Clinical Significance of MUC4 and Associated Proteins in Pancreatic and Periampullary Cancers.

OBJECTIVE: This study primarily aimed to assess the expression of MUC4 in patients with pancreatic ductal adenocarcinoma (PDAC) as compared with controls and assess its clinical relevance. MATERIALS AND METHODS: Serum MUC4 levels and MUC4 gene expression in snap-frozen tissue were analyzed through surface plasmon resonance and quantitative polymerase chain reaction, respectively. Tumor tissues and control tissues were analyzed for MUC4 and other mucins through immunohistochemistry. RESULT: MUC4 expression in tumor tissue was found to be significantly elevated in PDAC patients as compared with chronic pancreatitis tissues and normal pancreatic tissues. Periampullary carcinoma and cholangiocarcinoma tissue also showed increased expression of MUC4 and other mucins. CONCLUSIONS: Differential expression of MUC4 in pancreatic tumor tissues can help to differentiate PDAC from benign conditions.

Quantification of COX-2 Level in Alzheimer's Disease Patients to Develop Potential Blood-Based Biomarker for Early Diagnosis and Therapeutic Target.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease and symptoms develop gradually over many years. The current direction for medication development in AD is focused on neuro-inflammation and oxidative stress. Amyloid-ß (Aß) deposition activates microglia leading to neuro-inflammation and neurodegeneration induced by activation of COX-2 via NFκB p50 in glioblastoma cells. Objective: The study aimed to evaluate the concentration of COX-2 and NFκB p50 in serum of AD, mild cognitive impairment (MCI), and geriatric control (GC) and to establish a blood-based biomarker for early diagnosis and its therapeutic implications. Methods: Proteins and their mRNA level in blood of study groups were measured by surface plasmon resonance (SPR) and quantitative polymerase chain reaction (qPCR), respectively. The level of protein was further validated by western blot. The binding study of designed peptide against COX-2 by molecular docking was verified by SPR. The rescue of neurotoxicity by peptide was also checked by MTT assay on SH-SY5Y cells (neuroblastoma cell line). Results: Proteins and mRNA were highly expressed in AD and MCI compared to GC. However, COX-2 decreases with disease duration. The peptide showed binding affinity with COX-2 with low dissociation constant in SPR and rescued the neurotoxicity of SH-SY5Y cells by decreasing the level of Aß, tau, and pTau proteins. Conclusions: It can be concluded that COX-2 protein can serve as a potential blood-based biomarker for early detection and can be a good platform for therapeutic intervention for AD.

50,000 years of Evolutionary History of India: Insights from ~2,700 Whole Genome Sequences.

India has been underrepresented in whole genome sequencing studies. We generated 2,762 high coverage genomes from India-including individuals from most geographic regions, speakers of all major languages, and tribal and caste groups-providing a comprehensive survey of genetic variation in India. With these data, we reconstruct the evolutionary history of India through space and time at fine scales. We show that most Indians derive ancestry from three ancestral groups related to ancient Iranian farmers, Eurasian Steppe pastoralists and South Asian hunter-gatherers. We uncover a common source of Iranian-related ancestry from early Neolithic cultures of Central Asia into the ancestors of Ancestral South Indians (ASI), Ancestral North Indians (ANI), Austro-asiatic-related and East Asian-related groups in India. Following these admixtures, India experienced a major demographic shift towards endogamy, resulting in extensive homozygosity and identity-by-descent sharing among individuals. At deep time scales, Indians derive around 1-2% of their ancestry from gene flow from archaic hominins, Neanderthals and Denisovans. By assembling the surviving fragments of archaic ancestry in modern Indians, we recover ~1.5 Gb (or 50%) of the introgressing Neanderthal and ~0.6 Gb (or 20%) of the introgressing Denisovan genomes, more than any other previous archaic ancestry study. Moreover, Indians have the largest variation in Neanderthal ancestry, as well as the highest amount of population-specific Neanderthal segments among worldwide groups. Finally, we demonstrate that most of the genetic variation in Indians stems from a single major migration out of Africa that occurred around 50,000 years ago, with minimal contribution from earlier migration waves. Together, these analyses provide a detailed view of the population history of India and underscore the value of expanding genomic surveys to diverse groups outside Europe.

Trajectories and correlates of poor mental health in India over the course of the COVID-19 pandemic: a nationwide survey.

INTRODUCTION: The COVID-19 pandemic had large impacts on mental health; however, most existing evidence is focused on the initial lockdown period and high-income contexts. By assessing trajectories of mental health symptoms in India over 2 years, we aim to understand the effect of later time periods and pandemic characteristics on mental health in a lower-middle income context. METHODS: We used data from the Real-Time Insights of COVID-19 in India cohort study (N=3709). We used covariate-adjusted linear regression models with generalised estimating equations to assess associations between mental health (Patient Health Questionnaire (PHQ-4) score; range 0-12) and pandemic periods as well as pandemic characteristics (COVID-19 cases and deaths, government stringency, self-reported financial impact, COVID-19 infection in the household) and explored effect modification by age, gender and rural/urban residence. RESULTS: Mental health symptoms dropped immediately following the lockdown period but rose again during the delta and omicron waves. Associations between mental health and later pandemic stages were stronger for adults 45 years of age and older (p<0.001). PHQ-4 scores were significantly associated with all pandemic characteristics considered, including estimated COVID-19 deaths (PHQ-4 difference of 0.10 units; 95% CI 0.06 to 0.13), government stringency index (0.14 units; 95% CI 0.11 to 0.18), self-reported major financial impacts (1.20 units; 95% CI 1.09 to 1.32) and COVID-19 infection in the household (0.36 units; 95% CI 0.23 to 0.50). CONCLUSION: While the lockdown period and associated financial stress had the largest mental health impacts on Indian adults, the effects of the pandemic on mental health persisted over time, especially among middle-aged and older adults. Results highlight the importance of investments in mental health supports and services to address the consequences of cyclical waves of infections and disease burden due to COVID-19 or other emerging pandemics.

Melamine Exacerbates Neurotoxicity in D-Galactose-Induced Neuronal SH-SY5Y Cells.

Numerous studies have depicted the role of diet and environmental toxins in aging. Melamine (Mel) is a globally known notorious food adulterant, and its toxicity has been shown in several organs including the brain. However, till now, there are no reports regarding Mel neurotoxicity in aging neurons. So, this study examined the in vitro neurotoxicity caused by Mel in the D-galactose (DG)-induced aging model of neuronal SH-SY5Y cells. In the present study, the neuronal SH-SY5Y cells were treated with DG and Mel separately and in combination to assess the neurotoxicity potential using MTT assay and neurite length measurement. Further, the superoxide dismutase (SOD), catalase (CAT), and total antioxidant activities were evaluated followed by the determination of the intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and caspase3 (Casp3) activity. The cotreatment of Mel and DG in neuronal SH-SY5Y cells showed maximum cell death than the cells treated with DG or Mel individually and untreated control cells. The neurite length shrinkage and ROS production were maximum in the DG and Mel cotreated cells showing exacerbated toxicity of Mel. The activity of SOD, CAT, and total antioxidants was also found to be lowered in the cotreatment group (Mel + DG) than in Mel- or DG-treated and untreated cells. Further, the combined toxicity of Mel and DG also elevated the Casp3 activity more than any other group. This is the first study showing the increased neurotoxic potential of Mel in an aging model of neuronal SH-SY5Y cells which implicates that Mel consumption by the elderly may lead to increased incidences of neurodegeneration like Alzheimer's disease and Parkinson's disease.

Defining anthropometric thresholds (mid-arm circumference and calf circumference) in older adults residing in the community: a cross-sectional analysis using data from the population representative Longitudinal Aging Study in India (LASI DAD).

OBJECTIVES: To identify factors associated with malnutrition (undernutrition and overnutrition) and determine appropriate cut-off values for mid-arm circumference (MAC) and calf circumference (CC) among community-dwelling Indian older adults. DESIGN: Data from the first wave of harmonised diagnostic assessment of dementia for Longitudinal Ageing Study in India (LASI-DAD) were used. Various sociodemographic factors, comorbidities, geriatric syndromes, childhood financial and health status were included. Anthropometric measurements included body mass index (BMI), MAC and CC. SETTING: Nationally representative cohort study including 36 Indian states and union territories. PARTICIPANTS: 4096 older adults aged >60 years from LASI DAD. OUTCOME MEASURES: The outcome variable was BMI, categorised as low (<18.5 kg/m2), normal (18.5-22.9 kg/m2) and high (>23 kg/m2). The cut-off values of MAC and CC were derived using ROC curve with BMI as the gold standard. RESULTS: 902 (weighted percentage 20.55%) had low BMI, 1742 (44.25%) had high BMI. Undernutrition was associated with age, wealth-quintile and impaired cognition, while overnutrition was associated with higher education, urban living and comorbidities such as hypertension, diabetes and chronic heart disease. For CC, the optimal lower and upper cut-offs for males were 28.1 cm and >31.5 cm, respectively, while for females, the corresponding values were 26 cm and >29 cm. Similarly, the optimal lower and upper cut-offs for MAC in males were 23.9 cm and >26.9 cm, and for females, they were 22.5 cm and >25 cm. CONCLUSION: Our study identifies a high BMI prevalence, especially among females, individuals with higher education, urban residents and those with comorbidities. We establish gender-specific MAC and CC cut-off values with significant implications for healthcare, policy and research. Tailored interventions can address undernutrition and overnutrition in older adults, enhancing standardised nutritional assessment and well-being.

The prevalence of frailty and its relationship with sociodemographic factors, regional healthcare disparities, and healthcare utilization in the aging population across India.

Objective: To estimate frailty prevalence and its relationship with the socio-economic and regional factors and health care outcomes. Methods: In this study, participants from the harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD) were included. The frailty index (FI) was calculated using a 32-variable deficit model, with a value of ≥ 25% considered as frail. Data on demographic (including caste and religion) and socioeconomic profiles and health care utilization were obtained. The state-wise health index maintained by the government based on various health-related parameters was used to group the participants' residential states into high-, intermediate-, and low-performing states. Multivariable and zero-inflated negative binomial regression was used to assess the relationship of frailty index with sociodemographic characteristics, health index, and health care expenditure or hospitalization. Results: Among the 3953 eligible participants, the prevalence of frailty was 42.34% (men = 34.99% and women = 49.35%). Compared to high-performing states, intermediate- and low-performing states had a higher proportion of frail individuals (49.7% vs. 46.8% vs. 34.5%, P < 0.001). In the adjusted analysis, frailty was positively associated with age, female sex, rural locality, lower education level, and caste (scheduled caste and other backward classes). After adjusting for the socio-economic profile, FI was inversely associated with the composite health index of a state (P < 0.001). FI was also significantly correlated with total 1-year health care expenditure and hospitalization (P < 0.001 and 0.020, respectively). Conclusion: There is a high prevalence of frailty among older Indian adults that is associated with sociodemographic factors and regional health care performance. Furthermore, frailty is associated with increased health care utilization and expenditure.

Association Between Cognitive Performance and Nutritional Status: Analysis From LASI-DAD.

Malnutrition in low- and middle-income countries causes cognitive decline and other health problems. Harmonized Diagnostic Assessment of Dementia for Longitudinal Aging Study in India (LASI DAD) is an extensive study on late-life cognition and dementia. This study examines the link between nutrition and cognitive abilities in older adults using data from the LASI DAD. We conducted descriptive statistics on nutritional parameters (body-mass index, waist-hip ratio, and Mini-Nutritional Assessment), cognitive functions, and socio-demographic variables in 2,892 adults aged ≥60 years. Cognitive domains assessed included delayed recall, orientation, language, executive function, abstract reasoning, and attention. Cognitive impairment was defined as impaired performance in two or more domains. Mean age was 69.3 ± 7.1 years, 52.9% were female, and 57.5% were illiterate. Low body-mass index (adjusted OR: 1.88, p < .001), at risk of malnutrition (adjusted OR: 1.89, p < .001) and malnourished (adjusted OR: 2.86, p < .001) on Mini-Nutritional Assessment were associated with the presence of cognitive impairment. Better cognitive performance was associated with increased body mass index (adjusted OR: 0.74, p-.03), hemoglobin (adjusted OR: 0.91, p-.006), and serum albumin (adjusted OR: 0.38, p < .001). This study shows that nutritional status assessed by anthropometric measures and blood markers is strongly linked to cognitive performance in older adults.

Trajectories and correlates of poor mental health in India over the course of the COVID-19 pandemic: a nation-wide survey.

Introduction: The COVID-19 pandemic had large impacts on mental health; however, most existing evidence is focused on the initial lockdown period and high-income contexts. By assessing trajectories of mental health symptoms in India over two years, we aim to understand the effect of later time periods and pandemic characteristics on mental health in a lower-middle income context. Methods: We used data from the Real-Time Insights of COVID-19 in India (RTI COVID-India) cohort study (N=3,662). We used covariate-adjusted linear regression models with generalized estimating equations to assess associations between mental health (PHQ-4 score) and pandemic periods as well as pandemic characteristics (COVID-19 cases and deaths, government stringency, self-reported financial impact, COVID-19 infection in the household) and explored effect modification by age, gender, and rural/urban residence. Results: Mental health symptoms dropped immediately following the lockdown period but rose again during the delta and omicron waves. Associations between mental health and later pandemic stages were stronger for adults 45 years of age and older (p<0.001). PHQ-4 scores were significantly and independently associated with all pandemic characteristics considered, including estimated COVID-19 deaths (PHQ-4 difference of 0.041 SD units; 95% Confidence Interval 0.030 - 0.053), government stringency index (0.060 SD units; 0.048 - 0.072), self-reported major financial impacts (0.45 SD units; 0.41-0.49), and COVID-19 infection in the household (0.11 SD units; 0.07-0.16). Conclusion: While the lockdown period and associated financial stress had the largest mental health impacts on Indian adults, the effects of the pandemic on mental health persisted over time, especially among middle-age and older adults. Results highlight the importance of investments in mental health supports and services to address the consequences of cyclical waves of infections and disease burden due to COVID-19 or other emerging pandemics.

Genome-wide identification and expression pattern analysis of lipoxygenase genes of chickpea (Cicer arietinum L.) in response to accelerated aging.

Seed aging is a major problem which is caused by various factors such as unfavorable physiological, biochemical, and metabolic alterations in seed. Lipoxygenase (LOXs), an oxidoreductase enzyme that catalyzes the oxidation of polyunsaturated fatty acids, acts as a negative regulator in seed viability and vigour during storage. In this study, we identified ten putative LOX gene family members in the chickpea genome, designated as "CaLOX" which are mainly located in the cytoplasm and chloroplast. These genes share different physiochemical properties and similarities in their gene structures and conserved functional regions. The promoter region contained the cis-regulatory elements and transcription binding factors, which were mainly linked to biotic and abiotic stress, hormones, and light responsiveness. In this study, chickpea seeds were treated with accelerated aging treatment for 0, 2, and 4 days at 45 °C and 85 % relative humidity. Increased level of reactive oxygen species, malondialdehyde, electrolyte leakage, proline, lipoxygenase (LOX) activity, and decreased catalase activity indicates cellular dysfunction which demonstrates seed deterioration. Quantitative real-time analysis reveals that 6 CaLOX genes were upregulated, and 4 CaLOX genes were downregulated during the seed aging process in chickpea. This comprehensive study will reveal the role of the CaLOX gene in response to aging treatment. The identified gene may be used to develop better-quality seeds in chickpea.

Surface plasmon resonance based-optical biosensor: Emerging diagnostic tool for early detection of diseases.

The development of diagnostic tools remains at the center of the health care system. In recent times optical biosensors have been widely applied in the scientific community, especially for monitoring protein-protein or nucleic acid hybridization interactions. Optical biosensors-derived surface plasmon resonance (SPR) technology has appeared as a revolutionary technology at the current times. This review focuses on the research work in molecular biomarker evaluation using the technique based on SPR for translational clinical diagnosis. The review has covered both communicable and noncommunicable diseases by using different bio-fluids of the patient's sample for diagnosis of the diseases. An increasing number of SPR approaches have been developed in healthcare research and fundamental biological studies. The utility of SPR in the area of biosensing basically lies in its noninvasive diagnostic and prognostic feature due to its label-free high sensitivity and specificity properties. This makes SPR an invaluable tool with precise application in the recognition of different stages of the disease.

Genome editing for improving nutritional quality, post-harvest shelf life and stress tolerance of fruits, vegetables, and ornamentals.

Agricultural production relies on horticultural crops, including vegetables, fruits, and ornamental plants, which sustain human life. With an alarming increase in human population and the consequential need for more food, it has become necessary for increased production to maintain food security. Conventional breeding has subsidized the development of improved verities but to enhance crop production, new breeding techniques need to be acquired. CRISPR-Cas9 system is a unique and powerful genome manipulation tool that can change the DNA in a precise way. Based on the bacterial adaptive immune system, this technique uses an endonuclease that creates double-stranded breaks (DSBs) at the target loci under the guidance of a single guide RNA. These DSBs can be repaired by a cellular repair mechanism that installs small insertion and deletion (indels) at the cut sites. When equated to alternate editing tools like ZFN, TALENs, and meganucleases, CRISPR- The cas-based editing tool has quickly gained fast-forward for its simplicity, ease to use, and low off-target effect. In numerous horticultural and industrial crops, the CRISPR technology has been successfully used to enhance stress tolerance, self-life, nutritional improvements, flavor, and metabolites. The CRISPR-based tool is the most appropriate one with the prospective goal of generating non-transgenic yields and avoiding the regulatory hurdles to release the modified crops into the market. Although several challenges for editing horticultural, industrial, and ornamental crops remain, this new novel nuclease, with its crop-specific application, makes it a dynamic tool for crop improvement.

Polygenic Risk Scores for Alzheimer's Disease and General Cognitive Function Are Associated With Measures of Cognition in Older South Asians.

Genome-wide association studies (GWAS) conducted in European ancestry (EA) have identified hundreds of single-nucleotide polymorphisms (SNPs) associated with general cognitive function and/or Alzheimer's disease (AD). The association between these SNPs and cognitive function has not been fully evaluated in populations with complex genetic substructure such as South Asians. This study investigated whether SNPs identified in EA GWAS, either individually or as polygenic risk scores (PRSs), were associated with general cognitive function and 5 broad cognitive domains in 932 South Asians from the Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD). We found that SNPs identified from AD GWAS were more strongly associated with cognitive function in LASI-DAD than those from a GWAS of general cognitive function. PRSs for general cognitive function and AD explained up to 1.1% of the variability in LASI-DAD cognitive domain scores. Our study represents an important stepping stone toward better characterization of the genetic architecture of cognitive aging in the Indian/South Asian population and highlights the need for further research that may lead to the identification of new variants unique to this population.

Genome-wide identification of the fibrillin gene family in chickpea (Cicer arietinum L.) and its response to drought stress.

Fibrillin family members play multiple roles in growth, development, and protection against abiotic stress. In this study, we identified 12 potential CaFBNs that are ranging from 25 kDa-42.92 kDa and are mostly basic. These proteins were hydrophilic in nature and generally resided in the chloroplast. The CaFBN genes were located on different chromosomes like 1, 4, 5, and 7. All FBNs shared conserved motifs and possessed a higher number of stress-responsive elements. For evolutionary analysis, a phylogenetic tree of CaFBNs with other plants' FBNs was constructed and clustered into 11 FBN subgroups. For expression analysis, 21 day old chickpea seedling was exposed to dehydration stress by withholding water. We also performed various physiological and biochemical analyses to check that plant changes at the physiological and cellular levels while undergoing stress conditions. The transcript expression of CaFBNs was higher in aerial parts, especially in stems and leaves. Dehydration-specific transcriptome and qPCR analysis showed that FBN-1, FBN-2, and FBN-6 were highly expressed. In addition, our study provides a comprehensive overview of the FBN protein family and their importance during the dehydration stress condition in Cicer arietinum.

Cohort Profile: Real-Time Insights of COVID-19 in India (RTI COVID-India).

BACKGROUND: The coronavirus disease (COVID) pandemic caused disruption globally and was particularly distressing in low- and middle-income countries such as India. This study aimed to provide population representative estimates of COVID-related outcomes in India over time and characterize how COVID-related changes and impacts differ by key socioeconomic groups across the life course. METHODS: The sample was leveraged from an existing nationally representative study on cognition and dementia in India: Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD). The wave-1 of LASI-DAD enrolled 4096 older adults aged 60 years and older in 3316 households from 18 states and union territories of India. Out of the 3316 LASI-DAD households, 2704 with valid phone numbers were contacted and invited to participate in the Real-Time Insights COVID-19 in India (RTI COVID-India) study. RTI COVID-India was a bi-monthly phone survey that provided insight into the individual's knowledge, attitudes, and behaviour towards COVID-19 and changes in the household's economic and health conditions throughout the pandemic. The survey was started in May 2020 and 9 rounds of data have been collected. FINDINGS TILL DATE: Out of the 2704 LASI-DAD households with valid phone numbers, 1766 households participated in the RTI COVID-India survey at least once. Participants were in the age range of 18-102 years, 49% were female, 66% resided in rural area. Across all rounds, there was a higher report of infection among respondents aged 60-69 years. There was a greater prevalence of COVID-19 diagnosis reported in urban (23.0%) compared to rural areas (9.8%). Respondents with higher education had a greater prevalence of COVID-19 diagnosis compared to those with lower or no formal education. Highest prevalence of COVID-19 diagnosis was reported from high economic status compared to middle and low economic status households. Comparing education gradients in experiencing COVID-19 symptoms and being diagnosed, we observe an opposite pattern: respondents with no formal schooling reported the highest level of experiencing COVID-19 symptoms, whereas the greatest proportion of the respondents with secondary school or higher education reported being diagnosed with COVID-19. FUTURE PLANS: The study group will analyse the data collected showing the real-time changes throughout the pandemic and will make the data widely available for researchers to conduct further studies.

The Role of Sirtuins in Sarcopenia and Frailty.

The population of older individuals is increasing rapidly, but only a small fraction among them is able to experiences a healthy life. Due to lack of physical exercise and oxidative stress, aging leads to sarcopenia and finally end up with frailty. Sarcopenia is a component of the frailty and described as age related degenerative changes in the skeletal muscle mass, strength and quality. Though the loss of muscle strength and mass gradually seem inevitable during aging, it can be partially prevented or overcome by a deeper insight into the pathogenesis. Sirtuin protein leads to longevity across different organisms ranging from worms to mammals. Expression of sirtuin protein increases during physical exercise and thus strengthens muscle mass. Satellite cells leads to muscle repair in a SIRT1 dependent manner. In addition, SIRT1 improves insulin sensitivity and induces autophagy in the aged mice. The current paper discussed the putative role of sirtuins in sarcopenia and frailty. Moreover, it highlighted the pathways by which sirtuins can inhibit ROS production, inflammation and mitochondrial dysfunctions and therefore confers a protective role against frailty and sarcopenia. The critical role of sirtuins in the sarcopenia and frailty pathogenesis can eventually fuel the development of novel interventions by targeting sirtuins.

Deep phenotyping and genomic data from a nationally representative study on dementia in India.

The Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD) is a nationally representative in-depth study of cognitive aging and dementia. We present a publicly available dataset of harmonized cognitive measures of 4,096 adults 60 years of age and older in India, collected across 18 states and union territories. Blood samples were obtained to carry out whole blood and serum-based assays. Results are included in a venous blood specimen datafile that can be linked to the Harmonized LASI-DAD dataset. A global screening array of 960 LASI-DAD respondents is also publicly available for download, in addition to neuroimaging data on 137 LASI-DAD participants. Altogether, these datasets provide comprehensive information on older adults in India that allow researchers to further understand risk factors associated with cognitive impairment and dementia.

Novel antioxidant protein target therapy to counter the prevalence and severity of SARS-CoV-2.

Background: This review analyzed the magnitude of the COVID-19 pandemic globally and in India and the measures to counter its effect using natural and innate immune booster molecules. The study focuses on two phases: the first focuses on the magnitude, and the second on the effect of antioxidants (natural compounds) on SARS-CoV-2. Methods: The magnitude of the prevalence, mortality, and comorbidities was acquired from the World Health Organization (WHO) report, media, a report from the Ministry of Health and Family Welfare (MoHFW), newspapers, and the National Centre of Disease Control (NCDC). Research articles from PubMed as well as other sites/journals and databases were accessed to gather literature on the effect of antioxidants. Results: In the elderly and any chronic diseases, the declined level of antioxidant molecules enhanced the reactive oxygen species, which in turn deprived the immune system. Conclusion: Innate antioxidant proteins like sirtuin and sestrin play a vital role in enhancing immunity. Herbal products and holistic approaches can also be alternative solutions for everyday life to boost the immune system by improving the redox balance in COVID-19 attack. This review analyzed the counteractive effect of alternative therapy to boost the immune system against the magnitude of the COVID-19 pandemic.

Circulatory Level of Inflammatory Cytoskeleton Signaling Regime Proteins in Cancer Invasion and Metastasis.

Early detection of metastatic breast cancer (MBC) is a serious issue for the healthcare system. It is essential to develop potential non-invasive, low-cost molecular biomarkers. The present study explored specific serum proteins of inflammatory, MAPK, and cytoskeletal signaling pathways involved in the progression of MBC to establish a panel of blood-based diagnostic and prognostic biomarkers. Healthy-control (HC), non-metastatic (NM), and metastatic (M) (pre- and post-therapy) breast cancer (BC) patients were recruited. LOX5, Rac1, Rac1b, p38α, phospho-p38α (Y182), LIMK1, phospho-LIMK1 (T508), cofilin1, and phospho-cofilin1 (S3) were quantified in the serum of the study group by real-time label-free surface plasmon resonance technology and verified by Western blot. Proteins were found to be significantly elevated in the serum of BC patients compared to HC and also higher in M compared to NM, which further downregulated in post-therapy M patients. Elevation of phospho-LIMK1 and phospho-cofilin1, which are critical for M, was also indicated in the serum level and can differentiate from NM. Receiver operating characteristics (ROC) derived area under the curve (AUC) (0.9) is very strong to differentiate between HC and BC. Moreover, the combined ROC of 3 molecules phospho-LIMK, p38α, and phospho-p38α were found to be a potent predictive panel of biomarkers between M and NM with AUC0.95. The panel of inflammatory cytoskeleton signaling regime proteins specified in this study can have significant clinical utility for diagnosis as well as prognosis of MBC at an early stage. The study may have a high translational value in a simple and cost-effective way by avoiding frequent CT/PET scans.

Blood Circulatory Level of Seven Sirtuins in Alzheimer's Disease: Potent Biomarker Based on Translational Research.

Alzheimer's disease (AD) is an accelerating neurodegenerative disorder. Dysfunction of mitochondria and oxidative stress contributes to the pathogenesis of AD. Sirtuins play a role in this pathway and can be a potential marker to study neurodegenerative changes. This study evaluated serum levels of all seven sirtuin (SIRT1-SIRT7) proteins in three study groups: AD, mild cognitive impairment (MCI) and geriatric control (GC) by surface plasmon resonance (SPR) technique. Further, it was validated by the Western blot experiment. ROC analysis was performed to differentiate the study group based on the concentration of serum SIRT proteins. Out of seven sirtuins, serum SIRT1, SIRT3 and SIRT6 levels (mean ± SD) were significantly decreased in AD (1.65 ± 0.56, 3.15 ± 0.28, 3.36 ± 0.32 ng/µl), compared to MCI (2.17 ± 0.39, 3.60 ± 0.51, 3.73 ± 0.48 ng/µl) and GC (2.84 ± 0.47, 4.55 ± 0.48, 4.65 ± 0.55 ng/µl). ROC analysis showed the cut-off value with high sensitivity and specificity for cognitive impairment (AD and MCI). The concentration declined significantly with the disease progression. No specific difference was observed in the case of other SIRTs between the study groups. This study reveals an inverse relation of serum SIRT1, SIRT3 and SIRT6 concentration with AD. ROC analysis showed that these serum proteins have greater accuracy in diagnosing of AD. This is the first report of estimation of all seven serum sirtuins and the clinical relevance of SIRT3 and SIRT6 as serum protein markers for AD.