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This article reviews the role of amyloid-beta (Abeta) and mitochondria in synaptic damage and cognitive decline found in patients with Alzheimer's disease (AD). Recent molecular, cellular, animal model, and postmortem brain studies have revealed that Abeta and mitochondrial abnormalities are key factors that cause synaptic damage and cognitive decline in AD. Abeta is reported to accumulate in subcellular compartments and to impair the normal function of neurons in AD patients. Further, recent studies using biochemical methods and electron microscopy have revealed that the accumulation of Abeta at nerve terminals affect synaptic activities, including the release of neurotransmitters and synaptic vesicles. Recent studies of the relationship between mitochondria and Abeta in AD patients suggest that in mitochondria, structural changes caused by Abeta result in increased mitochondrial fragmentation, decreased mitochondrial fusion, mitochondrial dysfunction, and synaptic damage. This paper discusses the latest research on Abeta, mitochondria, age-dependent factors of AD in the brain, and synaptic damage in AD. This paper also briefly discusses potential mitochondrial therapeutics in the treatment of patients with AD. [ABSTRACT FROM AUTHOR]

The purpose of our study was to investigate the effects of the mitochondria-targeted antioxidants, MitoQ and SS31, and the anti-aging agent resveratrol on neurons from a mouse model (Tg2576 line) of Alzheimer's disease (AD) and on mouse neuroblastoma (N2a) cells incubated with the amyloid-beta (Abeta) peptide. Using electron and confocal microscopy, gene expression analysis, and biochemical methods, we studied mitochondrial structure and function and neurite outgrowth in N2a cells treated with MitoQ, SS31, and resveratrol, and then incubated with Abeta. In N2a cells only incubated with the Abeta, we found increased expressions of mitochondrial fission genes and decreased expression of fusion genes and also decreased expression of peroxiredoxins. Electron microscopy of the N2a cells incubated with Abeta revealed a significantly increased number of mitochondria, indicating that Abeta fragments mitochondria. Biochemical analysis revealed that function is defective in mitochondria. Neurite outgrowth was significantly decreased in Abeta-incubated N2a cells, indicating that Abeta affects neurite outgrowth. However, in N2a cells treated with MitoQ, SS31, and resveratrol, and then incubated with Abeta, abnormal expression of peroxiredoxins and mitochondrial structural genes were prevented and mitochondrial function was normal; intact mitochondria were present and neurite outgrowth was significantly increased. In primary neurons from amyloid-beta precursor protein transgenic mice that were treated with MitoQ and SS31, neurite outgrowth was significantly increased and cyclophilin D expression was significantly decreased. These findings suggest that MitoQ and SS31 prevent Abeta toxicity, which would warrant the study of MitoQ and SS31 as potential drugs to treat patients with AD. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is defined as mood disorder causing a persistent loss of interest and despair for two weeks or greater, with related symptoms. Depression can interfere with daily life and can cause those affected to not work, study, eat, sleep, and enjoy previously enjoyed hobbies and life events as they did previously. If untreated, it can become a serious health condition. Depression is multifactorial with a variety of factors influencing the condition. These factors include: (1) poor diet and exercise, (2) socioeconomic status, (3) gender, (4) biological clocks, (5) genetics and epigenetics, and (6) personal stressors. Treatment of depressive disorders is thus also multifactorial and utilizes the following therapies: (1) diet and exercise, (2) bright light therapy, (3) cognitive behavioral therapy, and (4) pharmaceutical therapy. Obesity is defined as body mass index over 30 and above, is believed to be causally linked to MDD through both psychological and molecular means. Atypical depression, a common form of MDD, is most strongly correlated with a high proclivity for obesity. Obesity and depression have a bidirectional relationship, a patient experiencing either condition singularly is more likely to develop the other due to the neural links between the two, including emotional lability, physical health of the brain, hormones, cytokine secretion, appetite, diet and feeding habits, inflammatory state. In individuals consuming a high fat diet (HFD) commonly ingested by those with obesity, the gut-microbiome is altered leading to systemic inflammation and the dysregulation of mood and the HPA axis impacting their neural health. The purpose of this paper is to examine the interplay of potential molecular, psychological, societal, and environmental causal factors of depressive disorders and how obesity perpetuates depression. A secondary aim of this paper is to examine current interventions that may help improve those affected by both conditions., Competing Interests: Declaration of competing interest Authors declare that they do not have any conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Currently, eight million people in the United States suffer from cancer and it is a major global health concern. Early detection and interventions are urgently needed for all cancers, including colorectal cancer. Colorectal cancer is the third most common type of cancer worldwide. Based on the diagnostic efforts to general awareness and lifestyle choices, it is understandable why colorectal cancer is so prevalent today. There is a notable lack of awareness concerning the impact of this cancer and its connection to lifestyle elements, as well as people sometimes mistaking symptoms for a different gastrointestinal condition. Artificial intelligence (AI) may assist in the early detection of all cancers, including colorectal cancer. The usage of AI has exponentially grown in healthcare through extensive research, and since clinical implementation, it has succeeded in improving patient lifestyles, modernizing diagnostic processes, and innovating current treatment strategies. Numerous challenges arise for patients with colorectal cancer and oncologists alike during treatment. For initial screening phases, conventional methods often result in misdiagnosis. Moreover, after detection, determining the course of which colorectal cancer can sometimes contribute to treatment delays. This article touches on recent advancements in AI and its clinical application while shedding light on why this disease is so common today., (©2024 American Association for Cancer Research.)

Depression is a complex and pervasive mental health disorder affecting millions globally. Serotonin, a critical neurotransmitter, plays a central role in the pathophysiology of depression. This review explores serotonin's multifaceted role in depression, focusing on its synthesis, bioavailability, receptor interactions, and the impact of various factors, including diet, stress, and gender differences. This review aims to provide a comprehensive understanding of serotonin's role in depression by examining its synthesis and structure, its bioavailability and dietary influences, and its interactions with stress and immune responses. Additionally, it investigates the influence of age, socioeconomic status, and gender on depression, and integrates findings from animal research to elucidate serotonin's impact on mood disorders and cognitive decline. A literature review was conducted using PubMed, Google Scholar, and Embase databases. Key focus areas included serotonin synthesis and receptor interactions, dietary effects on serotonin bioavailability, and the relationship between serotonin, immune responses, and stress. Gender differences, age-related factors, and socioeconomic influences on depression were also examined. Studies were thematically categorized and analyzed to provide a cohesive overview. Our review highlights that serotonin synthesis involves a complex enzymatic process, with recent structural studies revealing intricate receptor interactions. Dietary factors significantly impact serotonin levels, with interventions potentially modulating mood disorders. Stress and immune responses are linked to serotonin dynamics, with chronic stress exacerbating mood disorders and influencing cognitive decline. Animal studies underscore serotonin's role in mood regulation and cognitive function, while human research reveals how age, gender, and socioeconomic factors affect depression. The findings emphasize the need for a multidimensional approach to understanding and treating depression. Various factors, including diet, stress, and immune responses, influence serotonin's role in mood disorders. The review suggests potential therapeutic pathways involving dietary interventions and stress management. Furthermore, gender-specific considerations and the impact of age and socioeconomic status on depression outcomes highlight the need for tailored treatment strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Several decades of research on cell and animal models contributed tremendously to understanding human diseases. Particularly, research on rodents and non-human primates revealed that animal research is a major and important component in biomedical research in learning complex pathophysiological processes. Further, animal research helped us to understand human diseases, such as Alzheimer's disease. In addition, animal research has also helped us to test hundreds of drugs and develop treatments for human use. Researchers can gain a better understanding of key biological and physiological processes in humans by comparing them to laboratory animals. Based on their relevance and resemblance to people, or even usual living conditions, scientists rationalize the use of particular animal models in their studies. It is suggested that in the National Institutes of Health and other agencies-funded research, animal models should be carefully selected to study the biology and pathophysiology of human health and diseases such as Alzheimer's disease and other dementias. However, it is critical to use a minimum number of animals for human research. Further, it is also noted that the use and reuse of behavioral,  molecular, and biochemical data from wild-type (WT) control mice with mutant lines of disease models, as long as the genetic background is the same in both WT and disease mice. On the other hand, anonymous readers have challenged the use and reuse of WT mice data for comparison. In the current article, we discuss the minimum utility of animals, covering the 3Rs, Replacement, Reduction, and Refinement, and also discuss the use and reuse of behavioral, molecular, and biochemical data., Competing Interests: The authors have no conflict of interest to report., (© 2024 – The authors. Published by IOS Press.)

The human brain stands as an intricate organ, embodying a nexus of structure, function, development, and diversity. This review delves into the multifaceted landscape of the brain, spanning its anatomical intricacies, diverse functional capacities, dynamic developmental trajectories, and inherent variability across individuals. The dynamic process of brain development, from early embryonic stages to adulthood, highlights the nuanced changes that occur throughout the lifespan. The brain, a remarkably complex organ, is composed of various anatomical regions, each contributing uniquely to its overall functionality. Through an exploration of neuroanatomy, neurophysiology, and electrophysiology, this review elucidates how different brain structures interact to support a wide array of cognitive processes, sensory perception, motor control, and emotional regulation. Moreover, it addresses the impact of age, sex, and ethnic background on brain structure and function, and gender differences profoundly influence the onset, progression, and manifestation of brain disorders shaped by genetic, hormonal, environmental, and social factors. Delving into the complexities of the human brain, it investigates how variations in anatomical configuration correspond to diverse functional capacities across individuals. Furthermore, it examines the impact of neurodegenerative diseases on the structural and functional integrity of the brain. Specifically, our article explores the pathological processes underlying neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Huntington's diseases, shedding light on the structural alterations and functional impairments that accompany these conditions. We will also explore the current research trends in neurodegenerative diseases and identify the existing gaps in the literature. Overall, this article deepens our understanding of the fundamental principles governing brain structure and function and paves the way for a deeper understanding of individual differences and tailored approaches in neuroscience and clinical practice-additionally, a comprehensive understanding of structural and functional changes that manifest in neurodegenerative diseases., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Sleep is established as an essential physiological need that impacts physical, emotional, and cognitive functions profoundly. Physiologically, inadequate sleep weakens immune function, heightening susceptibility to infections and chronic illnesses such as obesity, diabetes, and cardiovascular diseases. Hormonal disruptions due to sleep loss further exacerbate metabolic dysregulation, contributing to weight gain and other health complications. Emotionally, sleep deprivation leads to mood disturbances, including increased irritability, heightened stress responses, and a greater likelihood of mood disorders like depression and anxiety. These effects are compounded by cognitive impairments such as reduced alertness, impaired memory consolidation, and compromised decision-making abilities, akin to the impairments caused by alcohol consumption. Motor skills and coordination also suffer, elevating the risk of accidents, particularly in high-stress environments. For older adults, sleep quality is closely linked to cognitive function and overall longevity. Optimal sleep patterns are associated with slower brain aging and improved health outcomes. However, sleep disorders exacerbate existing conditions such as epilepsy and asthma, necessitating interventions like cognitive behavioral therapy (CBT) and medications such as melatonin to mitigate their impact. Education emerges as a crucial tool in promoting healthier sleep habits across all age groups. Addressing misconceptions about sleep and integrating sleep health into public health policies are essential steps toward improving overall well-being. Additionally, lifestyle factors such as diet and physical activity play significant roles in regulating sleep patterns, further emphasizing the interconnectedness of sleep with broader health outcomes. In summary, the articles underscore the intricate mechanisms through which sleep influences physiological functions and advocate for comprehensive approaches to enhance sleep hygiene and mitigate the adverse effects of sleep deprivation on human health., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The use of housekeeping genes and proteins to normalize mRNA and protein levels in biomedical research has faced growing scrutiny. Researchers encounter challenges in determining the optimal frequency for running housekeeping proteins such as β-actin, Tubulin, and GAPDH for nuclear-encoded proteins, and Porin, HSP60, and TOM20 for mitochondrial proteins alongside experimental proteins. The regulation of these proteins varies with age, gender, disease progression, epitope nature, gel running conditions, and their reported sizes can differ among antibody suppliers. Additionally, anonymous readers have raised concerns about peer-reviewed and published articles, creating confusion and concern within the research and academic institutions. To clarify these matters, this minireview discusses the role of reference housekeeping proteins in Western blot analysis and outlines key considerations for their use as normalization controls. Instead of Western blotting of housekeeping proteins, staining of total proteins, using Amido Black and Coomassie Blue can be visualized the total protein content on a membrane. The reducing repeated Western blotting analysis of housekeeping proteins, will save resources, time and efforts and in turn increase the number of competitive grants from NIH and funding agencies. We also discussed the use of dot blots over traditional Western blots, when protein levels are low in rare tissues/specimens and cell lines. We sincerely hope that the facts, figures, and discussions presented in this article will clarify the current controversy regarding housekeeping protein(s) use, reuse, and functional aspects of housekeeping proteins. The contents presented in our article will be useful to students, scholars and researchers of all levels in cell biology, protein chemistry and mitochondrial research., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

MicroRNAs are small non-coding RNAs evolutionary conserved molecules. They regulate cellular processes, including RNA silencing, post-translational gene expression and neurodegeneration. MicroRNAs are involved with human diseases such as cancer, Alzheimer's disease (AD) and others. Interestingly, cerebrospinal fluids (CSF) and the blood of AD patients have altered expressions of many RNAs, which may serve as potential peripheral biomarkers. The intensive investigation from our lab revealed that microRNA-455-3 P (miR-455-3p) is a strong candidate as a potential biomarker and therapeutic target for AD. Several genes implicated in the pathogenesis of AD are directly targeted by miR-455-3p. Several years of our lab research revealed that miR-455-3p regulates important physiological processes associated with AD, such as the processing of the amyloid precursor protein (APP), TGF-β signaling, the regulation of oxidative stress, mitochondrial biogenesis, and synaptic damages. The expression of miR-455-3p in mild cognitive impaired subjects and AD patients pointed out its involvement in AD progression. Recently, our lab generated both transgenic and knockout mice for miR-455-3p. Interestingly miR-455-3p transgenic mice showed superior cognitive learning, improved memory and extended lifespan compared to age matched wild-type mice, whereas miR-455-3-p knockout mice showed cognitive decline and reduced lifespan. Information derived from mouse models further demonstrated the advantageous impact of miR-455-3p on dendritic growth, synaptogenesis, and mitochondrial biogenesis in preventing the onset and progression of AD. The identification of miR-455-3p as a biomarker was suggested by its presence in postmortem AD brains, B-lymphocytes, and fibroblasts. Our hypothesis that miR-455-3p could be a peripheral biomarker and therapeutic target for AD., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Alzheimer's disease (AD) is related to one or more chronic illnesses, which may develop cognitive decline and dementia. Cognitive impairment is increasing, and public health officials must address risk factors for AD to improve the health of rural West Texas communities., Objective: The purpose of this study was to explore the sociodemographic and chronic disease risk factors related to cognitive impairment among elderly adults living in Cochran, Parmer, and Bailey counties in rural West Texas., Methods: Statistical methods such as Pearson's chi-squared, proportion tests, univariate binary logistic regression, and a multivariable logistic regression were utilized to analyze data. SPSS software was used to detect the significant relationship between cognitive impairment and risk factors., Results: Summary statistics were obtained for sociodemographic and chronic diseases by using cross-tabulation analysis and comparing the county respondents with proportion tests. A univariate binary logistic regression method was utilized and found that age group 60-69, anxiety, depression, diabetes, hypertension, and cardiovascular disease were significantly associated with cognitive impairment. Using a multivariable logistic regression approach, it was found that Bailey County (age group 60-69) had a higher likelihood ( p  = 0.002) of cognitive impairment than Parmer ( p  = 0.067) and Cochran counties ( p  = 0.064). The risk of females ( p  = 0.033) in Parmer County was 78.3% lower compared to males in developing AD., Conclusions: Identifying significant risk factors for cognitive impairment are important in addressing issues of geographic variations and integrating such factors may guide relevant policy interventions to reduce cognitive impairment incidence in rural communities within West Texas., Competing Interests: The authors have no conflict of interest to report., (© 2024 – The authors. Published by IOS Press.)

An imbalance in estrogen signaling is a critical event in breast tumorigenesis. The majority of breast cancers (BCs) are hormone-sensitive; they majorly express the estrogen receptor (ER+) and are activated by 17β-estradiol (E2). The steroidogenic acute regulatory protein (StAR) mediates the rate-limiting step in steroid biosynthesis. The dysregulation of the epigenetic machinery, modulating E2 levels, is a primary occurrence for promoting breast tumorigenesis. StAR expression, concomitant with E2 synthesis, was reported to be aberrantly high in human and mouse hormone-dependent BC cells compared with their non-cancerous counterparts. However, the mechanism of action of StAR remains poorly understood. We discovered StAR as an acetylated protein and have identified a number of lysine (K) residues that are putatively acetylated in malignant and non-malignant breast cells, using LC-MS/MS (liquid chromatography-tandem mass spectrometry), suggesting they differently influence E2 synthesis in mammary tissue. The treatment of hormone-sensitive MCF7 cells with a variety of histone deacetylase inhibitors (HDACIs), at therapeutically and clinically relevant doses, identified a few additional StAR acetylated lysine residues. Among a total of fourteen StAR acetylomes undergoing acetylation and deacetylation, K111 and K253 were frequently recognized either endogenously or in response to HDACIs. Site-directed mutagenesis studies of these two StAR acetylomes, pertaining to K111Q and K253Q acetylation mimetic states, resulted in increases in E2 levels in ER+ MCF7 and triple negative MB-231 BC cells, compared with their values seen with human StAR. Conversely, these cells carrying K111R and K253R deacetylation mutants diminished E2 biosynthesis. These findings provide novel and mechanistic insights into intra-tumoral E2 regulation by elucidating the functional importance of this uncovered StAR post-translational modification (PTM), involving acetylation and deacetylation events, underscoring the potential of StAR as a therapeutic target for hormone-sensitive BC.

Dementia, a prevalent condition in the United States, affecting millions of individuals and their families, underscores the importance of healthy cognitive ageing, which involves maintaining cognitive function and mental wellness as individuals grow older, promoting overall well-being and quality of life. Our original research study investigates the correlation between lifestyle factors and brain atrophy in individuals with mild cognitive impairment (MCI) or Alzheimer's disease (AD), as well as healthy older adults. Conducted over six months in West Texas, the research involved 20 participants aged 62-87. Findings reveal that sleep deprivation in MCI subjects and AD patients correlate with posterior cingulate cortex, hippocampal atrophy and total brain volume, while both groups exhibit age-related hippocampal volume reduction. Notably, fruit/vegetable intake negatively correlates with certain brain regions' volume, emphasizing the importance of diet. Lack of exercise is associated with reduced brain volume and hippocampal atrophy, underlining the cognitive benefits of physical activity. The study underscores lifestyle's significant impact on cognitive health, advocating interventions to promote brain health and disease prevention, particularly in MCI/AD cases. While blood profile data showed no significant results regarding cognitive decline, the study underscores the importance of lifestyle modifications in preserving cognitive function., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest with the scientific contents of this manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Parkinson's disease (PD) is the second most common neurodegenerative disorder, globally affecting men and women at an exponentially growing rate, with currently no cure. Disease progression starts when dopaminergic neurons begin to die. In PD, the loss of neurotransmitter, dopamine is responsible for the overall communication of neural cells throughout the body. Clinical symptoms of PD are slowness of movement, involuntary muscular contractions, speech & writing changes, lessened automatic movement, and chronic tremors in the body. PD occurs in both familial and sporadic forms and modifiable and non-modifiable risk factors and socioeconomic conditions cause PD. Early detectable diagnostics and treatments have been developed in the last several decades. However, we still do not have precise early detectable biomarkers and therapeutic agents/drugs that prevent and/or delay the disease process. Recently, artificial intelligence (AI) science and machine learning tools have been promising in identifying early detectable markers with a greater rate of accuracy compared to past forms of treatment and diagnostic processes. Artificial intelligence refers to the intelligence exhibited by machines or software, distinct from the intelligence observed in humans that is based on neural networks in a form and can be used to diagnose the longevity and disease severity of disease. The term Machine Learning or Neural Networks is a blanket term used to identify an emerging technology that is created to work in the way of a "human brain" using many intertwined neurons to achieve the same level of raw intelligence as that of a brain. These processes have been used for neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease, to assess the severity of the patient's condition. In the current article, we discuss the prevalence and incidence of PD, and currently available diagnostic biomarkers and therapeutic strategies. We also highlighted currently available artificial intelligence science and machine learning tools and their applications to detect disease and develop therapeutic interventions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD) is characterized by the accumulation of amyloid β and phosphorylated τ protein aggregates in the brain, which leads to the loss of neurons. Under the microscope, the function of mitochondria is uniquely primed to play a pivotal role in neuronal cell survival, energy metabolism, and cell death. Research studies indicate that mitochondrial dysfunction, excessive oxidative damage, and defective mitophagy in neurons are early indicators of AD. This review article summarizes the latest development of mitochondria in AD: 1) disease mechanism pathways, 2) the importance of mitochondria in neuronal functions, 3) metabolic pathways and functions, 4) the link between mitochondrial dysfunction and mitophagy mechanisms in AD, and 5) the development of potential mitochondrial-targeted therapeutics and interventions to treat patients with AD., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

In recent years, the acronym NRF2 has garnered significant attention in scientific discourse. However, this attention has occasionally led to confusion due to the existence of two distinct proteins sharing the same acronym: Nuclear Respiratory Factor 2 (NRF2), also known as GA-binding protein transcription factor subunit alpha (GABPA), and Nuclear Factor Erythroid 2-related Factor 2 (NFE2L2 or NRF2). This confusion has been highlighted in various scientific forums, including PubPeer and anonymous reader comments, where the confusion between the two proteins has been expressed. In this article, we aim to elucidate the disparities between these two proteins. Both are transcription factors that play pivotal roles in cellular homeostasis and response to stress, with some overlapping functional aspects. Nuclear Factor Erythroid 2-related Factor 2 (NFE2L2) is a key regulator of the antioxidant response element (ARE) pathway. It functions by binding to antioxidant response elements in the promoters of target genes, thereby orchestrating the expression of various cytoprotective enzymes and proteins involved in detoxification, redox balance, and cellular defense against oxidative stress. Conversely, Nuclear Respiratory Factor 2 (GABPA) is primarily associated with the regulation of mitochondrial biogenesis, in relation to PGC1α, and maintaining cellular energy metabolism. It is important to recognize and differentiate between these two proteins to avoid misconceptions and misinterpretations in scientific literature and discussions. Our laboratories (Arubala P Reddy and P. Hemachandra Reddy) focued on Nuclear Respiratory Factor 2 (NRF2), but not on Nuclear Factor Erythroid 2-related Factor 2 (NFE2L2). We hope that the facts, figures, and discussions presented in this article will clarify the current controversy regarding the sizes, structural features, and functional aspects of these proteins., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Mild cognitive impairment (MCI) marks the initial phase of memory decline or other cognitive functions like language or spatial perception, while individuals typically retain the capacity to carry out everyday tasks independently. Our comprehensive article investigates the intricate landscape of cognitive disorders, focusing on MCI and Alzheimer's disease (AD) and Alzheimer's disease-related dementias (ADRD). The study aims to understand the signs of MCI, early Alzheimer's disease, and healthy brain aging while assessing factors influencing disease progression, pathology development and susceptibility. A systematic literature review of over 100 articles was conducted, emphasizing MCI, AD and ADRD within the elderly populations. The synthesis of results reveals significant findings regarding ethnicity, gender, lifestyle, comorbidities, and diagnostic tools. Ethnicity was found to influence MCI prevalence, with disparities observed across diverse populations. Gender differences were evident in cognitive performance and decline, highlighting the need for personalized management strategies. Lifestyle factors and comorbidities were identified as crucial influencers of cognitive health. Regarding diagnostic tools, the Montreal Cognitive Assessment (MoCA) emerged as superior to the Mini-Mental State Examination (MMSE) in early MCI detection. Overall, our article provides insights into the multifaceted nature of cognitive disorders, emphasizing the importance of tailored interventions and comprehensive assessment strategies for effective cognitive health management., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 Elsevier B.V. All rights reserved.)

The administration of promising medications for the treatment of neurodegenerative disorders (NDDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) is significantly hampered by the blood-brain barrier (BBB). Nanotechnology has recently come to light as a viable strategy for overcoming this obstacle and improving drug delivery to the brain. With a focus on current developments and prospects, this review article examines the use of nanoparticles to overcome the BBB constraints to improve drug therapy for AD The potential for several nanoparticle-based approaches, such as those utilizing lipid-based, polymeric, and inorganic nanoparticles, to enhance drug transport across the BBB are highlighted. To shed insight on their involvement in aiding effective drug transport to the brain, methods of nanoparticle-mediated drug delivery, such as surface modifications, functionalization, and particular targeting ligands, are also investigated. The article also discusses the most recent findings on innovative medication formulations encapsulated within nanoparticles and the therapeutic effects they have shown in both preclinical and clinical testing. This sector has difficulties and restrictions, such as the need for increased safety, scalability, and translation to clinical applications. However, the major emphasis of this review aims to provide insight and contribute to the knowledge of how nanotechnology can potentially revolutionize the worldwide treatment of NDDs, particularly AD, to enhance clinical outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Graceful healthy ageing and extended longevity is the most desired goal for human race. The process of ageing is inevitable and has a profound impact on the gradual deterioration of our physiology and health since it triggers the onset of many chronic conditions like dementia, osteoporosis, diabetes, arthritis, cancer, and cardiovascular disease. However, some people who lived/live more than 100 years called 'Centenarians" and how do they achieve their extended lifespans are not completely understood. Studying these unknown factors of longevity is important not only to establish a longer human lifespan but also to manage and treat people with shortened lifespans suffering from age-related morbidities. Furthermore, older adults who maintain strong cognitive function are referred to as "SuperAgers" and may be resistant to risk factors linked to cognitive decline. Investigating the mechanisms underlying their cognitive resilience may contribute to the development of therapeutic strategies that support the preservation of cognitive function as people age. The key to a long, physically, and cognitively healthy life has been a mystery to scientists for ages. Developments in the medical sciences helps us to a better understanding of human physiological function and greater access to medical care has led us to an increase in life expectancy. Moreover, inheriting favorable genetic traits and adopting a healthy lifestyle play pivotal roles in promoting longer and healthier lives. Engaging in regular physical activity, maintaining a balanced diet, and avoiding harmful habits such as smoking contribute to overall well-being. The synergy between positive lifestyle choices, access to education, socio-economic factors, environmental determinants and genetic supremacy enhances the potential for a longer and healthier life. Our article aims to examine the factors associated with healthy ageing, particularly focusing on cognitive health in centenarians. We will also be discussing different aspects of ageing including genomic instability, metabolic burden, oxidative stress and inflammation, mitochondrial dysfunction, cellular senescence, immunosenescence, and sarcopenia., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A caregiver is a constantly evolving role that an individual most likely undertakes at some point in their lifetime. With discoveries and research in increasing life expectancy, the prevalence of neurological-related diseases, such as Alzheimer's disease (AD) and dementia, is certainly likely to require more caregivers. The demand for AD caregivers is escalating as the prevalence of the disease continues to rise. The projected rise in AD within the Hispanic population in the United States over the next few decades is expected to be the most significant among all ethnic groups. The Hispanic population faces unique dementia risks due to cultural factors like language barriers, lower education, and limited healthcare access. Higher rates of conditions such as diabetes and cardiovascular disease further elevate dementia risk. Family dynamics and caregiving responsibilities also differ, affecting dementia management within Hispanic households. Addressing these distinct challenges requires culturally sensitive approaches to diagnosis, treatment, and support for Hispanic individuals and their family's facing dementia. With AD and other dementia becoming more prevalent, this article will attempt to expand upon the status of caregivers concerning their economic, health, and cultural statuses. We will attempt to focus on the Hispanic caregivers that live in Texas and more specifically, West Texas due to the lack of current literature that applies to this area of Texas. Lastly, we discuss the ramifications of a multitude of factors that affect caregivers in Texas and attempt to provide tools that can be readily available for Hispanics and others alike., Competing Interests: The authors have no conflict of interest to report., (© 2024 – The authors. Published by IOS Press.)

Alzheimer's disease (AD) is a age-related neurodegenerative disease and is a major public health concern both in Texas, US and Worldwide. This neurodegenerative disease is mainly characterized by amyloid-beta (Aβ) and phosphorylated Tau (p-Tau) accumulation in the brains of patients with AD and increasing evidence suggests that these are key biomarkers in AD. Both Aβ and p-tau can be detected through various imaging techniques (such as positron emission tomography, PET) and cerebrospinal fluid (CSF) analysis. The presence of these biomarkers in individuals, who are asymptomatic or have mild cognitive impairment can indicate an increased risk of developing AD in the future. Furthermore, the combination of Aβ and p-tau biomarkers is often used for more accurate diagnosis and prediction of AD progression. Along with AD being a neurodegenerative disease, it is associated with other chronic conditions such as cardiovascular disease, obesity, depression, and diabetes because studies have shown that these comorbid conditions make people more vulnerable to AD. In the first part of this review, we discuss that biofluid-based biomarkers such as Aβ, p-Tau in cerebrospinal fluid (CSF) and Aβ & p-Tau in plasma could be used as an alternative sensitive technique to diagnose AD. In the second part, we discuss the underlying molecular mechanisms of chronic conditions linked with AD and how they affect the patients in clinical care.

Dementia is a major health concern in society, particularly in the aging population. It is alarmingly increasing in ethnic minorities such as Native Americans, African Americans, Hispanics/Latinos, and to some extent Asians. With increasing comorbidities of dementia such as diabetes, obesity, and hypertension, dementia rates are expected to increase in the next decade and beyond. Understanding and treating dementia, as well as determining how to prevent it, has become a healthcare priority across the globe for all races and genders. Awareness about dementia and its consequences such as healthcare costs, and caregiver burden are immediate needs to be addressed. Therefore, it is high time for all of us to create awareness about dementia in society, particularly among Hispanics/Latinos, Native Americans, and African Americans. In the current article, we discuss the status of dementia, cultural, and racial impacts on dementia diagnosis and care, particularly in Hispanic populations, and possible steps to increase dementia awareness. We also discussed factors that need to be paid attention to, including, cultural & language barriers, low socioeconomic status, limited knowledge/education, religious/spiritual beliefs and not accepting modern medicine/healthcare facilities. Our article also covers both mental & physical health issues of caregivers who are living with patients with dementia, Alzheimer's disease, and Alzheimer's disease-related dementias. Most importantly, we discussed possible measures to create awareness about dementia, including empowering community advocacy, promoting healthy lifestyle choices, education on the impact of nutrition, encouraging community participation, and continued collaboration and evaluation of the success of dementia awareness., Competing Interests: The authors have no conflict of interest to report., (© 2024 – The authors. Published by IOS Press.)

Alzheimer's disease (AD) is an age-related neurodegenerative disease that is characterized by memory loss and multiple cognitive impairments. AD is pathologically characterized by age-dependent accumulation of amyloid-β protein and the phosphorylation of tau protein in the brains of patients with AD. Clinically, manifestations of AD include cognitive decline, dementia, alterations of high-order brain functions, and movement disorders. Double-stranded DNA breaks are a lethal form of DNA damage and are typically repaired via non-homologous end joining and homologous recombination. However, in AD brain, repair mechanism is disrupted, leading to a cascade of events, cognitive dysfunction, organ failure and reduced lifespan. Increased circulating cell-free DNA in the blood, cerebrospinal fluid, and urine in patients with AD, can be used as early detectable biomarkers for AD. The purpose of our article is to explore the potential uses of cell-free DNA and double-stranded DNA breaks as prognostic markers for AD and examine the recent research on the application of these markers in studies., Competing Interests: The authors have no conflict of interest to report., (© 2024 – The authors. Published by IOS Press.)

Alzheimer's disease (AD) and Alzheimer's disease-related disorders (ADRD) are progressive neurodegenerative diseases without cure. Alzheimer's disease occurs in 2 forms, early-onset familial AD and late-onset sporadic AD. Early-onset AD is a rare (~1%), autosomal dominant, caused by mutations in presenilin-1, presenilin-2, and amyloid precursor protein genes and the other is a late-onset, prevalent and is evolved due to age-associated complex interactions between environmental and genetic factors, in addition to apolipoprotein E4 polymorphism. Cellular senescence, promoting the impairment of physical and mental functions is constituted to be the main cause of aging, the primary risk factor for AD, which results in progressive loss of cognitive function, memory, and visual-spatial skills for an individual to live or act independently. Despite significant progress in the understanding of the biology and pathophysiology of AD, we continue to lack definitive early detectable biomarkers and/or drug targets that can be used to delay the development of AD and ADRD in elderly populations. However, recent developments in the studies of DNA double-strand breaks result in the release of fragmented DNA into the bloodstream and contribute to higher levels of cell-free DNA (cf-DNA). This fragmented cf-DNA can be released into the bloodstream from various cell types, including normal cells and cells undergoing apoptosis or necrosis and elevated levels of cf-DNA in the blood have the potential to serve as blood blood-based biomarker for early detection of AD and ADRD. The overall goal of our study is to discuss the latest developments in circulating cell-free DNA into the blood in the progression of AD and ADRD. Our article summarized the status of research on double-strand breaks and circulating cell-free DNA in both healthy and disease states and how these recent developments can be used to develop early detectable biomarkers for AD and ADRD. Our article also discussed the impact of lifestyle and epigenetic factors that are involved in DNA double-strand breaks and circulating cell-free DNA in AD and ADRD.

Our commentary aims to elucidate the importance of participant recruitment strategy in healthy brain aging study, particularly in rural West Texas, where more than 50% of the population are Hispanics and Latinos. The objective of our health aging study is to investigate the possible influence of biological, sociodemographic, and lifestyle factors on the occurrence of chronic diseases and dementia in the aging populations of West Texas. The success of this initiative is, in large part, reliant on high-quality, effective recruitment of participants. To that end, we propose an increase in our strategic recruitment efforts for both healthy, cognitively superior agers as well as those with mild cognitive impairment and patients with Alzheimer's disease in rural west Texas. We discussed, multi-advertising approaches, including ads in the local newspapers, local TV Channels and poster boards in senior centers., Competing Interests: The authors have no conflict of interest to report., (© 2024 – The authors. Published by IOS Press.)

The purpose of our study is to develop age-related phosphorylated tau (p-tau) inhibitors, for Alzheimer's disease (AD). There are wide-ranging therapeutic molecules available in the market and tested for age-related p-tau inhibition to enhance phosphatase activity and microtubule stability in AD neurons. Until now there are no such small molecules claimed to show promising results to delay the disease process of AD. However, a recently developed molecule, DDQ, has been shown to reduce abnormal protein-protein interactions and protect neurons from mutant protein-induced toxicities in the disease process. In addition, DDQ reduced age- and Aβ-induced oxidative stress, mitochondrial dysfunction, and synaptic toxicity. To date, there are no published reports on the p-tau interaction of DDQ and Sirt3 upregulation with CREB-mediated mitophagy activation in AD neurons. In the current study, HT22 cells were transfected with mutant Tau (mTau) cDNA and treated with the novel molecule DDQ. Cell survival, immunoblotting, and immunofluorescence analysis were conducted to assess cell viability and synaptic and mitophagy proteins in treated and untreated cell groups. As expected, we found cell survival was decreased in mTau-HT22 cells when compared with control HT22 cells. However, cell survival was increased in DDQ-treated mTau-HT22 cells when compared with mTau HT22 cells. P-tau and total tau proteins were significantly reduced in DDQ-treated mTau-HT22 cells, and MAP2 levels were increased. Anti-aging proteins like Sirt3, and CREB levels were increased in DDQ-treated HT22 cells and also in mTau-HT22 cells treated DDQ. Mitophagy proteins were decreased in mTau-HT22 cells and these were increased in DDQ-treated mTau-HT22 cells. These observations strongly suggest that DDQ has anti-p-tau and anti-aging properties, via Sirt3 overexpression and increased mitophagy proteins. Our study findings may have implications for healthy aging to the development of p-tau targeted therapeutics in AD and tauopathies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. and Mitochondria Research Society. All rights reserved.)

Pain is a complex, subjective experience that can significantly impact quality of life, particularly in aging individuals, by adversely affecting physical and emotional well-being. Whereas acute pain usually serves a protective function, chronic pain is a persistent pathological condition that contributes to functional deficits, cognitive decline, and emotional disturbances in the elderly. Despite substantial progress that has been made in characterizing age-related changes in pain, complete mechanistic details of pain processing mechanisms in the aging patient remain unknown. Pain is particularly under-recognized and under-managed in the elderly, especially among patients with Alzheimer's disease (AD), Alzheimer's disease-related dementias (ADRD), and other age-related conditions. Furthermore, difficulties in assessing pain in patients with AD/ADRD and other age-related conditions may contribute to the familial caregiver burden. The purpose of this article is to discuss the mechanisms and risk factors for chronic pain development and persistence, with a particular focus on age-related changes. Our article also highlights the importance of caregivers working with aging chronic pain patients, and emphasizes the urgent need for increased legislative awareness and improved pain management in these populations to substantially alleviate caregiver burden., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Alzheimer's disease is a progressive neurodegenerative disorder with a complex etiology, and effective interventions to prevent or delay its onset remain a global health challenge. In recent years, there has been growing interest in the potential role of probiotic and vitamin supplementation as complementary strategies for Alzheimer's disease prevention. This review paper explores the current scientific literature on the use of probiotics and vitamins, particularly vitamin A, D, E, K, and B-complex vitamins, in the context of Alzheimer's disease prevention and management. We delve into the mechanisms through which probiotics may modulate gut-brain interactions and neuroinflammation while vitamins play crucial roles in neuronal health and cognitive function. The paper also examines the collective impact of this combinational therapy on reducing the risk factors associated with Alzheimer's disease, such as oxidative stress, inflammation, and gut dysbiosis. By providing a comprehensive overview of the existing evidence and potential mechanisms, this review aims to shed light on the promise of probiotic and vitamin co-supplementation as a multifaceted approach to combat Alzheimer's disease, offering insights into possible avenues for future research and clinical application.

Several converging lines of evidence from our group support a potential role of RLIP76 (AKA Rlip) in neurodegenerative disorders, including Alzheimer's Disease (AD). However, the role of Rlip in Alzheimer's and other neurodegenerative diseases is not well understood. The purpose of the present study is to determine the role of Rlip in the brains of AD patients and control subjects. To achieve our goals, we used frozen tissues and formalin-fixed paraffin-embedded postmortem brains from AD patients of different Braak stages and age-matched control subjects. Our immunohistology and immunoblotting blotting analysis revealed that expression of Rlip protein gradually and significantly decreased (p = 0.0001) with AD progression, being lowest in Braak stage IV-V. Rlip was colocalized with Amyloid beta (Aβ) and phosphorylated tau (p-Tau) as observed by IHC staining and co-immunoprecipitation studies. Lipid peroxidation (4-HNE generation) and H 2 O 2 production were significantly higher (p = 0.004 and 0.0001 respectively) in AD patients compared to controls, and this was accompanied by lower ATP production in AD (p = 0.0009). Oxidative DNA damage was measured by 8-Hydroxyguanosine (8-OHdG) in tissue lysates by ELISA and COMET assay. AD 8-OHdG levels were significantly higher (p = 0.0001) compared to controls. COMET assay was performed in brain cells, isolated from frozen postmortem samples. The control samples showed minimal DNA in comets representing few DNA strand breaks (<20 %), (score-0-1). However, the AD group showed an average of 50 % to 65 % of DNA in comet tails (score-4-5) indicating numerous DNA strand breaks. The difference between the two groups was significant (p = 0.001), as analyzed by Open Comet by ImageJ. Elevated DNA damage was further examined by western blot analysis for phosphorylated histone variant H2AX (γH2AX). Induction of γH2AX was very significant (p < 0.0001) and confirmed the presence of double-strand breaks in DNA. Overall, our results indicate an important role for Rlip in maintaining neuronal health and homeostasis by suppressing cellular oxidative stress and DNA damage. Based on our findings, we cautiously conclude that Rlip is a promising therapeutic target for Alzheimer's disease., Competing Interests: Declaration of competing interest Authors declare that a pending disclosure is in progress with contents of this study., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Depression is among the most common neuropsychiatric comorbidities in Alzheimer's disease (AD) and other Tauopathies. Apart from its anti-depressive and anxiolytic effects, selective serotonin reuptake inhibitor (SSRI) treatment also offers intracellular modifications that may help to improve neurogenesis, reduce amyloid burden & Tau pathologies, and neuroinflammation in AD. Despite its multifaceted impact in the brain, the exact physiological and molecular mechanism by which SSRIs such as Citalopram improve neurogenesis and synaptogenesis in dementia is poorly understood. In the current study, we investigated the protective role of SSRI, Citalopram, in serotonergic, medullary raphe neurons (RN46A-B14). RN46A-B14 cells were transfected with wild-type and mutant APP and Tau cDNAs for 24 h and then treated with 20 μM Cit for 24 h. We then assessed mRNA and protein levels of pTau, total Tau, serotonin related proteins such as TPH2, SERT, and 5HTR1a, synaptic proteins and the cytoskeletal structure. We also assessed cell survival, mitochondrial respiration and mitochondrial morphology. The mutant APP and Tau transfected cells showed increased levels of serotonin related proteins and mRNA, while the mRNA and protein levels of synaptic proteins were downregulated. Citalopram treatment significantly reduced pathologically pTau level along with the serotonin related protein levels. On the other hand, there was a significant increase in the mRNA and protein levels of synaptic genes and cytoskeletal structure in the treated groups. Further, Citalopram also improved cell survival, mitochondrial respiration and mitochondrial morphology in the treated cells that express mAPP and mTau. Taken together these findings suggest Citalopram could not only be a promising therapeutic drug for treating patients with depression, but also for AD patients., Competing Interests: Declaration of competing interest Authors declare that they do not have any conflict of interest., (Published by Elsevier B.V.)

Cancer is the second leading cause of death worldwide, despite recent advances in its identification and management. To improve cancer patient diagnosis and care, it is necessary to identify new biomarkers and molecular targets. In recent years, long non-coding RNAs (lncRNAs) have surfaced as important contributors to various cellular activities, with growing proof indicating their substantial role in the genesis, development, and spread of cancer. Their unique expression profiles within specific tissues and their wide-ranging functionalities make lncRNAs excellent candidates for potential therapeutic intervention in cancer management. They are implicated in multiple hallmarks of cancer, such as uncontrolled proliferation, angiogenesis, and immune evasion. This review article explores the innovative application of CRISPR-Cas9 technology in targeting lncRNAs as a cancer therapeutic strategy. The CRISPR-Cas9 system has been widely applied in functional genomics, gene therapy, and cancer research, offering a versatile platform for lncRNA targeting. CRISPR-Cas9-mediated targeting of lncRNAs can be achieved through CRISPR interference, activation or the complete knockout of lncRNA loci. Combining CRISPR-Cas9 technology with high-throughput functional genomics makes it possible to identify lncRNAs critical for the survival of specific cancer subtypes, opening the door for tailored treatments and personalised cancer therapies. CRISPR-Cas9-mediated lncRNA targeting with other cutting-edge cancer therapies, such as immunotherapy and targeted molecular therapeutics can be used to overcome the drug resistance in cancer. The synergy of lncRNA research and CRISPR-Cas9 technology presents immense potential for individualized cancer treatment, offering renewed hope in the battle against this disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD) is a neurodegenerative disease that affects a large proportion of the aging population. RalBP1 (Rlip) is a stress-activated protein, that plays an important role in aging and neurodegenerative diseases such as Alzheimer's disease. Mutant APP and mutant Tau interact with the Rlip protein which leads to decreased wild-type Rlip levels and disrupt Rlip function in Alzheimer's disease. Rlip is a promising new target for aging, Alzheimer's disease, and other neurological diseases., Competing Interests: Declaration of competing interest The authors declare that a pending disclosure is in progress with the contents of this study., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The intricate and complex molecular mechanisms that underlie the progression of Alzheimer's disease (AD) have prompted a concerted and vigorous research endeavor aimed at uncovering potential avenues for therapeutic intervention., Objective: This study aims to elucidate the role of miRNA PC-5P-12969 in the pathogenesis of AD., Methods: We assessed the differential expression of miRNA PC-5P-12969 in postmortem AD brains, AD animal and cell models using real-time reverse-transcriptase RT-PCR, we also checked the gene and protein expression of GSK3α and APP., Results: Our investigation revealed a notable upregulation of miRNA PC-5P-12969 in postmortem brains of AD patients, in transgenic mouse models of AD, and in mutant APP overexpressing-HT22 cells. Additionally, our findings indicate that overexpression of miRNA PC-5P-12969 exerts a protective effect on cell survival, while concurrently mitigating apoptotic cell death. Further-more, we established a robust and specific interaction between miRNA PC-5P-12969 and GSK3α. Our luciferase reporter assays provided confirmation of the binding between miRNA PC-5P-12969 and the 3'-UTR of the GSK3α gene. Manipulation of miRNA PC-5P-12969 levels in cellular models of AD yielded noteworthy alterations in the gene and protein expression levels of both GSK3α and APP. Remarkably, the manipulation of miRNA PC-5P-12969 levels yielded significant enhancements in mitochondrial respiration and ATP production, concurrently with a reduction in mitochondrial fragmentation, thus unveiling a potential regulatory role of miRNA PC-5P-12969 in these vital cellular processes., Conclusions: In summary, this study sheds light on the crucial role of miRNA PC-5P-12969 and its direct interaction with GSK3α in the context of AD.

Alzheimer's disease (AD) and Alzheimer's disease-related dementias (ADRD) are the primary public health concerns in the United States and around the globe. AD/ADRD are irreversible mental illnesses that primarily impair memory and thought processes and may lead to cognitive decline among older individuals. The prevalence of AD/ADRD is higher in Native Americans, followed by African Americans and Hispanics. Increasing evidence suggests that Hispanics are the fastest-growing ethnic population in the USA and worldwide. Hispanics develop clinical symptoms of AD/ADRD and other comorbidities nearly seven years earlier than non-Hispanic whites. The consequences of AD/ADRD can be challenging for patients, their families, and caregivers. There is a significant increase in the burden of illness, primarily affecting Hispanic/Latino families. This is partly due to their strong sense of duty towards family, and it is exacerbated by the inadequacy of healthcare and community services that are culturally and linguistically suitable and responsive to their needs. With an increasing age population, low socioeconomic status, low education, high genetic predisposition to age-related conditions, unique cultural habits, and social behaviors, Hispanic Americans face a higher risk of AD/ADRD than other racial/ethnic groups. Our article highlights the status of Hispanic older adults with AD/ADRD. We also discussed the intervention to improve the quality of life in Hispanic caregivers., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Breast cancer (BC) is a heterogeneous condition and comprises molecularly distinct subtypes. An imbalance in the levels of epigenetic histone deacetylases (HDACs), modulating estrogen accumulation, especially 17β-estradiol (E2), promotes breast tumorigenesis. In the present study, analyses of The Cancer Genome Atlas (TCGA) pan-cancer normalized RNA-Seq datasets revealed the dysregulation of 16 epigenetic enzymes (among a total of 18 members) in luminal BC subtypes, in comparison to their non-cancerous counterparts. Explicitly, genomic profiling of these epigenetic enzymes displayed increases in HDAC1, 2, 8, 10, 11, and Sirtuins (SIRTs) 6 and 7, and decreases in HDAC4-7, -9, and SIRT1-4 levels, respectively, in TCGA breast tumors. Kaplan-Meier plot analyses showed that these HDACs, with the exception of HDAC2 and SIRT2, were not correlated with the overall survival of BC patients. Additionally, disruption of the epigenetic signaling in TCGA BC subtypes, as assessed using both heatmaps and boxplots, was associated with the genomic expression of factors that are instrumental for cholesterol trafficking/utilization for accelerating estrogen/E2 levels, in which steroidogenic acute regulatory protein (STAR) mediates the rate-limiting step in steroid biosynthesis. TCGA breast samples showed diverse expression patterns of a variety of key steroidogenic markers and hormone receptors, including LIPE, CYP27A1, STAR, STARD3, CYP11A1, CYP19A1, ER, PGR, and ERBB2 . Moreover, regulation of STAR-governed steroidogenic machinery was found to be influenced by various transcription factors, i.e., CREB1, CREM, SF1, NR4A1, CEBPB, SREBF1, SREBF2, SP1, FOS, JUN, NR0B1, and YY1 . Along these lines, ingenuity pathway analysis (IPA) recognized a number of new targets and downstream effectors influencing BCs. Of note, genomic, epigenomic, transcriptional, and hormonal anomalies observed in human primary breast tumors were qualitatively similar in pertinent BC cell lines. These findings identify the functional correlation between dysregulated epigenetic enzymes and estrogen/E2 accumulation in human breast tumors, providing the molecular insights into more targeted therapeutic approaches involving the inhibition of HDACs for combating this life-threatening disease.

Healthy aging is the process of preserving and enhancing one's independence, physical and mental well-being, and overall quality of life. It involves the mental, emotional, and cognitive wellness. Although biological and genetic factors have a significant influence on the process of aging gracefully, other adjustable factors also play a crucial role. Adopting positive behaviors such as maintaining a nutritious and balanced diet, engaging in regular physical activity, effectively managing stress and anxiety, ensuring sufficient sleep, nurturing spiritual coping mechanisms, and prioritizing overall well-being from an early stage can collectively influence both lifespan and the quality of health during advanced years. We aim to explore the potential impacts of biological, psychosocial, and environmental factors on the process of healthy cognitive aging in individuals who exhibit healthy aging. Additionally, we plan to present initial findings that demonstrate how maintaining good cognitive health during aging could potentially postpone the emergence of neurodegenerative disorders. We hypothesize that there will be strong associations between biological, environmental, and social factors that cause some elderly to be superior in cognitive health than others. For preliminary data collection, we recruited 25 cognitively healthy individuals and 5 individuals with MCI/AD between the ages of 60-90 years. We conducted anthropometric measurements, and blood biomarker testing, administered surveys, and obtained structural brain magnetic resonance imaging (MRI) scans. The Montreal Cognitive Assessment (MoCA) scores and sub-scores for the healthy group were also reported. We found that at baseline, individuals exhibiting healthy cognitive aging, and those with MCI/AD had comparable measures of anthropometrics and blood biomarkers. The healthy group exhibited lower signs of brain volume loss and the ones observed were age-related. Moreover, within the healthy group, there was a significant correlation (p = 0.003) between age and MoCA scores. Conversely, within the individuals with MCI/AD, the MRI scans showed disease signs of grey and white matter and loss of cerebral volume. Healthy brain aging is a scientific area that remains under-explored. Our current study findings support our hypothesis. Future studies are required in diverse populations to determine the various biological, psychological, environmental, lifestyle, and social factors that contribute to it., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD) is a progressive neurodegenerative disease, characterized by memory loss and multiple cognitive impairments. Genetic mutations cause a small proportion (1-2%) of early-onset AD, with mutations in amyloid precursor protein (APP), presenilin 1 (PS1) and presenilin 2 (PS2). Major contributing factors of late-onset AD are ApoE4 genotype, traumatic brain injury, diabetes, obesity, hypertension, cardiovascular conditions, in addition to lifestyle factors, such as unhealthy diet and lack of physical exercise. Disease progression can be delayed and/or prevented to a greater extent by adopting healthy lifestyle with balanced and antioxidant enriched diet and daily exercise. The interaction and interplay of diet, exercise, age, and pharmacological interventions holds a crucial role in the progression, pathogenesis and management of AD and its comorbidities, including diabetes, obesity, hypertension and cardiovascular conditions. Antioxidant enriched diet contributes to brain health, glucose control, weight management, and cardiovascular well-being. Regular exercise removes toxins including free radicals and enhances insulin sensitivity, and supports cardiovascular function. In the current article, we discussed, the role of diet, and exercise in aging, AD and other conditions including diabetes, obesity, hypertension, cardiovascular conditions. This article also highlights the impact of medication, socioeconomic and lifestyle factors, and pharmacological interventions. These aspects were discussed in different races and ethnic groups in Texas, and the US., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Pancreatic ductal adenocarcinoma (PDAC) cells have a great demand for nutrients in the form of sugars, amino acids, and lipids. Particularly, amino acids are critical for cancer growth and, as intermediates, connect glucose, lipid and nucleotide metabolism. PDAC cells meet these requirements by upregulating selective amino acid transporters. Here we show that SLC38A5 (SN2/SNAT5), a neutral amino acid transporter is highly upregulated and functional in PDAC cells. Using CRISPR/Cas9-mediated knockout of SLC38A5, we show its tumor promoting role in an in vitro cell line model as well as in a subcutaneous xenograft mouse model. Using metabolomics and RNA sequencing, we show significant reduction in many amino acid substrates of SLC38A5 as well as OXPHOS inactivation in response to SLC38A5 deletion. Experimental validation demonstrates inhibition of mTORC1, glycolysis and mitochondrial respiration in KO cells, suggesting a serious metabolic crisis associated with SLC38A5 deletion. Since many SLC38A5 substrates are activators of mTORC1 as well as TCA cycle intermediates/precursors, we speculate amino acid insufficiency as a possible link between SLC38A5 deletion and inactivation of mTORC1, glycolysis and mitochondrial respiration, and the underlying mechanism for PDAC attenuation. Overall, we show that SLC38A5 promotes PDAC, thereby identifying a novel, hitherto unknown, therapeutic target for PDAC., (© 2023. Springer Nature Limited.)

Alzheimer's disease (AD) is a neurodegenerative disease that affects a large proportion of the aging population. RalBP1 (Rlip) is a stress-activated protein that plays a crucial role in oxidative stress and mitochondrial dysfunction in aging and neurodegenerative diseases but its precise role in the progression of AD is unclear. The purpose of our study is to understand the role of Rlip in the progression and pathogenesis of AD in mutant APP/amyloid beta (Aβ)-expressed mouse primary hippocampal (HT22) hippocampal neurons. In the current study, we used HT22 neurons that express mAPP, transfected with Rlip-cDNA and/or RNA silenced, and studied cell survival, mitochondrial respiration, mitochondrial function, immunoblotting & immunofluorescence analysis of synaptic and mitophagy protein's and colocalization of Rlip and mutant APP/Aβ proteins and mitochondrial length and number. We also assessed Rlip levels in autopsy brains from AD patients and control subjects. We found cell survival was decreased in mAPP-HT22 cells and RNA-silenced HT22 cells. However, cell survival was increased in Rlip-overexpressed mAPP-HT22 cells. Oxygen consumption rate (OCR) was decreased in mAPP-HT22 cells and RNA-silenced Rlip-HT22 cells. OCR was increased in Rlip-overexpressed in mAPP-HT22 cells. Mitochondrial function was defective in mAPP-HT22 cells and RNA silenced Rlip in HT22 cells, however, it was rescued in Rlip overexpressed mAPP-HT22 cells. Synaptic and mitophagy proteins were decreased in mAPP-HT22 cells, further reducing RNA-silenced Rlip-HT22 cells. However, these were increased in mAPP+Rlip-HT22 cells. Colocalization analysis revealed Rlip is colocalized with mAPP/Aβ. An increased number of mitochondria and decreased mitochondrial length were found in mAPP-HT22 cells. These were rescued in Rlip overexpressed mAPP-HT22 cells. Reduced Rlip levels were found in autopsy brains from AD patients. These observations strongly suggest that Rlip deficiency causes oxidative stress/mitochondrial dysfunction and Rlip overexpression reduced these defects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD) is a neurodegenerative disease that manifests its pathology through synaptic damage, mitochondrial abnormalities, microRNA deregulation, hormonal imbalance, increased astrocytes & microglia, accumulation of amyloid β (Aβ) and phosphorylated Tau in the brains of AD patients. Despite extensive research, the effective treatment of AD is still unknown. Tau hyperphosphorylation and mitochondrial abnormalities are involved in the loss of synapses, defective axonal transport and cognitive decline in patients with AD. Mitochondrial dysfunction is evidenced by enhanced mitochondrial fragmentation, impaired mitochondrial dynamics, mitochondrial biogenesis and defective mitophagy in AD. Hence, targeting mitochondrial proteins might be a promising therapeutic strategy in treating AD. Recently, dynamin-related protein 1 (Drp1), a mitochondrial fission protein, has gained attention due to its interactions with Aβ and hyperphosphorylated Tau, altering mitochondrial morphology, dynamics, and bioenergetics. These interactions affect ATP production in mitochondria. A reduction in Drp1 GTPase activity protects against neurodegeneration in AD models. This article provides a comprehensive overview of Drp1's involvement in oxidative damage, apoptosis, mitophagy, and axonal transport of mitochondria. We also highlighted the interaction of Drp1 with Aβ and Tau, which may contribute to AD progression. In conclusion, targeting Drp1 could be a potential therapeutic approach for preventing AD pathology., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The ageing process begins at birth. It is a life-long process, and its exact origins are still unknown. Several hypotheses attempt to describe the normal ageing process, including hormonal imbalance, formation of reactive oxygen species, DNA methylation & DNA damage accumulation, loss of proteostasis, epigenetic alterations, mitochondrial dysfunction, senescence, inflammation, and stem cell depletion. With increased lifespan in elderly individuals, the prevalence of age-related diseases including, cancer, diabetes, obesity, hypertension, Alzheimer's, Alzheimer's disease and related dementias, Parkinson's, and other mental illnesses are increased. These increased age-related illnesses, put tremendous pressure & burden on caregivers, family members, and friends who are living with patients with age-related diseases. As medical needs evolve, the caregiver is expected to experience an increase in duties and challenges, which may result in stress on themselves, and impact their own family life. In the current article, we assess the biological mechanisms of ageing and its effect on body systems, exploring lifestyle and ageing, with a specific focus on age-related disorders. We also discussed the history of caregiving and specific challenges faced by caregivers in the presence of multiple comorbidities. We also assessed innovative approaches to funding caregiving, and efforts to improve the medical system to better organize chronic care efforts, while improving the skill and efficiency of both informal and formal caregivers. We also discussed the role of caregiving in end-of-life care. Our critical analysis strongly suggests that there is an urgent need for caregiving in aged populations and support from local, state, and federal agencies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Huntington's disease (HD) is a complex progressive neurodegenerative disorder affected by genetic, environmental, and metabolic factors contributing to its pathogenesis. Gut dysbiosis is termed as the alterations of intestinal microbial profile. Emerging research has highlighted the pivotal role of gut dysbiosis in HD, focusing on the gut-brain axis as a novel research parameter in science. This review article provides a comprehensive overview of gut microbiota dysbiosis and its relationship with HD and its pathogenesis along with the future challenges and opportunities. The focuses on the essential mechanisms which link gut dysbiosis to HD pathophysiology including neuroinflammation, immune system dysregulation, altered metabolites composition, and neurotransmitter imbalances. We also explored the impacts of gut dysbiosis on HD onset, severity, and symptoms such as cognitive decline, motor dysfunction, and psychiatric symptoms. Furthermore, we highlight recent advances in therapeutics including microbiota-based therapeutic approaches, including dietary interventions, prebiotics, probiotics, fecal microbiota transplantation, and combination therapies with conventional HD treatments and their applications in managing HD. The future challenges are also highlighted as the heterogeneity of gut microbiota, interindividual variability, establishing causality between gut dysbiosis and HD, identifying optimal therapeutic targets and strategies, and ensuring the long-term safety and efficacy of microbiota-based interventions. This review provides a better understanding of the potential role of gut microbiota in HD pathogenesis and guides the development of novel therapeutic approaches., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Alzheimer's disease (AD) and Alzheimer's related dementias (ADRD) are growing public health concerns in aged populations of all ethnic and racial groups. AD and ADRD are caused by multiple factors, such as genetic mutations, modifiable and non-modifiable risk factors, and lifestyle. Studies of postmortem brains have revealed multiple cellular changes implicated in AD and ADRD, including the accumulation of amyloid beta and phosphorylated tau, synaptic damage, inflammatory responses, hormonal imbalance, mitochondrial abnormalities, and neuronal loss. These changes occur in both early-onset familial and late-onset sporadic forms. Two-thirds of women and one-third of men are at life time risk for AD. A small proportion of total AD cases are caused by genetic mutations in amyloid precursor protein, presenilin 1, and presenilin 1 genes, and the APOE4 allele is a risk factor. Tremendous research on AD/ADRD, and other comorbidities such as diabetes, obesity, hypertension, and cancer has been done on almost all ethnic groups, however, very little biomedical research done on US Native Americans. AD/ADRD prevalence is high among all ethnic groups. In addition, US Native Americans have poorer access to healthcare and medical services and are less likely to receive a diagnosis once they begin to exhibit symptoms, which presents difficulties in treating Alzheimer's and other dementias. One in five US Native American people who are 45 years of age or older report having memory issues. Further, the impact of caregivers and other healthcare aspects on US Native Americans is not yet. In the current article, we discuss the history of Native Americans of United States (US) and health disparities, occurrence, and prevalence of AD/ADRD, and shedding light on the culturally sensitive caregiving practices in US Native Americans. This article is the first to discuss biomedical research and healthcare disparities in US Native Americans with a focus on AD and ADRD, we also discuss why US Native Americans are reluctant to participate in biomedical research., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest with the contents of this article.