The Evaluation of Tumor Budding in Oral Squamous Cell Carcinoma Arising in the Background of Oral Submucous Fibrosis.

Background and objective Oral submucous fibrosis (OSMF) is a common and potentially malignant disorder with a high risk of malignant transformation to oral squamous cell carcinoma (OSCC). Tumor budding is a scattered pattern of invasion and is related to the aggressive behavior of malignant tumors, increased depth of invasion, higher clinical staging, size, and grade of the tumor. The present study aimed to evaluate tumor budding in OSCC arising in the background of OSMF. Materials and methods A total of 120 patients with OSCC (30 each of OSCC arising in the background of OSMF, well-differentiated, moderately differentiated, and poorly differentiated OSCC) were included in the study. Hematoxylin and eosin (H&E)-stained sections were evaluated for the presence of tumor buds at the invasive front of the tumor. Kappa statistics and chi-square tests were employed to statistically compare the results by using IBM SPSS Statistics 23 software (IBM Corp., Armonk, NY). A p-value of less than or equal to 0.05 was considered statistically significant.  Results The mean age of the occurrence of OSCC arising in the background of OSMF was 45.3 ±7.62 years. A progressive increase in the tumor buds was noted in OSCC arising in the background of OSMF, well-differentiated squamous cell carcinoma (WDSCC), moderately differentiated squamous cell carcinoma (WDSCC), and poorly differentiated squamous cell carcinoma (PDSCC). The chi-square test showed no significant difference between OSCC in the setting of OSMF and WDSCC (p=0.604) groups; however, a significant difference was noted with MDSCC (p=0.001) and PDSCC (p=0.000) groups. Conclusions OSCC arising in the background of OSMF shows lower tumor budding at the invasive front of the tumor. This histopathological parameter can be easily identified in the H&E sections and is fairly reproducible. Hence, reporting the presence of tumor budding will help in predicting the prognosis of these patients.

Molecular profiling of oral epithelial dysplasia and oral squamous cell carcinoma using next generation sequencing.

BACKGROUND: Next generation sequencing (NGS) is a massive, high-throughput sequencing technology used to analyze various mutations and genetic changes in cancer. Oral squamous cell carcinoma (OSCC) is the most common malignancy of the head and neck region. OSCC usually arises from oral potentially malignant disorders, like oral leukoplakia, oral submucous fibrosis and erythroplakia, and shows mutation of tumor suppressor genes, and several other critical genes involved in apoptotic pathways, cell migration, and cell growth. AIM: To analyze the molecular profiles of oral epithelial dysplasia and different grades of oral squamous cell carcinoma using NGS in the Indian subpopulation. METHODOLOGY: 21 patients (5 patients each of well differentiated, moderately differentiated, poorly differentiated squamous cell carcinoma, severe epithelial dysplasia, and 1 normal appearing mucosal tissue from apparently healthy individuals) were included in the study. Next generation sequencing was carried out using 50 hotspot gene panel. Protein-protein analysis was carried out using STRING Consortium 2023 and the methylation profile of the expressed genes was evaluated using the UALCAN portal. RESULTS: Severe epithelial dysplasia showed TP53 (c.743G>A, p.R248Q) pathogenic mutations (SNV) in suboptimal QC parameters. Well differentiated squamous cell carcinoma showed TP53 (c.328delC, p.Arg110fs*13), APC (c.4135G>T, p.Glu1379*), and FBXW7 (c.832C>T, p.Arg278*) mutations. CTNNB1 (c.134C>T, p.Ser45PheS45F), TP53 (c.637C>T, Arg213TerR213*), NRAS (c.183A>C, p.Gln61HisQ61H) and PDGFRA (c.1672C>T, p.Arg558Cys) mutations were seen in moderately differentiated squamous cell carcinoma. No pathogenic mutations were evident in poorly differentiated squamous cell carcinoma. STRING analysis showed that all the expressed proteins in each group were interrelated to each other. No significant difference was evident in the methylation profile of all the expressed genes when compared to the normal controls. CONCLUSION: The results obtained in this study explain the diverse genetic mutations in various grades of oral squamous cell carcinoma. Identification of these mutations would help in providing better treatment, designing a proper treatment plan for the patients with OSCC and support minimal intervention medicine.

Comparative Assessment of Lipid Peroxidase in Oral Cancer and Oral Potentially Malignant Disorders.

Introduction Oral potentially malignant disorders (OPMD) are abnormally altered tissues that could potentially develop into oral cancer. From the literature, it is understandable that not all OPMDs develop into oral cancer. Hence, it is essential to identify the high-risk lesions that are more likely to develop into oral cancer. Lipid peroxidase (LPO) is a byproduct of phospholipid metabolism, and its levels are an oxidative stress marker that can probably help us predict the onset of cancer in OPMDS. This study aimed to assess the levels of LPO in OPMD, oral cancer, and normal patients. Materials and methods The sample size estimated was 15 per group. There were four groups in total. The estimation was done with the Abbkine LPO enzyme-linked immunosorption assay (ELISA) kit (Atlanta, Georgia, USA). An enzyme-substrate reaction was carried out, and the degree of the color change was measured using a microplate reader. The values were tabulated, and statistics were carried out using Statistical Package for Social Sciences (SPSS) version 26.0 (IBM Corp., Armonk, NY, USA). Both descriptive and inferential statistics were carried out. Results LPO levels (nmol/L) in each of the four groups were as follows: Group 1 (oral cancer): 171.86±78.86, Group 2 (controls): 71.66±28.36, Group 3: (oral leukoplakia): 127.50±103.53, and Group 4 (oral submucous fibrosis and oral lichen planus): 100.39±41.06. The results, when compared, were statistically significant (P< 0.05). Discussion From the above results, it is understandable that oral cancer patients experience increased oxidative stress compared to the OPMD group. The current study concluded that the obtained results showed differences in LPO levels, suggesting LPO could be used as a marker and screening tool to assess the rate and severity of cellular damage in patients with oral potentially malignant disorders.

Identifying the molecular mechanisms of action of wound healing properties of Mathan tailam and Mahamegarajanga tailam in Wistar albino rats: Evidence through IL-10/VEGF/TNF-α signalling pathways.

The Siddha system of medicine (SSM) is the oldest medical science practised in the ancient period of the southern part of India and Sri Lanka. Many formulations were described for wound healing in the SSM, with specific diagnostic differentiation in the Siddha literature. Most preparations for wound healing were available in the form of oil-based formulations, especially for external usage. Mathan tailam (MT) and Mahamegarajanga tailam (MMRT) have been used by Siddha physicians and traditional practitioners to treat wounds. Mathan tailam is a popular regimen for skin lacerations, burns, skin infections, diabetic wounds, and dermatitis. Mahamegarajanga tailam has long been used by traditional vaidyars to treat cuts and burns. Both MT and MMRT are clinically well-appreciated drugs for wound healing and need to be studied for their mechanisms of action for scientific documentation. In an in vivo study on albino rats -excisional wound model, the histopathological changes, histo-immune response, biomarker analysis, and mRNA expression were studied and analysed. Wounds treated with MT and MMRT healed faster (p < 0.05) than the untreated group (CNT). Histological investigation showed rapid re-epithelialization, dense collagen deposition, increased enzymatic antioxidant activities and decreased lipid peroxidation in the MT and MMRT groups. mRNA expression reveals MT and MMRT-treated tissues able to induce convergent cell motility in wound space. Our study for the first time provides strong in vivo experimental evidence that Mathan tailam and Mahamegarajanga tailam play a crucial role in promoting skin tissue wound healing through IL-6/VEGF/TNF-α mediated mechanisms. Traditional practices continue to teach us valuable lessons, as seen by their continuous use in their locality for years.

In silico and in vitro studies for the identification of small molecular inhibitors from Euphorbia hirta Linn for rheumatoid arthritis: targeting TNF-α-mediated inflammation.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that is now potentially lethal and has a significant detrimental influence on people's daily lives by affecting bone joints. Inflammation plays a vital role in this type of autoimmune disorder. In rheumatoid arthritis, long-term production of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) stimulates the immune system against cells in bone joints and helps to develop the pathogenesis of rheumatoid arthritis. So, while treating rheumatoid arthritis, we need to block these kinds of mechanisms. We employed soxhlet extraction, thin-layer chromatography (TLC), and gas chromatography-mass spectroscopy (GC-MS) to analyze the phytocompound information in E. hirta leaves. Furthermore, our research included in vitro investigations using Western blotting and mRNA expression analysis (TNF-α, IL-1ß, IL-6) to affirm the anti-inflammatory effectiveness of our extract. For identifying the lead-like molecules, virtual screening and molecular dynamics simulations were used. TLC results confirmed the presence of phytocompounds in E. hirta crude through spots. The structure elucidation of the phytocompounds was confirmed by the GC-MS chromatogram. The in vitro outcomes collectively underscore the inhibitory influence of E. hirta on cell proliferation and its capacity to attenuate the expression of TNF- α within THP-1 cells. The results of in silico methodologies confirmed six lead-like molecules. We could conclude that phytocompounds from ethanol leaf crude have effective lead-like molecules against the TNF-α.

Sesuvium Portulacastrum Potentiates Anticancer Activity by Facilitating the Expression of IRS-1/AKT Signalling: An In vitro Study.

Sesuvium portulacastrum, a coastal medicinal plant with traditional uses has shown promising biological activities including anti-inflammatory, antioxidant and antimicrobial properties. However, the mechanisms of action active ingredients of this plant have not been studied. Aim of the current study is to investigate the anticancer activity of Sesuvium portulacastrum using in vitro and in silico analysis. The in vitro assays included NO radical scavenging activity, total phenolic and flavonoid content determination. The data were analysed by one-way-ANOVA and p<0.05 was considered as statistically significant. The phytochemical analysis showed the presence of tannins, steroids, terpenoids and phenols. Antioxidant activity of S. portulacastrum showed the dose dependent effect of nitric oxide radical scavenging activity. In silico analysis showed a better binding affinity with IR, IRS1 and Akt molecules which demonstrated the action of bioactive compound of S. portulacastrum against IRS-1/AKT signalling pathway.

Anti-metastatic Effect of Heliotropium bacciferum on MCF-7 Human Breast Cancer Cell Line.

Background Heliotropium bacciferum, often known as wild heliotrope or wild quailplant, is a flowering plant from the borage family. This study examines the anti-metastatic impact of H. bacciferum on Michigan Cancer Foundation-7 (MCF-7) breast cancer cells and its ability to disrupt signaling pathways. Aim To explore the anti-metastatic effect of H. bacciferum on the MCF-7 breast cancer cell line. Materials and methods For this research, MCF-7 breast cancer cells were used. Cells were cultured and subjected to 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, as well as gene expression analysis for glycogen synthase kinase 3 beta (GSK3ß), wingless-related integration site 2 (Wnt2), and ß-catenin. The plant extract was tested to determine if it successfully blocked the signalling pathway or not.  Results The MTT test was performed to study the cytotoxic impact of H. bacciferum. At an increasing concentration of 100 µg/mL, the extract inhibited growth by 55%, whereas at 150 µg/mL, it inhibited growth by 52.5%. Maximum inhibition was seen at 150 µg/mL. H. bacciferum suppressed the GSK3ß and Wnt2 signaling pathways in MCF-7 breast cancer cell lines, acting as an anti-metastatic and anticancer agent. The heliotrine compound in H. bacciferum showed high binding energy to metastatic targets such as GSK3ß, Wnt2, and ß-catenin. Moreover, chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties also support the study. Conclusion In this study, we can infer that H. bacciferum has a favourable anticancer impact on MCF-7 breast cancer cell lines and may be utilised as an anticancer drug against breast cancer cells. It can also be further evaluated for different breast cancers and cell lines.

The Oncolytic Effect of Aerva lanata on Osteosarcoma Cell Lines via the Apoptotic Signaling Pathway.

Introduction Osteosarcoma, a malignant bone tumor, poses significant treatment challenges, necessitating the development of alternative therapeutic strategies. Aerva lanata (A. lanata), a medicinal plant with traditional use in various healthcare systems, has anti-cancer properties. This study looks at the oncolytic effect of A. lanata extract on osteosarcoma cell lines (sarcoma osteogenic-Saos2). Aim The aim of this study was to investigate the oncolytic effect of Aerva lanata on Saos2 cell lines through the apoptotic signaling pathway. Materials and methods A. lanata extract was prepared using Soxhlet extraction, and its cytotoxic effects on Saos2 cells were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Real-time polymerase chain reaction (RT-PCR) analysis of gene activity was used to assess the extract's effect on apoptotic signaling pathways. Results The MTT assay demonstrated a dose-dependent decrease in Saos2 proliferation following treatment with A. lanata extract at concentrations ranging from 50 µg to 200 µg. The standard deviations observed ranged from 1.414 to 7.071. Gene expression analysis revealed that the extract led to a reduction in the messenger ribonucleic acid (mRNA) levels of the anti-apoptotic marker B-cell lymphoma 2 (Bcl2), with standard deviations ranging from 1 to 0.535. Conversely, it induced an increase in the mRNA levels of the tumor suppressor protein p53, with standard deviations ranging from 1 to 1.835. These findings suggest that the extract modulates the apoptotic pathways of the Bcl2 and p53 genes.  Conclusion A. lanata extract exhibits promising anti-cancer activity against Saos2 osteosarcoma cell lines, inducing apoptosis by downregulating Bcl2 and increasing p53. The study's findings suggest that A. lanata may be useful as a natural treatment for osteosarcoma.

Blueberry extract and its bioactive compounds mitigate oxidative stress and suppress human lung cancer cell (A549) growth by modulating the expression of p53/EGFR/STAT3/IL6-mediated signaling molecules.

Bioactive phytocompounds are crucial components in all plants. Since the time of traditional medicine, the utilization of plants has been grounded in the potential of these bioactive compounds to treat or manage specific illnesses. These natural bioactive compounds have sparked growing interest in employing medicinal plants for addressing various conditions, such as inflammatory diseases, diabetes, and cancer. This study focuses on assessing the qualitative phytochemical composition, antioxidant potential, and cytotoxic effects of blueberry (Vaccinium sect. Cyanococcus) extract using three different solvents, namely water, ethanol, and methanol. The extract exhibited notable antioxidant activities, as evidenced by DPPH and H2O2 free radical scavenging assays. The cell viability assay also demonstrated cell growth inhibition in A549 cells. Furthermore, nine specific phytocompounds sourced from existing literature were selected for molecular docking studies against CDK6 and, AMPK key protein kinases which enhance the cancer progression. The molecular docking results also revealed favorable binding scores, with a high score of -9.5 kcal/mol in CDK6 protein and a maximum score of AMPK with targets of -8.8 kcal/mol. The selected phytocompounds' pharmacodynamic properties such as ADMET also supported the study. Furthermore, rutin stated that pre-dominantly present in blueberry plants shows a potent cytotoxicity effect in A549 cells. Functional annotations by bioinformatic analysis for rutin also revealed the strong enrichment in the involvement of PI3K/AKT1/STAT, and p53 signaling pathways. Based on this analysis, the identified rutin and other compounds hold a promising anticancer activity. Overall, the comprehensive evaluation of both in vitro and in silico data suggests that the Vaccinium sect. Cyanococcus extract could serve as a valuable source of pharmaceutical agents and may prove effective in future therapeutic applications.

Heavy Metal Exposure-Induced Cardiovascular Diseases: Molecular Mechanisms and Therapeutic Role of Antioxidants.

Globally, cardiovascular diseases (CVDs) are the main cause of mortality every year worldwide. CVD health is influenced by various health factors, such as blood pressure, cholesterol levels, and glucose control. The main risk factors include smoking, physical activity, food intake, and body mass index. Around 90% of CVDs could be prevented by controlling these risk factors. Heavy metals are indigenous to the environment of the earth. However, modern lifestyles have led to the exploitation of our environment by unconstrained use of heavy metals. Though heavy metals are essential components, they are hazardous to humans and living systems due to their persistent and non-degradable nature. The mainpurpose of this study is to provide a literature review on the mechanisms of heavy metals, particularly arsenic, lead, and cadmium, that cause cardiovascular diseases. The major mechanism by which heavy metals result in various modalities of cardiovascular disease is the generation of reactive species and the depletionof the antioxidant reserves inside the biological system. The generation of reactive species gradually leads to the activation of various signaling pathways, resulting in either apoptosis or unrestricted cell growth. These unfavorable conditions result in a state when there is an imbalance between reactive species generation and antioxidant activity. Both endogenously present antioxidants and dietary antioxidants are very much essential in regulating the redox potential of the body. They help in the detoxification and excretion of heavy metals and their metabolites in the biological system. Therefore, recognizing the role of heavy metals in cardiovascular health is crucial for developing preventive strategies and interventions aimed at mitigating their adverse effects on human health.

The role of MicroRNAs in the diagnosis and treatment of oral premalignant disorders.

Oral premalignant disorders (OPMDs) are a group of potentially malignant conditions that pose a significant health burden globally. MicroRNAs (miRNAs), small non-coding RNA molecules, have emerged as crucial regulators of gene expression and have been implicated in various biological processes, including carcinogenesis. This review synthesizes existing knowledge to provide a comprehensive understanding of the molecular mechanisms underlying OPMDs and to highlight the potential of miRNAs as promising biomarkers and therapeutic targets. Additionally, this review seeks to explore the potential of miRNA-based diagnostic biomarkers for early detection of OPMDs in the current literature on miRNAs in OPMDs, examining their involvement in disease pathogenesis, diagnostic potential, and therapeutic implications. Dysregulated miRNAs can target genes involved in critical cellular processes, such as cell cycle regulation, apoptosis, and DNA repair, leading to disease progression. Notably, miR-21, miR-31, miR-135b, and miR-486-5p have shown promise as potential biomarkers for early detection of oral premalignant lesions. Furthermore, the paper discusses the therapeutic implications of miRNAs in OPMDs. Preclinical studies have demonstrated the efficacy of miRNA-targeted therapies, such as miRNA mimics and inhibitors, in suppressing the growth of oral premalignant lesions. Early-phase clinical trials have shown promising results, indicating the potential for personalized treatment approaches. The findings underscore the importance of understanding the molecular mechanisms underlying these disorders and provide insights for the development of improved diagnostic and therapeutic strategies. However, they pose certain limitations given their intrinsic variability in expression profiles, the need for optimized isolation and detection methods, and potential hurdles in transitioning from preclinical success to clinical applications. Thus, future clinical studies are warranted to fully exploit the potential of miRNAs in the management of OPMDs.

Merremia emarginata Extract Potentiates the Inhibition of Human Colon Cancer Cells (HT-29) via the Modulation of Caspase-3/Bcl-2-Mediated Pathways.

Background This study investigates Merremia emarginata's curative effectiveness against colon cancer cells. M. emarginata, often known as Elika jemudu, is a Convolvulaceae family plant. The inhibitory ability of anticancer herbal extracts against cancer cell growth and mediators is tested.  Aim This study aims to evaluate the potent anticancer activity of M. emarginata against colon cancer cell line (HT-29). Materials and methods M. emarginata leaves were gathered and processed using solvent extraction. Anticancer activity on colon cancer cells was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test and cysteine aspartic acid protease-3 (caspase 3), B-cell lymphoma 2 (Bcl-2), and B-cell lymphoma-extra large (Bcl-xL) mRNA expressions. The data was reported as the mean ± SD of three separate experiments done in triplicate. The statistical analysis was carried out using one-way analysis of variance (ANOVA), with a p-value less than 0.05 indicating statistical significance. Results The cell viability test showed a gradual decrease in cell growth and proliferation as the concentration increased. The ethanolic extract of M. emarginata was found to be cytotoxic against colon caller cell lines. The extract was able to induce apoptosis of cancer as revealed by Bcl-2, Bcl-xL, and caspase-3 (p<0.05 and p<0.001) signaling pathways. Conclusion M. emarginata extracts showed good anticancer activity against colon cancer cell lines. Further work is required to establish and identify the chemical constituent responsible for its anticancer activity.

A review on advancements in the application of starch-based nanomaterials in biomedicine: Precision drug delivery and cancer therapy.

The burgeoning field of starch-based nanomaterials in biomedical applications has perceived notable progressions, with a particular emphasis on their pivotal role in precision drug delivery and the inhibition of tumor growth. The complicated challenges in current biomedical research require innovative approaches for improved therapeutic outcomes, prompting an exploration into the possible of starch-based nanomaterials. The conceptualization of this review emerged from recognizing the need for a comprehensive examination of the structural attributes, versatile properties, and mechanisms underlying the efficiency of starch-based nanomaterials in inhibiting tumor growth and enabling targeted drug delivery. This review delineates the substantial growth in utilizing starch-based nanomaterials, elucidating their small size, high surface-volume ratio, and biocompatibility, predominantly emphasizing their possible to actively recognize cancer cells, deliver anticancer drugs, and combat tumors efficiently. The investigation of these nanomaterials encompasses to improving biocompatibility and targeting specific tissues, thereby contributing to the evolving landscape of precision medicine. The review accomplishes by highlighting the auspicious strategies and modern developments in the field, envisioning a future where starch-based nanomaterials play a transformative role in molecular nanomaterials, evolving biomedical sciences. The translation of these advancements into clinical applications holds the potential to revolutionize targeted drug delivery and expand therapeutic outcomes in the realm of precision medicine.

Epigenetic modulation of long noncoding RNA H19 in oral squamous cell carcinoma-A narrative review.

Oral squamous cell carcinoma (OSCC) showed a seemingly increasing incidence in the last decade. In India, despite the use of tobacco decreased rapidly, in the past five years, the incidence pattern of OSCC over gender and age showed a drastic shift. About 51 % of the head and neck cancers are not associated with habits. Studies exploring various contributing factors in the incidence of this malignancy have documented. Recently, the epigenetic factors associated with the induction and progression of OSCC were explored. More than 90 % of the human genome is made up of non-coding transcriptome, which believed to be noises. However, these non-coding RNAs were identified to be the major epigenetic modulators, which raises concern over incidence of carcinoma in non-habit patients. H19 is a long non coding RNA which proved to be an effective biomarker in various carcinoma. Its role in oral squamous cell cancer was not investigated in depth. This review discusses in detail the various epigenetic role of H19 in inducing oral carcinogenesis.

Anticancer Effects of Rosmarinus officinalis Leaf Extract on KB Cell Lines.

Background The value and use of medicinal plants, including the widespread cultivation of Rosmarinus officinalis, have increased rapidly. R. officinalis, a medicinal plant native to the Mediterranean, has received attention for its potential therapeutic benefits. This study evaluates R. officinalis anticancer activity using human epithelial carcinoma (KB) cell lines derived from nasopharyngeal epidermoid carcinoma. The KB cell line is known for its increased sensitivity to specific chemotherapeutic agents (CA), making it a useful model in cancer research. The impact of R. officinalis is assessed using comprehensive analyses of cell viability and gene expression. Aim This study aims to evaluate the anti-cancer effects of R. officinalis on KB cell lines. Materials and methods The R. officinalis leaf extract was separated and used to treat KB cell lines. The cell viability of treated KB cells was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Real-time polymerase chain reaction (RT-PCR) was used to analyze the expressions of matrix metalloproteinase (MMP-9) and tumor-inducing metalloproteins (TIMP-1) messenger ribonucleic acid (mRNA) genes. The statistical analysis was performed. Results This study analyzes the anticancer properties of R. officinalis on KB cell lines. The results show that increasing the concentration of rosemary extract reduces cell viability in malignant cells. Furthermore, the R. officinalis effect on the apoptotic signaling system is demonstrated by a decrease in MMP-9 and TIMP-1 mRNA expressions, as observed by RT-PCR analysis. Conclusion Patients looking for natural anticancer treatments may benefit from biogenically prepared anticancer drugs. The current research focuses on R. officinalis as a potential alternative to chemically synthesized anticancer drugs.

Expression Profile of Circulating Exosomal microRNAs in Leukoplakia, Oral Submucous Fibrosis, and Combined Lesions of Leukoplakia and Oral Submucous Fibrosis.

OBJECTIVES: This study aims to elucidate the expression of circulating exosomal miRNAs miRNA 21, miRNA 184, and miRNA 145 in the studied groups, including patients with (i) leukoplakia; (ii) oral submucous fibrosis; (iii) oral submucous fibrosis with leukoplakia; (iv) oral squamous cell carcinoma; and (v) healthy individuals. STUDY DESIGN: An observational study was conducted among 54 patients who reported to the outpatient department of Saveetha Dental College and Hospitals. The patients were divided into three groups: Group I healthy individuals (n = 18), Group II: case group (leukoplakia, OSMF, and leukoplakia and OSMF) (n = 18), and Group III: OSCC (n = 18). Real-time polymerase chain reaction analysis was carried out to assess the expression profiles of miRNA 21, miRNA 184, and miRNA 145. The statistical analysis was calculated using SPSS software version 23. RESULTS: All three miRNAs showed a statistically significant difference in the one-way ANOVA test between the case group (leukoplakia, OSMF, and leukoplakia and OSMF), healthy group, and OSCC group (p < 0.005). The case group (leukoplakia, OSMF, leukoplakia and OSMF) showed upregulated expression of miRNA 21 and miRNA 184 with threefold change and fourfold change and downregulated expression of miRNA 145 with 1.5-fold change when compared to apparently healthy individuals. CONCLUSION: Plasma circulating exosomal miRNAs miRNA 21, miRNA 145, and miRNA 184 expression could be a novel panel of plasma biomarkers to categorise case group (leukoplakia, OSMF, leukoplakia and OSMF) patients with a high risk of malignant transformation.

Hesperidin Inhibits Oral Cancer Cell Growth via Apoptosis and Inflammatory Signaling-Mediated Mechanisms: Evidence From In Vitro and In Silico Analyses.

Background Oral carcinoma presents a significant health challenge, prompting the need for innovative therapeutic approaches. Elevation of inflammatory mediators, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), has promoted cellular proliferation, inhibited apoptosis, and fostered oral cancer progression through complex signaling pathways. Hesperidin, a flavanone glycoside found in citrus fruits, is of keen interest in this study as it has been proven to have multiple health benefits through in vivo and in vitro studies. However, the mechanism behind the anticancer activity of hesperidin in oral carcinoma remains obscure. Aim The study aimed to explore the anticancer potential of hesperidin on human oral cancer cells (KB cells) by modulating pro-inflammatory and apoptotic signaling mechanisms. Methods Cancer cell growth inhibitory activity was assessed using the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay. Gene expression analysis was performed using real-time RT-PCR analysis. In addition, in silico docking analysis was conducted to confirm the binding affinity of hesperidin with pro-inflammatory and apoptosis signaling molecules. The data were analyzed using one-way ANOVA and the "t" test. Results Utilizing the MTT assay, a dose-dependent cytotoxic effect of hesperidin was unveiled, with a remarkable IC50 value indicative of its potent inhibition of cell proliferation. Complementing these findings (p<0.05), qRT-PCR analysis demonstrated hesperidin's regulatory influence on key molecular targets within the KB cell line. Hesperidin treatment resulted in a noteworthy reduction in TNF-α, interleukin-1 beta (IL-1-ß), IL-6, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and B-cell lymphoma 2 (Bcl-2) mRNA expression levels (p<0.05), highlighting its inhibitory role in cell proliferation, migration, and inflammation processes. Simultaneously, hesperidin promoted the expression of BAX mRNA (p<0.05), indicating an enhancement in cell death. Molecular docking simulations further revealed robust binding affinities between hesperidin and target proteins, suggesting its potential to disrupt cellular functions and inflammatory signaling pathways in oral cancer cells. Conclusion The cytotoxic effects on the KB cell line and its anti-inflammatory properties position hesperidin as a compelling candidate for further exploration in the quest for effective oral carcinoma treatments. These findings shed light on the intricate molecular mechanisms underlying hesperidin's promise as a therapeutic agent against oral carcinoma.

Molecular analysis to identify novel potential biomarkers as drug targets in colorectal cancer therapy: an integrated bioinformatics analysis.

Colorectal cancer (CRC) is a heterogeneous disease that requires new diagnostic and prognostic markers. Integrated bioinformatics approach to identify novel therapeutic targets associated with CRC. Using GEO2R identified DEGs in CRC, and Funrich software facilitated the visualization of DEGs through Venn diagrams. From a total of 114 enhanced DEGs, potential hub genes were further filtered based on their nodal strength and edges using STRING database. To gain insights into the functional roles of these hub genes, gene ontology and pathway enrichment were conducted thorough g: profiler web server. Subsequently, overall survival plots from GEPIA and oncogenic predictive functions like mRNA expressions for stages and nodal metastasis were employed to identify hub genes in CRC patient samples. Additionally, the cBioPortal and HPA databases also revealed genetic alterations and expression levels in these hub genes in CRC patients, further supporting their involvement in colorectal cancer. Gene expression by RT-PCR shows upregulation of hub genes in HT-29 cells. Finally, our integrated bioinformatic analysis revealed that ABCE1, AURKA, HSPD1, PHKA1, CDK4, and YWHAE as hub genes with potential oncogenic roles in CRC. These genes hold promise as diagnostic and prognostic markers for colorectal tumorigenesis, providing insights into targeted therapies for improved patient outcomes.

The Association of miRNA10a and Glucose Transporters in Oral Squamous Cell Carcinoma With Diabetes: A Pilot Study.

INTRODUCTION: MicroRNAs (miRNAs) are well-established post-translational non-coding RNAs that play crucial roles in mRNA degradation and repression. Glucose transporter 1 (GLUT1) showed correlation along with various miRNA, specifically miRNA10a expression in lung cancers. The role of miRNA10a along with glucose upregulation leading to cancer proliferation in oral squamous cell carcinoma (OSCC) is unknown. This study aimed to investigate the expression levels of miRNA10a and GLUT1 in OSCC patients with diabetes. MATERIALS AND METHODS: miRNA10a and GLUT1 expression were estimated in OSCC, precancerous, and healthy tissues using quantitative reverse transcriptase polymerase chain reaction (RT-PCR). miRNA10a and GLUT1 expression levels were recorded as fold change. Further, a one-way analysis of variance (ANOVA) test was performed to find whether there is any difference in miRNA10a and GLUT1 expression between OSCC, precancerous, and healthy tissues. RESULTS: The RT-PCR findings revealed an increased expression of miRNA10a and GLUT1 in OSCC compared to precancerous and healthy tissue. There is a positive correlation between miRNA10a and GLUT1 expression levels in both potentially malignant and control tissues, with a marked increase in cancerous tissue. This study demonstrated the significance of upregulated miRNA10a expression, indicating a direct correlation with OSCC proliferation via GLUT1 overexpression. Specifically, miRNA10a exhibited a fold change of 1.2±0.072 in potentially malignant tissue and 1.4±0.05 in cancer tissue, while GLUT1 exhibited a fold change of 1.25±0.092 in potentially malignant tissue and 0.092±0.08 in cancer tissue, respectively. CONCLUSION: This research highlights the role of miRNA10a in cancer progression by facilitating proliferation through the regulation of GLUT1 in cancerous tissues, particularly in hyperglycemic conditions. This mechanism further contributes to increased glucose transport in cancer patients, which may potentially impede tumor prognosis. These findings underscore the potential significance of targeting miRNA10a and GLUT1 as therapeutic interventions in cancer management.