Breast cancer derived exosomes: Theragnostic perspectives and implications.

Breast cancer (BC) is the most prevalent malignancy affecting women worldwide. Although conventional treatments such as chemotherapy, surgery, hormone therapy, radiation therapy, and biological therapy are commonly used, they often entail significant side effects. Therefore, there is a critical need to investigate more cost-effective and efficient treatment modalities in BC. Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, play a crucial role in modulating recipient cell behaviour and driving cancer progression. Among the EVs, exosomes provide valuable insights into cellular dynamics under both healthy and diseased conditions. In cancer, exosomes play a critical role in driving tumor progression and facilitating the development of drug resistance. BC-derived exosomes (BCex) dynamically influence BC progression by regulating cell proliferation, immunosuppression, angiogenesis, metastasis, and the development of treatment resistance. Additionally, BCex serve as promising diagnostic markers in BC which are detectable in bodily fluids such as urine and saliva. Targeted manipulation of BCex holds significant therapeutic potential. This review explores the therapeutic and diagnostic implications of exosomes in BC, underscoring their relevance to the disease. Furthermore, it discusses future directions for exosome-based research in BC, emphasizing the necessity for further exploration in this area.

Identifying Biomarkers and Therapeutic Targets by Multiomic Analysis for HNSCC: Precision Medicine and Healthcare Management.

Background: Head and neck squamous cell carcinoma (HNSCC) is one of the major types of cancer, with 900,000 cases and over 400,000 deaths annually. It constitutes 3-4% of all cancers in Europe and western countries. As early diagnosis is the key to treating the disease, reliable biomarkers play an important role in the precision medicine of HNSCC. Despite treatments, the survival rate of cancer patients remains unchanged, and this is mainly due to the failure to detect the disease early. Thus, the objective of this study is to identify reliable biomarkers for head and neck cancers for better healthcare management. Methods: In this study, all available, curated human genes were screened for their expression against HNSCC TCGA patient samples using genomic and proteomic data by various bioinformatic approaches and datamining. Docking studies were performed using AutoDock or online virtual screening tools for identifying potential ligands. Results: Sixty genes were short-listed, and most of them show a consistently higher expression in head and neck patient samples at both the mRNA and the protein level. Irrespective of human papillomavirus (HPV) status, all of them show a higher expression in cancer samples. The higher expression of 30 genes shows adverse effects on patient survival. Out of the 60 genes, 12 genes have crystal structures and druggable potential. We show that genes such as GTF2H4, HAUS7, MSN, and MNDA could be targets of Pembrolizumab and Nivolumab, which are approved monoclonal antibodies for HNSCC. Conclusion: Sixty genes are identified as potential biomarkers for head and neck cancers based on their consistent and statistically significantly higher expression in patient samples. Four proteins have been identified as potential drug targets based on their crystal structure. However, the utility of these candidate genes has to be further tested using patient samples.

Tar Formation in Gasification Systems: A Holistic Review of Remediation Approaches and Removal Methods.

Gasification is an advanced thermochemical process that converts carbonaceous feedstock into syngas, a mixture of hydrogen, carbon monoxide, and other gases. However, the presence of tar in syngas, which is composed of higher molecular weight aromatic hydrocarbons, poses significant challenges for the downstream utilization of syngas. This Review offers a comprehensive overview of tar from gasification, encompassing gasifier chemistry and configuration that notably impact tar formation during gasification. It explores the concentration and composition of tar in the syngas and the purity of syngas required for the applications. Various tar removal methods are discussed, including mechanical, chemical/catalytic, and plasma technologies. The Review provides insights into the strengths, limitations, and challenges associated with each tar removal method. It also highlights the importance of integrating multiple techniques to enhance the tar removal efficiency and syngas quality. The selection of an appropriate tar removal strategy depends on factors such as tar composition, gasifier operating and design factors, economic considerations, and the extent of purity required at the downstream application. Future research should focus on developing cleaning strategies that consume less energy and cause a smaller environmental impact.

Disease diagnostics using machine learning of immune receptors.

Clinical diagnosis typically incorporates physical examination, patient history, and various laboratory tests and imaging studies, but makes limited use of the human system's own record of antigen exposures encoded by receptors on B cells and T cells. We analyzed immune receptor datasets from 593 individuals to develop MAchine Learning for Immunological Diagnosis (Mal-ID) , an interpretive framework to screen for multiple illnesses simultaneously or precisely test for one condition. This approach detects specific infections, autoimmune disorders, vaccine responses, and disease severity differences. Human-interpretable features of the model recapitulate known immune responses to SARS-CoV-2, Influenza, and HIV, highlight antigen-specific receptors, and reveal distinct characteristics of Systemic Lupus Erythematosus and Type-1 Diabetes autoreactivity. This analysis framework has broad potential for scientific and clinical interpretation of human immune responses.

Re-visiting humoral constitutive antibacterial heterogeneity in bloodstream infections.

Although cellular immunity has garnered much attention in the era of single-cell technologies, humoral innate immunity has receded in priority due to its presumed limited roles. Hence, despite the long-recognised bactericidal activity of serum-a functional characteristic of constitutive humoral immunity-much remains unclear regarding mechanisms underlying its inter-individual heterogeneity and clinical implications in bloodstream infections. Recent work suggests that the immediate antimicrobial effect of humoral innate immunity contributes to suppression of the excessive inflammatory responses to infection by reducing the amount of pathogen-associated molecular patterns. In this Personal View, we propose the need to re-explore factors underlying the inter-individual heterogeneity in serum antibacterial competence as a new approach to better understand humoral innate immunity and revisit the clinical use of measuring serum antibacterial activity in the management of bacterial bloodstream infections. Given the current emphasis on subtyping sepsis, a serum bactericidal assay might prove useful in defining a distinct sepsis endotype, to enable more personalised management.

Development and validation of Empagliflozin and Linagliptin simultaneous estimation in rat plasma using freezing lipid precipitation and SCX-SPE assisted HPLC-MS/MS method and its application in pharmacokinetic studies.

A quick and sensitive liquid chromatography-mass spectrometry technique was designed, improved, and validated for simultaneous determination of Empagliflozin (EPG) and Linagliptin (LNG) using Empagliflozin-d4 (EPG-d4) and linagliptin-d4 (LNG-d4) as internal standards (IS) in rat plasma. Target analytes and the IS were extracted using freezing lipid precipitation (FLP) and optimized using the strong cation exchange solid phase extraction (SCX-SPE) method to achieve the maximum sample clean-up. In particular, when combined with SPE clean-up, FLP can efficiently eliminate the plasma sample's high lipid content. More than 84.14% of plasma lipids were rapidly removed during the FLP procedure, with minimal loss of EPG and LNG. We used LC-atmospheric chemical ionization (APCI)-mass spectrometry was employed to assess the efficiency of FLP in lipid removal. The SCX-SPE cartridges removed the remaining impurities from EPG and LNG, allowing for further purification. The samples were chromatographically separated using a Spherisorb RP/Cyano column by pumping a gradient mobile phase comprised of acetonitrile and 25 mM ammonium acetate buffer (pH 8.1) in positive ion mode at a flow rate of 0.8 mL/min. The selected reaction monitoring technique was performed using a Waters triple-stage quadrupole tandem mass spectrometer equipped with an electrospray ionization (ESI) source. The chromatographic separation was accomplished using a Waters Acquity® high-performance liquid chromatography (HPLC) system. Mass transition (m/z) of 451.15/71.12 for EPG, m/z 473.27/419.94 for LNG; m/z 455.19/71.12 for EPG-d4, and 477.27/423.94 for LNG-d4 was successfully achieved. This study successfully examined the concentration ranges of 25-1050 ng/mL for EPG and 0.35-15 ng/mL for LNG. The results showed that the linearity of EPG ranged from 25.14 to 985.26 ng/mL, while the linearity of LNG ranged from 0.59 to 14.86 ng/mL. The relative standard deviation (RSD) for both EPG and LNG, within and between days, were below 3.83%, indicating that they fall within acceptable limits. This novel approach demonstrated favourable outcomes in a pharmacokinetic study involving healthy rats, where EPG and LNG were co-administered. This study found that the co-administration of both drugs did not have a significant impact on their pharmacokinetic behavior, suggesting the absence of any drug-drug interactions.

Unravelling the secrets of lesser florican: a study of their home range and habitat use in Gujarat, India.

The home range of a species is determined by a complex interplay of extrinsic and intrinsic factors, which can have profound impacts on the species' resource use. Understanding these dynamics is especially important for conserving critically endangered species. In this study, we used satellite telemetry to investigate the home range of the critically endangered lesser florican (Sypheotides indicus) in Gujarat, India. We analysed GPS locations from 10 lesser floricans deployed with GPS/GSM transmitters between 2020 and 2022. The average home range size (95% KDE) was 10.73 ± 10.70 km2 (mean ± SD), while the average core area (50% KDE) was 1.95 ± 1.56 km2 (mean ± SD). The monthly and daily distances covered were 286.29 ± 599.42 km and 10.11 ± 19.78 km, respectively. Our analysis indicated that suitable habitats and movement patterns were the most important factors explaining the variation in home range size. Specifically, our results suggest that lesser floricans prefer multi-use agro-grassland habitat systems with heterogeneous structures to accommodate different life history requirements. This preference may reflect the depletion and degradation of grasslands across the species' range. Therefore, managing grassland habitats amidst croplands should be one of the key conservation strategies for the lesser florican.

Neutrophil Extracellular Traps have DNAzyme activity that drives bactericidal potential.

The mechanisms of bacterial killing by neutrophil extracellular traps (NETs) are unclear. DNA, the largest component of NETs is believed to merely be a scaffold with minimal antimicrobial activity through the charge of the backbone. Here, we report that NETs DNA is beyond a scaffold and produces hydroxyl free radicals through the spatially concentrated G-quadruplex/hemin DNAzyme complexes, driving bactericidal effects. Immunofluorescence staining showed colocalization of G-quadruplex and hemin in extruded NETs DNA, and Amplex UltraRed assay portrayed its peroxidase activity. Proximity labeling of bacteria revealed localized concentration of radicals resulting from NETs bacterial trapping. Ex vivo bactericidal assays revealed that G-quadruplex/hemin DNAzyme is the primary driver of bactericidal activity in NETs. NETs are DNAzymes that may have important biological consequences.

Detailed Morphometric Analysis on Left Coronary Artery in the Population of North-East India.

Introduction The left ventricle, the cardiac chamber responsible for blood supply to the whole of systemic vasculature, receives most of its blood supply from the left coronary arteries (LCAs). Atherosclerosis of these vessels leading to myocardial infarction is a leading cause of death. Several invasive diagnostic or therapeutic coronary interventions are available for such patients. Just like any vascular procedure, a prior comprehensive knowledge of the dimensions of these vessels and their branching pattern is essential to perform these procedures uneventfully. No previous study in the population of North-Eastern India documents the population-specific reference for morphometric values of left coronary arteries and their anatomic variations. So, this study aims to fill up this lacuna. Methods This study was conducted in the Department of Anatomy in collaboration with the Catheterization Lab, Department of Cardiology, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences (NEIGRIHMS), Shillong. Coronary angiograms (CAG) of 100 subjects - 38 females and 62 males - were obtained from the Cardiac Catheterization Lab. Coronary angiograms were studied for the normal variant anatomy and morphometry of the LCAs - the left main coronary artery (LMCA), left anterior descending (LAD), and left circumflex (LCX).  Results The mean length and luminal diameter of LMCA were found to be 9.13±3.23 mm and 4.38±0.58 mm, respectively. The mean length of LAD and LCX were 109.46±14.49 mm and 66.27±11.56 mm, respectively. Ramus intermedius was present in 32% of the subjects, whereas the remaining subjects had bifurcations of LMCA. We also found that 86% of patients had "wrap-around LAD", while in 11% of our subjects, LAD failed to reach the apex. Diagonal branches originating from LAD were single, duplicated, and multiple in 14%, 62%, and 24% respectively. The marginal branches were found to be single, double, and multiple in 20%, 51%, and 29% respectively. Conclusion This study establishes a baseline reference on morphometry of the left coronary artery specific to the population of North-East India. This study may be of assistance to radiologists and cardiologists when performing procedures on the left coronary arteries in the population of North-Eastern India, with respect to the prevalence of anatomic variations.

The semi-arid ecosystem of Asiatic Lion Landscape in Saurashtra, Gujarat: Population density, biomass and conservation of nine wild prey species.

The present study aimed to assess the population density, structure, and population change of nine wild prey species in the semi-arid landscape of Saurashtra, Gujarat, India. A total of eight sites, representing a gradient from highly protected woodlands and grasslands to unreserved grasslands, were selected for sampling. We employed the road transect methodology under a distance sampling framework to achieve our objectives. We evaluated the realized growth rate of the Gir ungulate population through linear regression analysis. Our findings revealed that deer species exhibited higher density and biomass in woodlands compared to grasslands and coastal forests. On the other hand, antelopes showed higher density and biomass in grasslands and coastal forests compared to woodlands. The density gradient of wild prey species was influenced by various factors, including habitat structure, social organization, grouping tendencies, and topography. Over the last four decades, the population of wild prey species in Gir showed minimal changes. Our study provides a comprehensive understanding of wild prey species' density and biomass patterns at the landscape level. The inclusion of findings from ecologically significant and unique areas, such as coastal forests, further enhances the importance of this study. The implications of this study extend beyond the conservation of wild prey species alone; they also contribute to the conservation of the large carnivore guild in the Saurashtra landscape.

Phage diversity in cell-free DNA identifies bacterial pathogens in human sepsis cases.

Bacteriophages, viruses that infect bacteria, have great specificity for their bacterial hosts at the strain and species level. However, the relationship between the phageome and associated bacterial population dynamics is unclear. Here we generated a computational pipeline to identify sequences associated with bacteriophages and their bacterial hosts in cell-free DNA from plasma samples. Analysis of two independent cohorts, including a Stanford Cohort of 61 septic patients and 10 controls and the SeqStudy cohort of 224 septic patients and 167 controls, reveals a circulating phageome in the plasma of all sampled individuals. Moreover, infection is associated with overrepresentation of pathogen-specific phages, allowing for identification of bacterial pathogens. We find that information on phage diversity enables identification of the bacteria that produced these phages, including pathovariant strains of Escherichia coli. Phage sequences can likewise be used to distinguish between closely related bacterial species such as Staphylococcus aureus, a frequent pathogen, and coagulase-negative Staphylococcus, a frequent contaminant. Phage cell-free DNA may have utility in studying bacterial infections.

Peutz-Jeghers Syndrome: Lessons to be Learned in the Clinical Diagnosis.

Introduction: Peutz-Jeghers Syndrome (PJS) is an autosomal dominant disease presenting with hamartomatous polyps in the gastrointestinal tract and hyperpigmented macules on lips and oral mucosa. The incidence of this syndrome is approximately 1 in 1,20,000 births. Materials and Methods: In this article, we are presenting 11 cases of PJS which were misdiagnosed and patients were compelled to visit hospital repeatedly. All these cases were diagnosed based on clinical suspicion, family history, and histopathological examination of specimens. Most of the cases presented with intussusception and required emergency surgical management. Results: PJS can be diagnosed by the presence of microscopically confirmed hamartomatous polyps and a minimum of two of the following clinical criteria: Family history, mucocutaneous melanotic spots, and small bowel polyps with bleeding per rectally. The diagnosis can be missed if the melanotic spots on the face are missed. Routine investigations, imaging, and endoscopy were done in all cases. PJS patients need regular follow-up due to chance of recurrence of symptoms and susceptibility to cancer. Conclusion: PJS needs a high index of suspicion for diagnosis in cases of recurrent abdominal pain with bleeding per rectum. Proper family history and meticulous clinical examination for melanosis are very important to prevent the misdiagnosis of these cases.

Perspectives on Rapid Antigen Tests for Downstream Validation and Development of Theranostics.

Point-of-care SARS-CoV-2 rapid antigen tests have proven to be useful over the years and have become more apparent to the public eye during COVID-19 pandemic due to their ease of use, rapid processing and result times, and low cost. Here, we have assessed the effectiveness and accuracy of rapid antigen tests in comparison to the standard real-time polymerase chain reaction analyses of the same samples.

Rapid Molecular Phenotypic Antimicrobial Susceptibility Test for Neisseria gonorrhoeae Based on Propidium Monoazide Viability PCR.

Neisseria gonorrhoeae (NG) is an urgent threat to antimicrobial resistance (AMR) worldwide. NG has acquired rapid resistance to all previously recommended treatments, leaving ceftriaxone monotherapy as the first and last line of therapy for uncomplicated NG. The ability to rapidly determine susceptibility, which is currently nonexistent for NG, has been proposed as a strategy to preserve ceftriaxone by using alternative treatments. Herein, we used a DNA-intercalating dye in combination with NG-specific primers/probes to generate qPCR cycle threshold (Ct) values at different concentrations of 2 NG-relevant antimicrobials. Our proof-of-concept dual-antimicrobial logistic regression model based on the differential Ct measurements achieved an AUC of 0.93 with a categorical agreement for the susceptibility of 84.6%. When surveying the performance against each antimicrobial separately, the model predicted 90 and 75% susceptible and resistant strains, respectively, to ceftriaxone and 66.7 and 83.3% susceptible and resistant strains, respectively, to ciprofloxacin. We further validated the model against the individual replicates and determined the accuracy of the model in classifying susceptibility agnostic of the inoculum size. We demonstrated a novel PCR-based approach to determine phenotypic ciprofloxacin and ceftriaxone susceptibility information for NG with reasonable accuracy within 30 min, a significant improvement compared to the conventional method which could take multiple days.

Rapid molecular phenotypic antimicrobial susceptibility test for Neisseria gonorrhoeae based on propidium monoazide viability PCR.

Neisseria gonorrhoeae (NG) is an urgent threat to antimicrobial resistance (AMR) worldwide. NG has acquired rapid resistance to all previously recommended treatments leaving ceftriaxone monotherapy as the first and last line of therapy for uncomplicated NG. The ability to rapidly determine susceptibility, which is currently nonexistent for NG, has been proposed as a strategy to preserve ceftriaxone by using alternative treatments. Herein, we used a DNA-intercalating dye in combination with NG-specific primers/probes to generate qPCR cycle threshold (Ct) values at different concentrations of 2 NG-relevant antimicrobials. Our proof of concept dual-antimicrobial logistic regression model based on the differential Ct measurements achieved an AUC of 0.93 with a categorical agreement for susceptibility of 84.6%. When surveying the performance against each antimicrobial separately, the model predicted 90% and 75% susceptible and resistant strains respectively to ceftriaxone and 66.7% and 83.3% susceptible and resistant strains respectively to ciprofloxacin. We further validated the model against the individual replicates and determined the accuracy of the model in classifying susceptibility agnostic of the inoculum size. We demonstrated a novel PCR-based approach to determine phenotypic ciprofloxacin and ceftriaxone susceptibility information for NG with reasonable accuracy in under 30 min, a significant improvement compared to the conventional method which takes 3 days.

Hernia of Umbilical Cord: An Enigma.

Introduction: Hernia of the umbilical cord (HUC) is an uncommon problem which is often misdiagnosed, leading to inadequate treatment and various complications which cause increased morbidity and mortality in neonates. To address this issue, we took up this study. Materials and Methods: Patients diagnosed with HUC from January 1, 2017, to December 31, 2021, were retrospectively analyzed. The following data of all these patients were collected and retrospectively analyzed: demography, radiological investigations, echocardiography, contents of hernia, type of surgery performed, and outcome. Results: Eighteen out of 19 patients included in the study were taken up for surgery after baseline investigations and echocardiography. Out of 19 patients, 15 were discharged successfully and are on regular follow-up. Of the remaining four patients, an anastomotic leak occurred in two and they went into sepsis and succumbed. One of the patients died before any intervention and one succumbed on 3rd postoperative day due to sepsis. Conclusion: Timely referral and intervention can save precious lives. We need to educate doctors and health-care providers so that proper diagnosis and timely management can be done for this anomaly which is associated with less morbidity and a lower rate of associated anomalies.

Living on the sea-coast: ranging and habitat distribution of Asiatic lions.

Endangered Asiatic lions (Panthera leo persica) are renowned for their resilience and as a flagship of successful conservation and management. Lions dispersing out of the Gir forest have established themselves in the coastal habitats for about 25 years. We propose that the home range and spatial distribution of lions inhabiting the coastal habitats would be distinct from the forested habitats of the protected area. Each individual was monitored for an average of 367.2 ± 99.05 days from 2019 to 2021. The mean core area was 33.8 km2 (50% FK, SE 8.7 km2) and the overall average range was 171.8 km2 (90% FK, SE 40.5 km2). The home ranges were significantly larger for lions residing in the coastal area compared to lions in the protected area. The lion distribution model was built on MaxEnt, and inputs included location fixes of lions and variables, including 18 land use categories and Euclidean distance to linear infrastructures and human settlements. Lions were shown to use forest habitat patches extensively, followed by available habitats around water sources and wasteland. The study highlights the importance of corridors connecting to the Gir protected area and the importance of coastal forest patches for lion conservation and management.

Using a 29-mRNA Host Response Classifier To Detect Bacterial Coinfections and Predict Outcomes in COVID-19 Patients Presenting to the Emergency Department.

Clinicians in the emergency department (ED) face challenges in concurrently assessing patients with suspected COVID-19 infection, detecting bacterial coinfection, and determining illness severity since current practices require separate workflows. Here, we explore the accuracy of the IMX-BVN-3/IMX-SEV-3 29 mRNA host response classifiers in simultaneously detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and bacterial coinfections and predicting clinical severity of COVID-19. A total of 161 patients with PCR-confirmed COVID-19 (52.2% female; median age, 50.0 years; 51% hospitalized; 5.6% deaths) were enrolled at the Stanford Hospital ED. RNA was extracted (2.5 mL whole blood in PAXgene blood RNA), and 29 host mRNAs in response to the infection were quantified using Nanostring nCounter. The IMX-BVN-3 classifier identified SARS-CoV-2 infection in 151 patients with a sensitivity of 93.8%. Six of 10 patients undetected by the classifier had positive COVID tests more than 9 days prior to enrollment, and the remaining patients oscillated between positive and negative results in subsequent tests. The classifier also predicted that 6 (3.7%) patients had a bacterial coinfection. Clinical adjudication confirmed that 5/6 (83.3%) of the patients had bacterial infections, i.e., Clostridioides difficile colitis (n = 1), urinary tract infection (n = 1), and clinically diagnosed bacterial infections (n = 3), for a specificity of 99.4%. Two of 101 (2.8%) patients in the IMX-SEV-3 "Low" severity classification and 7/60 (11.7%) in the "Moderate" severity classification died within 30 days of enrollment. IMX-BVN-3/IMX-SEV-3 classifiers accurately identified patients with COVID-19 and bacterial coinfections and predicted patients' risk of death. A point-of-care version of these classifiers, under development, could improve ED patient management, including more accurate treatment decisions and optimized resource utilization. IMPORTANCE We assay the utility of the single-test IMX-BVN-3/IMX-SEV-3 classifiers that require just 2.5 mL of patient blood in concurrently detecting viral and bacterial infections as well as predicting the severity and 30-day outcome from the infection. A point-of-care device, in development, will circumvent the need for blood culturing and drastically reduce the time needed to detect an infection. This will negate the need for empirical use of broad-spectrum antibiotics and allow for antibiotic use stewardship. Additionally, accurate classification of the severity of infection and the prediction of 30-day severe outcomes will allow for appropriate allocation of hospital resources.

Estimation of Fluoride and Sirtuin1 in Patients with Diabetic Nephropathy in Kolar District of Karnataka, India.

Objective Prevalence of type-2 diabetes mellitus (DM) and diabetic nephropathy is growing rapidly in Asian countries, affecting low- and middle-income groups. One of the epidemiological issues of Kolar district is fluorosis; advanced glycation end product, carboxymethyl lysine (CML), and a molecule of interest Sirtuin1 are employed in the present study. In the correlation of fluoride with sirtuin1and CML with sirtuin1 of cases lies the important rationale of the study to assess the extent of kidney damage. Materials and Methods This is a comparative cross-sectional study with three groups, each with 70 patients, as follows: G1, control; G2, diabetes with diabetic nephropathy; and G3, type-2 DM without any complications. Informed written consent was obtained from all study patients. All the routine investigations were performed by fully automated Vitro 5, 1 Fs, Vitros. Fasting insulin was analyzed by Vitro eCI and glycated hemoglobin was estimated by BioRad D10. Sirtuin1, CML, and fructosamine were estimated by double antibody sandwich technique. Statistical Analysis The statistical analysis was performed by SPSS 20 (IBM) software. Means of normally distributed data were compared using analysis of variance (ANOVA), and not normally distributed data were compared by Kruskal-Wallis test. A p -value of less than 0.05 was considered statistically significant. Results A decrease in sirtuin1, serum, and urine fluoride of group 2 (34.74 [25.08-53.2], 0.24 [0.2-0.5], and 0.24 [0.16-0.41]) was observed compared with other groups. Increased CML and fluoride act as prooxidant, restricting the effect of sirtuin1 on cellular damage, causing further complications such as increased insulin resistance and decreased insulin sensitivity. Conclusion The alterations in serum sirtuin1 levels indicate the severity of damage due to stress during hyperglycemia and fluoride toxicity; hence, sirtuin1 can be considered as biomarker of aging. Subsequently, the correlation of CML, estimated glomerular filtration rate (eGFR), and fluoride with sirtuin1 indicates that increasing sirtuin1 may defend the forthcoming damage and could be considered in therapeutics.