Small molecule inhibitor DDQ-treated hippocampal neuronal cells show improved neurite outgrowth and synaptic branching.

ABSTRACT: The process of neurite outgrowth and branching is a crucial aspect of neuronal development and regeneration. Axons and dendrites, sometimes referred to as neurites, are extensions of a neuron's cellular body that are used to start networks. Here we explored the effects of diethyl (3,4-dihydroxyphenethylamino)(quinolin-4-yl) methylphosphonate (DDQ) on neurite developmental features in HT22 neuronal cells. In this work, we examined the protective effects of DDQ on neuronal processes and synaptic outgrowth in differentiated HT22 cells expressing mutant Tau (mTau) cDNA. To investigate DDQ characteristics, cell viability, biochemical, molecular, western blotting, and immunocytochemistry were used. Neurite outgrowth is evaluated through the segmentation and measurement of neural processes. These neural processes can be seen and measured with a fluorescence microscope by manually tracing and measuring the length of the neurite growth. These neuronal processes can be observed and quantified with a fluorescent microscope by manually tracing and measuring the length of the neuronal HT22. DDQ-treated mTau-HT22 cells (HT22 cells transfected with cDNA mutant Tau) were seen to display increased levels of synaptophysin, MAP-2, and ß-tubulin. Additionally, we confirmed and noted reduced levels of both total and p-Tau, as well as elevated levels of microtubule-associated protein 2, ß-tubulin, synaptophysin, vesicular acetylcholine transporter, and the mitochondrial biogenesis protein-peroxisome proliferator-activated receptor-gamma coactivator-1α. In mTau-expressed HT22 neurons, we observed DDQ enhanced the neurite characteristics and improved neurite development through increased synaptic outgrowth. Our findings conclude that mTau-HT22 (Alzheimer's disease) cells treated with DDQ have functional neurite developmental characteristics. The key finding is that, in mTau-HT22 cells, DDQ preserves neuronal structure and may even enhance nerve development function with mTau inhibition.

Caring for Individuals with Alzheimer's Disease: A Spotlight on Hispanic Caregivers.

 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.

Optimizing Process Parameters for Controlled Drug Delivery: A Quality by Design (QbD) Approach in Naltrexone Microspheres.

The formulation of microspheres involves a complex manufacturing process with multiple steps. Identifying the appropriate process parameters to achieve the desired quality attributes poses a significant challenge. This study aims to optimize the critical process parameters (CPPs) involved in the preparation of naltrexone microspheres using a Quality by Design (QbD) methodology. Additionally, the research aims to assess the drug release profiles of these microspheres under both in vivo and in vitro conditions. Critical process parameters (CPPs) and critical quality attributes (CQAs) were identified, and a Box-Behnken design was utilized to delineate the design space, ensuring alignment with the desired Quality Target Product Profile (QTPP). The investigated CPPs comprised polymer concentration, aqueous phase ratio to organic phase ratio, and quench volume. The microspheres were fabricated using the oil-in-water emulsion solvent extraction technique. Analysis revealed that increased polymer concentration was correlated with decreased particle size, reduced quench volume resulted in decreased burst release, and a heightened aqueous phase ratio to organic phase ratio improved drug entrapment. Upon analyzing the results, an optimal formulation was determined. In conclusion, the study conducted in vivo drug release testing on both the commercially available innovator product and the optimized test product utilizing an animal model. The integration of in vitro dissolution data with in vivo assessments presents a holistic understanding of drug release dynamics. The QbD approach-based optimization of CPPs furnishes informed guidance for the development of generic pharmaceutical formulations.

Clinical and radiological spectrum of acquired inflammatory demyelinating diseases of the central nervous system in a tertiary care center.

Objectives: Demyelinating diseases of central nervous system (CNS) are a broad spectrum of conditions with autoimmune process against myelin. In a resource limited country like India, it is imperative to perform proper clinical evaluation, neuroimaging to differentiate among various categories of CNS demyelinating diseases to decide regarding further workup and treatment. The objective of our study was to determine clinical presentation, imaging findings, serology results, diagnosis, and treatment outcome of primary demyelinating disorders of CNS. Materials and Methods: In this prospective study, a total of 44 patients were enrolled over a period of 1 year. After proper evaluation, patients were categorized into different groups applying newer diagnostic criteria. Patients were treated with steroids, appropriate immunomodulatory therapy, and outcomes were analyzed. Results: The majority of cases were of neuromyelitis optica spectrum disorder (NMOSD) (45.5%) with an overall female-to-male ratio of 3.4:1 and mean age of presentation was 30.5 ± 11.15. Myelitis (52.3%) followed by optic neuritis (45.5%) was the most common initial presentation. The most common site of involvement on magnetic resonance imaging was the spinal cord (particularly the cervicodorsal cord). The majority showed good response to therapy (77.27%) and two patients did not survive. Conclusion: Higher disability observed among seropositive NMOSD patients warrants aggressive treatment during the first attack itself. It is important to suspect myelin oligodendrocyte glycoprotein antibody disease in patients with preceding viral infection. A good outcome in the majority is likely due to the availability of serological assays and aggressive immunomodulatory therapy.

Circulating Cell Free DNA and DNA Double-Strand Breakage in Alzheimer's Disease.

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-ß 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.

Creating Cultural and Lifestyle Awareness About Dementia and Co-morbidities.

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.

Application of machine-learning model to optimize colonic adenoma detection in India.

AIMS: There is limited data on the prevalence and risk factors of colonic adenoma from the Indian sub-continent. We aimed at developing a machine-learning model to optimize colonic adenoma detection in a prospective cohort. METHODS: All consecutive adult patients undergoing diagnostic colonoscopy were enrolled between October 2020 and November 2022. Patients with a high risk of colonic adenoma were excluded. The predictive model was developed using the gradient-boosting machine (GBM)-learning method. The GBM model was optimized further by adjusting the learning rate and the number of trees and 10-fold cross-validation. RESULTS: Total 10,320 patients (mean age 45.18 ± 14.82 years; 69% men) were included in the study. In the overall population, 1152 (11.2%) patients had at least one adenoma. In patients with age > 50 years, hospital-based adenoma prevalence was 19.5% (808/4144). The area under the receiver operating curve (AUC) (SD) of the logistic regression model was 72.55% (4.91), while the AUCs for deep learning, decision tree, random forest and gradient-boosted tree model were 76.25% (4.22%), 65.95% (4.01%), 79.38% (4.91%) and 84.76% (2.86%), respectively. After model optimization and cross-validation, the AUC of the gradient-boosted tree model has increased to 92.2% (1.1%). CONCLUSIONS: Machine-learning models may predict colorectal adenoma more accurately than logistic regression. A machine-learning model may help optimize the use of colonoscopy to prevent colorectal cancers. TRIAL REGISTRATION: ClinicalTrials.gov (ID: NCT04512729).

Comparative Retention Analysis of Intercalated Cations Inside the Interlayer Gallery of Lamellar and Nonlamellar Graphene Oxide Membranes in Reverse Osmosis Process: A Molecular Dynamics Study.

Over the past decade, multilayered graphene oxide (GO) membranes have emerged as promising candidates for desalination applications. Despite their potential, a comprehensive understanding of separation mechanisms remains elusive due to the intricate morphology and structural arrangement of interlayer galleries. Moreover, a critical concern of multilayered GO membranes is their susceptibility to swelling within aqueous environments, which hinders their practical implementation. Therefore, this study introduces cation intercalation within GO laminates to elucidate the underlying factors governing swelling behavior and subsequently mitigate it. Moreover, this study performed nonequilibrium molecular dynamics simulations on the cation (Mg2+ or K+)-intercalated lamellar and nonlamellar GO membranes to understand the effect of the arrangement of GO sheets on the retention time of intercalated cations within GO layers, water permeance, and salt rejection mechanism in the reverse osmosis process using cation-intercalated GO membranes. Our results highlight that lamellar GO membranes exhibit higher water permeance, attributed to their well-defined interlayer gallery structure. On the other hand, nonlamellar GO membranes display superior salt rejection due to their complex interlayer gallery structure that impedes salt permeation. Moreover, the structural complexity of nonlamellar GO membranes contributes to greater stability by retention of the more intercalated cations for a longer time within the layers. Furthermore, it is observed that a higher percentage of Mg2+ cations remained inside the GO laminates as compared to K+ cations, hence resulting in the greater stability of the Mg2+-intercalated GO membrane in the aqueous environment.

Ruthenium-106 (106Ru) plaque brachytherapy for treatment of circumscribed choroidal hemangioma.

PURPOSE: To describe the clinical and imaging features of circumscribed choroidal hemangiomas (CCH) and their treatment outcomes with Ruthenium-106 (106Ru) plaque brachytherapy. METHODS: Retrospective study of 24 patients (24 eyes) diagnosed with CCH and treated with 106Ru plaque between 2017 and 2022. Analysis included pre- and post-treatment clinical and imaging features such as tumor regression, reduction in height, subretinal fluid (SRF) resolution, and change in best-corrected visual acuity (BCVA). RESULTS: The mean age at presentation was 36 years (range, 16-57). The most common tumor location was the temporal quadrant (n = 19) with macular involvement (n = 13). Associated features were macular SRF (n = 22) and inferior exudative retinal detachment (n = 10). Nineteen of the 24 patients underwent primary treatment, whereas 5 patients underwent plaque as a salvage treatment. The mean tumor apex dose was 40 Gy. At a median follow-up of 7.5 months (range 3-65 months), 18 eyes showed complete regression, whereas 6 eyes showed partial regression. The mean height decreased from 4.8 (SD 1.28) mm at presentation to 2.5 (SD 1.63) mm. Median BCVA improved from logMAR 1.2 (IQR 0.4-2) at baseline to logMAR 1.05 (IQR 0.1-1.95) (p = 0.4). Complete resolution of the macula and tumor SRF was observed in 15 (68%) and 13 (57%) eyes, respectively. The radiation-related complications observed were radiation maculopathy (4 eyes), retinopathy (1 eye), and vitreous hemorrhage (1 eye). CONCLUSION: Ruthenium-106 plaque brachytherapy is effective for CCH (> 3 mm height) as a primary and salvage treatment for tumors unresponsive to other modalities.

Overlooked cases of mild cognitive impairment: Implications to early Alzheimer's disease.

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.

Unraveling the NRF2 confusion: Distinguishing nuclear respiratory factor 2 from nuclear erythroid factor 2.

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.

RET Alterations Differentiate Molecular Profile of Medullary Thyroid Cancer.

PURPOSE: Medullary thyroid cancer (MTC) is a rare cancer originating from parafollicular C cells of the thyroid gland. Therapeutically relevant alterations in MTC are predominantly reported in RET oncogene, and lower-frequency alterations are reported in KRAS and BRAF. Nevertheless, there is an unmet need existing to analyze the MTC in the Indian cohort by using in-depth sequencing techniques that go beyond the identification of known therapeutic biomarkers. MATERIALS AND METHODS: Here, we characterize MTC using integrative whole-exome and whole-transcriptome sequencing of 32 MTC tissue samples. We performed clinically relevant variant analysis, molecular pathway analysis, tumor immune-microenvironment analysis, and structural characterization of RET novel mutation. RESULTS: Mutational landscape analysis shows expected RET mutations in 50% of the cases. Furthermore, we observed mutations in known cancer genes like KRAS, HRAS, SF3B1, and BRAF to be altered only in the RET-negative cohort. Pathway analysis showed differential enrichment of mutations in transcriptional deregulation genes in the RET-negative cohort. Furthermore, we observed novel RET kinase domain mutation Y900S showing affinity to RET inhibitors accessed via molecular docking and molecular dynamics simulation. CONCLUSION: Altogether, this study provides a detailed genomic characterization of patients with MTC of Indian origin, highlighting the possible utility of targeted therapies in this disease.

Amyloid-ß and Phosphorylated Tau are the Key Biomarkers and Predictors of Alzheimer's Disease.

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 (Aß) 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 Aß 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 Aß 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 Aß, p-Tau in cerebrospinal fluid (CSF) and Aß & 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.

Cell-Free DNA As Peripheral Biomarker of Alzheimer's Disease.

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.

SuperAgers and centenarians, dynamics of healthy ageing with cognitive resilience.

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.

Treating Alzheimer's disease using nanoparticle-mediated drug delivery strategies/systems.

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.

Authentication of traditional meat products (Haleem) sold in India: a first report confirming species mislabelling.

Traditional meat products like Haleem play a pivotal role in the culinary landscapes of Indian consumers, along with high economic value and business potential. Due to anticipated gains associated with adulterating 'Haleem' and constant evasion from regulatory oversight, the susceptibility to adulteration has substantially increased. Furthermore, no reports/surveillance regarding their labelling compliance has been reported. Hence, we conducted a 2-year surveillance using 100 samples collected from Hyderabad, India, using the Chipron™ DNA macroarray analysis technique. The method was validated for sensitivity (1%), specificity, and with proficiency test samples. Following this, the surveillance samples (beef, chicken, and mutton Haleem) were tested. The surveillance revealed an alarming adulteration of 46% of the samples, with different proportions of adulterant species. Adulteration of unconventional meat like camel meat was also found. These concerning results necessitate the requirement of stricter and constant regulatory surveillance to safeguard consumer trust and preserve the authenticity of traditional meat products. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-024-05947-9.

Unveiling the Role of Novel miRNA PC-5P-12969 in Alleviating Alzheimer's Disease.

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.