Netrin 1 as a biomarker in cancer: scoping diagnostic, prognostic, and therapeutic perspectives with a focus on oral squamous cell carcinoma.

Goal of the review: The utilization of biomarkers to predict cancer risk, prognosis, and treatment outcomes is paramount. Netrin-1 (NTN1), known for its role in commissural axon guidance during embryonic development, has emerged as a versatile molecule with significant implications in cancer and neurobiology. Structurally resembling laminin, Netrin-1 regulates neuronal connectivity and plasticity in adulthood, influencing axonal and dendritic growth, neurotransmission, and cell migration. In addition to its neurological functions, Netrin-1 is increasingly recognized for its involvement in maintaining epithelial tissue and its regulatory roles in fundamental cellular processes, including adhesion, proliferation, differentiation, apoptosis, and angiogenesis. In cancer biology, Netrin-1's interactions with its receptors, such as DCC [Deleted in Colorectal Cancer] and UNC5 (a homolog of DCC), have been implicated in tumor progression across various physiological systems. Elevated levels of Netrin-1 in colorectal cancer and head and neck squamous cell carcinoma are correlated with increased tumorigenic potential, mediated through pathways involving NFκB activation and anti-apoptotic mechanisms. Mechanically induced hypermethylation and downstream signaling cascades that inhibit apoptosis and promote cell survival are observed upon Netrin-1 binding to DCC. Furthermore, Netrin-1 shows promise as a biomarker for detecting inflammatory activity in diseases such as multiple sclerosis and as a potential diagnostic, prognostic, and therapeutic indicator in oral squamous cell carcinoma. Elevated levels of Netrin-1 in bodily fluids, alongside immunohistochemical evidence, support its potential as a valuable clinical marker in cancer management. This abstract emphasizes Netrin-1's diverse biological roles, underscoring its potential as a diagnostic tool and therapeutic target in cancer research. The need for further exploration of Netrin-1's molecular interactions and clinical applications is urgent and crucial to advance personalized medicine approaches and enhance patient outcomes in oncology and neurology.

A comprehensive health assessment approach using ensemble deep learning model for remote patient monitoring with IoT.

The goal of this research is to create an ensemble deep learning model for Internet of Things (IoT) applications that specifically target remote patient monitoring (RPM) by integrating long short-term memory (LSTM) networks and convolutional neural networks (CNN). The work tackles important RPM concerns such early health issue diagnosis and accurate real-time physiological data collection and analysis using wearable IoT devices. By assessing important health factors like heart rate, blood pressure, pulse, temperature, activity level, weight management, respiration rate, medication adherence, sleep patterns, and oxygen levels, the suggested Remote Patient Monitor Model (RPMM) attains a noteworthy accuracy of 97.23%. The model's capacity to identify spatial and temporal relationships in health data is improved by novel techniques such as the use of CNN for spatial analysis and feature extraction and LSTM for temporal sequence modeling. Early intervention is made easier by this synergistic approach, which enhances trend identification and anomaly detection in vital signs. A variety of datasets are used to validate the model's robustness, highlighting its efficacy in remote patient care. This study shows how using ensemble models' advantages might improve health monitoring's precision and promptness, which would eventually benefit patients and ease the burden on healthcare systems.

Longitudinal study on salivary IL-6 trajectories in postoperative OSCC patients after chemotherapy and radiotherapy.

BACKGROUND: Oral squamous cell carcinoma (OSCC) poses a significant healthcare challenge globally, necessitating precise biomarkers for effective management. Interleukin-6 (IL-6) in saliva has emerged as a potential biomarker, yet its dynamics post-chemotherapy and radiotherapy remain underexplored. AIM: The aim of our study is to investigate the longitudinal dynamics of salivary interleukin-6 (IL-6) expression in postoperative OSCC patients over a one-year follow-up period after chemotherapy and radiotherapy. METHODS: This longitudinal study enrolled 60 participants, including postoperative OSCC patients and controls, collecting saliva samples over one year. RT-PCR and ELISA techniques measured IL-6 expression. Statistical analyses, including repeated measures ANOVA and univariate tests, evaluated IL-6 dynamics. RESULTS: Pre-treatment, OSCC patients exhibited elevated IL-6 levels compared to controls. Post-therapy, IL-6 levels decreased significantly with p < .0001, indicating treatment response and further result to baseline normalizing at 6-month follow-up. Significant differences were observed across treatment stages, supporting IL-6 as a diagnostic and prognostic marker for OSCC. RT-PCR and ELISA results showed the statistical significance of IL-6's role as a predictive marker. CONCLUSION: Salivary IL-6 emerges as a promising biomarker in OSCC management, necessitating further research to harness its diagnostic and therapeutic potential. By understanding IL-6 dynamics, personalized treatment approaches can be developed to improve patient outcomes. Longitudinal studies with larger cohorts and multi-omics approaches are warranted to validate findings and identify novel therapeutic targets.

Studies on the Effect of Piperine on Hepatocyte Nuclear Factor 1 Alpha (HNF-1α) and Sterol Regulatory Element-Binding Protein 1c (SREBP-1c) Levels in High-Fat-Diet and Sucrose-Induced Type 2 Diabetes Mellitus Rats.

BACKGROUND: Piperine, a naturally occurring compound in black pepper (Piper nigrum), is known for its potential health benefits, including its reported enhancement of insulin sensitivity. However, the precise impact of piperine on hepatocyte nuclear factor 1 alpha (HNF-1α) and sterol regulatory element-binding protein 1c (SREBP-1c), transcription factors for insulin signaling and glucose metabolism in hepatocytes, remains unclear. OBJECTIVE: This study aims to investigate the effect of piperine, compared to metformin, on blood glucose and insulin levels by modifying the expression of hepatic HNF-1α and SREBP-1c in high-fat-diet (HFD) and sucrose-induced type 2 diabetes mellitus (T2DM) rats and in human Chang liver cells. METHODS: Adult male albino rats were categorized into four groups: group 1 as the control, group 2 as T2DM, group 3 as T2DM rats treated with piperine (40 mg), and group 4 as T2DM rats treated with metformin (50 mg). Fasting blood glucose (FBG) and serum insulin levels were measured using enzyme-linked immunosorbent assay (ELISA), while real-time polymerase chain reaction (RT-PCR) analysis was conducted to assess the mRNA expression of HNF-1α and SREBP-1c. Further, piperine was treated with normal and high glucose-induced Chang liver cells, and gene expression was analysed. Data analysis was performed using one-way analysis of variance (ANOVA), with a significance set at p<0.05. RESULTS: Treatment with piperine led to a notable decrease in blood glucose levels and circulating insulin when compared with T2DM rats (group 2). Additionally, piperine administration resulted in the upregulation of HNF-1α mRNA expression and downregulation of SREBP-1c mRNA levels whose effects were found to be near that of the control and standard drug metformin's effects. In vitro study also confirmed that piperine improved the HNF-1α expression and reduced the expression of SREBP-1c in Chang liver cells. CONCLUSION: Our findings suggest that piperine treatment effectively regulates hyperglycemic and hyperinsulinemic insulin resistance in the liver by modulating the expression of HNF-1α and SREBP-1c. Consequently, piperine emerges as a promising candidate for therapeutic intervention in managing T2DM.

Identification of Potential Phytochemical Inhibitors From Conium maculatum Targeting the Epidermal Growth Factor Receptor in Metastatic Colorectal Cancer via Molecular Docking Analysis.

Background Metastatic colorectal cancer (mCRC) continues to rank as the second deadliest cancer on the global scale. CRC diagnosed at metastatic (stage IV) makes treatment strategies more challenging. Even though there are numerous therapeutic options available, the side effects of these treatments threaten the human health. Therefore, we are in the phase of searching new molecules that are less harmful and cost-effective. The common source of many pharmaceutical medications is plants. This study focuses on virtually screening phytochemicals from Conium maculatum as potential inhibitors of the epidermal growth factor receptor (EGFR), a crucial target in cancer therapy. Methods and materials C. maculatum was selected due to its phytochemicals and prior indications of its anticancer properties. In silico investigations encompass druglikeness screening, pharmacokinetics assessment, molecular docking, toxicity prediction, molecular target screening, and molecular dynamics simulations. A comprehensive analysis led to the identification of promising lead compounds. Results A total of 25 compounds exhibited favorable pharmacokinetic and drug-like characteristics. Among them, 12 compounds displayed a high affinity for EGFR as determined by molecular docking experiments. Further safety assessment using ProTox-II revealed that seven compounds had no anticipated toxicity, affirming their safety profiles.  Conclusion These findings collectively predicted the efficacy of seven phytochemicals from C. maculatum as EGFR inhibitors in mCRC. Further experimental investigations and optimization of the identified leads were needed to validate the efficacy and safety of identified lead compounds and explore their therapeutic potential in CRC.

Fabrication of Biogenic Titanium Nanoparticles and Investigating Their Biological Properties for Dental Applications.

INTRODUCTION: Oral inflammation, often triggered by infections, injuries, or immune responses, can compromise treatment outcomes, delay healing, and contribute to patient discomfort. The development of green nanoparticle synthesis methods is receiving attention due to their potential advantages over existing approaches. These procedures use commonly available, affordable, and environmentally friendly natural plant extracts. Due to their numerous uses in various industries, titanium oxide nanoparticles (TiO2NPs) have attracted the most attention among the nanoparticles. In this study, we present the green synthesis of Myristica fragrans (mace) extract as a reductant and stabilizer for the production of curcumin-functionalized TiO2NPs (CTN). We additionally evaluated the effectiveness of these nanoparticles as anti-inflammatory agents. OBJECTIVE: In this study, we aim to develop biogenic TiO2NPs using Myristica fragrans as a natural capping agent and functionalized with curcumin for effectively managing oral inflammation in dental applications. METHODS: The nanoparticles were synthesized using the green synthesis method and characterized using various characterization techniques. Biocompatibility was evaluated using hemolytic assays, and the bioactivity of the nanoparticles was assessed using anti-inflammatory assays. RESULTS: Curcumin-coated M-TiO2NPs (MCTN) were successfully synthesized and characterized by various techniques, confirming their morphology, crystallinity, functionalization, elemental composition, size, and stability. In vitro bioactivity studies revealed that MCTN exhibited significant anti-inflammatory activity, as evidenced by the inhibition of protein denaturation with minimal hemolytic potential. These findings highlight the potential of MCTN as a promising candidate for anti-inflammatory applications. CONCLUSION: Our results suggest that MCTN exhibits promising anti-inflammatory and anti-hemolytic properties. However, further in-depth in vivo analysis is required to fully understand their efficacy and toxicity.

Massively Parallel High-Throughput Single-Cell Patterning and Large Biomolecular Delivery in Mammalian Cells Using Light Pulses.

The recent advancements of single-cell analysis have significantly enhanced the ability to understand cellular physiology when compared to bulk cellular analysis. Here a massively parallel single-cell patterning and very large biomolecular delivery is reported. Micro-pillar polydimethyl siloxane stamp with different diameters (40-100 µm with 1 cm × 1 cm patterning area) is fabricated and then imprint distinct proteins and finally pattern single-cell to small clusters of cells depending on the micro-pillar diameters. The maximum patterning efficiency is achieved 99.7% for SiHa, 96.75% for L929, and 98.6% for MG63 cells, for the 100 µm micro-pillar stamp. For intracellular delivery of biomolecules into the patterned cells, a titanium micro-dish device is aligned on top of the cells and exposed by infrared light pulses. The platform successfully delivers small to very large biomolecules such as PI dyes (668 Da), dextran 3000 Da, siRNA (20-24 bp), and large size enzymes (464 KDa) in SiHa, L929 and MG63 cells. The delivery efficiency for PI dye, Dextran 3000, siRNA, and enzyme for patterned cells are ≈95 ± 3%, 97 ± 1%, 96 ± 1% and 94 ± 3%, with cell viability of 98 ± 1%. Thus, the platform is compact, robust, easy for printing, and potentially applicable for single-cell therapy and diagnostics.

Prediction of Novel Natural Small Molecules From Schinus molle as an Inhibitor of PI3K Protein Target in Cancer Cells Using In Silico Screening.

Introduction Cancer continues to pose a significant challenge in medical research. Phytochemicals derived from plants have emerged as a promising avenue for pioneering drug discovery due to their potential for reduced toxicity. The phosphatidylinositol 3-kinase (PI3K) pathway has gained recognition as a pivotal signaling pathway with implications across multiple facets of cancer initiation and progression. This study focuses on the virtual screening of phytochemicals from Schinus molle, evaluating their potential as inhibitors of PI3K, a crucial target in cancer therapy. Methods and materials The present study involved a comprehensive in silico screening of phytochemicals derived from S. molle. The screening process encompassed various parameters, such as drug-likeness, pharmacokinetics, molecular docking, toxicity analysis, bioavailability assessment, and molecular target exploration. The primary objective of this systematic approach was to identify potential lead compounds. The study aimed to provide a detailed understanding of the molecular properties of the phytochemicals and their potential as drug candidates. Results Upon analyzing 18 compounds, two compounds were noteworthy. Beta-spathulene and kaempferol demonstrated significant affinity for PI3K and favorable attributes concerning drug-likeness, pharmacokinetics, and bioavailability. Conclusion While our computational investigation lays a promising foundation, it is essential to emphasize that further experimental studies, including in vitro and in vivo experiments, are imperative to validate the action of these lead compounds.

Antioxidant Vitamins Attenuate Glyphosate-Induced Development of Type-2 Diabetes Through the Activation of Glycogen Synthase Kinase-3 ß and Forkhead Box Protein O-1 in the Liver of Adult Male Rats.

INTRODUCTION:  Glyphosate is a well-known broad-spectrum desiccant and herbicide. It is an active component used widely in popular weed control products like Roundup (BigHaat Agro Pvt Ltd, Bangalore, Karnataka, India), Rodeo (Corteva, Inc., Indianapolis, Indiana, United States), and PondMaster (PBI-Gordon Corporation, Shawnee, Kansas, United States). However, due to sustained presence, they tend to get deposited in the environmental resources and leach into the living system. It has been shown to develop various cancers and diabetes. However, its impact on GSK-3ß (glycogen synthase kinase-3 beta) and FOXO-1 (forkhead box protein O1), both critical proteins involved in the regulation of glucose metabolism and insulin signaling, is unknown.  Objective: The primary objective of this study was to check whether antioxidant vitamins (C and E) can reduce hyperglycemia and hyperinsulinemia in response to glyphosate exposure and the secondary objective was to investigate whether antioxidant vitamins have the capacity to downregulate GSK-3ß and FOXO-1-mediated oxidative stress in the liver of glyphosate induced rats.  Methods: We divided the experimental animals into three groups. Group 1 - control rats (animals were injected with olive oil (0.8ml) intraperitoneally), Group 2 - glyphosate-treated rats orally for ten weeks, Group 3 - glyphosate-treated rats received vitamin C and vitamin E. After 30 days of treatment, the animals were anesthetized, sera were separated and used for the biochemical analysis. Liver tissues from control and treated animals were dissected and stored at -20°C for further gene expression analysis. Fasting blood glucose (FBG) was assessed by calorimetric analysis, while serum insulin was measured by enzyme-linked immunosorbent assay (ELISA). Gene expression studies of specific genes (FOXO1 and GSK3) were analyzed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. RESULTS: The expression level of FOX01 and GSK3ß genes was higher in glyphosate-induced animals compared with the control group but was reduced significantly (p＜0.05) upon treatment with antioxidant vitamins (C and E). Other biochemical parameters, including FBG, serum insulin, and antioxidant enzyme assays, also showed that antioxidant vitamins reduce glyphosate-induced insulin resistance and type-2 diabetes.  Conclusion: The current study provides in vivo experimental evidence that antioxidant vitamins (C and E) reduce the glyphosate-mediated development of type-2 diabetes risk via the downregulation of FOX01 and GS-3ß mRNA expression in the liver. Hence, vitamins C and E may be considered as therapeutics for the treatment of diabetes.

Evaluation of Immunohistochemistry Technique for Diagnosis of Extrapulmonary Tuberculosis in Biopsy Tissue Specimen as Compared to Composite Diagnostic Criteria.

Introduction: Diagnosis of extrapulmonary tuberculosis (EPTB) has been challenging owing to its paucibacillary nature and diverse clinical manifestations. Immunohistochemistry (IHC) on biopsy specimens has presented a new perspective toward improving tuberculosis diagnosis. MPT64 is a unique antigen that has shown high sensitivity and specificity compared to other conventional techniques in its ability to diagnose tuberculosis as well as differentiate it from nontubercular mycobacteria. In this study, we aimed to analyze the utility of anti-MPT64 in the diagnosis of EPTB. Methods: In this cross-sectional study, conducted over a period of 1 year, 52 nonrepetitive samples from 52 participants with a presumptive diagnosis of EPTB were collected and processed. The specimens were subjected to Ziehl-Neelsen staining, GeneXpert, tissue culture by mycobacterium growth indicator tube, H and E staining, and IHC with anti-MPT64. The sensitivity and specificity of anti-MPT64 was computed against a composite diagnostic criterion. Results: Fifty-two consecutive participants satisfying the study criteria were recruited. The mean age of the study population was 37.35 ± 18.71 years. Lymph node specimen accounted for majority of the specimen processed (n = 20, 38.5%). The sensitivity of anti-MPT64 in the diagnosis of EPTB was 68.29%, specificity was 90.90%, positive predictive value was 96.55%, and negative predictive value was 43.47%, when composite criteria were considered standard for diagnosis. Conclusion: Immunohistochemical staining by anti-MPT64 is useful in establishing microbiological diagnosis of EPTB on biopsy specimens.

Genotypic characterization of Streptococcus mutans in child-mother pair-A PCR based study.

OBJECTIVES: At present, there is lack of evidence in literature regarding the transmission of Streptococcus Mutans from a caries-free mother to child by genetic methods, so the present study aimed to identify the genetic characterization of Streptococcus Mutans strains isolated from caries-free and caries active children and their mother being caries-free in both the groups and also to identify the genetic patterns of Streptococcus Mutans between caries-free and caries-active individuals. METHODS: Twenty child-mother pair were selected and divided into 2 groups and the mothers being caries-free in both the groups. Saliva samples were collected using a sterile tube, followed by microbial culture of Streptococcus mutans, DNA isolation and PCR amplification. The molecular weights of each band were converted into a binary data and data were entered into SPSS software version 20.0 to generate similarity dendrograms. RESULTS: Amplified products of Streptococcus Mutans demonstrated a same genetic distance between the mother-child pair, indicative of a closely related species. Dendrogram interpretation represented a greater genetic polymorphism of Streptococcus Mutans between caries-free and caries-active children. CONCLUSIONS: Identical genetic distance between child-mother pair showed that, these Streptooccus Mutans were closely related and could have vertically transmitted from their mothers. Different genotypic pattern between caries-free and caries active subjects showed a genetic polymorphism among the Streptococcus Mutans strains.

Profile of two hundred children with Autism Spectrum Disorder from a tertiary child and adolescent psychiatry centre.

BACKGROUND: There is a recent trend of increase in diagnosis of Autism Spectrum Disorder in India. Till date, there are few retrospective and prospective Indian studies with limited sample sizes ranging from 16 to 94 children. With this background, we planned a retrospective chart review of all new cases of Autism Spectrum Disorder for a period of 1 year in our tertiary care child psychiatry centre. METHODOLOGY: Objectives of this study were to compare the sociodemographic and clinical profile of children below and above 3 years of age and between those who were self-referred versus those referred by professionals. RESULTS: Out of a total of 1957 case records, 201 children (10.3%) were diagnosed with Autism Spectrum Disorder. Male to female ratio was 4:1.2. Mean age of consultation was significantly higher in males. Seventy six percent had a comorbid disorder with Intellectual disability, Attention Deficit Hyperactivity Disorder and Epilepsy being the most common comorbidities. Most caregivers (92.5%) recognized symptoms by 3 years of age. Presenting complaint of poor social response was more prevalent in children <3 years and co-morbidities in children above 3 years. Presenting complaint of speech delay was more common in children who were referred by professionals when compared with those who were self-referred. DISCUSSION: There is a need to sensitize parents and professionals for early intervention and to standardize protocols for assessment and intervention.