The authors have studied the academic basis for the operation of the standards and were deeply in-volved as researchers in establishing one of the standards. This paper describes the interna-tional standards and some representative examples of the authors' actual use of these standards and explains the current status and future problems.

Abstract: In the last decade, gypsogenin has widely grabbed the attention of medicinal chemists by virtue of its prominent anti-cancer potential. Despite its late identification, gypsogenin proved itself as a new an-ti-proliferative player battling for a front position among other classic pentacyclic triterpenes such as oleanolic acid, glycyrrhetinic acid, ursolic acid, betulinic acid, and celastrol. Herein, we present insights into the anti-cancer activity of gypsogenin and its semisynthetic derivatives and go further by introducing our perspective to judiciously guide the prospect rational design. The present article opens a new venue for better exploitation of gypsogenin chemical entity as a lead compound in cancer chemotherapy. To the best of our knowledge, this is the first review article exploring the anti-cancer activity of gypsogenin derivatives.

The synthesis of the presented benzo[d]thiazol-2-amine derivatives was performed by condensing-(4-chlorobenzylidene) benzo[d]thiazol-2-amine with a number of substituted phenols in the presence of potassium iodide and anhydrous potassium carbonate in dry acetone. IR spectroscopy, 1HNMRspectroscopy and spectroscopy methods were used to characterize the structural properties of newly synthesized derivatives. In order to observe the attributes of drug-like candidates of these derivatives, the number of their molecular properties was estimated. Benzo[d]thiazol-2-amine derivatives were molecularly docked with selective enzymes COX-1 and COX-2. Findings suggested that Compounds G3, G4, G6, G8 and G11 possess higher binding affinity than diclofenac sodium, when docking was performed with enzyme COX-1. Compounds G1, G3, G6, G8and G10 showed lower binding affinity than Indomethacin when docking performed with enzyme COX-2.In vitro evaluation of the COX-1 and COX-2 enzyme inhibitory activities were performed for synthesized compounds. Compounds 10 and 11 exhibited significant COX-1 and COX- enzyme inhibitory action with IC50 values of 5.0 and 10 µM, respectively. Using the hot plate method and the carrageenan-induced rat paw edema model, the synthesized compounds were screened for their biological activities, including analgesic and anti-inflammatory activities. The highest analgesic action was exhibited by derivative G11and the compound G10 showed the highest anti-inflammatory response.

Polyacetylene phytochemicals are emerging as potentially responsible for the chemoprotective effects of consuming apiaceous vegetables. There is some evidence suggesting that polyacetylenes impact carcinogenesis by influencing a wide variety of signalling pathways, which are important in regulating inflammation, apoptosis, cell cycle regulation, etc. Studies have shown a correlation between human dietary intake of polyacetylene-rich vegetables with reduced risk of inflammation and cancer. Polyacetylene supplementation can influence cell growth, gene expression, and immunological responses, and reduce tumour number in rat and mouse models. Cancer chemoprevention by dietary polyacetylenes involves several mechanisms, including effects on inflammatory cytokines, the NF-κB pathway, antioxidant response elements, UPR pathway, growth factor signalling, cell cycle progression, and apoptosis. This review summarises the published research on falcarinol-type polyacetylene compounds and their mechanisms of action regarding cancer chemoprevention and treatment, and also identifies some gaps in our current understanding of the health benefits of these polyacetylenes.

Background: Antiphospholipid antibodies (aPL) are a laboratory criterion for the classification of antiphospholipid syndrome (APS), and are known to cause clinical symptoms: vascular thrombosis or obstetric complications. It is suggested that aPL may be associated with thromboembolism in severe COVID-19 cases. Aim: to combine clinical data with aPL findings at 4 time points (admission, worsening, discharge, 3-month follow-up) in patients hospitalized with COVID-19 pneumonia. Methods: current and past history of thrombosis and obstetric complications; aPL determined at 4 time points: anticardiolipin (aCL), anti-β2-glycoprotein I (anti- β2GPI) and antiphosphatidylserine/prothrombin (aPS/PT) of the IgM, IgG or IgA isotypes. Results: 111 patients with COVID-19 pneumonia were enrolled. During hospitalization, 7 patients died, 3 of them due to pulmonary artery thromboembolism (none was aPL positive). Only one of the five who developed pulmonary artery thrombosis was aPL positive. Of 9/101 patients with a history of thrombosis, 5 had arterial thrombosis and none was aPL positive at admission and follow-up; 4 had venous thrombosis and one was aPL positive at all time points (newly diagnosed APS). Of these 9/101 patients, 55.6% were transiently aPL positive at discharge only, compared to 26.1% without history of thrombosis (p=0.05). Conclusions: aPL were not associated with fatal outcomes and vascular thrombosis; aPL were transiently positive in more than half of patients with a history of thrombosis.

Background and Objectives: Age-related macular degeneration (AMD) is one of the major causes of central vision loss in the older age group and its dry form accounts for the majority of cases. Although several causes and mechanisms for the development and progression of AMD have previously been identified, the pathogenesis of this complex disease is still not entirely understood. As the inflammation and involvement of the immune system are strongly suggested to have a central role to promote the degenerative process and to stimulate the onset of complications, we aimed to analyze the prevalence of serum anti-retinal (ARA) and anti-endothelial cell antibodies (AECA) in patients with dry AMD and to determine their relationship with the clinical features of the disease, notably area of geographic atrophy (GA). Materials and Methods: We enrolled 41 patients with dry AMD and 50 sex- and age-matched healthy controls without AMD. The presence of ARA was determined by indirect immunofluorescence using monkey retina as an antigen substrate, while the presence of AECA was determined using cultivated human umbilical vein endothelial cells and primate skeletal muscle. Results: ARA were detected 36 (87.8%) AMD patients (titers range from 1:20 to 1:320) and in 16 (39.0%) (titers range from 1:10 to 1:40) of controls (p=0.0000). Twenty of the 41 patients (48.8%) were positive for AECA, while in a control group AECA were present only in 5 sera (10.0%). The titers of AECA in AMD patients ranged from 1:100 to 1:1000 and in the control group the AECA titers were 1:100 (p=0.0001). There were no significant correlations between the presence of AECA and disease activity. Conclusions: This study provides evidence for the possible involvement of an autoimmune process against retina and retinal vessel antigens in the pathogenesis of geographic atrophy associated with dry AMD.

The West-African variety of Sorghum bicolor leaf sheath (SBLS) Jobelyn® is a natural remedy, which has gained international recognition for its anti-anemic effect and energy boosting qualities in debilitating diseases. The widespread use of traditional medicine in the region usually confirms its safety, but not its efficacy or deep assessment of their pharmacological properties. The other major issue for herbal-based treatments is the lack of definite and complete information about the composition of the extracts. Despite limitations, efforts have been made in isolation and characterisation of active compounds in this specie of sorghum showing various subclasses of flavonoids including apigeninidin, a stable 3-deoxyanthocyanidin and potential fungal growth inhibitor, which accounts for 84% of the total extract. Non-clinical in vitro and in vivo studies support previous indications that this variety of Sorghum bicolor possesses several biologically active compounds with potent antioxidant, anti-inflammatory, anti-aging and neuro-protective properties. Clinical studies show that SBLS has the ability to boost hemoglobin concentrations in anemic conditions and most remarkably to increase CD4 count in HIV-positive patients. The multiple effects and high safety profiles of this extract may encourage its development as a therapeutic agent for the treatment of anemia, chronic inflammatory conditions or in the symptomatic management of HIV infections. This review describes the potential therapeutic aspects of SBLS extract and its potential benefits.

Despite extensive use of intravitreal anti-vascular endothelial growth factor (anti-VEGF) biologics for over a decade, neovascular age-related macular degeneration (nAMD) or choroidal neovascularization (CNV) continues to be a major cause of irreversible vision loss in developed countries. Many nAMD patients demonstrate persistent disease activity or experience declined responses over time despite anti-VEGF treatment. The underlying mechanisms of anti-VEGF resistance are poorly understood, and no effective treatment strategies are available to date. Here we review evidence from animal models and clinical studies that supports the roles of neovascular remodeling and arteriolar CNV formation in anti-VEGF resistance. Cholesterol dysregulation, inflammation, and ensuing macrophage activation are critically involved in arteriolar CNV formation and anti-VEGF resistance. Combination therapy by neutralizing VEGF and enhancing cholesterol removal from macrophages is a promising strategy to combat anti-VEGF resistance in CNV.

Cellular aging is considered as one of the main factors leading to female infertility. The process called “inflammaging”, which was proposed by C. Franceschi in 2014 is characterized by chronic asymptomatic inflammation state resulting to whole body aging and age-associated diseases. In this work the inflammaging model was developed; markers expression associated with SASP (senescence associated secretory phenotype) and cell aging were verified in endometrial cells; the correlation analysis with the known inflammaging markers was done; as well as the age dynamic of markers expression in the groups of young reproductive age and late reproductive age was evaluated. For the first time, the comparative study of the expression of the key signalling molecules involved in the mechanisms of the aging was carried out: IL-6, IL-8, IL-1a, MMP3, SIRT1,6, TERF-1, CALR in endometrial cells in the age aspect and under the influence of the genotoxic stress. The SASP phenotype characterizing the phenomenon of inflammaging can be significantly expanded by the including of the studied molecules - SIRT-1, SIRT-6, TERF, CALR, that we demonstrated for the first time. These signalling molecules may be new therapeutic targets for the age-associated female reproductive system diseases treatment.

Sensory integration is an essential function of human life, and its decline causes difficulties in the quality of life, especially in older adults. In this study, we proposed an arm-reaching task based on a virtual reality head-mounted display (VR-HMD) system to assess sensory integration in daily life, and examined whether reaching task performance was associated with age and resting-state functional connectivity (rsFC) between the brain regions of interest involved in sensory integration. We hypothesized that performance during a reaching task with multiple cognitive loadings would be affected by aging. The gap angle between the reaching hand and target positions was compared between older and middle-aged adults as a measure of sensory integration function. In addition, rsFC, which was significantly correlated with the gap angles of individual participants in the older adult group, was identified using resting-state functional magnetic resonance imaging data. The mean gap angle was significantly larger in the older adults than in the middle-aged group and was also significantly correlated with connections between the left primary motor area and the left inferior temporal gyrus, temporo-occipital part. Because the connectivity between the areas is known to be related to visuomotor integration, the results suggest the involvement of visuomotor integration in the decline of sensory integration function in old age and the validity of the gap angle during the proposed VR-HMD task as an index for the decline in function.

The nickel-chromium-molybdenum alloy 625 exhibits an excellent combination of mechanical properties and corrosion resistance. However, the high temperature plastic deformation process and the heat treatment represent critical aspects and the adoption of non-optimal parameters can result in excessive grain coarsening and loss in mechanical strength. This detrimental behavior is worsened by the presence of a narrow region of temperatures and strain rates for complete recrystallization and the absence of phase transformation temperatures. In this alloy, the presence of sufficient amounts of niobium, titanium and aluminum permits slow age-hardening response upon single-aging treatments. Therefore, when the soft- or solution-annealed condition is associated with insufficient mechanical properties, this potentiality can be exploited to improve the mechanical strength and prevent waste of material and resources. Since the precipitation kinetic of the hardening γ^'' phase can be accelerated by prior nucleation treatment, different time-temperature combinations of double aging at 732 °C and 621 °C are investigated to reduce the overall heat treatment time. However, the simultaneous formation of Cr-rich carbides can dramatically affect the intergranular corrosion resistance. For this reason, a performance map is developed to compare all the tested conditions and identify the best compromise in terms of mechanical strength and corrosion rate.

Background: Here, we investigated the inflammaging and physical performance in older adults before and after the COVID-19 pandemic. Methods: Women(n=18) and men(n=7) older were evaluated before the COVID-19 pandemic(PRE), 12 months after the lockdown(POST), and 10 months after resuming exercise training(POS-TR). Physical tests [gait speed(GS) and timed-up-and-go(TUG)]; muscle strength (handgrip-HG), and serum cytokine levels were assessed. Results: The older women showed higher GS and TUG at POST than PRE and POST-TR, besides lower HG at POST-TR than PRE, whereas older men exhibited lower HG at POST and POST-TR than PRE. Both groups presented (1)lower IL-10 and IL-12p70 values in contrast to higher IL-6/IL-10 and IL-8/IL-10 ratios at POST than PRE; (2)higher IL-10 values and lower IL-8/IL-10 ratio at POST-TR than POST; (3)higher IL-12p70/IL-10 ratio at POST-TR than PRE and POST. Particularly older women showed: (4)lower IL-6 values at POST and POST-TR than PRE; (5)lower IL-8 and IL-10 values at POST-TR than POST; (6)and higher TNF-α/IL-10 and IFN-γ/IL-10 ratios at POST than PRE and POST-TR. Significant correlations between the variables were found in both groups. Conclusion: During the COVID-19 pandemic, detraining and resumption of exercise training promoted distinct alterations in physical capacity and inflammaging among older women and older men population.

Emerging data support associations between depletion of the healthy gut microbiome and aging-related physiological decline and disease. In humans, fecal microbiota transplantation (FMT) has been used successfully to restore gut microbiome structure and function to treat C. difficile infections, but application to healthy aging has been scarcely investigated. The marmoset is an excellent model for evaluating microbiome-mediated changes with age and interventional treatments due to their relatively shorter lifespan and many social, behavioral, and physiological functions that mimic human aging. This review 1) provides an overview of the rationale for FMT to support healthy aging using the marmoset as a translational geroscience model, 2) summarizes prior use of FMT in marmosets, 3) outlines a protocol for studying FMT in aging marmosets, and 4) describes knowledge gaps and future research needs in this field.

In recent years, marine natural products have become one of the most important resources of novel lead compounds for critical diseases associated with age. Spirulina, a dietary supplement made from blue-green algae (cyanobacteria: scientific name Arthrospira platensis), is particularly rich in phycocyanin, a phycobiliprotein, which accounts for up to 20% of this cyanobacterium’s dry weight and is considered responsible for its anti-cancer, anti-inflammatory and antioxidant activities. Although the anti-aging activity of phycocyanin has been investigated, how exactly this compound works against aging remains elusive. Aim of our research is to use the yeast Saccharomyces cerevisiae as a model organism to investigate the anti-aging properties of phycocyanin from A. platensis. Our results show that phycocyanin has a powerful anti-aging effect, greatly extending the chronological life span of yeast cells in a dose-dependent way, being the effect pronounced also when cells were grown in SD medium under calorie restriction conditions (0.2% glucose). Both ROS and accumulation of dead cells were followed by staining chronologically aged cells with dihydrorhodamine 123 (DHR123) and propidium iodide (PI). Interestingly, we found that most of the aged phycocyanin treated cells, which were unable to form colonies, were actually ROS+/PI–. Finally, we show that the moment in which phycocyanin is added to the culture does not substantially influence its effectiveness in counteracting chronological 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.

Introduction: Sarcopenia, muscle loss, often coexists with MASLD, a common liver disorder, which is more prevalent in those with sarcopenia. Sarcopenia also increases the risk of liver conditions like steatosis and fibrosis. Studies on sarcopenia in MASLD are common in developed countries, but fewer follow the EWGSOP2 guidelines in Brazil. Aim: to assess sarcopenia prevalence in MASLD patients. Methods: Cross-sectional study conducted at the Gastroen-terology/Hepatology Service of ISCMPA with patients diagnosed with MASLD. The EWGSOP2 criteria were used to evaluate sarcopenia. Categorical data presented as absolute and relative frequency; parametric continuous data ex-pressed as mean±standard deviation; non-parametric continuous data as me-dian and IQR. Gender differences in were analyzed using Fisher's Exact Test or Chi-squared tests, and for continuous variables, T Student tests (parametric) and Mann-Whitney U tests for independent samples (non-parametric). The significance level was set at 5% (p<0.05). Results: The study involved 103 MASLD patients with an average age of 60.39 years, comprising 48 (46.60%) adults and 55 (53.40%) older individuals. Concerning sarcopenia diagnosis, four individuals exhibited decreased muscle strength; two had reduced MME (sarcopenia); and one showed decreased walking speed (severe sarcopenia). Among the participants, 63 (60.6%) were physically active. 35 (62.5%) had mild to moderate steatosis, while 21 (37.5%) had severe steatosis. In terms of EHNA, 13 subjects (24.08%) had moderate to severe EHNA. Regarding fibrosis classi-fication, 68 (72.34%) individuals had undetermined or high probability based on the NAFLD score, with higher prevalence in males (n=23; 88.5%). Fibrosis assessment via liver biopsy revealed 27 (28.72%) in F1 and F2 and 15 (16.96%) in F3 and F4. Stratification of fibrosis into F3 and F4 was more com-mon among men (n=9; 47.4%). Conclusion: Most of the population was physi-cally active. The parameters indicating sarcopenia exceeded the thresholds recommended by EWGSOP2. The prevalence of sarcopenia was low in individuals with MASLD.

Following ischemic stroke, the degradation of myelin and other cellular membranes surpasses the lipid-processing capabilities of resident microglia and infiltrating macrophages. This imbalance leads to foam cell formation in the infarct and areas of secondary neurodegeneration, instigating sustained inflammation and furthering neurological damage. Given that mitochondria are the primary sites of fatty acid metabolism, augmenting mitochondrial biogenesis (MB) may enhance lipid processing, curtailing foam cell formation and post-stroke chronic inflammation. Previous studies have shown that the pharmacological activation of the β2-adrenergic receptor (β2-AR) stimulates MB. Consequently, our study sought to discern the effects of intensified β2-AR signal-ing on MB, the processing of brain lipid debris, and neurological outcome using a mouse stroke model. To achieve this goal, aged mice were treated with formoterol, a long-acting β2-AR ago-nist, daily for two and eight weeks following stroke. Formoterol increased MB in the infarct re-gion, modified fatty acid metabolism, and reduced foam cell formation. However, it did not re-duce markers of post-stroke neurodegeneration or improve recovery. Our findings suggest that boosting MB in myeloid cells is one component of a therapeutic avenue for improving brain lipid debris processing after stroke.

As the world's population ages and the resulting health problems become more serious, medical and health policies in developed countries are focused on how to prevent and treat the diseases of the aging population and how to maintain their quality of life. Typical age-related diseases include deafness, cataracts, osteoarthritis, chronic obstructive pulmonary disease, diabetes mellitus, and dementia. Although the mechanisms by which these diseases develop differ, they are all caused by the accumulation of molecular and cellular damage over time. In addition, age-related diseases can cause a decline in physical and mental functions and the ability to perform activities of daily living, as well as the loss of roles in society and a sense of fulfillment in life. Therefore, there is a need for treatment and measures to accurately grasp and maintain their quality of life.

The CuCrSn alloy is promising as high-strength and high-conductivity Cu alloy due to its relative low smelting requirement, while thus far reports on the CuCrSn alloy is still quite lacked. In this study, the microstructure and properties of Cu-0.20Cr-0.25Sn (wt%) specimens prepared under different rolling and aging combinations were comprehensively characterized, in order to reveal the effects of cold rolling and aging on the CuCrSn alloy. The results show that increasing the aging temperature from 400 ºC to 450 ºC can obviously accelerates the precipitation, and the cold rolling before aging significantly increases the initial microhardness and promotes the precipitation. Whereas, the deformation hardening will be eliminated during the aging process, making the microhardness even decrease monotonically when the aging temperature and the rolling ratio before aging are high. Performing the cold rolling after the aging can maximize the effects of precipitation strengthening and deformation strengthening, and its adverse impact on the conductivity is not serious. A tensile strength of 506.5 MPa and a conductivity of 70.33% IACS were obtained with such a treatment, only the elongation decreases. Different strength-conductivity combinations of the CuCrSn alloy can be achieved through appropriate combinations of the aging and post aging cold rolling conditions.

Cardiorespiratory fitness (CRF) is essential for sustained work ability in good health, but declines with aging as does the functionality of the immune system, the latter process commonly referred to as immunosenescence. This study aimed to compare the capacity of immunosenescence biomarkers with chronological age for predicting low CRF in a cross-sectional sample recruited from the regional working population. CRF was determined by submaximal bicycle ergometer testing in a cross-sectional sample of 597 volunteers aged 20–70 years from the ’Dortmund Vital Study’ (DVS, ClinicalTrials.gov Identifier: NCT05155397). Low CRF was scored, if the ergometer test was not completed due to medical reasons or if the power output projected to a heart rate of 130 bpm divided by body mass was below sex-specific reference values of 1.25 W/kg for females and 1.5 W/kg for males, respectively. In addition to established biomarkers of immunosenescence, we calibrated a comprehensive metric of immune age to our data and compared its predictive capacity for low CRF to chronological age while adjusting our analysis for the influence of sex, obesity, and level of regular physical activity by applying univariate and multiple logistic regression. While obesity, low physical activity, chronological and immune age were all associated with increased probability for low CRF in univariate analyses, multiple logistic regression revealed that obesity and physical activity together with immune age, but not chronological age, were statistically significant predictors of low CRF outcome. Sex was non-significant due to the applied sex-specific reference values. These results demonstrate that biological age assessed by our immunological metric can outperform chronological age as a predictor for CRF and indicate a potential role for immunosenescence in explaining the inter-individual variability of the age-related decline in cardiorespiratory fitness.

Scientific literature shows increased interest in the aged and the aging phenomenon. The Aging Attitudes Questionnaire - AAQ was validated for the Portuguese population to understand the importance of attitudes towards old age and their impact on the subjective well-being of the elderly. A sample of 400 subjects (from 18 to 93 years) answered a socio-demographic questionnaire, and the AAQ was composed of three subscales (psychosocial losses, physical change, and psychological growth). The CFA confirmed the tri-factorial structure with very good adjustment of the model to the data with the Cronbach alpha of the total scale scoring .84 and ranging from .65 to .77 for each factor. A total of 9 items were omitted both for poor factor loadings (<0.50. Notwithstanding, 3 items below the criteria were maintained, as they conceptually fit into the factor. Of the final 15 AAQp items, 5 belong to the Psychosocial Loss factor, 6 to Physical Change, and 4 to Psychosocial Growth. This tree factor model explained 50.1 % of the total variance. In conclusion, this study supports that AAQ has acceptable validity, confirming the composite reliability and the discriminant validity, but not the convergent validity. Through multi-group analysis, the invariance of the scale was confirmed. This validation is of pivotal importance once it allows measuring the attitudes towards aging, thus facilitating the promotion of wellbeing across the lifespan.

Age-related alterations in the gut microbiome composition and its impacts on the host’s health have been well described; however, detailed analyses of the gut microbial structure defining ecological microbe-microbe interactions is limited. One of the ways to determine these interactions is by understanding microbial co-occurrence patterns. We previously showed promising abilities of Lactobacillus acidophilus DDS-1 on the aging gut microbiome and immune system. However, the potential of the DDS-1 strain to modulate microbial co-occurrence patterns is unknown. Hence, we aimed to investigate the ability of L. acidophilus DDS-1 to modulate the fecal, mucosal and cecal-related microbial co-occurrence networks in young and aging C57BL/6J mice. Our Kendall’s tau correlation measures of co-occurrence revealed age-related changes in the gut microbiome, which were characterized by reduced number of nodes and associations across sample types when compared to younger mice. After four-week supplementation, L. acidophilus DDS-1 differentially modulated the overall microbial community structure in fecal and mucosal samples as compared to cecal samples. Beneficial bacteria such as Lactobacillus and Akkermansia acted as connectors in aging networks in response to L. acidophilus DDS-1 supplementation. Our findings provided the first evidence of the DDS-1-induced gut microbial ecological interactions revealing the complex structure of microbial ecosystems with age.

Epigenetics, specifically DNA methylation, allows for estimation of animal age from blood or remotely sampled skin. This multi tissue epigenetic aging clock uses 110 longitudinal samples from 34 Navy bottlenose dolphins (Tursiops truncatus), identifying 195 cytosine-phosphate-guanine sites associated with chronological aging via leave-one-individual-out-cross-validation (R2=0.95). With a median absolute error of 2.5 years this clock improves age estimation capacity in wild dolphins, expanding conservation efforts, enabling better understanding of population demographics.

Age-related macular degeneration (AMD) is a complex, multifactorial neurodegenerative disease that constitutes the most common cause of irreversible blindness in the elderly in developed countries. Incomplete knowledge about its pathogenesis prevents the search for effective methods of prevention and treatment of AMD, primarily its “dry” type, which is by far the most common (90% of all AMD cases). In recent years, AMD became younger: late stages of the disease are now detected in relatively young people. It is known that AMD pathogenesis—according to the age-related structural and functional changes in the retina—is linked with inflammation, hypoxia, oxidative stress, mitochondrial dysfunction, and an impairment of neurotrophic support, but the mechanisms that trigger the conversion of normal age-related changes to the pathological process as well as the reason for early AMD development remain unclear. In the adult mammalian retina, de novo neurogenesis is very limited. Therefore, the structural and functional features that arise during its maturation and formation can exert long-term effects on further ontogenesis of this tissue. The aim of this review is to discuss possible contributions of the changes/disturbances in retinal neurogenesis to the early development of AMD.

The ability to express and recognize emotion via facial expressions is well known to change with age. The present study investigated the differences in the facial recognition and facial expression of the elderly (n = 57) and the young (n = 115) and measure how each group uses different facial muscles for each emotion with Facial Action Coding System (FACS). In facial recognition task, the elderly did not recognize facial expressions better than young people and reported stronger feelings of fear and sad from photographs. In making facial expression task, the elderly rated all their facial expressions as stronger than the younger, but in fact, they expressed strong expressions in fear and anger. Furthermore, the elderly used more muscles in the lower face when making facial expressions than younger people. These results help to understand better how the facial recognition and expression of the elderly change, and show that the elderly do not effectively execute the top-down processing concerning facial expression.

The recent COVID-19 outbreak in China led to a worldwide pandemic associated with a severe acute respiratory illness. A higher incidence of COVID-19 infection was demonstrated in cancer patients, including patients with lung cancer. This study was conducted to get insights into the reasons for this enhanced frequency of COVID-19 infection. Methods: Using different bioinformatic tools, the expression and methylation pattern of ACE2 and TMPRSS2 gene were analyzed in healthy and malignant tissues with a focus on lung adenocarcinoma (LUAD) and correlated to clinical parameters and smoking history. Results: ACE2 and TMPRSS2 were heterogeneously expressed across 36 healthy tissues with the highest expression in digestive, urinary and reproductive organs, while their expression was significantly lower in 36 cancer tissues. In LUAD, ACE2, but not TMPRSS2 was overexpressed, which inversely correlated to the promoter methylation. An age-dependent upregulation of ACE2 expression was found in LUAD compared to normal lung tissues. In a healthy lung, TMPRSS2 expression was dependent on sex and smoking history and downregulated in LUAD of smokers. Cancer progression was associated with decreased TMPRSS2, but unaltered ACE2 expression, while ACE2 expression in lung metastases of different cancers was higher than in metastasis of other sites. TMPRSS2, but not ACE2 expression, was associated with LUAD patients’ survival. Conclusions: Comprehensive molecular analyses revealed a heterogeneous, distinct expression and methylation profile of ACE2 and TMPRSS2 in healthy lung vs LUAD tissues across sex, age and smoking history, which is associated with clinical parameters and might have implications for COVID-19 disease.

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.

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.

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.

Background The evolution of treatment patterns in neovascular age-related macular degeneration (nAMD) warrants investigation into the impact of patients’ adherence to anti-vascular endothelial growth factor (VEGF) treatment on visual outcomes. This retrospective, non-randomized, non-comparative study aimed to investigate real-world adherence to anti-VEGF treatment. Methods Patients (eyes) (≥ 50 years) with a diagnosis of nAMD who had a first injection of aflibercept or ranibizumab between January 2016 and December 2018 and 12 months of follow-up were included. Visual acuity (VA; logarithm of the minimum angle of resolution letters) and duration of injection intervals were recorded. Adherence was defined as < 20% of visits deviating from the schedule by ≥ 14 days. Results Overall, 133 patient eyes were included: 129 adherent, 4 non-adherent. Mean (± standard deviation) baseline VA was 57.0 (± 23.6) and 53.8 (± 35.3) letters in adherent and non-adherent patient eyes, respectively. Mean change in VA by month 12 was higher in adherent (6.3 letters) than non-adherent patient eyes (−11 letters). In non-adherent patient eyes, no improvement in VA was recorded following completion of the loading period (month 3). Compared with the previous visit, adherent visits were associated with a mean increase in VA of 0.67 letters and non-adherent visits with a decrease of 2.30 letters. Conclusions These results emphasize the importance of adherence to appropriate dosing regimens to optimize visual outcomes in patients with nAMD.

Bangladeshi medicinal plants (BMP) have been used as traditional medicinal plants to treat chronic inflammatory diseases, but the antioxidant and anti-inflammatory effects of the bark of BMP are not yet known. The objective of this study was to determine antioxidant and anti-inflammatory activities using methanolic extracts of bark obtained from 15 medicinal spices of Bangladesh plants. The bark methanol extracts of BMP evaluated the total antioxidant activity and anti-inflammatory effect of lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages. Among the 15 bark extracts of BMP, Albizia odoratissima (A. odoratissima), Engelhardia spicata (E. spicata), and Shorea robusta (S. robusta) showed the highest total phenolic contents and total antioxidant capacity by reducing free radicals scavenging activity. In particular, the three bark extracts significantly reduced the mRNA expression of LPS-induced inflammatory cytokines and inflammation-inducible enzymes in macrophages. Also, the mRNA expression of NADPH oxidase 2 was significantly suppressed by three bark extracts in LPS-induced RAW 264.7 macrophages. The results suggest that among the 15 bark extracts obtained from medicinal plant in Bangladesh, three bark extracts of A. odoratissima, E. spicata, and S. robusta exert total antioxidant capacity by reducing free radicals scavenging activity and inhibitory effects on LPS-stimulated inflammation in macrophages.

Two-dimensional (2D) ice I is an atomic-level ice that is composed of two interlocked atom-ic layers saturated with hydrogen bonds. It has recently been experimentally observed but its properties have yet to be clarified. Accordingly, we theoretically studied the hydrophobic properties of 2D ice I. On the contrary, simulation of a hydrogen fluoride molecule on a 2D ice surface manifested that it destroyed the 2d ice structure and connected new hydrogen bonds with water molecules. Investigations of the interfacial effect between 2D and three-dimensional (3D) ice films indicated that the network structure of 2D ice was not de-stroyed by a 3D ice surface, as the former was saturated with hydrogen bonds. However, the surface of 3D ice reorganized to form as many hydrogen bonds as possible. Thus, the 2D ice film was hydrophobic and inhibited the growth of 3D ice. This shows that if 2D ice can be produced on an industrial scale, it could be used as an anti-3D-icing agent under low tem-perature.

This work is based on identifying the analysis techniques used to evaluate the antioxidant and anti-inflammatory effects using the zebrafish model. In this context, a literature review was performed with the Web of Science database. We used the terms zebra fish, antioxidant, anti-inflammatory, model, and Danio rerio. Fifty articles were reviewed, of which thirty-three were chosen to perform this review and were classified according to the source of plant extracts, compounds extracted from plants, chemical compounds, and other sources. This paper is an effort to provide a literature review on zebrafish models and elucidate their pros and cons to evaluate anti-inflamatory and antioxidant activity.

The purpose of this scoping review was to examine the literature on the use of anti-gravity treadmill and its effects on lower limb motor functions in children and adolescents with locomotor impairments. Four databases (MEDLINE, CINAHL, Embase, Web of Science) were searched for articles from inception to August 2021. Inclusion criteria were: (1) experimental or quasi-experimental studies using the anti-gravity training as the primary intervention; (2) studies conducted in paediatricpediatric participants; (3) articles reporting outcomes related to the lower limb functions; and (4) studies published in French or English. Fifteen articles were included in the review. Studies included children and adolescents aged 4–18 years with locomotor impairments. The intervention duration was ranged from 2 and to 12 weeks, with 2-5 sessions per week. Included studies showed reported that anti-gravity training induces improvements in muscle strength, balance, spatiotemporal gait parameters, and walking endurance in children with locomotor impairments. This review provides relevant information about the modalities, outcomes and limits associated with the anti-gravity training protocol reported in the literature. Overall, the anti-gravity treadmill training could be viewed as a valuable training modality for children with cerebral palsy. However, more precise, and comprehensive description of anti-gravity rehabilitation protocols would be useful.

Acquired Immunodeficiency Syndrome (AIDS) which is chiefly originated by a retrovirus named Human Immunodeficiency Virus (HIV), has influenced about 70 million populations worldwide. Even though several advancements have been invented in the field of antiretroviral combination therapy, still HIV has become the dominant reason for death in South Africa, for example. The current antiretroviral therapies have achieved success in providing instant HIV suppression but with countless undesirable adverse effects. In the present day, the biodiversity of the plant kingdom is being explored by several researchers for the discovery of potent anti-HIV drugs with different mechanisms of action. The primary challenge is to afford a treatment that is free from any sort of risk of drug resistance and serious side effects. Hence, there is a strong demand to evaluate the drugs obtained from natural plants as well as the synthetic derivatives that have been derived from the natural compounds by various chemical reactions. Several plants such as Andrographis paniculata, Dioscorea bulbifera, Aegle marmelos, Wistaria floribunda, Lindera chunii, Xanthoceras sorbifolia and others have displayed significant anti-HIV activity showing more potent anti-HIV activity along with their structures, SARs & important key findings.

As the time passes the modification in technology world lead to the evaluation in mobile application as well. With evaluation in mobile industry it is an open challenge for software quality researcher that how to enhance software quality to meet the needs of changes? Quality assurance play a key role in differentiating good application from bed application. With the continuous evaluation of mobile application developing process should be quick and efficient to comply with user requirements and satisfaction. While the listed requirement leads to bad design choices known as antipatterns, which in turn affect the reliability of the code. A tool based method PAPRIKA is used in the proposed re-search to identify and monitor these antipatterns together with a two-step assessment model for software quality assurance and object oriented software quality matrix.

The iridoids of H. diffusa play an important role in the anti-inflammatory process, but the specific iridoid with anti-inflammatory effect and its mechanism is lack of study. An iridoid compound named scandoside (SCA) was isolated from H. diffusa and its anti-inflammatory effect was investigated in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Its anti-inflammatory mechanism was confirmed by in intro experiment and molecular docking analysis. As results, SCA significantly decreased the productions of nitric oxide (NO), prostaglandin E₂ (PGE₂), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and inhibited the levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α and IL-6 mRNA expression in LPS-induced RAW 264.7 cells. SCA treatment suppressed the phosphorylation of inhibitor of nuclear transcription factor kappa-B alpaha (IκB-α), p38, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). The docking data suggested that SCA had great binding abilities to COX-2, iNOS and IκB. Taken together, the results indicated that the anti-inflammatory effect of SCA is due to inhibition of pro-inflammatory cytokines and mediators via suppressing the nuclear transcription factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, which provided useful information for its application and development.